Sam-e appears to be a powerful antidepressant without nasty side effects.
A naturally occurring chemical, s-adenosylmethionine (SAM-e) plays hundreds of roles in the human body. Manufactured from the essential amino acid methionine and the energy-giving compound adenosine triphosphate, SAM-e (sometimes written SAMe or SAM) is essential for more than 35 of the body’s biochemical actions and can be found in the tissues of all plants and animals. The nutrient is integral to the synthesis, activation and metabolism of hormones, neurotransmitters, nucleic acids (found in DNA) and proteins and to the maintenance of all cell membranes.
Perhaps SAM-e’s chief metabolic role is the detoxification of harmful chemicals in the body, a process called methylation, which it accomplishes with the help of vitamin B12 and folic acid. But SAM-e also synthesizes neurotransmitters, the chemical messengers that carry nerve signals to the brain. It is this function that makes SAM-e a member of the brain’s mood-regulating team.
Despite its essential role, you’d never notice SAM-e unless your body suddenly didn’t have enough of it. A deficiency of methionine, vitamin B12 and folic acid can inhibit the body’s production of SAM-e. Although we can get SAM-e from protein-rich foods, these sources do not boost the availability of SAM-e in the body as much as supplements do. The elderly and those already suffering from depression are most at risk for SAM-e deficiency.

MOOD ELEVATOR
During the last 20 years, studies in Europe and the United States have confirmed that SAM-e supplements can be effective in the treatment of depression, among other conditions, according to Teodoro Bottiglieri, Ph.D., of the Baylor University Medical Center Institute of Metabolic Disease in Dallas. In fact, SAM-e appears to be comparable to such prescription drugs as imipramine and clomipramine for treating depression. “SAM-e enhances brain dopamine and serotonin-neurotransmitter metabolism and receptor function,” explains Bottiglieri. “These mechanisms are probably responsible for the antidepressant effect of SAM-e.”
Richard Brown, M.D., of Columbia University College of Physicians and Surgeons in New York City, concurs that SAM-e supplements are effective in treating patients with mild to severe depression. His patients often notice an improvement within seven to 11 days, he says. A meta-analysis of several studies of more than 1,000 patients revealed that SAM-e was an effective anti-depressant in 38 percent of cases. Compare that to prescription anti-depressants, which have a success rate of only 20 percent.
Sam-e has been approved in Italy, Spain and Russia, where it can be purchased over the counter for the treatment of depression. Additionally, the nutrient seems to have a faster action than anti-depressants like imipramine. Further, Sam-e does not cause the side effects that prescription anti-depressants may bring on, including dry mouth, constipation, bladder problems, sexual dysfunction, dizziness, headache, drowsiness, nausea, insomnia and blurred vision.
Sam-e appears to be safe for pregnant women and nursing mothers, although more research is needed. And take note: SAM-e should not be taken in combination with monoamine oxidase inhibitors (MAOs), a widely prescribed class of anti-depressant.

WHAT TO TAKE
For Depression: For patients with mild to moderate depression, Richard Brown, M.D., of Columbia University College of Physicians and Surgeons in New York City, recommends 200 to 400 mg. of SAM-e per day, taken on an empty stomach in divided doses in the morning and the evening.
For Joint Mobility: Peter W. Billingmann, M.D., of the Institute of Sports Medicine, University of Landau in Germany, prescribes 400 mg. per day of SAM-e to athletes. For patients with hip or knee fractures, he prescribes 600 to 1,200 mg. per day. For a patient with osteoarthritis, he usually begins with 200 mg. per day.

GETTING PHYSICAL
In addition to helping to treat depression, SAM-e may be just as promising for several bodily ailments. “SAM-e seems to stop and reverse degenerative joint disease be promoting cartilage formation and enhancing the repair of damaged joints,” say Teodoro Bottiglieri, Ph.D., of the Baylor University Medical Center Institute of Metabolic Disease in Dallas. John H. Weisburger, Ph.D., M.D., of the American Health Foundation in Valhalla, N.Y., adds that SAM-e plays a significant role in joint mobility, psychiatric disorders and liver health. The supplement is also said to be useful for patients with a wide range of other problems, including asthma, gout, obesity, fibromyalgia, alcoholism and Parkinson’s and Alzheimer’s diseases. Among its many attributes, SAM-e deactivates homocysteine, the amino acid that can build up in the bloodstream and increase the risk of heart disease, stroke and blood clots in the legs and lungs.

What is S-Adenosyl Methionine (SAMe)?
S-Adenosyl Methionine (S-adenosyl-L-methionine or SAMe) is active methionine. It is formed when the body combines the amino acid L-methionine with ATP (adenosine triphosphate), the primary energy molecule found in physiologic processes. Italian researches first discovered SAMe in 1952, and Italy remains the main country for research into the properties of this compound. The activated S-methyl group of SAMe is readily available for transfer in biochemical reactions, and SAMe is probably the most active and efficient of the various methyl-donors currently known. G. Strementinoli, one of the major figures in SAMe studies, argues that SAMe “is probably second only to ATP in the variety of reactions in which it serves as a co-factor.”

Is SAMe Found in Food?
Very little SAMe is found in foodstuffs for several reasons. First, active methionine is produced only in small amounts in living organisms as a co-factor for use in methylation and other reactions. Unlike enzymes, which are conserved when employed as cofactors, SAMe is used up through the loss of its S-methyl group. Second, SAMe is highly unstable molecule. Even some of the supposedly purified forms now available break down rapidly.
Dietary proteins, of course, contain methionine, and it might be assumed that merely supplementing with this amino acid or eating more protein would be sufficient to increase SAMe levels in the body. Unfortunately this is not the case. Although exposure to a protein-deficient diet can reduce the bodys ability to synthesize SAMe, eating large amounts of protein will not necessarily increase SAMe synthesis and can have negative effects. Increased levels of methionine in the diet must be matched by increased intakes of the vitamins B6, B12 and folic acid. Without adequate intakes of these vitamins and/or trimethyglycine (TMG), increased methionine levels will lead to increased levels of homocysteine thiolactone (S-adenosyl-L-homocysteine), which is strongly associated with the development of arteriosclerosis.
The amount of SAMe available to the body typically declines with age. Tissue levels are also low in quite a number of conditions, including osteoarthritis, depression and many liver disorders.

The Benefits: Transmethylation, Transsulfuration and Aminopropytation
Transmethylation - SAMe is the most important donor of methyl groups active in mammalian tissues. Methyl groups are single carbon units with the structure CH3 (one carbon and three hydrogen atoms). Transmethylation (the donation of methyl groups) is especially important in a number of areas.
In the area of energy metabolism, L-carnitine, which ferries long-chain fatty acids into the mitrochondria for oxidation, and creatine phosphate, which is the quick burst energy/ATP reservoir of muscle cells, both are created via methylation reactions. Similarly, most of the neurotransmitters, such as L-dopa and dopamine and related hormones, are the products of methylation reactions. These compounds include acetyl-L-carnitine, epinephrine (adrenaline) and phosphatidyl choline (a component of lecithin).
Certain molecules that are important to cellular DNA also are the products of methylations. In fact, the methylation of cellular DNA appears to be important in the suppression of DNA imperfections and influences longevity. The demethylation of DNA is increasingly coming to be viewed as a significant aspect of aging.
Transsulfuration - SAMe is part of a complex biochemical pathway. Once SAMe has donated its methyl group, the resulting S-adenosyl-L-homocysteine becomes the starting point for the production of a number of important compounds as part of the process usually called transsulfuration.
One endpoint of this process is the production of L-cysteine, an important amino acid used by the body to construct a family of sulfur-containing compounds of critical importance. These include the elements of the antioxidant enzyme pathway built around glutathione: glutathione (GSH), glutathione peroxidase and glutathione-S-transferase. The amino acid taurine is another end product of cysteine metabolism. Glutathione is necessary for the scavenging of free radicals produced by glycolysis, the breakdown of carbohydrates for energy. The glutathione family of compounds and taurine are important for liver detoxification reactions.
Paradoxically, although cysteine can be obtained fro the diet, some researchers argue that the main source of cysteine used by the body in the production of glutathione is actually SAMe, and not cysteine. The reason for this is that as much as 80% of the active sulfur groups of cysteine (sulfhydryl groups) may be cleaved from the amino acid during digestion such that the compound is no longer cysteine. It should be added that at least some of the sulfur liberated from SAMe is contributed to the sulfuration of glucosamine and the chondroitin sulfates to produce the building blocs needed for the synthesis of cartilage, ligaments, tendons, the bone matrix, etc., that is all tissues that contain collagen and chondroitin sulfates.

MIGRAINE
SAM is beneficial in the treatment of migraine headaches. The benefits manifest gradually and require long-term treatment for therapeutic effectiveness.

Dosage Ranges
In general the long SAM is used, the more beneficial the results. It is perfectly suited for long-term use because of its excellent safety profile. Here are the dosage ranges for the various clinical indications:
*Depression: Four hundred milligrams three to four times daily. Because SAM can cause nausea and gastrointestinal disturbances in some people. It should be started at a dosage of 200 milligrams twice daily for the first day, increased to 400 milligrams twice daily on day three, 400 milligrams three times daily on day ten and finally to the full dosage of 400 milligrams four times daily after 20 days, if needed.
*Osteoarthritis: Start out as above for depression. After 21 days at a dosage of 1,200 milligrams daily reduce dosage to the maintenance of 200 milligrams twice daily.
*Fibromyalgia: 200 milligrams to 400 milligrams two times daily.
*Liver Disorders: 200 milligrams to 400 milligrams two to three times daily.
*Migraine Headaches: 200 milligrams to 400 milligrams two times daily.

SAFETY ISSUES
No significant side effects have been reported with oral SAM other than the occasional nausea and gastrointestinal disturbances. However, individuals with bipolar (manic) depression should not take SAM unless under strict medical supervision - SAM’s antidepressant activity may lead to the manic phase in these individuals. This effect is exclusive to some individuals with bipolar depression.

INTERACTIONS
SAM functions very closely with vitamin B12, folic acid, vitamin B6 and choline in methylation reactions. Because of SAM’s effects on the liver, it may enhance the elimination of various drugs from the body. The clinical significance of this particular effect has not been fully determined.