Nutrient chapter

Acetyl-L-carnitine

Acetyl-L-carnitine. Species, exposure and limitations are retained in each linked claim.

91 recorded mechanisms · 12 availability situations · 4 preserved sources. Source recording and scientific verification are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

Expressed human OCTN2 transported acetyl-L-carnitine in a sodium-dependent manner with a measured Km of 8.5 micromolar.
Human carnitine transporter OCTN2 / SLC22A5 → Acetyl-L-carnitine Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human OCTN2 in HEK293 cells.
limitations
A kinetic constant is not a treatment target.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The transporter also carries the acetylated form.
primary_references
Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10525100/
transport_effect
raises Sodium-dependent acetylcarnitine transport with a measured Km of 8.5 micromolar.
transport_pool
the expressing cell Sodium-dependent acetylcarnitine transport with a measured Km of 8.5 micromolar.
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 50–56
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human OCTN2 in HEK293 cells. · Recorded from source · Recorded from source
## l-carnitine-octn2-acetyl The transporter also carries the acetylated form. Expressed human OCTN2 transported acetyl-L-carnitine in a sodium-dependent manner with a measured Km of 8.5 micromolar. Model: Human OCTN2 in HEK293 cells. Limitations: A kinetic constant is not a treatment target. Evidence access: Primary abstract Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10525100/
Complete structured claim and evidence
Muscle Crat deletion reduced short-chain acyltransferase activity and acetylcarnitine pools, supporting transfer of acetyl groups from acetyl-CoA to carnitine.
Mouse carnitine acetyltransferase / Crat → Acetyl-L-carnitine Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary abstract and full-text Figures 1-4
experimental_model
Muscle-specific mouse knockout, enzyme assays and metabolomics.
limitations
Crat buffer function depends on tissue and substrate conditions.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Carnitine can carry excess acetyl groups as well as long fatty-acid groups.
primary_references
Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 154–160
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Muscle-specific mouse knockout, enzyme assays and metabolomics. · Recorded from source · Recorded from source
## l-carnitine-crat-buffer Carnitine can carry excess acetyl groups as well as long fatty-acid groups. Muscle Crat deletion reduced short-chain acyltransferase activity and acetylcarnitine pools, supporting transfer of acetyl groups from acetyl-CoA to carnitine. Model: Muscle-specific mouse knockout, enzyme assays and metabolomics. Limitations: Crat buffer function depends on tissue and substrate conditions. Evidence access: Primary abstract and full-text Figures 1-4 Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005
Complete structured claim and evidence
Adding carnitine stimulated PDH activity 1.8-fold in control muscle mitochondria but did not stimulate it in Crat-null mitochondria.
L-Carnitine → Mouse muscle mitochondrial pyruvate dehydrogenase activity Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full-text Figure 4
experimental_model
Isolated mouse muscle mitochondria; pyruvate-only respiratory context and direct PDH assay.
limitations
The effect is context-dependent; liver mitochondria also lacked the stimulation.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Carnitine needs the acetyl-transfer enzyme to relieve this brake on glucose oxidation.
primary_references
Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 162–168
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Isolated mouse muscle mitochondria; pyruvate-only respiratory context and direct PDH assay. · Recorded from source · Recorded from source
## l-carnitine-crat-pdh Carnitine needs the acetyl-transfer enzyme to relieve this brake on glucose oxidation. Adding carnitine stimulated PDH activity 1.8-fold in control muscle mitochondria but did not stimulate it in Crat-null mitochondria. Model: Isolated mouse muscle mitochondria; pyruvate-only respiratory context and direct PDH assay. Limitations: The effect is context-dependent; liver mitochondria also lacked the stimulation. Evidence access: Primary full-text Figure 4 Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005
Complete structured claim and evidence
Silencing CRAT in primary human myotubes reduced acetylcarnitine export by 47%.
Human carnitine acetyltransferase / CRAT → Human primary myotube acetylcarnitine export Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full-text Figure 6 and methods
experimental_model
Human myotubes; adenoviral silencing, approximately 60% lower enzyme activity.
limitations
Cell culture, not human supplementation.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
An independent enzyme controls acetyl-group export from muscle cells.
primary_references
Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 170–176
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human myotubes; adenoviral silencing, approximately 60% lower enzyme activity. · Recorded from source · Recorded from source
## l-carnitine-crat-knockdown-export An independent enzyme controls acetyl-group export from muscle cells. Silencing CRAT in primary human myotubes reduced acetylcarnitine export by 47%. Model: Human myotubes; adenoviral silencing, approximately 60% lower enzyme activity. Limitations: Cell culture, not human supplementation. Evidence access: Primary full-text Figure 6 and methods Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005
Complete structured claim and evidence
Silencing CRAT in human myotubes reduced glucose uptake by 13% while increasing oleate oxidation.
Human carnitine acetyltransferase / CRAT → Human primary myotube glucose uptake Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full-text Figure 6
experimental_model
Primary human myotube loss-of-function experiment.
limitations
No universal reciprocal rule for all tissues.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
More fat oxidation did not mean better glucose handling in this experiment.
primary_references
Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 178–184
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Primary human myotube loss-of-function experiment. · Recorded from source · Recorded from source
## l-carnitine-crat-knockdown-glucose More fat oxidation did not mean better glucose handling in this experiment. Silencing CRAT in human myotubes reduced glucose uptake by 13% while increasing oleate oxidation. Model: Primary human myotube loss-of-function experiment. Limitations: No universal reciprocal rule for all tissues. Evidence access: Primary full-text Figure 6 Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22560225/ · DOI 10.1016/j.cmet.2012.04.005
Complete structured claim and evidence
Isotope-labeled acetylcarnitine supplied acetyl-CoA and fatty-acid carbon in glucose-limited human U87MG glioma cells.
Acetyl-L-carnitine → Human U87MG acetyl-CoA labeling from acetylcarnitine Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human U87MG culture, isotope tracing.
limitations
Does not show that oral acetylcarnitine causes or treats cancer.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The acetylated form can deliver carbon for cellular synthesis.
primary_references
Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 210–216
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human U87MG culture, isotope tracing. · Recorded from source · Recorded from source
## l-carnitine-acetyl-carbon The acetylated form can deliver carbon for cellular synthesis. Isotope-labeled acetylcarnitine supplied acetyl-CoA and fatty-acid carbon in glucose-limited human U87MG glioma cells. Model: Human U87MG culture, isotope tracing. Limitations: Does not show that oral acetylcarnitine causes or treats cancer. Evidence access: Primary abstract Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848
Complete structured claim and evidence
Deleting CROT reduced labeling of acetyl-CoA and palmitate from exogenous acetylcarnitine; CROT cDNA rescue restored acetyl-CoA labeling.
Human carnitine octanoyltransferase / CROT → Human U87MG acetyl-CoA labeling from acetylcarnitine Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full-text Figure 5 and enzyme assays
experimental_model
Human U87MG cells, CROT knockout and rescue; 1 mM tracer under glucose limitation.
limitations
Compartment and substrate supply may explain why this enzyme dominates in these cells.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Another carnitine enzyme provided this carbon route.
primary_references
Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 218–224
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human U87MG cells, CROT knockout and rescue; 1 mM tracer under glucose limitation. · Recorded from source · Recorded from source
## l-carnitine-crot-knockout Another carnitine enzyme provided this carbon route. Deleting CROT reduced labeling of acetyl-CoA and palmitate from exogenous acetylcarnitine; CROT cDNA rescue restored acetyl-CoA labeling. Model: Human U87MG cells, CROT knockout and rescue; 1 mM tracer under glucose limitation. Limitations: Compartment and substrate supply may explain why this enzyme dominates in these cells. Evidence access: Primary full-text Figure 5 and enzyme assays Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848
Complete structured claim and evidence
Deleting CRAT did not diminish acetyl-CoA labeling from supplied acetylcarnitine in U87MG cells.
Human carnitine acetyltransferase / CRAT → Human U87MG acetyl-CoA labeling from acetylcarnitine Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full-text Figure 4
experimental_model
Human U87MG knockout and tracer experiment.
limitations
Incoming acetylcarnitine utilization differs from mitochondrial production; not a conflict with muscle export.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The enzyme needed to make acetylcarnitine need not be the one that uses it.
primary_references
Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 226–232
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human U87MG knockout and tracer experiment. · Recorded from source · Recorded from source
## l-carnitine-crat-null-assimilation The enzyme needed to make acetylcarnitine need not be the one that uses it. Deleting CRAT did not diminish acetyl-CoA labeling from supplied acetylcarnitine in U87MG cells. Model: Human U87MG knockout and tracer experiment. Limitations: Incoming acetylcarnitine utilization differs from mitochondrial production; not a conflict with muscle export. Evidence access: Primary full-text Figure 4 Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848
Complete structured claim and evidence
Adding acetylcarnitine increased histone acetylation in lipid-depleted mouse HCC cells lacking both ACLY and ACSS2.
Acetyl-L-carnitine → Mouse HCC-cell histone acetylation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full-text Figure 6 and cell-line methods
experimental_model
Mouse hepatocellular carcinoma double-knockout cells; supplementation and isotope tracing.
limitations
An engineered cancer-cell bypass is not a general epigenetic benefit.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Acetyl-group transport can connect energy metabolism to chromatin chemistry.
primary_references
Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37134161/ · DOI 10.1126/sciadv.adf0115
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 234–240
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse hepatocellular carcinoma double-knockout cells; supplementation and isotope tracing. · Recorded from source · Recorded from source
## l-carnitine-histone-carbon Acetyl-group transport can connect energy metabolism to chromatin chemistry. Adding acetylcarnitine increased histone acetylation in lipid-depleted mouse HCC cells lacking both ACLY and ACSS2. Model: Mouse hepatocellular carcinoma double-knockout cells; supplementation and isotope tracing. Limitations: An engineered cancer-cell bypass is not a general epigenetic benefit. Evidence access: Primary full-text Figure 6 and cell-line methods Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37134161/ · DOI 10.1126/sciadv.adf0115
Complete structured claim and evidence
Removing Crat impaired glucose-derived lipid synthesis in ACLY-deficient mouse HCC cells.
Mouse carnitine acetyltransferase / Crat → Mouse HCC-cell glucose-derived lipid synthesis Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text and cell-line methods
experimental_model
Mouse HCC cell genetic perturbation and carbon tracing.
limitations
Dependence arises in the specified metabolic background.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The acetyl shuttle can supply lipid synthesis when a usual route is missing.
primary_references
Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37134161/ · DOI 10.1126/sciadv.adf0115
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 242–248
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse HCC cell genetic perturbation and carbon tracing. · Recorded from source · Recorded from source
## l-carnitine-crat-lipogenesis The acetyl shuttle can supply lipid synthesis when a usual route is missing. Removing Crat impaired glucose-derived lipid synthesis in ACLY-deficient mouse HCC cells. Model: Mouse HCC cell genetic perturbation and carbon tracing. Limitations: Dependence arises in the specified metabolic background. Evidence access: Primary full text and cell-line methods Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37134161/ · DOI 10.1126/sciadv.adf0115
Complete structured claim and evidence
Acetyl-L-carnitine treatment increased Grm2-associated H3K27 acetylation and mGlu2 expression in Flinders Sensitive Line rats.
Acetyl-L-carnitine → Rat hippocampal and prefrontal Grm2-associated acetylation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Rat depression-model hippocampus and prefrontal cortex.
limitations
Histone acetylation differs from DNA methylation; this is not proof of human antidepressant efficacy.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The acetylated form altered a glutamate-signaling pathway in a rodent model.
primary_references
L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23382250/ · DOI 10.1073/pnas.1216100110
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 314–320
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Rat depression-model hippocampus and prefrontal cortex. · Recorded from source · Recorded from source
## l-carnitine-brain-acetylation The acetylated form altered a glutamate-signaling pathway in a rodent model. Acetyl-L-carnitine treatment increased Grm2-associated H3K27 acetylation and mGlu2 expression in Flinders Sensitive Line rats. Model: Rat depression-model hippocampus and prefrontal cortex. Limitations: Histone acetylation differs from DNA methylation; this is not proof of human antidepressant efficacy. Evidence access: Primary abstract L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23382250/ · DOI 10.1073/pnas.1216100110
Complete structured claim and evidence
Acetyl-L-carnitine did not produce the reported behavioral benefit in mGlu2-knockout mice exposed to chronic unpredictable stress.
Mouse metabotropic glutamate receptor 2 / Grm2 → Mouse stress-model behavioral response to acetylcarnitine Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse knockout and stress-behavior experiments.
limitations
Behavioral tests are not human depression outcomes.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Removing the receptor tested whether the rodent effect depended on it.
primary_references
L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23382250/ · DOI 10.1073/pnas.1216100110
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 322–328
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse knockout and stress-behavior experiments. · Recorded from source · Recorded from source
## l-carnitine-brain-receptor-required Removing the receptor tested whether the rodent effect depended on it. Acetyl-L-carnitine did not produce the reported behavioral benefit in mGlu2-knockout mice exposed to chronic unpredictable stress. Model: Mouse knockout and stress-behavior experiments. Limitations: Behavioral tests are not human depression outcomes. Evidence access: Primary abstract L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23382250/ · DOI 10.1073/pnas.1216100110
Complete structured claim and evidence
In a 409-patient randomized trial during adjuvant taxane chemotherapy, acetyl-L-carnitine did not significantly improve the primary 12-week neuropathy endpoint.
Acetyl-L-carnitine → Human taxane-associated peripheral neuropathy severity Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Women with breast cancer; 3 g/day acetyl-L-carnitine versus placebo.
limitations
A finding for this derivative and treatment context, not every carnitine use.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
A plausible nerve-protection idea failed its main clinical test.
primary_references
Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy in women undergoing adjuvant breast cancer therapy. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23733756/ · DOI 10.1200/JCO.2012.44.8738
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 330–336
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Women with breast cancer; 3 g/day acetyl-L-carnitine versus placebo. · Recorded from source · Recorded from source
## l-carnitine-alc-neuropathy-null A plausible nerve-protection idea failed its main clinical test. In a 409-patient randomized trial during adjuvant taxane chemotherapy, acetyl-L-carnitine did not significantly improve the primary 12-week neuropathy endpoint. Model: Women with breast cancer; 3 g/day acetyl-L-carnitine versus placebo. Limitations: A finding for this derivative and treatment context, not every carnitine use. Evidence access: Primary abstract Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy in women undergoing adjuvant breast cancer therapy. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23733756/ · DOI 10.1200/JCO.2012.44.8738
Complete structured claim and evidence
At 24 weeks in the same taxane trial, the acetyl-L-carnitine arm had worse neuropathy scores and more severe neurotoxicity than placebo.
Acetyl-L-carnitine → Human taxane-associated peripheral neuropathy severity Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Same randomized trial; prespecified secondary follow-up.
limitations
Not a demonstrated molecular explanation of the harm; keep the clinical outcome visible.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
Longer follow-up revealed harm in that setting.
primary_references
Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy in women undergoing adjuvant breast cancer therapy. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23733756/ · DOI 10.1200/JCO.2012.44.8738
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 338–344
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Same randomized trial; prespecified secondary follow-up. · Recorded from source · Recorded from source
## l-carnitine-alc-neuropathy-harm Longer follow-up revealed harm in that setting. At 24 weeks in the same taxane trial, the acetyl-L-carnitine arm had worse neuropathy scores and more severe neurotoxicity than placebo. Model: Same randomized trial; prespecified secondary follow-up. Limitations: Not a demonstrated molecular explanation of the harm; keep the clinical outcome visible. Evidence access: Primary abstract Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy in women undergoing adjuvant breast cancer therapy. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23733756/ · DOI 10.1200/JCO.2012.44.8738
Complete structured claim and evidence
Purified recombinant human CRAT transferred short-chain acyl groups including acetyl from acyl-CoA substrates to carnitine in enzyme assays.
Human carnitine acetyltransferase / CRAT → Acetyl-L-carnitine Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full-text Table 1 and recombinant enzyme methods
experimental_model
Human CRAT expressed in E. coli; steady-state kinetic substrate panel.
limitations
Purified-enzyme capacity does not identify the dominant flux in every compartment.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
The human enzyme directly connects carnitine and the CoA pool.
primary_references
Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 498–504
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human CRAT expressed in E. coli; steady-state kinetic substrate panel. · Recorded from source · Recorded from source
## l-carnitine-human-crat-reaction The human enzyme directly connects carnitine and the CoA pool. Purified recombinant human CRAT transferred short-chain acyl groups including acetyl from acyl-CoA substrates to carnitine in enzyme assays. Model: Human CRAT expressed in E. coli; steady-state kinetic substrate panel. Limitations: Purified-enzyme capacity does not identify the dominant flux in every compartment. Evidence access: Primary full-text Table 1 and recombinant enzyme methods Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36587768/ · DOI 10.1016/j.jbc.2022.102848
Complete structured claim and evidence
Proteolysis releases free trimethyllysine from trimethyllysine-containing protein, providing a precursor for carnitine biosynthesis.
Protein-bound N-epsilon-trimethyllysine residues → Free N-epsilon-trimethyl-L-lysine Recorded from sourceungraded
Experimental context and source evidence
experimental_model
Radiolabeled asialofetuin metabolism in rats and perfused rat liver
limitations
Direct tracer evidence is rat; do not replace this with a direct free-lysine-to-carnitine edge.
organism
Rattus norvegicus
plain_language
Protein breakdown releases the modified lysine used to make carnitine.
primary_references
[labadie1976] Hepatic synthesis of carnitine from protein-bound trimethyl-lysine. Lysosomal digestion of methyl-lysine-labelled asialo-fetuin (1976). https://pubmed.ncbi.nlm.nih.gov/64247/ DOI: 10.1042/bj1600085
tissue_or_cell_type
Liver lysosomes and downstream metabolism
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 156–164
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiolabeled asialofetuin metabolism in rats and perfused rat liver · Recorded from source · Recorded from source
### protein-tml-release Proteolysis releases free trimethyllysine from trimethyllysine-containing protein, providing a precursor for carnitine biosynthesis. Plain language: Protein breakdown releases the modified lysine used to make carnitine. Condition category: normal organism: Rattus norvegicus tissue_or_cell_type: Liver lysosomes and downstream metabolism experimental_model: Radiolabeled asialofetuin metabolism in rats and perfused rat liver limitations: Direct tracer evidence is rat; do not replace this with a direct free-lysine-to-carnitine edge. [labadie1976] Hepatic synthesis of carnitine from protein-bound trimethyl-lysine. Lysosomal digestion of methyl-lysine-labelled asialo-fetuin (1976). https://pubmed.ncbi.nlm.nih.gov/64247/ DOI: 10.1042/bj1600085
Complete structured claim and evidence
Human TMLHE hydroxylates free trimethyllysine to (2S,3S)-hydroxytrimethyllysine, coupled to 2-oxoglutarate oxidation.
Free N-epsilon-trimethyl-L-lysine → (2S,3S)-3-Hydroxy-N-epsilon-trimethyllysine Recorded from sourceungraded
Experimental context and source evidence
experimental_model
Recombinant human TMLH, synthetic standards and NMR; Recombinant human TMLH and substrate analogue assays
limitations
The substrate is free trimethyllysine after proteolysis, not ordinary free lysine.
organism
Homo sapiens
plain_language
TMLHE begins conversion of released trimethyllysine toward carnitine.
primary_references
[lesniak2017] Human carnitine biosynthesis proceeds via (2S,3S)-3-hydroxy-Nε-trimethyllysine (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5644716/ DOI: 10.1039/C6CC08381A [tmlh2016scope] Substrate scope for trimethyllysine hydroxylase catalysis (2016). https://pubs.rsc.org/en/content/articlehtml/2016/cc/c6cc07845a DOI: 10.1039/C6CC07845A
tissue_or_cell_type
Mitochondrial carnitine-biosynthesis step
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 166–175
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human TMLH, synthetic standards and NMR; Recombinant human TMLH and substrate analogue assays · Recorded from source · Recorded from source
### tmlhe-hydroxylation Human TMLHE hydroxylates free trimethyllysine to (2S,3S)-hydroxytrimethyllysine, coupled to 2-oxoglutarate oxidation. Plain language: TMLHE begins conversion of released trimethyllysine toward carnitine. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial carnitine-biosynthesis step experimental_model: Recombinant human TMLH, synthetic standards and NMR; Recombinant human TMLH and substrate analogue assays limitations: The substrate is free trimethyllysine after proteolysis, not ordinary free lysine. [lesniak2017] Human carnitine biosynthesis proceeds via (2S,3S)-3-hydroxy-Nε-trimethyllysine (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5644716/ DOI: 10.1039/C6CC08381A [tmlh2016scope] Substrate scope for trimethyllysine hydroxylase catalysis (2016). https://pubs.rsc.org/en/content/articlehtml/2016/cc/c6cc07845a DOI: 10.1039/C6CC07845A
Complete structured claim and evidence
Purified human SHMT1 cleaves hydroxytrimethyllysine into trimethylaminobutyraldehyde and glycine.
(2S,3S)-3-Hydroxy-N-epsilon-trimethyllysine → 4-Trimethylaminobutyraldehyde Recorded from sourceungraded
Experimental context and source evidence
experimental_model
Purified human enzyme; NMR and coupled activity assays
limitations
Whole-body flux contribution remains unquantified.
organism
Homo sapiens
plain_language
SHMT1 can perform the second carnitine-synthesis reaction.
primary_references
[osmes2024] One substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse (2024). https://www.nature.com/articles/s41467-024-47466-3 DOI: 10.1038/s41467-024-47466-3
tissue_or_cell_type
Cytosolic enzyme tested in vitro
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 177–185
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human enzyme; NMR and coupled activity assays · Recorded from source · Recorded from source
### shmt1-html-cleavage Purified human SHMT1 cleaves hydroxytrimethyllysine into trimethylaminobutyraldehyde and glycine. Plain language: SHMT1 can perform the second carnitine-synthesis reaction. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Cytosolic enzyme tested in vitro experimental_model: Purified human enzyme; NMR and coupled activity assays limitations: Whole-body flux contribution remains unquantified. [osmes2024] One substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse (2024). https://www.nature.com/articles/s41467-024-47466-3 DOI: 10.1038/s41467-024-47466-3
Complete structured claim and evidence
Purified human SHMT2 also cleaves hydroxytrimethyllysine, with lower measured catalytic efficiency than SHMT1.
(2S,3S)-3-Hydroxy-N-epsilon-trimethyllysine → 4-Trimethylaminobutyraldehyde Recorded from sourceungraded
Experimental context and source evidence
experimental_model
Purified human enzyme kinetic assay
limitations
Mouse Tha1 specialization should not be assigned to a human THA1 enzyme.
organism
Homo sapiens
plain_language
SHMT2 provides another demonstrated aldolase activity.
primary_references
[osmes2024] One substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse (2024). https://www.nature.com/articles/s41467-024-47466-3 DOI: 10.1038/s41467-024-47466-3
tissue_or_cell_type
Mitochondrial enzyme tested in vitro
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 187–195
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human enzyme kinetic assay · Recorded from source · Recorded from source
### shmt2-html-cleavage Purified human SHMT2 also cleaves hydroxytrimethyllysine, with lower measured catalytic efficiency than SHMT1. Plain language: SHMT2 provides another demonstrated aldolase activity. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial enzyme tested in vitro experimental_model: Purified human enzyme kinetic assay limitations: Mouse Tha1 specialization should not be assigned to a human THA1 enzyme. [osmes2024] One substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse (2024). https://www.nature.com/articles/s41467-024-47466-3 DOI: 10.1038/s41467-024-47466-3
Complete structured claim and evidence
Omission controls with recombinant human MBP-TMLH-a showed that ascorbate, Fe(II) and 2-oxoglutarate were each needed for efficient conversion of free trimethyllysine to 3-hydroxytrimethyllysine.
L-Ascorbate → Trimethyllysine hydroxylase / TMLHE Recorded from sourceungraded
Experimental context and source evidence
cross_nutrient
Vitamin C + iron support hydroxylation of a modified lysine precursor; downstream existing SHMT steps use B6-derived PLP and ALDH9A1 uses NAD+.
experimental_model
Recombinant human MBP-TMLH-a; mass spectrometry and NMR
exposure
500 micromolar trimethyllysine and 3 micromolar enzyme, FeSO4/2OG/ascorbate, 37 C for 30 minutes; cofactor omission controls.
limitations
New record isolates the ascorbate cofactor dependence; the existing substrate-to-product UUID is reused. Fusion-protein assay does not quantify whole-body flux.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Homo sapiens
plain_language
The first carnitine-synthesis hydroxylation needs vitamin C support alongside iron and 2-oxoglutarate.
primary_references
[tmlh2016] Substrate scope for trimethyllysine hydroxylase catalysis. (2016). https://pubmed.ncbi.nlm.nih.gov/27730239/ DOI: 10.1039/c6cc07845a
tissue_or_cell_type
Cell-free recombinant enzyme
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 689–700
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MBP-TMLH-a; mass spectrometry and NMR · Recorded from source · Recorded from source
### vc-enzyme-tmlh-ascorbate-dependency Omission controls with recombinant human MBP-TMLH-a showed that ascorbate, Fe(II) and 2-oxoglutarate were each needed for efficient conversion of free trimethyllysine to 3-hydroxytrimethyllysine. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: The first carnitine-synthesis hydroxylation needs vitamin C support alongside iron and 2-oxoglutarate. organism: Homo sapiens tissue_or_cell_type: Cell-free recombinant enzyme experimental_model: Recombinant human MBP-TMLH-a; mass spectrometry and NMR limitations: New record isolates the ascorbate cofactor dependence; the existing substrate-to-product UUID is reused. Fusion-protein assay does not quantify whole-body flux. cross_nutrient: Vitamin C + iron support hydroxylation of a modified lysine precursor; downstream existing SHMT steps use B6-derived PLP and ALDH9A1 uses NAD+. exposure: 500 micromolar trimethyllysine and 3 micromolar enzyme, FeSO4/2OG/ascorbate, 37 C for 30 minutes; cofactor omission controls. [tmlh2016] Substrate scope for trimethyllysine hydroxylase catalysis. (2016). https://pubmed.ncbi.nlm.nih.gov/27730239/ DOI: 10.1039/c6cc07845a
Complete structured claim and evidence
Expressing human ALDH9 in bacteria produced NAD+-dependent trimethylaminobutyraldehyde dehydrogenase activity, completing the aldehyde-to-gamma-butyrobetaine step.
ALDH9A1 → gamma-Butyrobetaine Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Recombinant human ALDH9 compared with purified and recombinant rat enzyme.
limitations
NAD+ dependence does not establish benefit from niacin supplementation.
nutrient_topic
L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine
plain_language
A niacin-derived coenzyme participates in making carnitine.
primary_references
Molecular and biochemical characterization of rat gamma-trimethylaminobutyraldehyde dehydrogenase and evidence for the involvement of human aldehyde dehydrogenase 9 in carnitine biosynthesis. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10702312/ · DOI 10.1074/jbc.275.10.7390
L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 18–24
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human ALDH9 compared with purified and recombinant rat enzyme. · Recorded from source · Recorded from source
## l-carnitine-aldehyde-step A niacin-derived coenzyme participates in making carnitine. Expressing human ALDH9 in bacteria produced NAD+-dependent trimethylaminobutyraldehyde dehydrogenase activity, completing the aldehyde-to-gamma-butyrobetaine step. Model: Recombinant human ALDH9 compared with purified and recombinant rat enzyme. Limitations: NAD+ dependence does not establish benefit from niacin supplementation. Evidence access: Primary abstract Molecular and biochemical characterization of rat gamma-trimethylaminobutyraldehyde dehydrogenase and evidence for the involvement of human aldehyde dehydrogenase 9 in carnitine biosynthesis. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10702312/ · DOI 10.1074/jbc.275.10.7390
Complete structured claim and evidence
ALCAR is the O-acetyl ester of L-carnitine; its zwitterionic structure has a positive quaternary ammonium and a negative carboxylate.
Acetyl-L-carnitine → L-Carnitine Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Official chemical identity record; not a biological experiment.
experimental_model
Chemical identity at near-neutral physiological conditions.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR is the O-acetyl ester of L-carnitine; its zwitterionic structure has a positive quaternary ammonium and a negative carboxylate.
primary_references
ChEBI 57589: O-acetyl-L-carnitine | https://www.ebi.ac.uk/chebi/CHEBI:57589
source_locator
Reviewed reference alcar-identity; ChEBI 57589 records formula C9H17NO4 and net charge zero. Net zero does not mean uncharged functional groups or unrestricted lipid diffusion. Hydrochloride salt mass differs from free ALCAR.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 15–21
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Chemical identity at near-neutral physiological conditions. · Recorded from source · Recorded from source
### alcar-identity ALCAR is the O-acetyl ester of L-carnitine; its zwitterionic structure has a positive quaternary ammonium and a negative carboxylate. ChEBI 57589 records formula C9H17NO4 and net charge zero. Net zero does not mean uncharged functional groups or unrestricted lipid diffusion. Hydrochloride salt mass differs from free ALCAR. Model and exposure: Chemical identity at near-neutral physiological conditions. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: ChEBI 57589: O-acetyl-L-carnitine | accessed 2026-10-06 | https://www.ebi.ac.uk/chebi/CHEBI:57589 | Access: Official chemical identity record; not a biological experiment.
Complete structured claim and evidence
CrAT-mediated transfer of an acetyl group from ALCAR to CoA produces acetyl-CoA and free carnitine.
Acetyl-L-carnitine → Acetyl-CoA Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_model
Reversible mammalian carnitine acetyltransferase reaction.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
CrAT-mediated transfer of an acetyl group from ALCAR to CoA produces acetyl-CoA and free carnitine.
primary_references
Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. | https://pubmed.ncbi.nlm.nih.gov/22560225/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC3348515/ | https://doi.org/10.1016/j.cmet.2012.04.005
primary_references
The cycling of acetyl-coenzyme A through acetylcarnitine buffers cardiac substrate supply: a hyperpolarized 13C magnetic resonance study. | https://pubmed.ncbi.nlm.nih.gov/22238215/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC3378498/ | https://doi.org/10.1161/circimaging.111.969451
source_locator
Reviewed reference crat-acetyl-donation; ALCAR + CoASH ⇄ acetyl-CoA + L-carnitine. This direction consumes free CoA; acetyl-CoA-to-ALCAR formation releases it. Net flux depends on compartmental substrate/product activities, not the name of the supplement.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 23–30
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Reversible mammalian carnitine acetyltransferase reaction. · Recorded from source · Recorded from source
### crat-acetyl-donation CrAT-mediated transfer of an acetyl group from ALCAR to CoA produces acetyl-CoA and free carnitine. ALCAR + CoASH ⇄ acetyl-CoA + L-carnitine. This direction consumes free CoA; acetyl-CoA-to-ALCAR formation releases it. Net flux depends on compartmental substrate/product activities, not the name of the supplement. Model and exposure: Reversible mammalian carnitine acetyltransferase reaction. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. | 2012 | https://pubmed.ncbi.nlm.nih.gov/22560225/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC3348515/ | https://doi.org/10.1016/j.cmet.2012.04.005 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated. Reference: The cycling of acetyl-coenzyme A through acetylcarnitine buffers cardiac substrate supply: a hyperpolarized 13C magnetic resonance study. | 2012 | https://pubmed.ncbi.nlm.nih.gov/22238215/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC3378498/ | https://doi.org/10.1161/circimaging.111.969451 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
Dichloroacetate increased cardiac acetylcarnitine production and pool size in fed rats.
Dichloroacetate → Rat cardiac acetylcarnitine pool Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_contrast
{"intervention": "Dichloroacetate-enhanced PDH flux", "comparator": "Fed control rats", "endpoint": "Dichloroacetate increased cardiac acetylcarnitine production and pool size in fed rats.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Male Wistar rats; hyperpolarized 13C-pyruvate and cardiac magnetic resonance.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Dichloroacetate increased cardiac acetylcarnitine production and pool size in fed rats.
primary_references
The cycling of acetyl-coenzyme A through acetylcarnitine buffers cardiac substrate supply: a hyperpolarized 13C magnetic resonance study. | https://pubmed.ncbi.nlm.nih.gov/22238215/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC3378498/ | https://doi.org/10.1161/circimaging.111.969451
source_locator
Reviewed reference heart-pdh-buffer; Production increased 35% and pool size 33%; the recorded intervention enhanced PDH flux. This is endogenous buffering, not oral ALCAR efficacy.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 32–38
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Male Wistar rats; hyperpolarized 13C-pyruvate and cardiac magnetic resonance. · Recorded from source · Recorded from source
### heart-pdh-buffer Dichloroacetate increased cardiac acetylcarnitine production and pool size in fed rats. Production increased 35% and pool size 33%; the recorded intervention enhanced PDH flux. This is endogenous buffering, not oral ALCAR efficacy. Model and exposure: Male Wistar rats; hyperpolarized 13C-pyruvate and cardiac magnetic resonance. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: The cycling of acetyl-coenzyme A through acetylcarnitine buffers cardiac substrate supply: a hyperpolarized 13C magnetic resonance study. | 2012 | https://pubmed.ncbi.nlm.nih.gov/22238215/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC3378498/ | https://doi.org/10.1161/circimaging.111.969451 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
Dobutamine-driven cardiac workload lowered acetylcarnitine production and pool size in rats.
Dobutamine → Rat cardiac acetylcarnitine pool Recorded from sourceungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_contrast
{"intervention": "Dobutamine-driven workload", "comparator": "Fed control rats", "endpoint": "Dobutamine-driven cardiac workload lowered acetylcarnitine production and pool size in rats.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Male Wistar rats; hyperpolarized 13C-pyruvate study.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Dobutamine-driven cardiac workload lowered acetylcarnitine production and pool size in rats.
primary_references
The cycling of acetyl-coenzyme A through acetylcarnitine buffers cardiac substrate supply: a hyperpolarized 13C magnetic resonance study. | https://pubmed.ncbi.nlm.nih.gov/22238215/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC3378498/ | https://doi.org/10.1161/circimaging.111.969451
source_locator
Reviewed reference heart-workload-buffer; Production decreased 37% and pool size 40%. Depletion of a buffer during demand does not independently diagnose nutritional carnitine deficiency.
trigger_kind
biomarker_context Imported condition classification; unverified.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 40–46
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Male Wistar rats; hyperpolarized 13C-pyruvate study. · Recorded from source · Recorded from source
### heart-workload-buffer Dobutamine-driven cardiac workload lowered acetylcarnitine production and pool size in rats. Production decreased 37% and pool size 40%. Depletion of a buffer during demand does not independently diagnose nutritional carnitine deficiency. Model and exposure: Male Wistar rats; hyperpolarized 13C-pyruvate study. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: The cycling of acetyl-coenzyme A through acetylcarnitine buffers cardiac substrate supply: a hyperpolarized 13C magnetic resonance study. | 2012 | https://pubmed.ncbi.nlm.nih.gov/22238215/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC3378498/ | https://doi.org/10.1161/circimaging.111.969451 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
Labeled pantothenate supplied the CoA backbone used to trace mitochondrial CoASH import in human cells.
Pantothenate (vitamin B5) → Coenzyme A Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_model
Human K562 cells; 13C3-15N-pantothenate labeling for three days followed by acyl-CoA extraction and mitochondrial uptake assay; Fig. 7a.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Labeled pantothenate supplied the CoA backbone used to trace mitochondrial CoASH import in human cells.
primary_references
Cellular pan-chain acyl-CoA profiling reveals SLC25A42/SLC25A16 in mitochondrial CoA import and metabolism. | https://pubmed.ncbi.nlm.nih.gov/40925986/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC12460162/ | https://doi.org/10.1038/s42255-025-01358-y
source_locator
Reviewed reference b5-coa-backbone; The isotope labels were on the CoA moiety, not its attached acetyl group. This connects vitamin B5 supply to the cofactor required for ALCAR use without asserting a benefit from excess B5.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 52–58
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Human K562 cells; 13C3-15N-pantothenate labeling for three days followed by acyl-CoA extraction and mitochondrial uptake assay; Fig. 7a. · Recorded from source · Recorded from source
### b5-coa-backbone Labeled pantothenate supplied the CoA backbone used to trace mitochondrial CoASH import in human cells. The isotope labels were on the CoA moiety, not its attached acetyl group. This connects vitamin B5 supply to the cofactor required for ALCAR use without asserting a benefit from excess B5. Model and exposure: Human K562 cells; 13C3-15N-pantothenate labeling for three days followed by acyl-CoA extraction and mitochondrial uptake assay; Fig. 7a. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Cellular pan-chain acyl-CoA profiling reveals SLC25A42/SLC25A16 in mitochondrial CoA import and metabolism. | 2025 | https://pubmed.ncbi.nlm.nih.gov/40925986/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC12460162/ | https://doi.org/10.1038/s42255-025-01358-y | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
Combined SLC25A16/SLC25A42 deletion depleted mitochondrial free CoASH in human K562 and HeLa cells.
Human mitochondrial CoA transporter SLC25A16 → Human-cell mitochondrial free CoASH pool Recorded from sourceungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_condition
Matched control cells deleted · Human mitochondrial CoA transporter SLC25A16 Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
Matched control cells deleted · Human mitochondrial coenzyme A transporter SLC25A42 Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "SLC25A16 and SLC25A42 double knockout", "comparator": "Matched control cells", "endpoint": "Combined SLC25A16/SLC25A42 deletion depleted mitochondrial free CoASH in human K562 and HeLa cells.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "human-slc25a16", "state": "deleted"}, {"entity_slug": "slc25a42", "state": "deleted"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human K562/HeLa double-knockout cells; mitochondrial isolation and LC-MS; Figs 4–7.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Combined SLC25A16/SLC25A42 deletion depleted mitochondrial free CoASH in human K562 and HeLa cells.
primary_references
Cellular pan-chain acyl-CoA profiling reveals SLC25A42/SLC25A16 in mitochondrial CoA import and metabolism. | https://pubmed.ncbi.nlm.nih.gov/40925986/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC12460162/ | https://doi.org/10.1038/s42255-025-01358-y
source_locator
Reviewed reference coa-import-joint; Loss of both transporters also depleted several matrix-enriched short-chain acyl-CoAs. Stable-isotope CoASH uptake was reduced. Do not split this double-knockout result into two independent single-gene effects.
trigger_kind
machinery_impairment Imported condition classification; unverified.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 60–66
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Human K562/HeLa double-knockout cells; mitochondrial isolation and LC-MS; Figs 4–7. · Recorded from source · Recorded from source
### coa-import-joint Combined SLC25A16/SLC25A42 deletion depleted mitochondrial free CoASH in human K562 and HeLa cells. Loss of both transporters also depleted several matrix-enriched short-chain acyl-CoAs. Stable-isotope CoASH uptake was reduced. Do not split this double-knockout result into two independent single-gene effects. Model and exposure: Human K562/HeLa double-knockout cells; mitochondrial isolation and LC-MS; Figs 4–7. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Cellular pan-chain acyl-CoA profiling reveals SLC25A42/SLC25A16 in mitochondrial CoA import and metabolism. | 2025 | https://pubmed.ncbi.nlm.nih.gov/40925986/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC12460162/ | https://doi.org/10.1038/s42255-025-01358-y | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
Combined SLC25A16/SLC25A42 deletion impaired fatty-acid oxidation and shifted TCA labeling toward reductive routes.
Human mitochondrial CoA transporter SLC25A16 → Human-cell fatty-acid oxidation during impaired CoA import Recorded from sourceungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_condition
Control cells deleted · Human mitochondrial CoA transporter SLC25A16 Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
Control cells deleted · Human mitochondrial coenzyme A transporter SLC25A42 Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "SLC25A16 and SLC25A42 double knockout", "comparator": "Control cells", "endpoint": "Combined SLC25A16/SLC25A42 deletion impaired fatty-acid oxidation and shifted TCA labeling toward reductive routes.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "human-slc25a16", "state": "deleted"}, {"entity_slug": "slc25a42", "state": "deleted"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
K562 and HeLa cells; mitochondrial metabolomics, respiration and 13C5-glutamine tracing.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Combined SLC25A16/SLC25A42 deletion impaired fatty-acid oxidation and shifted TCA labeling toward reductive routes.
primary_references
Cellular pan-chain acyl-CoA profiling reveals SLC25A42/SLC25A16 in mitochondrial CoA import and metabolism. | https://pubmed.ncbi.nlm.nih.gov/40925986/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC12460162/ | https://doi.org/10.1038/s42255-025-01358-y
source_locator
Reviewed reference coa-import-fao; Long-chain acylcarnitines accumulated while free CoA fell. More acyl carrier is not equivalent to restored matrix CoA. ALCAR supplementation was not tested as rescue in this comparison.
trigger_kind
machinery_impairment Imported condition classification; unverified.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 68–74
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · K562 and HeLa cells; mitochondrial metabolomics, respiration and 13C5-glutamine tracing. · Recorded from source · Recorded from source
### coa-import-fao Combined SLC25A16/SLC25A42 deletion impaired fatty-acid oxidation and shifted TCA labeling toward reductive routes. Long-chain acylcarnitines accumulated while free CoA fell. More acyl carrier is not equivalent to restored matrix CoA. ALCAR supplementation was not tested as rescue in this comparison. Model and exposure: K562 and HeLa cells; mitochondrial metabolomics, respiration and 13C5-glutamine tracing. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Cellular pan-chain acyl-CoA profiling reveals SLC25A42/SLC25A16 in mitochondrial CoA import and metabolism. | 2025 | https://pubmed.ncbi.nlm.nih.gov/40925986/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC12460162/ | https://doi.org/10.1038/s42255-025-01358-y | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
Isolated K562 mitochondria showed negligible uptake of acetyl-labeled acetyl-CoA under the tested assay.
Acetyl-CoA → Human isolated-mitochondrial acetyl-CoA uptake Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_model
Fig. 7d–e; 10 micromolar 13C2-acetyl-CoA, 6 min, 20–25 C.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Isolated K562 mitochondria showed negligible uptake of acetyl-labeled acetyl-CoA under the tested assay.
primary_references
Cellular pan-chain acyl-CoA profiling reveals SLC25A42/SLC25A16 in mitochondrial CoA import and metabolism. | https://pubmed.ncbi.nlm.nih.gov/40925986/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC12460162/ | https://doi.org/10.1038/s42255-025-01358-y
source_locator
Reviewed reference coa-import-acetyl-null; CoA-backbone labeling after free CoASH uptake must not be mistaken for direct import of intact acetyl-CoA. A small residual signal could reflect membrane binding or minimal import.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 76–82
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Fig. 7d–e; 10 micromolar 13C2-acetyl-CoA, 6 min, 20–25 C. · Recorded from source · Recorded from source
### coa-import-acetyl-null Isolated K562 mitochondria showed negligible uptake of acetyl-labeled acetyl-CoA under the tested assay. CoA-backbone labeling after free CoASH uptake must not be mistaken for direct import of intact acetyl-CoA. A small residual signal could reflect membrane binding or minimal import. Model and exposure: Fig. 7d–e; 10 micromolar 13C2-acetyl-CoA, 6 min, 20–25 C. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Cellular pan-chain acyl-CoA profiling reveals SLC25A42/SLC25A16 in mitochondrial CoA import and metabolism. | 2025 | https://pubmed.ncbi.nlm.nih.gov/40925986/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC12460162/ | https://doi.org/10.1038/s42255-025-01358-y | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
SLC25A42 N291D failed to restore mitochondrial CoA pools that wild-type SLC25A42 rescued.
Human mitochondrial coenzyme A transporter SLC25A42 → Human-cell mitochondrial free CoASH pool Recorded from sourceungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_contrast
{"intervention": "N291D SLC25A42 re-expression", "comparator": "Wild-type SLC25A42 re-expression in knockout cells", "endpoint": "SLC25A42 N291D failed to restore mitochondrial CoA pools that wild-type SLC25A42 rescued.", "effect_direction": "mixed", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human K562 SLC25A42 knockout with re-expression; Fig. 6.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
SLC25A42 N291D failed to restore mitochondrial CoA pools that wild-type SLC25A42 rescued.
primary_references
Cellular pan-chain acyl-CoA profiling reveals SLC25A42/SLC25A16 in mitochondrial CoA import and metabolism. | https://pubmed.ncbi.nlm.nih.gov/40925986/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC12460162/ | https://doi.org/10.1038/s42255-025-01358-y
source_locator
Reviewed reference coa-mutant-rescue; The mutant protein reached mitochondria; protein presence did not establish transport function. Mitochondrially targeted COASY also failed to restore the depleted pool.
trigger_kind
machinery_impairment Imported condition classification; unverified.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 84–90
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Human K562 SLC25A42 knockout with re-expression; Fig. 6. · Recorded from source · Recorded from source
### coa-mutant-rescue SLC25A42 N291D failed to restore mitochondrial CoA pools that wild-type SLC25A42 rescued. The mutant protein reached mitochondria; protein presence did not establish transport function. Mitochondrially targeted COASY also failed to restore the depleted pool. Model and exposure: Human K562 SLC25A42 knockout with re-expression; Fig. 6. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Cellular pan-chain acyl-CoA profiling reveals SLC25A42/SLC25A16 in mitochondrial CoA import and metabolism. | 2025 | https://pubmed.ncbi.nlm.nih.gov/40925986/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC12460162/ | https://doi.org/10.1038/s42255-025-01358-y | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
Defective Octn2 reduced initial ALCAR brain uptake and thalamic extracellular ALCAR in jvs mice.
Mouse carnitine transporter Octn2 / Slc22a5 → Mouse blood-to-brain ALCAR uptake Recorded from sourceungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_contrast
{"intervention": "Defective OCTN2 in jvs mice", "comparator": "Wild-type mice", "endpoint": "Defective Octn2 reduced initial ALCAR brain uptake and thalamic extracellular ALCAR in jvs mice.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse wild-type versus juvenile visceral steatosis model; microdialysis and zero-net-flux analysis.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Defective Octn2 reduced initial ALCAR brain uptake and thalamic extracellular ALCAR in jvs mice.
primary_references
Acetyl-L-carnitine permeability across the blood-brain barrier and involvement of carnitine transporter OCTN2. | https://pubmed.ncbi.nlm.nih.gov/14595704/ | https://doi.org/10.1002/bdd.371
source_locator
Reviewed reference octn2-brain; The study supports at least partial OCTN2 involvement, not a universal human uptake multiplier or exclusive transporter dependence.
trigger_kind
machinery_impairment Imported condition classification; unverified.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 96–102
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Mouse wild-type versus juvenile visceral steatosis model; microdialysis and zero-net-flux analysis. · Recorded from source · Recorded from source
### octn2-brain Defective Octn2 reduced initial ALCAR brain uptake and thalamic extracellular ALCAR in jvs mice. The study supports at least partial OCTN2 involvement, not a universal human uptake multiplier or exclusive transporter dependence. Model and exposure: Mouse wild-type versus juvenile visceral steatosis model; microdialysis and zero-net-flux analysis. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Acetyl-L-carnitine permeability across the blood-brain barrier and involvement of carnitine transporter OCTN2. | 2003 | https://pubmed.ncbi.nlm.nih.gov/14595704/ | https://doi.org/10.1002/bdd.371 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
Repeated ALCAR administration increased plasma and CSF ALCAR in an 11-patient Alzheimer pharmacokinetic study.
Acetyl-L-carnitine → Human CSF acetylcarnitine concentration Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_contrast
{"intervention": "Sequential IV then oral ALCAR regimen", "comparator": "Run-in/sham period", "endpoint": "Repeated ALCAR administration increased plasma and CSF ALCAR in an 11-patient Alzheimer pharmacokinetic study.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
1992 study with corrected indexed regimen: 30 mg/kg IV for 10 days followed by 1.5 g/day orally for 50 days.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Repeated ALCAR administration increased plasma and CSF ALCAR in an 11-patient Alzheimer pharmacokinetic study.
primary_references
Pharmacokinetics of IV and oral acetyl-L-carnitine in a multiple dose regimen in patients with senile dementia of Alzheimer type. | https://pubmed.ncbi.nlm.nih.gov/1541322/ | https://doi.org/10.1007/bf00314926
source_locator
Reviewed reference human-csf; The indexed abstract includes corrected dosing and an erratum reference. CSF exposure is not cognitive efficacy or proof of intact labeled ALCAR reaching neuronal nuclei.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 104–110
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · 1992 study with corrected indexed regimen: 30 mg/kg IV for 10 days followed by 1.5 g/day orally for 50 days. · Recorded from source · Recorded from source
### human-csf Repeated ALCAR administration increased plasma and CSF ALCAR in an 11-patient Alzheimer pharmacokinetic study. The indexed abstract includes corrected dosing and an erratum reference. CSF exposure is not cognitive efficacy or proof of intact labeled ALCAR reaching neuronal nuclei. Model and exposure: 1992 study with corrected indexed regimen: 30 mg/kg IV for 10 days followed by 1.5 g/day orally for 50 days. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Pharmacokinetics of IV and oral acetyl-L-carnitine in a multiple dose regimen in patients with senile dementia of Alzheimer type. | 1992 | https://pubmed.ncbi.nlm.nih.gov/1541322/ | https://doi.org/10.1007/bf00314926 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
A nominal 1.5-g oral ALCAR dose produced a nonsignificant plasma ALCAR increase in a small healthy-volunteer study.
Acetyl-L-carnitine → Human plasma acetylcarnitine concentration Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_contrast
{"intervention": "Single nominal 1.5-g ALCAR dose", "comparator": "Predose baseline", "endpoint": "A nominal 1.5-g oral ALCAR dose produced a nonsignificant plasma ALCAR increase in a small healthy-volunteer study.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Open-label pharmacokinetics; ALCAR 1.5-g group n=11; Results/Fig. 2, 2025.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
A nominal 1.5-g oral ALCAR dose produced a nonsignificant plasma ALCAR increase in a small healthy-volunteer study.
primary_references
Low Bioavailability and High TMAO Production: Novel Insights Into Acetylcarnitine and Carnitine Metabolism. | https://pubmed.ncbi.nlm.nih.gov/41243468/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC12700042/ | https://doi.org/10.1002/mnfr.70316
source_locator
Reviewed reference pk-alcar-null; Median 9.4 to 12.5 micromolar, peak around 4 h. The study had no IV ALCAR reference or isotope-resolved mass balance; endogenous-pool change cannot measure absolute intact-drug bioavailability.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 112–118
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Open-label pharmacokinetics; ALCAR 1.5-g group n=11; Results/Fig. 2, 2025. · Recorded from source · Recorded from source
### pk-alcar-null A nominal 1.5-g oral ALCAR dose produced a nonsignificant plasma ALCAR increase in a small healthy-volunteer study. Median 9.4 to 12.5 micromolar, peak around 4 h. The study had no IV ALCAR reference or isotope-resolved mass balance; endogenous-pool change cannot measure absolute intact-drug bioavailability. Model and exposure: Open-label pharmacokinetics; ALCAR 1.5-g group n=11; Results/Fig. 2, 2025. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Low Bioavailability and High TMAO Production: Novel Insights Into Acetylcarnitine and Carnitine Metabolism. | 2025 | https://pubmed.ncbi.nlm.nih.gov/41243468/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC12700042/ | https://doi.org/10.1002/mnfr.70316 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
Oral L-carnitine also increased the circulating ALCAR pool in the 2025 study.
L-Carnitine → Human plasma acetylcarnitine concentration Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_contrast
{"intervention": "Single nominal 1.5-g L-carnitine dose", "comparator": "Predose baseline", "endpoint": "Oral L-carnitine also increased the circulating ALCAR pool in the 2025 study.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Healthy-volunteer open-label pharmacokinetics; carnitine 1.5-g group n=12.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Oral L-carnitine also increased the circulating ALCAR pool in the 2025 study.
primary_references
Low Bioavailability and High TMAO Production: Novel Insights Into Acetylcarnitine and Carnitine Metabolism. | https://pubmed.ncbi.nlm.nih.gov/41243468/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC12700042/ | https://doi.org/10.1002/mnfr.70316
source_locator
Reviewed reference pk-carnitine-alcar; Median ALCAR 12.1 to 20.9 micromolar at 4 h after 1.5 g carnitine. Baselines differed among groups; this is not a matched tissue-efficacy comparison.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 120–126
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Healthy-volunteer open-label pharmacokinetics; carnitine 1.5-g group n=12. · Recorded from source · Recorded from source
### pk-carnitine-alcar Oral L-carnitine also increased the circulating ALCAR pool in the 2025 study. Median ALCAR 12.1 to 20.9 micromolar at 4 h after 1.5 g carnitine. Baselines differed among groups; this is not a matched tissue-efficacy comparison. Model and exposure: Healthy-volunteer open-label pharmacokinetics; carnitine 1.5-g group n=12. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Low Bioavailability and High TMAO Production: Novel Insights Into Acetylcarnitine and Carnitine Metabolism. | 2025 | https://pubmed.ncbi.nlm.nih.gov/41243468/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC12700042/ | https://doi.org/10.1002/mnfr.70316 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
Oral ALCAR markedly increased plasma TMAO in the 2025 healthy-volunteer study.
Acetyl-L-carnitine → Human plasma TMAO after oral ALCAR Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_contrast
{"intervention": "Single nominal 1.5-g ALCAR dose", "comparator": "Predose baseline", "endpoint": "Oral ALCAR markedly increased plasma TMAO in the 2025 healthy-volunteer study.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Single nominal 1.5-g ALCAR; plasma and urine collection over 48 h.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Oral ALCAR markedly increased plasma TMAO in the 2025 healthy-volunteer study.
primary_references
Low Bioavailability and High TMAO Production: Novel Insights Into Acetylcarnitine and Carnitine Metabolism. | https://pubmed.ncbi.nlm.nih.gov/41243468/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC12700042/ | https://doi.org/10.1002/mnfr.70316
source_locator
Reviewed reference pk-tmao; Median TMAO increased approximately 2.2 to 47 micromolar; adjusted exposure was comparable to L-carnitine. The acetyl group did not prevent this metabolite signal. Cardiovascular events were not measured.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 128–134
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Single nominal 1.5-g ALCAR; plasma and urine collection over 48 h. · Recorded from source · Recorded from source
### pk-tmao Oral ALCAR markedly increased plasma TMAO in the 2025 healthy-volunteer study. Median TMAO increased approximately 2.2 to 47 micromolar; adjusted exposure was comparable to L-carnitine. The acetyl group did not prevent this metabolite signal. Cardiovascular events were not measured. Model and exposure: Single nominal 1.5-g ALCAR; plasma and urine collection over 48 h. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Low Bioavailability and High TMAO Production: Novel Insights Into Acetylcarnitine and Carnitine Metabolism. | 2025 | https://pubmed.ncbi.nlm.nih.gov/41243468/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC12700042/ | https://doi.org/10.1002/mnfr.70316 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
Antibiotic suppression of gut microbes markedly reduced TMAO production after a labeled carnitine challenge.
L-Carnitine → Human microbiome-dependent TMAO response to carnitine Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_contrast
{"intervention": "Microbiota suppression during carnitine challenge", "comparator": "Same challenge before suppression", "endpoint": "Antibiotic suppression of gut microbes markedly reduced TMAO production after a labeled carnitine challenge.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human isotope challenge before/after antibiotic suppression and recovery; Koeth et al. 2013.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Antibiotic suppression of gut microbes markedly reduced TMAO production after a labeled carnitine challenge.
primary_references
Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. | https://pubmed.ncbi.nlm.nih.gov/23563705/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC3650111/ | https://doi.org/10.1038/nm.3145
source_locator
Reviewed reference carnitine-microbiome; The intervention was L-carnitine, not ALCAR. Mouse atherosclerosis and human cardiovascular associations in the paper are separate findings; neither proves an ALCAR cardiovascular outcome.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 136–142
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Human isotope challenge before/after antibiotic suppression and recovery; Koeth et al. 2013. · Recorded from source · Recorded from source
### carnitine-microbiome Antibiotic suppression of gut microbes markedly reduced TMAO production after a labeled carnitine challenge. The intervention was L-carnitine, not ALCAR. Mouse atherosclerosis and human cardiovascular associations in the paper are separate findings; neither proves an ALCAR cardiovascular outcome. Model and exposure: Human isotope challenge before/after antibiotic suppression and recovery; Koeth et al. 2013. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. | 2013 | https://pubmed.ncbi.nlm.nih.gov/23563705/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC3650111/ | https://doi.org/10.1038/nm.3145 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
ALCAR-derived labeled acetyl groups entered acetylcholine in rat-brain preparations and coupled enzyme assays.
Acetyl-L-carnitine → Rat brain acetylcholine labeling from ALCAR Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_model
1990 coupled carnitine acetyltransferase/choline acetyltransferase systems and rat synaptosomal-membrane preparations.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR-derived labeled acetyl groups entered acetylcholine in rat-brain preparations and coupled enzyme assays.
primary_references
Acetyl-L-carnitine as a precursor of acetylcholine. | https://pubmed.ncbi.nlm.nih.gov/2215852/ | https://doi.org/10.1007/bf00973749
source_locator
Reviewed reference acetylcholine-carbon; Conversion depended on ALCAR concentration and required CoA. CHAT transfers acetyl-CoA-derived acetyl to choline; the whole carnitine molecule does not become acetylcholine.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 148–154
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · 1990 coupled carnitine acetyltransferase/choline acetyltransferase systems and rat synaptosomal-membrane preparations. · Recorded from source · Recorded from source
### acetylcholine-carbon ALCAR-derived labeled acetyl groups entered acetylcholine in rat-brain preparations and coupled enzyme assays. Conversion depended on ALCAR concentration and required CoA. CHAT transfers acetyl-CoA-derived acetyl to choline; the whole carnitine molecule does not become acetylcholine. Model and exposure: 1990 coupled carnitine acetyltransferase/choline acetyltransferase systems and rat synaptosomal-membrane preparations. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Acetyl-L-carnitine as a precursor of acetylcholine. | 1990 | https://pubmed.ncbi.nlm.nih.gov/2215852/ | https://doi.org/10.1007/bf00973749 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
Omitting CoA prevented the reported transfer of ALCAR acetyl groups into acetylcholine.
Coenzyme A → Rat brain acetylcholine labeling from ALCAR Recorded from sourceungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_condition
CoA present omitted · Coenzyme A Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
CoA present acetyl donor supplied · Acetyl-L-carnitine Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "CoA omitted from transfer system", "comparator": "CoA present", "endpoint": "Omitting CoA prevented the reported transfer of ALCAR acetyl groups into acetylcholine.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "coenzyme-a", "state": "omitted"}, {"entity_slug": "acetylcarnitine", "state": "acetyl donor supplied"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Coupled enzyme and rat-brain preparation assays; indexed primary abstract.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Omitting CoA prevented the reported transfer of ALCAR acetyl groups into acetylcholine.
primary_references
Acetyl-L-carnitine as a precursor of acetylcholine. | https://pubmed.ncbi.nlm.nih.gov/2215852/ | https://doi.org/10.1007/bf00973749
source_locator
Reviewed reference acetylcholine-coa; This is a reaction requirement. Neither choline nor acetyl substrate is established as always rate-limiting in living humans.
trigger_kind
machinery_impairment Imported condition classification; unverified.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 156–162
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Coupled enzyme and rat-brain preparation assays; indexed primary abstract. · Recorded from source · Recorded from source
### acetylcholine-coa Omitting CoA prevented the reported transfer of ALCAR acetyl groups into acetylcholine. This is a reaction requirement. Neither choline nor acetyl substrate is established as always rate-limiting in living humans. Model and exposure: Coupled enzyme and rat-brain preparation assays; indexed primary abstract. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Acetyl-L-carnitine as a precursor of acetylcholine. | 1990 | https://pubmed.ncbi.nlm.nih.gov/2215852/ | https://doi.org/10.1007/bf00973749 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
Repeated ALCAR increased pain thresholds in mouse and rat behavioral assays.
Acetyl-L-carnitine → Rodent nociceptive threshold under ALCAR Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_contrast
{"intervention": "Repeated ALCAR", "comparator": "Control treatment", "endpoint": "Repeated ALCAR increased pain thresholds in mouse and rat behavioral assays.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
100 mg/kg subcutaneous twice daily for 7 days; hot-plate, abdominal constriction and paw-pressure tests.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Repeated ALCAR increased pain thresholds in mouse and rat behavioral assays.
primary_references
Acetyl-l-carnitine induces muscarinic antinocieption in mice and rats. | https://pubmed.ncbi.nlm.nih.gov/12504925/ | https://doi.org/10.1016/s0028-3908(02)00225-3
source_locator
Reviewed reference muscarinic-pain; Atropine, M1-selective antagonists, M1 antisense and hemicholinium-3 prevented the response. These experiments support indirect cholinergic involvement, not direct ALCAR agonism or clinical analgesic efficacy.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 164–170
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · 100 mg/kg subcutaneous twice daily for 7 days; hot-plate, abdominal constriction and paw-pressure tests. · Recorded from source · Recorded from source
### muscarinic-pain Repeated ALCAR increased pain thresholds in mouse and rat behavioral assays. Atropine, M1-selective antagonists, M1 antisense and hemicholinium-3 prevented the response. These experiments support indirect cholinergic involvement, not direct ALCAR agonism or clinical analgesic efficacy. Model and exposure: 100 mg/kg subcutaneous twice daily for 7 days; hot-plate, abdominal constriction and paw-pressure tests. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Acetyl-l-carnitine induces muscarinic antinocieption in mice and rats. | 2002 | https://pubmed.ncbi.nlm.nih.gov/12504925/ | https://doi.org/10.1016/s0028-3908(02)00225-3 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
ALCAR increased p75NGFR mRNA, immunoprecipitable receptor and NGF binding in PC12 cells.
Acetyl-L-carnitine → Rat PC12 p75 neurotrophin-receptor expression Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_contrast
{"intervention": "ALCAR treatment", "comparator": "Untreated PC12 control", "endpoint": "ALCAR increased p75NGFR mRNA, immunoprecipitable receptor and NGF binding in PC12 cells.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Rat PC12 cell experiments, 1992; abstract access, dose/time not extracted.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR increased p75NGFR mRNA, immunoprecipitable receptor and NGF binding in PC12 cells.
primary_references
Stimulation of nerve growth factor receptors in PC12 by acetyl-L-carnitine. | https://pubmed.ncbi.nlm.nih.gov/1324679/ | https://doi.org/10.1016/0006-2952(92)90452-o
source_locator
Reviewed reference ngfr-expression; This concerns NGFR/p75, not an automatic claim about NTRK1/TrkA expression or direct NGF-receptor agonism.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 172–178
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Rat PC12 cell experiments, 1992; abstract access, dose/time not extracted. · Recorded from source · Recorded from source
### ngfr-expression ALCAR increased p75NGFR mRNA, immunoprecipitable receptor and NGF binding in PC12 cells. This concerns NGFR/p75, not an automatic claim about NTRK1/TrkA expression or direct NGF-receptor agonism. Model and exposure: Rat PC12 cell experiments, 1992; abstract access, dose/time not extracted. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Stimulation of nerve growth factor receptors in PC12 by acetyl-L-carnitine. | 1992 | https://pubmed.ncbi.nlm.nih.gov/1324679/ | https://doi.org/10.1016/0006-2952(92)90452-o | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
Chronic ALCAR attenuated loss of measured NMDA receptor sites in aged rat brain.
Acetyl-L-carnitine → Aged-rat NMDA receptor binding-site abundance Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_contrast
{"intervention": "Six-month ALCAR treatment", "comparator": "Aged comparison animals", "endpoint": "Chronic ALCAR attenuated loss of measured NMDA receptor sites in aged rat brain.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Twenty-four-month-old rats; ALCAR in drinking water for six months; hippocampus, frontal cortex, striatum.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Chronic ALCAR attenuated loss of measured NMDA receptor sites in aged rat brain.
primary_references
Age-dependent loss of NMDA receptors in hippocampus, striatum, and frontal cortex of the rat: prevention by acetyl-L-carnitine. | https://pubmed.ncbi.nlm.nih.gov/7969747/ | https://doi.org/10.1007/bf00967446
source_locator
Reviewed reference nmda-receptor-number; The finding is receptor-site abundance, not proof of direct receptor activation or a human cognitive benefit. Dose and subtype were not resolved from the indexed abstract.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 180–186
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Twenty-four-month-old rats; ALCAR in drinking water for six months; hippocampus, frontal cortex, striatum. · Recorded from source · Recorded from source
### nmda-receptor-number Chronic ALCAR attenuated loss of measured NMDA receptor sites in aged rat brain. The finding is receptor-site abundance, not proof of direct receptor activation or a human cognitive benefit. Dose and subtype were not resolved from the indexed abstract. Model and exposure: Twenty-four-month-old rats; ALCAR in drinking water for six months; hippocampus, frontal cortex, striatum. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Age-dependent loss of NMDA receptors in hippocampus, striatum, and frontal cortex of the rat: prevention by acetyl-L-carnitine. | 1994 | https://pubmed.ncbi.nlm.nih.gov/7969747/ | https://doi.org/10.1007/bf00967446 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
A single ALCAR exposure transiently increased Grm2 mRNA in rat dorsal-root-ganglion cultures.
Acetyl-L-carnitine → Rat DRG Grm2 transcript abundance Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_contrast
{"intervention": "250 micromolar ALCAR, 1 h", "comparator": "Vehicle culture", "endpoint": "A single ALCAR exposure transiently increased Grm2 mRNA in rat dorsal-root-ganglion cultures.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Rat primary DRG cultures; 250 micromolar ALCAR, 1 h versus 1–4 days.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
A single ALCAR exposure transiently increased Grm2 mRNA in rat dorsal-root-ganglion cultures.
primary_references
Transcriptional regulation of metabotropic glutamate receptor 2/3 expression by the NF-kappaB pathway in primary dorsal root ganglia neurons: a possible mechanism for the analgesic effect of L-acetylcarnitine. | https://pubmed.ncbi.nlm.nih.gov/16764720/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC1550235/ | https://doi.org/10.1186/1744-8069-2-20
source_locator
Reviewed reference drg-grm2; Increase was detected at 1 h and was no longer detectable at later 1–4-day measurements.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 192–198
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Rat primary DRG cultures; 250 micromolar ALCAR, 1 h versus 1–4 days. · Recorded from source · Recorded from source
### drg-grm2 A single ALCAR exposure transiently increased Grm2 mRNA in rat dorsal-root-ganglion cultures. Increase was detected at 1 h and was no longer detectable at later 1–4-day measurements. Model and exposure: Rat primary DRG cultures; 250 micromolar ALCAR, 1 h versus 1–4 days. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Transcriptional regulation of metabotropic glutamate receptor 2/3 expression by the NF-kappaB pathway in primary dorsal root ganglia neurons: a possible mechanism for the analgesic effect of L-acetylcarnitine. | 2006 | https://pubmed.ncbi.nlm.nih.gov/16764720/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC1550235/ | https://doi.org/10.1186/1744-8069-2-20 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
ALCAR did not increase Grm3 mRNA in the same DRG culture experiment.
Acetyl-L-carnitine → Rat DRG Grm3 transcript abundance Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_contrast
{"intervention": "ALCAR exposure", "comparator": "Vehicle", "endpoint": "ALCAR did not increase Grm3 mRNA in the same DRG culture experiment.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Rat primary DRG cultures; 250 micromolar ALCAR.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR did not increase Grm3 mRNA in the same DRG culture experiment.
primary_references
Transcriptional regulation of metabotropic glutamate receptor 2/3 expression by the NF-kappaB pathway in primary dorsal root ganglia neurons: a possible mechanism for the analgesic effect of L-acetylcarnitine. | https://pubmed.ncbi.nlm.nih.gov/16764720/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC1550235/ | https://doi.org/10.1186/1744-8069-2-20
source_locator
Reviewed reference drg-grm3-null;
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 200–206
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Rat primary DRG cultures; 250 micromolar ALCAR. · Recorded from source · Recorded from source
### drg-grm3-null ALCAR did not increase Grm3 mRNA in the same DRG culture experiment. Model and exposure: Rat primary DRG cultures; 250 micromolar ALCAR. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Transcriptional regulation of metabotropic glutamate receptor 2/3 expression by the NF-kappaB pathway in primary dorsal root ganglia neurons: a possible mechanism for the analgesic effect of L-acetylcarnitine. | 2006 | https://pubmed.ncbi.nlm.nih.gov/16764720/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC1550235/ | https://doi.org/10.1186/1744-8069-2-20 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
ALCAR increased p65/RelA acetylation in the DRG culture study.
Acetyl-L-carnitine → Rat DRG p65/RelA acetylation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_contrast
{"intervention": "ALCAR exposure", "comparator": "Vehicle", "endpoint": "ALCAR increased p65/RelA acetylation in the DRG culture study.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Rat primary DRG cultures; 250 micromolar exposure.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR increased p65/RelA acetylation in the DRG culture study.
primary_references
Transcriptional regulation of metabotropic glutamate receptor 2/3 expression by the NF-kappaB pathway in primary dorsal root ganglia neurons: a possible mechanism for the analgesic effect of L-acetylcarnitine. | https://pubmed.ncbi.nlm.nih.gov/16764720/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC1550235/ | https://doi.org/10.1186/1744-8069-2-20
source_locator
Reviewed reference drg-p65; Free carnitine did not reproduce the p65 acetylation or Grm2 mRNA changes. This comparison does not establish acetate equivalence or a universal carnitine/ALCAR distinction in every cell.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 208–214
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Rat primary DRG cultures; 250 micromolar exposure. · Recorded from source · Recorded from source
### drg-p65 ALCAR increased p65/RelA acetylation in the DRG culture study. Free carnitine did not reproduce the p65 acetylation or Grm2 mRNA changes. This comparison does not establish acetate equivalence or a universal carnitine/ALCAR distinction in every cell. Model and exposure: Rat primary DRG cultures; 250 micromolar exposure. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Transcriptional regulation of metabotropic glutamate receptor 2/3 expression by the NF-kappaB pathway in primary dorsal root ganglia neurons: a possible mechanism for the analgesic effect of L-acetylcarnitine. | 2006 | https://pubmed.ncbi.nlm.nih.gov/16764720/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC1550235/ | https://doi.org/10.1186/1744-8069-2-20 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
CAPE blocked the ALCAR-associated rise in Grm2 transcript in DRG cultures.
Caffeic acid phenethyl ester / CAPE → Rat DRG Grm2 transcript abundance Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_condition
ALCAR without CAPE pretreatment · Caffeic acid phenethyl ester / CAPE Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
ALCAR without CAPE 250 micromolar · Acetyl-L-carnitine Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "CAPE pretreatment plus ALCAR", "comparator": "ALCAR without CAPE", "endpoint": "CAPE blocked the ALCAR-associated rise in Grm2 transcript in DRG cultures.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "caffeic-acid-phenethyl-ester", "state": "pretreatment"}, {"entity_slug": "acetylcarnitine", "state": "250 micromolar"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
CAPE 2.5 micrograms/mL for 30 min before 250 micromolar ALCAR; 1-h transcript measurement.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
CAPE blocked the ALCAR-associated rise in Grm2 transcript in DRG cultures.
primary_references
Transcriptional regulation of metabotropic glutamate receptor 2/3 expression by the NF-kappaB pathway in primary dorsal root ganglia neurons: a possible mechanism for the analgesic effect of L-acetylcarnitine. | https://pubmed.ncbi.nlm.nih.gov/16764720/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC1550235/ | https://doi.org/10.1186/1744-8069-2-20
source_locator
Reviewed reference drg-cape; Pharmacological NF-kappaB inhibition is not a selective genetic test of one acetylation site.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 216–222
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · CAPE 2.5 micrograms/mL for 30 min before 250 micromolar ALCAR; 1-h transcript measurement. · Recorded from source · Recorded from source
### drg-cape CAPE blocked the ALCAR-associated rise in Grm2 transcript in DRG cultures. Pharmacological NF-kappaB inhibition is not a selective genetic test of one acetylation site. Model and exposure: CAPE 2.5 micrograms/mL for 30 min before 250 micromolar ALCAR; 1-h transcript measurement. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Transcriptional regulation of metabotropic glutamate receptor 2/3 expression by the NF-kappaB pathway in primary dorsal root ganglia neurons: a possible mechanism for the analgesic effect of L-acetylcarnitine. | 2006 | https://pubmed.ncbi.nlm.nih.gov/16764720/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC1550235/ | https://doi.org/10.1186/1744-8069-2-20 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
ALCAR increased acetylated p65 in Flinders Sensitive Line rats, without the same increase in control FRL rats.
Acetyl-L-carnitine → Rat FSL hippocampal/prefrontal p65 K310 acetylation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_contrast
{"intervention": "ALCAR in FSL and FRL animals", "comparator": "Corresponding saline-treated strain", "endpoint": "ALCAR increased acetylated p65 in Flinders Sensitive Line rats, without the same increase in control FRL rats.", "effect_direction": "mixed", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
100 mg/kg intraperitoneal daily; 21-day biochemical comparison; Fig. 3C, anti-acetyl-K310-p65 assay.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR increased acetylated p65 in Flinders Sensitive Line rats, without the same increase in control FRL rats.
primary_references
L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors. | https://pubmed.ncbi.nlm.nih.gov/23382250/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC3607061/ | https://doi.org/10.1073/pnas.1216100110
source_locator
Reviewed reference fsl-p65; H3K27 promoter enrichment and p65 acetylation are distinct measurements. The study did not trace administered ALCAR acetyl atoms into these sites.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 224–230
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · 100 mg/kg intraperitoneal daily; 21-day biochemical comparison; Fig. 3C, anti-acetyl-K310-p65 assay. · Recorded from source · Recorded from source
### fsl-p65 ALCAR increased acetylated p65 in Flinders Sensitive Line rats, without the same increase in control FRL rats. H3K27 promoter enrichment and p65 acetylation are distinct measurements. The study did not trace administered ALCAR acetyl atoms into these sites. Model and exposure: 100 mg/kg intraperitoneal daily; 21-day biochemical comparison; Fig. 3C, anti-acetyl-K310-p65 assay. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors. | 2013 | https://pubmed.ncbi.nlm.nih.gov/23382250/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC3607061/ | https://doi.org/10.1073/pnas.1216100110 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
Sodium salicylate prevented ALCAR-induced mGlu2 protein upregulation in FSL rats.
Sodium salicylate → Rat metabotropic glutamate receptor 2 / Grm2 Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_condition
ALCAR alone 50 mg/kg · Sodium salicylate Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
ALCAR alone 100 mg/kg · Acetyl-L-carnitine Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "Salicylate plus ALCAR", "comparator": "ALCAR alone", "endpoint": "Sodium salicylate prevented ALCAR-induced mGlu2 protein upregulation in FSL rats.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "sodium-salicylate", "state": "50 mg/kg"}, {"entity_slug": "acetylcarnitine", "state": "100 mg/kg"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Salicylate 50 mg/kg intraperitoneal with ALCAR 100 mg/kg intraperitoneal for 21 days; Fig. 3D.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Sodium salicylate prevented ALCAR-induced mGlu2 protein upregulation in FSL rats.
primary_references
L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors. | https://pubmed.ncbi.nlm.nih.gov/23382250/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC3607061/ | https://doi.org/10.1073/pnas.1216100110
source_locator
Reviewed reference fsl-salicylate; The inhibitor was nonselective. This does not establish an ordinary aspirin-food interaction or prove acetyl-group provenance.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 232–238
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Salicylate 50 mg/kg intraperitoneal with ALCAR 100 mg/kg intraperitoneal for 21 days; Fig. 3D. · Recorded from source · Recorded from source
### fsl-salicylate Sodium salicylate prevented ALCAR-induced mGlu2 protein upregulation in FSL rats. The inhibitor was nonselective. This does not establish an ordinary aspirin-food interaction or prove acetyl-group provenance. Model and exposure: Salicylate 50 mg/kg intraperitoneal with ALCAR 100 mg/kg intraperitoneal for 21 days; Fig. 3D. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors. | 2013 | https://pubmed.ncbi.nlm.nih.gov/23382250/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC3607061/ | https://doi.org/10.1073/pnas.1216100110 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
ALCAR reduced immobility and increased sucrose preference in the reported FSL rat model.
Acetyl-L-carnitine → Rat FSL immobility and sucrose-preference readouts Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_contrast
{"intervention": "ALCAR treatment", "comparator": "Saline-treated FSL rats", "endpoint": "ALCAR reduced immobility and increased sucrose preference in the reported FSL rat model.", "effect_direction": "mixed", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
100 mg/kg intraperitoneal; early response at 3 days, followed through treatment and withdrawal.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR reduced immobility and increased sucrose preference in the reported FSL rat model.
primary_references
L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors. | https://pubmed.ncbi.nlm.nih.gov/23382250/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC3607061/ | https://doi.org/10.1073/pnas.1216100110
source_locator
Reviewed reference fsl-behavior; Reported persistence after withdrawal is a rodent behavioral observation, not a demonstrated three-day human antidepressant response.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 240–246
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · 100 mg/kg intraperitoneal; early response at 3 days, followed through treatment and withdrawal. · Recorded from source · Recorded from source
### fsl-behavior ALCAR reduced immobility and increased sucrose preference in the reported FSL rat model. Reported persistence after withdrawal is a rodent behavioral observation, not a demonstrated three-day human antidepressant response. Model and exposure: 100 mg/kg intraperitoneal; early response at 3 days, followed through treatment and withdrawal. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors. | 2013 | https://pubmed.ncbi.nlm.nih.gov/23382250/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC3607061/ | https://doi.org/10.1073/pnas.1216100110 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
ALCAR still increased histone acetylation when ACLY and Crat were absent and ACSS2 was inhibited.
Acetyl-L-carnitine → Mouse HCC-cell histone acetylation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_condition
Matched perturbed cells without ALCAR deleted · Mouse carnitine acetyltransferase / Crat Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
Matched perturbed cells without ALCAR deleted · Mouse ATP-citrate lyase / Acly Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
Matched perturbed cells without ALCAR supplied · Acetyl-L-carnitine Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
Matched perturbed cells without ALCAR inhibited · Mouse acyl-CoA synthetase short-chain family member 2 / Acss2 Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "ALCAR in ACLY/CrAT-deficient cells with ACSS2 inhibition", "comparator": "Matched perturbed cells without ALCAR", "endpoint": "ALCAR still increased histone acetylation when ACLY and Crat were absent and ACSS2 was inhibited.", "effect_direction": "increase", "combination": "joint", "conditions": [{"entity_slug": "acetylcarnitine", "state": "supplied"}, {"entity_slug": "mouse-acly", "state": "deleted"}, {"entity_slug": "mouse-crat", "state": "deleted"}, {"entity_slug": "mouse-acss2", "state": "inhibited"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse HCC cells; ACLY/CrAT knockout plus ACSS2 inhibitor; Fig. 7F and supplementary S8I.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR still increased histone acetylation when ACLY and Crat were absent and ACSS2 was inhibited.
primary_references
Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. | https://pubmed.ncbi.nlm.nih.gov/37134161/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC10156126/ | https://doi.org/10.1126/sciadv.adf0115
source_locator
Reviewed reference hcc-crat-independent; ACSS2 inhibition slightly suppressed the response but did not abolish it. This is a bypass in a perturbed cancer-cell model, not proof that all ALCAR use bypasses these enzymes.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 252–258
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Mouse HCC cells; ACLY/CrAT knockout plus ACSS2 inhibitor; Fig. 7F and supplementary S8I. · Recorded from source · Recorded from source
### hcc-crat-independent ALCAR still increased histone acetylation when ACLY and Crat were absent and ACSS2 was inhibited. ACSS2 inhibition slightly suppressed the response but did not abolish it. This is a bypass in a perturbed cancer-cell model, not proof that all ALCAR use bypasses these enzymes. Model and exposure: Mouse HCC cells; ACLY/CrAT knockout plus ACSS2 inhibitor; Fig. 7F and supplementary S8I. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. | 2023 | https://pubmed.ncbi.nlm.nih.gov/37134161/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC10156126/ | https://doi.org/10.1126/sciadv.adf0115 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
CrAT-null HCC-cell lysates retained enzyme-dependent conversion of ALCAR plus CoA to acetyl-CoA.
Acetyl-L-carnitine → Mouse HCC-lysate acetyl-CoA formation from ALCAR Recorded from sourceungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_model
Wild-type, ACLY-null and ACLY/CrAT-null cell lysates; Fig. 7H.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
CrAT-null HCC-cell lysates retained enzyme-dependent conversion of ALCAR plus CoA to acetyl-CoA.
primary_references
Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. | https://pubmed.ncbi.nlm.nih.gov/37134161/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC10156126/ | https://doi.org/10.1126/sciadv.adf0115
source_locator
Reviewed reference hcc-lysate-conversion; Boiled lysates failed to generate acetyl-CoA. This establishes residual catalytic capacity without identifying a universal cytosolic catalyst.
trigger_kind
machinery_impairment Imported condition classification; unverified.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 260–266
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Wild-type, ACLY-null and ACLY/CrAT-null cell lysates; Fig. 7H. · Recorded from source · Recorded from source
### hcc-lysate-conversion CrAT-null HCC-cell lysates retained enzyme-dependent conversion of ALCAR plus CoA to acetyl-CoA. Boiled lysates failed to generate acetyl-CoA. This establishes residual catalytic capacity without identifying a universal cytosolic catalyst. Model and exposure: Wild-type, ACLY-null and ACLY/CrAT-null cell lysates; Fig. 7H. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. | 2023 | https://pubmed.ncbi.nlm.nih.gov/37134161/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC10156126/ | https://doi.org/10.1126/sciadv.adf0115 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
p300/CBP inhibition blocked the ALCAR-associated proliferation rescue in lipid-depleted ACLY/ACSS2-null HCC cells.
A-485 p300/CBP catalytic inhibitor → Mouse HCC proliferation rescued by acetylcarnitine Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_condition
ALCAR-treated double-knockout cells without A-485 deleted · Mouse ATP-citrate lyase / Acly Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
ALCAR-treated double-knockout cells without A-485 present · Acetyl-L-carnitine Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
ALCAR-treated double-knockout cells without A-485 present · A-485 p300/CBP catalytic inhibitor Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
ALCAR-treated double-knockout cells without A-485 deleted · Mouse acyl-CoA synthetase short-chain family member 2 / Acss2 Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "A-485 plus ALCAR in lipid-depleted double-knockout cells", "comparator": "ALCAR-treated double-knockout cells without A-485", "endpoint": "p300/CBP inhibition blocked the ALCAR-associated proliferation rescue in lipid-depleted ACLY/ACSS2-null HCC cells.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "a-485", "state": "present"}, {"entity_slug": "acetylcarnitine", "state": "present"}, {"entity_slug": "mouse-acly", "state": "deleted"}, {"entity_slug": "mouse-acss2", "state": "deleted"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse HCC cells; A-485; Fig. 6G–H.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
p300/CBP inhibition blocked the ALCAR-associated proliferation rescue in lipid-depleted ACLY/ACSS2-null HCC cells.
primary_references
Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. | https://pubmed.ncbi.nlm.nih.gov/37134161/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC10156126/ | https://doi.org/10.1126/sciadv.adf0115
source_locator
Reviewed reference hcc-p300-block; A-485 suppressed H3K27 acetylation but not H3K23 acetylation in this comparison. ACC inhibition did not block the growth rescue, separating acetylation from obligatory de novo lipogenesis.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 268–274
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Mouse HCC cells; A-485; Fig. 6G–H. · Recorded from source · Recorded from source
### hcc-p300-block p300/CBP inhibition blocked the ALCAR-associated proliferation rescue in lipid-depleted ACLY/ACSS2-null HCC cells. A-485 suppressed H3K27 acetylation but not H3K23 acetylation in this comparison. ACC inhibition did not block the growth rescue, separating acetylation from obligatory de novo lipogenesis. Model and exposure: Mouse HCC cells; A-485; Fig. 6G–H. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. | 2023 | https://pubmed.ncbi.nlm.nih.gov/37134161/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC10156126/ | https://doi.org/10.1126/sciadv.adf0115 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
ALCAR supplementation did not change measured fatty-acid abundance across the tested HCC genotypes.
Acetyl-L-carnitine → Mouse HCC fatty-acid abundance Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_contrast
{"intervention": "ALCAR supplementation", "comparator": "Corresponding unsupplemented genotype", "endpoint": "ALCAR supplementation did not change measured fatty-acid abundance across the tested HCC genotypes.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse HCC, wild-type/ACLY-null/ACLY-ACSS2-null; supplementary S7H–I described in Results.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR supplementation did not change measured fatty-acid abundance across the tested HCC genotypes.
primary_references
Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. | https://pubmed.ncbi.nlm.nih.gov/37134161/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC10156126/ | https://doi.org/10.1126/sciadv.adf0115
source_locator
Reviewed reference hcc-fatty-acid-pool-null; A change in isotope labeling or synthesis contribution is not necessarily an increase in total fatty-acid abundance.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 276–282
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Mouse HCC, wild-type/ACLY-null/ACLY-ACSS2-null; supplementary S7H–I described in Results. · Recorded from source · Recorded from source
### hcc-fatty-acid-pool-null ALCAR supplementation did not change measured fatty-acid abundance across the tested HCC genotypes. A change in isotope labeling or synthesis contribution is not necessarily an increase in total fatty-acid abundance. Model and exposure: Mouse HCC, wild-type/ACLY-null/ACLY-ACSS2-null; supplementary S7H–I described in Results. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis. | 2023 | https://pubmed.ncbi.nlm.nih.gov/37134161/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC10156126/ | https://doi.org/10.1126/sciadv.adf0115 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
TMLHE knockdown reduced histone acetylation and nuclear acetyl-CoA in the 2026 cancer-cell study.
Trimethyllysine hydroxylase / TMLHE → Human cancer-cell histone acetylation Recorded from sourceungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_contrast
{"intervention": "TMLHE knockdown", "comparator": "Control shRNA", "endpoint": "TMLHE knockdown reduced histone acetylation and nuclear acetyl-CoA in the 2026 cancer-cell study.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human FT282-CCNE1 and Ovcar8-CCNE1 models; Fig. 3g,j.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
TMLHE knockdown reduced histone acetylation and nuclear acetyl-CoA in the 2026 cancer-cell study.
primary_references
αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7
source_locator
Reviewed reference tmlhe-histone-loss; L-carnitine or ALCAR rescued acetylation downstream of TMLHE loss; alpha-ketoglutarate did not. This distinguishes a blocked enzyme step from insufficient upstream cosubstrate.
trigger_kind
machinery_impairment Imported condition classification; unverified.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 288–294
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Human FT282-CCNE1 and Ovcar8-CCNE1 models; Fig. 3g,j. · Recorded from source · Recorded from source
### tmlhe-histone-loss TMLHE knockdown reduced histone acetylation and nuclear acetyl-CoA in the 2026 cancer-cell study. L-carnitine or ALCAR rescued acetylation downstream of TMLHE loss; alpha-ketoglutarate did not. This distinguishes a blocked enzyme step from insufficient upstream cosubstrate. Model and exposure: Human FT282-CCNE1 and Ovcar8-CCNE1 models; Fig. 3g,j. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | 2026 | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
ALCAR restored histone acetylation after CRAT knockdown, whereas L-carnitine did not, in the 2026 cancer models.
Acetyl-L-carnitine → Human cancer-cell histone acetylation Recorded from sourceungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_condition
CRAT-knockdown cells without ALCAR knocked down · Human carnitine acetyltransferase / CRAT Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
CRAT-knockdown cells without ALCAR supplied · Acetyl-L-carnitine Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "ALCAR added after CRAT knockdown", "comparator": "CRAT-knockdown cells without ALCAR", "endpoint": "ALCAR restored histone acetylation after CRAT knockdown, whereas L-carnitine did not, in the 2026 cancer models.", "effect_direction": "increase", "combination": "joint", "conditions": [{"entity_slug": "acetylcarnitine", "state": "supplied"}, {"entity_slug": "human-crat", "state": "knocked down"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human cancer-cell CRAT knockdown; Extended Data Fig. 6c.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR restored histone acetylation after CRAT knockdown, whereas L-carnitine did not, in the 2026 cancer models.
primary_references
αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7
source_locator
Reviewed reference cancer-crat-bypass; Supplying the acetylated product bypassed this perturbation under the tested conditions. The result does not establish a neuron-wide pathway.
trigger_kind
machinery_impairment Imported condition classification; unverified.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 296–302
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Human cancer-cell CRAT knockdown; Extended Data Fig. 6c. · Recorded from source · Recorded from source
### cancer-crat-bypass ALCAR restored histone acetylation after CRAT knockdown, whereas L-carnitine did not, in the 2026 cancer models. Supplying the acetylated product bypassed this perturbation under the tested conditions. The result does not establish a neuron-wide pathway. Model and exposure: Human cancer-cell CRAT knockdown; Extended Data Fig. 6c. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | 2026 | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
ALCAR failed to restore histone acetylation after CROT knockdown in the 2026 cancer models.
Acetyl-L-carnitine → Human cancer-cell histone acetylation Recorded from sourceungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_condition
CROT-knockdown cells without added ALCAR supplied · Acetyl-L-carnitine Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
CROT-knockdown cells without added ALCAR knocked down · Human carnitine octanoyltransferase / CROT Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "ALCAR added after CROT knockdown", "comparator": "CROT-knockdown cells without added ALCAR", "endpoint": "ALCAR failed to restore histone acetylation after CROT knockdown in the 2026 cancer models.", "effect_direction": "no_detected_change", "combination": "joint", "conditions": [{"entity_slug": "acetylcarnitine", "state": "supplied"}, {"entity_slug": "human-crot", "state": "knocked down"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human cancer-cell CROT knockdown; Extended Data Fig. 6d.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR failed to restore histone acetylation after CROT knockdown in the 2026 cancer models.
primary_references
αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7
source_locator
Reviewed reference cancer-crot-no-bypass; The result implicates CROT-dependent processing in this setting; it does not mean that CROT is the only enzyme capable of using ALCAR in all tissues.
trigger_kind
machinery_impairment Imported condition classification; unverified.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 304–310
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Human cancer-cell CROT knockdown; Extended Data Fig. 6d. · Recorded from source · Recorded from source
### cancer-crot-no-bypass ALCAR failed to restore histone acetylation after CROT knockdown in the 2026 cancer models. The result implicates CROT-dependent processing in this setting; it does not mean that CROT is the only enzyme capable of using ALCAR in all tissues. Model and exposure: Human cancer-cell CROT knockdown; Extended Data Fig. 6d. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | 2026 | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
Labeled ALCAR supplied approximately 5–8% of measured cellular acetyl-CoA in the 2026 tracing experiment.
Acetyl-L-carnitine → Human cancer-cell acetyl-CoA labeling from ALCAR Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_model
13C2-acetylcarnitine tracing; Extended Data Fig. 6a.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Labeled ALCAR supplied approximately 5–8% of measured cellular acetyl-CoA in the 2026 tracing experiment.
primary_references
αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7
source_locator
Reviewed reference cancer-labeling; A fraction of a measured pool is not a whole-body uptake percentage or a flux independent of labeling time. It cannot be extrapolated to oral dosing.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 312–318
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · 13C2-acetylcarnitine tracing; Extended Data Fig. 6a. · Recorded from source · Recorded from source
### cancer-labeling Labeled ALCAR supplied approximately 5–8% of measured cellular acetyl-CoA in the 2026 tracing experiment. A fraction of a measured pool is not a whole-body uptake percentage or a flux independent of labeling time. It cannot be extrapolated to oral dosing. Model and exposure: 13C2-acetylcarnitine tracing; Extended Data Fig. 6a. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | 2026 | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
ALCAR acetyl carbon was traced into H3K23ac, H4K8ac and H4K12ac in the 2026 cancer-cell study.
Acetyl-L-carnitine → Human cancer-cell H3K23/H4K8/H4K12 acetyl carbon Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_model
Stable-isotope tracing, Extended Data Fig. 8e; site-specific histone mass spectrometry.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR acetyl carbon was traced into H3K23ac, H4K8ac and H4K12ac in the 2026 cancer-cell study.
primary_references
αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7
source_locator
Reviewed reference cancer-histone-sites; These marks were sensitive to the alpha-ketoglutarate/TMLHE/carnitine axis. They are not the same promoter-specific H3K27 readout measured in the rat depression study.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 320–326
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Stable-isotope tracing, Extended Data Fig. 8e; site-specific histone mass spectrometry. · Recorded from source · Recorded from source
### cancer-histone-sites ALCAR acetyl carbon was traced into H3K23ac, H4K8ac and H4K12ac in the 2026 cancer-cell study. These marks were sensitive to the alpha-ketoglutarate/TMLHE/carnitine axis. They are not the same promoter-specific H3K27 readout measured in the rat depression study. Model and exposure: Stable-isotope tracing, Extended Data Fig. 8e; site-specific histone mass spectrometry. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | 2026 | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
ALCAR did not rescue DNA-damage sensitivity when histone acetyltransferase activity was inhibited.
Acetyl-L-carnitine → Human cancer-cell survival with DNA-damaging treatment Recorded from sourceungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_contrast
{"intervention": "ALCAR plus HAT inhibition and DNA-damaging treatment", "comparator": "Same HAT inhibition and DNA-damaging treatment without ALCAR", "endpoint": "ALCAR did not rescue DNA-damage sensitivity when histone acetyltransferase activity was inhibited.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
CCNE1-driven human cell models; HAT inhibition plus DNA-damaging agents; Extended Data Fig. 5.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR did not rescue DNA-damage sensitivity when histone acetyltransferase activity was inhibited.
primary_references
αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7
source_locator
Reviewed reference cancer-hat-no-rescue; Supplying substrate failed when downstream acetylation machinery was blocked. The tested HAT inhibitor and individual drug concentrations are not fully extracted here; no universal inhibitor equivalence is asserted.
trigger_kind
machinery_impairment Imported condition classification; unverified.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 328–334
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · CCNE1-driven human cell models; HAT inhibition plus DNA-damaging agents; Extended Data Fig. 5. · Recorded from source · Recorded from source
### cancer-hat-no-rescue ALCAR did not rescue DNA-damage sensitivity when histone acetyltransferase activity was inhibited. Supplying substrate failed when downstream acetylation machinery was blocked. The tested HAT inhibitor and individual drug concentrations are not fully extracted here; no universal inhibitor equivalence is asserted. Model and exposure: CCNE1-driven human cell models; HAT inhibition plus DNA-damaging agents; Extended Data Fig. 5. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | 2026 | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
ALCAR reversed increased sensitivity to DNA-damaging agents caused by disruption of the alpha-ketoglutarate–carnitine axis.
Acetyl-L-carnitine → Human cancer-cell survival with DNA-damaging treatment Recorded from sourceungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_model
Human HR-proficient CCNE1 cancer-cell models; Results and supplementary Fig. 3.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR reversed increased sensitivity to DNA-damaging agents caused by disruption of the alpha-ketoglutarate–carnitine axis.
primary_references
αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7
source_locator
Reviewed reference cancer-drug-rescue; The study tested distinct upstream restrictions including IDH1 inhibition, glutamine starvation and TMLHE knockdown. Propionylcarnitine and butyrylcarnitine did not reproduce this rescue. This is a context-qualified summary of rescue contrasts, not an isolated basal ALCAR effect.
trigger_kind
machinery_impairment Imported condition classification; unverified.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 336–342
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Human HR-proficient CCNE1 cancer-cell models; Results and supplementary Fig. 3. · Recorded from source · Recorded from source
### cancer-drug-rescue ALCAR reversed increased sensitivity to DNA-damaging agents caused by disruption of the alpha-ketoglutarate–carnitine axis. The study tested distinct upstream restrictions including IDH1 inhibition, glutamine starvation and TMLHE knockdown. Propionylcarnitine and butyrylcarnitine did not reproduce this rescue. This is a context-qualified summary of rescue contrasts, not an isolated basal ALCAR effect. Model and exposure: Human HR-proficient CCNE1 cancer-cell models; Results and supplementary Fig. 3. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | 2026 | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
ALCAR restored impaired RAD51-foci responses under IDH1-inhibited DNA-repair conditions.
Acetyl-L-carnitine → Human cancer-cell RAD51 repair foci Recorded from sourceungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_contrast
{"intervention": "ALCAR plus IDH1 inhibition", "comparator": "IDH1 inhibition without ALCAR", "endpoint": "ALCAR restored impaired RAD51-foci responses under IDH1-inhibited DNA-repair conditions.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human U2OS inducible double-strand-break system; Fig. 4h. Methods: ALCAR 1 mM, GSK864 10 micromolar for five days before induced breaks.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR restored impaired RAD51-foci responses under IDH1-inhibited DNA-repair conditions.
primary_references
αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7
source_locator
Reviewed reference cancer-rad51-rescue; RAD51 recruitment is a repair readout, not proof that ALCAR prevents cancer or that a dietary dose changes tumor survival.
trigger_kind
machinery_impairment Imported condition classification; unverified.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 344–350
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Human U2OS inducible double-strand-break system; Fig. 4h. Methods: ALCAR 1 mM, GSK864 10 micromolar for five days before induced breaks. · Recorded from source · Recorded from source
### cancer-rad51-rescue ALCAR restored impaired RAD51-foci responses under IDH1-inhibited DNA-repair conditions. RAD51 recruitment is a repair readout, not proof that ALCAR prevents cancer or that a dietary dose changes tumor survival. Model and exposure: Human U2OS inducible double-strand-break system; Fig. 4h. Methods: ALCAR 1 mM, GSK864 10 micromolar for five days before induced breaks. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | 2026 | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
Higher serum ALCAR was associated with shorter progression-free survival in the reported ovarian-cancer cohort.
Human plasma acetylcarnitine concentration → Ovarian-cancer progression-free survival associated with serum ALCAR Recorded from sourceungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_model
Patient serum upper-versus-lower quartile analysis; Fig. 5h; log-rank HR 2.439, P=0.0364.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Higher serum ALCAR was associated with shorter progression-free survival in the reported ovarian-cancer cohort.
primary_references
αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7
source_locator
Reviewed reference cancer-serum-association; Observational association, not an ALCAR supplementation trial. Tumor metabolism, disease burden and other factors may influence circulating ALCAR. No causal direction from the blood measurement is established.
trigger_kind
biomarker_context Imported condition classification; unverified.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 352–358
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Patient serum upper-versus-lower quartile analysis; Fig. 5h; log-rank HR 2.439, P=0.0364. · Recorded from source · Recorded from source
### cancer-serum-association Higher serum ALCAR was associated with shorter progression-free survival in the reported ovarian-cancer cohort. Observational association, not an ALCAR supplementation trial. Tumor metabolism, disease burden and other factors may influence circulating ALCAR. No causal direction from the blood measurement is established. Model and exposure: Patient serum upper-versus-lower quartile analysis; Fig. 5h; log-rank HR 2.439, P=0.0364. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | 2026 | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
Chronic ALCAR increased cortical phosphocreatine and its ratio to creatine in healthy mice.
Acetyl-L-carnitine → Mouse cortical phosphocreatine/creatine ratio Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_contrast
{"intervention": "Chronic ALCAR", "comparator": "Untreated control mice", "endpoint": "Chronic ALCAR increased cortical phosphocreatine and its ratio to creatine in healthy mice.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Healthy mice; approximately 0.5 g/kg/day in drinking water for 25 days, followed by 13C-glucose tracing.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Chronic ALCAR increased cortical phosphocreatine and its ratio to creatine in healthy mice.
primary_references
Chronic acetyl-L-carnitine alters brain energy metabolism and increases noradrenaline and serotonin content in healthy mice. | https://pubmed.ncbi.nlm.nih.gov/22549035/ | https://doi.org/10.1016/j.neuint.2012.04.008
source_locator
Reviewed reference mouse-pcr; A pool and ratio measurement does not identify a single creatine-kinase flux.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 364–370
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Healthy mice; approximately 0.5 g/kg/day in drinking water for 25 days, followed by 13C-glucose tracing. · Recorded from source · Recorded from source
### mouse-pcr Chronic ALCAR increased cortical phosphocreatine and its ratio to creatine in healthy mice. A pool and ratio measurement does not identify a single creatine-kinase flux. Model and exposure: Healthy mice; approximately 0.5 g/kg/day in drinking water for 25 days, followed by 13C-glucose tracing. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Chronic acetyl-L-carnitine alters brain energy metabolism and increases noradrenaline and serotonin content in healthy mice. | 2012 | https://pubmed.ncbi.nlm.nih.gov/22549035/ | https://doi.org/10.1016/j.neuint.2012.04.008 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
Chronic ALCAR increased hippocampal noradrenaline content in healthy mice.
Acetyl-L-carnitine → Mouse hippocampal noradrenaline content Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_contrast
{"intervention": "Chronic ALCAR", "comparator": "Untreated control mice", "endpoint": "Chronic ALCAR increased hippocampal noradrenaline content in healthy mice.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Healthy mice; approximately 0.5 g/kg/day in drinking water for 25 days, followed by 13C-glucose tracing.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Chronic ALCAR increased hippocampal noradrenaline content in healthy mice.
primary_references
Chronic acetyl-L-carnitine alters brain energy metabolism and increases noradrenaline and serotonin content in healthy mice. | https://pubmed.ncbi.nlm.nih.gov/22549035/ | https://doi.org/10.1016/j.neuint.2012.04.008
source_locator
Reviewed reference mouse-ne; Tissue content is not release or receptor activation.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 372–378
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Healthy mice; approximately 0.5 g/kg/day in drinking water for 25 days, followed by 13C-glucose tracing. · Recorded from source · Recorded from source
### mouse-ne Chronic ALCAR increased hippocampal noradrenaline content in healthy mice. Tissue content is not release or receptor activation. Model and exposure: Healthy mice; approximately 0.5 g/kg/day in drinking water for 25 days, followed by 13C-glucose tracing. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Chronic acetyl-L-carnitine alters brain energy metabolism and increases noradrenaline and serotonin content in healthy mice. | 2012 | https://pubmed.ncbi.nlm.nih.gov/22549035/ | https://doi.org/10.1016/j.neuint.2012.04.008 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
Chronic ALCAR increased cortical serotonin content in healthy mice.
Acetyl-L-carnitine → Mouse cortical serotonin content Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_contrast
{"intervention": "Chronic ALCAR", "comparator": "Untreated control mice", "endpoint": "Chronic ALCAR increased cortical serotonin content in healthy mice.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Healthy mice; approximately 0.5 g/kg/day in drinking water for 25 days, followed by 13C-glucose tracing.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Chronic ALCAR increased cortical serotonin content in healthy mice.
primary_references
Chronic acetyl-L-carnitine alters brain energy metabolism and increases noradrenaline and serotonin content in healthy mice. | https://pubmed.ncbi.nlm.nih.gov/22549035/ | https://doi.org/10.1016/j.neuint.2012.04.008
source_locator
Reviewed reference mouse-serotonin; This is not proof of clinical antidepressant efficacy.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 380–386
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Healthy mice; approximately 0.5 g/kg/day in drinking water for 25 days, followed by 13C-glucose tracing. · Recorded from source · Recorded from source
### mouse-serotonin Chronic ALCAR increased cortical serotonin content in healthy mice. This is not proof of clinical antidepressant efficacy. Model and exposure: Healthy mice; approximately 0.5 g/kg/day in drinking water for 25 days, followed by 13C-glucose tracing. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Chronic acetyl-L-carnitine alters brain energy metabolism and increases noradrenaline and serotonin content in healthy mice. | 2012 | https://pubmed.ncbi.nlm.nih.gov/22549035/ | https://doi.org/10.1016/j.neuint.2012.04.008 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
Chronic ALCAR reduced hippocampal GABA content in the healthy-mouse study.
Acetyl-L-carnitine → Mouse hippocampal GABA content Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_contrast
{"intervention": "Chronic ALCAR", "comparator": "Untreated control mice", "endpoint": "Chronic ALCAR reduced hippocampal GABA content in the healthy-mouse study.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Healthy mice; approximately 0.5 g/kg/day in drinking water for 25 days, followed by 13C-glucose tracing.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Chronic ALCAR reduced hippocampal GABA content in the healthy-mouse study.
primary_references
Chronic acetyl-L-carnitine alters brain energy metabolism and increases noradrenaline and serotonin content in healthy mice. | https://pubmed.ncbi.nlm.nih.gov/22549035/ | https://doi.org/10.1016/j.neuint.2012.04.008
source_locator
Reviewed reference mouse-gaba; A different direction for a distinct neurotransmitter is retained.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 388–394
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Healthy mice; approximately 0.5 g/kg/day in drinking water for 25 days, followed by 13C-glucose tracing. · Recorded from source · Recorded from source
### mouse-gaba Chronic ALCAR reduced hippocampal GABA content in the healthy-mouse study. A different direction for a distinct neurotransmitter is retained. Model and exposure: Healthy mice; approximately 0.5 g/kg/day in drinking water for 25 days, followed by 13C-glucose tracing. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Chronic acetyl-L-carnitine alters brain energy metabolism and increases noradrenaline and serotonin content in healthy mice. | 2012 | https://pubmed.ncbi.nlm.nih.gov/22549035/ | https://doi.org/10.1016/j.neuint.2012.04.008 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
Chronic ALCAR did not change glucose-derived labeling of glutamate, GABA or glutamine in the reported mouse experiment.
Acetyl-L-carnitine → Mouse brain glucose-derived amino-acid labeling Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_contrast
{"intervention": "Chronic ALCAR", "comparator": "Untreated control mice", "endpoint": "Chronic ALCAR did not change glucose-derived labeling of glutamate, GABA or glutamine in the reported mouse experiment.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Healthy mice; approximately 0.5 g/kg/day in drinking water for 25 days, followed by 13C-glucose tracing.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Chronic ALCAR did not change glucose-derived labeling of glutamate, GABA or glutamine in the reported mouse experiment.
primary_references
Chronic acetyl-L-carnitine alters brain energy metabolism and increases noradrenaline and serotonin content in healthy mice. | https://pubmed.ncbi.nlm.nih.gov/22549035/ | https://doi.org/10.1016/j.neuint.2012.04.008
source_locator
Reviewed reference mouse-glucose-label-null; This limits a blanket claim that ALCAR uniformly increases TCA-cycle neurotransmitter labeling.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 396–402
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Healthy mice; approximately 0.5 g/kg/day in drinking water for 25 days, followed by 13C-glucose tracing. · Recorded from source · Recorded from source
### mouse-glucose-label-null Chronic ALCAR did not change glucose-derived labeling of glutamate, GABA or glutamine in the reported mouse experiment. This limits a blanket claim that ALCAR uniformly increases TCA-cycle neurotransmitter labeling. Model and exposure: Healthy mice; approximately 0.5 g/kg/day in drinking water for 25 days, followed by 13C-glucose tracing. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Chronic acetyl-L-carnitine alters brain energy metabolism and increases noradrenaline and serotonin content in healthy mice. | 2012 | https://pubmed.ncbi.nlm.nih.gov/22549035/ | https://doi.org/10.1016/j.neuint.2012.04.008 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
ALCAR treatment restored depressed cardiac cytochrome oxidase activity in aged rats.
Acetyl-L-carnitine → Aged-rat cardiac complex IV activity Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_contrast
{"intervention": "ALCAR treatment of aged rats", "comparator": "Untreated aged rats", "endpoint": "ALCAR treatment restored depressed cardiac cytochrome oxidase activity in aged rats.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Aged-rat heart mitochondrial preparation; indexed primary abstract, dose/time not extracted.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR treatment restored depressed cardiac cytochrome oxidase activity in aged rats.
primary_references
Effect of aging and acetyl-L-carnitine on the activity of cytochrome oxidase and adenine nucleotide translocase in rat heart mitochondria. | https://pubmed.ncbi.nlm.nih.gov/8070566/ | https://doi.org/10.1016/0014-5793(94)00763-2
source_locator
Reviewed reference rat-complexiv; Cardiolipin-mediated explanation was proposed; these observations do not establish a direct ALCAR cardiolipin-remodeling enzyme reaction or human cardiac benefit.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 404–410
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Aged-rat heart mitochondrial preparation; indexed primary abstract, dose/time not extracted. · Recorded from source · Recorded from source
### rat-complexiv ALCAR treatment restored depressed cardiac cytochrome oxidase activity in aged rats. Cardiolipin-mediated explanation was proposed; these observations do not establish a direct ALCAR cardiolipin-remodeling enzyme reaction or human cardiac benefit. Model and exposure: Aged-rat heart mitochondrial preparation; indexed primary abstract, dose/time not extracted. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Effect of aging and acetyl-L-carnitine on the activity of cytochrome oxidase and adenine nucleotide translocase in rat heart mitochondria. | 1994 | https://pubmed.ncbi.nlm.nih.gov/8070566/ | https://doi.org/10.1016/0014-5793(94)00763-2 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
ALCAR treatment restored depressed adenine nucleotide translocase activity in aged rat heart mitochondria.
Acetyl-L-carnitine → Aged-rat cardiac adenine nucleotide translocase activity Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_contrast
{"intervention": "ALCAR treatment of aged rats", "comparator": "Untreated aged rats", "endpoint": "ALCAR treatment restored depressed adenine nucleotide translocase activity in aged rat heart mitochondria.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Aged-rat heart mitochondrial preparation; indexed primary abstract, dose/time not extracted.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR treatment restored depressed adenine nucleotide translocase activity in aged rat heart mitochondria.
primary_references
Effect of aging and acetyl-L-carnitine on the activity of cytochrome oxidase and adenine nucleotide translocase in rat heart mitochondria. | https://pubmed.ncbi.nlm.nih.gov/8070566/ | https://doi.org/10.1016/0014-5793(94)00763-2
source_locator
Reviewed reference rat-ant; Cardiolipin-mediated explanation was proposed; these observations do not establish a direct ALCAR cardiolipin-remodeling enzyme reaction or human cardiac benefit.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 412–418
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Aged-rat heart mitochondrial preparation; indexed primary abstract, dose/time not extracted. · Recorded from source · Recorded from source
### rat-ant ALCAR treatment restored depressed adenine nucleotide translocase activity in aged rat heart mitochondria. Cardiolipin-mediated explanation was proposed; these observations do not establish a direct ALCAR cardiolipin-remodeling enzyme reaction or human cardiac benefit. Model and exposure: Aged-rat heart mitochondrial preparation; indexed primary abstract, dose/time not extracted. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Effect of aging and acetyl-L-carnitine on the activity of cytochrome oxidase and adenine nucleotide translocase in rat heart mitochondria. | 1994 | https://pubmed.ncbi.nlm.nih.gov/8070566/ | https://doi.org/10.1016/0014-5793(94)00763-2 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
ALCAR treatment reversed reduced phosphate-carrier activity in aged rat heart mitochondria.
Acetyl-L-carnitine → Aged-rat mitochondrial phosphate-carrier activity Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_contrast
{"intervention": "ALCAR treatment of aged rats", "comparator": "Untreated aged rats", "endpoint": "ALCAR treatment reversed reduced phosphate-carrier activity in aged rat heart mitochondria.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Aged-rat heart mitochondrial preparation; indexed primary abstract, dose/time not extracted.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR treatment reversed reduced phosphate-carrier activity in aged rat heart mitochondria.
primary_references
The effect of aging and acetyl-L-carnitine on the activity of the phosphate carrier and on the phospholipid composition in rat heart mitochondria. | https://pubmed.ncbi.nlm.nih.gov/1543717/ | https://doi.org/10.1016/0005-2736(92)90103-s
source_locator
Reviewed reference rat-phosphate; Cardiolipin-mediated explanation was proposed; these observations do not establish a direct ALCAR cardiolipin-remodeling enzyme reaction or human cardiac benefit.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 420–426
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Aged-rat heart mitochondrial preparation; indexed primary abstract, dose/time not extracted. · Recorded from source · Recorded from source
### rat-phosphate ALCAR treatment reversed reduced phosphate-carrier activity in aged rat heart mitochondria. Cardiolipin-mediated explanation was proposed; these observations do not establish a direct ALCAR cardiolipin-remodeling enzyme reaction or human cardiac benefit. Model and exposure: Aged-rat heart mitochondrial preparation; indexed primary abstract, dose/time not extracted. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: The effect of aging and acetyl-L-carnitine on the activity of the phosphate carrier and on the phospholipid composition in rat heart mitochondria. | 1992 | https://pubmed.ncbi.nlm.nih.gov/1543717/ | https://doi.org/10.1016/0005-2736(92)90103-s | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
ALCAR treatment restored reduced mitochondrial cardiolipin content in aged rats.
Acetyl-L-carnitine → Aged-rat heart mitochondrial cardiolipin Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_contrast
{"intervention": "ALCAR treatment of aged rats", "comparator": "Untreated aged rats", "endpoint": "ALCAR treatment restored reduced mitochondrial cardiolipin content in aged rats.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Aged-rat heart mitochondrial preparation; indexed primary abstract, dose/time not extracted.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR treatment restored reduced mitochondrial cardiolipin content in aged rats.
primary_references
The effect of aging and acetyl-L-carnitine on the activity of the phosphate carrier and on the phospholipid composition in rat heart mitochondria. | https://pubmed.ncbi.nlm.nih.gov/1543717/ | https://doi.org/10.1016/0005-2736(92)90103-s
source_locator
Reviewed reference rat-cardiolipin; Cardiolipin-mediated explanation was proposed; these observations do not establish a direct ALCAR cardiolipin-remodeling enzyme reaction or human cardiac benefit.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 428–434
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Aged-rat heart mitochondrial preparation; indexed primary abstract, dose/time not extracted. · Recorded from source · Recorded from source
### rat-cardiolipin ALCAR treatment restored reduced mitochondrial cardiolipin content in aged rats. Cardiolipin-mediated explanation was proposed; these observations do not establish a direct ALCAR cardiolipin-remodeling enzyme reaction or human cardiac benefit. Model and exposure: Aged-rat heart mitochondrial preparation; indexed primary abstract, dose/time not extracted. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: The effect of aging and acetyl-L-carnitine on the activity of the phosphate carrier and on the phospholipid composition in rat heart mitochondria. | 1992 | https://pubmed.ncbi.nlm.nih.gov/1543717/ | https://doi.org/10.1016/0005-2736(92)90103-s | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
Acute ALCAR treatment reversed impaired carnitine/acylcarnitine exchange in aged rat heart mitochondria.
Acetyl-L-carnitine → Aged-rat heart mitochondrial carnitine exchange Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_contrast
{"intervention": "ALCAR treatment of aged rats", "comparator": "Untreated aged rats", "endpoint": "Acute ALCAR treatment reversed impaired carnitine/acylcarnitine exchange in aged rat heart mitochondria.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Aged-rat heart mitochondrial preparation; indexed primary abstract, dose/time not extracted.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Acute ALCAR treatment reversed impaired carnitine/acylcarnitine exchange in aged rat heart mitochondria.
primary_references
Carnitine-acylcarnitine translocase activity in cardiac mitochondria from aged rats: the effect of acetyl-L-carnitine. | https://pubmed.ncbi.nlm.nih.gov/8788238/ | https://doi.org/10.1016/0047-6374(95)01636-8
source_locator
Reviewed reference rat-acyl-exchange; Cardiolipin-mediated explanation was proposed; these observations do not establish a direct ALCAR cardiolipin-remodeling enzyme reaction or human cardiac benefit.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 436–442
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Aged-rat heart mitochondrial preparation; indexed primary abstract, dose/time not extracted. · Recorded from source · Recorded from source
### rat-acyl-exchange Acute ALCAR treatment reversed impaired carnitine/acylcarnitine exchange in aged rat heart mitochondria. Cardiolipin-mediated explanation was proposed; these observations do not establish a direct ALCAR cardiolipin-remodeling enzyme reaction or human cardiac benefit. Model and exposure: Aged-rat heart mitochondrial preparation; indexed primary abstract, dose/time not extracted. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Carnitine-acylcarnitine translocase activity in cardiac mitochondria from aged rats: the effect of acetyl-L-carnitine. | 1995 | https://pubmed.ncbi.nlm.nih.gov/8788238/ | https://doi.org/10.1016/0047-6374(95)01636-8 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
ALCAR improved reduced CrAT activity and apparent substrate affinity in aged rat brain.
Acetyl-L-carnitine → Aged-rat brain CrAT activity and apparent substrate affinity Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.; Full primary correction read: adds Juvenon financial-interest disclosures, not a changed biochemical result.
experimental_contrast
{"intervention": "ALCAR-fed old rats", "comparator": "Unsupplemented old rats", "endpoint": "ALCAR improved reduced CrAT activity and apparent substrate affinity in aged rat brain.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Fischer 344 males; 0.5% ALCAR in water for seven weeks; young/old comparisons.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR improved reduced CrAT activity and apparent substrate affinity in aged rat brain.
primary_references
Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid. | https://pubmed.ncbi.nlm.nih.gov/11854488/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC122287/ | https://doi.org/10.1073/pnas.261709098
primary_references
Correction | https://pmc.ncbi.nlm.nih.gov/articles/PMC124428/
source_locator
Reviewed reference rat-crat-affinity; ALCAR alone and ALCAR plus dietary R-lipoic acid improved kinetic measures. Oxidative aldehyde damage was studied separately; a dietary effect is not proof of human enzyme repair.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 444–451
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Fischer 344 males; 0.5% ALCAR in water for seven weeks; young/old comparisons. · Recorded from source · Recorded from source
### rat-crat-affinity ALCAR improved reduced CrAT activity and apparent substrate affinity in aged rat brain. ALCAR alone and ALCAR plus dietary R-lipoic acid improved kinetic measures. Oxidative aldehyde damage was studied separately; a dietary effect is not proof of human enzyme repair. Model and exposure: Fischer 344 males; 0.5% ALCAR in water for seven weeks; young/old comparisons. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid. | 2002 | https://pubmed.ncbi.nlm.nih.gov/11854488/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC122287/ | https://doi.org/10.1073/pnas.261709098 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated. Reference: Correction | 2002 | https://pmc.ncbi.nlm.nih.gov/articles/PMC124428/ | Access: Full primary correction read: adds Juvenon financial-interest disclosures, not a changed biochemical result.
Complete structured claim and evidence
R-lipoic acid, alone or with ALCAR, lowered lipid-peroxidation readouts in the old-rat study.
Free R-alpha-lipoic acid → Aged-rat brain lipid peroxidation Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.; Full primary correction read: adds Juvenon financial-interest disclosures, not a changed biochemical result.
experimental_contrast
{"intervention": "R-lipoic-acid-containing treatment", "comparator": "Untreated aged animals", "endpoint": "R-lipoic acid, alone or with ALCAR, lowered lipid-peroxidation readouts in the old-rat study.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Fischer 344 rats; 0.2% R-lipoic acid diet, with/without 0.5% ALCAR water; seven weeks.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
R-lipoic acid, alone or with ALCAR, lowered lipid-peroxidation readouts in the old-rat study.
primary_references
Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid. | https://pubmed.ncbi.nlm.nih.gov/11854488/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC122287/ | https://doi.org/10.1073/pnas.261709098
primary_references
Correction | https://pmc.ncbi.nlm.nih.gov/articles/PMC124428/
source_locator
Reviewed reference rat-lipoic-peroxidation; Total brain iron and copper were not lowered. Distinct intervention arms do not establish a synergistic interaction or mineral chelation.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 453–460
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Fischer 344 rats; 0.2% R-lipoic acid diet, with/without 0.5% ALCAR water; seven weeks. · Recorded from source · Recorded from source
### rat-lipoic-peroxidation R-lipoic acid, alone or with ALCAR, lowered lipid-peroxidation readouts in the old-rat study. Total brain iron and copper were not lowered. Distinct intervention arms do not establish a synergistic interaction or mineral chelation. Model and exposure: Fischer 344 rats; 0.2% R-lipoic acid diet, with/without 0.5% ALCAR water; seven weeks. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid. | 2002 | https://pubmed.ncbi.nlm.nih.gov/11854488/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC122287/ | https://doi.org/10.1073/pnas.261709098 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated. Reference: Correction | 2002 | https://pmc.ncbi.nlm.nih.gov/articles/PMC124428/ | Access: Full primary correction read: adds Juvenon financial-interest disclosures, not a changed biochemical result.
Complete structured claim and evidence
R-lipoic-acid-containing treatment did not lower total brain iron or copper in the reported old-rat study.
Free R-alpha-lipoic acid → Aged-rat brain total iron and copper Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.; Full primary correction read: adds Juvenon financial-interest disclosures, not a changed biochemical result.
experimental_contrast
{"intervention": "R-lipoic acid alone or with ALCAR", "comparator": "Untreated aged rats", "endpoint": "R-lipoic-acid-containing treatment did not lower total brain iron or copper in the reported old-rat study.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Seven-week aged-rat intervention; total-metal measurement.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
R-lipoic-acid-containing treatment did not lower total brain iron or copper in the reported old-rat study.
primary_references
Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid. | https://pubmed.ncbi.nlm.nih.gov/11854488/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC122287/ | https://doi.org/10.1073/pnas.261709098
primary_references
Correction | https://pmc.ncbi.nlm.nih.gov/articles/PMC124428/
source_locator
Reviewed reference rat-lipoic-metal-null; A null total-metal result is not a measurement of labile-metal pools.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 462–469
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Seven-week aged-rat intervention; total-metal measurement. · Recorded from source · Recorded from source
### rat-lipoic-metal-null R-lipoic-acid-containing treatment did not lower total brain iron or copper in the reported old-rat study. A null total-metal result is not a measurement of labile-metal pools. Model and exposure: Seven-week aged-rat intervention; total-metal measurement. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid. | 2002 | https://pubmed.ncbi.nlm.nih.gov/11854488/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC122287/ | https://doi.org/10.1073/pnas.261709098 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated. Reference: Correction | 2002 | https://pmc.ncbi.nlm.nih.gov/articles/PMC124428/ | Access: Full primary correction read: adds Juvenon financial-interest disclosures, not a changed biochemical result.
Complete structured claim and evidence
ALCAR improved reported sural fiber-number and regenerating-cluster measurements in pooled diabetic-neuropathy trials.
Acetyl-L-carnitine → Human diabetic-neuropathy sural nerve morphometry Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_contrast
{"intervention": "ALCAR regimen", "comparator": "Placebo", "endpoint": "ALCAR improved reported sural fiber-number and regenerating-cluster measurements in pooled diabetic-neuropathy trials.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Two 52-week placebo-controlled trials; 1,257 ITT patients; 500 or 1,000 mg three times daily.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR improved reported sural fiber-number and regenerating-cluster measurements in pooled diabetic-neuropathy trials.
primary_references
Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: an analysis of two randomized placebo-controlled trials. | https://pubmed.ncbi.nlm.nih.gov/15616239/ | https://doi.org/10.2337/diacare.28.1.89
source_locator
Reviewed reference dpn05-biopsy; Two 52-week trials, 1,257 intention-to-treat patients; 500 or 1,000 mg three times daily. Morphometry is not an ulcer/amputation endpoint.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 475–481
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Two 52-week placebo-controlled trials; 1,257 ITT patients; 500 or 1,000 mg three times daily. · Recorded from source · Recorded from source
### dpn05-biopsy ALCAR improved reported sural fiber-number and regenerating-cluster measurements in pooled diabetic-neuropathy trials. Two 52-week trials, 1,257 intention-to-treat patients; 500 or 1,000 mg three times daily. Morphometry is not an ulcer/amputation endpoint. Model and exposure: Two 52-week placebo-controlled trials; 1,257 ITT patients; 500 or 1,000 mg three times daily. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: an analysis of two randomized placebo-controlled trials. | 2005 | https://pubmed.ncbi.nlm.nih.gov/15616239/ | https://doi.org/10.2337/diacare.28.1.89 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
ALCAR improved vibration perception in both 52-week diabetic-neuropathy trials.
Acetyl-L-carnitine → Human diabetic-neuropathy vibration perception Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_contrast
{"intervention": "ALCAR regimen", "comparator": "Placebo", "endpoint": "ALCAR improved vibration perception in both 52-week diabetic-neuropathy trials.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Two 52-week placebo-controlled trials; 1,257 ITT patients; 500 or 1,000 mg three times daily.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR improved vibration perception in both 52-week diabetic-neuropathy trials.
primary_references
Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: an analysis of two randomized placebo-controlled trials. | https://pubmed.ncbi.nlm.nih.gov/15616239/ | https://doi.org/10.2337/diacare.28.1.89
source_locator
Reviewed reference dpn05-vibration; Separate endpoint from conduction and pain; effects do not prove universal nerve regeneration.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 483–489
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Two 52-week placebo-controlled trials; 1,257 ITT patients; 500 or 1,000 mg three times daily. · Recorded from source · Recorded from source
### dpn05-vibration ALCAR improved vibration perception in both 52-week diabetic-neuropathy trials. Separate endpoint from conduction and pain; effects do not prove universal nerve regeneration. Model and exposure: Two 52-week placebo-controlled trials; 1,257 ITT patients; 500 or 1,000 mg three times daily. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: an analysis of two randomized placebo-controlled trials. | 2005 | https://pubmed.ncbi.nlm.nih.gov/15616239/ | https://doi.org/10.2337/diacare.28.1.89 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
Nerve-conduction velocities and amplitudes did not improve in the pooled 2005 ALCAR trial analysis.
Acetyl-L-carnitine → Human diabetic-neuropathy nerve conduction Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_contrast
{"intervention": "ALCAR regimen", "comparator": "Placebo", "endpoint": "Nerve-conduction velocities and amplitudes did not improve in the pooled 2005 ALCAR trial analysis.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Two 52-week placebo-controlled trials; 1,257 ITT patients; 500 or 1,000 mg three times daily.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Nerve-conduction velocities and amplitudes did not improve in the pooled 2005 ALCAR trial analysis.
primary_references
Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: an analysis of two randomized placebo-controlled trials. | https://pubmed.ncbi.nlm.nih.gov/15616239/ | https://doi.org/10.2337/diacare.28.1.89
source_locator
Reviewed reference dpn05-conduction-null; Negative electrophysiology is retained alongside favorable vibration and morphometry.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 491–497
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Two 52-week placebo-controlled trials; 1,257 ITT patients; 500 or 1,000 mg three times daily. · Recorded from source · Recorded from source
### dpn05-conduction-null Nerve-conduction velocities and amplitudes did not improve in the pooled 2005 ALCAR trial analysis. Negative electrophysiology is retained alongside favorable vibration and morphometry. Model and exposure: Two 52-week placebo-controlled trials; 1,257 ITT patients; 500 or 1,000 mg three times daily. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: an analysis of two randomized placebo-controlled trials. | 2005 | https://pubmed.ncbi.nlm.nih.gov/15616239/ | https://doi.org/10.2337/diacare.28.1.89 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
Pain improved in one study and the pooled 1,000-mg-three-times-daily subgroup, rather than uniformly across both trials and doses.
Acetyl-L-carnitine → Human diabetic-neuropathy pain score Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_contrast
{"intervention": "ALCAR regimen", "comparator": "Placebo", "endpoint": "Pain improved in one study and the pooled 1,000-mg-three-times-daily subgroup, rather than uniformly across both trials and doses.", "effect_direction": "mixed", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Two 52-week placebo-controlled trials; 1,257 ITT patients; 500 or 1,000 mg three times daily.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Pain improved in one study and the pooled 1,000-mg-three-times-daily subgroup, rather than uniformly across both trials and doses.
primary_references
Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: an analysis of two randomized placebo-controlled trials. | https://pubmed.ncbi.nlm.nih.gov/15616239/ | https://doi.org/10.2337/diacare.28.1.89
source_locator
Reviewed reference dpn05-pain; Pain was assessed in participants for whom it was the most bothersome symptom. This is not consistent benefit in every randomized participant.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 499–505
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Two 52-week placebo-controlled trials; 1,257 ITT patients; 500 or 1,000 mg three times daily. · Recorded from source · Recorded from source
### dpn05-pain Pain improved in one study and the pooled 1,000-mg-three-times-daily subgroup, rather than uniformly across both trials and doses. Pain was assessed in participants for whom it was the most bothersome symptom. This is not consistent benefit in every randomized participant. Model and exposure: Two 52-week placebo-controlled trials; 1,257 ITT patients; 500 or 1,000 mg three times daily. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: an analysis of two randomized placebo-controlled trials. | 2005 | https://pubmed.ncbi.nlm.nih.gov/15616239/ | https://doi.org/10.2337/diacare.28.1.89 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
ALCAR hydrochloride improved the 24-week mTCNS composite more than placebo in the 2024 trial.
Acetyl-L-carnitine → Human diabetic-neuropathy modified Toronto score Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_contrast
{"intervention": "ALCAR hydrochloride 1,500 mg/day for 24 weeks", "comparator": "Placebo", "endpoint": "ALCAR hydrochloride improved the 24-week mTCNS composite more than placebo in the 2024 trial.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Multicenter China trial: 516 randomized; eight type-1 participants excluded from ITT/FAS analyses; FAS 505 (254 ALC,251 placebo). 1,500 mg/day for 24 weeks.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR hydrochloride improved the 24-week mTCNS composite more than placebo in the 2024 trial.
primary_references
Acetyllevocarnitine Hydrochloride for the Treatment of Diabetic Peripheral Neuropathy: A Phase 3 Randomized Clinical Trial in China. | https://pubmed.ncbi.nlm.nih.gov/38320260/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC11043058/ | https://doi.org/10.2337/db23-0377
source_locator
Reviewed reference dpn24-score; Mean change −6.9 versus −4.7 points, P<0.001. The draft count of 458 randomized was incorrect. Trial medication was acetyllevocarnitine hydrochloride, 500 mg three times daily.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 507–513
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Multicenter China trial: 516 randomized; eight type-1 participants excluded from ITT/FAS analyses; FAS 505 (254 ALC,251 placebo). 1,500 mg/day for 24 weeks. · Recorded from source · Recorded from source
### dpn24-score ALCAR hydrochloride improved the 24-week mTCNS composite more than placebo in the 2024 trial. Mean change −6.9 versus −4.7 points, P<0.001. The draft count of 458 randomized was incorrect. Trial medication was acetyllevocarnitine hydrochloride, 500 mg three times daily. Model and exposure: Multicenter China trial: 516 randomized; eight type-1 participants excluded from ITT/FAS analyses; FAS 505 (254 ALC,251 placebo). 1,500 mg/day for 24 weeks. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Acetyllevocarnitine Hydrochloride for the Treatment of Diabetic Peripheral Neuropathy: A Phase 3 Randomized Clinical Trial in China. | 2024 | https://pubmed.ncbi.nlm.nih.gov/38320260/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC11043058/ | https://doi.org/10.2337/db23-0377 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
The 2024 trial did not find a significant between-group mTCNS change at 12 weeks.
Acetyl-L-carnitine → Human diabetic-neuropathy modified Toronto score Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_contrast
{"intervention": "ALCAR hydrochloride through 12 weeks", "comparator": "Placebo", "endpoint": "The 2024 trial did not find a significant between-group mTCNS change at 12 weeks.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Same randomized trial; 12-week change −5.0 versus −4.3, P=0.120.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
The 2024 trial did not find a significant between-group mTCNS change at 12 weeks.
primary_references
Acetyllevocarnitine Hydrochloride for the Treatment of Diabetic Peripheral Neuropathy: A Phase 3 Randomized Clinical Trial in China. | https://pubmed.ncbi.nlm.nih.gov/38320260/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC11043058/ | https://doi.org/10.2337/db23-0377
source_locator
Reviewed reference dpn24-early-null; The later significant composite endpoint must not be back-projected to the earlier assessment.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 515–521
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Same randomized trial; 12-week change −5.0 versus −4.3, P=0.120. · Recorded from source · Recorded from source
### dpn24-early-null The 2024 trial did not find a significant between-group mTCNS change at 12 weeks. The later significant composite endpoint must not be back-projected to the earlier assessment. Model and exposure: Same randomized trial; 12-week change −5.0 versus −4.3, P=0.120. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Acetyllevocarnitine Hydrochloride for the Treatment of Diabetic Peripheral Neuropathy: A Phase 3 Randomized Clinical Trial in China. | 2024 | https://pubmed.ncbi.nlm.nih.gov/38320260/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC11043058/ | https://doi.org/10.2337/db23-0377 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
The 24-week foot-pain component did not reach statistical significance in the 2024 ALCAR trial.
Acetyl-L-carnitine → Human diabetic-neuropathy pain score Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_contrast
{"intervention": "ALCAR hydrochloride for 24 weeks", "comparator": "Placebo", "endpoint": "The 24-week foot-pain component did not reach statistical significance in the 2024 ALCAR trial.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Same trial; component analysis P=0.066.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
The 24-week foot-pain component did not reach statistical significance in the 2024 ALCAR trial.
primary_references
Acetyllevocarnitine Hydrochloride for the Treatment of Diabetic Peripheral Neuropathy: A Phase 3 Randomized Clinical Trial in China. | https://pubmed.ncbi.nlm.nih.gov/38320260/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC11043058/ | https://doi.org/10.2337/db23-0377
source_locator
Reviewed reference dpn24-pain-null; More than half of participants had baseline numeric pain scores of 0–1. A composite neuropathy benefit is not automatically a demonstrated analgesic effect.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 523–529
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Same trial; component analysis P=0.066. · Recorded from source · Recorded from source
### dpn24-pain-null The 24-week foot-pain component did not reach statistical significance in the 2024 ALCAR trial. More than half of participants had baseline numeric pain scores of 0–1. A composite neuropathy benefit is not automatically a demonstrated analgesic effect. Model and exposure: Same trial; component analysis P=0.066. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Acetyllevocarnitine Hydrochloride for the Treatment of Diabetic Peripheral Neuropathy: A Phase 3 Randomized Clinical Trial in China. | 2024 | https://pubmed.ncbi.nlm.nih.gov/38320260/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC11043058/ | https://doi.org/10.2337/db23-0377 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
The 2024 neuropathy benefit did not coincide with significant HbA1c, total-cholesterol or triglyceride changes.
Acetyl-L-carnitine → Human DPN-trial HbA1c and lipid measurements Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_contrast
{"intervention": "ALCAR hydrochloride for 24 weeks", "comparator": "Placebo", "endpoint": "The 2024 neuropathy benefit did not coincide with significant HbA1c, total-cholesterol or triglyceride changes.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Same randomized trial; supplementary Table 5 described in Results.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
The 2024 neuropathy benefit did not coincide with significant HbA1c, total-cholesterol or triglyceride changes.
primary_references
Acetyllevocarnitine Hydrochloride for the Treatment of Diabetic Peripheral Neuropathy: A Phase 3 Randomized Clinical Trial in China. | https://pubmed.ncbi.nlm.nih.gov/38320260/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC11043058/ | https://doi.org/10.2337/db23-0377
source_locator
Reviewed reference dpn24-metabolic-null; This limits a claim that the composite benefit was demonstrated to result from improved systemic glycemic control.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 531–537
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Same randomized trial; supplementary Table 5 described in Results. · Recorded from source · Recorded from source
### dpn24-metabolic-null The 2024 neuropathy benefit did not coincide with significant HbA1c, total-cholesterol or triglyceride changes. This limits a claim that the composite benefit was demonstrated to result from improved systemic glycemic control. Model and exposure: Same randomized trial; supplementary Table 5 described in Results. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Acetyllevocarnitine Hydrochloride for the Treatment of Diabetic Peripheral Neuropathy: A Phase 3 Randomized Clinical Trial in China. | 2024 | https://pubmed.ncbi.nlm.nih.gov/38320260/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC11043058/ | https://doi.org/10.2337/db23-0377 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
ALCAR met the reported noninferiority comparison with methylcobalamin on combined NSS/NDS scores.
Acetyl-L-carnitine → Human DPN combined symptom and disability score Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_contrast
{"intervention": "ALCAR 500 mg three times daily", "comparator": "Methylcobalamin 0.5 mg three times daily", "endpoint": "ALCAR met the reported noninferiority comparison with methylcobalamin on combined NSS/NDS scores.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
232 randomized; ALCAR 500 mg three times daily versus methylcobalamin 0.5 mg three times daily for 24 weeks.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR met the reported noninferiority comparison with methylcobalamin on combined NSS/NDS scores.
primary_references
Effects of acetyl-L-carnitine and methylcobalamin for diabetic peripheral neuropathy: A multicenter, randomized, double-blind, controlled trial. | https://pubmed.ncbi.nlm.nih.gov/27180954/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC5009142/ | https://doi.org/10.1111/jdi.12493
source_locator
Reviewed reference dpn16-b12-comparator; No significant superiority difference (P=0.14); this was an active-comparator trial without placebo. It did not test combined ALCAR+B12 synergy or establish B12 deficiency as the cause of symptoms.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 539–545
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · 232 randomized; ALCAR 500 mg three times daily versus methylcobalamin 0.5 mg three times daily for 24 weeks. · Recorded from source · Recorded from source
### dpn16-b12-comparator ALCAR met the reported noninferiority comparison with methylcobalamin on combined NSS/NDS scores. No significant superiority difference (P=0.14); this was an active-comparator trial without placebo. It did not test combined ALCAR+B12 synergy or establish B12 deficiency as the cause of symptoms. Model and exposure: 232 randomized; ALCAR 500 mg three times daily versus methylcobalamin 0.5 mg three times daily for 24 weeks. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Effects of acetyl-L-carnitine and methylcobalamin for diabetic peripheral neuropathy: A multicenter, randomized, double-blind, controlled trial. | 2016 | https://pubmed.ncbi.nlm.nih.gov/27180954/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC5009142/ | https://doi.org/10.1111/jdi.12493 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
Adjusting for baseline carnitine status did not remove the adverse ALCAR effect in the taxane trial.
Human taxane-trial baseline serum carnitine status → Human taxane-associated peripheral neuropathy severity Recorded from sourceungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_model
Women receiving adjuvant paclitaxel/docetaxel; ALCAR 3 g/day for 24 weeks. Trial-defined deficiency was the lowest carnitine quartile.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Recorded association/adjustment only. Neither proves all patients were replete nor tests every clinically deficient population.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Adjusting for baseline carnitine status did not remove the adverse ALCAR effect in the taxane trial.
primary_references
Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy in women undergoing adjuvant breast cancer therapy. | https://pubmed.ncbi.nlm.nih.gov/23733756/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC3699727/ | https://doi.org/10.1200/jco.2012.44.8738
source_locator
Reviewed reference taxane-low-quarter; The baseline definition was not a validated clinical deficiency threshold and did not isolate plasma ALCAR as the causal factor. Adjusted week-24 FACT-NTX difference −2.3 points, P=0.007; baseline status was not associated with neuropathy in either arm.
trigger_kind
biomarker_context Imported condition classification; unverified.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 551–557
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Women receiving adjuvant paclitaxel/docetaxel; ALCAR 3 g/day for 24 weeks. Trial-defined deficiency was the lowest carnitine quartile. · Recorded from source · Recorded from source
### taxane-low-quarter Adjusting for baseline carnitine status did not remove the adverse ALCAR effect in the taxane trial. The baseline definition was not a validated clinical deficiency threshold and did not isolate plasma ALCAR as the causal factor. Adjusted week-24 FACT-NTX difference −2.3 points, P=0.007; baseline status was not associated with neuropathy in either arm. Model and exposure: Women receiving adjuvant paclitaxel/docetaxel; ALCAR 3 g/day for 24 weeks. Trial-defined deficiency was the lowest carnitine quartile. Limitations: Recorded association/adjustment only. Neither proves all patients were replete nor tests every clinically deficient population. Reference: Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy in women undergoing adjuvant breast cancer therapy. | 2013 | https://pubmed.ncbi.nlm.nih.gov/23733756/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC3699727/ | https://doi.org/10.1200/jco.2012.44.8738 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
The taxane trial follow-up found worse average neuropathy over two years after 24 weeks of ALCAR.
Acetyl-L-carnitine → Human taxane-associated peripheral neuropathy severity Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_contrast
{"intervention": "Original 3-g/day ALCAR allocation", "comparator": "Original placebo allocation", "endpoint": "The taxane trial follow-up found worse average neuropathy over two years after 24 weeks of ALCAR.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Same S0715 cohort, not an independent replication; longitudinal FACT-NTX model, 12–104 weeks.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Outcome sign denotes worse neuropathy, not the decreasing FACT-NTX score. Same cohort as the 2013 trial; no automatic transfer to every neuropathy cause.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
The taxane trial follow-up found worse average neuropathy over two years after 24 weeks of ALCAR.
primary_references
Two-Year Trends of Taxane-Induced Neuropathy in Women Enrolled in a Randomized Trial of Acetyl-L-Carnitine (SWOG S0715). | https://pubmed.ncbi.nlm.nih.gov/29361042/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC6005110/ | https://doi.org/10.1093/jnci/djx259
source_locator
Reviewed reference taxane-followup; Average difference −1.39 points (95% CI −2.48 to −0.30), P=0.01. Significant separation at weeks 24,36,52; the 104-week point alone was not significant (P=0.17).
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 559–565
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Same S0715 cohort, not an independent replication; longitudinal FACT-NTX model, 12–104 weeks. · Recorded from source · Recorded from source
### taxane-followup The taxane trial follow-up found worse average neuropathy over two years after 24 weeks of ALCAR. Average difference −1.39 points (95% CI −2.48 to −0.30), P=0.01. Significant separation at weeks 24,36,52; the 104-week point alone was not significant (P=0.17). Model and exposure: Same S0715 cohort, not an independent replication; longitudinal FACT-NTX model, 12–104 weeks. Limitations: Outcome sign denotes worse neuropathy, not the decreasing FACT-NTX score. Same cohort as the 2013 trial; no automatic transfer to every neuropathy cause. Reference: Two-Year Trends of Taxane-Induced Neuropathy in Women Enrolled in a Randomized Trial of Acetyl-L-Carnitine (SWOG S0715). | 2018 | https://pubmed.ncbi.nlm.nih.gov/29361042/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC6005110/ | https://doi.org/10.1093/jnci/djx259 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
Patients with major depressive disorder had lower plasma ALCAR in the 2018 case-control study.
Acetyl-L-carnitine → Plasma ALCAR in human major depressive disorder Recorded from sourceungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_model
71 MDD participants and 45 controls across two centers; observational human plasma measurements.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Patients with major depressive disorder had lower plasma ALCAR in the 2018 case-control study.
primary_references
Acetyl-l-carnitine deficiency in patients with major depressive disorder. | https://pubmed.ncbi.nlm.nih.gov/30061399/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC6112703/ | https://doi.org/10.1073/pnas.1801609115
source_locator
Reviewed reference mdd-alcar-low; Exploratory severity, onset and treatment-resistance associations were reported. The study did not measure neuronal nuclear acetyl-CoA, Grm2 promoter acetylation or randomized supplementation response.
trigger_kind
biomarker_context Imported condition classification; unverified.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 571–577
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · 71 MDD participants and 45 controls across two centers; observational human plasma measurements. · Recorded from source · Recorded from source
### mdd-alcar-low Patients with major depressive disorder had lower plasma ALCAR in the 2018 case-control study. Exploratory severity, onset and treatment-resistance associations were reported. The study did not measure neuronal nuclear acetyl-CoA, Grm2 promoter acetylation or randomized supplementation response. Model and exposure: 71 MDD participants and 45 controls across two centers; observational human plasma measurements. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Acetyl-l-carnitine deficiency in patients with major depressive disorder. | 2018 | https://pubmed.ncbi.nlm.nih.gov/30061399/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC6112703/ | https://doi.org/10.1073/pnas.1801609115 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
Free carnitine was not reduced in the same MDD comparison despite lower ALCAR.
L-Carnitine → Free carnitine in human major depressive disorder Recorded from sourceungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_contrast
{"intervention": "MDD cohort membership (observational)", "comparator": "Age/sex-matched controls", "endpoint": "Free carnitine was not reduced in the same MDD comparison despite lower ALCAR.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Same human case-control cohorts.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Free carnitine was not reduced in the same MDD comparison despite lower ALCAR.
primary_references
Acetyl-l-carnitine deficiency in patients with major depressive disorder. | https://pubmed.ncbi.nlm.nih.gov/30061399/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC6112703/ | https://doi.org/10.1073/pnas.1801609115
source_locator
Reviewed reference mdd-carnitine-null; Distinct metabolite pools cannot be collapsed into a generalized carnitine-deficiency diagnosis.
trigger_kind
biomarker_context Imported condition classification; unverified.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 579–585
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Same human case-control cohorts. · Recorded from source · Recorded from source
### mdd-carnitine-null Free carnitine was not reduced in the same MDD comparison despite lower ALCAR. Distinct metabolite pools cannot be collapsed into a generalized carnitine-deficiency diagnosis. Model and exposure: Same human case-control cohorts. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: Acetyl-l-carnitine deficiency in patients with major depressive disorder. | 2018 | https://pubmed.ncbi.nlm.nih.gov/30061399/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC6112703/ | https://doi.org/10.1073/pnas.1801609115 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence
The ALCAR–amisulpride trial did not meet its prespecified two-point noninferiority margin.
Acetyl-L-carnitine → Human dysthymia Hamilton depression score Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_contrast
{"intervention": "ALCAR regimen", "comparator": "Amisulpride regimen", "endpoint": "The ALCAR–amisulpride trial did not meet its prespecified two-point noninferiority margin.", "effect_direction": "mixed", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
204 randomized; ALCAR 500 mg twice daily versus amisulpride 50 mg/day for 12 weeks.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
The ALCAR–amisulpride trial did not meet its prespecified two-point noninferiority margin.
primary_references
A double-blind, randomised, controlled clinical trial of acetyl-L-carnitine vs. amisulpride in the treatment of dysthymia. | https://pubmed.ncbi.nlm.nih.gov/16316746/ | https://doi.org/10.1016/j.euroneuro.2005.10.005
source_locator
Reviewed reference dysthymia-noninferiority; The confidence interval exceeded the prespecified margin by 0.46 points. A wider three-point margin discussed afterward does not replace the original test. Both arms improved; nonsignificant superiority does not prove equivalence.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 587–593
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · 204 randomized; ALCAR 500 mg twice daily versus amisulpride 50 mg/day for 12 weeks. · Recorded from source · Recorded from source
### dysthymia-noninferiority The ALCAR–amisulpride trial did not meet its prespecified two-point noninferiority margin. The confidence interval exceeded the prespecified margin by 0.46 points. A wider three-point margin discussed afterward does not replace the original test. Both arms improved; nonsignificant superiority does not prove equivalence. Model and exposure: 204 randomized; ALCAR 500 mg twice daily versus amisulpride 50 mg/day for 12 weeks. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: A double-blind, randomised, controlled clinical trial of acetyl-L-carnitine vs. amisulpride in the treatment of dysthymia. | 2006 | https://pubmed.ncbi.nlm.nih.gov/16316746/ | https://doi.org/10.1016/j.euroneuro.2005.10.005 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
ALCAR did not slow overall primary cognitive/clinical decline in the 431-participant Alzheimer trial.
Acetyl-L-carnitine → Human Alzheimer trial cognitive and functional decline Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_contrast
{"intervention": "ALCAR 3 g/day for one year", "comparator": "Placebo", "endpoint": "ALCAR did not slow overall primary cognitive/clinical decline in the 431-participant Alzheimer trial.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mild-to-moderate probable AD; 3 g/day versus placebo, 12 months, 1996.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
ALCAR did not slow overall primary cognitive/clinical decline in the 431-participant Alzheimer trial.
primary_references
A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease. | https://pubmed.ncbi.nlm.nih.gov/8797468/ | https://doi.org/10.1212/wnl.47.3.705
source_locator
Reviewed reference ad96-null; Post hoc age-subgroup trends were exploratory and motivated prospective testing.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 595–601
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · Mild-to-moderate probable AD; 3 g/day versus placebo, 12 months, 1996. · Recorded from source · Recorded from source
### ad96-null ALCAR did not slow overall primary cognitive/clinical decline in the 431-participant Alzheimer trial. Post hoc age-subgroup trends were exploratory and motivated prospective testing. Model and exposure: Mild-to-moderate probable AD; 3 g/day versus placebo, 12 months, 1996. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease. | 1996 | https://pubmed.ncbi.nlm.nih.gov/8797468/ | https://doi.org/10.1212/wnl.47.3.705 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
The prospective early-onset Alzheimer trial also found no primary intention-to-treat benefit of ALCAR.
Acetyl-L-carnitine → Human Alzheimer trial cognitive and functional decline Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
experimental_contrast
{"intervention": "ALCAR 3 g/day for one year", "comparator": "Placebo", "endpoint": "The prospective early-onset Alzheimer trial also found no primary intention-to-treat benefit of ALCAR.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
experimental_model
229 randomized, ages 45–65; ALCAR 1 g three times daily versus placebo for one year.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
The prospective early-onset Alzheimer trial also found no primary intention-to-treat benefit of ALCAR.
primary_references
A 1-year controlled trial of acetyl-l-carnitine in early-onset AD. | https://pubmed.ncbi.nlm.nih.gov/10994000/ | https://doi.org/10.1212/wnl.55.6.805
source_locator
Reviewed reference ad00-null; A completer-only MMSE signal did not overturn null primary ADAS-cognitive and CDR results.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 603–609
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · 229 randomized, ages 45–65; ALCAR 1 g three times daily versus placebo for one year. · Recorded from source · Recorded from source
### ad00-null The prospective early-onset Alzheimer trial also found no primary intention-to-treat benefit of ALCAR. A completer-only MMSE signal did not overturn null primary ADAS-cognitive and CDR results. Model and exposure: 229 randomized, ages 45–65; ALCAR 1 g three times daily versus placebo for one year. Limitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation. Reference: A 1-year controlled trial of acetyl-l-carnitine in early-onset AD. | 2000 | https://pubmed.ncbi.nlm.nih.gov/10994000/ | https://doi.org/10.1212/wnl.55.6.805 | Access: Indexed primary abstract/metadata only; unextracted doses, figures and methods remain unknown.
Complete structured claim and evidence
Psychosis occurred five days after ALCAR was started in a published bipolar-disorder case report.
Acetyl-L-carnitine → Reported psychosis after starting ALCAR Recorded from sourceungraded
Experimental context and source evidence
evidence_access
Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
experimental_model
52-year-old man; ALCAR 500 mg/day alongside newly added vitamins C/E, ongoing lithium and citalopram; prior recurrent illness.
interpretation_status
Source-derived curation with stated access limits; ungraded, not independent replication.
limitations
Single confounded case; this is a signal, not a quantified risk or proof that ALCAR invariably triggers psychosis.
nutrient_topic
Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation. · Acetyl-L-carnitine
plain_language
Psychosis occurred five days after ALCAR was started in a published bipolar-disorder case report.
primary_references
Psychosis Precipitated by Acetyl-l-Carnitine in a Patient With Bipolar Disorder. | https://pubmed.ncbi.nlm.nih.gov/17599177/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC1894836/ | https://doi.org/10.4088/pcc.v09n0114d
source_locator
Reviewed reference psychosis-case; Temporal association and author attribution are recorded. No rechallenge, incidence estimate or proven dopamine-mediated cause is established.
Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026) · lines 611–617
AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed. · supports · 52-year-old man; ALCAR 500 mg/day alongside newly added vitamins C/E, ongoing lithium and citalopram; prior recurrent illness. · Recorded from source · Recorded from source
### psychosis-case Psychosis occurred five days after ALCAR was started in a published bipolar-disorder case report. Temporal association and author attribution are recorded. No rechallenge, incidence estimate or proven dopamine-mediated cause is established. Model and exposure: 52-year-old man; ALCAR 500 mg/day alongside newly added vitamins C/E, ongoing lithium and citalopram; prior recurrent illness. Limitations: Single confounded case; this is a signal, not a quantified risk or proof that ALCAR invariably triggers psychosis. Reference: Psychosis Precipitated by Acetyl-l-Carnitine in a Patient With Bipolar Disorder. | 2007 | https://pubmed.ncbi.nlm.nih.gov/17599177/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC1894836/ | https://doi.org/10.4088/pcc.v09n0114d | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

Low brain ALCAR during impaired OCTN2 delivery

Condition: machinery_impairment · Defective Octn2 in jvs mice

Normal role: Reversible acetyl transfer coupled to transport and compartment-specific CoA availability.

Recorded consequence: Reduced initial uptake and thalamic extracellular ALCAR; substrate alone does not prove bypass.