S-adenosylmethionine and brain health


  • Vitamins & Supplements
  • Updated June 17, 2019

S-adenosylmethionine (SAM or SAMe) is a molecule that is formed naturally in the body. It plays a role in many biological reactions by donating a carbon to other molecules such as DNA, lipids, or proteins. When SAM donates a carbon, it becomes S-adenosylhomocysteine (SAH), which is thought to be a biomarker of some diseases. While some inconsistent evidence suggests there are altered levels of SAM and SAH in Alzheimer's patients, there is little evidence from human studies that supplementation with SAM will reduce the risk of Alzheimer's. SAM supplements are generally safe but care should be taken by people with bipolar disorder.


No studies have tested whether SAM can prevent cognitive decline or dementia; inconsistent evidence suggests that there are altered levels of SAM and SAH in patients with Alzheimer's disease.

Our search identified:

  • 3 small pilot studies in Alzheimer's patients
  • 9 studies suggesting there may be altered SAM and SAH levels in patients with Alzheimer's
  • Multiple preclinical studies suggesting that SAM may be beneficial

Potential Benefit

No studies have tested whether SAM can prevent dementia or cognitive decline. One study reported that levels of SAH are increased in the blood and cerebral spinal fluid of older adults with cognitive impairment [1].

Preclinical studies suggest that SAM may improve cognition and reduce levels of Alzheimer's biomarkers [2-6], but these findings have not been validated in human studies.

APOE4 Carriers:

One study reported cerebral spinal fluid levels of SAM were lower in individuals with Alzheimer's who also had the APOE4 gene allele [7]. But no studies have evaluated whether SAM treatment selectively affect APOE4 carriers versus non-carriers. For more information on what the APOE4 gene allele means for your health, read our APOE4 information page.

For Dementia Patients

Small pilot studies suggest that SAM can reach the brain and may improve cognition and mood in patients with Alzheimer's disease [8][9]. However, no large, randomized-controlled studies have examined whether SAM may be beneficial in Alzheimer's patients.

Studies suggest that altered levels of SAM and SAH are associated with Alzheimer's disease, but the data is mixed. One study reported decreased levels of SAM and SAH in brain tissue of Alzheimer's patients [10]. Other studies reported increased levels of SAH, decreased levels of SAM, or no change in the levels of SAM or SAH in the cerebral spinal fluid of patients with Alzheimer's disease [1][7][11-14]. Finally, other studies reported increased levels of SAH in the cerebral spinal fluid were associated with increased levels of tau and amyloid, two markers of Alzheimer's disease, in the cerebral spinal fluid of Alzheimer's patients and cognitively healthy individuals [12][15].


Clinical trials suggest that SAM is generally safe with few and mild side effects. Some side effects may include headache, dizziness, anxiety, gastrointestinal problems, and insomnia. SAM has been reported to induce mania in some individuals with bipolar disorder [16][17]. Clinical studies have not evaluated the long-term safety of SAM.

SAM should not be taken with dextromethorphan (found in many cough medicines), levodopa (Parkinson's medication) and MAO inhibitors (antidepressants), or narcotic medications such as meperidine. SAM can also increase serotonin, so drugs that affect the serotonin system (such as many antidepressants or other medications such as tramadol) should not be taken with SAM.

NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.

How to Use

SAM is available in tablet form as an over-the-counter supplement. Products with enteric-coating have barrier coating such that SAM is not degraded in the stomach and instead released in the small intestine for better absorption. Most studies have used up to 1,200mg/day.

Learn More

More information on potential side effects or drug interactions can be found at Drugs.com.

More information on SAM can be found at the NIH's National Center for Complementary and Integrative Health.

Several B vitamins are involved in the metabolism of SAM. Find out about B vitamins on our Cognitive Vitality rating page.


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