SAMe: A Supplement for the 21st Century
By Hyla Cass, MD Recently a great deal of media attention has focused on the supplement SAMe, or s-adenosyl-l-methionine. Clinical trials in Europe and the United States have shown that SAMe can be beneficial in modifying brain function, making it a useful supplement for treating depression. SAMe is also shown beneficial in treating degenerative joint disease and liver problems.
Biochemistry and Actions
SAMe is manufactured in the body from the amino acid methionine, with the aid of the co-factors vitamin B12 and folic acid. A deficiency in any of these nutrients can result in decreased SAMe synthesis. As a “methyl donor” SAMe contributes a methyl group (a single carbon unit) to another molecule. This methylating action is what makes SAMe so essential in the production of nucleic acids (DNA, RNA), proteins, specific vitamins, neurotransmitters, antioxidants, hormones, and phospholipids. SAMe is also involved in the biosynthesis of many sulfur-containing compounds, including the antioxidant glutathione, the amino acids taurine and cysteine, and the sulfur-containing components of connective tissue.
SAMe is essential for the manufacture of brain neurotransmitters, or chemical messenger molecules, such as dopamine, norepinephrine, epinephrine, and serotonin. SAMe facilitates the binding of the neurotransmitters to their receptor sites, enhancing their activity. By methylating certain phospholipids, such as phosphatidylcholine and phosphatidylserine, in the cell membranes, SAMe also enhances cell membrane fluidity and improves cellular communication between neurons.
Treating Depression
Statistics show that depression affects about 17 million Americans, with 25% of the population likely to suffer diagnosable depression during their lifetime. Prescription antidepressants are the conventional treatment, with their accompanying side effects, and overdose potential.
SAMe: Comparisons with Placebo and Antidepressants
Over 100 placebo-controlled, double-blind studies provide well-documented evidence for SAMe's benefit in depression. Many of these show SAMe to be equal or superior to antidepressants, with more rapid onset, most often within a few days, and, unlike the antidepressants, with no side effects. According to one meta-analysis of these studies, 92% of patients responded to SAMe, compared to 85% for the medications.
One caution: a common occurrence with all antidepressants is the possibility of causing a rapid switch to mania in bipolar disorder, thus requiring close monitoring in these patients.
While antidepressants can cause liver damage, SAMe has been shown in numerous studies to be liver-protective. SAMe also has no withdrawal reaction, commonly found when antidepressants are stopped abruptly. SAMe has also been shown to prevent migraine headaches in many cases.
SAMe for Joint and Connective Tissue Function
SAMe is essential for the rebuilding of connective tissue and manufacture of cartilage components. Deficient levels of SAMe in joint tissues may be linked to a loss of the gel-like nature and shock absorbing qualities of connective tissues. Studies with SAMe have shown that individuals with osteoarthritis given 1,200 mg per day demonstrated increased cartilage formation over time as demonstrated by Magnetic Resonance Imaging (MRI). In fact, lower doses can be equally effective in treating arthritis, with an average of 400 mg daily (see dosage guidelines below).
Numerous clinical studies indicated that SAMe can reduce pain, stiffness and inflammation associated with degenerative joint problems, as well as enhance the range of motion of specific joints. When compared to nonsteroidal anti-inflammatory drugs (NSAIDs), such as Naproxen or Ibuprofen, SAMe was equally effective in reducing pain and inflammation over a three-month period, and without the gastrointestinal damage caused by these types of drugs.
Fibromyalgia
Clinical studies show SAMe works well in countering the fatigue, inflammation and pain associated with fibromyalgia, a puzzling and hard to treat condition. Patients have reported significant benefits from taking 400 to 800 mg daily of SAMe, including improved sleep, reduced fatigue, reduction in trigger points and painful areas and improvement in mood.
Support of Liver Function
Except for the adrenal and pineal glands, the liver contains the largest stores of SAMe of any body organ. Depletion of SAMe can seriously impair proper liver function. The liver depends on SAMe for regeneration, detoxification, bile production, methylation, and for the production of glutathione, the liver's natural antioxidant. SAMe aids the liver in neutralizing toxins, free radicals and carcinogens. Methylation reactions carried out by SAMe allow the body to eliminate toxins and protect the liver. The improvement of liver function as shown by reduction in levels of liver enzymes, demonstrated the ability of SAMe to regenerate the liver and enhance the liver's antioxidant defense system.
Because of SAMe's positive effects on the liver, it may also enhance the elimination of various drugs from the body. Similarly, SAMe has also been shown to protect the liver and body from the effects of excess and unbalanced estrogen levels, seen in some estrogen replacement therapy, oral contraceptive use, and premenstrual syndrome. Another possible use is to counter depression secondary to interferon, used in treating hepatitis C. While antidepressants put additional strain on the liver for their metabolism, SAMe is non-toxic, and in addition, can actually help heal the liver in these cases.
Overall, it can be stated that SAMe offers one of the best choices for nutritional support and protection of liver function due to the extensive ways that this nutrient enhances the structure and function of the liver.
How to Take SAMe
SAMe should be taken on an empty stomach, preferably one hour before or after eating, starting at a dosage of 200 mg once daily. If results aren't seen in a few days, the dose can be gradually increased (every five days or so), to the maximum dose of 800 milligrams daily, if needed. Most often, 400 mg per day is sufficient. While a positive response is often felt within a week of starting the program, and often within days, it may take as long as four weeks. Since SAMe is unstable at higher temperatures, it should be kept refrigerated whenever possible. Enteric coated tablets should be used to ensure product stability, maximize absorption and avoid nausea and gastrointestinal disturbances. Reducing the dose size and taking it with meals will usually overcome this problem, although food can interfere with its potency.
In general, the longer SAMe is used, the more beneficial the results. It can be used safely during pregnancy and lactation. However, SAMe's antidepressant activity may lead to the manic phase in individuals with bipolar (manic) depression. Though not reported in the literature, higher doses may occasionally lead to anxiety even in non-bipolar individuals. If the anxiety continues even on the lowest dose, the product should be discontinued. There are no reported negative interactions with other medications or nutritional supplements.
Cofactors
To avoid conversion of SAMe into high levels of homocysteine, known for its increasing the risk of cardiovascular disease, you should also be taking the cofactors, vitamin B6 (50 mg), vitamin B12 (1000 mcg), and folic acid (800 mcg), to enhance production of the SAMe precursor, methionine. This is most easily taken as part of a multivitamin, preferably with food, and not necessarily along with the SAMe dose.
Forms of SAMe
Pharmaceutical-grade SAMe comes in two forms, tosylate and a newer, more stable form called butanedisulfonate. Both forms are relatively stable in a pharmaceutical grade, enteric coated, dosage system.
Conclusion
SAMe provides a safe, effective treatment for a variety of conditions, including depression, degenerative joint problems and liver conditions. Due to biochemical individuality, results may vary.
References:
Depression:
Baldessarini RJ, Neuropharmacology of S-adenosyl-L-methionine. Am J Med 83 (Suppl. 5A), 95-103, 1987
Reynolds E, Carney M, and 2. Toone B, Methylation and mood. Lancet ii, 196-199, 1983.
Bottiglieri T, Laundry M, Martin R, et al., S-adenosylmethionine influences monoamine metabolism. Lancet ii, 224, 1984.
Janicak PG, et al., Parenteral S-adenosylmethionine in depression: A literature review and preliminary report. Psychopharmacology Bulletin 25, 238-241, 1989.
Bell, K.M. ,et al S-adenosylmethionine treatment of depression: A clinical trial. Am J Psychiatry 1988,145:110-14
De Vanna M and Rigamonti R, Oral S-adenosyl-L-methionine in depression. Curr Ther Res 52, 478-485, 1992.
Carney MWP, Toone BK, and Reynolds EH, S-adenosylmethionine and affective disorder. Am J Med 83 Suppl. 5A), 104-106, 1987.
Salmaggi P, et al., Double-blind, placebo-controlled study of S-adenosyl-L-methionine in depressed postmenopausal women. Psychother Psychosom 59, 34-40, 1993.
Kagan FL, et al. Oral S-adenosylmethionine in depression: A randomized, double-blind placebo-controlled trial. Am J Psychiatry 147, 591-595, 1990.
Russo A, et al., Efficacy of S-adenosyl-L-methionine in relieving psychological distress associated with detoxification in opiate abusers. Curr Ther Res 55, 905-013, 1994.
Arthritis:
Solomon L, Drug induced arthropathy and necrosis of the femoral head. J Bone Joint Surg 55B, 246-251, 1973.
Konig H, et al., Magnetic resonance tomography of finger polyarthritis: Morphology and cartilage signals after ademethionine therapy. Aktuelle Radiol 5, 36-40, 1995.
Glorioso S, et al., Double-blind multicenter study of the activity of S-adenosylmethionine in hip and knee osteoarthritis. Int J Clin Pharmacol Res 5, 39-49, 1985.
Marcolongo R, et al., Double-blind multicentre study of the activity of S-adenosyl-methionine in hip and knee osteoarthritis. Curr Ther Res 37, 82-94, 1985.
Domljan Z, et al., A double-blind trial of ademethionine vs naproxen in activated gonarthrosis. Int J. Clin Pharmacol Ther Toxicol 27, 329-333, 1989.
Muller-Fassbender H, Double-blind clinical trial of S-adenosylmethionine versus ibuprofen in the treatment of osteoarthritis. Am J Med 83 (Suppl. 5A), 81-83, 1987
Berger R and Nowak H, A new medical approach to the treatment of osteoarthritis: Report of an open phase IV study with ademethionine (Gumbaral). Am J Med 83 (Suppl. 5A), 84-88, 1987.
Fibromyalgia:
Jacobsen S, et al., Oral S-adenosylmethionine in primary fibromyalgia: Double-blind clinical evaluation. Scand J Rheumatol 20, 294-302, 1991.
Tavoni A, et al., Evaluation of S-adenosylmethionine in primary fibromyalgia: A double-blind crossover study. Am J Med 83 (Suppl. 5A), 107-110, 1987.
Pascale RM, et al., Chemoprevention of rat liver carcinogenesis by S-adenosyl-L-methionine: A long-term study. Cancer Res 52, 4979-4986, 1992. Scandinavian J. of (Gastroenterology 24, 407, 1989.)
Liver:
Mazzanti R, et al., On the antisteatosic effects of S-adenosyl-L-methionine in various chronic liver diseases: A multicenter study. Curr Ther Res 25, 25-32, 1979.
Frezza M, et al., Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis: A double-blind, placebo-controlled study. Gastroenterology 99, 211-215, 1990.
Di Benedetto P, Iona LG and Zidarich V, Clinical evaluation of S-adenosyl-L-methionine versus transcutaneous nerve stimulation in primary fibromyalgia. Curr Ther Res 53, 222-229, 1993.
Total glutathione before and after 6 months treatment with 1,200 mg oral SAMe. (Scand. J. Gastroent 24:407, 1989)
Bombarbieri G, Milani A, Bernardi L and Rossi L, Effects of S-adenosyl-L-methionine (SAMe) in the treatment of Gilbert's syndrome. Curr Ther Res 37, 580-585, 1985.
Angelico M, et al., Oral S-adenosyl-L-methionine (SAMe) administration enhances bile salt conjugation with taurine in patients with liver cirrhosis. Scand J Clin Lab Invest 54, 459-464, 1994.
