S-Adenosyl Methionine

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.

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.

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects s-adenosyl methionine has on your body, and how strong these effects are.

Grade	Level of Evidence [show legend]
	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
	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
	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.
	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.
	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)
	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)
	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
	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.
	Attention	-	- See study	No significant alterations in attention in persons given SAMe in conjunction with their SSRI antidepressant medication
	Bilirubin	-	- See study	No significant alterations in serum bilirubin seen with supplementation
	C-Reactive Protein	-	- See study	No significant influence on C-Reactive Protein
	Homocysteine	-	Very High See all 3 studies	No significant alterations in plasma homocysteine occur following supplemental SAMe ingestion
	Liver Damage	-	- See study	Supplemental SAMe in a study of persons with liver damage failed to confer rehabilitative effects
	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
	Motivation	-	- See study	No significant differences in self-reported motivation
	Cholestasis	Minor	- See study	Cholestasis is somewhat reduced with supplemental SAMe
	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

• Confounded with other nutrients^[1][2][3]