Chondroitin Quality Concerns

Not only is efficacy an issue, but also product quality. This article highlights the inconsistency of the product available in the marketplace. As a consumer, how do you know which brand to use?

From Journal of the American Pharmacists Association
Chondroitin Product Selection for the Glucosamine/Chondroitin Arthritis Intervention Trial

Posted 01/30/2006 Jamie G. Barnhill; Carol L. Fye; David W. Williams; Domenic J. Reda; Crystal L. Harris; Daniel O. Clegg

Abstract and Introduction

Abstract

Objective:
To select a high-quality chondroitin dosage form and/or an appropriate source of sodium chondroitin for the National Institutes of Health's Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT).

Design: Controlled experimental trials.

Setting: Laboratory.

Patients or Participants: Not applicable.

Interventions: Commercially available chondroitin products were reviewed, and purified sodium chondroitin from two suppliers was evaluated through tests (infrared and near-infrared identification, moisture content, pH, optical rotation, color and clarity of aqueous solutions prepared from the powders, protein contamination, total residue following ignition and nitrogen content, determination of sodium chondroitin molecular weight, disaccharide analysis, and measurement of chondroitin, sodium, and total glycosaminoglycan content) and an onsite supplier audit.

Main Outcome Measures: Purity, potency, and quality of sodium chondroitin powders.

Results: No commercially available chondroitin product was deemed appropriate for use in GAIT. Samples of sodium chondroitin powder from two suppliers exhibited similar disaccharide and glycosaminoglycan content. Each contained approximately 2% hyaluronic acid and 8%-9% unsulfated disaccharide. Potency was inconsistent across groups, which might have resulted from different analytical methods and choice of reference standard. Mean potency obtained by five separate methods ranged from 82.2% to 95.5% for one supplier, 92.5% to 110.1% for another, and 95.1% to 112.5% for a commercially obtained reference standard. Critical issues raised by the results include choice of reference standard, selection of assay method, and the consistent appearance of an unidentifiable contaminant present in all three lots from one supplier.

Conclusion: This blinded study determined methods to identify acceptable agents and provided results, which, in addition to regulatory compliance supplier audits, formed the basis for chondroitin product selection in GAIT.

Introduction

Osteoarthritis is the most frequently occurring form of arthritis and a very common disease in the United States.[1] Current medical therapies for osteoarthritis are primarily directed at symptomatic relief and can produce adverse effects. As a result, treatment with alternative agents such as glucosamine and chondroitin has gained broad public acceptance. Health food stores and the media, through recommendations and testimonials, promote the use of glucosamine and chondroitin to control the pain associated with osteoarthritis. Patients with osteoarthritis frequently approach health care professionals for advice concerning the use and safety of glucosamine and chondroitin. Unfortunately, little objective, scientific information has been available for practitioners to use in formulating their recommendations.

In January 1998, the Office of Alternative Medicine (now the National Center for Complementary and Alternative Medicine), within the National Institutes of Health (NIH), convened a group of experts in osteoarthritis, alternative medicine, biostatistics, and family practice to discuss the need, rationale, and feasibility of conducting a Phase III trial on the efficacy of glucosamine and chondroitin in the treatment of osteoarthritis. The group reported a "real and urgent public health need" to rigorously test these agents. In February 1998, NIH issued a Request for Proposals and in September 1999, awarded the contract to the University of Utah School of Medicine. The Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) began recruiting patients in November 2000.

GAIT was a 24-week, placebo-controlled, parallel, double-blind, five-arm trial designed to determine whether glucosamine, chondroitin, and/or the combination were more effective than placebo in treating knee pain of osteoarthritis. To establish that the study was able to detect significant treatment effects, celecoxib (Celebrex—Pfizer), an effective osteoarthritis treatment, was compared with placebo. All patients received a rescue analgesic medication, acetaminophen, to take as needed for severe pain. The 16 participating centers enrolled the required 1,583 subjects over a 37-month recruitment period.

During the GAIT implementation phase, researchers had to identify a source of chondroitin for the study. One major concern with chondroitin was how the purity had been determined previously as well as how it should be determined. Several problems were identified:

1. Recent studies and reviews had highlighted several problems found with commercially available dietary supplements containing chondroitin.[2-4] One study demonstrated that among 32 commercially available products, the chondroitin content ranged from 0% to 115% of the labeled claim.[3]

2. Much of the assay work previously conducted on chondroitin by manufacturers used a method not capable of determining the form of chondroitin or the molecular weight.

3. No established United States Pharmacopeia (USP) chondroitin reference standard was available for use in any analytical method.

4. Regulated as a dietary supplement in the United States, chondroitin is subject to the production and marketing regulations outlined in the Dietary Supplement Health and Education Act (DSHEA), and these are not as strict as the regulations that govern the manufacture of pharmaceuticals.

Objective

The objective of this study was to select a high-quality chondroitin product for GAIT. aClinical results from GAIT were presented in November 2005 at the annual scientific meeting of the American College of Rheumatology, and this created a spate of coverage in the consumer media. Publication of results in a peer-reviewed journal is expected shortly.

Here is an interview with WebMD regarding the quality and quantity in commercial brands of glucosamine and chondroitin.

Glucosamine/Chondroitin Products Not Measuring Up

WebMD Medical News
April 2, 2000 (San Diego) -- So that glucosamine or chondroitin product doesn't seem to be doing much for the sore joints? There could be a simple reason, according to a study presented at the American Nutraceutical Association's annual conference. Researchers have found some brands contain only miniscule amounts of these supposedly active ingredients.

"What we're trying to do here is raise consciousness about dietary supplements ... and it's not just glucosamine and chondroitin," says Natalie Eddington, PhD, director of the Pharmacokinetics-Biopharmaceutics Lab at the University of Maryland School of Pharmacy in Baltimore. "This is a problem with a number of dietary supplements and herbals on the market, because they're not regulated by a federal agency. So the buyer has to beware."

In all, Eddington studied 14 products containing glucosamine and another 11 containing chondroitin -- both ingredients touted as promoting joint health, usually in patients with osteoarthritis. Among the glucosamine products, one contained only 25% of the active ingredient claimed on the label. Others fell significantly shy of label claims -- though not quite so dramatically -- and a few actually exceeded them.

Results were much worse for chondroitin. Four products contained less than half what the label claimed, and one actually hovered near zero. In addition, Eddington noted a disturbing variability within bottles of two brands, meaning that the content of active ingredient was so wide-ranging that consumers using those particular products can't be sure how much chondroitin they're getting with each dose.

A second analysis -- involving 32 brands -- found even more evidence of a chondroitin-content problem. Eddington found that only five products among this group -- about 16% -- contained what their labels claimed they did, with many of those tested having almost no supplement at all.

"It could be the raw ingredients. [Or, it] could be the manufacturer is not focussed on quality control," Eddington tells WebMD. Whatever the reason, she says any prescription product that fared so poorly in testing "would not be on the market."

What darkens the picture even more for chondroitin users is an analysis Eddington performed on five batches of the raw material used to make the products. Using a well-accepted pharmaceutical technique, she found four of the five exhibited poor "permeability" and thus a low likelihood of absorption in the human body. In other words, even capsules containing the right amount of chondroitin might do the consumer little good if made with those raw materials.

"There are many manufacturers and no manufacturing standards, and that concerns us," says John Klippel, MD, medical director for The Arthritis Foundation. Klippel tells WebMD consumers can follow a couple of guidelines that might steer them toward a fair deal -- but emphasizes that evidence that glucosamine/chondroitin products actually work in the long run for osteoarthritis is still somewhat scant.

"Consider using products that have been subject of scientific research," says Klippel. If possible, identify a product that has been used in a human study. Furthermore, use those from reputable manufacturers. "That is a little complicated because the consumer is not sure what that means," he adds. To the Arthritis Foundation, it means, at the very least, a company they've heard of. But patients should not look for a recommendation from the Foundation -- they're not endorsing any of these products.

Randall Tackett, PhD, professor of pharmacology at the University of Georgia in Athens, says he's not surprised with the study results, and adds that it puts pharmacists in a difficult position when patients ask for recommendations on nutritional products. "We're seeing more pharmacists taking more training in [supplements], but still, there is no [instructor] who is going to say 'this is the best brand.'"

"It can create a very confusing situation," Tackett says. "To consumers, glucosamine is glucosamine. They may go into a pharmacy and see one advertised at two for ten dollars. I'd say err on the side of caution. You've got to wonder how much quality assurance can be put in when the brand is priced way below competing compounds."

But Eddington found 'getting what you pay for' apparently doesn't apply to chondroitin products. While many of the worst performers did cost the least, that wasn't always the case. Two expensive -- four-dollar-a-day -- products tested terribly: Both contained almost no chondroitin.