Get access to everything we publish when you sign up for Outside+.
Two surprising but impressive new studies published in the last year might revive interest in what was once almost every runner’s favorite supplement — glucosamine-chondroitin (GC). In the 1980s and 1990s, many runners took GC because it has few to no side effects and was thought protective against knee pain and knee arthritis — a runner’s greatest fear.
Interest faded after results from a two-year, national, randomized trial (Glucosamine/chondroitin Arthritis Intervention Trial — GAIT) were published in the New England Journal of Medicine in 2006. This report concluded: “Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee.” Several “exploratory analyses” nonetheless indicated that GC “may be effective” in those with “moderate-to-severe knee pain.” Despite inconclusive evidence, many runners continue to take the supplement, just in case.
The two recent population studies provide evidence that GC could have an unexpected benefit — extending lifespan. A U.S. paper, published in late 2020, scoured records of 16,686 American adults and showed that GC use was linked with a 27 percent lower rate of all-cause mortality during 8 years, 11 months of follow-up. A similar British paper, also from 2020, tracked more than 495,000 adults and found that glucosamine alone, or with chondroitin, was associated with a 15 percent lower rate of total mortality during 8.9 years of follow-up.
Observational studies like these can not prove cause-and-effect. Also, teasing clear evidence from supplement papers is often like finding a needle in a haystack. There are so many confounding issues — diet, exercise, weight, and the like — that it’s difficult to isolate individual factors. Nonetheless, both recent studies did include multivariable adjustments intended to limit confounders.
“These two studies make an important contribution because they were conducted in large cohorts with robust sample sizes, and the analyses controlled for demographic and lifestyle factors,” notes Johanna Lampe, a glucosamine investigator at the Fred Hutchinson Cancer Research Center in Seattle who was not involved with either of the news reports. “Still it’s difficult to completely disentangle the effects of glucosamine from other factors contributing to longevity.”
The British paper was based on an open-access dataset named the U.K. Biobank, which is yielding many important epidemiological results. About 19 percent of Biobank participants indicated “regular use” of a glucosamine supplement on their questionnaires. On follow-up, these individuals were 15 percent less likely than non-glucosamine users to die from any cause. They also enjoyed other lower risks: 18 percent lower for heart disease, 6 percent for cancers, 27 percent for respiratory mortality, and 26 percent lower for digestive mortality.
The Biobank research team from Southern Medical University in Guangzhou, China, was able to separate the likely effects of glucosamine alone from those of glucosamine and chondroitin taken together. They found no difference, reporting, “Therefore it is likely that glucosamine may reduce the risk of mortality, regardless of the co-administration of chondroitin.”
The U.S. study, led by family medicine physician Dana King at West Virginia University, was based on a well-known “nationally representative” federal survey, NHANES (National Health and Nutrition Examination Survey), administered every two years in the U.S. The analysis targeted those who reported GC use for a year or longer. On follow-up, these individuals had a 27 percent lower risk for all-cause mortality, and a 58 percent lower risk for cardiovascular mortality.
Athletes Already Using
King, an avid cyclist, first got interested in launching a large study after learning that almost all his bike club buddies used GC. “I knew about the Biobank results and studies from Washington state,” King notes. “I thought it was a good time to try a U.S. national test.”
Reports on GC’s mortality links first began surfacing around 2010. That’s when a group from the Hutchinson Center, Johanna Lampe’s workplace, analyzed data on more than 77,000 Washington state adults to see if any commonly used supplements had an effect on cancer risks. Among “non-vitamin, non-mineral” supplements, only GC was significantly associated with lower mortality (17 percent lower) during five years of follow-up.
Both glucosamine and chondroitin exist naturally in the human body, where they appear to assist healthy joint function. Glucosamine sulfate is “used by the body to produce a variety of other chemicals involved in building tendons, ligaments, cartilage, and the thick fluid that surrounds joints,” states the National Institute of Health’s MedlinePlus page. Medline Plus rates glucosamine sulfate “likely safe in most adults,” an assessment shared by researchers in the field.
Glucosamine-chondroitin is a supplement — not a prescription medicine tightly regulated by the U.S. Food and Drug Administration. This means different commercial products may vary in quality. Some have even been found to contain no trace of the presumed key ingredient. Various formulations also include additional ingredients, making comparison difficult. Many commercial versions recommend 1500 mg daily of glucosamine sulfate and 1200 mg of chondroitin sulfate.
No one can say for sure why glucosamine-chondroitin might lower mortality risks. The leading candidate is its potential anti-inflammatory effect. A 2015 randomized, controlled trial found a 23 percent lower level of C-reactive protein (CRP) in GC users. CRP is considered a marker for systemic inflammation, and in many studies has been associated with increased rates of cancer, heart disease, diabetes, and other chronic diseases.
Authors of both the Biobank and NHANES studies believe that glucosamine-chondroitin has anti-inflammatory action. The Biobank paper highlighted a telling association: Glucosamine had a larger mortality-sparing effect on smokers, known to have high levels of CRP, than on non-smokers.
King, the senior NHANES analyst, agrees with this conclusion. “The most plausible hypothesis is that glucosamine-chondroitin supplements are anti-inflammatory, which is what results in lower death rates,” he says.
He adds that while his study and the Biobank research represent “fairly powerful epidemiological studies, they are not randomized controlled trials and cannot prove causation.” King recommends that individuals interested in GC supplements should discuss options with their physician.
Runners already taking GC for its possible protection against joint pain can also hope that the supplement has additional anti-inflammatory and longevity benefits.