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S-adenosyl methionine

Generic Name: S-Adenosylmethionine

Brand Names: Natrol SAMe, SAM-e Complete

Drug Class: Herbals

Available Dosage Forms: Tablet, capsule, and injection

S-Adenosylmethionine (SAMe): Uses, Side effects. Natrol SAMe, SAM-e Complete
Courtesy: Unsplash

What is S-Adenosylmethionine?

S-adenosylmethionine is an endogenous compound that serves as a mediator in the synthesis of:1


-Neurotransmitters (catecholamines, monoamines


Methionine adenosyltransferase enzyme converts methionine to SAMe for use in several pathways of neurotransmitter synthesis and transmission. A link between methionine converter enzyme deficiency and depression has been established in several studies.1 Whether the link is causal or simply an association remains a mystery to researchers. S-Adenosylmethionine upregulated gene expression of neurotrophic factor, a molecule critical for the growth and differentiation of neurons. Nervous system abnormalities associated with SAMe deficiencies include:2



-Parkinsons disease

-Major depressive disorder

An articulate mode of action of S-Adenosylmethionine is yet to be discovered. However, a hypothesis states that it enhances the availability of mood-modulating neurotransmitters (serotonin, dopamine, and norepinephrine). Clinical trials noted the following therapeutic effects  with the administration of SAMe supplements:2

-Reduction in Levodopa-induced neurotoxicity in PD patients

-Analgesia and anti-inflammatory effects in fibromyalgia

-Lowers the degree of impaired libido and erectile dysfunction in men taking SNRIs and SSRIs

-Improvement in memory-related cognitive performance in depressed patients

-Cognitive improvement in early-stage dementia

-Decreased aggression in patients with chronic schizophrenia

-Improvement of liver function in depressed individuals with comorbid alcohol addiction

-Reduced incidence of medication-induced liver impairment

Evidence from a range of studies encourages the therapeutic role of S-Adenosylmethionine in depression when administered as monotherapy or as an adjunct with antidepressant agents.


How to use S-Adenosylmethionine?

It can be taken orally as tablets or capsules or by injection.

– The dosage of injection for depression is 200-400 mg/day for adults

-The maximum per day dosage of oral tablets is 1600 mg in adults

-Consult your doctor if you plan on taking SAMe supplements

-You can take the supplements with prescription antidepressants after approval from the doctor


What are the side effects of S-Adenosylmethionine?

S-Adenosylmethionine has a broad tolerability profile. However, common side effects may occur, which include:




-Stomach cramps




Rare adverse effects with S-Adenosylmethionine include:

-Manic, hypomanic exacerbation in patients with a diagnosis of bipolar disorder after parenteral administration

-Methionine toxicity


Who should not use S-Adenosylmethionine?

Anyone with the following conditions should not use S-Adenosylmethionine:

-Liver dysfunction

-Bipolar disorder



  1. Cuomo A, Beccarini Crescenzi B, Bolognesi S, et al. S-Adenosylmethionine (SAMe) in major depressive disorder (MDD): a clinician-oriented systematic review. Ann Gen Psychiatry. 2020;19:50. Published 2020 Sep 5. doi:10.1186/s12991-020-00298-z
  1. Sharma A, Gerbarg P, Bottiglieri T, et al. S-Adenosylmethionine (SAMe) for Neuropsychiatric Disorders: A Clinician-Oriented Review of Research. J Clin Psychiatry. 2017;78(6):e656-e667. doi:10.4088/JCP.16r11113

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