SAMe is crucial for the biosynthesis of both DNA and RNA nucleic acids, phospholipids, proteins, epinephrine, melatonin, creatine and other molecules.

SAMe is used as a drug in Europe for the treatment of depression, liver disorders, osteoarthritis and fibromyalgia.

The dose for use in depression has been in the range of 400 to 1,600 mg daily in divided doses.
For liver problems, usual doses reported are up to 1,600 mg daily in divided doses.
For bone and joint health, the daily dose is typically 200 to 1,200 milligrams in divided doses.

SAMe is effective in offsetting depression: in a meta-analysis of the most significant clinical studies, SAMe's efficacy was shown to equal or slightly better that of tricyclic antidepressants (such as imipramine, amitriptyline, desipramine, and nortriptyline), which commonly have side effects such as insomnia, nervousness, nausea and sexual dysfunction. SAMe also worked more quickly, with results shown in roughly half the time of standard antidepressants. SAMe deficiencies have been linked to various neuropsychiatric disorders.

Those with joint or bone problems may benefit from its anti-inflammatory properties: SAMe is an intermediate step along the pathway (series of chemical reactions) transforming homocysteine into methionine; in excess amounts, homocysteine can cause atherosclerosis. Increased blood fats and other potential dangers to heart function are more commonly being seen in HIV+ people using protease inhibitors.

It’s a good idea to use SAMe with adequate levels of vitamins B₆, B₁₂, folic acid, and, possibly, betaine (TMG): this provides cofactors for the natural conversion of SAMe to L-homocysteine - and then safely to L-cysteine - so as to not raise homocysteine levels.

SAMe is probably the most active and efficient methyl-donor known, vitamin B₁₂ is another excellent one. Methyl groups are needed for the body to synthesize its own carnitine and various neurotransmitters (brain chemicals) like L-dopa, acetyl-L-carnitine, epinephrine and other compounds. Methylation of DNA can help protect and preserve it.

SAMe has been used to treat some inherited conditions that result in demyelination of nerves that causes neuropathy; whether this would help those with HIV- or HAART-related neuropathy is not known, although low levels of SAMe have been seen in people with HIV-related neuropathy.

Reduced levels of SAMe are associated with: fatty liver as well as other pathologies. In addition, since cotrimoxazole (Bactrim, Septra) can inhibit folate, this might be a good idea to use since it may be the Bactrim causing the observed increase in homocysteine.

Because SAMe is expensive, another approach to gaining its benefits is to supplement with the things that the body uses to make SAMe. This would include the amino acid methionine, tri-methyl glycine (TMG), folic acid, and vitamin B₁₂, all taken daily. Whether this would work as well as taking SAMe has not been shown, but it would at least provide the building blocks for the substance.

It is often reported in the literature that doses can usually be cut in half when a positive effect is achieved, and that its effects, if any, are usually evident within two weeks of starting supplementation.

SAMe is extremely sensitive to degradation from air and moisture: keep dry and sealed tight!

Studies report virtually no side effects at all. However, there is a theoretical, but as yet unobserved, concern for people with bipolar manic/depressive disorder: one case report of a woman receiving SAMe and clomipramine suggested a synergistic reaction that caused serious anxiety, heart dysregulation, confusion and stupor.

Detailed scientific information about SAMe cand be found on the Physician's Desk Reference website.