LA JOLLA, CALIF. – The recall of Vioxx and safety warnings about Celebrex and Bextra created “a very insecure time for pain management,” Robert Bonakdar, M.D., said at a meeting on natural supplements in evidence-based practice sponsored by the Scripps Clinic.
But well before concern surfaced about the safety of those drugs, patients with inflammatory disease increasingly began to seek care from providers of complementary and alternative medicine (CAM) because they were dissatisfied with traditional care results.
“They thank their doctor for the NSAIDs, for the advice, for [the referral to] physical therapy, but they still have pain,” said Dr. Bonakdar, director of pain management at the Scripps Center for Integrative Medicine, La Jolla, Calif. “Also, people with higher pain intensity and duration, and those with a greater degree of self-care, are going to end up in more CAM offices.”
He discussed the following natural supplements, which have been found useful in treating pain associated with inflammatory disease:
▸ Willow bark (Salix spp.). This agent contains multiple constituents including phenolic glycosides, tannins, and flavanoids. In a double-blind, placebo-controlled trial of 21 patients who took 240 mg of salicin over a 2-week period, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores were reduced 40%, compared with a 16% reduction among those on placebo. At 2 weeks, the analgesic effect from willow bark was assessed to be about 40% of that from high-dose NSAIDs.
“There is a dose-response relationship,” Dr. Bonakdar said at the meeting, cosponsored by the University of California, San Diego. A randomized, double-blind placebo-controlled trial of 210 patients with low back pain who took 120 mg or 240 mg salicin demonstrated complete relief from pain in 21% and 39% of patients, respectively (Am. J. Med. 2000;109:9–14).
Only 6% of patients in the placebo group reported complete relief from pain.
The dosage used in trials varies, but it is typically standardized to 240 g salicin/day.
▸ Phytodolor. Available since 1963, this patented supplement is from Germany. It contains 1 mg salicin/mL, Populus tremula, Fraxinus excelsior, and Solidago virgaurea. Of the nine randomized, controlled trials involving phytodolor, those with a placebo arm demonstrated superiority of phytodolor; six trials with a comparison group showed no benefit of phytodolor over NSAIDs.
One trial found a dose response to double-strength phytodolor vs. regular dosing at 2 weeks.
The typical dose in trials is 30 drops of standardized extract t.i.d.
▸ Devil's claw (Harpagophytum procumbens). This South African plant is used for arthritis, myalgia, and as an external ointment for burns or sores. Its active ingredients are harpagoside and β-sitosterol.
There have been four double-blind, placebo-controlled trials involving 50–197 patients with osteoarthritis and low back pain. Patients were treated for 3–8 weeks with 50–100 mg harpagosides/iridoid content of 1.5%–3% (the typical dose in trials).
The treatments significantly improved the pain level and joint mobility in study participants. Side effects have included mild and infrequent GI symptoms (BMC Complement. Altern. Med. 2004;4:13).
▸ SAMe (S-adenosylmethionine). This is an endogenous methyl donor that is a naturally occurring product of the reaction between methionine and adenosine triphosphate (ATP). It is postulated to have anti-inflammatory effects through inhibition of tumor necrosis factor-α and upregulation of proteoglycan synthesis and secretion into chondrocytes. SAMe also appears to have a serotonergic effect that may support its pain-modulating abilities.
In a metaanalysis of 11 osteoarthritis trials, SAMe appeared to be as effective as NSAIDs in reducing pain and improving functionality with fewer adverse effects than NSAIDS (J. Fam. Pract. 2002;51:425–30). SAMe is typically initiated in the 200- to 400-mg range and titrated to between 600 and 1,200 mg with caution regarding its serotonergic effects.
Other natural supplements such as ginger (Zingiber officinale), boswellia (Boswellia serrata), turmeric (Curcuma longa), and essential fatty acids have also demonstrated anti-inflammatory activity in preliminary basic research or human trials. While these and other natural supplements have been documented for the treatment of pain, Dr. Bonakdar emphasized that “further well-done trials are required to advance understanding.”