Only introduced to the American public 20 years ago, this supplement was first tested in Italy as a treatment for schizophrenia in the 1970s. But while doing so, doctors noticed it also lifted the mood of their patients.

This set off a plethora of studies which were so successful, S-Adenosyl Methionine (SAMe) became a prescription drug for the treatment of depression in Italy, Germany, Spain and Russia. It’s now available in the U.S. over-the-counter and seems to be considered a supplement.

As you’ll discover, the brain benefits of SAMe go well beyond being a safe, well-tolerated, fast-acting and effective anti-depressant.

Methylation and Why You Need It

SAMe is found in all body cells. It’s formed from the combination of the amino acid methionine with ATP, the main carrier of energy in cells. ATP is the energy output from mitochondria, the cells’ little energy factories.

One of SAMe’s most prolific and important functions is to act as a methyl donor, transferring one atom of carbon and three atoms of hydrogen.

Methylation is a vital process that supports a great many biochemical reactions involved with gene expression, DNA repair, synthesis of proteins and neurotransmitters, fat and mineral metabolism, and maintaining cell membrane fluidity.

The ability to methylate declines as we get older, giving rise to an increased risk of neurodegeneration and other chronic diseases.

Raises Brain Glutathione

Methylation involves a series of reactions, one of which creates glutathione. This is the body’s most important inside-the-cell antioxidant and detoxifier.

The brain is especially vulnerable to free radical assault because neurons lack high levels of antioxidant enzymes that depend on glutathione.

In an article published in the Annals of the New York Academy of Sciences, scientists conducted a number of studies involving Alzheimer’s patients. They concluded that “decreased glutathione content may be involved in Alzheimer’s disease pathology in humans.”

This is where SAMe comes in, because it can boost glutathione in the brain.

In a rodent study, SAMe decreased TBARS (harmful byproducts formed when free radicals damage fats) by 46% compared to controls. SAMe also increased glutathione levels by 50% and boosted two glutathione-dependent antioxidant enzymes in the brain by 115% and 81.4%.

Reduces Risk of Alzheimer’s

While low levels of SAMe are found in patients with depression, severely reduced amounts are found in those with Alzheimer’s. One study found deficiencies of between 67% and 85% in eleven subjects post mortem.

Improved cognition following SAMe supplementation was found in several early studies. More recently, SAMe demonstrated beneficial effects on the beta amyloid proteins and tau tangles associated with the disease.

In a mouse study, supplementation reduced the production and spread of amyloid, inhibited tau, and increased spatial memory (the animals’ ability to find their way round a maze)

In another study, beta amyloid brain deposits were reduced by 80% after just one month of treatment.

Scientists from The University of Massachusetts wrote in the Journal of Alzheimer’s Disease in 2008 that “dietary supplementation with S-adenosyl methionine alleviates a variety of risk factors and hallmarks associated with Alzheimer’s disease.”

Supports Better Brain Function in Parkinson’s

Researchers from Germany tested blood samples from 87 Parkinson’s patients whose average age was 68.

They found that markers of neurodegeneration such as amyloid are related to levels of SAMe, and better cognitive function was found in the patients with higher ratios.

The researchers tried administering SAMe to Parkinson’s patients who received either no benefit from antidepressant drugs or suffered intolerable side effects.

They found that SAMe reduced symptoms of depression by 65%, and concluded that SAMe “may be a safe and effective alternative” to antidepressants.

Promotes a Better Night’s Sleep

SAMe is believed to work in its traditional role as an antidepressant by raising brain levels of melatonin and the neurotransmitters serotonin and dopamine. Low levels of these molecules are commonly found in mood disorders such as anxiety and depression.

But serotonin and melatonin also play important roles in promoting sleep.

SAMe is able to raise melatonin levels by increasing the activity of the enzyme that converts serotonin to melatonin. This major methylation reaction typically occurs around 9 pm to relax you and help you go to sleep.

SAMe is available as a supplement, but to optimize methylation it is best to also take vitamins B2, B6, B12, folic acid, vitamin D, magnesium and betaine (trimethylglycine).


  1. https://www.ncbi.nlm.nih.gov/pubmed/15247041
  2. https://www.ncbi.nlm.nih.gov/pubmed/10651146
  3. https://www.ncbi.nlm.nih.gov/pubmed/8752143
  4. https://www.ncbi.nlm.nih.gov/pubmed/22221883
  5. https://www.ncbi.nlm.nih.gov/pubmed/22045486
  6. https://www.ncbi.nlm.nih.gov/pubmed/18334758
  7. https://www.ncbi.nlm.nih.gov/pubmed/19679632
  8. https://www.ncbi.nlm.nih.gov/pubmed/11104210