Pain is the most common reason people seek complementary or alternative remedies.1 Standard pharmaceutical pain medications provide potent relief, but their use may be complicated by side effects ranging from mild stomach upset to life-threatening gastrointestinal bleeding, liver and kidney damage, and heart problems, not to mention the addiction potential that accompanies some strong pain relievers. Chronic or recurrent pain presents additional challenges, because treatment must also be safe when taken on a long-term basis.

In spite of numerous positive clinical studies, critics still dispute the efficacy and safety of many supplements commonly used to relieve pain, even the popular glucosamine/chondroitin sulfate combinations used for osteoarthritis pain. Just how effective and safe are the complementary remedies your customers take for pain relief?

Here's a review of recent research on some of the most popular supplements. Because of space constraints, the list is far from comprehensive. Other popular supplements that have undergone significant clinical research on pain-relieving effects include anti-inflammatory enzymes such as bromelain (from pineapple, Ananas comosus), white willow bark (Salix alba), curcumin from turmeric (Curcuma longa), topical capsaicin preparations from the active component of chiles (Capsicum), avocado-soybean unsaponifiables, green-lipped mussel extract and various traditional herbal formulas.

Take the edge off

Osteoarthritis is the most common form of arthritis and the leading cause of disability in older adults. As baby boomers age, supplements for this condition will likely continue to increase in popularity. Up to 47 percent of older adults with osteoarthritis already use some form of complementary medicine.2 Musculoskeletal pain, including the pain of rheumatoid arthritis and low back pain, accounts for at least 40 percent of complaints made to health care practitioners.3

Glucosamine-chondroitin sulfate: The highly publicized GAIT (Glucosamine/chondroitin Arthritis Intervention Trial) concluded that the popular combination did not provide adequate relief of OA pain among all study participants.4 A smaller subgroup of patients with moderate to severe pain, however, did experience significant pain relief with the formula. The large-scale placebo- and drug-controlled study involved 1,583 people with osteoarthritis of the knee. The study participants were randomly assigned to take 1,500 mg/day of glucosamine, 1,200 mg/day of chondroitin, both glucosamine (1,500 mg/day) and chondroitin (1,200 mg/day), 200 mg of Vioxx (a COX-2 inhibitor) or placebo in divided doses for 24 weeks.

The primary outcome measurement was a 20 percent decrease in knee pain by the end of the study; results were stratified according to pain severity. People taking Vioxx experienced statistically significant pain relief (70 percent versus 60 percent in the placebo group), but no significant overall differences from placebo were observed with any of the supplement regimens. However, among those with moderate-to-severe pain, 79 percent had a 20 percent or more reduction in pain, compared with 54 percent in the placebo group.4 These results add to an already contradictory body of evidence on the effectiveness of glucosamine sulfate.

One group of researchers performed an analysis to investigate why results have varied so widely from study to study.⁵ After carefully analyzing 13 studies that met their criteria for quality, the authors concluded that glucosamine sulfate is effective against OA pain, but that in trials with positive results, larger amounts of pain relief were associated with studies that had greater industry involvement—for example, more funding or a supply of a proprietary test supplements for use in the study.⁵ While this may indicate some kind of research bias, there is not enough evidence to draw such a conclusion.

Perhaps the most interesting recent study on glucosamine sulfate suggests that it may have effects not just on OA symptoms, but also on the underlying disease process. This study assessed changes in joint-space narrowing via radiograph in 136 patients followed for up to eight years. Results showed that three years of treatment with glucosamine sulfate significantly decreased the need for knee replacement, probably due to positive effects on joint structure during treatment. Specifically, glucosamine decreased the proportion of people with joint-space narrowing by more than 60 percent during the course of the study.⁶

MSM

Methylsulfonulmethane is often combined with glucosamine sulfate and chondroitin sulfate to support joint health and relieve musculoskeletal pain, but few studies have investigated the effectiveness of MSM alone. A recent randomized, double blind, placebo-controlled pilot trial examined the effects of MSM against knee pain in 50 people with OA. The study concluded MSM produced statistically significant decreases in pain and improvements in function compared with placebo. The dosage of MSM used in this study was 6 g, given in divided amounts of 3 g twice a day for 12 weeks.7 A similar low incidence of minor gastrointestinal side effects was reported in both the MSM and placebo groups.

Rose hip

The fruit and seeds of the dog rose (Rosa canina) are listed as a traditional remedy for arthritis and many other disorders in The Complete German Commission E Monographs (The American Botanical Council, 1998). In one recent randomized, placebo-controlled, double-blind study involving 94 people with OA of the knee or hip, those who took rose hip powder for three weeks showed 82 percent symptom improvement compared to 49 percent for placebo.

A 2006 systematic review of rose hip studies also concluded that rose hip powder (5 g/day) was significantly more effective than placebo in relieving pain, improving function and lowering consumption of pharmaceutical pain relievers.9

Ginger (Zingiber officinale)

Long known as an important herb for musculoskeletal pain in both traditional Chinese medicine and Ayurveda, ginger is almost always used in combination formulas with other herbs.

One randomized, placebo-controlled, crossover study compared the activity of ginger with ibuprofen (a nonsteroidal anti-inflammatory drug, or NSAID). While both ginger extract and ibuprofen proved more effective than placebo during the first treatment period, there was no significant difference between ginger and placebo during the study as a whole.10

Another double-blind, placebo-controlled, crossover study tested the effects of a ginger extract against pain and other symptoms in 29 people with OA of the knee. The patients were randomly assigned to take either ginger or placebo; after three months, the two groups were switched. The ginger extract was only as effective as placebo for the first three months of the study, but by the end of six months (three months after crossover) it was significantly more effective than placebo. The authors believe that in the first phase, no significant difference was observed because of the remarkable placebo effect of different remedies used in OA. In the second phase, the groups reached a statistically significant difference only at week 24 because of a delayed effect from the ginger and the lack of a washout period. Study participants took four enteric-coated capsules delivering 250 mg of ginger a day in divided amounts. The Israeli manufacturer of the ginger extract funded the study.11

A 2004 review of literature on ginger concluded that its effectiveness against arthritic pain "remains to be confirmed," even though it is clear that certain ginger constituents do interfere with the inflammatory cascade. Some ginger constituents are potent inhibitors of cyclooxygenase-2, or COX-2; others inhibit 5-lipoxygenase, or 5-LOX.12

Lei gong teng

A small, double-blind, placebo-controlled study investigated the effectiveness of the herb Tripterygium wilfordii in relieving RA pain. This traditional Chinese medicine, commonly known as lei gong teng, has a reputation for helping with RA and other autoimmune conditions, but the authors believe their study is one of the first to examine the remedy under controlled conditions. For the study, which enrolled 35 people with treatment-resistant RA, participants were randomly assigned to receive a high dose of Tripterygium extract (360 mg/day), a low dose of Tripterygium (180 mg/day) or placebo.

Among the 32 people who completed four weeks of treatment, 80 percent of those in the high-dose group and 40 percent in the low-dose group experienced a statistically significant symptomatic improvement of at least 20 percent, compared with none in the placebo group. What's more, 50 percent in the high-dose group experienced at least a 50 percent improvement.13

Fish oil

This supplement is widely recommended for musculoskeletal pain, and a strong body of clinical evidence supports its use for OA and RA.14^,15 Taking it in a different direction, a recent study investigated the anti-inflammatory and pain-relieving effects of fish oil in people with spine pain, primarily due to degenerative disk disease in the lumbar or cervical spine. All of the 250 original study participants were taking NSAIDs for pain relief at the start of the study; at least 75 percent were taking COX-2 inhibitors. As part of the study, the participants were gradually weaned off their medications while taking fish oil.

Results were assessed via questionnaire; 125 participants returned the questionnaire after an average of 75 days on fish oil (78 percent taking 1,200 mg/day and 22 percent taking 2,400 mg/day). Among them, 59 percent had completely discontinued their medications and 60 percent said their joint pain had improved. Overall, 80 percent reported they were satisfied with their improvement, and 88 percent said they would continue to take fish oil. No significant side effects were reported. Weaknesses of the study included the fact that it was not placebo-controlled and results were collected via survey. There was no long-term follow-up, and the investigators did not state the amount of EPA and DHA contained in the fish oil supplement they used.14

Devil's claw (Harpagophytum procumbens)

A traditional African herbal remedy for pain, inflammation and other conditions, devil's claw has been studied and promoted for its ability to relieve low back pain. The herb is believed to inhibit both the COX- and LOX-mediated pathways of the inflammatory cascade, but more research on its mechanism of action is needed.3

In 2003, a randomized, double-blind pilot study compared the effects of a standardized devil's claw extract to Vioxx against low back pain. The 88 study participants were randomly assigned to take either Vioxx (12.5 mg/day) or a standardized devil's claw extract (delivering 60 mg/day of harpagosides). Results showed that after six weeks of treatment, Vioxx and devil's claw were equally effective in relieving low back pain, although the researchers caution that larger trials are necessary to validate their preliminary results. An equal number of side effects were reported in the two study groups; the most common was gastrointestinal upset, which was more severe in the Vioxx group.

However, an analysis of devil's claw research to date concluded that of 20 trials assessed, only eight were adequately controlled, and even among those studies, serious methodological problems existed. The main author of this analysis, part of the same research team that performed the 2003 devil's claw trial, concluded: "Evidence of effectiveness of Harpagophytum products is not transferable from product to product. The results of some studies suggest some effectiveness for some products, but for none of the clinically available products is the quality of evidence satisfactory."16