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S-Adenosyl-L-methionine (SAM-e) affects cellular function. It helps to treat dementia and neurological disorders, liver diseases, and depression. I recommend SAM-e to a variety of my clients, you can find a compiled list of what biohacks have had the biggest impact in the lives of my clients and myself in our book, SelfHacked Secrets. To receive the first chapter absolutely free click here. Read more below to learn more about the health benefits of SAM-e.



S-Adenosyl-L-methionine, also referred to as SAM, AdoMet, or SAM-e, is of great importance in living organisms (R).

SAM-e occurs naturally in the human body and is synthesized from methionine (R).

Any changes in the availability of S-Adenosyl-L-methionine in the body affects cellular function. Abnormalities in energy production often result in liver diseases and neurological disorders (R).

Therefore, SAM-e has been used orally to treat liver diseases, fibromyalgia, mood disorders such as depression and neurological disorders, dementia, and Alzheimer’s disease (R).

The SAM-e That I Recommend

Health Benefits of SAM-e

1) S-Adenosyl-L-Methionine Improves Depression


Major depression is a common mental health disorder and for some patients, the standard method of treatment is often inadequate (R).

Sometimes the use of a supplementary medicine, such as high-dose S-Adenosyl-L-methionine, along with antidepressant medication has proven to be beneficial (R).

SAM-e produces therapeutic effects similar to common antidepressants and is relatively toxic free (R).

It has a faster onset than some conventional antidepressants and is tolerated in high doses (R, R).

2) SAM-e Helps Treat Liver Disorders

SAM-e helps restore liver function in the presence of chronic liver diseases such as alcoholic and non-alcoholic cirrhosis as well as cholestasis (R).

SAM-e also prevents or reverses liver toxicity due to drugs like Tylenol and steroids (R).

SAM-e reduced liver dysfunction in humans who had alcoholic cirrhosis over a two-year period (R).

3) SAM-e Improves Brain Function


Cerebrospinal fluid (CSF) SAM-e levels are significantly lower in severely depressed patients and in patients with Alzheimer’s or dementia. Treatment with SAM-e increased CSF SAM-e and improved moods and brain function (R).

SAM-e is linked to the folate cycle and vitamin B12 energy production, which provide methyl groups required for SAM-e mediated methylation reactions (R).

Mice raised on a diet deficient in vitamins B6 and B12 increased Alzheimer’s-like features (R).

SAM-e inhibits the increase of progression of these Alzheimer’s-like features and also improves spatial memory (R).

4) S-Adenosyl-L-Methionine Treats Osteoarthritis

Osteoarthritis is associated with pain, stiffness and reduced range of motion in the body. SAM-e alleviates the discomfort associated with osteoarthritis (R).

When tested on humans for knee osteoarthritis, it has a slower onset than other medication and there was no real difference in pain tolerability (R).

5) SAM-e Reduces Symptoms Associated with Sjögren’s Syndrome and Fibromyalgia


Fibromyalgia or fibrositis is a painful, nonarticular, non-inflammatory condition predominantly involving muscles (R).

It occurs alone or in conjunction with other connective tissue disorders such as Sjögren’s Syndrome. This syndrome is an autoimmune inflammatory disease that mainly affects mouth and eye glands (R).

In female patients with both conditions, SAM-e usage drastically reduced the number of tender points and painful areas (R).

Patients with these conditions tend to have moderately severe depression. However, treatment with antidepressants worsen the oral and eye symptoms associated with Sjögren’s Syndrome. SAM-e is an effective treatment as it improves mood without exacerbating these symptoms (R).


  • S-Adenosyl-L-methionine acts as a methyl donor in transmethylation reactions. Methylation reactions are critical in numerous cellular processes ranging from gene production to membrane fluidity (R)
  • The liver is responsible for the control of SAM-e, as it is the major site of its synthesis and degradation (R)
  • SAM-e is important in three biochemical pathways: transmethylation, transsulfuration, and aminopropylation
  • When SAM-e molecules release methyl groups, this results in the activation of the transsulfuration pathway which leads to the formation of glutathione (R)
  • Glutathione is a cellular antioxidant responsible for detoxification of compounds in the body such as lead and Tylenol. These reactions show why SAM-e is effective in treating liver diseases (R)
  • SAM-e is responsible for numerous transmethylation reactions, such as those involving the synthesis of neurotransmitters (R)
  • Antidepressants inhibit the reuptake of neurotransmitters, for example, serotonin. However, the role of SAM-e as a methylating agent enhances synthesis of neurotransmitters associated with moods such as serotonin, norepinephrine, and monoamines (R)

Side Effects

  • Stomach problems (R)
  • Anxiety (R)


For treatment of liver disorders such as cholestasis, scientists recommend 800 mg parenterally or 1600 mg orally of SAM-e (R, R).

For depressive illnesses, scientists recommend 200 to 400 mg per day for 15 to 20 days. (R).

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    This article is surprisingly incomplete. First, if you have a tendency towards mania or are bipolar, never try SAM-e.

    I have seen people take SAM-e for the first time and 20 minutes later come alive as if awakening from a deep depression for the first time. It’s fast acting, but you must take it on an empty stomach.

    SAM-e is strong stuff. Pretty much all the capsules are too high a dose for many people. This is a problem with many supplements, not just SAM-e. Even 50mg of SAM-e can have a pretty strong effect. The capsules are typically 400mg, or 200mg — just too high a dose unless you are pretty depressed.

    If you need a lot of SAM-e (hundreds or even thousands of mg) to feel well then something is wrong with your gut, liver or your methylation is compromised somehow. You are most likely quite depressed and should seek professional care to figure out why.

    I recommend if you’ve tried SAM-e in the past and you couldn’t tolerate it, to try just 25 or 50mg and see what happens. Either get liquid SAM-e, or a pill cutter. Be sure your folate, B12, and B6 status are good before taking SAM-e. If it’s your first time, absolutely go slow and try 50mg first, then slowly up the dose if you don’t have any bad reactions. SAM-e is treated as a drug in Europe for a reason.

    If you get super anxious or insomnia you have taken way too much. Niacin can help with the side effects of SAM-e.

    Also note that if you are unhealthy and your methylation is too low SAM-e can be very unhealthy to take as it increases homocysteine. TMG is a safer, cheaper, and more gentle way of boosting SAM-e levels.

    Personally, I avoid SAM-e because it’s just too close a precursor to homocysteine.

  • Alison

    I checked on the Pure Encapsulation website and you have to be a Health Practitioner to order from them.

  • Robin

    Can you say more about copper? I’m low (but not without) in ceruloplasmin, serum copper, plasma copper, and very low normal ferritin. I appear to have a copper deficiency that may be related to poor copper transport. Trying to figure out how to raise ceruloplasmin—exome testing says I have a rare pathological CP variant.

    So much has been written about copper toxicity, I’m hesitant to throw copper at my system without knowing more about ceruloplasmin…I should go back to the copper page here at self hacked.

  • Robin

    The only SAMe that I’ve found that does not have nasty fillers is the SAMe by Pure Encapsulations.

    I have multiple snps on the HNMT gene. I believe SAMe helps with my cns histamine metabolism:

    To avoid getting overstimulated, I am experimenting with the dosage. I don’t take more than one a day. Right now I’m skipping a dose every 3 days or so, if my energy feels good.

  • Stuart Hill

    try copper

  • steve

    I’ve heard that TMG gets converted to sam-E as needed. Maybe that would be better.
    I already have anxiety so afraid to try sam-E again, especially since they all have such bad excipients like mannitol and plastics

  • Nancy

    I can’t take it-have tried several times-alot of anxiety.My genes don’t show that it should be a problem for me-but unfortunately -it is.

  • Steve

    The biggest problem with sam-e are the horrible ingredients such as mannitol in almost all of the brands.

  • Nancy Smith

    I am unable to tolerate SAM E. I am sure it is due to one of my genes or variances. But it seems I would need it.Isn’t there a b vitamin with a small amount of SAM E

  • Daniel Crawford

    Sam-e gives me gum recession. Which is a real shame as I find it very uplifting.

  • John Macgregor

    FYI, I doubt if most people would experience sfx with SAMe, but I & a few others do, & they are most unpleasant & take a couple of weeks to abate.

  • Emilie

    In the reference for the negative effect Anxiety, there came another article ( about knee pain ).
    kind regards from Europe, France

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