Research is finding more and more a correlation with various health conditions, including heart disease, and depression. Low levels of SAMe may have something to do with these disease states. Perhaps it is the common thread. SAMe is a naturally occurring molecule distributed throughout all body tissues and fluids. The concentration of SAMe is highest in childhood, decreasing with age. It plays an essential role in more than one hundred chemical reactions (involving enzymatic transmethylation). It contributes to the synthesis, activation, and/or metabolism of hormones, neurotransmitters, nucleic acid, proteins, phospholipids, and some drugs.

Although it seems to have antidepressant properties, its actual mechanism of action is unknown. It is associated however, with an increase in serotonin turnover (facilitates higher levels of serotonin to be found and used outside the cell) and elevated dopamine and norepinephrine levels. These are three major neurotransmitters that are related to mood. By altering cellular membrane fluidity (improves traffic in and out of the cell), it facilitates signal transduction across membranes and consequently increases the efficiency of receptor effector coupling (the neurotransmitter finds a parking space). Neuroimaging studies indicate that SAMe affects the brain similarly to conventional antidepressants.

There appears to be hepatic SAMe deficiency in liver disease. Exogenously, it may act as an essential nutrient by restoring biochemical factors that are depleted in people with liver dysfunction. People with acute or chronic liver disease lose the ability to synthesize SAMe from methionine. This might be due to low activity of methionine adenosyl transferase (MAT), the enzyme that converts methionine to SAMe. As a result, this can lead to deficiencies in cysteine and choline, as well as depletion of glutathione, which plays a major role in liver detoxification and antioxidant reactions (gets rid of free radicals which harm cells and ultimately kills cells). This depletion in turn, exacerbates liver disease. SAMe also has a gastric cytoprotective effect (protects the cells of the stomach).

As was mentioned there are over one hundred chemical reactions in which SAMe is involved in; the following is one of the more important reactions and one that is well understood:

SAMe-------->Homocysteine---->---(remethylated,via folate and B12)---->Methionine

Methionine coverts back to-------->SAMe

Or

Through transulfuration converts to-------->Glutathione

If these reactions are uninterrupted the result is the production of more SAMe and Glutathionine (antioxidant). However, if for example, an individual is deficient in Vitamin B12, Folate or Vitamin B6 (pyridoxine); SAMe will be converted to homocysteine and the reaction ends there. This outcome is unwelcome since high levels of homocyteine are associated with renal and cardiovascular disease. Recent studies show no significant increases however under normal circumstances, to the contrary, adequate levels of SAMe seems to promote the formation of glutathione by converting homocysteine. Low levels of SAMe have actually been correlated with coronary artery disease. Doses of 1200mg per day are used in people with liver disease.

SAMe taken orally has low bioavailability (isn’t absorbed well) because of first pass effect (liver metabolism). That is why higher doses are required and should be taken on an empty stomach. Levels peak 3 to 5 hours post ingestion. Although well tolerated, common side effects may be: flatulence, nausea, vomiting, diarrhea, constipation, dry mouth, and headache. But these are rare and usually seen with higher doses. Clinical trials used a dose of 1600mg/day, but the normal range is between 400mg-1600mg/day in divided doses. People with fibromyalgia take 800mg/day. It is available intravenously, but seldom used, for depression.
Not recommended for bipolar disorder since it can at times exacerbate the mania part of this condition. It should not be used concomitantly with antidepressants. It could potentiate serotonergic effects and serotonin syndrome like effects. Avoid if you have Parkinson’s. It may reduce effectiveness of levodopa given for this disease. Also avoid taking dextromethorphan (cough syrups), meperidine and DO NOT USE with MAO inhibitors. The body must be clear of MAOs for at least 2 weeks. Also avoid tramadol.