SAMe (s-adenosyl-methionine) is a naturally occurring metabolite found in the human body, as well as in plant and animal foods. SAMe is synthesized in humans from the amino acid methionine in the presence of the co-factors B12 and folate.

SAMe is the most active of all methyl donors. Simply put, a methyl donor is a substance that can transfer a methyl group (which consists of a carbon atom attached to three hydrogen atoms [CH3]) to another substance. This methylation process is crucial for many important biological functions, including the metabolism of lipids and DNA. Though more research is needed, it is thought that adequate methylation of DNA may be able to prevent the expression of harmful genes, such as those are found in many forms of cancer.

SAMe has been compared to ATP (adenosine triphosphate) in its importance for the body. It is involved in the synthesis of neurotransmitters, melatonin, phospholipids, and polyamines, which are substances that control cellular growth. SAMe is also the source of methyl groups inside the nucleus for the DNA methylation process mentioned above; this process controls gene expression and the masking of genetic damage.

Even if the body is producing normal or average levels of SAMe, certain physiological states can create an increased demand for it. These might include aging, dietary deficiencies, elevated states of inflammation, emotional and/or physical stress, or genetic polymorphisms.

Sub-optimal levels of SAMe in some individuals may be due to insufficient amounts of the precursor amino acid methionine, a state sometimes found in those who follow a vegetarian diet, or who otherwise may have an inadequate intake of protein. Age-related declines in enzyme efficiencies throughout the body can be partially compensated for by increasing the supply in the body of enzyme co-factors such as SAMe, the B vitamins or magnesium.

Inadequate levels of SAMe in tissues, plasma and cerebrospinal fluid have been found to be highly correlated with conditions such as depression, Alzheimer’s disease and dementia. This could be partly due to the fact that SAMe is important in the following ways:

  • As a co-factor in synthesizing neurotransmitters such as serotonin, dopamine or epinephrine.
  • As a co-factor in synthesizing brain cell membrane phospholipids, such as phosphatidyl choline  and phosphatidyl serine.
  • As an ameliorating agent in the binding process of neurotransmitters to their receptors.
  • As a co-factor in the synthesis of melatonin, thus leading to improved sleep quality.


SAMe has been found clinically to be as effective as tricyclic antidepressants in alleviating depression, in doses ranging from 200-1600 mg/day.  It has also been found to improve the cognitive decline associated with senile dementia.

SAMe and the Liver

SAMe has been shown to improve liver function and provide protection from medications (such as acetominophen) as well as from the effects of alcohol. It increases synthesis of glutathione, and is a precursor of taurine and phosphatidyl choline, all of which play essential roles in the liver’s detoxification pathways.

It is because of these beneficial effects that SAMe may be helpful in cases of cholestasis (a condition marked by the impairment or obstruction of bile flow). It may also be helpful for women taking hormone replacement therapy or birth control pills, and those individuals who have been diagnosed with heavy metal toxicity.

SAMe and the Joints

SAMe was found to be very helpful in preventing and reversing the damage caused by both osteo- and rheumatoid arthritis through the following mechanisms:

  • Regenerates the joint tissues by increasing the number of chondrocyte cells, which are responsible for the production of the collagen matrix,  proteoglycans, and chondroitin sulfate.
  • Counteracts the destructive effect of the inflammatory cytokine TNF-alpha.


In addition, by improving serotonin levels SAMe might be helpful with pain tolerance levels, especially in conditions like fibromyalgia.


Suggested Usage

Patients should start with the lowest dose of 200mg early in the day, and increase as needed. SAMe should not be taken in the evening, due to the fact that its natural circadian rhythm is to be at high levels during the day, and then lowering during the evening and overnight period. The dose can be increased 200mg at a time, after five or more days, while its effectiveness is being gauged.

Absorption of SAMe is better on an empty stomach; taking SAMe with meals, however, will slow its delivery in the blood stream and create a more natural increase in SAMe concentrations. This will produce an effect more similar to what is found naturally in the body.

SAMe can have some potentially adverse effects. Patients with severe neurochemical imbalances, such as those found in manic and bipolar depression, should only use SAMe under the careful supervision of their physician. This is due to the increased production of all neurotransmitters, which could then cause increased leverls of anxiety and manic behavior. Other possible side effects might include nervousness, dry mouth, nausea, appetite suppression and constipation. These are all signs of excessive dopamine/adrenaline production.

SAMe is extremely sensitive to degradation from air and moisture. The SAMe product that Dr. Allen prescribes to his patients has been specially manufactured and packaged in such a way so that the product’s viability and stability has been maximized.  It is also enteric-coated, which makes it more bio-available in the body.

This coating prevents breakdown by stomach acid after ingestion, and promotes intact absorption in the small intestine. In addition, vitamins B6, B12 and folate have been added in order to provide co-factors for the natural conversion of SAMe to l-homocysteine, and then to l-cysteine.


Dr. Allen gives free lectures at the Library three to four times each year, on topics of interest from the cutting edge of integrative medicine.  If you would like to be added to our mailing list for these lectures and his other speaking engagements, please email