The Pitfalls of Meta-Analysis Should be More Widely Recognized and Acknowledged. (from a US government report) Our evidence report draws heavily on six study-level meta-analyses of glucosamine/chondroitin and five of viscosupplementation. While we used a validated instrument to appraise the quality of the systematic reviews, the instrument does not address the question of when meta-analysis is appropriate to a systematic review. Meta-analysis is a technique with underlying assumptions that may or may not hold when a particular collection of results are pooled. Furthermore, metaanalyses may fail to convey the real uncertainty and potential bias accompanying pooled estimates. Uncertainty in the magnitude of effects pooled is influenced by factors intrinsic to the underlying trials. Among these are variable patient characteristics, trial characteristics, and the indication that a few trial results were outliers and influential on pooled estimates. The metaanalyses frequently reported high inter-trial heterogeneity. Random effects models were used in the face of high heterogeneity, but a consequence is to increase the influence of smaller trials on the pooled results. The meta-analyses did not address a threshold question, one that has not been clearly resolved by practitioners of meta-analysis: when is heterogeneity too high to justify pooling trial results. A related concern is the practice of reporting on multiple outcome measures and time intervals, which may be represented by a small portion of studies, thus potentially introducing bias. Evidence Report/Technology Assessment Number 157 Treatment of Primary and Secondary Osteoarthritis of the Knee Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 540 Gaither Road, Rockville, MD 20850 www.ahrq.gov Contract No. 290-02-0026 Prepared by: Blue Cross and Blue Shield Association Technology Evaluation Center Evidence-based Practice Center Chicago, Illinois Investigators David J. Samson, M.S. Mark D. Grant, M.D., M.P.H. Thomas A. Ratko, Ph.D. Claudia J. Bonnell, B.S.N., M.L.S. Kathleen M. Ziegler, Pharm.D. Naomi Aronson, Ph.D. AHRQ Publication No. 07-E012 September 2007
Wednesday, October 10, 2007
Friday, October 05, 2007
Nutrients for Joint Health By Neil E. Levin, CCN, DANLA Most people know that glucosamine sulfate and chondroitin sulfate are important components of joint health. They help to form spongy tissues (like articular cartilage) that hold moisture and cushion the body’s joints, protecting them from excessive wear and tear. But this takes time. Some people notice a change in joint function within days, but more typically over several weeks. Studies show that these substances help to maintain distances between joint structures over many months, a key measure of joint integrity as these structural components may slowly collapse if not nourished. This particular effect has been accepted as evidence-based by conventional physicians at a medical joint health center associated with a major university hospital. People with osteoarthritis typically may have low levels of glucosamine and chondroitin sulfates, as well as MSM, and may benefit by supplementing to restore normal levels of these soft tissue nutrients. MSM is a safe form of the mineral sulfur that may preserve joint function and structures. In order to affect joint health on a short-term basis, it may be useful to supplement the diet with herbs that inhibit the activity of the enzymes that are involved in normal inflammatory processes. These herbs may mediate COX-2 or 5-LOX enzymes. COX-2 is also the target of some widely used drugs. Some of these herbs are safe, common spices like turmeric, ginger, cayenne and the enzyme bromelain. While drugs may offer similar yet faster COX-2 inhibition, herbs can also modulate 5-LOX activity. The safety profiles and beneficial side effects associated with nutrients and herbs can be preferable to the known side effects of drugs. The antioxidant components in the herbs also improve the body's ability to repair tissues by stimulating collagen formation. A diet high in animal fat is implicated in joint problems, and experts frequently recommend that sufferers reduce their intake of most animal fats. It is important to take natural healthy essential fats, especially Omega-3 fats (cold water fatty fish, fish oil, flax seeds, flax oil) and Omega-6 fats CLA and GLA from vegetable oils. All fish oils are well-filtered and/or molecularly distilled to remove environmental contaminants and heavy metals. A low-fat, gluten-free vegetarian diet has been helpful if maintained for several months, but does not produce fast results and is best combined with other approaches, such as supplementation. Wheat and milk are often implicated in immune reactions, and it is sometimes best to avoid them, at least while addressing the problems. Joint problems have also been linked to leaky gut and maldigestion of food, leading to the body’s immune cells attacking undigested proteins. This trains immune cells to recognize food proteins as invasive organisms and respond to them aggressively, leading to food sensitivities that are not classic allergies. Since some undigested or partially digested proteins may be similar to body tissues, maldigestion could partially explain why the body sometimes attacks its own tissues. If so, there are aids to proper digestion that should be considered. Good digestion is a tool to prevent immune reactions to food and the human gut should serve as an immune barrier to pathogens in food. Take time to smell and think about your food before you eat. Avoid stress or distractions during meals. Carefully chew food to a liquid before swallowing, and even chew liquids to enhance contact with digestive enzymes in saliva. If necessary, take a high quality plant enzyme or a milk-digestive enzyme. In some cases, more stomach acid is needed to digest proteins (and minerals). HCl and Pepsin supplements do this, but sometimes much larger amounts of acid than normal are recommended by health professionals (600-2400 mg), which do have risks if you don’t need that much acid, so these high doses must be taken under medical supervision. A traditional home test to determine whether more acid would help digestion is to mix a tablespoon of (preferably raw and organic) apple cider vinegar into a glass of (pure) water and drink with a meal. If it helps digestion, you may need more acid. It may not noticeably help if you require very much acid, though. A tablespoon of raw honey can also be added to this beverage to enhance digestion, also making it taste more like apple juice. If it helps, this can be taken daily with meals. Some digestive enzymes like Bromelain and Serrazimes (serratopeptidase) can be taken between meals to help control substances associated with temporary joint discomfort. A protective layer of probiotics - acidophilus, bifidus and other “friendly bacteria” - actually lines healthy GI tracts like chain mail, preventing leakage of undigested food remnants from the gut that provoke immune responses. It is wise to supplement with healthy bacterial supplements such probiotic products. Fairly high doses of Vitamin E have been shown to help maintain joint health, but I recommend taking the full Vitamin E Complex containing eight forms of natural Vitamin E compounds, not just the alpha tocopherol. Other antioxidants are important to maintain joint health. These include the minerals selenium and zinc, vitamins A, C, E and many plant compounds. GliSODin® raises body levels of key antioxidant enzymes, such as SOD and glutathione. Celadrin® products may help to maintain joint mobility, taken orally or topically applied, and contain acetylated fatty acids from beef fat. MicroLactin™ is a milk protein fraction that helps prevent certain immune cells (cytokines) from overwhelming an area and maintaining a prolonged reaction. Time and patience may be required to find a program that works for any individual’s joint health. Many supplements work best over weeks, months or years. Stretching and gentle exercise often help people, so should be part of any comprehensive program. Yoga and Tai Chi, and variants such as water Ai Chi, are low-impact activities that aid posture and build muscle strength. Glucosamine, Chondroitin and MSM (methylsulphonylmethane, an organic form of sulfur found in all living organisms) are three of the most popular and effective nutrients for supporting joint health. There are other formulations of Glucosamine, including a vegetarian version from fungal fermentation. Studies have shown that these nutrients provide dietary components that support healthy joint structure and function. Look for substances, forms and potencies successfully used in clinical studies. REFERENCES: Chan PS, Caron JP, Orth MW. Effect of glucosamine and chondroitin sulfate on regulation of gene expression of proteolytic enzymes and their inhibitors in interleukin-1-challenged bovine articular cartilage explants. Am J Vet Res. 2005 Nov;66(11):1870-6. Chan PS, Caron JP, Rosa GJ, Orth MW. Glucosamine and chondroitin sulfate regulate gene expression and synthesis of nitric oxide and prostaglandin E(2) in articular cartilage explants. Osteoarthritis Cartilage. 2005 May;13(5):387-94. Deal CL, Moskowitz RW. Nutraceuticals as therapeutic agents in osteoarthritis. The role of glucosamine, chondroitin sulfate, and collagen hydrolysate. Rheum Dis Clin North Am. 1999 May;25(2):379-95. Kelly GS. The role of glucosamine sulfate and chondroitin sulfates in the treatment of degenerative joint disease. Altern Med Rev. 1998 Feb;3(1):27-39. Bijlsma JW. [Glucosamine and chondroitin sulfate as a possible treatment for osteoarthritis] Ned Tijdschr Geneeskd. 2002 Sep 28;146(39):1819-23. Ameye LG, Chee WS. Osteoarthritis and nutrition. From nutraceuticals to functional foods: a systematic review of the scientific evidence. Arthritis Res Ther. 2006;8(4):R127. Kim LS, Axelrod LJ, Howard P, Buratovich N, Waters RF. Efficacy of methylsulfonylmethane (MSM) in osteoarthritis pain of the knee: a pilot clinical trial. Osteoarthritis Cartilage. 2006 Mar;14(3):286-94. Ebisuzaki K. Aspirin and methylsulfonylmethane (MSM): a search for common mechanisms, with implications for cancer prevention. Anticancer Res. 2003 Jan-Feb;23(1A):453-8. Parcell S. Sulfur in human nutrition and applications in medicine. Altern Med Rev. 2002 Feb;7(1):22-44. Bruyere O, Pavelka K, Rovati LC,et al. Glucosamine sulfate reduces osteoarthritis progression in postmenopausal women with knee osteoarthritis: evidence from two 3-year studies. Menopause. 2004 Mar-Apr;11(2):138-43.