A lot of supplements are sold ostensibly to improve joint pain – in fact, so many that I had to break this information into two posts, and even so, it’s a lot of material. By the year 2040, it’s been estimated that more than 78 million people will have doctor-diagnosed arthritis. At this time, 38% of Americans take a specialty supplement, 29% use herbal/botanical supplements, and 22% use nutrition supplements. Obviously, there are a lot of people who are betting on the fact that people will spend a good deal of money to feel better. Unfortunately, most of the “joint health” supplements are bologna. Even among those that seem to be potentially effective, there hasn’t been enough research done to recommend them.
Glucosamine and Chondroitin
Both glucosamine and chondroitin are naturally found in the joint cartilage and are known to keep that cartilage lubricated and healthy. Therefore, it makes sense that people believe taking the supplements will reduce joint pain and inflammation. However, results in studies are inconclusive. In studies funded by manufacturers, there is a benefit, but in government-funded trials, they are not useful. Go figure.
The National Institute of Health completed a large randomized controlled, multi-center trial, known as the Glucosamine/chondroitin Arthritis Intervention Trial (GAIT). A total of 1583 participants, aged 40 and above, were enrolled in the trial. These participants, for 24 weeks, were assigned to one of five regimens:
- Glucosamine HCl 500 mg three times a day
- Chondroitin sulfate 400 mg three times a day
- Glucosamine HCl 500 mg AND chondroitin sulfate 400 mg three times a day
- Celecoxib 200 mg daily
This study was unique in that all of the compounds used were analyzed and certified by the Food and Drug Administration (FDA). The primary outcome measurement was the Western Ontario and McMaster Osteoarthritis (WOMAC) score at baseline and week 24. The WOMAC Index is a 24-question validated survey assessing pain, function, and mobility; it is a self-assessment. Secondary assessments included an evaluation by the patient and evaluator of disease state and therapy response, changes in pain score using the visual analog scale (VAS), quality of life assessed by the SF-46 General Health Survey, and use of rescue medication (up to 4000 mg of acetaminophen per day).
- There was no difference among the treatment groups compared with placebo in a combined analysis for the primary outcome measure.
- Sub-group analysis showed that, in 78% of those with mild osteoarthritis, there was no significant change when compared with placebo for the four therapy groups.
- In those with moderate-severe osteoarthritis, there was an improvement in the primary outcome measure (WOMAC score) in the glucosamine HCl plus chondroitin sulfate treatment group when compared with placebo. However, there was no significant improvement in other therapy groups.
- All groups had a gradual improvement in pain over the 24 weeks, but the celecoxib group had the fastest improvement at four weeks.
The results of many other studies and a full discussion of the GAIT trial can be reviewed in the Glucosamine Hydrochloride for the Treatment of Osteoarthritis Symptoms study published in Clinical Interventions in Aging in 2007.
In the conclusion of the GAIT study, the authors state, “Some studies did suggest an improvement, but the results were not statistically significant. In the largest, most talked about and awaited trial, the GAIT trial, the results were confusing and difficult to interpret. Statistically, significant improvement was seen only in those with moderate-to-severe knee OA with the combination therapy of glucosamine HCl and chondroitin sulfate…this current review of the available literature suggests little benefit with the use of glucosamine HCl alone to those suffering from OA. Certain combination products may be of benefit in selected subgroups of patients.”
Others have criticized this trial and say that it used an ineffective form of glucosamine. They state that glucosamine sulfate is much more effective than glucosamine hydrochloride. Some researchers and physicians also report that chondroitin blocks the absorption of glucosamine, and state that the two should never be taken together.
A meta-analysis including ten trials and 3,803 patients completed in 2010 concluded that “Compared with placebo, glucosamine, chondroitin, and their combination do not reduce joint pain or have an impact on narrowing of joint space. Health authorities and health insurers should not cover the costs of these preparations, and new prescriptions to patients who have not received treatment should be discouraged.”
Vegetarians and others with dietary restrictions should note that glucosamine supplements are made from the shells of shrimp, lobster, and crab, while chondroitin supplements derive from cow trachea or pork byproducts.
MSM is found naturally in a wide variety of foods, including fresh vegetables, meat, and dairy products. The hypothesis is that since MSM contains sulfur, which is used by the body to form connective tissue, it must be helpful for the joints.
In a small Chinese study of 100 elderly participants randomly assigned to either an MSM group or a placebo group, the scores of joint function and joint problems associated with join degeneration (including pain, stiffness, swelling, difficulty getting out of bed, trouble going down stairs, etc.) was improved among participants in the MSM group. The MSM group also had improved quality-of-life scores. In another randomized, double-blind, placebo-controlled study of 100 patients prescribed either six grams of MSM or a placebo each day for 26 weeks, the MSM group presented significant decreases in all subscales of the Western Ontario and McMaster University Osteoarthritis Index visual analog scale (WOMAC). Early animal research shows some promise for MSM decreasing joint degeneration.
No extensive, well-controlled, studies comparing MSM to placebo have been completed. The National Center for Complementary and Integrative Health (NCCAM) states that clinical trials on MSM offer “no evidence of significant reduction in pain compared to a placebo.” MSM can cause gastrointestinal discomfort. Anyone taking blood thinners should avoid MSM.
Hyaluronic acid works to relieve arthritic pain when it is injected directly into the affected knees, but there is not much high-quality evidence for oral supplements. In some of the small studies that have been conducted, the researchers have used substantial doses of hyaluronic acid and the appropriate dosage for supplementation has not been determined yet. Even more concerning, there are different sources and types of hyaluronic acid, with different biological effects. There is no proof that hyaluronic acid is even absorbed when ingested. In 2011, the Food and Drug Administration warned one company that it was illegally marketing hyaluronic acid products as drugs and making unsubstantiated health claims. In theory, hyaluronic acid supplements might promote cell growth and could be potentially hazardous for individuals with cancer.
Used in Chinese, Japanese, and Indian medicine, ginger inhibits the same COX-2 enzyme that Celebrex works against, suppresses leukotrienes (inflammatory molecules), and switches off specific inflammatory genes. In a 2012 in vitro study, a specialized ginger extract reduced inflammatory reactions in RA synovial cells as effectively as steroids. In a trial of more than 200 subjects, the same extract improved osteoarthritis pain after standing and walking. In other studies, ginger has performed no better than a placebo. Ginger can increase the risk of bleeding and should not be used by individuals on blood thinners or before surgery. No one with gallstones should use ginger, and it has caused heartburn and other GI side effects in some studies.
Avocado/Soybean Unsaponifiables (ASU)
ASU is said to block pro-inflammatory chemicals and prevent the deterioration of the cells that line the joints, as well as possibly regenerate connective tissue. In one study, participants taking ASU (300 mg/day) for two to five months didn’t require as many nonsteroidal anti-inflammatory drugs (NSAIDS) as they did before the study. In another study of short duration, participants demonstrated an improved score on the Lequesne Functional Index. However, there is no evidence that ASU prevents cartilage breakdown. In a longer-term study (two years), no benefit was seen with ASU in reducing joint space loss among patients with hip osteoarthritis. ASU is available by prescription in France, and no safety issues have been reported in the past 15 years. Reported side effects include stomach upset, nausea and vomiting, headaches, and migraine headaches. Anyone with a latex allergy should avoid ASU.
It’s important to choose supplements made by a large company with strict quality controls, and that carries a USP (United States Pharmacopeia) symbol on the bottle. Always discuss any supplements with your doctor before taking them. A study done by Consumer Reports in 2013 found that among 16 popular joint supplements, at least seven did not contain the amount of key ingredients listed on the label and two did not dissolve sufficiently.
In summary, I would trust ginger or ASU the most. There isn’t enough evidence for MSM or hyaluronic acid. Glucosamine chondroitin might help moderate to severe arthritis but seems to have no effect on mild arthritis.