In part II of this two part series, you will learn about how SAMe works to treat depression, fibromyalgia and liver disorders. You will also find some guidelines on taking SAMe supplements, and the comprehensive scientific reference section. When reading this article keep in mind that with any health issue, individuals with known disorders should always consult their doctor before starting a dietary intervention. So if you are reading this article for yourself or your client, when using nutritional or exercise programs as supportive treatment of a disease condition, working under doctor supervision is mandatory.
SAMe Is An Effective Treatment For Fibromyalgia
Equally impressive are the clinical studies showing how SAMe is helpful for improving not only the degree of pain experienced by people with fibromyalgia, but also their mood. Fibromyalgia is a chronic condition that afflicts people mostly between the ages of 20 to 50 years old. Symptoms of fibromyalgia include generalized muscle pain and aches throughout the body, disturbed sleep, depression, fatigue, and gastrointestinal disturbances.
Fibromyalgia is diagnosed by determining the muscle tenderness at 11 or more of the 18 so-called tender points. These symptoms are often accompanied by anxiety and stiffness, especially upon awakening from sleep. It has been suggested that there is a close resemblance between fibromyalgia and chronic fatigue syndrome (CFS) -- a condition associated with extreme fatigue -- because there is an overlap in the symptoms associated with the two conditions. Both CFS and fibromyalgia tend to run in families, suggesting a possible genetic predisposition to these disorders.
In clinical studies, SAMe has proven to be useful for relieving several symptoms associated with fibromyalgia, including depression, swelling, and localized tenderness and irritation. Moreover, all of these symptoms suggest the possible need for supplementing the methylation process. And if nerve health is, in fact, a contributing factor in this disorder, then SAMe has even more to offer.
Researchers who have used SAMe in clinical trials for the treatment of fibromyalgia have found it to be especially useful for reducing subjective feelings of pain and fatigue and for lifting depression. In a double-blind, crossover study that tested SAMe by injection (intramuscular) in doses of 200 milligrams per day, SAMe reduced the number of tender points experiencing pain within twenty-one days in study subjects. The subjects also noticed an improvement in their mood.
Another trial compared treatment with orally administered SAMe (800 milligrams a day) to treatment with a placebo for six weeks in patients with primary fibromyalgia. The results of this study showed that those subjects receiving SAMe had noticeable improvements in their condition. These studies show that in addition to using SAMe as a nutritional treatment for depression and osteoarthritis, sufferers of fibromyalgia can also expect to experience other beneficial effects from taking SAMe.
SAMe Treats Depression, Too
Depression has both mental and physical causes. Events involving extreme stress, including divorce, the death of a loved one, accidents, or loss of employment are common triggers of depression. Sometimes depression is the result of an illness, such as thyroid insufficiency. Diets that are deficient in one or more of the essential vitamins and minerals, and in some cases protein, are often associated with depression. Eating diets high in "junk foods" such as sugar, refined carbohydrates and snack foods can contribute to fueling the depressive state. When a person's overall state of health and fitness is poor, it's no surprise that mental functioning and emotional well-being may be at risk. However, for people suffering from chronic depression, medical research has shown that taking SAMe can have antidepressant activities.
From a dietary standpoint, intake of caffeine and alcohol is sometimes associated with depression and mood swings. The consumption of excessive quantities of alcohol, especially before bedtime, can have disastrous effects on your sleep and ultimately adversely effect your mood. Excessive alcohol consumption may adversely effect sleep and mood because it can interfere with natural production of melatonin. Melatonin is a hormone that controls the daily sleep/wake cycle. As a result, excessive alcohol consumption can alter melatonin secretions and disturb a good night's sleep.
SAMe Is Essential For Brain Function
SAMe is the primary methyl donor available in the brain. Some of the biochemicals essential for proper nervous system function that benefit from SAMe include epinephrine, norepinephrine, serotonin and dopamine. Transmethylation in the brain includes actions upon the phospholipids that are the primary components of all cell membranes.
Supplementation with SAMe improves the body's ability to manufacture phospholipids for use in the brain and helps keep neurotransmitters in balance.
SAMe Is A Well-Established Antidepressant
SAMe's role as an antidepressant has been studied in clinical settings since the 1970s. In 1994, Giorgio Bressa, of the Department of Psychiatry, University Cattolica Sacro Cuora School of Medicine, in Rome, Italy, evaluated clinical studies on SAMe. He found that studies using SAMe on hundreds of people produced favorable results in many cases. Giorgio Bressa concluded that the clinical trials of SAMe in treating depressive syndromes and disorders are superior to that of placebo and comparable to that of standard tricyclic antidepressants.
Since SAMe is a naturally occurring compound with relatively few side effects, its antidepressant effect makes it a potentially important tool in the treatment of depressive disorders. Oral dosages of SAMe ranged from 800 to 1,600 milligrams per day, with 1,600 milligrams per day being used the most and thought to be the most effective. These dosages were divided throughout the day.
It was also interesting to note that one of the most recent studies on SAMe rated its effectiveness in depressed postmenopausal women. During a 30-day period, researchers measured the effects that taking 1,600 milligrams per day or placebo had on 80 women between the ages of 45 and 59. After the 30-day period, the researchers discovered that there was a significantly greater improvement in depressive symptoms in the group of women who were treated with SAMe, compared to the placebo group. When side effects were observed they were only mild and transient.
How Fast Does SAMe Work To Alleviate Depression?
A study conduced by researcher M. Fava using 400 milligrams of SAMe per day, found that depressive symptoms were remitted within two weeks. Fava also reported that during the study periods no serious adverse effects were observed. This research indicates that SAMe is a safe and relatively fast-acting antidepressant.
Other Benefits Of SAMe
SAMe plays an important role in liver function. In fact, it is a key element in the liver's production of cysteine, glutathione and taurine, which are important in liver protection and detoxification. Feelings of fatigue, poor digestion, allergies and elevated responses to environmental toxins are often linked to inadequate liver function. Intrahepatic cholestasis -- the failure of the liver to produce or release normal amounts of bile into the small intestine -- is one of the conditions that benefits by improvements to liver health. In addition, SAMe has proven its worth in cases of sluggish liver function and even in the very serious disorder known as cirrhosis of the liver.
SAMe promotes liver health by intervening in all three of the primary pathways known to be important in this regard. For example, SAMe is used as a methyl donor by the liver to convert phosphatidylethanolamine into phosphatidylcholine (PC). PC is one of the best known and most useful of all lipotropics. Trials have shown that PC is very helpful to subjects with several types of liver inflammation, in cases of fatty degeneration, and even in cases of fibrotic damage -- the thickening and scarring of connective tissues.
SAMe encourages the secretion and elimination of bile. This action may also explain SAMe's usefulness in cases of Gilbert's syndrome. In this condition, bilirubin -- a substance produced by the liver -- is found in elevated amounts in the blood. A dosage of 400 milligrams of SAMe taken three times per day has been shown to be beneficial to those people who have been diagnosed with this syndrome.
SAMe is a superb liver protector because its role as a methyl donor allows it to aid in the detoxification process. For example, it can help in the inactivation of estrogens -- caused by premenstrual syndrome and/or the use of oral contraceptives -- which are known to impair liver function. A number of trials have demonstrated that SAMe is successful in protecting the liver and in maintaining liver function under conditions of excess estrogen. Likewise, animal trials have shown that SAMe is important in protecting the liver against the fatty infiltration that can be induced through the excessive use of alcohol. When you consider that synthetic estrogens and alcohol are two of the most common liver toxins, supplementation with SAMe might be viewed as a wise promoter of liver health.
Other benefits that scientists are beginning to discover include SAMe's role in anti-aging, in promoting normal sleep/wake cycles, and for the treatment of migraine headaches. Due to the numerous metabolic functions SAMe affects, we can expect new and exciting health benefits of taking SAMe to be discovered soon.
Modern SAMe Usage
After its discovery in 1953, researchers worked hard to make a stable form of SAMe for use in human studies. The first studies on SAMe used intravenous solutions. Eventually, studies using a solid dosage form of SAMe were made, and clinical trials using orally administered SAMe were conducted. Oral dosages of SAMe were found to be well absorbed and used by the body quickly. Single dosages as low as 400 milligrams were shown to increase blood levels of SAMe almost four times higher then normal in only six hours.
This early research also found that most of the SAMe absorbed was used in the body for various biochemical reactions. These studies also showed that SAMe was safe and effective when administered intravenously or orally. The bioavailibility of SAMe is important due to the fact that low levels of SAMe are associated with such disorders as arthritis, depression, coronary artery disease, liver disease, and premature aging.
Today, oral SAMe formulations are widely used by millions of people worldwide. Due to the fact that SAMe is by nature an unstable substance, make sure that you check with the company whose brand of SAMe you are taking to confirm that they have proven their product's potency and stability.
SAMe Supplement Use
The amount of SAMe supplement taken will range depending on body weight and medical condition. Generally speaking, taking higher dosages during the first two months is indicated for most people. This is called SAMe loading, which will increase body levels of SAMe. Taking 1,600 milligrams per day has been shown to be effective for raising the body's SAMe levels. Sometimes people may have to work your way up to this dosage if they experience minor gastrointestinal upset.
If this occurs, start by taking 400 milligrams per day during the first week; then 800 milligrams per day during the second week; 1,200 milligrams per day during the third week; then 1,600 milligrams a day during weeks four through eight.
After the loading period, reduce the daily dosage between 800 milligrams to 400 milligrams of SAMe per day. Take SAMe in divided dosages, two, three or four times per day for best results.
For people who are interested in taking SAMe as part of their daily nutritional health program, a daily dosage of 200 milligrams to 400 milligrams will be adequate. Remember that SAMe not only cures disorders like arthritis and depression, but it boosts the body's anti-aging mechanisms and should be taken as part of a nutritional longevity program.
Although SAMe is found in the tissues of living organisms, due to its unstable nature it is not found in significant amounts in the food you eat. Therefore, your body has to make the SAMe it needs or you can get extra amounts from SAMe supplements.
Following a healthy lifestyle and diet is important for maximizing your body's natural production of SAMe. Remember that SAMe is made from the amino acid methionine, which you need to get from the foods you eat, that is, proteins. In addition, certain vitamins and minerals are also required for the proper production and use of SAMe in your body. So, eating a proper diet, taking your daily vitamin and mineral supplements is important for the optimum production and use of SAMe in your body.
The medical research studies conducted on over 25,000 people taking SAMe have reported that side effects are rare and when they do occur are minor. Gastrointestinal upset, such as feelings of nausea, are the most common of these minor side effects. Dizziness is another reported side effect. One long-term study reported that daily consumption of SAMe was safe over a two-year period. Individuals taking medication or who have a medical condition should consult their doctor before taking SAMe. Millions of people worldwide take SAMe supplements safely.
Note: This is part two, click here for part one!
Angelico M, et al., "Oral S-adenosyl-L-methionine (SAMe) Administration Enhances Bile Salt Conjugation With Taurine in Patients with Liver Cirrhosis," Scandinavian Journal of Clinical & Laboratory Investigations Vol. 54 (1994):459-464.
Baldessarini RJ, "Neuropharmacology of S-adenosyl-L-methoionine," American Journal of Medicine Vol. 83 (Suppl. 5A) (1987):95-103.
Bell KM, et al., "S-adenosylmethionine Blood Levels in Major Depression: Changes with Drug Treatment," Acta Neurological Scandinavian Vol. 154 (Suppl.) (1994):15-18.
Bell KM, et al., "S-adenosylmethionine treatment of depression: a controlled clinical trial," Am J Psychiatry, Vol. 145 (1988): 1110-1114
Berger R and Nowak H, "A New Medical Approach to the Treatment of Osteoarthritis: Report of an open phase IV study with ademetionine (Gumbaral)," American Journal of Medicine Vol. 83 (Suppl. 5A) (1987):84-88.
Bombardieri G, et al., "Intestinal Absorption of S-adenosyl-L-methionine in Humans," Scandinavian Journal of Clinical & International Journal of Clinical Pharmacology, Therapy & Toxicology Vol. 21 (1983):186-188.
Bombardieri G, Milani A., Bernardi L, and Rossi L, "Effects of S-adenosyl-L-methionine (SAMe) in the Treatment of Gilbert's Syndrome," Current Therapeutic Research Vol. 37 (1985):580-585.
Bottiglieri T, et al., "The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders," Drugs, Vol. 48(2) (1994): 137-152.
Bottiglieri T and Hyland K, "S-adenosylmethionine levels in psychiatric and neurological disorders: a review," Acta Neuro Scand Suppl, Vol. 154 (1994): 19-26.
Bottiglieri T, Laundry M, Martin R, et al., "S-adenosylmethionine Influences Monoamine Metabolism," Lancet (1984):224.
Bressa GM, "S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies," Acta Neurologica Scandinavica, Suppl. 154:1-14.
Cantoni, GL, "S-adenosylmethionine: a new intermediate formed enzymatically from L-methionine and adenosinetriphosphate," J Biol Chem, Vol 203 (1953): 403-416.
Carney MWP, Toone BK, and Reynold EH, "S-adenosylmethionine and Affective Disorder," American Journal of Medicine Vol. 83 (Suppl. 5A) (1987):104-106.
Caruso I and Pietrogrande V, "Italian Double-blind Multicenter Study Comparing S-adenosylmethionine, Naproxen, and Placebo in the Treatment of Degenerative Joint Disease," American Journal of Medicine Vol. 83 (Suppl. 5A) (1987):66-71.
Cerutti R, et al., "Psychological Distress During Peurperium: A Novel Therapeutic Approach Using S-adenosylmethionine," Current Therapeutic Research Vol. 53 (1993):707-717.
Chawla RK, et al., "Biochemistry and Pharmacology of S-adenosyl-L-methionine and rationale for its use in liver disease," Drugs Vol. 40 (Suppl. 3) (1990): 98-110
Chiang, PK, et al., "S-adenosylmethionine and methylation," FASEB J, Vol. 10 (1996): 471-480.
Coulter AW, et al., "Structural and conformational analogues of L-methionine as inhibitors of the enzymatic synthesis of S-adenosyl-L-methionine," Molecular Pharmacology, Vol. 10 (1974): 319-334.
DeVanna M and Rigamonti R, "Oral S-adenosyl-L-methionine in Depression," Current Therapeutic Research Vol. 52 (1992):478-485.
DiBenedetto P, Lona LG, and Zidarich V, "Clinical Evaluation of S-adenosyl-L-methionine Versus Transcutaneous Nerve Stimulation in Primary Fibromyalgia," Current Therapeutic Research Vol. 53 (1993):222-229.
Fava M, et al., "Rapidity of onset of the antidepressant effect of parenteral S-adenosyl-L-methionine," Psychiatry Res, Vol. 56(3) (1995): 295-297.
Franziska M., et al., "Influence of Oral S-adenosylmethionine on plasma 5-methyltetrahydrofolate, S-adenosylhomocysteine, homocysteine and methionine in healthy humans," The Journal of Pharmacology and Experimental Therapeutics, Vol. 282, No. 2 (1997): 345-350.
Friedel HA, Goa KL, and Benfield P, "S-adenosylmethionine," Drugs Vol. 38 (1989): 389-416.
Glorioso S, et al., "Double-blind Multicentre Study of the Activity of S-adenosylmethionine in Hip and Knee Osteoarthritis," International Journal of Clinical Pharmacology Research Vol. 5(1) (1985):39-49.
Harmand MF, et al., "Effects of S-adenosylmethionine On Human articular Chondrocyte Differentiation: An in vitro study", American Journal of Medicine Vol. 83 (Suppl. 5A)(1987):48-54.
Jacobsen S, et al., "Oral S-adenosylmethionine in Primary Fibromyalgia: Double-blind Clinical Evaluation," Scandinavian Journal of Rheumatology Vol. 20 (1991):294-302.
Janicak PC, et al., "Parenteral S-adenosylmethionine in Depression: A Literature Review and Preliminary Report," Psychopharmacology Bulletin Vol. 25 (1989):238-241.
Kagan L, et al., "Oral S-adenosylmethionine in Depression: A Randomized, Double-blind Placebo-controlled Trial," American Journal of Psychiatry Vol. 147 (1990):591-595.
Kaye GL, et al., "Metabolism of exogenous S-adenosyl-L-methionine in patients with liver disease," Drugs, Vol. 40(Suppl. 3) (1990): 124-128.
Konig B, "A Long-Term (two years) Clinical Trial With S-adenosylmethionine for the Treatment of Osteoarthritis," American Journal of Medicine Vol. 83 (Suppl. 5A) (1987):89-94.
Maccagno A, et al., "Double-blind Controlled Clinical Trial of Oral S-adenosylmethionine Versus Piroxicam in Knee Osteoarthritis," American Journal of Medicine Vol. 83 (Suppl. 5A) 1987):72-77.
Marcolongo R, et al., "Double-blind Multicentre Study of the Activity of S-adenosyl-methionine in Hip and Knee osteoarthritis," Current Therapeutic Research Vol. 37 (1985):82-94.
Mato JM, et al., "S-adenosylomethionine synthesis: molecular mechanisms and clinical implications," Pharmcol Ther, Vol. 73(3) (1997): 265-280.
Mazzanti R, et al., "On the Antisteatosic Effects of S-adenosyl-L-methionine in Various Chronic Liver Diseases: A Multicenter Study," Current Therapeutic Research 25 (1979):25-32.
Metz J, "Pathogenesis of Cobalamin Neuropathy: Deficiency of nervous system S-adenosylmethionine?," Nutrition Reviews, Vol. 51, No. 1 (1992): 12-15.
Morrison LD, Smith DD, Kish SJ, "Brain S-adenosylmethionine Levels are Severely Decreased in Alzheimer's Disease," Journal of Neurochemistry 67 (1996):1,328-1,331.
Muller-Fassbender H, "Double-blind Clinical Trial of S-adenosylmethionine Versus ibuprofen int eh Treatment of Osteoarthritis," American Journal of Medicine 83 (Suppl. 5A) (1987):81-83.
Reynolds EH, et al., "Methylation and Mood," Lancet, July 28, 1984: 196-198.
Rosenbaum JF, et al., "The antidepressant potential of oral S-adenosyl-l-methionine," Acta Psychiar Scand, Vol. 81 (1990): 432-436.
Rosenbaum JF, et al., "An Open-Label Pilot Study of Oral S-adenosylmethionine in Major Depression," Psychopharmacology Bulletin 24 (1988):189-194.
Salmaggi P., et al., "Double-blind, placebo-controlled study of S-adenosyl-L-methionine in depressed postmenopausal women," Psychother Psychomosom, Vol. 59(1) (1993): 34-40.
Sherer MA, et al., "Effects of S-adenosyl-methionine on plasma norepinephrine, blood pressure, and heart rate in healthy volunteers," Psychiatry Res, Vol 17(2) (1986): 111-118.
Stramentinoli G, "Pharmacological Aspects of S-adenosylmethionine: Pharmacokinetcs and Pharmacodynamics," The American Journal of Medicine, Vol. 83 (Suppl. 5A) (1987):35-42.
Tramoni AV, and Azorin JM, "Therapeutic indicaitons of S-adenosyl methionine in neuropsychiatry," Encephale, Vol. 14(3) (1988): 113-118.
Tavoni A, et al., "Evaluation of S-adenosylmethinine in Primary Fibromyalgia: A Double-blind Crossover Study," American Journal of Medicine 83 (Suppl. 5A) (1987):107-110.
Vahora SA and Malek-Ahmadi P, "S-adenosylmethionine in Depression," Neuroscience Biobehavioral Review, 12 (1988):139-141.
Vetter G, "Double-blind Comparative Clinical Trial With S-adenosylmethionine and Indomethacin in the Treatment of Osteoarthritis," American Journal of Medicine 83 (Supp. 5A) (1987):78-80.
Author: Daniel Gastelu, M.S., MFS
Reprinted with Permission. Copyright 2004 Daniel Gastelu. All rights reserved. This article is not intended to replace medical advice; consult your doctor for all matters related to your health.