Life Extension Magazine February 2005
Arthritis after Vioxx®
By Richard P. Huemer, MD
EPA and DHA reduce levels
of joint-destroying inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6 (IL-6).30 These omega-3 fatty acids also suppress levels of the inflammatory mediators leukotriene B4 and prostaglandin E2.31 EPA also is metabolized to an anti-inflammatory prostaglandin, PGE-3.30 Excellent dietary sources of DHA and EPA are salmon, other oily cold-water fish, and fish oil. The body can also make EPA from alpha-linolenic acid, a fatty acid found in flaxseed oil.
Modern eating habits promote an imbalance in dietary fatty acids, creating a biochemical environment that is conducive to inflammatory pathologies. The ancestral human diet contained about an equal balance of omega-6 fatty acids (such as arachidonic acid) and omega-3 fatty acids (such as EPA and DHA). A century ago, this dietary ratio of omega-6 fats to omega-3 fats was approximately 4:1, but today it equals or exceeds 20:1, mainly due to increased consumption of omega-6-rich vegetable oils, such as corn oil.32 Supplementing with omega-3 fatty acids is a beneficial strategy for reducing the inflammation inherent in many modern health disorders, including arthritis. An appropriate daily dose of fish oil is 2-3 grams of an EPA-DHA combination. This dosage has been found to relieve painful joints and reduce morning stiffness in patients with rheumatoid arthritis.33
Boswellia Inhibits 5-LOX
Native to Asia, the Boswellia serrata tree produces a gummy sap that traditional medical practitioners have used for inflammation and arthritis. A key constituent of the sap is beta-boswellic acid, which scientists have found to be an effective inhibitor of the 5-LOX inflammatory enzyme.20 A standardized beta-boswellic acid preparation called 5-Loxin™, available in certain natural anti-inflammatory preparations, makes it possible to obtain the benefits of 5-LOX inhibition without consuming large quantities of ordinary boswellia extract.
Anti-Inflammatory Citrus Flavonoids
A specialized group of flavonoids from citrus offers numerous benefits in fighting inflammation. These compounds, called polymethoxylated flavonoids, have been found to benefit the cardiovascular system by lowering levels of cholesterol, LDL, and triglycerides. (See “Novel Dietary Supplement Shows Dramatic Effects in Lowering Cholesterol, LDL, and Triglycerides,” Life Extension, November 2004.) In light of recent findings regarding Vioxx®, which improves arthritis symptoms while placing the cardiovascular system at risk, this is a welcome side benefit to citrus flavonoids.
Polymethoxylated flavonoids provide antioxidant protection and suppress inflammation. One of these flavonoids is very effective at inhibiting expression of the inflammatory cytokines tumor necrosis factor-alpha and IL-10.34 Several flavonoids, including tangeretin, sinensetin, and nobiletin, have been shown to suppress PGE-2 and matrix metalloproteinase production in joint cells, suggesting a chondroprotective effect of citrus bioflavonoids.35
In particular, the flavonoid nobiletin has been identified as a novel anti-inflammatory agent that has the potential to inhibit the degradation of articular cartilage in osteoarthritis and rheumatoid arthritis.35 Nobiletin has also been found to interfere with numerous inflammatory cytokines, including interleukin-1 beta and interleukin-6.36 These anti-inflammatory effects are comparable to those seen with powerful anti-inflammatory steroids such as dexamethasone. Tangeretin, another citrus flavonoid, has been found to offer complementary effects against inflammation.37
Glucosamine Promotes Healthy Joints
The cartilage between joints acts as a shock absorber, protecting the bones and tissues from the impact creating during walking and other bodily movements. Glycosamino-glycans are long, unbranched molecules of repeating pairs of sugars that help cushion the joints from wear and tear. These highly viscous molecules exist in the extracellular matrix, making them ideal as a lubricating fluid for the joints.
Glucosamine is a natural remedy that has been found to be useful in promoting healthy joints. Glucosamine is an amino sugar that is crucial for the construction of glycosaminoglycans in articular cartilage. Reduced glycosaminoglycans content in osteoarthritic cartilage matrix has been found to correlate with the severity of osteoarthritis. Oral glucosamine appears to promote the secretion of more glycosaminoglycans by chondrocytes. Clinically, glucosamine has demonstrated benefits in patients with arthritis of the hip or knee.38
Clinical evidence suggests that glucosamine helps maintain the joint space and may help rebuild damaged cartilage. By contrast, NSAIDs have a propensity to make cartilage deteriorate.39 Glucosamine also inhibits certain enzymes that destroy cartilage, including collagenase and phospholipase. By blocking pathogenic mechanisms that lead to joint degeneration, glucosamine delays the progression of osteoarthritis and relieves symptoms even for weeks after termination of the treatment.40
Glucosamine is becoming recognized as a treatment of choice for osteoarthritis. Its ability to repair and improve joint function, in addition to providing pain relief, gives it a significant advantage over conventional treatments. Additionally, glucosamine may stimulate new tissue growth and suppress the enzymes that otherwise break down cartilage.
Multiple Benefits of Methylsulfonylmethane
Methylsulfonylmethane is another natural remedy that may benefit individuals with arthritis. A naturally occurring, organic sulfur compound found in human diets and those of virtually all other vertebrates, methylsulfonylmethane is produced by the body as a result of the foods we eat. In vertebrates, the body’s concentration of methylsulfonylmethane decreases with age. Some research suggests a minimum concentration of methylsulfonylmethane must be maintained in the body to preserve normal function and structure.
In experiments using radiolabeled sulfur, it was shown that after ingestion, methylsulfonylmethane gives up its sulfur to the essential amino acids methionine, cysteine, and other serum proteins, eventually finding its way into the collagen of skin, joints, and blood vessels. It is also incorporated in the keratin of hair and nails.
Animal studies have shown that joints affected by osteoarthritis have lower sulfur content,41 and that arthritic mice given methylsulfonylmethane experience less joint degeneration.42 In a double-blind trial in people with osteoarthritis, subjects who received methylsulfonylmeth-ane experienced significant pain relief.43 Methylsulfonylmethane is known to be safe and nontoxic.
A small, uncontrolled study of arthritic women conducted by Stanley W. Jacob, MD, indicated that methylsulfonylmethane was as effective as ibuprofen, but without the latter’s side effects.44 Much of what we know about methylsulfonylmethane comes from Dr. Jacob’s 20 years of experience in the renowned DMSO Clinic at Oregon Health Sciences University. Methylsulfonylmethane is in fact a derivative of DMSO (dimethylsulfoxide), another powerful arthritis fighter.
Methylsulfonylmethane is a small but highly effective molecule that inhibits pain impulses along nerve fibers, quells inflammation, increases blood supply, reduces muscle spasms, and softens scar tissue. Methylsulfonylmethane relieves pain and inflammation in osteoarthritis, rheumatoid arthritis, lupus, scleroderma, and fibromyalgia. It has also been reported to be helpful in allergies, back pain, headaches, temporomandibular joint dysfunction, tendonitis, and more. Most users take 1000-3000 mg daily, but some require more. Methylsulfonylmethane can be applied topically as well as taken orally.44
Synergistic Effects of Glucosamine, Methylsulfonylmethane
In an exciting new study, the combination of glucosamine with methylsulfonylmethane was found to be more effective in improving the signs and symptoms of osteoarthritis than the use of either agent alone.45 Glucosamine is known as a chondroprotective agent since it helps to protect and restore joint cartilage. Methylsulfonylmethane is known to be an effective natural analgesic and anti-inflammatory.
In this study, 118 patients with mild to moderate osteoarthritis were treated three times daily for 12 weeks with either 500 mg of glucosamine, 500 mg of methylsulfonylmethane, a combination of both, or an inactive placebo. The patients were evaluated for pain, inflammation, and swelling at 0, 2, 4, 8, and 12 weeks.45
Glucosamine, methylsulfonylmethane, and the combination of glucosamine and methylsulfonylmethane significantly relieved the pain and swelling of osteoarthritis compared with placebo. After 12 weeks of treatment, the average pain score in the glucosamine-only group dropped from 1.74 to 0.65. In the methylsulfonylmethane-only group, the score fell from 1.53 to 0.74. In the group taking both glucosamine and methylsulfonylmethane, however, the average pain score dropped from 1.70 to 0.36. The researchers also found that the combination therapy had a faster effect on pain and inflammation than either glucosamine or methylsulfonylmethane alone.45 The study authors concluded that the combination of glucosamine with methylsulfonylmethane provides better and more rapid improvement in patients with osteoarthritis than either agent alone.
Practical Advice on Nutrients and Drugs
The nutritional management of arthritis goes far beyond the items discussed in this article. Additional nutrients important for those suffering with arthritis include vitamin C, antioxidants, B-complex vitamins, and trace minerals, especially selenium and copper. A healthy, natural diet is fundamental to managing inflammatory conditions such as arthritis (see the sidebar, “Nutrients for Healthy Joints”).
Nutritional and herbal remedies may offer a safe, effective first line of therapy for many arthritis sufferers. Natural remedies—including fish oil, boswellia, citrus flavonoids, glucosamine, and methylsulfonylmethane—have been found to effectively reduce inflammation and protect joint health. For those experiencing more severe arthritis that requires powerful drugs such as COX-2 inhibitors, nutritional and herbal agents used concomitantly may allow lower drug doses. A physician should be consulted when combining prescription drugs with natural remedies.
Prescription and over-the-counter medications are often the doctor’s first choice for treating pain and inflammation. Given the risks inherent in these drugs, as evidenced by the recent withdrawal of Vioxx® from the market, this may not be a safe or prudent choice. When nutritional substances like fish oil, boswellia, citrus flavonoids, glucosamine, and methylsulfonylmethane are used as a first line against arthritis pain, drugs can become a last resort. Some people will need drugs, but many others will find relief from pain and inflammation without the risk of toxic side effects.