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S-Adenosyl Methionine - a product of natural body processes, vital to every living cell. Sold in the US under the marketing name SAMe or SAM-e — pronounced "sammy," aka AdoMet. Ademethionine is a salt of SAM.

Mechanisms and effects

  1. Transmethylation: most important methyl group donor, producing...
    1. Carnitine — fat burner
    2. Acetyl-L-carnitine — neuronutrient
    3. Creatine phosphate — primary ATP energy reservoir
    4. Adrenaline —stress hormone and neurotransmitter
    5. Phosphatidyl choline— neuronutrient, main membrane phospholipid
    6. Methyladenine and methylcytosine — DNA bases
  2. Transsulfuration
    1. S-Adenosylhomocysteine (SAH - left after transmethylation) + SAH hydrolase...
    2. to Homocysteine...
    3. to Cysteine...
    4. to Glutathione (GSH) anti-oxidant
      • GSH peroxidase
      • GSH-S-transferase
      • taurine
    5. GSH group essential in liver detox
    6. Also provides sulfur for glucosamine sulphate and chondroitin sulphate (essential for cartilage, damaged in arthritis)
  3. Aminopropylation
    1. converts putrescine to spermindine and sepermine, necessary for cell growth
    2. by-product: methylthioadenosine (MTA): analgesic, anti-inflammatory
    3. probably stimulates production of more dopamine and serotonin, amine antidepressant neurotransmitters, resulting (among other effects) in
      • mood elevation
      • better alertness (corrects "foggy brain")
  4. Highest concentration of SAM in body (in order):
    1. adrenal gland
    2. pineal gland
      • enables conversion of serotonin to melatonin
      • [serotonin too? LEF says "Without adequate SAMe during the day, neither melatonin nor serotonin can be synthesized"]
    1. liver. [need more info on adrenal & pineal]
  5. protects against cholestasis (insufficient bile), biliary obstruction and gallstones
  6. increases glycogen
  7. useful for Fibromyalgia: "reduced pain at the tender points, as well as fatigue, morning stiffness and resting pain. — see LEF magazine, September 1997 (reporting Jacobsen, et al)
  8. [Need more info on how it stimulates peristalsis]

How the body makes SAM

  1. ATP pathway
    1. ATP combines with methionine
    2. using enzymes
      • S-adenosylmethionine synthetase
      • phospholipid methyltransferase
      • [need more info]
  2. Betaine pathway (if SAMe synthetase is impaired)
    1. Using Trimethylglycine (TMG) / anhydrous betaine / glycine betaine (not betaine hydrochloride the digestive aid, which is much weaker).
    2. James South recommends using some TMG in addition when supplementing SAMe.
  3. [DMG?]
  4. Requires (South): "Deficiencies of any of the active coenzyme forms of vitamins B2, B6, B12 and folic acid will disrupt SAMe production, and conversely diminished SAMe production will impair conversion of folic acid and B12 to their coenzyme forms!

    Furthermore impaired B6-B12-folate-SAMe metabolism will lead to the blood/ cellular accumulation of the heart/ artery toxic metabolite homocysteine. ...The two enzymes necessary to convert homocysteine to cysteine and ultimately to the detoxicant glutathione, are two that commonly suffer slight genetic abnormalities that may impair normal cysteine/ glutathione production, especially when dietary B6 is low."
  5. Affected also by:
    1. Choline
    2. ?Molybdenum? to assist sulfoxidation, to keep the sulfur moving along that pathway? See the pages referenced at Sulfation Links. Raffelock apparently thinks it's a good idea if one takes MSM, for example.

Caution: Check your homocysteine

My experience so far:

  1. Frequently it helps a lot
    1. If I have taken it first thing in the morning and my liver starts to go down around noon, when the SAMe kicks in around 3 pm it will decrease the liver attack . (This is wonderful!)
    2. Chemical exposures that normally wipe me out are less devastating.
    3. Peristalsis improves
    4. Mood improves
    5. Body heat improves
    6. Nerve pinching and stiffness decrease
    7. I have better attention, feel more "here." A cure for "brain fog" (a Canary's term) — I assume, by increasing neurotransmitter production.
  2. Sometimes it makes me worse
    1. If I take it in the afternoon
      • I am not sleepy at night
      • I have very painful gas at night (I have this if I eat sulfur-containing foods after 5 pm. I can't tolerate many of those at all, but I try to get some sulfur into me.)
    2. If a liver attack is already under way, SAMe can make it worse. If I eat a lot of sulfur the same day, I get a liver attack.
    3. If I take it every day, I get sulfur gas and/or my liver goes down.
    4. If I take it every other day, I get diarrhoea.
    5. Currently I'm not taking it, waiting for tests of homocysteine; of Vitamins B2, B6, & B12; and of Folic Acid.

More information:

  1. James South on SAMe — a good overview, with supplementation dose information and references
  2. Life Extension Foundation — including info on how SAMe affects cholesterol, lipids in cell membranes, cancer, cirrhosis, heart disease and arthritis; SAMe's relation to melatonin and glutatyione, and summaries of studies showing SAMe's superiority to other pain-relievers. Long, with many references.
  3. Mother — much more succinct, citing results of studies without details on mechanisms. Many references. Reports concern that treating Parkinson's with SAMe may "cause the depletion of dopamine and block the effects of L-dopa" through excessive methylation. Drug Interactions Safety Check warns that SAMe has a supportive interaction with Tricyclic Antidepressants.
  4. S-adenosyl methionine regulation of metabolic pathways and its use in diagnosis and therapy - This is a description of United States Patent 6020139. Most of the text details a "new paradigm" for understanding disease in general, in terms of the functions of SAM: very interesting, very useful. But apparently there are also some specific diagnostic methods or processes which are patented. It makes me a little queasy to read this privatization of medical science.
  5. S-adenosyl methionine - Wikipedia's page

I am not advising anyone to do what I'm doing. Your body may react entirely differently from mine. I am not a doctor, and do not know enough about these supplements to recommend them.

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copyright © 2002 by Catherine Holmes Clark. Last updated 29 January 2002