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What About "SAM"? A Non-Pharmaceutical Supplement for Depression & Anxiety

What is SAM?

S-adenosylmethionine (SAM) or SAMe, is a supplement that has been tested to promote and improve emotional moods, joint health, mobility, and overall liver health. It is also found naturally throughout the human body to support cell functions. High concentrations are partically found in the liver, adrenal glands, and the pineal gland. SAM is an important molecule that serves as a major donor of methyl groups. There are several targets in the body that require methylation. SAM methyl groups are part of transmethylation reactions because they are donated to acceptor substrates that include phospholipids, DNA, ribonucleic acid, neurotransmitters, and proteins. An example of this is folate, a water-soluble B-Vitamin (1 of the 13 essential vitamins), which primary functions to transfer methyl groups for cell growth, reproduction, breakdown for the use of proteins, formation of nucleic acids, red blood cell maturation, and various CNS reactions.[2]

Functions of SAM

Aside from being the body’s principal methyl donor, SAM has several other functions to help build up emotional moods by playing key roles in hormone and neurotransmitter support. This includes a variety of functions such as synthesis of choline, carnitine, creatine, epinephrine, melatonin, during process of metabolism of arsenic, as well as in the maintenance of myelin. SAM also supports DNA methylation and polyamines synthesis and affects membrane fluidity.

Are SAM Supplements Beneficial?

SAM (as well as folate variations) has proven to be a safe and beneficial supplement to help lower major depressive disorders, including individuals with depression and or anxiety . Studies have reported positive outcomes as it supports cellular metabolism, liver and brain health, and cartilage production. Its repair tolerability, and unique mechanism of action, makes it a useful addition to the antidepressant armamentarium. [2]

Challenges of SAM

Potential interest and benefits of SAM supplementation have increased significantly over the past decades in treatment of depression and anxiety, but it remains unclear as further research is needed in dosing and long-term effects. To-date, there are limited randomized control trials that have studied for optimal dosing regimens, (only one double-blind, placebo-controlled study) so, the overall evidence for exact dosing could be mixed or depended on individual by basis.[2] This can make it challenging for individuals to determine how much SAM they actually need. It is important for individuals seeking treatment for major depressive disorder, to discuss treatments with their medical doctor prior to using S-adenosylmethionine (SAM) supplementation. Taking this step of action can determine if it is suitable for their needs and prepare for proper supplement instruction.

Nutritional Interventions for Depression & Anxiety

Individuals seeking nutritional intervention for depression and/or anxiety, it is recommended to create a healthy eating pattern or lifestyle that promotes optimal health. [1] This may include foods such as a Mediterranean diet (which involves lean proteins, olive oil, seafood, essential fatty-acids and vitamin B-12) or other healthy dietary meals that may assist in the prevention of a depressive illnesses or treatment of behavioral health disorders. Include foods that will help support the regulation of your mood, appetite, and cognition. For example, glutamic acid which helps neurotransmitter production (serotonin, dopamine, and norepinephrine), can be beneficial in your diet. [1]

Examples of Supporting Nutrients for Optimal Behavior Health:

  • Tryptophan – Poultry, fish, dairy, nuts, seeds, legumes

  • Vitamin B6 – Lean meats, sweet potatoes, bananas, avocados, whole-grain oats, wheat-germ

  • Vitamin B12 –Shellfish, eggs, some fortified plant-based milks

  • Folic acid (Folate) – Leafy greens, asparagus, broccoli, brussels sprouts, citrus fruits

  • Phenylalanine, Tyrosine & Histidine – Soy products and protein rich foods

  • Choline – Eggs, liver, seafood, poultry

  • Glutamic acid – Protein rich foods, fermented foods, aged cheeses, mushrooms, seaweed

Best in Health... and Namaste!



  1. Kris-Etherton P, Petersen KS, Hibbeln JR, et al. Nutrition and behavioral health disorders: Depression and anxiety. Nutr Rev. 2021;79(3):247-260. doi: 10.1093/nutrit/nuaa025.

  2. Papakostas GI, Cassiello CF, Iovieno N. Folates and S-adenosylmethionine for major depressive disorder. CAN J PSYCHIAT REV CAN PSYCHIAT. 2012;57(7):406-413. doi: 10.1177/070674371205700703.


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