The Effect of Nutritional Supplements on Osteoarthritis

Alternative Medicine Review,  Sept, 2004  by Yuanyuan Wang,  Louise F. Prentice,  Luis Vitetta,  Anita E. Wluka,  Flavia M. Cicuttini

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Introduction

Osteoarthritis (OA) is the most common cause of musculoskeletal disability in the elderly. with a prevalence of 10-30 percent in persons over age 65. OA can cause a substantial burden of disability and economic cost, particularly with an aging population. (1,2) Despite its frequency in the population, OA remains a poorly understood condition for which few therapeutic options are available. (3)

OA is a heterogeneous and multifactorial disease characterized by progressive degeneration of articular cartilage and joint pain, discomfort. and reduces mobility. (4-5) Several pathological mechanisms have been implicated in the development of OA, including obesity, joint injury. metabolic diseases, bone and joint malformations. and genetic factors. (6-9)

Management of OA is primarily focused on the relief of symptoms, using agents such as analgesics and non-steroidal anti-inflammatory drugs (NSAIDs). Stick an approach has been criticized for failing to prevent continued articular cartilage degeneration and, in the case of certain NSAIDs, exacerbating its progression by inhibiting prostaglandin synthesis. (10,11) Identifying agents capable of preventing, slowing, or reversing the structural and pathological alterations in osteoarthritic joints is an important research and clinical objective for which there is emerging evidence for a role of nutritional factors. The purpose of this article is to review the available literature on the

effectiveness and safety of nutritional supplements for the treatment of OA.

Antioxidant Vitamins

A variety of reactive oxygen species (ROS) are formed continuously in tissues by endogenous and exogenous mechanisms. (12) There is emerging evidence that ROS may have a role in the pathogenesis of OA. (13,14) The antioxidants ascorbic acid, alpha-tocopherol, and beta-carotene are free-radical scavenging nutrients that protect cells from damage by pro-oxidants. (15,16)

Ascorbic Acid (Vitamin C)

Ascorbic acid stimulates collagen synthesis and modestly stimulates synthesis of aggrecan (a proteoglycan present in articular cartilage), (17) Sulfated proteoglycan biosynthesis is significantly increased in the presence of ascorbic acid. (18) In human plasma, ascorbate is the only antioxidant that can completely protect lipids from detectable peroxidative damage induced by aqueous peroxyl radicals. Ascorbate appears to trap virtually all peroxyl radicals in the aqueous phase before they diffuse into the plasma lipids. Ascorbate is a highly effective antioxidant, as it not only completely protects lipids from detectable peroxidative damage, but also spares alpha-tocopherol, urate, and bilirubin. (19)

Evidence from Animal Studies

In guinea pigs, which, like humans, cannot make vitamin C, supplementation with vitamin C had a protective effect on experimentally induced cartilage degeneration of the knee. (20-22)

Schwartz et al investigated the effect of variation in dietary ascorbic acid on surgically induced OA in the stifle joints of guinea pigs. (20,21) Guinea pigs were maintained either on a high (150 mg/day) or low (2.4 mg/day) dietary intake of vitamin C. The animals maintained on the high vitamin C level consistently showed less severe joint damage than animals on the lower level. In a later experiment, Meacock et al studied the appearance and progression of surgically induced OA in the cartilage of the hind knees of guinea pigs. (22) The animals were maintained on either a standard diet or a diet containing extra ascorbic acid in drinking water. It was reported that the extra ascorbic acid had a slight chondroprotective effect on the development of spontaneous lesions.

Evidence from Human Studies

In the Framingham Osteoarthritis Cohort Study, a moderate intake of vitamin C (120-200 mg/day) resulted in a three-fold lower risk of OA progression. The association was strong and highly significant, and was consistent between sexes, among non-supplement users, and among individuals with different severities of OA. The higher vitamin C intake also reduced the likelihood of development of knee pain. Vitamin C had no significant effect on the incidence of OA. (14) Despite these data, few randomized, controlled trials have examined the effect of vitamin C on human OA.

A multicenter, double-blind, randomized, placebo-controlled, crossover trial was performed on 133 patients with radiographically verified symptomatic OA of the hip and/or knee joints. The patients were treated with l g calcium ascorbate (containing 898 mg vitamin C) or placebo daily for 14 [+ or -] 3 days, separated by 7 [+ or -] 3 days wash out. The main outcome measured was difference on the 100 mm visual analog scale (VAS) score for pain. The secondary outcomes were Lequesne score for function and patient preference. Calculated on an intention-to-treat principle and using the VAS scale, calcium ascorbate reduced pain significantly compared to placebo. Similar superiority was found for the Lequesne index and patient preference. The demonstrated effect was less than half as pronounced as commonly reported for NSAIDs. (23) Further controlled trials with longer duration are needed.