SAN DIEGO—Glucosamine and chondroitin may be the best known non-pharmaceutical therapies for osteoarthritis, but they are not the only ones.

Pycnogenol, an extract of French Maritime Pine bark, and Avocado-Soybean Unsaponifiables (ASU), compounds extracted from soy and avocado oils, deserve a place on the top shelf of arthritis remedies, said Jason Theodosakis, MD, at the 6th annual Evidence-Based Update on Natural Supplements, sponsored by the Scripps Center for Integrative Medicine.

ASU and Pycnogenol can do what neither glucosamine/chondroitin nor anti-arthritis drugs can do: they can slow the destruction of joint cartilage while improving joint function. “These supplements work as well or better than available drugs, have fewer side-effects, and cost no more and often cost less,” said Dr. Theodosakis, assistant professor of medicine, University of Arizona.

He reminded conference attendees that currently, “there are no true disease-modifying drugs for osteoarthritis.” Non-steroidal anti-inflammatory agents have their place, mainly in reducing acute OA pain. But they offer little over the long-haul, and should only be used for short-term pain management.

ASU: Arthritis Suffering Undone

As a nutraceutical, ASU is a newcomer to the US market, though it has been marketed for years in France as an over-the-counter arthritis remedy called Piascledine.

There are 4 well-designed randomized trials of 3–24 months’ duration supporting the use of ASU for treatment of OA. Blotman and colleagues randomized 164 patients with hip/femoro-orbital OA to either ASU, 300 mg per day, or placebo, for 3 months. The active treatment markedly reduced the percentage of patients regularly taking NSAIDS by the close of the study (43% versus 69.7% in the placebo group). The ASU patients also had better functional index scores (Blotman F, et al. Rev Rheum Engl. 1997; 64(12): 825–834).

A second trial involving 144 patients with hip or knee OA, showed that those taking ASU for 6 months had greater reductions in Lequesne Functional Index (from a mean of 9.7 at baseline to 6.8) compared with those on placebo (9.4 at baseline to 8.9 at 6 months). Pain level and NSAID use were also reduced among the ASU patients compared with those on placebo.

The improvement seemed to be strongest in patients with hip versus knee arthritis. The authors note that the symptom reduction among the ASU-treated patients persisted for as much as two months after they stopped taking the product (Maheu E, et al. Arthritis Rheum. 1998; 41(1): 81–91).

A study from Erasmus University Hospital, Brussels, showed similar benefits—reduced pain, improved joint function, and reduced medication use—in OA patients taking ASU, 300–600 mg/day (Appelboom T, et al. Scand J Rheumatol. 2001; 30(4): 242–247). These authors found no therapeutic difference between the lower and higher dose levels. The 300 mg dose is standard in Europe.

One of the most promising aspects of ASU is its apparent ability to increase chondrocyte collagen synthesis, said Dr. Theodosakis. He cited a radiographic study by Lequesne and colleagues showing that ASU reduces the progression of joint space loss in people with severe hip OA. This strongly suggests a true disease-modifying effect (Lequesne M, et al. Arthritis Rheum. 2002; 47(1): 50–58).

According to Dr. Theodosakis, ASU has anabolic and anti-catabolic effects: It increases collagen production, stimulates production of aggrecan and TIMP-1, and increases expression of transforming growth factor-β and plasminogen activator inhibitor (PAI-1). It also suppresses TNF-α, IL-1b, COX-2 and other inflammatory cytokines.

ASU has won the favor of the notoriously rigorous Cochrane Collaboration, which noted in a 2008 report that “ASU has beneficial effects on functional index, pain, use of NSAIDs and global evaluation,” and that “The evidence for ASU in OA is convincing.”

It would be nice if one could obtain ASU by eating avocado and soy, but Dr. Theodosakis stressed that this is not possible. The unsaponifiable compounds are tightly bound to fiber within the plant tissue, and impervious to human digestion. The only way to get ASU is via supplementation. ASU is available in the US under the brand name, Avoca, and also in combination with glucosamine-chondroitin (Nutramax Laboratories, www.nutramaxlabs.com). Several other companies also sell branded products. Dr. Theodosakis sells his own private labeled brand, called AvoSoy, via his website (www.drtheo.com).

Bark Takes Bite Out of OA Pain

Pycnogenol, the standardized extract of French Maritime Pine bark, is the other emerging star on the OA horizon. It, too, is available as an OTC medication in Europe but sold as a nutraceutical in the US. In fact, it is one of the most widely-researched supplement ingredients, with documented benefits in reducing cardiovascular disease, deep vein thrombosis, asthma and many other inflammatory conditions (visit www.holisticprimarycare.net and read, “Pycnogenol-Nattokinase Combination Prevents In-Flight Venous Thrombosis,” from our Spring 2004 issue, Vol. 5, No. 1).

Research into pycnogenol’s potential for ameliorating OA began several years ago. In a 3-way international collaboration between the Arizona College of Public Health, the University of Munster, Germany, and the Ghaem General Hospital, Mashhad, Iran, researchers showed that OA patients treated with 50 mg of pycnogenol, thrice daily for three months showed marked improvements in WOMAC scores, especially for pain and physical function by 90 days, compared with those taking placebo.

Pain scores dropped by 43% and stiffness by 35%, with a 52% overall improvement in function (Farid R, et al. Nutr Res. 2007; 27(11): 692–697).

A subsequent study of 100 OA patients randomized to either 150 mg pycnogenol per day or placebo, showed a 40% reduction in both pain and joint stiffness in the active-treatment group, and a 22% increase in physical function compared with those on placebo (Cisar P, et al. Phytother Res. 2008; 22(8): 1087–1092).

There is also evidence that pycnogenol can induce substantial reductions in c-reactive protein among OA patients, at a dose of 100 mg per day, versus placebo This finding underscores the anti-inflammatory properties of the compound. In this study of 156 patients, there was a concomitant 55% reduction in pain and 53% reduction in stiffness (Belcaro G, et al. Redox Rep. 2008; 13(6): 271–276).

Pycnogenol is manufactured by Horphag, a Swiss botanical ingredient manufacturer with a strong commitment to clinical research (www.pycnogenol.com/health).

Take a Load Off, Fannie

Dr. Theodosakis said that both pycnogenol and ASU have a rightful place alongside the better-known glucosamine-chondroitin and omega-3 fatty acids for treatment of OA. But he also stressed that neither supplements nor drugs alone make for a complete therapeutic plan.

Long-term OA care needs to be grounded in nutrition-based strategies to reduce inflammation, rebuild cartilage, facilitate weight loss, and improve overall health. “Non-pharmacologic approaches should be your first line.”

Encourage patients to adopt a vegetable-rich Mediterranean diet that will provide plenty of anti-inflammatory phytochemicals that attenuate inflammation. The Mediterranean dietary pattern is also low in trans-fats, omega-6 fatty acids, and refined carbohydrates, all of which drive inflammation.

Anything you can do to safely help overweight patients lose weight will also help reduce OA symptom burden. The direct mechanical impact of excess pounds on the weight-bearing joints is pretty obvious. Less apparent but no less damaging is the fact that adipose tissue secretes a lot of inflammatory cytokines that stoke the osteoarthritic disease process.

“Fat is an endocrine organ. To be sure, obese people break down weight-bearing cartilage, but they also lose cartilage in the finger joints and other non-weight bearing joints, and this is due to the excess inflammation,” Dr. Theodosakis explained.

A systematic review of 35 trials (including 4 randomized controlled studies) on the impact of weight loss on OA showed that a weight reduction of 6 kg produces a pooled effect size of 0.20 for reduction in pain and a pooled effect size of 0.23 for reduction in disability (Christensen et al. Ann Rheumatic Dis. 2007; 56: 433–439). These effects are small, but when viewed in light of the many other benefits of weight loss, they should not be discounted.