SAMe
SAMe (S-adenosylmethionine) is studied for depression, osteoarthritis, and liver-related outcomes.
Overview
What is SAMe?
SAMe (S-adenosylmethionine) is a metabolite that is made in the body. Low levels of SAMe in the body are linked to conditions including chronic kidney disease, coronary artery disease, depression, dementia and Alzheimer's disease.
S-adenosylmethionine regulates methionine metabolism and helps maintain cellular functions like DNA and protein methylation. Supplementing SAMe may improve liver function and depression symptoms, but further research is needed for confirmation. The body tightly controls SAMe levels to support metabolism and detoxification processes.
Dosage
A typical dose of SAMe is 200–1,600 mg per day.
Effect graph
Effect heatmap
SupplementDEX Database
17 conditions for , and rated at least stars. All purchase bands. No minimum star filter.
Database Snapshot
Most same research is concentrated in a handful of conditions.
- Osteoarthritis accounts for 12 of 50 studies (24%).
- Cholestasis of pregnancy accounts for 9 of 50 studies (18%).
- Depression accounts for 8 of 50 studies (16%).
- Sparse coverage remains for Cardiovascular health, Chronic liver disease, Hepatitis C.
Safety
SAMe is possibly safe when used in typical doses but may cause serious adverse effects including mania in some people with underlying health conditions.
Frequently Asked Questions
References
Sources48 references
SupplementDEX uses only high-quality sources to determine supplement effectiveness.
1.SupplementDEX Database: Cholestasis of pregnancy — Pharmacological interventions for treating intrahepatic cholestasis of pregnancy2020
A Cochrane review found ursodeoxycholic acid more consistently effective than SAMe for intrahepatic cholestasis of pregnancy, with combination therapy possibly additive.
2.SupplementDEX Database: Cholestasis of pregnancy — Randomized prospective comparative study of ursodeoxycholic acid and S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis of pregnancy2006
In 78 ICP pregnancies, UDCA monotherapy improved pruritus and bile acids more than SAMe monotherapy in a randomized comparative study.
3.SupplementDEX Database: Cholestasis of pregnancy — A randomised controlled trial of ursodeoxycholic acid and S-adenosyl-l-methionine in the treatment of gestational cholestasis2004
In severe gestational cholestasis, SAMe 500 mg twice daily and UDCA 300 mg twice daily both reduced bile acids, with UDCA showing stronger biochemical effects.
4.SupplementDEX Database: Cholestasis of pregnancy — A randomised placebo-controlled trial of ursodeoxycholic acid and S-adenosylmethionine in the treatment of intrahepatic cholestasis of pregnancy1998
In 32 ICP women, UDCA, SAMe, or their combination improved pruritus and liver tests versus placebo, with combination therapy most effective.
5.SupplementDEX Database: Cholestasis of pregnancy — S-adenosylmethionine versus ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy: preliminary results of a controlled trial1996
In 20 ICP patients, UDCA reduced bile acids and pruritus more than SAMe, though both improved symptoms versus baseline.
6.SupplementDEX Database: Cholestasis of pregnancy — [A meta-analysis of therapeutic trials with ademetionine in the treatment of intrahepatic cholestasis]1993
A meta-analysis of 6 trials found ademetionine (SAMe) superior to placebo for relieving pruritus in intrahepatic cholestasis.
7.SupplementDEX Database: Cholestasis of pregnancy — Role of S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis1990
In 639 cholestatic patients across 4 trials, SAMe 800 mg IV or 1.6 g oral daily for 2 weeks improved pruritus and liver enzymes versus placebo.
8.SupplementDEX Database: Cholestasis of pregnancy — Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis. A double-blind, placebo-controlled study1990
In 220 cholestatic patients with chronic liver disease, oral SAMe improved pruritus and bilirubin versus placebo over the treatment period.
9.SupplementDEX Database: Cholestasis of pregnancy — S-adenosylmethionine for the treatment of intrahepatic cholestasis of pregnancy. Results of a controlled clinical trial1990
In 30 ICP patients, SAMe 800 mg/day IV reduced bile acids and conjugated bilirubin versus placebo before delivery.
SupplementDEX Database · Depression
8 references10.SupplementDEX Database: Depression — S-Adenosylmethionine (SAMe) as an adjuvant therapy for patients with depression: An updated systematic review and meta-analysis2024
A meta-analysis found SAMe as adjunct or monotherapy reduced depressive symptoms versus placebo, with combination antidepressant therapy showing added benefit.
11.SupplementDEX Database: Depression — Efficacy and acceptability of S-adenosyl-L-methionine (SAMe) for depressed patients: A systematic review and meta- analysis2024
A meta-analysis of 23 trials (2,183 patients) found SAMe reduced depression scores and had similar acceptability to placebo or antidepressants.
12.SupplementDEX Database: Depression — Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce2022
WFSBP/CANMAT 2022 guidelines rated acetyl-L-carnitine as not recommended for ADHD based on Grade A evidence from meta-analyses and RCTs.
13.SupplementDEX Database: Depression — S-adenosyl methionine (SAMe) for depression in adults2016
A Cochrane review found SAMe may reduce depressive symptoms versus placebo and be similar to some antidepressants, though evidence quality was moderate.
14.SupplementDEX Database: Depression — S-adenosyl methionine (SAMe) versus escitalopram and placebo in major depression RCT: efficacy and effects of histamine and carnitine as moderators of response2014
In 144 adults with major depression, SAMe 1600–3200 mg/day did not significantly outperform escitalopram or placebo on primary depression outcomes in this substudy.
15.SupplementDEX Database: Depression — Effects of S-adenosylmethionine augmentation of serotonin-reuptake inhibitor antidepressants on cognitive symptoms of major depressive disorder2011
A secondary analysis of 46 SSRI non-responders with major depression in a 6-week adjunctive SAMe RCT found greater improvement in recall (p=0.04) and a trend for word-finding vs placebo.
16.SupplementDEX Database: Depression — S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial2010
A 6-week double-blind RCT in 73 SSRI non-responders with major depression found adjunctive SAMe 1600 mg/day raised HAM-D response (36.1% vs 17.6%) and remission (25.8% vs 11.7%) vs placebo.
17.SupplementDEX Database: Depression — S-adenosyl-L-methionine for treatment of depression, osteoarthritis, and liver disease2003
A review concluded SAMe has evidence for depression, osteoarthritis, and liver disease, though indication-specific trial quality varies.
SupplementDEX Database · Osteoarthritis
11 references18.SupplementDEX Database: Osteoarthritis — S-Adenosylmethionine for osteoarthritis of the knee or hip2009
A Cochrane review of 4 RCTs in 656 knee or hip osteoarthritis patients found SAMe vs placebo showed only a small, non-significant pain benefit and inconclusive evidence overall.
19.SupplementDEX Database: Osteoarthritis — Comparative clinical trial of S-adenosylmethionine versus nabumetone for the treatment of knee osteoarthritis: an 8-week, multicenter, randomized, double-blind, double-dummy, Phase IV study in Korean patients2009
An 8-week RCT in 134 Korean knee osteoarthritis patients found SAMe 1200 mg/day and nabumetone 1000 mg/day reduced pain similarly, with no significant between-group differences.
20.SupplementDEX Database: Osteoarthritis — S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind cross-over trial. [ISRCTN36233495]2004
A 16-week cross-over RCT in 61 adults with knee osteoarthritis found celecoxib 200 mg reduced pain faster than SAMe 1200 mg, but both were equally effective by the second month.
21.SupplementDEX Database: Osteoarthritis — Safety and efficacy of S-adenosylmethionine (SAMe) for osteoarthritis2002
A meta-analysis of 11 osteoarthritis RCTs found SAMe comparable to NSAIDs for pain and function with fewer adverse effects; vs placebo it improved function but not pain based on two studies.
22.SupplementDEX Database: Osteoarthritis — A randomized, double blind, placebo controlled trial of intravenous loading with S-adenosylmethionine (SAM) followed by oral SAM therapy in patients with knee osteoarthritis1994
An RCT in 81 knee osteoarthritis patients found IV SAMe 400 mg daily for 5 days followed by oral 600 mg/day for 23 days reduced overall and rest pain vs placebo at one site with milder disease.
23.SupplementDEX Database: Osteoarthritis — Italian double-blind multicenter study comparing S-adenosylmethionine, naproxen, and placebo in the treatment of degenerative joint disease1987
A double-blind Italian multicenter trial in 734 osteoarthritis patients found SAMe 1200 mg/day matched naproxen 750 mg/day for analgesia, both beating placebo, with better SAMe tolerability than naproxen.
24.SupplementDEX Database: Osteoarthritis — A long-term (two years) clinical trial with S-adenosylmethionine for the treatment of osteoarthritis1987
A 24-month open trial in 108 osteoarthritis patients found SAMe 600 mg/day initially then 400 mg/day improved stiffness, rest pain, and movement pain from early weeks through 2 years with good tolerance.
25.SupplementDEX Database: Osteoarthritis — A new medical approach to the treatment of osteoarthritis. Report of an open phase IV study with ademetionine (Gumbaral)1987
An open phase IV trial in 20,641 osteoarthritis patients treated with ademetionine for 8 weeks reported good or very good efficacy in 71% and good or very good tolerance in 87%.
26.SupplementDEX Database: Osteoarthritis — Double-blind clinical trial of S-adenosylmethionine versus ibuprofen in the treatment of osteoarthritis1987
A 4-week double-blind trial in 36 osteoarthritis patients found SAMe 1200 mg/day and ibuprofen 1200 mg/day improved total joint scores equally, with both well tolerated.
27.SupplementDEX Database: Osteoarthritis — Double-blind comparative clinical trial with S-adenosylmethionine and indomethacin in the treatment of osteoarthritis1987
A 4-week double-blind trial in 36 osteoarthritis patients found SAMe 1200 mg/day and indomethacin 150 mg/day improved clinical scores similarly, with adverse effects in 2 vs 7 patients.
28.SupplementDEX Database: Osteoarthritis — Double-blind controlled clinical trial of oral S-adenosylmethionine versus piroxicam in knee osteoarthritis1987
An 84-day double-blind trial in 45 knee osteoarthritis patients found SAMe 1200 mg/day and piroxicam 20 mg/day both improved pain by day 28, with SAMe maintaining benefit longer after treatment.
SupplementDEX Database · Cardiovascular health
2 references29.SupplementDEX Database: Cardiovascular health — Dietary supplement S-adenosyl-L-methionine (AdoMet) effects on plasma homocysteine levels in healthy human subjects: a double-blind, placebo-controlled, randomized clinical trial2009
In 52 healthy volunteers, SAMe 800 mg/day for 4 weeks increased plasma homocysteine versus placebo, raising potential cardiovascular concern.
30.SupplementDEX Database: Cardiovascular health — Influence of oral S-adenosylmethionine on plasma 5-methyltetrahydrofolate, S-adenosylhomocysteine, homocysteine and methionine in healthy humans1997
A single oral SAMe 400 mg dose increased plasma 5-methyltetrahydrofolate and altered homocysteine metabolism in healthy subjects.
31.SupplementDEX Database: Chronic liver disease — S-adenosyl-L-methionine for the treatment of chronic liver disease: a systematic review and meta-analysis2015
A meta-analysis found SAMe may improve liver function tests in chronic liver disease, though effects on hard clinical outcomes were uncertain.
SupplementDEX Database · Fibromyalgia
4 references32.SupplementDEX Database: Fibromyalgia — Evaluation of S-adenosylmethionine in secondary fibromyalgia: a double-blind study1998
A double-blind study evaluated SAMe for secondary fibromyalgia; published details on dose, duration, and outcomes were not available in the abstract.
33.SupplementDEX Database: Fibromyalgia — Double-blind, placebo-controlled cross-over study of intravenous S-adenosyl-L-methionine in patients with fibromyalgia1997
In 34 fibromyalgia outpatients, a 10-day cross-over trial of IV SAMe 600 mg/day vs placebo found no significant tender-point improvement and no clear benefit in this short-term study.
34.SupplementDEX Database: Fibromyalgia — Oral S-adenosylmethionine in primary fibromyalgia. Double-blind clinical evaluation1991
A 6-week double-blind trial in 44 primary fibromyalgia patients found oral SAMe 800 mg/day improved disease activity, weekly pain, fatigue, morning stiffness, and mood vs placebo.
35.SupplementDEX Database: Fibromyalgia — Evaluation of S-adenosylmethionine in primary fibromyalgia. A double-blind crossover study1987
A crossover study in 17 primary fibromyalgia patients found SAMe reduced trigger points and improved Hamilton and SAD depression scores vs placebo.
SupplementDEX Database · Liver health
2 references36.SupplementDEX Database: Liver health — S-adenosyl-L-methionine treatment for alcoholic liver disease: a double-blinded, randomized, placebo-controlled trial2011
A 24-week RCT in 37 alcoholic liver disease patients found SAM 1.2 g/day was no more effective than placebo for liver enzymes or histology, though abstinence improved liver function in both groups.
37.SupplementDEX Database: Liver health — S-adenosylmethionine (AdoMet) supplementation for treatment of chemotherapy-induced liver injury2003
In 50 cancer patients with first-time chemotherapy-induced liver toxicity, oral AdoMet significantly reduced AST, ALT, and LDH within 1–2 weeks and allowed scheduled chemotherapy with fewer dose delays.
38.SupplementDEX Database: Attention deficit-hyperactivity disorder (ADHD) — S-adenosyl-L-methionine (SAM) in adults with ADHD, RS: preliminary results from an open trial1990
In adults with ADHD, SAMe showed preliminary benefit on attention symptoms in an early randomized study, though evidence remained very limited.
39.SupplementDEX Database: Cancer-related fatigue — S-Adenosylmethionine Supplementation May Reduce Cancer-Related Fatigue: A Prospective Evaluation Using the FACIT-F Questionnaire in Colon Cancer Patients Undergoing Oxaliplatin-Based Chemotherapy Regimens2021
A prospective study suggested SAMe supplementation may reduce cancer-related fatigue, though controlled trial evidence is still limited.
SupplementDEX Database · Cirrhosis
1 reference40.SupplementDEX Database: Cirrhosis — Beneficial effects of S-adenosyl-L-methionine on post-hepatectomy residual liver function: a prospective, randomized, controlled clinical trial2013
In 79 post-hepatectomy cirrhosis patients, postoperative IV SAMe improved residual liver function versus control after resection.
41.SupplementDEX Database: Gilbert's syndrome (GS) — Effect of different doses of S-adenosyl-L-methionine (SAMe) on nicotinic acid-induced hyperbilirubinaemia in Gilbert's syndrome1988
In 10 men with Gilbert's syndrome (mean age 24), IV SAMe 800 mg/day for 10 days lowered unconjugated bilirubin and nicotinic acid half-life vs placebo; 200 mg/day had no effect.
SupplementDEX Database · Hepatitis C
2 references42.SupplementDEX Database: Hepatitis C — S-adenosyl methionine improves early viral responses and interferon-stimulated gene induction in hepatitis C nonresponders2011
In 24 hepatitis C genotype 1 prior nonresponders, adding SAMe 1600 mg/day to peginterferon and ribavirin improved phase-2 viral decline and interferon-stimulated gene induction vs control.
43.SupplementDEX Database: Hepatitis C — S-adenosyl-methionine and betaine improve early virological response in chronic hepatitis C patients with previous nonresponse2010
An open-label pilot in 29 prior-treatment-failure chronic hepatitis C patients given SAMe, betaine, pegIFN, and ribavirin found 59% early virological response but only 10% sustained virological response.
SupplementDEX Database · Menopause
1 reference44.SupplementDEX Database: Menopause — Phase II evaluation of S-adenosyl-L-methionine (SAMe) for the treatment of hot flashes2016
A phase II single-arm trial in 43 women treated with SAMe 400 mg twice daily found a 35.4% hot-flash score reduction that was not significantly better than the historical placebo rate of 25%.
45.SupplementDEX Database: Nonalcoholic fatty liver disease (NAFLD) — Association of serum methionine metabolites with non-alcoholic fatty liver disease: a cross-sectional study2022
A cross-sectional study of 2814 adults aged 40–75 found higher SAH and homocysteine and a lower SAM/SAH ratio independently associated with non-alcoholic fatty liver disease.
SupplementDEX Database · Parkinson's disease
1 reference46.SupplementDEX Database: Parkinson's disease — S-Adenosyl-Methionine improves depression in patients with Parkinson's disease in an open-label clinical trial2000
An open-label pilot in 13 depressed Parkinson's disease patients found SAMe 800–3600 mg/day for 10 weeks produced at least 50% Hamilton Depression Scale improvement in 10 of 11 completers.
SupplementDEX Database · Schizophrenia
1 reference47.SupplementDEX Database: Schizophrenia — Improvement of aggressive behavior and quality of life impairment following S-adenosyl-methionine (SAM-e) augmentation in schizophrenia2009
An 8-week double-blind RCT in 18 chronic schizophrenia patients with low-activity COMT found adjunctive SAMe 800 mg reduced aggression and improved quality of life, though two patients had increased irritability.
SupplementDEX Database · Smoking cessation
1 reference48.SupplementDEX Database: Smoking cessation — S-adenosyl-L-methionine (SAMe) for smoking abstinence: a randomized clinical trial2012
An 8-week RCT in 120 smokers found SAMe 800 or 1600 mg/day with behavioral counseling did not increase biochemically confirmed abstinence at 8 or 24 weeks vs placebo.