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Met4.0
L-Methionine Research
Mostly mechanism / observational
58 peer-reviewed studies
What the evidence says
Mostly mechanism / observational
Most L-Methionine studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from high-quality meta-analyses and randomised trials published 1975–2026 with a typical study size of 132 participants.
Based on 58 studies · 13 meta-analyses · 29 RCTs · 66,724 total participants
Confidence
High confidence
What the studies found
2helped· 56 more without graded effect data
By outcome
Therapeutic & clinical
Mostly mechanism / observational19 studies
Depression & mood
Mostly mechanism / observational18 studies
Methylation & amino-acid metabolism
Mostly mechanism / observational14 studies
Women's health
Mostly mechanism / observational6 studies
Liver health
Mostly mechanism / observational4 studies
InflammationMethylation/detox precursor role; no trials show an anti-inflammatory benefit · 2-4 weeks
Mostly mechanism / observational4 studies
Cognitive function
Mostly mechanism / observational3 studies
Glucose & metabolic
Mostly mechanism / observational3 studies
Heart & blood pressure
Too few graded studies2 studies
Safety profile
Too few graded studies2 studies
Anxiety & stress
Too few graded studies1 study
Pain & analgesia
Too few graded studies1 study
Immune support
Too few graded studies1 study
By the numbers
Pulled from 19 studies with measurable effects
Likely real effects
67%
across studies
People studied
67k
typical study: 132 people
Strongest designs
42
13 pooled, 29 randomised
Showed benefit
100%
2/2 studies
How long studies ran
1–3 months
2
3+ months
2
Populations Studied
Patients with depression2
General population2
Patients with chronic liver disease1
MDD patients1
Active research area
27 studies in the last 5 years · Latest meta-analysis: 2026
197520002026
1Depression symptoms reliefMeta-Analysisn=1,522 · large study2024
In plain English: SAMe may provide relief of depression symptoms similar to imipramine or escitalopram.
Peng TR et al. · General hospital psychiatry (2024)
SAMe may provide relief of depression symptoms similar to imipramine or escitalopram.
However, the results of the comparisons should be interpreted with caution due to the small number of studies and the large range of SAMe doses that were used in the included trials.
Therefore, we recommend that patients discuss treatment options with their doctor before taking SAMe.
2Treatment of chronic liver diseaseMeta-Analysisn=705 · large study2015
In plain English: However, SAMe also demonstrated limited clinical value in the treatment of certain chronic liver diseases.
Guo T et al. · PloS one (2015)
In a subgroup analysis of gravidas and children, several of the included data indicated that there was a significant difference in the pruritus score.
Furthermore, the results regarding ursodeoxycholic acid (UDCA) and stronger neo-minophagen C (SNMC) indicated that both treatments were more effective than SAMe was in certain chronic liver diseases.
These findings suggest that SAMe could be used as the basis of a medication regimen for liver function improvement because of its safety.
5Peripheral blood metabolites in major depressive disorderMeta-Analysisn=46 · small study2021
In plain English: MDD patients were characterized by higher levels of asymmetric dimethylarginine, tyramine, 2-hydroxybutyric acid, phosphatidylcholine (32:1), and taurochenodesoxycholic acid and lower levels of L-acetylcarnitine, creatinine, L-asparagine, L-glutamine, linoleic acid, pyruvic acid, palmitoleic acid, L-serine, oleic acid, myo-inositol, dodecanoic acid, L-methionine, hypoxanthine, palmitic acid, L-tryptophan, kynurenic acid, taurine, and 25-hydroxyvitamin D compared with controls.
Pu J et al. · Molecular psychiatry (2021)
Pathway and network analyses revealed altered amino acid metabolism and lipid metabolism, especially for the tryptophan-kynurenine pathway and fatty acid metabolism, in the peripheral system of MDD patients.
Our findings may facilitate biomarker development and the elucidation of the molecular mechanisms that underly MDD.
In plain English: Moderate-certainty evidence suggests that SAMe monotherapy may offer a moderate therapeutic benefit in alleviating depressive symptoms.
Limveeraprajak N et al. · Progress in neuro-psychopharmacology & biological psychiatry (2024)
Moderate-certainty evidence suggests that SAMe monotherapy may offer a moderate therapeutic benefit in alleviating depressive symptoms.
Considering its favorable acceptability profile, SAMe monotherapy should be considered as a treatment option for patients with depression.
However, uncertainties regarding its efficacy as an adjunct to AD and its comparative efficacy with ADs remain unresolved.
In plain English: S-adenosylmethionine holds promise as a treatment for multiple neuropsychiatric conditions, but the body of evidence has limitations.
Sharma A et al. · The Journal of clinical psychiatry (2017)
S-adenosylmethionine holds promise as a treatment for multiple neuropsychiatric conditions, but the body of evidence has limitations.
The encouraging findings support further study of SAMe in both psychiatric and comorbid medical illnesses.
In plain English: No recommendations were made when the evidence was low quality or trade-offs were so closely balanced that any recommendation would be too speculative.
Crawford C et al. · Pain medicine (Malden, Mass.) (2019)
No recommendations were made when the evidence was low quality or trade-offs were so closely balanced that any recommendation would be too speculative.
Research recommendations are provided to enhance the quality and body of evidence for the most promising ingredients.
Clinicians and those with chronic pain can rely on evidence-based recommendations to inform their decisions.
In plain English: However, there is currently a paucity of high-quality data regarding the use of add-on treatments in patients with MDD who are inadequate responders to antidepressants, with quetiapine XR presenting the most comprehensive evidence base to date.
Turner P et al. · Journal of psychopharmacology (Oxford, England) (2014)
Comparison of the different drug classes indicated that most interventions had similar efficacy.
The likelihood of response was significantly greater with SAMe versus placebo and lithium and with quetiapine XR versus placebo.
Most add-on interventions demonstrated comparable efficacy in patients with MDD and an inadequate response to initial antidepressants.
In plain English: Currently the scientific evidence is insufficiently robust to establish definitive clinical practice guidelines, but processes could be established to track the impact of these ingredients.
Crawford C et al. · Pain medicine (Malden, Mass.) (2019)
Currently the scientific evidence is insufficiently robust to establish definitive clinical practice guidelines, but processes could be established to track the impact of these ingredients.
Until then, providers have the evidence needed to make informed decisions about the safe use of these dietary ingredients, and future research can address existing gaps.
In plain English: The methodological shortcoming of existing studies and directions for future research are discussed to facilitate high-quality research in this evolving area of nutritional psychiatry.
Qureshi FM et al. · Aggressive behavior (2021)
Out of the 14 studies, 5 reported a beneficial effect of nutritional supplementation (omega-3 fatty acids, vitamins/minerals, S-adenosyl-l-methionine, or tryptophan).
The results overall indicated that research in this area is in its infancy: very few studies examined the same composition of nutritional supplementation and when they did so the results were contradictory.
The methodological shortcoming of existing studies and directions for future research are discussed to facilitate high-quality research in this evolving area of nutritional psychiatry.
14hypertension riskMeta-Analysisn=57,913 · very large study2025
In plain English: Future research with standardized methodologies is needed to confirm these associations and inform clinical and public health guidance.
Izadi N, Hadi R, Shafiee A, Fathi H, Niknam M, Amiri P. · BMC public health (2025)
Large benefit
← WorseNo effectBetter →
Prospectively, higher intake of branched-chain amino acids significantly increased the hazard of hypertension.
Conversely, glycine intake was consistently associated with a protective effect (pooled OR = 0.75; 95% CI: 0.64-0.89).
Conclusion Specific dietary amino acids have distinct associations with HTN risk.
Du H, Hu Y, Ye H, Di S, Yan H. · Frontiers in endocrinology (2026)
Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were synthesized using a random-effects model accounting for the potential influence of heterogeneity.
Overall, HHcy was significantly associated with uRPL (OR 3.46, 95% CI 2.33-5.14; I² = 57%).
The association was stronger in studies with Hcy cutoff > 12 μmol/L compared to ≤ 12 μmol/L (OR 4.02 vs. 2.00; p = 0.02), and in studies using HPLC or immunoassay compared with enzymatic methods (OR 3.59 and 4.53 vs. 1.84; p = 0.02).
16Depression treatment outcomesMeta-Analysisn=185 · medium study2010
In plain English: Participants in CAM trials were more likely to be female and to have a lower placebo-response rate compared to those in standard antidepressant trials for MDD.
Freeman MP et al. · The Journal of clinical psychiatry (2010)
Participants in CAM trials were more likely to be female and to have a lower placebo-response rate compared to those in standard antidepressant trials for MDD.
Trials of standard antidepressants and CAM therapies were composed of patients with similar depression severity.
In plain English: Therefore, ursodeoxycholic acid, pirfenidone, S-adenosyl-L-methionine, and N-acetylcysteine could represent therapeutic strategies for the treatment of liver pathologies.
Muriel P et al. · International journal of molecular sciences (2026)
N-acetylcysteine (NAC) is a precursor to L-cysteine and GSH and is used in clinical settings to treat cancer, nephropathy, heart disease, pulmonary fibrosis, polycystic ovary syndrome, and influenza.
Regarding the liver, NAC is the most accepted treatment for DILI, especially after paracetamol overdose.
Owing to its antioxidant and anti-inflammatory actions, NAC has been successfully used to treat chronic liver injuries, including hepatosteatosis and fibrosis.
18Antioxidant treatment effectiveness for ALSSystematic Reviewn=23 · very small study2008
In plain English: While there is no substantial clinical trial evidence to support their clinical use, there is no clear contraindication.
Orrell RW et al. · Amyotrophic lateral sclerosis : official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases (2008)
Further well-designed trials of medications such as vitamin C and E are unlikely to be performed.
If future trials of antioxidant medications are performed, careful attention should be given to sample size, outcome measures, and duration of the trial.
The high tolerance and safety, and relatively low cost of vitamins C and E, and other considerations related to the lack of other effective treatments for amyotrophic lateral sclerosis, explain the continuing use of these vitamins by physicians and people with amyotrophic lateral sclerosis.
19Subclinical depression symptomsRCTn=140 · medium study2023
In plain English: Conclusions: The received results confirm the available evidence for the properties of SAMe in depression and complement them with evidence of the ef-fectiveness of the Deprilium® complex that contains SAMe and L-methylfolate with methylcobalamin, which together produce pharmacological and clinical synergy to reduce the severity of subclinical depressive manifestations in patients with NCD.
Results: After 60 days a statistically significant difference was observed in all clinical indicators between the intervention group and the control group.
When comparing the indicators of the intervention group on the 1st and on the 60th day of the study, statistically significant changes (p <0.000) were observed in all three indicators.
Further studies of the effectiveness of the use of the Deprilium® complex in patients with NCD are required.