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Are you thinking of trying a new form of treatment you have heard of in the media, online or perhaps from someone who owns a vitamin franchise? Please do your homework before spending your money on any treatments offered and consult with your care provider first.
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DHEA May Be No Help For Fibromyalgia Complementary and alternative medicine: 5 steps in considering any treatment.The Internet offers an ideal way to keep up with the latest on complementary and alternative treatments a fast-changing field. But beware the Internet is also one of the greatest sources of misinformation. Homeopathic Arnica 30x is ineffective for muscle soreness after long-distance running; Clinical Journal of Pain, September 1998, 14:227-231.A.J.Vickers, P.Fisher, C.Smith, et al., Straight Talk About Herbal Supplements If you have high blood pressure, did you know you probably shouldn't take ginseng? Or that St. John's wort can interfere with chemotherapy? Or that garlic capsules and gingko biloba can hinder blood coagulation, a potentially major problem if you had to undergo surgery? A new Web site created by experts at Memorial Sloan-Kettering Cancer Center in New York City provides up-to-date information on the safety and efficacy of 135 of the most popular herbal remedies and dietary supplements, from bee pollen to shark cartilage and skullcap to milk thistle. Each entry includes a summary and a critique of all the known medical studies on the supplement, as well as a link to the original research on the National Institutes of Health's Medline. In the past decade, use of alternative treatments has skyrocketed, says Barrie Cassileth, chief of integrative medicine at Memorial Sloan-Kettering, who started the site. "But until now there was no easy access to current, comprehensive information about these agents," she adds. Research is under way around the globe to scientifically document the effects of hundreds of herbs and other dietary supplements. Some studies have proven that certain natural substances do have benefits, though in nearly all cases research is mixed. The element zinc, for example, has shown promise in lessening the duration of a cold by making it difficult for the rhinovirus to replicate. And some research shows St. Johns wort can help ease depression. But that means the converse is also true -- herbs can be dangerous. "Herbs are powerful, biologically active products that do have important biological effects," Cassileth says. "Those effects can be useful at some times and harmful under other circumstances." "Herbs should not be used in a casual fashion because they are serious medicines," she adds. For instance, ginseng can cause low blood sugar in diabetics. And valerian and kava can lessen the effectiveness of prescription drugs by interfering with the liver's ability to process the medicines, Cassileth says. Another thing to keep in mind: While much is known about the effects of herbs on the body, much more is not known. Dietary supplements are not regulated by the U.S. Food and Drug Administration, or any government agency. That means the potency in one bottle of St. Johns wort, for example, can -- and often does -- vary dramatically from that in another bottle, Cassileth says. And you can't even be sure you're getting St. Johns Wort. "Anybody can put anything on a bottle and put it on a health food store shelf," she says. "Some of the herbal remedies have virtually none of what is assumed to be the active ingredient, some have much higher levels and some are contaminated with other substances." On the new Web site, the 135 supplements are listed in alphabetical order by scientific name. The common name is below it. (Acanthopanax Senticosus is better known as ginseng. Allium Sativun is better known as garlic). Each entry includes the brand names the herb is sold under, its purported uses, its chemical properties, and what's known about how the herb works on the body. Each entry also includes a summary and a critique of all the known published medical studies, instances of adverse reactions, and warnings about potentially dangerous drug interactions. Each critique is fully cited and linked to Medline, so that doctors or patients can retrieve the original research and read further if they wish. The site will be continually updated, Cassileth says. In a few weeks, Cassileth and her colleagues are planning to launch a second Web site that will be less technical and more easily understood by patients. Dr. David Rosenthal, past president of the American Cancer Society, endorses the Web site. "This resource is an invaluable tool for both doctors and patients looking for comprehensive information about dietary supplements," Rosenthal says. More information To visit the Sloan-Kettering site, click here. For more on herbal medicine, visit the National Institutes of Health. FDA Designate to Certify Supplements Sid Kirchheimer Dec. 18, 2002 Some vitamin and dietary supplements are sporting a new certification seal from the U.S. Food and Drug Administration (FDA) designated representative in hopes of assuring consumers that the product lives up to its ingredient labeling claims. The United States Pharmacopeia (USP), an independent agency that serves as the government's official compendium for dietary supplement standards, has begun to issue the certification on hundreds of products that it has independently tested as part of its Dietary Supplement Verification Program (DSVP). This new program is voluntary and open to all manufacturers of dietary supplements operating in the U.S., a $17-billion-a-year market that includes vitamins, minerals, herbs, botanicals, and sports supplements sold over the counter and consumed by two of every three Americans. "This is not a rubber stamp co-brand," said USP chief operating officer John T. Fowler. "There is a great deal of work done. This is not inexpensive, but the value is worth a lot in the minds of consumers when they take a product off the shelf and know it has the ingredients that it should and it doesn't have anything it shouldn't have." To receive the certification, manufacturers must submit products they select to a "vigorous" seven-step testing and evaluation process that the USP says it ensures meets all labeling claims first in independent laboratories and then on store shelves. This process includes testing and auditing of declared ingredients, their amounts or dosages, and meeting requirements of limits on contaminants. So far, hundreds of supplements by two leading manufacturers have been tested and issued the certification. Products that will receive the certification label include those by Nature Made, which just began to hit shelves at some 30,000 stores nationwide, and those under the Kirkland brand, which will be displayed at Costo stores beginning next week. Together, Nature Made and Kirkland produce about 30% of all vitamins and minerals consumed nationally, and about 20% of the total supplement market, said Richard Wailes, USP's head of sales and marketing. Four other manufacturers have signed up for the certification program and their products will carry the "Dietary Supplement Verified" certification in 2003. Under the program, manufacturers can submit any products they choose and pay for all testing by USP, which has been establishing drug and other product standards since 1820 and has worked hand-in-hand with the FDA since the federal agency was created in 1938. Because the FDA regulates dietary supplements as foods and not "conventional" medicines, manufacturers typically do not have to get FDA approval before producing or selling dietary supplements. The FDA can take action only if a product is deemed unsafe and is already on the market. Advertising claims for dietary supplements are regulated by the Federal Trade Commission, not the FDA. The USP certification does not ensure that a product is deemed safe or lives up to reported health claims a move that could mislead consumers, says one consumer advocacy group. "We applaud USP for trying to help consumers identify high-quality dietary supplements," said David Schardt of the Center for Science in the Public Interest. "But we are concerned that some consumers will assume that the USP mark means the product is safe and beneficial. USP risks losing its credibility if it is not clear about what is being certified and what is not." Mr. Fowler says that monitoring product safety is "not an appropriate role for USP. Our emphasis is on the quality of ingredients." However, he adds that USP will provide consumer literature on various supplements on its Web site and in stores where the certified supplements are sold. Reviewed by Gary D. Vogin, MD Medscape Medical News 2002. © 2002 Medscape Herbs And Drugs: Never Mix, Never Worry Source: Tufts University Health & Nutrition Letter, July 1999. Dr. Dean. Ive discussed the dangers of taking ginkgo with aspirin. It can increase your risk of a stroke, but this isnt mentioned on product labels. MY COMMENTS - This would also apply to Ibuprofen.) In fact, ginkgo shouldnt be used with any anticoagulant drugs or with vitamin E, according to a nutrition newsletter from Tufts University. The reason is ginkgo acts as a blood thinner and taking it with other blood-thinning agents can put you at-risk for excessive bleeding or even stroke. Shouldnt manufacturers be required to mention the adverse effects of mixing some herbs and drugs? Ginkgo isnt the only one you have to be careful with. Echinacea is an immune stimulant commonly used to ward off colds, but it shouldnt be mixed with corticosteroids, which work to suppress the immune system. Here are some other examples of herbs and medicines that shouldnt go together: --Echinacea Might counteract immune-suppressant drugs such as glucocorticoids taken for lupus and rheumatoid arthritis. Might increase side effects of methotrexate. --Evening Primrose oil Can counteract the effects of anti-convulsant drugs. --Folic acid: Interferes with methotrexate; ask your doctor how to take it. --Ginseng: Dont mix with coumadin (warfarin) because the herb can reverse the drugs effects. --G.L.A.: May increase effects of blood-thinning drugs and herbs. --Garlic Can increase effects of blood-thinning drugs and herbs. --Ginger: Can increase NSAID side effects and effects of blood-thinning drugs and herbs --Ginkgo: May increase effects of blood-thinning drugs and herbs. --Ginseng May increase effects of blood-thinning drugs, estrogens and glucocorticoids; shouldnt be used by those with diabetes; may interact with MAO inhibitors. --Kava Kava: Dont mix with alcohol, anti-Parkinsons medications, antipsychotics, sedatives, sleeping pills. The reason is kava can add to the effects of drugs that depress the central nervous system, causing oversedation as well as tremors, muscle spasms or abnormal movements. --Natural licorice: Dont mix with blood pressure medication because of the risk of counteracting the effects of the drugs treating hypertension. --Magnesium: May interact with blood pressure medications. --St. Johns Wort: Dont mix with antidepressants. Studies raise concerns of adverse side effects from the interaction. May enhance effects of narcotics, alcohol, and antidepressants; increase risk of sunburn; interfere with iron absorption. --Valerian: Dont use with alcohol, sedatives or sleeping pills because it may result in extreme drowsiness. --Zinc:Can interfere with glucocorticoids and other immunosuppressing drugs. If mixing herbs and certain drugs causes adverse effects, shouldnt we be aware of this? I think herbal supplement labels should include these warnings. Chinese Herbal Medicines May Contain Modern Drugs By Richard Woodman LONDON (Reuters Health) - Chinese herbal medicines may sometimes work--and may sometimes cause serious harm--because they are adulterated with synthetic drugs, a British research group said on Tuesday. Arthritis Today's Supplement Guide. A free book containing updated scientific information on 26 of todays top billed supplements, written by a panel of medical experts. Milk Thistle: Effects on Liver Disease and Cirrhosis and Clinical Adverse Effects. The Agency for Healthcare Research and Quality (AHRQ) is developing scientific information for other agencies and organizations on which to base clinical guidelines, performance measures, and other quality improvement tools. Click HERE to read the entire piece. Evaluating the Prevalence, Content and Readability of Complementary and Alternative Medicine (CAM) Web Pages on the Internet. Proc AMIA Symp 2002;:672-6 Sagaram S, Walji M, Bernstam E. Houston, TX, USA. Herbal medication: potential for adverse interactions with analgesic drugs. Abebe W. Department of Oral Biology and Maxillofacial Pathology, School of Dentistry, Medical College of Georgia, Augusta, GA, USA. The Effects of St. John's Wort Extract on Heart Rate Variability, Cognitive Function and Quantitative EEG: A Comparison With Amitriptyline and Placebo in Healthy Men Increased heart rate was noted in patients treated with amitriptyline (P < .001) but not with the other treatments. HRV was affected by amitriptyline but not St. John's wort extract. Cognitive performance was not affected by either amitriptyline or St. John's wort extract. Amitriptyline decreased self-rated activity (P < .05) that was not observed with St. John's wort extract. Both active treatments caused significant quantitative EEG changes. Editor's Comment This study demonstrates differences in unwanted physiologic effects of amitriptyline and St. John's wort extract. Increasing our understanding of both the effectiveness (not evaluated here) and the adverse event profile of therapeutic doses of St. John's wort extract will enable more informed decision making about the optimal treatment of depression for individual patients. In the United States, concerns remain over the inconsistency of ingredients in available herbal therapies. Supplemental Folate May Ease Depression ProHealthNetwork.com 07-14-2003 By Garret Condon / Hartford Courant
Pain-relieving magnets attract scientific scrutiny Magnets and pain are an old married couple. As early as 200 AD, Greek healers prescribed magnetic rings to people wracked by arthritic pains. In 19th century America, magnetic salves, corsets, belts, suspenders, insoles, liniments and even underwear were sold as balms for joint pain. Magnets fail to ease back pain JOHN FAUBER of the Journal Sentinel staff In a test that pitted one of America's most common health complaints against one of the hottest forms of alternative medicine, therapeutic magnets failed to help low back pain, according to a study published today in JAMA, the Journal of the American Medical Association. It is estimated that 85% of Americans will experience back pain during their lives. At the same time, a media campaign promoting magnets for pain has resulted in worldwide sales of $5 billion, according to the authors of the study. The study found that magnet therapy applied for six hours a day, three times during one week of treatment had no effect on chronic low back pain. But the study, which looked at 20 patients from a Veterans Affairs hospital in Arizona, is not likely to end the debate over whether magnets are humbug or healing. The patients all had chronic low back pain that had lasted an average of 19 years. Each patient received a week of treatment with both sham magnets and real magnets. At the end of each treatment regimen, the patients were given standard tests designed to assess pain levels. The magnet group fared no better the placebo group. Although the study is one of the few randomized, double-blind, placebo-controlled tests of magnet therapy, the study's authors said it was not intended to definitively prove or disprove the effectiveness of magnets in general. Stronger magnets might have yielded different results, the authors said. For the study, researchers used 300 gauss, bipolar permanent magnets. Gauss is the unit of measurement used in rating a magnet's strength. Although the popularity of magnets has grown, testimonials are easier to find than scientific evidence showing they have benefit. There have been only two previous, small double-blind, placebo- controlled studies, one involving patients with post-polio pain and the other involving peripheral neuropathy, foot pain caused by a circulation problem. The Arthritis Foundation, the Food and Drug Administration and the Federal Trade Commission warn that science does not support the use of magnets. Effect of Magnetic vs Sham-Magnetic Insoles on Plantar Heel Pain A Randomized Controlled Trial Mark H. Winemiller, MD; Robert G. Billow, DO; Edward R. Laskowski, MD; W. Scott Harmsen, MS JAMA. 2003;290:1474-1478. Context Despite anecdotal reports, rigorous scientific evidence of the effectiveness of magnetic insoles for the pain of plantar fasciitis is lacking. Objective To determine whether magnetic insoles provide greater subjective improvement for treatment of plantar heel pain compared with identical nonmagnetized insoles. Design, Setting, and Participants Randomized, double-blind, placebo-controlled trial conducted from February 12, 2001, to November 9, 2001, of a volunteer sample of 101 adults with diagnoses of plantar heel pain for at least 30 days from a multispecialty group practice clinic in Rochester, Minn. Daily pain diaries were kept for 8 weeks. Interventions Cushioned insoles, with either active bipolar magnets or sham magnets, which were worn daily by the participants for 8 weeks. Main Outcome Measures Reported average daily foot pain (by metered visual analog scale [VAS] and by categorical response of change from baseline) at 4 and 8 weeks, and impact of insoles on employment performance and enjoyment. Results No significant between-group differences were found on any outcome variables studied when comparing active vs sham magnets. Both the nonmagnetic and magnetic groups reported significant improvements in morning foot pain intensity, with mean (SD) VAS scores improving from 6.9 (2.3) and 6.7 (2.0), respectively, at baseline to 3.9 (2.6) for each group at 8 weeks (P = .94). At 8 weeks, 33% of the nonmagnetic group and 35% of the magnetic group reported being all or mostly better (P = .78). At baseline, foot pain interfered moderately with participants' employment enjoyment (mean VAS, 4.2) and improved in both groups by 8 weeks (1.3 and 1.5, respectively; P = .68). Conclusion Static bipolar magnets embedded in cushioned shoe insoles do not provide additional benefit for subjective plantar heel pain reduction when compared with nonmagnetic insoles.
CONTEXT: Chronic low back pain is one of the most prevalent and costly medical conditions in the United States. Permanent magnets have become a popular treatment for various musculoskeletal conditions, including low back pain, despite little scientific support for therapeutic benefit. OBJECTIVE: To compare the effectiveness of 1 type of therapeutic magnet, a bipolar permanent magnet, with a matching placebo device for patients with chronic low back pain. DESIGN: Randomized, double-blind, placebo-controlled, crossover pilot study conducted from February 1998 to May 1999. SETTING: An ambulatory care physical medicine and rehabilitation clinic at a Veterans Affairs hospital. PATIENTS: Nineteen men and 1 woman with stable low back pain of a mean of 19 years' duration, with no past use of magnet therapy for low back pain. Twenty patients were determined to provide 80% power in the study at P<.05 to detect a difference of 2 points (the difference believed to be clinically significant) on a visual analog scale (VAS). INTERVENTIONS: For each patient, real and sham bipolar permanent magnets were applied, on alternate weeks, for 6 hours per day, 3 days per week for 1 week, with a 1-week washout period between the 2 treatment weeks. MAIN OUTCOME MEASURES: Pretreatment and posttreatment pain intensity on a VAS; sensory and affective components of pain on the Pain Rating Index (PRI) of the McGill Pain Questionnaire; and range of motion (ROM) measurements of the lumbosacral spine, compared by real vs sham treatment. RESULTS: Mean VAS scores declined by 0.49 (SD, 0.96) points for real magnet treatment and by 0.44 (SD, 1.4) points for sham treatment (P = .90). No statistically significant differences were noted in the effect between real and sham magnets with any of the other outcome measures (ROM, P = .66; PRI, P = .55). CONCLUSIONS: Application of 1 variety of permanent magnet had no effect on our small group of subjects with chronic low back pain. PMID: 10714732 Magnet Therapy: A Skeptical View Stephen Barrett, M.D. Study on Using Magnets to Treat Pain Surprises Skeptics By LAWRENCE K. ALTMAN, M.D. NO ONE was more skeptical about using magnets for pain relief than Dr. Carlos Vallbona, former chairman of the department of community medicine at Baylor College of Medicine in Houston. So Dr. Vallbona was amazed when a study he did found that small, low intensity magnets worked, at least for patients experiencing symptoms that can develop years after polio. Dr. Vallbona had long been fascinated by testimonials about magnets from his patients, and even from medical leaders. But his interest in magnet therapy became more serious in 1994 when he and a colleague, Carlton F. Hazlewood, tried them for their own knee pain. The pain was gone in minutes. ''That was too good to be true,'' Dr. Vallbona said. Dr. Vallbona knew that the power of suggestion can fool both patient and doctor. But he also wondered: could strapping small, low intensity magnets to the most sensitive areas of the body for several minutes relieve chronic muscular and joint pains among patients in his post-polio clinic at Baylor's Institute for Rehabilitation Research. Valid studies could allow consumers to make informed choices. And if magnet therapy were found to be safe and effective, it could relieve pain with fewer drugs -- and their unwanted side effects. Endorsements from professional athletes are one reason Americans spend large sums on magnets to seek pain relief. But most doctors take a ''buyer beware'' attitude because many claims lack scientific proof or explanation of how they might work. The Food and Drug Administration has warned doctors and manufacturers about health claims for magnets. Aware of the medical profession's skepticism about magnet therapy, Dr. Vallbona sought to conduct science's most rigorous type of study. Participants would agree to allow the investigators to randomly assign them to groups getting treatment with active magnets or sham devices. But neither the patients nor the doctors treating them would know what therapy was used on which patient. First, Dr. Vallbona informally tested magnets on a few patients. One was a priest with post-polio syndrome who celebrated mass with difficulty due to marked back pain that prevented him from raising his left hand. After applying a magnet for a few minutes the pain was gone, Dr. Vallbona recalled, and, ''the priest said this was a miracle.'' Then a human experimentation committee allowed Dr. Vallbona to test 50 volunteers with magnets that at 300 to 500 gauss, were slightly stronger than refrigerator magnets. They were made in different sizes so they could fit over the anatomic area identified as setting off their pain. It was difficult to design a system to prevent participants from learning whether they were being treated with a magnet or a sham. So Dr. Vallbona asked Magnaflex Inc., a magnet manufacturer in Corpus Christi, Tex., to prepare active magnets and inactive devices that could not be told apart. The devices were labeled in code. As a further precaution, a staff member observed the patients throughout the 45-minute period of therapy to make sure they would not try to find out -- by testing with a paper clip, say -- what treatment they were receiving. After the investigators identified the source of the pain and then pressed on it, the 39 women and 11 men in the study graded the pain on a scale of 0 (none) to 10 (worst). Then after the experimental treatment, the participants rated their pain in a standard questionnaire. The volunteers were tested only one time. The 29 who received an active magnet reported a reduction in pain to 4.4 from 9.6, compared with a smaller decline to 8.4 from 9.5 among the 21 treated with a sham magnet. The Baylor scientists emphasized that their study applied only to pain from the post-polio condition. Nevertheless, their report in last month's issue of Archives of Physical and Rehabilitation Medicine, a leading specialty journal, has shocked many doctors who have scoffed at claims for magnets' medical benefits. Ionized Bracelets for Musculoskeletal Pain Mayo Clin Proc, November 2002, Vol 77 1164 Mayo Clin Proc. 2002;77:1164-1168 1164 © 2002 Mayo Foundation for Medical Education and Research Effect of "Ionized" Wrist Bracelets on Musculoskeletal Pain: A Randomized, Double-Blind, Placebo-Controlled Trial ROBERT L. BRATTON, MD; DANIEL P. MONTERO, MD; KEVIN S. ADAMS, MD; CAPT MARK A. NOVAS, USAF, MC; TRACY C. MCKAY, DO; LINDA J. HALL, CCRC; JOSEPH G. FOUST, MD;MICHAEL B. MUELLER, DO; PETER C. OBRIEN, PHD; ELIZABETH J. ATKINSON, MS; AND MEGAN S. MAURER, BS From the Department of Family Medicine (R.L.B., D.P.M., K.S.A., M.A.N., T.C.M., J.G.F., M.B.M.) and Division of Research Services, Clinical Studies Unit (L.J.H.), Mayo Clinic, Jacksonville, Fla; and Division of Biostatistics, Mayo Clinic, Rochester, Minn (P.C.O., E.J.A., M.S.M.). Dr Montero is in private practice in Chesapeake, Va. Dr Adams is in private practice in Athens, Ga. Dr Novas is in the Medical Corps, United States Air Force, San Antonio, Tex. Dr McKay is in private practice in Dade City, Fla. Dr Mueller is in private practice in Crystal River, Fla. Address reprint requests and correspondence to Robert L. Bratton, MD, Department of Family Medicine, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224. Objective: To assess objectively the perceived benefits of wearing an "ionized" wrist bracelet to treat muscle or joint pain. Subjects and Methods: This study was performed at the Mayo Clinic in Jacksonville, Fla, in 2000 and 2001. In a randomized, double-blind design, 305 participants wore an ionized bracelet and 305 wore a placebo bracelet for 4 weeks. For each location where pain was present at baseline, participants rated the intensity of pain. Followup ratings were made after 1, 3, 7, 14, 21, and 28 days of wearing the bracelet. Two primary end points were defined for evaluating efficacy. The first was the change at 4- week follow-up (day 28) in the pain score at the location with the highest baseline value (maximum pain score). The second was the change at 4-week follow-up in the sum of the pain scores for all locations. Results: Analysis of the data showed significant improvement in pain scores in both groups, but no differences were observed between the group wearing the placebo bracelet and the group wearing the ionized bracelet. Conclusion: The finding that subjective improvement in pain scores was equivalent with ionized and placebo bracelet use questions the benefit of using an ionized bracelet. New treatments in alternative medical therapy must be shown to be effective through vigorous, unbiased, objective testing before physicians acknowledge potential benefits or recommend these treatments to patients. Mayo Clin Proc. 2002;77:1164-1168 Magnesium, Malic Acid, Super Malic The Role of Magnesium in Fibromyalgia. An investigatory paper by Mark London Treatment of fibromyalgia syndrome with Super Malic: a randomized, double blind, placebo controlled, crossover pilot study. J Rheumatol 1995 May;22(5):953-8 Russell IJ, Michalek JE, Flechas JD, Abraham GE. Return to Top Magnesium and affective disorders. Intravenous magnesium sulfate relieves cluster headaches in patients with low serum ionized magnesium levels.Headache Prevention Institute http://www.h-p-i.com
In a report titled Management of Fibromyalgia, the American College of Physicians & American Society of Internal Medicine listed malic acid among treatments recommended for Fibromyalgia pain. The report was published in the December 1999 issue of the Annals of Internal Medicine and was authored by Lawrence J. Levanthal, M.D. In their 1999 book, Making Sense of Fibromyalgia, by Daniel J. Wallace, M.D. and Janice Brock Wallace, the authors noted the success of malic acid and magnesium in FM patients with the following observations: An interesting preparation, containing magnesium and malic acid is now available& Controlled studies from England and Texas in peer-reviewed journals have documented modest effects of this preparation in muscle spasm, fatigue and pain in Fibromyalgia. If patients take a dose larger than recommended on the bottle&its effects become apparent within a week; side effects are uncommon. This combination may work as a result of interactions between magnesium and calcium channels within muscles and the generation of adenosine triphosphate (ATP), our cellular fuel. Research Confirms Malic Acids Use to Alleviate Pain and Fatigue Leading healthcare professionals familiar with CFS are continuing to recommend malic acid for the chronic muscle soreness and fatigue that most patients experience. They have found that patients using a combination of malic acid and magnesium hydroxide report improvements with reduction of muscle pain and tiredness. Among those physicians recommending the malic acid/magnesium hydroxide combination are Daniel Peterson, M.D., of Incline Village, CA, Paul Cheney, M.D. and Jay Goldstein, M.D., director of the CFS Institute. Dr. Peterson comments, the patients who improved reported diminishing symptoms&and an increase in exercise tolerance. Similarly, Dr. Goldstein has found malic acid to be a safe, inexpensive nutritional supplement for CFS symptoms and suggests it should be added to the list of therapeutic approaches. He currently prescribes it for his patients with symptoms associated with CFS, and those diagnosed with FM. He explains,&it may have a modest effect on fatigue and/or other symptoms. Fibromyalgia pain may respond within 48 hours, while fatigue may take about two weeks. The effectiveness of the supplement has a sound scientific base. Malic acid, a fruit acid extracted from apples and widely used in the food industry, is essential in the formation of ATP, which is our bodys energy source. Malic acid has the ability to allow the body to make ATP more efficiently, even under low oxygen, or hypoxic, conditions. Magnesium is a mineral that is required for over 100 enymatic reactions in the body. Interestingly, many researchers such as Dr. Cheney, have noted that a large percentage of patients are magnesium depleted on an intra-cellular basis (inside the cell). Standard blood tests are not sensitive to intra-cellular magnesium. In a study published in the May, 1995 edition of the Journal of Rheumatology, the results of FM treatment with malic acid were assessed in terms of pain, tenderness, ability to function, and psychological well-being. The results showed no therapeutic effects on Fibromyalgia symptoms when malic acid was taken at the dosage of 600mg for twice a day for four weeks. However, when the dosage of malic acid was increased to 1200mg twice a day there were significant reductions in the pain and tenderness of the Fibromyalgia symptoms. [Treatment of Fibromyalgia syndrome with Super Malic: a randomized, double-blind, placebo-controlled, crossover pilot study. Russell IJ; Michalek JE; Flechas JD; Abraham GE; J Rheumatol, 22(5):953-8 1995 May] Jorge Flechas, M.D., M.PH., a holistic practitioner in Hendersonville, N.D., has participated in two medical studies that have tested the combination of malic acid and magnesium for Fibromyalgia patients. In these studies, patients reported a significant reduction in pain and tenderness within 48 hours and without any side effects. In his practice, Flechas has used this supplement combination for six years on about 500 Fibromyalgia patients. I have found the results are positive 90 percent of the time, he says. Billie Jay Sahley, Ph.D., a San Antonio nutritional specialist and author of the indepth book, Malic Acid and Magnesium for Fibromyalgia and Chronic Pain Syndrome reports impressive results in Fibromyalgia patients. The sooner malic acid and magnesium are started, the faster patients begin to return to their normal lifestyles, remarks Sahley. HW MAGNESIUM DEFICIENCY IN FIBROMYALGIA SYNDROME Magazine: Journal of Nutritional Medicine, Spring, 1994 Section: ORIGINAL RESEARCH MAGNESIUM - A VITAL MINERAL One of the most important components of any osteoporosis programme is magnesium. As much as 60% of all magnesium in the body is found in the bones. A defect of bone crystal formation in magnesium-deficiency women is thought to be one of the factors that increase fracture risk. Magnesium works in many ways to preserve the health of the nervous system. During times of stress, magnesium stores are depleted and large amounts of this mineral are lost in the urine. With its ability to exert a calming effect on the nervous system together with its muscle relaxing role, magnesium, taken 30-40 minutes before retiring, may help those suffering stress or insomnia. Studies have shown a low intracellular magnesium content in patients with bronchial asthma. Magnesium deficiency can also increase the release of histamine into the bloodstream. Thereby increasing allergic reactivity in general. Magnesium also plays a central role in the secretion and action of insulin. Without adequate magnesium levels within the body's cells, control over blood sugar levels is impossible. Magnesium has also been found to play a role in the aetiology of migraines, fibromyalgia, PMS, kidney stones and attention deficit hyperactivity disorder (ADHD). Williams, E. NUTRIT. PRACT. 1999,1 (3) 27-9 A supplement called SAM-e could be a new ally in the battle against the pain of osteoarthritis and fibromyalgia and the depression that so often accompanies chronic illness. Until last spring, hardly anybody in this country had heard of a European supplement called S-adenosylmethionine. But when it hit the market as a natural remedy named SAM-e (pronounced "sammy") it zoomed in a matter of months from an unknown import to one of the top-selling dietary supplements in the country. With that user-friendly nickname, you almost expect "sammy" pills to be wearing a little smiley face. And no wonder: Its being touted as a treatment for depression and osteoarthritis (OA) pain (because of regulations, vaguely referenced on labels as "emotional well-being" and "joint health"). Studies suggest it can also help fibromyalgia symptoms and alcoholdamaged livers, and there are claims that it may help with migraine headaches and maybe even Alzheimers disease. And it seems to have no serious side effects and no known drug interactions. These kinds of sweeping claims have a tendency to make doctors wary, says James McKoy, MD, chief of rheumatology at Kaiser Permanente in Honolulu, Hawaii. "Whenever something is promised to be a cure-all for so many diseases, physicians are very skeptical because so many miracle cures usually only benefit the producer and the seller," he says. "But I think this substance has promise," he adds, and several other doctors agree. Dr. McKoy says he has some arthritis patients using SAM-e supplements, "and they like it. SAM-e might be one of the most effective alternative supplements for osteoarthritis and fibromyalgia, and I think it is going to prove to be a great alternative for depression," he says. People particularly like SAM-e supplements because they dont have the side effects of nonsteroidal anti-inflammatory drugs (NSAIDs), which can cause gastrointestinal damage; or of antidepressants, which can include sexual dysfunction, dry mouth or nausea. It takes a week or so for SAM-e to take effect, which is slower than NSAIDs but about twice as fast as most antidepressant drugs. Also, SAM-e has shown no signs of drug interaction and so can be taken along with most, if not all, prescription drugs, according to Richard Brown, MD, a New York psychiatrist who has been using SAM-e for years in his practice. The Science Behind Sam-E Doctors in Europe have been studying and using SAM-e for more than two decades as a treatment for osteoarthritis and depression. There are dozens of European studies, including controlled clinical trials that show it relieves osteoarthritis pain as well as NSAIDs; and that it works as well as tricyclic antidepressants in improving mood. In several countries, its a prescription drug, says Teodoro Bottiglieri, PhD, a neuropharmacologist at the Baylor University Institute for Metabolic Diseases in Dallas. Bottiglieri, who has been studying SAM-e for some 15 years, also recently co-wrote a book on SAM-e, Stop Depression Now (Putnam Publishing Group, 1999), along with Dr. Brown. SAM-e is a compound that occurs naturally in all living cells, and is a key player in a process called methylation that affects more than 100 complex biochemical reactions in the human body. SAM-e helps our bodies make and regulate hormones, cell membranes and the neurotransmitters that affect mood. SAM-e also contributes to the building blocks for cartilage, and is involved in making glutathione, which the liver uses to remove poisons such as alcohol. Our bodies usually make all the SAM-e we need. But the level of SAM-e decreases as we age, and levels are low in those who are depressed, or who have deficiencies of B vitamins or methionine, says Bottiglieri. Good diet and vitamin B supplements can help our bodies better use SAM-e, but unfortunately they are not going to do much to help people who have low levels of SAM-e, he says. SAM-e supplements, however, can raise levels of this compound. And while scientists dont know for certain how taking SAM-e supplements works, science has shown it relieves OA pain and some fibromyalgia symptoms, as well as depression. Fibromyalgia And Depression The antidepressant effects of SAM-e are documented in several studies. Its being prescribed by some psychiatrists to treat depression, particularly for people who havent responded to other drugs, or who are reluctant to take prescription antidepressants because of side effects. "Its a promising drug," says Maurizio Fava, MD, lead author of a study that shows SAM-e is an effective antidepressant. Dr. Fava is director of the Clinical Depression Research Program at Massachusetts General Hospital, where he uses SAM-e to treat some of his patients. But there are mixed results in studies of SAM-e for fibromyalgia. In one small European study of fibromyalgia and SAM-e, 200-mg daily injections reduced the number of tender points and improved mood in patients with fibromyalgia. In another, those taking 800 mg of SAM-e in pill form had less pain, fatigue and morning stiffness than patients taking placebo, but no effect on tender points. A third study showed no benefit. There are also mixed opinions from physicians. "I think SAM-e is even better for fibromyalgia than for osteoarthritis," says Dr. McKoy, who has several patients using it. Dr. Brown agrees, saying he finds the supplement more effective than antidepressants for fibromyalgia, and that some of his patients get significant pain relief from taking it. However, Don Goldenberg, MD, a fibromyalgia specialist and chief of rheumatology at Newton-Wellesley Hospital in the Boston area, says hes not convinced SAM-e has much to offer people with fibromyalgia. His laboratory began and abandoned a study on SAM-e about eight years ago when it didnt appear to have any benefit for fibromyalgia patients. However, Dr. Goldenberg notes that the SAM-e product that was used in the discontinued trial could have been too old and thus not effective. He says he would like to see more studies. The Downsides and the Bottom Line Few rheumatologists know enough about SAM-e or its research to be able to advise you. And the appropriate dosage isnt known: Between 200 and 1,600 mg per day of SAM-e was used in studies, with the highest dosage used for depression. SAM-e is not a cure: You have to keep taking it to get the effects, and its pricey for some: SAM-e costs approximately $60 to $230 per month, depending on the amount taken, and its not covered by insurance. And, as with all supplements, loose regulations mean that there is no guarantee that consumers are getting active ingredients in the products they buy. However, all agreed SAM-e appears to be safe when it is used short term. Both Bottiglieri and Dr. Brown say it can be taken with most prescription drugs, including antidepressants, under a doctors supervision. None of the experts interviewed thought SAM-e had any serious side effects "except poverty," one scientist said, half-joking about the cost of the supplement. "We really dont have enough information to say if its effective or not," says Dr. Moskowitz. "But we need to keep an open mind." Good Advice
Spotlight on SAM-e by Stacey Booth 11-16-1999 What is SAM-e? Not a prescription drug or an herb, SAM-e (S-adenosylmethionine) is a synthetic replication of a compound that the body makes naturally from methionine, an amino acid found in protein-rich foods. Used in Europe for over twenty years, SAM-e is just beginning to make national headlines in publications like Newsweek magazine and the Los Angeles Times and in books and on major television networks. How Does it Work? The key to understanding the way SAM-e works is by recognizing its role in a process called methylation. Methylation happens a billion times a second throughout the body and is responsible for, among other things, the regulation of brain function, preserving bone health and protecting against heart disease. It helps regulate various hormones and neurotransmitters including serotonin, melatonin, dopamine and adrenaline. During the methylation process a molecule in the body "gives up" a methyl group comprised of four atoms to another molecule, changing both the original molecule and the recipient of the methyl group in the process. "It [SAM-e] is involved in almost everything," says Teodoro Bottiglieri, Ph.D. and co-author of the book, "Stop Depression Now," which discusses his extensive use of SAM-e to treat a number of illnesses.1 How does it ease depression? There are a few theories. One may be SAM-e's regulation of serotonin and dopamine, which are mood-lifting neurotransmitters. This hypothesis was confirmed in one study where SAM-e was shown to cross the blood-brain barrier. This research further found that the cerebrospinal fluid levels of SAM-e were significantly lower in patients with severe depression, as compared to the control group. Researchers concluded that SAM-e has antidepressant effects.2 Actually, there is little, if any, debate over SAM-e's depression-easing abilities. In fact, SAM-e's ability to lift mood is comparable to that of standard antidepressants, yet without the possible side-effects of headache, stomach upset and sexual dysfunction that prescription drugs often bring.3 Richard Brown, who authored "Stop Depression Now" with Teodoto Bottiglieri and has treated several hundred patients with SAM-e, calls it, "...the best antidepressant I've ever prescribed. I've seen only benefits." 4 Can SAM-e Stop Pain? SAM-e was first given to patients for use in treating depression, but when some of those same patients began to report relief from osteoarthritis joint pain, researchers began to study this second benefit of the product. Over 22,000 arthritis sufferers reported, after only four weeks of treatment, that SAM-e gave comparable results to NSAID pain relievers like ibuprofen.3 The vital distinction is that instead of causing stomach upset like NSAIDs often do, SAM-e may actually protect the stomach lining. Furthermore, animal studies show that SAM-e could help restore damaged cartilage in addition to relieving pain.1 This happens when B-vitamins convert homocysteine into the antioxidant glutathione. This glutathione conversion yields molecules called sulfate groups that actually help to restore cartilage. Proof positive: the Arthritis Foundation recently stated that they were satisfied that SAM-e provides pain relief. Can it Treat Fibromyalgia? Drs. Brown and Bottiglieri dedicate an entire chapter on SAM-e's positive effects on Fibromyalgia in their book, "Stop Depression Now." They state that depression and soreness, of all of FM's symptoms, are the most stubborn. They are careful to point out that the depression that is common among FM's sufferers is not a symptom of the disease, but often a by-product of living with chronic illness. They support the benefit of SAM-e's non-prescription effects: "...fibromyalgia patients get the best of all worlds--relief from depression and muscle soreness without the side-effects or possible adverse interactions with other medications." 1 They are not alone in their findings. In a study of 47 FM patients treated daily with 200mg of SAM-e intramuscularly and 400mg orally, patients reported significant reduction in tender points, significant improvement in well-being, and significant reduction in the mean scores of the Hamilton Rating Scale for Depression, the Zung SelRating Scale, the Hamilton Rating Scale for Anxiety, and the Lorish and Maisiak's Face Scale. All reported that SAM-e was well-tolerated, with no adverse side effects.5 In another study of 30 patients with FM, Sjogren's Syndrome, or both, the patients were treated with 200mg of SAM-e daily through intramuscular injection. At the end of the four week study, the patients with Sjogren's Syndrome and FM reported a significant reduction in painful areas and tender points. The patients with only Sjogren's Syndrome reported a significant reduction on the Hamilton Rating Scale for Depression. Finally, the patients with FM finished the trial with significant reductions in symptoms of FM, numbers of tender point areas and painful areas, pain severity scores and depression scales.6 Which SAM-e Should I Take and How Much? Not all SAM-e is created equal and those who wish to make SAM-e a part of their supplementation program should look for two distinctive qualities before purchasing: type and coating. First, full-strength SAM-e is in a form called butanedisulfonate, which should not be confused with tosylate or SAM-e sulfate. Second, look for SAM-e tablets that are enteric coated, meaning that the tablets pass through the acidic environment of the stomach intact, and can be absorbed most efficiently by the body. Lastly, the amounts used in various SAM-e studies vary widely, leaving the consumer confused about effective dosage. The starting dose is 400mg of SAM-e daily on an empty stomach.1 Are There Are Precautions or Warnings About Taking SAM-e? Even those who have jumped on the SAM-e bandwagon are clear to point out that it is not a "cure" for severe depression and advise consumers to consult with their physician before taking SAM-e (good advice for anyone beginning a new supplementation program). There is at least one group of people who should avoid SAM-e: those with bi-polar disorder. Commonly called manic depression, these individuals should be aware that SAM-e may induce mania in those with the disorder. In conclusion Since the mass availability of SAM-e earlier this year, the buzz has been strong and the research to support it very promising, if not yet iron-clad. As stated above, it's a good idea to consult your physician when beginning any new supplementation program. However, it does appear that for those wishing to lift their mood, soothe painful joints and muscles, and lighten the load of FM's many symptoms, SAM-e is a safe complimentary treatment, nearly without side-effect. Sources: 1. Brown, Richard, M.D., Bottigileri, Teodoro, Ph.D., Colman, Carol. Stop Depression Now. New York, 1999. 2. J Neurol Neurosurg Psychiatry (England) Dec. 1990, 53 (12) p1096-8. "Cerebrospinal Fluid S-andenosylmethionine in Depression and Dementia: Effects of Treatment with Parenteral and Oral S-andenosylmethionine." 3. Cowley, Geoffrey and Underwood, Anne. "What is SAM-e?" Newsweek, July 5, 1999. 4. Curr. Ther. Res. Clin. Exp. (USA), 1994, 55/7 (797-806). "Primary Fibromyalgia is Responsive to S-adenosylmethionine." 5. Curr. Ther. Res. Clin. Exp. (USA), 1994, 55/6 (699-706). "S-adenosylmethionine in Sjogren's Syndrome and Fibromyalgia." What is SAM-e? SAM-e is short for S-adenosylmethionine, an essential molecule naturally occurring in the cells of plants and animals. SAM-e is not an herb. As we age, our bodies produce less SAM-e, so some think that SAM-e may be a helpful supplement when used to treat depressive symptoms. It has been available in European countries through prescription. What is SAM-e used for? SAM-e has been getting attention in recent years in the United States for the treatment of depression or to preserve emotional well-being, as well as for other conditions. Initial studies indicate that SAM-e may be effective in helping with depressive symptoms; however, studies are ongoing, and no clinical trials have proven SAM-e safe or effective in the treatment of depression. Is SAM-e safe? At present, the safety of SAM-e has not been proven. The U.S. Food and Drug Administration (FDA) does not approve or regulate the distribution of supplements in the United States. Not all formulations of SAM-e are the same. Some brands are more potent than others, depending upon the quality of the ingredients used. SAM-e can have numerous adverse side effects, including:
Another issue in deciding whether to use SAM-e is cost. The recommended oral dose is 200 to 800 mg twice per day. Most studies used 1,600 mg per day to get any positive effects in relieving depressive symptoms. A 1-month supply of SAM-e at 1,600 mg per day would cost about $228. Other herbal treatments are more cost-effective. For more information Ask your doctor about any evidence on the safety and effectiveness of SAM-e. Clinical trials are ongoing. Since there is no current evidence that SAM-e is helpful in the treatment of depression, you may want to delay trying it. Investigating SAM-e by Leslie Knowlton and GT Staff For more than eight years, Richard P. Brown, M.D., associate professor of clinical psychiatry at Columbia University College of Physicians and Surgeons, has used the natural dietary supplement S-adenosylmethionine (SAM-e) to treat an estimated 400 patients suffering from depression, many of whom were previously treatment-resistant. Brown also has co-authored the book Stop Depression Now: SAM-e, the Breakthrough Supplement that Works as Well as Prescription Drugs in Half the Time... With No Side Effects. His primary collaborator was Teodoro Bottiglieri, Ph.D., director of neuropharmacology and senior research scientist at Baylor University's Institute for Metabolic Disease. Bottiglieri, also associate professor of biomedical studies at Baylor, has been conducting research on SAM-e for 15 years. In an interview with Geriatric Times, Brown reviewed research on, and his clinical experience with, SAM-e. Although SAM-e has only been on the U.S. market since 1999, it has been studied for decades internationally and is approved as a prescription drug in Spain, Italy, Russia and Germany. More than 1 million Europeans have used it, primarily for depression and arthritis. "I first heard about SAM-e 20 years ago when I was doing my residency in psychiatry at New York Hospital, Cornell Medical Center," Brown recalled. "At a meeting of the American College of Neuropsychopharmacology, a colleague had learned about an exciting new antidepressant being studied in Europe that was nontoxic, without side effects, and worked better and faster than traditional medications." Fifteen years later, after Brown had developed a subspecialty practice treating patients resistant to conventional drug therapy by integrating alternative approaches such as nutrients and herbs with prescription medications, a patient brought him information about SAM-e from the Internet. According to Brown, SAM-e was discovered in Italy about four decades ago (Cantoni, 1952). Since then, SAM-e "has been evaluated for various disorders in more than 75 clinical trials involving over 23,000 people," Brown added. However, the first clinical study of its use for depression was not completed until the 1970s (Agnoli et al., 1976). Biochemistry Brown explained that SAM-e is produced in the body from methionine, a sulfur-containing amino acid, and the energy-producing compound adenosine triphosphate. SAM-e is a physiologically essential compound, he said, adding that some chemists believe it ranks with adenosine triphosphase (ATP) as a pivotal molecule in living cells. Distributed throughout the body, SAM-e is most concentrated in the brain and liver and is crucial to three central pathways of metabolism that stimulate more than 35 different reactions. "The three major pathways are transmethylation, transulfuration and transaminopropylation," he said. "Animal studies show that the transmethylation pathway boosts levels of the neurotransmitters serotonin, dopamine and norepinephrine. This process probably contributes to the antidepressant action" (Andreoli et al., 1978; Curcio et al., 1978; Czyrak et al., 1992; Fava et al., 1990; Losada and Rubio, 1989; Otero-Losada and Rubio, 1989). Brown said that donation of carbon groups by SAM-e protects catecholamine neurons and that SAM-e improves nerve cell membrane uptake of phospholipids, enabling the coupling of protein receptors to second messengers within a more fluid lipid bi-layer and enhancing transmission of impulses by neurons. "SAM-e is vital to the production of our most important antioxidant glutathione, as well as the secondary antioxidants cysteine and taurine," he noted. "The American diet yields insufficient quantities of SAM-e either for wellness or treatment of illness. Moreover, the form of SAM-e found in food is not stable. It oxidizes too rapidly to absorb well. Our bodies can only generate a small amount of SAM-e...Therefore, SAM-e levels are most easily increased through dietary supplementation." Reviewing the Literature According to Brown, lower than normal levels of SAM-e are found in cerebrospinal fluid in some patients with depression, Alzheimer's disease, dementia, Parkinson's disease treated with levodopa (Atamet, Sinemet), disorders of folate metabolism and other illnesses (Bottiglieri et al., 1994, 1990). He cited a study indicating that folate, B12 and B6 are necessary for efficient use of SAM-e (Crellin et al., 1993) and reported that SAM-e has been effective for treating major depressive disorder in 13 trials comparing it to placebo and 19 trials comparing it to tricyclic antidepressants (TCAs), with more than 1,400 patients studied. "From 1973 to 1988, 14 double-blind, European studies [Janicak et al., 1988] showed that intravenous and intramuscular preparations of SAM-e were more effective than placebo and comparable to imipramine [Tofranil], amitriptyline [Elavil, Endep] and clomipramine [Anafranil] for treatment of major depression," Brown said. In 1988, American psychopharmacologists Bell and colleagues conducted a double-blind, randomized, two-week trial comparing intravenous SAM-e to oral imipramine. By the end of week 2, 66% of the patients treated with SAM-e "had a clinically significant improvement in depressive symptoms, compared to 22% of the imipramine patients," the study authors reported. Since 1988, double- and single-blind studies using higher doses of SAM-e have shown it to be effective in treating major depression (Bressa, 1994; Delle Chiaie and Boissard, 1997; Delle Chiaie et al., 2000), depression secondary to medical illness (Criconia et al., 1994), postmenopausal depression (Salmaggi et al., 1993) and treatment-resistant depression (Rosenbaum et al., 1990), Brown reported. "Rapid response to SAM-e was shown in a double-blind trial of 30 depressed inpatients who received either 1600 mg/day of oral SAM-e or imipramine (averaging 140 mg/day) for six weeks," Brown added. "The SAM-e group was significantly better by day 10. Both groups were comparably improved by week 6" (De Vanna and Rigamonti, 1992). Furthermore, Brown reported that in a small, double-blind, four-week inpatient study of oral SAM-e (1600 mg/day) versus 250 mg/day of desipramine (Norpramin), improvement in depression in those who responded to either SAM-e or desipramine correlated with their SAM-e blood levels (Bell et al., 1994). "These findings highlight the need for larger and longer-term studies to elucidate the role of SAM-e in recovery from depression and the use of SAM-e in combination with prescription antidepressants," he said. He added that the longest controlled-trial studies of SAM-e efficacy for depression were 42 days (Delle Chiaie et al., 2000; De Vanna and Rigamonti, 1992; Fava et al., 1992). Brown said he has also found SAM-e effective for fibromyalgia (Jacobsen et al., 1991; Tavoni et al, 1998, 1987, as cited in Brown et al., 2000), depression in Parkinson's disease, the aging brain, liver diseases (Friedel et al., 1989) and arthritis (Bradley et al., 1994, as cited in Brown et al., 2000; Konig, 1987). It also seems to reverse some effects of alcoholic hepatitis and cirrhosis (Mato et al., 1999) and is used to dissolve gallstones. Practical Considerations Brown noted that American companies only sell SAM-e in 50 mg, 100 mg and 200 mg tablets. He recommended a daily dose of 400 mg for mild depression. "Keep in mind that absorption is better on an empty stomach," he said. "Starting patients with 200 mg 30 minutes before breakfast and 30 minutes before lunch minimizes the overstimulation and insomnia which some patients report in the first few weeks [Berger and Nowak, 1987]. This can be switched to 400 mg before breakfast after a few weeks." Patients typically notice improvement in energy within two weeks. Brown continued, "As with most medications, clinical sense indicates starting with lower doses in geriatric, medically ill and anxious patients. SAM-e, like all antidepressants, should be used with some caution in patients with a history of cardiac arrhythmia." Treatment for severe depression, Brown said, generally requires higher doses. "Some studies have started unipolar patients on 800 mg or 1600 mg per day," he said. Side effects occurring at the higher doses include mild jitteriness, loose bowels and headaches. (To date, SAM-e has not been systematically studied in well-defined samples of psychotic depressed patients-Ed.) Brown noted that SAM-e is generally available in two forms: a butanedisulfonate form and a tosylate form. "In my practice, the butanedisulfonate seems superior, particularly the enteric-coated form," he said, adding that good brands currently available in this country include Nature Made and GNC. "If a patient hasn't responded to an appropriate dose of SAM-e, the physician must be sure that the patient is using a potent brand. "Only about 3% to 5% of patients discontinue SAM-e because of side effects, primarily gastrointestinal," Brown said. "That is a relatively low rate compared to placebo discontinuation rates. In study after study, the investigators said there was no difference from placebo in the side effect rate." The biggest study of SAM-e, Brown said, was a two-year postmarketing study of 20,641 patients conducted in Germany after SAM-e was approved for treatment of osteoarthritis (Berger and Nowak, 1987). "The investigators found that 80% of patients said they basically felt great on it and had no side effects, [while the other] 20% complained of mild side effects in the first month on high doses like 1200 mg/day to 1600 mg/day," Brown said. At starting doses of 400 mg/day to 600 mg/day for mild depression, Brown said, there are no significant side effects. At higher doses, there are some "mild, temporary side effects." Reports of drug interactions have been nearly nonexistent, according to Brown. He mentioned a case report of an elderly woman who was given clomipramine together with SAM-e. The patient exhibited symptoms of what the clinicians diagnosed as serotonin syndrome (Iruela et al., 1993). The investigators attributed the side effects to a "toxic interaction produced by S-adenosylmethionine and clomipramine association." Brown had some misgivings about the case report, however, explaining, "If you look at the world's literature of serotonin syndrome, the preponderance of cases are from clomipramine." There have been no reports of SAM-e effects on cytochrome P450 metabolism or on the binding of prescription drugs to serum proteins (Brown et al., 2000). Treatment Resistance Research studies (Bell et al., 1994; Criconia et al., 1994; De Vanna and Rigamonti, 1992; Kagan et al., 1990) and his own clinical experience, Brown said, demonstrate that some patients have a dramatic response to SAM-e even after failing on prescription antidepressants. Brown said he has treated more than 30 patients with treatment-resistant depression who responded well to SAM-e augmentation of all categories of antidepressants without adverse reactions, and noted a review of four studies suggesting that SAM-e boosted and hastened response to TCAs, mianserin and fenoterol, a ß-agonist (Friedel et al., 1989). He also cited a randomized, double-blind study (Berlanga et al., 1992) of 40 outpatients with moderate to severe major depression that confirmed his own clinical experience of using SAM-e to augment imipramine. Brown said accumulated evidence indicates that SAM-e in higher doses is perhaps as effective for major depression as TCAs. "SAM-e starts to work in approximately half the time needed for tricyclics. Studies show very few side effects, and SAM-e does not cause the sexual dysfunction or weight gain associated with other medications," he said. Brown expressed concern about the need for most depressed patients to take antidepressants for long periods of time. "Conventional medicine hasn't yet tackled the issue of long-term effects of prescription drugs," he said. "We hope they are insignificant, but there are no studies to assure us that these drugs are safe in the long-term. Part of our confidence derives from the clinical experience of prescribing tricyclics for over 35 years. Our experience with fluoxetine [Prozac] is only 12 years and with other SSRIs is even less." Brown said that considering SAM-e's efficacy in treating depression, its mild side-effect profile, and its ability to boost antioxidants and protect DNA through methylation, this nutrient has advantages over prescription antidepressants. Further Research Needed "Further research is needed to clarify SAM-e's role as a possible first-line treatment for affective disorders," Brown said. There have been about eight controlled studies comparing SAM-e in the oral version in decent doses from 1989 through 1997, Brown said, adding that a published review article describes the details of those studies (Brown et al., 2000). "What everybody wants right now is a study comparing SAM-e to an SSRI," he said. "There are five studies showing that SAM-e boosts regular antidepressants [e.g., TCAs] in both their efficacy and speed of onset of therapeutic efficacy (Berlanga et al., 1992; Friedel et al., 1989; Torta et al., 1988). And we need more controlled studies showing that SAM-e can be a booster for other antidepressants&Those studies will probably get going in the United States within the next year or two." He added that there is a planned study comparing the combination of SAM-e and an SSRI to an SSRI alone, but it has not yet been funded. "In the future, perhaps SAM-e will become available...as a prescription drug approved by the [U.S. Food and Drug Administration]," Brown said. "In the meantime, physicians should be knowledgeable about SAM-e in order to advise patients on its appropriate use as a complementary treatment or as an alternative to traditional pharmacotherapy." SAMe Benefits Depression, Osteoarthritis, Liver Disease Laurie Barclay, MD Oct. 15, 2002 The U.S. Agency for Healthcare Research and Quality (AHRQ), a division of the Department of Health and Human Services, has assembled the evidence available on s-Adenosyl-L-Methionine (SAMe) and has shown actual benefit for the treatment of depression, osteoarthritis, and liver disease. "The [AHRQ] report indicates that that this is a compound worthy of further investigation," Maurizio Fava, MD, director of the depression clinic and research program at Massachusetts General Hospital in Boston, tells Medscape. "True, these are very small studies, but they consistently suggest the efficacy of this compound in depression." In treating depression, SAMe is more effective than placebo and as effective as standard antidepressants, with fewer adverse effects. Compared with nonsteroidal anti-inflammatory drugs (NSAIDs), SAMe also relieves the pain of osteoarthritis, but with fewer gastrointestinal adverse effects. It also reduces cholestasis secondary to use of oral contraceptives or estrogen, pregnancy, or birth defects, for which there is currently no other effective treatment. The AHRQ report reviewed the literature on the use of SAMe in these conditions and identified 294 meta-analyses, clinical trials, and reports, of which 99 articles referencing 102 studies met the screening criteria. Of these 102 studies, most of which enrolled small numbers of patients, 47 focused on depression, 14 focused on osteoarthritis, and 41 focused on liver disease. In a meta-analysis of 28 studies, treatment with SAMe was associated with an improvement, compared with placebo, of approximately 6 points on the Hamilton Rating Scale for Depression score measured at three weeks (95% confidence interval [CI], 2.2 to 9.0). Compared with conventional antidepressants, treatment with SAMe was not associated with a statistically significant difference in outcomes. "We've never had a large double-blind study [of SAMe in depression] in the U.S.," Fava says. It's time for researchers to look at this more closely." Of 13 unique studies considered, 10 studies were included in a meta-analysis of the efficacy of SAMe to decrease the pain of osteoarthritis. In one large randomized clinical trial, SAMe reduced the pain of osteoarthritis by 20% (95% CI, -0.39 to - 0.02) compared with placebo, which was not significantly different from results with NSAIDs. In a meta-analysis of eight studies of the efficacy of SAMe to relieve pruritus and decrease elevated serum bilirubin levels associated with cholestasis of pregnancy, treatment with SAMe was associated with an effect size compared with placebo of nearly a full standard deviation (-0.95; 95% CI, -1.45 to -0.45) for decrease in pruritus and of over one and one-third standard deviations (-1.32; 95% CI, -1.76 to -0.88) for decrease in serum bilirubin levels. Two clinical trials which were not pooled favored ursodeoxycholic acid over SAMe for the treatment of pruritus. In a meta-analysis of six studies of the efficacy of SAMe to relieve pruritus and decrease elevated bilirubin levels associated with intrahepatic cholestasis, treatment with SAMe for pruritus was more than twice as likely to reduce pruritus as was placebo (risk ratio 0.45; 95% CI, 0.37 to 0.58). "A need exists for additional review studies, studies elucidating the pharmacology of SAMe, and clinical trials," the authors write. "A better understanding of the risk benefit ratio of SAMe compared to conventional therapy, especially for depression and osteoarthritis, is very important. To that end, additional analysis of existing data could be done, but it would likely be more productive to support new definitive clinical studies to address this issue." Sept. 30, 2002 |
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