• This study examined the efficacy and safety of chondroitin sulfate (CS) capsules administered with glucosamine sulfate (GS) capsules or sachet preparations of glucosamine hydrochloride (GH) for patients with knee osteoarthritis. In total, 1120 patients were randomized 1:1:1 to receive GS and CS capsules three times daily, GH/CS sachet once daily, or GH and CS three times daily. All groups had significant decreases in pain (P < .001), with no difference among groups. All groups also had improvement in disease activity, decreased acetaminophen consumption, and better adherence (P < .005).

• For patients with knee osteoarthritis, GS/CS and GH/CS provided sustained analgesia.

Written by David Rakel MD, FAAFP
Glucosamine sulfate or hydrochloride for knee OA?

Glucosamine and chondroitin are commonly used supplements for osteoarthritis (OA). They differ from symptomatic treatment (acetaminophen, NSAIDS) in that their mechanism of action may not only improve pain, but also modify the disease process.

Glucosamine mainly works by retaining the fluid content within the cartilage allowing for more cushioning in the joint. Chondroitin increases the viscosity of the synovial fluid, increasing the joint’s buoyancy. But do they work?

The evidence is mixed but promising. Both have a proven safety record. There have been well-done trials showing improvement in hand OA with chondroitin.1 In the research evaluating glucosamine, studies using glucosamine sulfate have had more favorable outcomes than those using glucosamine hydrochloride.

This study has limitations in that it was an open-label, industry-sponsored randomized study without a placebo group. But it is the largest study to date to compare glucosamine sulfate and glucosamine hydrochloride for knee OA. It also evaluates once a day dosing vs dosing with 500 mg glucosamine and 400 mg chondroitin capsules three times a day. Both the sulfate and hydrochloride were equivalent, and it did not appear to matter if the dosing was all at once or divided into three daily doses. All formulations reduced pain and the need for acetaminophen use.

Summary of what we think we know in using glucosamine and chondroitin for OA2-4

• Glucosamine sulfate and glucosamine hydrochloride appear to be equivalent in their efficacy.
• Individuals with more severe symptoms appear to have a greater response.
• Those who are obese respond poorly.
• The average dose for glucosamine is 1500 mg daily, and the average dose for chondroitin is 1200 mg. These can be given once daily or in divided doses.
• Both supplements have a proven safety record. Glucosamine does not affect serum glucose levels.
• It can take 6 to 8 weeks for the positive effects to be seen and felt.
• Glucosamine is made from crustacean shells, and those with a shellfish allergy should avoid it.
• Chondroitin is often made from bovine trachea (vegetarians beware).

References

1. Gabay C, Medinger-Sadowski C, Gascon D, et al. Symptomatic effects of chondroitin 4 and chondroitin 6 sulfate on hand osteoarthritis: a randomized, double-blind, placebo-controlled clinical trial at a single center. Arthritis Rheum. 2011;63:3383-3391.
2. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. 2006;354:795-808.
3. Simon RR, Marks V, Leeds AR, Anderson JW. A comprehensive review of oral glucosamine use and effects on glucose metabolism in normal and diabetic individuals. Diabetes Metab Res Rev. 2011;27:14-27.
4. Provenza JR, Shinjo SK, Silva JM, Peron CR, Rocha FA. Combined glucosamine and chondroitin sulfate, once or three times daily, provides clinically relevant analgesia in knee osteoarthritis [published online ahead of print August 3, 2014]. Clin Rheumatol. DOI: 10.1007/s10067

Abstract

We compared the analgesic efficacy and safety of glucosamine sulfate (GS) and chondroitin sulfate (CS) capsules or sachet preparations with glucosamine hydrochloride (GH) and CS capsules in knee osteoarthritis (OA) patients. 1,120 subjects with radiographic knee OA (Kellgren/Lawrence 2–3) were randomized (1:1:1) at 16 centers to receive GS 500 mg/CS 400 mg three times daily capsules (GI) or once daily sachet (GII) or GH 500 mg/CS 400 mg three times daily (GIII) for a 16-week trial. Primary outcome, intention-to-treat (ITT) was change from baseline of patient reported pain intensity (0–100 mm visual analogue scale) in the affected knee and variation of Lequesne’s index (LI). Monthly secondary outcomes were changes from baseline in patient reported pain and LI, patient and physician global assessments of disease activity, acetaminophen consumption, and adherence. ITT population comprised 302, 301, and 306 patients in GI, GII, and GIII. Pain significantly decreased (GI = −30.9 ± 1.5; GII = −28.7 ± 1.5; GIII = −29.7 ± 1.5 mm) in all groups (P < 0.001) as well as LI (GI = −3.8 ± 0.2; GII = −3.7 ± 0.2; GIII = −3.9 ± 0.2; P < 0.001). All secondary outcomes improved (P  < 0.005) for all groups. Patients that did not complete the study were 77 (44.8 %) for lack of adherence, 16 (9.3 %) consent withdrawal, 11 (6.4 %) adverse events, eight (4.7 %) lost to follow-up, and 17 (9.9 %) for other causes. Non-inferiority analysis found no differences among groups. This is a large study showing that GS/CS and GH/CS provide clinically meaningful and sustained analgesia in knee OA regardless of dose fractionation and capsule or sachet formulations.

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