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S-Adenosyl Methionine

S-Adenosylmethionine (SAMe) is a methyl donating compound that circulates in the blood and provides methyl groups to maintain other metabolic reactions. Lowered SAMe levels are associated with depressive symptoms, and supplementation may aid a partial deficiency.

Our evidence-based analysis on s-adenosyl methionine features 95 unique references to scientific papers.

Kamal Patel
Research analysis led by and reviewed by the Examine team.
Last Updated:

Summary of S-Adenosyl Methionine

Primary information, health benefits, side effects, usage, and other important details

S-Adenosyl Methionine (SAMe) is the amino acid methionine bound to an ATP molecule; this molecule circulates in the blood naturally and acts as a 'methyl donor'. A methyl group in chemistry is simply a carbon molecule (bound to some hydrogens), and donating a methyl group to other molecules can accelerate or preserve reactions in the body as a form of metabolic 'maintenance'. Choline is another prominent methyl donor in the body, but due to selectivity of some reactions the two are not necessarily interchangeable.

Some body states appear to be associated with lower circulating levels of SAMe, including osteoarthritis and depression where SAMe appears to hold potent therapeutic potential; after a build-up period of 1-2 months, supplemental SAMe at 800-1600mg daily appears to be as potent as some pharmaceutical options for both osteoarthritis and depression and appears to enhance some anti-depressants. Although lower circulating levels of SAMe are also seen in diabetes, the benefits of SAMe and glucose control are not as well established as depression and osteoarthritis.

SAMe appears to follow many nutrient-like motifs in the body, being regulated within a certain serum range and being associated with adverse effects when that range is perturbed. It potentially holds a lot of benefit in body states where circulating SAMe levels decline.

Although side-effects are not commonly reported with SAMe, numerous studies note a small set of participants who experience mania after supplementing SAMe. It is not common, but it does appear to be related to SAMe supplementation for unknown reasons; it has been reported in some persons without history of mania as well and does not appear to be related to any pathological condition per se.

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How to Take

Recommended dosage, active amounts, other details

Supplementation of S-adenosylmethionine tends to be in the 600-1,200mg range over the course of a day, divided into two or three separated doses with meals. The higher dosage (1,200mg) tends to be used more often, with the lower dosage (600mg) being used to cut costs.

For S-adenosylmethionine to benefit osteoarthritis, it appears to require a few weeks or up to a month of continual usage for benefits to show. Benefits to depressive symptoms may be much more rapid.

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Human Effect Matrix

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The Human Effect Matrix summarizes human studies to tell you what effects S-Adenosyl Methionine has on your body, how much evidence there is, and how strong these effects are.

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Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
grade-b
Symptoms of Osteoarthritis
Notable Very High See all 4 studies
Decreases in symptoms of osteroarthritis appear to be reduced to similar levels with SAMe as with pharmaceuticals like Naproxen, although SAMe requires a longer period of time for efficacy to occur
grade-b
Functionality in Elderly or Injured
Minor Very High See all 3 studies
Somewhat of an increase in functionality of elderly persons, most likely secondary to the beneficial effects on joint health.
grade-c
Depression
Notable Very High See all 3 studies
Has been noted to augment SSRI therapy (similar to creatine) and monotherapy with SAMe appears to be of similar potency to tricyclic antidepressants for some studies.
grade-c
Pain
Notable Very High See 2 studies
The decrease in pain associated with osteoarthritis appears to be similar to the reference drugs Aleve (Naproxen) and Celecoxib, but requires more time to act (up to one month)
grade-c
Memory
Minor - See study
In persons with SSRIs, adding SAMe confers a cognitive promoting effect; it is unsure if this persists in persons without SSRIs, and this augmenting effect with SSRIs is only seen in limited other instances (ie. with creatine)
grade-c
Numerical Memory
Minor - See study
A decrease in numerical memory has been noted once in elderly subjects, which is thought to be secondary to some sedation rather than indicative of damaging effects
grade-c
Symptoms of Fibromyalgia
Minor - See study
A decrease in soreness symptoms of fibromyalgia (with no apparent effect on force production) has been noted with SAMe supplementation.
grade-c
Attention
- - See study
No significant alterations in attention in persons given SAMe in conjunction with their SSRI antidepressant medication
grade-c
Bilirubin
- - See study
No significant alterations in serum bilirubin seen with supplementation
grade-c
C-Reactive Protein (CRP)
- - See study
No significant influence on C-Reactive Protein
grade-c
Homocysteine
- Very High See all 3 studies
No significant alterations in plasma homocysteine occur following supplemental SAMe ingestion
grade-c
Liver Damage
- - See study
Supplemental SAMe in a study of persons with liver damage failed to confer rehabilitative effects
grade-c
Liver Enzymes
- Moderate See all 3 studies
No significant rehabilitative effects on liver function in persons with impaired liver function, and no significant alterations in serum liver enzymes in otherwise healthy persons
grade-c
Motivation
- - See study
No significant differences in self-reported motivation
grade-d
Cholestasis
Minor - See study
Cholestasis is somewhat reduced with supplemental SAMe
grade-d
Early Virologic Response
Minor - See study
An increase in the time taken to achieve a virological response was reduced, and SAMe is thought to confer an anti-viral effect

Studies Excluded from Consideration

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Things to Note

Is a Form Of

Other Functions:

Also Known As

SAME, SAMe, Ademethionine, S-adenosyl-L-methionine, Adomet

Do Not Confuse With

Methionine (the isolated amino acid)

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Research Breakdown on S-Adenosyl Methionine

1Sources and Structure

1.1Endogenous Regulation

1.2Deficiency and Excess (Correlations)

1.3Stability

2Pharmacology

2.1Bioavailability

2.2Serum

2.3Distribution (Serum, Cellular)

2.4Excretion

3Interactions with Neurology

3.1Acetylcholine

3.2Depression

3.3Schizophrenia

3.4Parkinson's Disease

3.5Cognition

4Cardiovascular Health

4.1Endothelial Function

4.2Homocysteine

5Interactions with Skeletal Muscle

5.1Fibromyalgia

6The Liver and Hepatology

6.1Fatty Liver and Cirrhosis

6.2Liver Enzymes

6.3Cholestasis

6.4Viral Responses

6.5Interventions

7Immunology and Inflammation

7.1Osteoarthritis

8Interactions with Hormones

8.1Testosterone

9Nutrient-Nutrient Interactions

9.1Folate

9.2Levodopa

10Safety and Toxicology

10.1Case Studies
Click here to see all 95 references.

This page is regularly updated, to include the most recently available clinical trial evidence.

Each member of our research team is required to have no conflicts of interest, including with supplement manufacturers, food companies, and industry funders. The team includes nutrition researchers, registered dietitians, physicians, and pharmacists. We have a strict editorial process.

This page features 95 references. All factual claims are followed by specifically-applicable references. Click here to see the full set of research information and references for S-Adenosyl Methionine.

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