Component

Methylmalonic acid

Independently recorded substance, clinical endpoint or assay readout. Claims retain study-specific population and measurement context.

10 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. MMA was elevated in 12.2% of the folate-deficient group; all but one were attributed to renal insufficiency or hypovolemia.

    Methylmalonic acid → B12 deficiency diagnosis source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    biomarker_context Imported condition classification; unverified.
    cross_nutrient
    Separates a shared diagnostic setting from direct cofactor identity.
    experimental_model
    Selected clear-cut deficiency series: 434 B12 episodes in 406 patients and 123 folate episodes in 119 patients.
    exposure
    Serum MMA and total homocysteine assays; elevation defined above three standard deviations of the reference mean.
    limitations
    These are authors’ clinical attributions, not randomized tests of renal causation. Folate does not thereby become the MMUT cofactor.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    An abnormal MMA result needs its clinical and kidney context.
    primary_references
    [b12-savage1994] Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies (1994). https://pubmed.ncbi.nlm.nih.gov/8154512/ DOI: 10.1016/0002-9343(94)90149-x
    tissue_or_cell_type
    Human blood or whole-person endpoints
    trigger_kind
    biomarker_context Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1487–1498

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Selected clear-cut deficiency series: 434 B12 episodes in 406 patients and 123 folate episodes in 119 patients. · source_derived_draft · unverified_draft

    ### b12-mma-folate-renal-confounding MMA was elevated in 12.2% of the folate-deficient group; all but one were attributed to renal insufficiency or hypovolemia. Condition category: biomarker_context nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: An abnormal MMA result needs its clinical and kidney context. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Selected clear-cut deficiency series: 434 B12 episodes in 406 patients and 123 folate episodes in 119 patients. limitations: These are authors’ clinical attributions, not randomized tests of renal causation. Folate does not thereby become the MMUT cofactor. exposure: Serum MMA and total homocysteine assays; elevation defined above three standard deviations of the reference mean. cross_nutrient: Separates a shared diagnostic setting from direct cofactor identity. [b12-savage1994] Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies (1994). https://pubmed.ncbi.nlm.nih.gov/8154512/ DOI: 10.1016/0002-9343(94)90149-x
    Complete structured claim and evidence

What acts on it

  1. MMA was elevated in 98.4% of 434 clear-cut B12-deficiency episodes in the diagnostic series.

    Vitamin B12 (cobalamins) → Methylmalonic acid source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    biomarker_context Imported condition classification; unverified.
    experimental_model
    Selected clear-cut deficiency series: 434 B12 episodes in 406 patients and 123 folate episodes in 119 patients.
    exposure
    Serum MMA and total homocysteine assays; elevation defined above three standard deviations of the reference mean.
    limitations
    Selected established deficiency overestimates performance for some borderline screening settings; renal insufficiency or hypovolemia can also raise MMA.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    A metabolite connected to the mitochondrial B12 pathway often provided an additional clue.
    primary_references
    [b12-savage1994] Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies (1994). https://pubmed.ncbi.nlm.nih.gov/8154512/ DOI: 10.1016/0002-9343(94)90149-x
    tissue_or_cell_type
    Human blood or whole-person endpoints
    trigger_kind
    biomarker_context Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1462–1472

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Selected clear-cut deficiency series: 434 B12 episodes in 406 patients and 123 folate episodes in 119 patients. · source_derived_draft · unverified_draft

    ### b12-deficiency-mma-frequency MMA was elevated in 98.4% of 434 clear-cut B12-deficiency episodes in the diagnostic series. Condition category: biomarker_context nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A metabolite connected to the mitochondrial B12 pathway often provided an additional clue. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Selected clear-cut deficiency series: 434 B12 episodes in 406 patients and 123 folate episodes in 119 patients. limitations: Selected established deficiency overestimates performance for some borderline screening settings; renal insufficiency or hypovolemia can also raise MMA. exposure: Serum MMA and total homocysteine assays; elevation defined above three standard deviations of the reference mean. [b12-savage1994] Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies (1994). https://pubmed.ncbi.nlm.nih.gov/8154512/ DOI: 10.1016/0002-9343(94)90149-x
    Complete structured claim and evidence

  2. After injection, total homocysteine fell 54% and MMA 84%; placebo showed no significant changes.

    Hydroxocobalamin → Methylmalonic acid source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    biomarker_context Imported condition classification; unverified.
    experimental_model
    Double-blind randomized trial: 79 referred infants younger than eight months with plasma total homocysteine at least 6.5 micromol/L, from 105 assessed.
    exposure
    One 400-microgram intramuscular hydroxocobalamin injection (42 infants) versus sham injection (37); one-month follow-up.
    limitations
    One-month response does not define a treatment regimen for other infants.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    Both connected metabolic markers responded to the intervention.
    primary_references
    [b12-torsvik2013] Cobalamin supplementation improves motor development and regurgitations in infants: results from a randomized intervention study (2013). https://pubmed.ncbi.nlm.nih.gov/24025626/ DOI: 10.3945/ajcn.113.061549
    tissue_or_cell_type
    Human blood or whole-person endpoints
    trigger_kind
    biomarker_context Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1734–1744

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized trial: 79 referred infants younger than eight months with plasma total homocysteine at least 6.5 micromol/L, from 105 assessed. · source_derived_draft · unverified_draft

    ### b12-infant-biochemical-response After injection, total homocysteine fell 54% and MMA 84%; placebo showed no significant changes. Condition category: biomarker_context nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Both connected metabolic markers responded to the intervention. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Double-blind randomized trial: 79 referred infants younger than eight months with plasma total homocysteine at least 6.5 micromol/L, from 105 assessed. limitations: One-month response does not define a treatment regimen for other infants. exposure: One 400-microgram intramuscular hydroxocobalamin injection (42 infants) versus sham injection (37); one-month follow-up. [b12-torsvik2013] Cobalamin supplementation improves motor development and regurgitations in infants: results from a randomized intervention study (2013). https://pubmed.ncbi.nlm.nih.gov/24025626/ DOI: 10.3945/ajcn.113.061549
    Complete structured claim and evidence

  3. MMA and homocysteine were significantly lower with methylcobalamin than placebo at months 9 and 27.

    Methylcobalamin → Methylmalonic acid source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    biomarker_context Imported condition classification; unverified.
    experimental_model
    Randomized placebo-controlled trial: 271 nondemented diabetic outpatients aged at least 70, plasma B12 150–300 pmol/L.
    exposure
    Oral methylcobalamin 1000 micrograms/day versus placebo for 27 months.
    limitations
    No direct cellular flux measurement and no head-to-head form comparison.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    This B12 form improved the measured metabolic markers.
    primary_references
    [b12-kwok2017] A randomized placebo controlled trial of vitamin B12 supplementation to prevent cognitive decline in older diabetic people with borderline low serum vitamin B12 (2017). https://pubmed.ncbi.nlm.nih.gov/27823800/ DOI: 10.1016/j.clnu.2016.10.018
    tissue_or_cell_type
    Human blood or whole-person endpoints
    trigger_kind
    biomarker_context Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1561–1571

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled trial: 271 nondemented diabetic outpatients aged at least 70, plasma B12 150–300 pmol/L. · source_derived_draft · unverified_draft

    ### b12-methylcobalamin-diabetes-metabolites MMA and homocysteine were significantly lower with methylcobalamin than placebo at months 9 and 27. Condition category: biomarker_context nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This B12 form improved the measured metabolic markers. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Randomized placebo-controlled trial: 271 nondemented diabetic outpatients aged at least 70, plasma B12 150–300 pmol/L. limitations: No direct cellular flux measurement and no head-to-head form comparison. exposure: Oral methylcobalamin 1000 micrograms/day versus placebo for 27 months. [b12-kwok2017] A randomized placebo controlled trial of vitamin B12 supplementation to prevent cognitive decline in older diabetic people with borderline low serum vitamin B12 (2017). https://pubmed.ncbi.nlm.nih.gov/27823800/ DOI: 10.1016/j.clnu.2016.10.018
    Complete structured claim and evidence

  4. At four months, mean MMA was 169 nmol/L with oral versus 265 with IM treatment; homocysteine was 10.6 versus 12.2 micromol/L. Oral-group MMA was significantly lower.

    Cyanocobalamin → Methylmalonic acid source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    experimental_model
    Randomized oral-versus-intramuscular study: 38 allocated; five subsequently identified as folate deficient excluded, leaving 18 oral and 15 injection participants.
    exposure
    Cyanocobalamin 2 mg orally each day for 120 days versus 1 mg IM on days 1, 3, 7, 10, 14, 21, 30, 60 and 90. Unequal cumulative exposures.
    limitations
    Different cumulative exposures prevent interpreting the result as inherent route superiority.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    The biochemical response was recorded separately from the clinical response.
    primary_references
    [b12-kuzminski1998] Effective treatment of cobalamin deficiency with oral cobalamin (1998). https://pubmed.ncbi.nlm.nih.gov/9694707/ DOI: 10.1182/blood.v92.4.1191
    tissue_or_cell_type
    Human blood or whole-person endpoints
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1697–1707

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized oral-versus-intramuscular study: 38 allocated; five subsequently identified as folate deficient excluded, leaving 18 oral and 15 injection participants. · source_derived_draft · unverified_draft

    ### b12-oral-im-metabolic-response At four months, mean MMA was 169 nmol/L with oral versus 265 with IM treatment; homocysteine was 10.6 versus 12.2 micromol/L. Oral-group MMA was significantly lower. Condition category: nutrient_deficiency nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The biochemical response was recorded separately from the clinical response. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Randomized oral-versus-intramuscular study: 38 allocated; five subsequently identified as folate deficient excluded, leaving 18 oral and 15 injection participants. limitations: Different cumulative exposures prevent interpreting the result as inherent route superiority. exposure: Cyanocobalamin 2 mg orally each day for 120 days versus 1 mg IM on days 1, 3, 7, 10, 14, 21, 30, 60 and 90. Unequal cumulative exposures. [b12-kuzminski1998] Effective treatment of cobalamin deficiency with oral cobalamin (1998). https://pubmed.ncbi.nlm.nih.gov/9694707/ DOI: 10.1182/blood.v92.4.1191
    Complete structured claim and evidence

  5. In low-serum-B12 strata, circulating methylmalonic acid increased as folate increased above approximately 20 nmol/L; the relationship ran oppositely in B12-replete strata.

    Serum folate concentration → Methylmalonic acid source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    biomarker_context Imported condition classification; unverified.
    cross_nutrient
    The measured interaction concerns B12 status and total folate, not all folate formulations equally.
    experimental_model
    Cross-sectional adult NHANES III 1991–1994 (4940) and NHANES 1999–2002 (5473) analyses, exclusions for several confounders.
    exposure
    Measured serum folate, B12, total homocysteine and MMA; stratification at serum B12 148 pmol/L; no randomized folate exposure.
    limitations
    No direct enzyme-flux measurement or causal proof of folate toxicity. Survey subsets and B12 definitions differ from the older-adult cognition analysis.
    nutrient_topic
    Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
    organism
    Homo sapiens
    plain_language
    More circulating folate did not guarantee a better B12-related marker.
    primary_references
    [fol-selhub2007] In vitamin B12 deficiency, higher serum folate is associated with increased total homocysteine and methylmalonic acid concentrations (2007). https://pubmed.ncbi.nlm.nih.gov/18056804/ DOI: 10.1073/pnas.0709487104
    tissue_or_cell_type
    Human blood or whole-person clinical endpoints
    trigger_kind
    biomarker_context Imported condition classification; unverified.

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1580–1591

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cross-sectional adult NHANES III 1991–1994 (4940) and NHANES 1999–2002 (5473) analyses, exclusions for several confounders. · source_derived_draft · unverified_draft

    ### fol-b12-interaction-mma In low-serum-B12 strata, circulating methylmalonic acid increased as folate increased above approximately 20 nmol/L; the relationship ran oppositely in B12-replete strata. Condition category: biomarker_context nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: More circulating folate did not guarantee a better B12-related marker. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person clinical endpoints experimental_model: Cross-sectional adult NHANES III 1991–1994 (4940) and NHANES 1999–2002 (5473) analyses, exclusions for several confounders. limitations: No direct enzyme-flux measurement or causal proof of folate toxicity. Survey subsets and B12 definitions differ from the older-adult cognition analysis. exposure: Measured serum folate, B12, total homocysteine and MMA; stratification at serum B12 148 pmol/L; no randomized folate exposure. cross_nutrient: The measured interaction concerns B12 status and total folate, not all folate formulations equally. [fol-selhub2007] In vitamin B12 deficiency, higher serum folate is associated with increased total homocysteine and methylmalonic acid concentrations (2007). https://pubmed.ncbi.nlm.nih.gov/18056804/ DOI: 10.1073/pnas.0709487104
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Fibroblasts from five asymptomatic newborns with elevated methylmalonic acid and homozygous CD320 p.Glu88del showed reduced uptake of holo-transcobalamin.

    Human CD320 p.Glu88del variant → Cellular uptake of transcobalamin-bound cobalamin source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    experimental_model
    Five newborn-derived fibroblast lines with homozygous CD320 deletion
    exposure
    Homozygous c.262_264delGAG / p.Glu88del
    limitations
    Asymptomatic neonatal ascertainment does not establish later clinical severity. Cellular uptake does not isolate binding from receptor expression or trafficking.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    A receptor deletion reduced B12 delivery in patient cells.
    primary_references
    [quadros-2010-e88del] Positive newborn screen for methylmalonic aciduria identifies the first mutation in TCblR/CD320, the gene for cellular uptake of transcobalamin-bound vitamin B(12). (2010). https://pubmed.ncbi.nlm.nih.gov/20524213/ DOI: 10.1002/humu.21297
    tissue_or_cell_type
    Human cultured fibroblasts
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 387–398

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five newborn-derived fibroblast lines with homozygous CD320 deletion · source_derived_draft · unverified_draft

    ### b12-abs-e88del-uptake Fibroblasts from five asymptomatic newborns with elevated methylmalonic acid and homozygous CD320 p.Glu88del showed reduced uptake of holo-transcobalamin. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A receptor deletion reduced B12 delivery in patient cells. organism: Homo sapiens tissue_or_cell_type: Human cultured fibroblasts experimental_model: Five newborn-derived fibroblast lines with homozygous CD320 deletion limitations: Asymptomatic neonatal ascertainment does not establish later clinical severity. Cellular uptake does not isolate binding from receptor expression or trafficking. exposure: Homozygous c.262_264delGAG / p.Glu88del cross_nutrient: false [quadros-2010-e88del] Positive newborn screen for methylmalonic aciduria identifies the first mutation in TCblR/CD320, the gene for cellular uptake of transcobalamin-bound vitamin B(12). (2010). https://pubmed.ncbi.nlm.nih.gov/20524213/ DOI: 10.1002/humu.21297
    Complete structured claim and evidence

  2. Metformin-treated patients had depressed cobalamin levels and elevated fasting methylmalonic acid and homocysteine levels.

    Metformin → Fasting plasma methylmalonic acid concentration source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    biomarker_context Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/metformin-research/19846797.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "801079bb07e94e223a1d7bd7fc99c9f229320aa56b6afa11700765f481558b33", "start_char": 0, "end_char": 1789, "text_sha256": "801079bb07e94e223a1d7bd7fc99c9f229320aa56b6afa11700765f481558b33"}
    experimental_model
    Prospective case-control study of 122 people with type 2 diabetes and symptomatic neuropathy
    exposure
    More than six months of metformin versus no metformin exposure
    limitations
    Case-control design with nerve conduction studies. Cumulative dose correlated with severity, but the design cannot establish that the drug caused the neuropathy.
    nutrient_topic
    Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin
    organism
    Human
    plain_language
    The marker that rises specifically when B12 is short also rose.
    primary_references
    [metformin-p19846797] Association of metformin, elevated homocysteine, and methylmalonic acid levels and clinically worsened diabetic peripheral neuropathy. (2010). https://pubmed.ncbi.nlm.nih.gov/19846797/ DOI: 10.2337/dc09-0606
    tissue_or_cell_type
    Peripheral nerve
    trigger_kind
    biomarker_context Imported condition classification; unverified.

    Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 1204–1215

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prospective case-control study of 122 people with type 2 diabetes and symptomatic neuropathy · source_derived_draft · unverified_draft

    ### metformin-mma-elevation Metformin-treated patients had depressed cobalamin levels and elevated fasting methylmalonic acid and homocysteine levels. Condition category: biomarker_context nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: The marker that rises specifically when B12 is short also rose. organism: Human tissue_or_cell_type: Peripheral nerve experimental_model: Prospective case-control study of 122 people with type 2 diabetes and symptomatic neuropathy limitations: Case-control design with nerve conduction studies. Cumulative dose correlated with severity, but the design cannot establish that the drug caused the neuropathy. exposure: More than six months of metformin versus no metformin exposure evidence_span: {"source_cache": "artifacts/metformin-research/19846797.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "801079bb07e94e223a1d7bd7fc99c9f229320aa56b6afa11700765f481558b33", "start_char": 0, "end_char": 1789, "text_sha256": "801079bb07e94e223a1d7bd7fc99c9f229320aa56b6afa11700765f481558b33"} [metformin-p19846797] Association of metformin, elevated homocysteine, and methylmalonic acid levels and clinically worsened diabetic peripheral neuropathy. (2010). https://pubmed.ncbi.nlm.nih.gov/19846797/ DOI: 10.2337/dc09-0606
    Complete structured claim and evidence

  3. Acsf3 depletion increased labeled-threonine conversion to methylmalonic acid in mouse primary hepatocytes.

    Mouse acyl-CoA synthetase family member 3 / Acsf3 → Mouse threonine-derived methylmalonate flux source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full-text Figure 3 results excerpt
    experimental_model
    Primary-paper Figure 3 isotope tracing and Acsf3-deficient mouse hepatocytes.
    limitations
    This mouse experiment must not be summarized as proven human threonine depletion or a clinical treatment.
    nutrient_topic
    L-Threonine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Threonine
    plain_language
    A downstream metabolic defect changed how threonine carbon accumulated.
    primary_references
    An ancient regulatory variant of ACSF3 influences the coevolution of increased human height and basal metabolic rate via metabolic homeostasis. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40403731/ · DOI 10.1016/j.xgen.2025.100855
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 402–408

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary-paper Figure 3 isotope tracing and Acsf3-deficient mouse hepatocytes. · source_derived_draft · unverified_draft

    ## l-threonine-acsf3-methylmalonate A downstream metabolic defect changed how threonine carbon accumulated. Acsf3 depletion increased labeled-threonine conversion to methylmalonic acid in mouse primary hepatocytes. Model: Primary-paper Figure 3 isotope tracing and Acsf3-deficient mouse hepatocytes. Limitations: This mouse experiment must not be summarized as proven human threonine depletion or a clinical treatment. Evidence access: Primary full-text Figure 3 results excerpt An ancient regulatory variant of ACSF3 influences the coevolution of increased human height and basal metabolic rate via metabolic homeostasis. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40403731/ · DOI 10.1016/j.xgen.2025.100855
    Complete structured claim and evidence

  4. Threonine in drinking water increased serum methylmalonic acid in Acsf3-null mice on a ketogenic diet, but not significantly in controls.

    L-Threonine → Serum methylmalonic acid in Acsf3-null mice source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full-text Figure 3 results excerpt
    experimental_model
    Mouse genotype-by-diet experiment; ketogenic diet with amino-acid supplementation.
    limitations
    Not a human supplementation trial or evidence that serum MMA exclusively reports B12 status.
    nutrient_topic
    L-Threonine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Threonine
    plain_language
    More substrate affected a blocked metabolic setting differently from controls.
    primary_references
    An ancient regulatory variant of ACSF3 influences the coevolution of increased human height and basal metabolic rate via metabolic homeostasis. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40403731/ · DOI 10.1016/j.xgen.2025.100855
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 410–416

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse genotype-by-diet experiment; ketogenic diet with amino-acid supplementation. · source_derived_draft · unverified_draft

    ## l-threonine-acsf3-threonine-addition More substrate affected a blocked metabolic setting differently from controls. Threonine in drinking water increased serum methylmalonic acid in Acsf3-null mice on a ketogenic diet, but not significantly in controls. Model: Mouse genotype-by-diet experiment; ketogenic diet with amino-acid supplementation. Limitations: Not a human supplementation trial or evidence that serum MMA exclusively reports B12 status. Evidence access: Primary full-text Figure 3 results excerpt An ancient regulatory variant of ACSF3 influences the coevolution of increased human height and basal metabolic rate via metabolic homeostasis. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40403731/ · DOI 10.1016/j.xgen.2025.100855
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

    Evidence, AI assistance and curation standards