Benefits
Joint comfort in short-term trials
In pooled analyses of placebo-controlled trials in adults with knee or hip osteoarthritis, chondroitin sulfate gave a small improvement in joint pain and function over up to 6 months. Most trials were rated low quality, and the benefit was no longer clear in the biggest, best-concealed or independently funded trials.
Prescription-grade and supplement-grade products
The clearest positive trial, in 604 adults with knee osteoarthritis, used 800 mg a day of a European prescription-grade product and was funded by its maker. A lab test of three US joint supplements found 7 to 15% less chondroitin than labeled, plus keratan sulfate, another cartilage sugar, left from incomplete purification. GAIT, which found chondroitin no better than placebo, also used pharmaceutical-grade chondroitin donated by Bioiberica, so product grade alone does not explain the different results.
Joint space on knee X-rays
Pooled data from two trials found slightly less loss of knee joint space with chondroitin than with placebo (4.7% less), but another pooled analysis judged the structural change clinically unimportant. In a separate 2-year trial of 605 adults, chondroitin alone did not slow joint-space narrowing.
Combining With Glucosamine
In the NIH funded GAIT trial, glucosamine plus chondroitin was not significantly better than placebo overall; only an exploratory subgroup with moderate to severe knee pain responded. Pooled analyses found too little evidence that the pair beats placebo, and a 2-year trial saw a small slowing of joint-space narrowing (0.10 mm) without a pain benefit.
Two-year joint pain results
In a 2-year continuation of the NIH trial in 662 adults with knee osteoarthritis, chondroitin (400 mg three times daily) did not improve pain more than placebo, and no treatment reached a clinically important difference in pain or function. Another 2-year trial found no pain benefit over placebo during its first year of pain tracking.
Mechanism of action
Part of the cartilage matrix
Chondroitin sulfate is a glycosaminoglycan built from repeating units of glucuronic acid and N-acetylgalactosamine. It is a natural component of the extracellular matrix of cartilage, which is the rationale for taking it as a joint supplement.
Inflammatory signaling in cartilage cells (laboratory)
In cartilage cells exposed to interleukin-1 beta, chondroitin sulfate reduced p38 MAPK and Erk1/2 activation and NF-kappaB movement into the nucleus, lowering IL-1 beta, TNF-alpha, COX-2 and NOS-2. These are cell and animal findings from a review partly written by a manufacturer, not measured effects in people.
Source and structure vary between products
Chondroitin is extracted from cow, pig, chicken or fish cartilage, and some products combine several sources. Its chain length and sulfation pattern differ by species and processing, which can change how much is absorbed and how active it is, so products are not interchangeable.
Clinical trials
Multicenter, randomized, double-blind, placebo-controlled NIH funded trial of glucosamine HCl 1,500 mg/day, chondroitin sulfate 1,200 mg/day, both, or placebo for 24 weeks, with a celecoxib arm as an active control. Bioiberica donated the chondroitin. Primary outcome: a 20% drop in knee pain. (Clegg et al. 2006, N Engl J Med)
1,583 adults with symptomatic knee osteoarthritis (mean age 59, 64% women); 1,229 with mild and 354 with moderate to severe pain.
Chondroitin alone was not significantly better than placebo: its response rate was 5.3 percentage points above the 60.1% placebo rate (P=0.17). The combination was 6.5 points higher (P=0.09). In an exploratory subgroup with moderate to severe pain, the combination responded more often (79.2% vs 54.3%, P=0.002). Adverse events were mild and evenly spread.
Double-blind, randomized, placebo-controlled 2-year trial run by the University of Sydney and funded by Australian government research grants (NHMRC), testing chondroitin sulfate 800 mg, glucosamine sulfate 1,500 mg, both, or placebo once daily. Outcomes: joint space narrowing on knee X-rays over 2 years and knee pain over the first year. (Fransen et al. 2015, Ann Rheum Dis)
605 adults aged 45 to 75 with chronic knee pain and narrowing of the inner knee joint on X-ray, about 151 per group.
Chondroitin alone did not significantly slow joint space narrowing over 2 years. The chondroitin plus glucosamine combination narrowed 0.10 mm less than placebo (P=0.046). All four groups reported less knee pain over the first year, with no significant difference between groups (P=0.93). 34 participants (6%) reported possibly related adverse events.
Randomized, double-blind, double-dummy, placebo-controlled 6-month trial in five European countries of pharmaceutical-grade chondroitin sulfate 800 mg once daily, sponsored by IBSA, which markets the product; a celecoxib arm was also included. (Reginster et al. 2017, Ann Rheum Dis)
604 adults with knee osteoarthritis.
At 6 months, knee pain on a 100 mm scale fell 42.6 mm with chondroitin vs 33.3 mm with placebo (P=0.001), and the Lequesne function index improved more (4.7 vs 3.7 points, P=0.023). The result applies to this prescription-grade product and does not show that other chondroitin supplements perform the same way.