Component

Experimentally methionine-restricted diet

Context-specific entity; species, compartment and exposure are stated on each claim.

12 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. Gcn2-null mice retained the methionine-restriction changes in adiposity, energy expenditure, insulin sensitivity and FGF21 induction.

    Experimentally methionine-restricted diet → Mouse GCN2 / Eif2ak4 source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Wild-type and Gcn2-knockout mice under the study diet.
    limitations
    Not a universal statement about GCN2 during total starvation or other amino-acid deficiencies.
    nutrient_topic
    L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Methionine
    plain_language
    This dietary response did not require the usual amino-acid stress sensor.
    primary_references
    Role of GCN2-Independent Signaling Through a Noncanonical PERK/NRF2 Pathway in the Physiological Responses to Dietary Methionine Restriction. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26936965/ · DOI 10.2337/db15-1324
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 380–386

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Wild-type and Gcn2-knockout mice under the study diet. · source_derived_draft · unverified_draft

    ## methionine-gcn2-dispensability This dietary response did not require the usual amino-acid stress sensor. Gcn2-null mice retained the methionine-restriction changes in adiposity, energy expenditure, insulin sensitivity and FGF21 induction. Model: Wild-type and Gcn2-knockout mice under the study diet. Limitations: Not a universal statement about GCN2 during total starvation or other amino-acid deficiencies. Evidence access: Primary abstract Role of GCN2-Independent Signaling Through a Noncanonical PERK/NRF2 Pathway in the Physiological Responses to Dietary Methionine Restriction. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26936965/ · DOI 10.2337/db15-1324
    Complete structured claim and evidence

  2. In twenty adults, four-week methionine-only restriction changed fewer metabolic markers than combined methionine/cysteine restriction; both increased FGF21 in the reported comparisons.

    Experimentally methionine-restricted diet → Human metabolic responses to methionine-only versus total sulfur restriction source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Controlled feeding; sequential control, moderate and greater restriction periods separated by washouts.
    limitations
    Small short-term study with fixed diet-period ordering; no lifespan or cancer outcomes.
    nutrient_topic
    L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Methionine
    plain_language
    Restricting one sulfur amino acid is not the same intervention as restricting both.
    primary_references
    Dietary Methionine and Total Sulfur Amino Acid Restriction in Healthy Adults. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36806866/ · DOI 10.1007/s12603-023-1883-3

    L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 396–402

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Controlled feeding; sequential control, moderate and greater restriction periods separated by washouts. · source_derived_draft · unverified_draft

    ## methionine-human-metr-saar Restricting one sulfur amino acid is not the same intervention as restricting both. In twenty adults, four-week methionine-only restriction changed fewer metabolic markers than combined methionine/cysteine restriction; both increased FGF21 in the reported comparisons. Model: Controlled feeding; sequential control, moderate and greater restriction periods separated by washouts. Limitations: Small short-term study with fixed diet-period ordering; no lifespan or cancer outcomes. Evidence access: Primary abstract Dietary Methionine and Total Sulfur Amino Acid Restriction in Healthy Adults. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36806866/ · DOI 10.1007/s12603-023-1883-3
    Complete structured claim and evidence

  3. Methionine restriction activated hepatic PERK and an antioxidant/ISR program in wild-type and Gcn2-null mice, without the measured ER-stress pattern.

    Experimentally methionine-restricted diet → Mouse PERK / Eif2ak3 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Mouse liver signaling and dietary experiments.
    limitations
    The proposed glutathione-sensing mechanism is not evidence of direct methionine binding to PERK.
    nutrient_topic
    L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Methionine
    plain_language
    Dietary sulfur status engaged an alternative stress-response route.
    primary_references
    Role of GCN2-Independent Signaling Through a Noncanonical PERK/NRF2 Pathway in the Physiological Responses to Dietary Methionine Restriction. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26936965/ · DOI 10.2337/db15-1324

    L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 388–394

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse liver signaling and dietary experiments. · source_derived_draft · unverified_draft

    ## methionine-perk-redox-response Dietary sulfur status engaged an alternative stress-response route. Methionine restriction activated hepatic PERK and an antioxidant/ISR program in wild-type and Gcn2-null mice, without the measured ER-stress pattern. Model: Mouse liver signaling and dietary experiments. Limitations: The proposed glutathione-sensing mechanism is not evidence of direct methionine binding to PERK. Evidence access: Primary abstract Role of GCN2-Independent Signaling Through a Noncanonical PERK/NRF2 Pathway in the Physiological Responses to Dietary Methionine Restriction. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26936965/ · DOI 10.2337/db15-1324
    Complete structured claim and evidence

  4. Reducing dietary methionine from 0.86% to 0.17% extended male F344 rat lifespan by about 30% while abolishing growth in the original experiment.

    Experimentally methionine-restricted diet → Lifespan and growth in methionine-restricted male F344 rats source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Lifelong controlled feeding of male Fischer 344 rats.
    limitations
    Not human lifespan evidence or a nutritionally appropriate target for children.
    nutrient_topic
    L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Methionine
    plain_language
    The longevity observation came with a substantial growth cost.
    primary_references
    Low methionine ingestion by rats extends life span. · 1993 · https://pubmed.ncbi.nlm.nih.gov/8429371/ · DOI 10.1093/jn/123.2.269

    L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 356–362

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Lifelong controlled feeding of male Fischer 344 rats. · source_derived_draft · unverified_draft

    ## methionine-rat-lifespan-growth The longevity observation came with a substantial growth cost. Reducing dietary methionine from 0.86% to 0.17% extended male F344 rat lifespan by about 30% while abolishing growth in the original experiment. Model: Lifelong controlled feeding of male Fischer 344 rats. Limitations: Not human lifespan evidence or a nutritionally appropriate target for children. Evidence access: Primary abstract Low methionine ingestion by rats extends life span. · 1993 · https://pubmed.ncbi.nlm.nih.gov/8429371/ · DOI 10.1093/jn/123.2.269
    Complete structured claim and evidence

  5. Methionine restriction reduced hepatic Scd1 expression and serum fatty-acid desaturation indices; cysteine supplementation reversed these changes.

    Experimentally methionine-restricted diet → Rat stearoyl-CoA desaturase 1 / Scd1 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Rat liver RNA/protein and serum lipid profiling.
    limitations
    Desaturation indices are indirect activity readouts; no isolated human enzyme effect is established.
    nutrient_topic
    L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Methionine
    plain_language
    Sulfur-amino-acid composition influenced a lipid-metabolism enzyme.
    primary_references
    Cysteine supplementation reverses methionine restriction effects on rat adiposity: significance of stearoyl-coenzyme A desaturase. · 2011 · https://pubmed.ncbi.nlm.nih.gov/20871132/ · DOI 10.1194/jlr.M010215

    L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 372–378

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat liver RNA/protein and serum lipid profiling. · source_derived_draft · unverified_draft

    ## methionine-rat-scd1-response Sulfur-amino-acid composition influenced a lipid-metabolism enzyme. Methionine restriction reduced hepatic Scd1 expression and serum fatty-acid desaturation indices; cysteine supplementation reversed these changes. Model: Rat liver RNA/protein and serum lipid profiling. Limitations: Desaturation indices are indirect activity readouts; no isolated human enzyme effect is established. Evidence access: Primary abstract Cysteine supplementation reverses methionine restriction effects on rat adiposity: significance of stearoyl-coenzyme A desaturase. · 2011 · https://pubmed.ncbi.nlm.nih.gov/20871132/ · DOI 10.1194/jlr.M010215
    Complete structured claim and evidence

  6. Methionine restriction or YTHDF1 depletion increased CD8 infiltration and improved tumor control with PD-1 blockade in the tested mouse models.

    Experimentally methionine-restricted diet → Antitumor response in the YTHDF1/m6A mouse study source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Murine tumor models; diet and YTHDF1 perturbations.
    limitations
    Other immune-competent models report harm; diet, tumor stage and microbiome differ. No universal direction or human efficacy is established.
    nutrient_topic
    L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Methionine
    plain_language
    One experimental setting favored restricting the tumor methylation pathway.
    primary_references
    Methionine deficiency facilitates antitumour immunity by altering m6A methylation of immune checkpoint transcripts. · 2023 · https://pubmed.ncbi.nlm.nih.gov/35803704/ · DOI 10.1136/gutjnl-2022-326928

    L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 452–458

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Murine tumor models; diet and YTHDF1 perturbations. · source_derived_draft · unverified_draft

    ## methionine-restriction-checkpoint-benefit One experimental setting favored restricting the tumor methylation pathway. Methionine restriction or YTHDF1 depletion increased CD8 infiltration and improved tumor control with PD-1 blockade in the tested mouse models. Model: Murine tumor models; diet and YTHDF1 perturbations. Limitations: Other immune-competent models report harm; diet, tumor stage and microbiome differ. No universal direction or human efficacy is established. Evidence access: Primary abstract Methionine deficiency facilitates antitumour immunity by altering m6A methylation of immune checkpoint transcripts. · 2023 · https://pubmed.ncbi.nlm.nih.gov/35803704/ · DOI 10.1136/gutjnl-2022-326928
    Complete structured claim and evidence

  7. A controlled human feeding component changed systemic metabolism in directions overlapping the mouse experiments.

    Experimentally methionine-restricted diet → Human systemic metabolome during controlled methionine restriction source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Small controlled human feeding study alongside animal cancer experiments.
    limitations
    No cancer response or survival benefit was demonstrated in the human feeding component.
    nutrient_topic
    L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Methionine
    plain_language
    Human metabolic feasibility was tested separately from tumor treatment.
    primary_references
    Dietary methionine influences therapy in mouse cancer models and alters human metabolism. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31367041/ · DOI 10.1038/s41586-019-1437-3

    L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 492–498

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Small controlled human feeding study alongside animal cancer experiments. · source_derived_draft · unverified_draft

    ## methionine-restriction-human-metabolome Human metabolic feasibility was tested separately from tumor treatment. A controlled human feeding component changed systemic metabolism in directions overlapping the mouse experiments. Model: Small controlled human feeding study alongside animal cancer experiments. Limitations: No cancer response or survival benefit was demonstrated in the human feeding component. Evidence access: Primary abstract Dietary methionine influences therapy in mouse cancer models and alters human metabolism. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31367041/ · DOI 10.1038/s41586-019-1437-3
    Complete structured claim and evidence

  8. Restriction reduced T-cell abundance and worsened tumor growth and immunotherapy response in immunocompetent mice, while inhibiting growth in immunocompromised mice.

    Experimentally methionine-restricted diet → Antitumor immunity in the sulfur/microbiome MR study source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Multiple mouse tumor settings with differing immune competence.
    limitations
    Comparison does not prove the exact cause of every difference from the YTHDF1 study; matched-model replication remains needed.
    nutrient_topic
    L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Methionine
    plain_language
    Tumor and immune-cell effects can point in opposite directions.
    primary_references
    Methionine restriction-induced sulfur deficiency impairs antitumour immunity partially through gut microbiota. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37537369/ · DOI 10.1038/s42255-023-00854-3

    L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 468–474

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Multiple mouse tumor settings with differing immune competence. · source_derived_draft · unverified_draft

    ## methionine-restriction-immune-harm Tumor and immune-cell effects can point in opposite directions. Restriction reduced T-cell abundance and worsened tumor growth and immunotherapy response in immunocompetent mice, while inhibiting growth in immunocompromised mice. Model: Multiple mouse tumor settings with differing immune competence. Limitations: Comparison does not prove the exact cause of every difference from the YTHDF1 study; matched-model replication remains needed. Evidence access: Primary abstract Methionine restriction-induced sulfur deficiency impairs antitumour immunity partially through gut microbiota. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37537369/ · DOI 10.1038/s42255-023-00854-3
    Complete structured claim and evidence

  9. Methionine restriction reduced microbial hydrogen-sulfide production and impaired immune-cell survival/activation in the study models.

    Experimentally methionine-restricted diet → Gut microbial hydrogen-sulfide production in the MR tumor study source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Immunocompetent male/female mouse tumor models with microbiome and sulfur interventions.
    limitations
    Microbial sulfur production is not identical to host CBS/CTH flux.
    nutrient_topic
    L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Methionine
    plain_language
    Dietary sulfur supply also changes support coming from gut microbes.
    primary_references
    Methionine restriction-induced sulfur deficiency impairs antitumour immunity partially through gut microbiota. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37537369/ · DOI 10.1038/s42255-023-00854-3

    L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 460–466

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Immunocompetent male/female mouse tumor models with microbiome and sulfur interventions. · source_derived_draft · unverified_draft

    ## methionine-restriction-microbial-sulfur Dietary sulfur supply also changes support coming from gut microbes. Methionine restriction reduced microbial hydrogen-sulfide production and impaired immune-cell survival/activation in the study models. Model: Immunocompetent male/female mouse tumor models with microbiome and sulfur interventions. Limitations: Microbial sulfur production is not identical to host CBS/CTH flux. Evidence access: Primary abstract Methionine restriction-induced sulfur deficiency impairs antitumour immunity partially through gut microbiota. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37537369/ · DOI 10.1038/s42255-023-00854-3
    Complete structured claim and evidence

  10. Restriction altered one-carbon, nucleotide and redox metabolism and improved treatment responses in colorectal xenograft and autochthonous sarcoma models.

    Experimentally methionine-restricted diet → Cancer treatment response in the methionine-restriction mouse study source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Patient-derived colorectal xenografts and Kras/Trp53-driven mouse sarcoma; antimetabolite/radiation settings.
    limitations
    Different models and immune contexts from other tumor studies; not a human cancer efficacy trial.
    nutrient_topic
    L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Methionine
    plain_language
    Diet composition modified pathways also targeted by cancer treatment.
    primary_references
    Dietary methionine influences therapy in mouse cancer models and alters human metabolism. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31367041/ · DOI 10.1038/s41586-019-1437-3

    L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 484–490

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Patient-derived colorectal xenografts and Kras/Trp53-driven mouse sarcoma; antimetabolite/radiation settings. · source_derived_draft · unverified_draft

    ## methionine-restriction-therapy-metabolism Diet composition modified pathways also targeted by cancer treatment. Restriction altered one-carbon, nucleotide and redox metabolism and improved treatment responses in colorectal xenograft and autochthonous sarcoma models. Model: Patient-derived colorectal xenografts and Kras/Trp53-driven mouse sarcoma; antimetabolite/radiation settings. Limitations: Different models and immune contexts from other tumor studies; not a human cancer efficacy trial. Evidence access: Primary abstract Dietary methionine influences therapy in mouse cancer models and alters human metabolism. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31367041/ · DOI 10.1038/s41586-019-1437-3
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Adding 0.5% cysteine for twelve weeks largely reversed the low-adiposity and related metabolic phenotype of methionine restriction without restoring serum methionine.

    L-Cysteine → Adiposity and metabolic responses to methionine restriction in rats source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Four-group rat feeding study.
    limitations
    Does not imply all restriction effects are exclusively due to cysteine in every species.
    nutrient_topic
    L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Methionine
    plain_language
    Changing the downstream sulfur supply changed the dietary response.
    primary_references
    Cysteine supplementation reverses methionine restriction effects on rat adiposity: significance of stearoyl-coenzyme A desaturase. · 2011 · https://pubmed.ncbi.nlm.nih.gov/20871132/ · DOI 10.1194/jlr.M010215

    L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 364–370

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Four-group rat feeding study. · source_derived_draft · unverified_draft

    ## methionine-rat-cysteine-reversal Changing the downstream sulfur supply changed the dietary response. Adding 0.5% cysteine for twelve weeks largely reversed the low-adiposity and related metabolic phenotype of methionine restriction without restoring serum methionine. Model: Four-group rat feeding study. Limitations: Does not imply all restriction effects are exclusively due to cysteine in every species. Evidence access: Primary abstract Cysteine supplementation reverses methionine restriction effects on rat adiposity: significance of stearoyl-coenzyme A desaturase. · 2011 · https://pubmed.ncbi.nlm.nih.gov/20871132/ · DOI 10.1194/jlr.M010215
    Complete structured claim and evidence

  2. Supplementation with an H2S donor, a precursor or methionine restored antitumor immune responses in the tested restriction setting.

    Hydrogen sulfide / H2S → Antitumor immunity in the sulfur/microbiome MR study source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Dietary/add-back mouse experiments reported in the primary study.
    limitations
    Donor identity and exposure matter; this is not a human H2S or methionine treatment recommendation.
    nutrient_topic
    L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Methionine
    plain_language
    Restoring sulfur support changed the net tumor response.
    primary_references
    Methionine restriction-induced sulfur deficiency impairs antitumour immunity partially through gut microbiota. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37537369/ · DOI 10.1038/s42255-023-00854-3

    L-Methionine: transport, methylation, sulfur metabolism 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 · Dietary/add-back mouse experiments reported in the primary study. · source_derived_draft · unverified_draft

    ## methionine-sulfur-rescue Restoring sulfur support changed the net tumor response. Supplementation with an H2S donor, a precursor or methionine restored antitumor immune responses in the tested restriction setting. Model: Dietary/add-back mouse experiments reported in the primary study. Limitations: Donor identity and exposure matter; this is not a human H2S or methionine treatment recommendation. Evidence access: Primary abstract Methionine restriction-induced sulfur deficiency impairs antitumour immunity partially through gut microbiota. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37537369/ · DOI 10.1038/s42255-023-00854-3
    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.

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