From Sept/Oct '99
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"Natural" Arthritis Drugs
As Americans age they become crippled and in pain from a disease known as osteoarthritis. The initial solution provided by most doctors is medication, like aspirin, nonsteroidal antiinflammatory drugs (NSAIDs), and Tylenol, with no long term benefits and many serious side effects. Fortunately, there is another approach that comes close to an ideal drug therapy -- an effective therapy with few side effects. This revolutionary pill is simply nutrients for joint tissues in the formulas of glucosamine and chondroitin. Veterinarians have used these substances for years to treat the arthritic problems of animals and to prevent damage to the joints of animals, like race horses. Although usually sold in a combination of both substances as dietary supplements, there is no information available to demonstrate that the combination produces better results than glucosamine or chondroitin alone.
Arthritis is ubiquitous in America:
The most common form of arthritis afflicting humans is osteoarthritis, often referred to degenerative arthritis because the joints slowly degenerate as a result of "normal wear and tear associated with aging" according to most medical people. Only 2% of women less than 45 years old living in the United States show signs of osteoarthritis; eventually this form of crippling arthritis is seen in x-rays of the hands of over 70% of people age 65 years and older. However, this same disease is comparatively rare in African and Asian countries, where people physically labor to survive (Br J Rheumatol 24:321, 1985). The reason for this, I believe, is their healthier diet that provides proper nourishment for the bones and joints.
In the joints, cartilage covers the surface of the bones allowing them to effortlessly glide one bone over the other. This articular cartilage is made of two types of large molecules, proteoglycans and collagen. Proteoglycans provide elasticity and stiffness on compression; collagen provides the strength. The earliest changes in osteoarthritis are due to disruption of the collagen which contains densely packed proteoglycans. What follows is a progressive loss of the cartilage proteoglycans due to an imbalance of synthesis and degradation. The result is disruption and loss of cartilage and eventually damage to the bones.
Osteoarthritis generally affects a single joint or only a few joints. Early on it is painless, but as the disease progresses the pain sends the victim to seek medical help. The pain is typically aggravated by activity and relieved by rest. In later stages the pain may persist all the time. Stiffness is common, especially upon arising in the morning. In advanced stages, gross deformity and loss of joint motion may be striking.
An Effective Alternative
Medical benefits for glucosamine and chondroitin have been reported in the scientific literature for more than 35 years (Dtsch Med J 5:446, 1965). Yet medical researchers and physicians in the United States have totally ignored this therapy, even with consistent evidence showing it is safe and effective. To date, over 300 scientific investigations and over 20 double-blind studies have been published on the use of glucosamine and chondroitin. Millions of people have tried it, and its popularity is growing because it works.
Glucosamine serves as the substrate for the building blocks of joint proteoglycans. Chondroitin is made of many glucosamine molecules, and serves the same purposes as glucosamine. Both medications lead to long-lasting pain reduction and functional improvement by increasing cartilage building activities, reducing enzymatic destruction of the cartilage, and by antiinflammatory effects. They also act to prevent the death of cartilage cells (chondrocytes) (Presse Med 27:1859, 1998). Not only is joint destruction halted, but reversal of damage is seen in many cases (Altern Med Rev 3:27, 1998).
Some people experience very rapid pain relief from these medications, which would suggest additional benefits over just the long term healing and strengthening of the joints. These immediate benefits are the result of the production of hyaluronic acid, which is primarily responsible for the lubricating and shock-absorbing properties of joint (synovial) fluids (Med Hypothesis 50:507, 1998). Hyaluronic acid also has antiinflammatory activities and promotes the cartilage building activities of chondrocytes. In osteoarthritis, hyaluronic acid levels are decreased in the synovial fluid. The hyaluronic acid concentration of synovial fluids has been shown to increase in humans with oral treatment using 800 mg of chondroitin sulfate for 10 days (Osteoarthritis Cartilage 6:A14, 1998). Further evidence of the rapidly beneficial role played by hyaluronic acid is demonstarted by direct injections into joints which results in rapid pain relief and improved mobility.
Disadvantages of Standard Medicine
Asprin and NSAIDs work by inhibiting the synthesis of prostaglandins. Unfortunately, in addition to inhibiting prostaglandins that mediate pain and inflammation, they also inhibit prostaglandins that repair cartilage. The result is accelerated destruction of the joints -- exactly the opposite effect of what you are trying to accomplish (Am J Med 81:36, 1986; Lancet 2:519, 1989). Serious toxicity to the gastrointestinal tract is common, and caused by interference with prostaglandin activity that maintains the integrity of the stomach lining -- the result can be pain, bleeding, and perforation of the stomach. Damage to the kidneys and liver, as well as fluid retention are seen with NSAIDs. Most (except for aspirin and Relafen) damage the gastrointestinal barrier causing a "leaky gut" that can lead to autoimmune diseases. Aspirin is a type of NSAID and it has many of the same adverse effects, especially on the gastrointestinal tract. Aspirin will also increase your risk of bleeding from many sources.
Tylenol (acetaminophen) is toxic to the liver, especially with heavy alcohol use. Liver failure due to a massive overdose, such as seen with an attempted suicide, is common. Maximum recommended dosage of Tylenol is 8 tablets a day in divided doses. Severe liver toxicity has been seen with doses, of as little as 4 to 10 grams (12 to 30 tablets) in 24 hours (JAMA 272:1845, 1994). Heavy users of Tylenol have an increased risk of kidney failure in a dose-dependent fashion. People who take more than one pill a day (366 pills a year) have twice the risk of losing their kidneys as those who take fewer than 104 pills a year (N Engl J Med 331:1675, 1994). Furthermore, people who take more than 1000 pills in their lifetime have twice the chance of kidney failure compared to those who take fewer than 1000 pills. Approximately 8 to 10 percent of the cases of kidney failure are believed to be due to heavy use of Tylenol.
Side effects of common arthritic drugs:
Few Adverse Effects from the Alternatives
Glucosamine and chondroitin do not act by prostaglandin synthesis inhibition and therefore they are not accompanied by side effects of progressive joint destruction, GI upset and bleeding. Nor do these substances adversely affect the liver or kidneys. Glucosamine is very well tolerated by patients of all ages under short- and long-term treatment. At the very most, mild gastrointestinal upset, drowsiness and headache may occur.
Costs and Dosages:
Glucosamine comes in a sulfate and hydrochloride form. Both are equally effective. Often glucosamine will be combined with chondroitin, and sometimes with magnesium, calcium, boron, and other minerals that make up bone tissues. There is some controversy as to whether both glucosamine and chondroitin must be taken together to get maximum effects. An effective dose of glucosamine is 1,500 mg daily and chondroitin is 800 to 1,200 mg daily. Unless side effects develop from a large dose, all of the medication can be taken as a single daily dose. Dividing into 3 smaller doses may make the medications more tolerable for some people. Cost of these medications is about $ 25 for 100 (500 mg) combination tablets, which means about 75 cents for a days treatment.
Strict vegetarians, especially those of an ethical persuasion who hold animal rights dearly, may have understandable objections to taking these medications. Chondroitin is made from bovine (cow) cartilage. Glucosamine often comes from sea shells. The national best-selling book The Arthritis Cure by Jason Theodosakis, MD can provide you with further information on this form of treatment.
Other Treatments of Osteoarthritis
Aspirin and NSAIDs should be reserved for treatment of intolerable pain. They should not be considered "chondro-protective," since they actually accelerate the destruction of the joints. Steroid injections may provide temporary relief for people desperate for help.
Other important steps for people with osteoarthritis to take are to lose weight, especially if they have disease of the joints of the lower extremities, and avoid prolonged and strenuous use of the affected joints. Complete immobilization is rarely advisable. Disuse of a joint can lead to muscle, cartilage, and bone atrophy. Exercises should be done to maintain the strength of the muscles around the joint. You may find help developing the right exercise program from a personal trainer at a health club or from a professionally trained physical therapist. Physical therapy with heat -- like a hot shower, bath or hot tub -- can soothe painful joints. Electrical stimulation with a transcutaneous electrical nerve stimulator (TENS unit) can sometimes make the pain more tolerable. Joint surgery is reserved for people with advanced disease in whom all other therapy has failed and the quality of their life is significantly affected. Joint replacement, especially of the hip, has proven to be of great benefit for people in need of this surgery.
All said about treatment, there is nothing better than prevention of joint disease. Injuries of joints often lead to osteoarthritis later in life. Be careful! Consider this when you are deciding whether or not your children should be involved in contact sports, or yourself in marathon running. A low-fat vegetarian diet will provide the best nourishment for your joints, and combined with non injurious activity you will have the best chance to avoid osteoarthritis later in life.
Studies on Glucosamine and Chondroitin:
A 16-week randomized, double-blind, placebo-controlled crossover trial of 1,500 mg of glucosamine with 1200 mg chondroitin sulfate and 228 mg of magnesium ascorbate found a decrease in pain (-28%) and an improvement in physical examination (-43%) of the knee joint in 34 males from the US Navy diving team. No benefit was seen in spine arthritis. (Mil Med 164:85, 1999).
A double-blind, randomized investigation of 178 Chinese patients suffering from arthritis of the knee who were treated with 1,500 mg of glucosamine sulfate or 1,200 mg of ibuprofen (a NSAID). Both improved the symptoms of osteoarthritis, but glucosamine was more effective and the benefits persisted longer than with ibuprofen, with no side effects from glucosamine. (Arzneimitteforschung 48:469,1998).
A multicenter, randomized, placebo-controlled, double-blind study of 155 outpatients with knee arthritis were treated with 400 mg intramuscular injections of glucosamine or placebo twice a week. In the glucosamine group 55% showed benefits, while 33% of the placebo group reported improvement. (Arzneimitteforschung 44:75, 1994).
A study conducted by 252 doctors throughout Portugal on 1208 patients who received 1,500 mg of glucosamine daily found 50% of patients reported "good results" and 36% reported "sufficient results." The improvement obtained lasted for a period of 6 to 12 weeks after the end of treatment. Oral glucosamine was fully tolerated by 86% of patients (Pharmatherapeutica 3:157, 1982).
A double-blind trial of 40 outpatients with arthritis in one knee only, treated with either 1,500 mg of glucosamine or 1,200 mg of ibuprofen daily for 8 weeks. Initially pain reduction was faster with the ibuprofen group, eventually, however, glucosamine showed significantly greater reduction in pain. Minor complaints were reported from 2 patients on glucosamine and 5 on ibuprofen. (Curr Med Res Opin 8:145, 1982)
Inpatients with chronic osteoarthritis were treated with daily injections of 400 mg of glucosamine or a piperazine/chlorbutano (drugs used to treat arthritic joints) l combination intramuscularly or intervenously for 7 days. During the following two weeks they were given either 1,500 mg glucosamine sulfate or placebo. During the injection period both groups improved, but the glucosamine group did significantly better. During the maintenance period those patients taking the glucosamine continued to improve, while those on placebo regressed to pretreatment levels. No definite drug related complaints were recorded. The authors concluded, "It is suggested that parental and/or oral treatment with glucosamine should be considered as basic therapy for the management of primary or secondary osteoarthrosis disorders." (Pharmatherapeutica 2:504, 1981).
A prospective, double-blind, trial on 20 outpatients with established osteoarthritis studied the effects of 1,500 mg of glucosamine sulfate or placebo for 6 to 8 weeks. Those taking glucosamine had significantly greater and earlier relief of symptoms. No adverse reactions were reported. (Curr Med Res Opin 7:110, 1980).
Chondroitin in a dose of 1,500 mg daily for several months was found to be more effective than placebo and as effective as NSAIDs in providing pain relief and improving joint function, without risk, in subjects with osteoarthritis of the hip and/or knee. The benefits persisted several weeks after the end of treatment. Economic benefits were realized with a 67% decrease in use of NSAIDs. Further savings were achieved by less use of physiotherapy and fewer co-prescriptions for drugs to protect the GI tract from the effects of NSAIDs. (Presse Med 27:1866, 1998).
A controlled, randomized study of 104 patients with osteoarthritis of the knee treated with 800 mg/day of chondroitin or placebo. After 1 year the functional impairment was reduced by approximately 50%. Improvement in the intraarticular space was seen by x-ray in the treated group. (Intraarticular space narrows in osteoarthritis as the joint cartilage is worn away.) Tolerance was excellent or good in 90% of cases. (Presse Med 21:1862, 1998).
A 1-year randomized, double-blind, controlled pilot study of 42 patients of both sexes, aged 35-78 years, with symptomatic knee osteoarthritis were treated with 800 mg of chondroitin daily or with placebo. Chondroitin relieved pain and increased overall mobility. Joint space was maintained, whereas, joint spaced narrowed in the placebo group. Biochemical markers of bone and joint destruction stabilized in the treated group, but continued to be abnormal in the placebo group. Chondroitin was found to be a safe and effective slow-acting drug for the treatment of osteoarthritis and may influence the natural course of deterioration of the joints by osteoarthritis in humans. (Osteoarthritis Cartilage 6:A39, 1998)
A randomized, double-blind, placebo-controlled study of 119 patients with osteoarthritis treated with 1,200 mg of chondroitin or placebo daily. The finger joints were examined by x-ray and those receiving the chondroitin had a significant decrease in the appearance of new erosive osteoarthritic finger joints. Erosive joints show physical changes of nodularity and deformity (Heberden's nodes). Treated patients were protected against erosive evolution. (Osteoarthritis Cartilage 6:A37, 1998).
A randomized, double-blind, placebo-controlled study of 80 patients with osteoarthritis of the knee treated with 800 mg of chondroitin or placebo daily. Walking time, as defined as the time required to walk 20 meters, was reduced in the chondroitin group only. Pain also decreased and mobility improved. The placebo group took more Tylenol than the treated group. Results suggest that chondroitin acts as a symptomatic, slow-acting, drug in knee osteoarthritis. (Osteoarthritis Cartilage 6:A31, 1998).
A multicentered, randomized, double-blind, placebo-controlled study of 127 patients with osteoarthritis of the knee treated with a single dose of 1,200 mg vs 400 mg 3 times a day of chondroitin, or placebo daily. Chondroitin worked equally well in both dosage forms and significantly better than placebo. (Osteoarthritis Cartilage 6:A25, 1998).
A multicenter study treated 61 patients with osteoarthritis of the hip, knee and/or finger joints with chondroitin sulfate for 3 months. Use of NSAIDs was reduced by 72%. Pain reduction was greater than that achieved with NSAIDs. There was a 97% compliance rate. (Wien Med Wochenschr 146:609, 1996).
A multicentered, randomized, double-blind, placebo-controlled study of 146 patients with osteoarthritis of the knee treated with 400 mg of chondroitin 3 times a day, a NSAID (diclofenac 150 mg/day), or placebo. Those treated with NSAIDs showed prompt reduction in symptoms which reappeared at the end of treatment. In the chondroitin group the response appeared later in time, but lasted for up to 3 months after the end of treatment. (J Rheumatol 23:1385, 1996).
From Sept/Oct '99
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