# Presentation: 049353

## In Support of OA Health Claims for Glucosamine & Chondroitin

- “Dr. Theo”
- 6-7-04
- University of Arizona College of Medicine
- Canyon Ranch Medical Department

**In Support of OA Health Claims for Glucosamine & Chondroitin**

## Disclosures

- Cargill ($5,000 + travel) for this appearance
- Pharmavite (consultant)
- Rexall (NBTY) (consultant)
- Sanofi/Synthelabo (consultant)
- York Nutritional Labs (consultant)
- Cyvex (consultant)
- Pfizer (speaker’s program)
- Own Merck/Pfizer stock
- Consultant - Oversight Committee NIH’s GAIT
- Expert Witness - Chondroitin import tariff case
- Author books on integrative osteoarthritis treatment
- Own branded products starting 2004
- Appearances on behalf of the Arthritis Foundation
- Contract talks with a number of other companies in the OA field

## Key Points

- OA incidence/prevalence has been underestimated
- 96% prevalence of ROA found in *asymptomatic* men and women ≥ 55 y/o1
- NSAIDs/analgesics are not disease-modifying treatments
- Rofecoxib users lost a whopping 0.27 mm of knee joint space width in one-year as measured by semi-flexed, quantitative X-rays2
- Celecoxib users lost a significant amount of hip JSW and had losses in knee JSW consistent with placebo in a 12-month open label trial 3
- NSAID/analgesic safety may be overstated - cost to society immense 4-7

- Le Graverand, M-P H, et. al.  Arthritis & Rheumatism. 2003; Vol. 49, No. 9 (Suppl)
- van Kuijk, et. al. Arthritis & Rheumatism. 2000; Vol. 43:S220
- Tindall EA, et al. Clinical Therapeutics.  24(12):2051-63, 2002 Dec.
- Singh, G. Am. J. of Med. Vol 105, No. 1, Suppl. 2, pp 31S-38S
- MacDonald TM, Wei L. Effect of ibuprofen on cardioprotective effect of aspirin. Lancet 2003; 361: 573–74
- BMJ. VOL. 324; 6/02 p.1287-8
- Arth. & Rheum. Vol. 48, No.9 (suppl.) p.S697

## Key Points

- OA treatments are difficult to study, but Glucosamine (G) and Chondroitin Sulfate (CS) have, very strong, long-term evidence for health claims compared to other dietary supplements
- G/CS span the spectrum from Basic Science (culture, animal, etc) to Clinical (function, placebo-controlled, NSAID comparator, x-ray quantification and even outcomes)

## Chondroitin’s Effect on NSAID Consumption

**Percent Change**

- Conrozier T. Chondroitin sulfates (CS 4&6): practical applications and economic impact [French]. Presse Med 1998 Nov 21;27(36):1866-8

**N = 11,000 patient records**

**- 67%**

**- 50%**

_**Conclusion**_:
- Net cost of supplying CS to French citizens with OA = $0

## Glucosamine Base, Not Sulfate is Important

- Glucosamine HCl is used to make G•Sulfate which is then converted back to G•HCL in the acid environment of the stomach. 1-2
- Glucosamine that reaches chondrocytes is base, not HCL or sulfate. Sulfate component is cleaved before absorption. All glucosamine salts are 100% ionized in the low pH environment of the stomach. 1-2
- Most of the earliest basic science work was performed using G•HCL1
- The one direct comparison of G•HCL to G•SO4 shows equality in stimulation of proteoglycan synthesis. N-acetyl glucosamine was not nearly as effective. 3

- www.wilkeresources.com/WILKEresources/GlucosamineHistorical.htm
- www.wilkeresources.com/WILKEresources/GlucosamineHClvsSulf.htm
- Pharmacology 5:337-345, 1971

## Glucosamine Base, Not Sulfate is Important

-  One study suggested that the glucosamine base, not the sulfate was the active component in beneficially altering OA pathways in equine cartilage explants.
- Conclusion: *Glucosamine HCL and G•Sulfate have similar abilities to prevent or reduce cartilage degeneration in vitro*.1
-  The two, small, negative clinical studies on G•HCL have major flaws
-  A disease-modifying, histologic animal study shows significant effects for both G•HCL and CS, with the combination yielding the best results2

- Fenton JI, et. al. Osteoarthritis and Cartilage (2000) 8, 444-451
- Lippiello L. J. Clin. Ortho. Rel. Res. (2000) 381; 229-240

## Chondroitin Key Points

- The dose of CS shown effective is 800-1,200 mg; Glucosamine 1,500 mg 1-2
- Oral CS absorption is about 12%.3 For alendronate, an FDA-approved drug treatment for osteoporosis, oral absorption is < 1%.4 Absorption determines dose, not effect of treatment
- All Chondroitin Sulfate (CS) clinical studies are positive for either WOMAC/Lesquene Index/VAS 1-2 or radiographic outcomes
- The largest, single structural study for either supplement randomized 300 subjects and lasted two years. The treated group took 800 mg of CS. Minimal joint space width actually *increased* in the CS users and decreased in the placebo group (p < 0.05). 20% flexed X-Ray positioning guidelines were used.5

- Arch Intern Med. 2003;163:1514-1522
- JAMA March 15, 2000 Vol 283, No. 11
- Osteoart. & Cart. (1998) 6;14-21
- PDR data
- Michel BA, Stucki G, et. al. Retardation of Knee Joint Space Narrowing Through Chondroitin 4&6 Sulphate. Arthritis & Rheumatism. Vol. 48, No. 9 (suppl) Sept. 2003 p. S77

## Summary

- G/CS clinical studies probably underestimate effect because they’re done on only primary, not secondary OA subjects
- Approval of health claims for Glucosamine HCl & Glucosamine Sulfate and Chondroitin Sulfate would allow industry to make claims that relate to the actual evidence, not what marketers are using now
- G/CS are beneficial *supplements* for osteoarthritis and should have health claim approval to support this to help better educate the public