N-Acetyl-L-cysteine

evidence_access

Primary abstract

experimental_model

Human A549 cytokine-stimulation experiment.

limitations

The experiment supports a chemical-reactivity dependency; it does not establish a human supplement interaction magnitude.

nutrient_topic

Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins

plain_language

A separately stored thiol changed the signaling result.

primary_references

Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35806134/ · DOI 10.3390/ijms23137130

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 228–234

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human A549 cytokine-stimulation experiment. · source_derived_draft · unverified_draft

## cucurbitacin-b-nac-icam-rescue A separately stored thiol changed the signaling result. Adding N-acetylcysteine attenuated cucurbitacin B inhibition of TNF-alpha-induced ICAM1 expression; L-cysteine had a smaller effect than the other tested thiols. Model: Human A549 cytokine-stimulation experiment. Limitations: The experiment supports a chemical-reactivity dependency; it does not establish a human supplement interaction magnitude. Evidence access: Primary abstract Cucurbitacin B Down-Regulates TNF Receptor 1 Expression and Inhibits the TNF-α-Dependent Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35806134/ · DOI 10.3390/ijms23137130

evidence_access

Primary abstract

experimental_model

Human NSCLC experiments plus separate cell-free interaction assays.

limitations

Compound trapping and redox effects are not distinguished by rescue alone.

nutrient_topic

Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins

plain_language

Thiol availability changed the experimental response.

primary_references

Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 148–154

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human NSCLC experiments plus separate cell-free interaction assays. · source_derived_draft · unverified_draft

## cucurbitacin-b-nac-rescue Thiol availability changed the experimental response. Adding N-acetylcysteine attenuated the reported cucurbitacin B cellular effects in the human NSCLC study. Model: Human NSCLC experiments plus separate cell-free interaction assays. Limitations: Compound trapping and redox effects are not distinguished by rescue alone. Evidence access: Primary abstract Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_location

Rat Model of TD; Results; Figures 6-7

evidence_span

NAC prevented downregulation of the transporter protein

experimental_model

Male Sprague-Dawley rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day, with or without N-acetylcysteine 163 mg/kg/day intraperitoneally; day-14 symptomatic stage; pair-fed controls.

exposure

Pyrithiamine-assisted depletion with pharmacological N-acetylcysteine co-treatment

limitations

N-acetylcysteine has multiple actions; this does not prove a specific glutathione mechanism or support a human dosing recommendation.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Rattus norvegicus

plain_language

An antioxidant intervention preserved a glutamate transporter in this experimental model.

primary_references

[hazell-2010-human-astrocytes] Loss of astrocytic glutamate transporters in Wernicke encephalopathy (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC3388119/ DOI: 10.1002/glia.20908

tissue_or_cell_type

Medial thalamus

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1283–1295

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Male Sprague-Dawley rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day, with or without N-acetylcysteine 163 mg/kg/day intraperitoneally; day-14 symptomatic stage; pair-fed controls. · source_derived_draft · unverified_draft

### thiamine-def-nac-preserves-rat-eaat2 N-acetylcysteine co-treatment prevented the loss of EAAT2 protein in medial thalamus of the depleted rats. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An antioxidant intervention preserved a glutamate transporter in this experimental model. organism: Rattus norvegicus tissue_or_cell_type: Medial thalamus experimental_model: Male Sprague-Dawley rats; thiamine-deficient diet plus pyrithiamine 0.5 mg/kg/day, with or without N-acetylcysteine 163 mg/kg/day intraperitoneally; day-14 symptomatic stage; pair-fed controls. limitations: N-acetylcysteine has multiple actions; this does not prove a specific glutathione mechanism or support a human dosing recommendation. evidence_location: Rat Model of TD; Results; Figures 6-7 evidence_span: NAC prevented downregulation of the transporter protein exposure: Pyrithiamine-assisted depletion with pharmacological N-acetylcysteine co-treatment [hazell-2010-human-astrocytes] Loss of astrocytic glutamate transporters in Wernicke encephalopathy (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC3388119/ DOI: 10.1002/glia.20908

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

Contused rat skeletal muscle with a reactive oxygen species scavenger and a nitric oxide synthase inhibitor

exposure

2.5 ATA 100% oxygen for 120 minutes daily for 5 consecutive days

limitations

Both inhibitors were given before treatment, which is what makes the requirement claim interpretable. The exposure is a therapy-like protocol, unlike the extreme-pressure studies recorded elsewhere here.

nutrient_topic

Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

organism

Rat

plain_language

Mopping up the reactive species, or blocking nitric oxide production, cancels the benefit.

primary_references

[hbot-p32066777] VEGF and bFGF induction by nitric oxide is associated with hyperbaric oxygen-induced angiogenesis and muscle regeneration. (2020). https://pubmed.ncbi.nlm.nih.gov/32066777/ DOI: 10.1038/s41598-020-59615-x

tissue_or_cell_type

Skeletal muscle

trigger_kind

machinery_impairment Imported condition classification; unverified.

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 699–710

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Contused rat skeletal muscle with a reactive oxygen species scavenger and a nitric oxide synthase inhibitor · source_derived_draft · unverified_draft

### hbot-nac-lname-block Administration of either N-acetylcysteine or L-NAME before treatment suppressed angiogenesis and muscle regeneration even after hyperbaric oxygen. Condition category: machinery_impairment nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Mopping up the reactive species, or blocking nitric oxide production, cancels the benefit. organism: Rat tissue_or_cell_type: Skeletal muscle experimental_model: Contused rat skeletal muscle with a reactive oxygen species scavenger and a nitric oxide synthase inhibitor limitations: Both inhibitors were given before treatment, which is what makes the requirement claim interpretable. The exposure is a therapy-like protocol, unlike the extreme-pressure studies recorded elsewhere here. exposure: 2.5 ATA 100% oxygen for 120 minutes daily for 5 consecutive days evidence_span: {"source_cache": "artifacts/hbot-research/32066777.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8915aa50d5b22722e66d20eb0542c6bb03b76a3182d37215a53bc9238ac697d", "start_char": 0, "end_char": 1357, "text_sha256": "f8915aa50d5b22722e66d20eb0542c6bb03b76a3182d37215a53bc9238ac697d"} [hbot-p32066777] VEGF and bFGF induction by nitric oxide is associated with hyperbaric oxygen-induced angiogenesis and muscle regeneration. (2020). https://pubmed.ncbi.nlm.nih.gov/32066777/ DOI: 10.1038/s41598-020-59615-x

evidence_span

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experimental_model

Curcumin analog chemistry and stimulated cellular NF-kappa-B assays

exposure

NAC 3 mM overnight before the curcumin/LPS reporter assay

limitations

Cell assay, not evidence that oral NAC cancels curcumin benefits in people; enhanced glutathione buffering was the authors proposed this explanation.

nutrient_topic

Curcumin research collection; topical membership is not evidence of a direct dietary effect. · Curcumin

organism

Mus musculus

plain_language

A glutathione precursor changed the response in the opposite direction from blocking glutathione synthesis.

primary_references

[curcumin-p29097552] The anti-inflammatory activity of curcumin is mediated by its oxidative metabolites. (2017). https://pubmed.ncbi.nlm.nih.gov/29097552/ DOI: 10.1074/jbc.ra117.000123

tissue_or_cell_type

RAW264.7 macrophage-like cells

Curcumin: metabolism, signaling and nutrient connections (2026-09-17) · lines 489–500

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Curcumin analog chemistry and stimulated cellular NF-kappa-B assays · source_derived_draft · unverified_draft

### curcumin-nac-buffering NAC pretreatment shifted the curcumin dose-response curve toward lower inhibitory potency in RAW264.7 cells. Condition category: normal nutrient_topic: Curcumin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A glutathione precursor changed the response in the opposite direction from blocking glutathione synthesis. organism: Mus musculus tissue_or_cell_type: RAW264.7 macrophage-like cells experimental_model: Curcumin analog chemistry and stimulated cellular NF-kappa-B assays limitations: Cell assay, not evidence that oral NAC cancels curcumin benefits in people; enhanced glutathione buffering was the authors proposed this explanation. exposure: NAC 3 mM overnight before the curcumin/LPS reporter assay evidence_span: {"source_cache": "artifacts/curcumin-research/29097552.publisher-preview.txt", "locator": "Primary public publisher preview, reference superscripts removed; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fe26fe4a94e0ab5b60d128b86deb5bc8723e13a0403fcbdba7ef97224a22ef9a", "start_char": 0, "end_char": 2711, "text_sha256": "fe26fe4a94e0ab5b60d128b86deb5bc8723e13a0403fcbdba7ef97224a22ef9a"} [curcumin-p29097552] The anti-inflammatory activity of curcumin is mediated by its oxidative metabolites. (2017). https://pubmed.ncbi.nlm.nih.gov/29097552/ DOI: 10.1074/jbc.ra117.000123

evidence_access

Primary abstract

experimental_model

Tumor-cell cotreatment experiment.

limitations

Does not establish a clinical fisetin-NAC interaction or show whether oral exposures reproduce it.

nutrient_topic

Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Fisetin

plain_language

An antioxidant intervention weakened the cell-killing response.

primary_references

Activation of reactive oxygen species/AMP activated protein kinase signaling mediates fisetin-induced apoptosis in multiple myeloma U266 cells. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22261340/ · DOI 10.1016/j.canlet.2012.01.008

Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 376–382

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Tumor-cell cotreatment experiment. · source_derived_draft · unverified_draft

## fisetin-u266-nac-rescue An antioxidant intervention weakened the cell-killing response. N-acetylcysteine blocked fisetin-induced apoptosis in human U266 cells. Model: Tumor-cell cotreatment experiment. Limitations: Does not establish a clinical fisetin-NAC interaction or show whether oral exposures reproduce it. Evidence access: Primary abstract Activation of reactive oxygen species/AMP activated protein kinase signaling mediates fisetin-induced apoptosis in multiple myeloma U266 cells. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22261340/ · DOI 10.1016/j.canlet.2012.01.008

evidence_access

Primary abstract

experimental_model

Recombinant human MPST assays.

limitations

This does not negate NAC metabolism to cysteine or its other mechanisms.

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

A cysteine precursor does not necessarily substitute for cysteine in each chemical reaction.

primary_references

Thioredoxin regulates human mercaptopyruvate sulfurtransferase at physiologically-relevant concentrations. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32179647/ · DOI 10.1074/jbc.RA120.012616

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 476–482

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human MPST assays. · source_derived_draft · unverified_draft

## l-cysteine-mpst-nac-distinction A cysteine precursor does not necessarily substitute for cysteine in each chemical reaction. N-acetylcysteine was a poor MPST sulfur acceptor in the reported kinetic experiments. Model: Recombinant human MPST assays. Limitations: This does not negate NAC metabolism to cysteine or its other mechanisms. Evidence access: Primary abstract Thioredoxin regulates human mercaptopyruvate sulfurtransferase at physiologically-relevant concentrations. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32179647/ · DOI 10.1074/jbc.RA120.012616

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse Slc1a1 deletion with NAC treatment.

limitations

NAC is the tested intervention, not free L-cysteine; no human cognitive benefit is established.

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

A different precursor bypassed part of the uptake limitation in this animal model.

primary_references

Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16311588/ · DOI 10.1038/nn1609

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 108–114

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse Slc1a1 deletion with NAC treatment. · source_derived_draft · unverified_draft

## l-cysteine-nac-neuronal-rescue A different precursor bypassed part of the uptake limitation in this animal model. N-acetylcysteine treatment reversed reduced neuronal glutathione and oxidant-related abnormalities in EAAC1-deficient mice. Model: Mouse Slc1a1 deletion with NAC treatment. Limitations: NAC is the tested intervention, not free L-cysteine; no human cognitive benefit is established. Evidence access: Primary abstract Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16311588/ · DOI 10.1038/nn1609

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse EAAC1-null ischemia model.

limitations

NAC and chelators are separate interventions; the study does not show that extra dietary cysteine and zinc are synergistic.

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

Restoring precursor supply and binding excess labile zinc were distinct rescue routes.

primary_references

EAAC1 gene deletion alters zinc homeostasis and exacerbates neuronal injury after transient cerebral ischemia. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21084597/ · DOI 10.1523/JNEUROSCI.2084-10.2010

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 124–130

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse EAAC1-null ischemia model. · source_derived_draft · unverified_draft

## l-cysteine-neuronal-zinc-rescue Restoring precursor supply and binding excess labile zinc were distinct rescue routes. NAC restored neuronal glutathione and normalized basal zinc levels in EAAC1-null mice; NAC or zinc chelation reduced ischemia-associated zinc movement, superoxide and neuronal death. Model: Mouse EAAC1-null ischemia model. Limitations: NAC and chelators are separate interventions; the study does not show that extra dietary cysteine and zinc are synergistic. Evidence access: Primary abstract EAAC1 gene deletion alters zinc homeostasis and exacerbates neuronal injury after transient cerebral ischemia. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21084597/ · DOI 10.1523/JNEUROSCI.2084-10.2010

evidence_access

Primary full text; Figure 5

experimental_model

Caco-2 co-exposure experiments.

limitations

Not evidence that NAC supplements prevent effects of dietary aspartame.

nutrient_topic

Aspartame collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Aspartame

plain_language

An antioxidant-related perturbation changed the pathway response.

primary_references

Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32580504/ · DOI 10.3390/nu12061862

Aspartame: digestion, taste, metabolite dependencies and experimental signaling (2026-09-20) · lines 226–232

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Caco-2 co-exposure experiments. · source_derived_draft · unverified_draft

## aspartame-nac-rescue An antioxidant-related perturbation changed the pathway response. N-acetylcysteine at 1 mM attenuated aspartame-associated oxidative and barrier changes. Model: Caco-2 co-exposure experiments. Limitations: Not evidence that NAC supplements prevent effects of dietary aspartame. Evidence access: Primary full text; Figure 5 Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32580504/ · DOI 10.3390/nu12061862

dose

N-acetylcysteine 2 mM before indicaxanthin 60 micromolar plus cisplatin 10 micromolar

duration

NAC 1 h before the 24 h combination exposure

evidence_access

Primary open full text, relevant results/methods and PubMed metadata.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Human HeLa cervical cancer cells with NAC pretreatment

limitations

NAC blunted the combination response without restoring every outcome to baseline. This experiment is not a recommendation for or against NAC during chemotherapy.

nutrient_topic

Dedicated indicaxanthin chapter; original betalain family identity and shared claims preserved. · Indicaxanthin

organism

Human HeLa cervical cancer cells with NAC pretreatment

plain_language

N-acetylcysteine pretreatment reduced apoptosis caused by the indicaxanthin/cisplatin combination in HeLa cells.

primary_references

The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis. (2020). https://pubmed.ncbi.nlm.nih.gov/32630700/ DOI: 10.3390/biom10070994

route

In vitro pretreatment/co-treatment

tissue

Cell death and redox assays

Indicaxanthin: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 327–336

Original AI-assisted curation of thirteen additional primary studies, with twenty-six existing claims from eight studies linked unchanged. Study-specific citations and limitations retained. Not publisher full text. · supports · Human HeLa cervical cancer cells with NAC pretreatment · source_derived_draft · unverified_draft

## indicaxanthin-nac-combination-antagonism N-acetylcysteine pretreatment reduced apoptosis caused by the indicaxanthin/cisplatin combination in HeLa cells. Model/species: Human HeLa cervical cancer cells with NAC pretreatment Tissue: Cell death and redox assays Exposure: N-acetylcysteine 2 mM before indicaxanthin 60 micromolar plus cisplatin 10 micromolar Route: In vitro pretreatment/co-treatment Duration: NAC 1 h before the 24 h combination exposure Limits: NAC blunted the combination response without restoring every outcome to baseline. This experiment is not a recommendation for or against NAC during chemotherapy. Primary reference: The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis. (2020). https://pubmed.ncbi.nlm.nih.gov/32630700/ DOI: 10.3390/biom10070994 Access: Primary open full text, relevant results/methods and PubMed metadata.

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

Targeted GGT gene disruption and NAC rescue

exposure

Ggt1-null versus wild type; oral NAC

limitations

Severe genetic salvage defect; high extracellular GSH did not mean adequate tissue stores.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Mouse

plain_language

Providing an alternative cysteine source bypassed part of the salvage problem.

primary_references

[glutathione-p8755578] Growth retardation and cysteine deficiency in gamma-glutamyl transpeptidase-deficient mice. (1996). https://pubmed.ncbi.nlm.nih.gov/8755578/ DOI: 10.1073/pnas.93.15.7923

tissue_or_cell_type

Plasma, urine, eye, liver and pancreas

trigger_kind

machinery_impairment Imported condition classification; unverified.

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 710–721

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Targeted GGT gene disruption and NAC rescue · source_derived_draft · unverified_draft

### glutathione-ggt-nac-rescue Oral NAC restored normal growth rates in the Ggt1-null mice. Condition category: machinery_impairment nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Providing an alternative cysteine source bypassed part of the salvage problem. organism: Mouse tissue_or_cell_type: Plasma, urine, eye, liver and pancreas experimental_model: Targeted GGT gene disruption and NAC rescue limitations: Severe genetic salvage defect; high extracellular GSH did not mean adequate tissue stores. exposure: Ggt1-null versus wild type; oral NAC evidence_span: {"source_cache": "artifacts/glutathione-research/8755578.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "94d2520bc0124611c649d943ab9acd9cdf73cd3cb99d66640338a57bda6f6dfb", "start_char": 0, "end_char": 1159, "text_sha256": "94d2520bc0124611c649d943ab9acd9cdf73cd3cb99d66640338a57bda6f6dfb"} [glutathione-p8755578] Growth retardation and cysteine deficiency in gamma-glutamyl transpeptidase-deficient mice. (1996). https://pubmed.ncbi.nlm.nih.gov/8755578/ DOI: 10.1073/pnas.93.15.7923

evidence_access

Primary abstract

experimental_model

Cell-free chemistry.

limitations

NAC rescue therefore does not uniquely prove ROS scavenging; it also does not rule out a role for ROS.

nutrient_topic

Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins

plain_language

An antioxidant can also change the amount of available test compound.

primary_references

Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 116–122

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cell-free chemistry. · source_derived_draft · unverified_draft

## cucurbitacin-b-nac-interaction An antioxidant can also change the amount of available test compound. UV spectroscopy and FTICR mass spectrometry detected physical interaction between cucurbitacin B and N-acetylcysteine in a cell-free system. Model: Cell-free chemistry. Limitations: NAC rescue therefore does not uniquely prove ROS scavenging; it also does not rule out a role for ROS. Evidence access: Primary abstract Cucurbitacin B potently suppresses non-small-cell lung cancer growth: identification of intracellular thiols as critical targets. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23340170/ · DOI 10.1016/j.canlet.2013.01.008

evidence_span

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experimental_model

Cell perturbation and xenograft experiments

exposure

DIM; NRF2 overexpression and pharmacological rescue controls

limitations

Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people.

nutrient_topic

Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM

organism

Human non-small-cell lung-cancer cells and mouse xenografts

plain_language

Perturbation controls helped connect the response to specific defenses.

primary_references

[dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z

tissue_or_cell_type

Ferroptosis and AHR/NRF2/GPX4

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1351–1362

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell perturbation and xenograft experiments · source_derived_draft · unverified_draft

### dim-nsclc-ferroptosis DIM induced ferroptosis that could be reversed by ferrostatin-1, NAC or the tested AHR antagonist; NRF2 overexpression also reversed it. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Perturbation controls helped connect the response to specific defenses. organism: Human non-small-cell lung-cancer cells and mouse xenografts tissue_or_cell_type: Ferroptosis and AHR/NRF2/GPX4 experimental_model: Cell perturbation and xenograft experiments limitations: Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people. exposure: DIM; NRF2 overexpression and pharmacological rescue controls evidence_span: {"source_cache": "artifacts/dim-research/40100489.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0", "start_char": 0, "end_char": 1722, "text_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0"} [dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z

evidence_access

Primary abstract

experimental_model

Human breast-cancer pharmacology.

limitations

Probe rescue does not identify the ROS-generating enzyme or prove the same route after human ingestion.

nutrient_topic

Cucurbitacins collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Cucurbitacins

plain_language

Two different probes help test the oxidative-stress route.

primary_references

Cucurbitacin I inhibits Rac1 activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of Janus tyrosine kinase 2 and P-Rex1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23478800/ · DOI 10.1124/mol.112.084293

Cucurbitacins: thiol chemistry, cytoskeleton, metabolic dependencies and signaling (2026-09-20) · lines 180–186

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human breast-cancer pharmacology. · source_derived_draft · unverified_draft

## cucurbitacin-i-mitoros-rescue Two different probes help test the oxidative-stress route. Mito-TEMPO and NAC prevented tested cucurbitacin I effects on Rac1 activation, supporting mitochondrial ROS involvement alongside the thiol-interception caveat for NAC. Model: Human breast-cancer pharmacology. Limitations: Probe rescue does not identify the ROS-generating enzyme or prove the same route after human ingestion. Evidence access: Primary abstract Cucurbitacin I inhibits Rac1 activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of Janus tyrosine kinase 2 and P-Rex1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23478800/ · DOI 10.1124/mol.112.084293

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/paracetamol-research/36191122.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "859db1958aeb26b75a34a32e4dd1c4713dc7db413717cefe62a3659856db7568", "start_char": 0, "end_char": 3325, "text_sha256": "859db1958aeb26b75a34a32e4dd1c4713dc7db413717cefe62a3659856db7568"}

experimental_model

Review of point-of-care testing and antidote guidance for acute overdose

exposure

Serum acetaminophen concentration interpreted against the Rumack-Matthew nomogram

limitations

A health-technology review rather than primary research. The nomogram figures it quotes are derived from patients not treated with antidote, which is stated.

nutrient_topic

Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. · Paracetamol

organism

Human

plain_language

Above a concentration that can be read off a chart, the liver fails in most people unless the antidote is given.

primary_references

[apap-p36191122] Point-of-Care Testing and N-Acetylcysteine for Acute Acetaminophen Overdose (2021). https://pubmed.ncbi.nlm.nih.gov/36191122/

tissue_or_cell_type

Liver

trigger_kind

biomarker_context Imported condition classification; unverified.

Paracetamol: the enzyme it reduces rather than blocks, the isoform that turned out not to exist, the metabolite that carries the analgesia, and the metabolite that destroys the liver (2026-09-22) · lines 428–439

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of point-of-care testing and antidote guidance for acute overdose · source_derived_draft · unverified_draft

### apap-the-nomogram-and-the-antidote Acetaminophen overdose is the leading cause of acute liver failure in Canada and around the world with approximately 4,500 hospitalisations each year in Canada and about 6% of those hospitalised developing liver injury including acute liver failure that may require transplant or lead to death, and on the Rumack-Matthew nomogram derived from patients not treated with antidote a serum concentration above 200 milligrams per litre at 4 hours carries a 60% incidence of severe hepatotoxicity and 5% mortality rising to 90% and 24% at 300 milligrams per litre, with treatment by N-acetylcysteine required above 140 milligrams per litre at 4 hours. Condition category: biomarker_context nutrient_topic: Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. plain_language: Above a concentration that can be read off a chart, the liver fails in most people unless the antidote is given. organism: Human tissue_or_cell_type: Liver experimental_model: Review of point-of-care testing and antidote guidance for acute overdose limitations: A health-technology review rather than primary research. The nomogram figures it quotes are derived from patients not treated with antidote, which is stated. exposure: Serum acetaminophen concentration interpreted against the Rumack-Matthew nomogram evidence_span: {"source_cache": "artifacts/paracetamol-research/36191122.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "859db1958aeb26b75a34a32e4dd1c4713dc7db413717cefe62a3659856db7568", "start_char": 0, "end_char": 3325, "text_sha256": "859db1958aeb26b75a34a32e4dd1c4713dc7db413717cefe62a3659856db7568"} [apap-p36191122] Point-of-Care Testing and N-Acetylcysteine for Acute Acetaminophen Overdose (2021). https://pubmed.ncbi.nlm.nih.gov/36191122/

evidence_span

{"source_cache": "artifacts/glutathione-research/35821844.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3", "start_char": 0, "end_char": 2083, "text_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3"}

experimental_model

Randomized controlled dose-ranging trial

exposure

2.4, 4.8 or 7.2 g/day GlyNAC, 1:1 ratio, for two weeks

limitations

Primary outcomes were null; the favorable low-GSH/high-MDA subgroup was post hoc and hypothesis-generating.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human

plain_language

Adding precursors did not reliably improve redox status in the overall trial.

primary_references

[glutathione-p35821844] A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. (2022). https://pubmed.ncbi.nlm.nih.gov/35821844/ DOI: 10.3389/fragi.2022.852569

tissue_or_cell_type

114 healthy older volunteers; 20 young reference participants

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1256–1267

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized controlled dose-ranging trial · source_derived_draft · unverified_draft

### glutathione-glynac-large-ratio-null GlyNAC did not significantly improve the GSH:GSSG ratio; high-dose versus placebo p=0.739. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding precursors did not reliably improve redox status in the overall trial. organism: Human tissue_or_cell_type: 114 healthy older volunteers; 20 young reference participants experimental_model: Randomized controlled dose-ranging trial limitations: Primary outcomes were null; the favorable low-GSH/high-MDA subgroup was post hoc and hypothesis-generating. exposure: 2.4, 4.8 or 7.2 g/day GlyNAC, 1:1 ratio, for two weeks evidence_span: {"source_cache": "artifacts/glutathione-research/35821844.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3", "start_char": 0, "end_char": 2083, "text_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3"} [glutathione-p35821844] A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. (2022). https://pubmed.ncbi.nlm.nih.gov/35821844/ DOI: 10.3389/fragi.2022.852569

evidence_span

{"source_cache": "artifacts/glutathione-research/35821844.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3", "start_char": 0, "end_char": 2083, "text_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3"}

experimental_model

Randomized controlled dose-ranging trial

exposure

2.4, 4.8 or 7.2 g/day GlyNAC, 1:1 ratio, for two weeks

limitations

Primary outcomes were null; the favorable low-GSH/high-MDA subgroup was post hoc and hypothesis-generating.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human

plain_language

The main trial result must remain visible alongside favorable subsets.

primary_references

[glutathione-p35821844] A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. (2022). https://pubmed.ncbi.nlm.nih.gov/35821844/ DOI: 10.3389/fragi.2022.852569

tissue_or_cell_type

114 healthy older volunteers; 20 young reference participants

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1269–1280

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized controlled dose-ranging trial · source_derived_draft · unverified_draft

### glutathione-glynac-large-total-null The primary total-GSH endpoint was not significantly increased; high-dose versus placebo p=0.278. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The main trial result must remain visible alongside favorable subsets. organism: Human tissue_or_cell_type: 114 healthy older volunteers; 20 young reference participants experimental_model: Randomized controlled dose-ranging trial limitations: Primary outcomes were null; the favorable low-GSH/high-MDA subgroup was post hoc and hypothesis-generating. exposure: 2.4, 4.8 or 7.2 g/day GlyNAC, 1:1 ratio, for two weeks evidence_span: {"source_cache": "artifacts/glutathione-research/35821844.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3", "start_char": 0, "end_char": 2083, "text_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3"} [glutathione-p35821844] A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. (2022). https://pubmed.ncbi.nlm.nih.gov/35821844/ DOI: 10.3389/fragi.2022.852569

evidence_span

{"source_cache": "artifacts/glutathione-research/35821844.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3", "start_char": 0, "end_char": 2083, "text_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3"}

experimental_model

Randomized controlled dose-ranging trial

exposure

2.4, 4.8 or 7.2 g/day GlyNAC, 1:1 ratio, for two weeks

limitations

Primary outcomes were null; the favorable low-GSH/high-MDA subgroup was post hoc and hypothesis-generating.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human

plain_language

A subgroup signal needs confirmation in a prespecified trial.

primary_references

[glutathione-p35821844] A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. (2022). https://pubmed.ncbi.nlm.nih.gov/35821844/ DOI: 10.3389/fragi.2022.852569

tissue_or_cell_type

114 healthy older volunteers; 20 young reference participants

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1282–1293

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized controlled dose-ranging trial · source_derived_draft · unverified_draft

### glutathione-glynac-posthoc A post-hoc high-MDA/low-baseline-GSH subgroup had higher total GSH with pooled medium/high doses (p=0.016). Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A subgroup signal needs confirmation in a prespecified trial. organism: Human tissue_or_cell_type: 114 healthy older volunteers; 20 young reference participants experimental_model: Randomized controlled dose-ranging trial limitations: Primary outcomes were null; the favorable low-GSH/high-MDA subgroup was post hoc and hypothesis-generating. exposure: 2.4, 4.8 or 7.2 g/day GlyNAC, 1:1 ratio, for two weeks evidence_span: {"source_cache": "artifacts/glutathione-research/35821844.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3", "start_char": 0, "end_char": 2083, "text_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3"} [glutathione-p35821844] A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. (2022). https://pubmed.ncbi.nlm.nih.gov/35821844/ DOI: 10.3389/fragi.2022.852569

evidence_span

{"source_cache": "artifacts/glutathione-research/35975308.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088", "start_char": 0, "end_char": 1950, "text_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088"}

experimental_model

Randomized placebo-controlled trial in older adults

exposure

Sixteen-week GlyNAC versus isonitrogenous alanine placebo

limitations

Small trial, many outcomes; no demonstrated lifespan extension. Reference young group was not an additional older randomized arm.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human

plain_language

Functional signals accompany the biochemical result, with replication still needed.

primary_references

[glutathione-p35975308] Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. (2023). https://pubmed.ncbi.nlm.nih.gov/35975308/ DOI: 10.1093/gerona/glac135

tissue_or_cell_type

24 older adults randomized 12 per arm; 12 young reference participants

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1308–1319

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled trial in older adults · source_derived_draft · unverified_draft

### glutathione-glynac-small-function Investigators reported improved physical-function assessments with GlyNAC but not placebo. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Functional signals accompany the biochemical result, with replication still needed. organism: Human tissue_or_cell_type: 24 older adults randomized 12 per arm; 12 young reference participants experimental_model: Randomized placebo-controlled trial in older adults limitations: Small trial, many outcomes; no demonstrated lifespan extension. Reference young group was not an additional older randomized arm. exposure: Sixteen-week GlyNAC versus isonitrogenous alanine placebo evidence_span: {"source_cache": "artifacts/glutathione-research/35975308.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088", "start_char": 0, "end_char": 1950, "text_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088"} [glutathione-p35975308] Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. (2023). https://pubmed.ncbi.nlm.nih.gov/35975308/ DOI: 10.1093/gerona/glac135

evidence_span

{"source_cache": "artifacts/glutathione-research/35975308.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088", "start_char": 0, "end_char": 1950, "text_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088"}

experimental_model

Randomized placebo-controlled trial in older adults

exposure

Sixteen-week GlyNAC versus isonitrogenous alanine placebo

limitations

Small trial, many outcomes; no demonstrated lifespan extension. Reference young group was not an additional older randomized arm.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human

plain_language

The small longer trial reported a biochemical benefit.

primary_references

[glutathione-p35975308] Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. (2023). https://pubmed.ncbi.nlm.nih.gov/35975308/ DOI: 10.1093/gerona/glac135

tissue_or_cell_type

24 older adults randomized 12 per arm; 12 young reference participants

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1295–1306

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled trial in older adults · source_derived_draft · unverified_draft

### glutathione-glynac-small-gsh The older GlyNAC group improved measured GSH deficiency relative to the placebo pattern. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The small longer trial reported a biochemical benefit. organism: Human tissue_or_cell_type: 24 older adults randomized 12 per arm; 12 young reference participants experimental_model: Randomized placebo-controlled trial in older adults limitations: Small trial, many outcomes; no demonstrated lifespan extension. Reference young group was not an additional older randomized arm. exposure: Sixteen-week GlyNAC versus isonitrogenous alanine placebo evidence_span: {"source_cache": "artifacts/glutathione-research/35975308.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088", "start_char": 0, "end_char": 1950, "text_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088"} [glutathione-p35975308] Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. (2023). https://pubmed.ncbi.nlm.nih.gov/35975308/ DOI: 10.1093/gerona/glac135

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/glutathione-research/21795440.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd", "start_char": 0, "end_char": 2139, "text_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd"}

experimental_model

Stable-isotope tracer study with before/after supplementation

exposure

Two weeks of glycine/cysteine-precursor supplementation in older participants

limitations

Small non-placebo-controlled intervention; age comparison and treatment response are not universal aging rules.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human

plain_language

The measured amount produced also increased.

primary_references

[glutathione-p21795440] Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. (2011). https://pubmed.ncbi.nlm.nih.gov/21795440/ DOI: 10.3945/ajcn.110.003483

tissue_or_cell_type

Eight older and eight younger adults; erythrocytes

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1113–1124

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope tracer study with before/after supplementation · source_derived_draft · unverified_draft

### glutathione-precursor-absolute-synthesis The absolute erythrocyte GSH synthesis rate increased 230.9% after supplementation. Condition category: nutrient_deficiency nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured amount produced also increased. organism: Human tissue_or_cell_type: Eight older and eight younger adults; erythrocytes experimental_model: Stable-isotope tracer study with before/after supplementation limitations: Small non-placebo-controlled intervention; age comparison and treatment response are not universal aging rules. exposure: Two weeks of glycine/cysteine-precursor supplementation in older participants evidence_span: {"source_cache": "artifacts/glutathione-research/21795440.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd", "start_char": 0, "end_char": 2139, "text_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd"} [glutathione-p21795440] Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. (2011). https://pubmed.ncbi.nlm.nih.gov/21795440/ DOI: 10.3945/ajcn.110.003483

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/glutathione-research/21795440.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd", "start_char": 0, "end_char": 2139, "text_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd"}

experimental_model

Stable-isotope tracer study with before/after supplementation

exposure

Two weeks of glycine/cysteine-precursor supplementation in older participants

limitations

Small non-placebo-controlled intervention; age comparison and treatment response are not universal aging rules.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human

plain_language

A low measured pool increased in this small study.

primary_references

[glutathione-p21795440] Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. (2011). https://pubmed.ncbi.nlm.nih.gov/21795440/ DOI: 10.3945/ajcn.110.003483

tissue_or_cell_type

Eight older and eight younger adults; erythrocytes

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1126–1137

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope tracer study with before/after supplementation · source_derived_draft · unverified_draft

### glutathione-precursor-pool The older group’s erythrocyte GSH concentration increased 94.6% after supplementation. Condition category: nutrient_deficiency nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A low measured pool increased in this small study. organism: Human tissue_or_cell_type: Eight older and eight younger adults; erythrocytes experimental_model: Stable-isotope tracer study with before/after supplementation limitations: Small non-placebo-controlled intervention; age comparison and treatment response are not universal aging rules. exposure: Two weeks of glycine/cysteine-precursor supplementation in older participants evidence_span: {"source_cache": "artifacts/glutathione-research/21795440.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd", "start_char": 0, "end_char": 2139, "text_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd"} [glutathione-p21795440] Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. (2011). https://pubmed.ncbi.nlm.nih.gov/21795440/ DOI: 10.3945/ajcn.110.003483

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/glutathione-research/21795440.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd", "start_char": 0, "end_char": 2139, "text_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd"}

experimental_model

Stable-isotope tracer study with before/after supplementation

exposure

Two weeks of glycine/cysteine-precursor supplementation in older participants

limitations

Small non-placebo-controlled intervention; age comparison and treatment response are not universal aging rules.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human

plain_language

The fraction of the pool synthesized each day increased.

primary_references

[glutathione-p21795440] Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. (2011). https://pubmed.ncbi.nlm.nih.gov/21795440/ DOI: 10.3945/ajcn.110.003483

tissue_or_cell_type

Eight older and eight younger adults; erythrocytes

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1100–1111

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope tracer study with before/after supplementation · source_derived_draft · unverified_draft

### glutathione-precursor-synthesis After supplementation, older participants had a 78.8% higher fractional GSH synthesis rate. Condition category: nutrient_deficiency nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The fraction of the pool synthesized each day increased. organism: Human tissue_or_cell_type: Eight older and eight younger adults; erythrocytes experimental_model: Stable-isotope tracer study with before/after supplementation limitations: Small non-placebo-controlled intervention; age comparison and treatment response are not universal aging rules. exposure: Two weeks of glycine/cysteine-precursor supplementation in older participants evidence_span: {"source_cache": "artifacts/glutathione-research/21795440.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd", "start_char": 0, "end_char": 2139, "text_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd"} [glutathione-p21795440] Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. (2011). https://pubmed.ncbi.nlm.nih.gov/21795440/ DOI: 10.3945/ajcn.110.003483