Source: Wegener T, Lupke NP. Treatment of patients with arthrosis of hip or knee with an aqueous extract of devil’s claw (Harpagophytum procumbens DC.). Phytother Res 2003;17:1165-1172.
Abstract: Preparations made from the secondary tubers of Devil’s claw (Harpagophytum procumbens) are used successfully in patients with rheumatic diseases (arthrosis and back pain). In order to add data on the efficacy and long-term safety of an aqueous extract (Doloteffin; 2,400 mg extract daily, corresponding to 50 mg harpagoside), which has been tested successfully in patients with low-back pain, an uncontrolled multicentre drug surveillance study for about 12 weeks was conducted in 75 patients with arthrosis of the hip or knee. To standardize the assessment of treatment effects, the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index (10-point scale) as well as the 10 cm visual analogue scale (VAS) pain scale were used. The results of the study revealed a strong reduction of pain and the symptoms of osteoarthritis. There was a relevant improvement of each WOMAC subscale as well as of the total WOMAC index: 23.8% for the pain subscale, 22.2% for the stiffness subscale, and 23.1% for the physical function subscale. The WOMAC total score was reduced by 22.9%. VAS pain scores were decreased by 25.8% for actual pain, 25.2% for average pain, 22.6% for worst pain, and 24.5% for the total pain score. The physicians reported a continuous improvement in typical clinical findings such as 45.5% for pain on palpation, 35% for limitation of mobility, and 25.4% for joint crepitus. Only two cases of possible adverse drug reactions (dyspeptic complaints and a sensation of fullness) were reported. Although this was an open clinical study, the results suggest that this Devil’s claw extract has a clinically beneficial effect in the treatment of arthrosis of the hip or knee.
Source: Walker AF, et al. Bromelain reduces mild acute knee pain and improves well-being in a dose-dependent fashion in an open study of otherwise healthy adults. Phytomedicine 2002;9:681-686.
Abstract: There is preliminary clinical evidence to support the contention that the anti-inflammatory and analgesic properties of bromelain help to reduce symptoms of osteoarthritis and rheumatoid arthritis. However, there have been no controlled studies of its effects on joint health in healthy subjects who lack such diagnosis. The current study investigated the effects of bromelain on mild acute knee pain of less than three months’ duration in otherwise healthy adults. The study was an open, dose-ranging postal study in volunteers who had been recruited through newspaper and magazine articles. Two validated questionnaires (WOMAC knee health index and the Psychological Well-Being Index) were completed at baseline and after one month’s intervention with bromelain, randomly allocated to volunteers at either 200 mg or 400 mg per day. Seventy-seven subjects completed the study. In both treatment groups, all WOMAC symptom dimension scores were significantly reduced compared with baseline, with reductions in the final battery (total symptom score) of 41% and 59% (P = 0.0001 and P < 0.0001) in the low- and high-dose groups, respectively. In addition, improvements in total symptom score (P = 0.036) and the stiffness (P = 0.026) and physical function (P = 0.021) dimensions were significantly greater in the high-dose compared with the low-dose group. Compared to baseline, overall psychological well-being was significantly improved in both groups after treatment (P = 0.015 and P = 0.0003 in the low- and high-dose groups, respectively), and again, a significant dose-response relationship was observed. The authors conclude that bromelain may be effective in ameliorating physical symptoms and improving general well-being in otherwise healthy adults suffering from mild knee pain in a dose-dependent manner. Double-blind, placebo-controlled studies are warranted to confirm these results.
Comments by Mary L. Hardy, MD
Osteoarthritis (OA), inflammation of joints due to focal loss of articular cartilage, affects almost 70 million Americans and is a major cause of impaired mobility in women.1,2 Although the incidence of arthritis is common in both genders and increases with age, after age 55 twice as many women as men report symptoms of OA.2 This disease, often thought to be "just a natural part of aging," is irreversible and accounts for more than 70 million physician visits each year. Given the aging of the baby boomers, it should be no surprise that OA is predicted to be the fourth leading cause of disability by the year 2020.3 Pain, loss of function, and decreased activity are the main complaints of OA sufferers. Indirect morbidity related to OA could include the incidence of side effects of medications used to treat OA (i.e., gastrointestinal bleeding) and the inability to modify risk of other diseases, such as osteoporosis and heart disease, by limiting ability to exercise.
Complementary and alternative medicine (CAM) often is used to relieve chronic conditions such as OA. Approximately 22-40% of current arthritis sufferers reported using CAM for their condition.4,5,6 Women and patients with higher levels of pain were more likely to use CAM therapies. Most commonly used therapies included vitamins, supplements, and herbs.4 Any therapy that could provide symptomatic relief from OA pain and would not include the risks associated with non-steroidal medications would be of interest to OA patients and their providers. This month’s review will look at two studies of herbal therapies for OA.
The first study examines the efficacy of the herb Devil’s claw (DC), Harpagophytum procumbens, in the treatment of arthritis in patients who have also had low-back pain.7 DC is a traditional South African remedy that has been approved by the German Commission E for arthritis pain. Seventy-five patients (68% female) with hip or knee OA were enrolled in an observational study. Patients were given 2,400 mg of a DC extract standardized to 50 mg harpagoside for 12 weeks. Both the patients and their physicians were surveyed regarding the outcomes of therapy and all adverse events were recorded. A number of standardized outcomes measures were used to assess the patient’s perception of the efficacy of treatment including Western Ontario and McMaster Universities (WOMAC) scale and a 10 cm visual analogue scale (VAS) for pain. After treatment, significant decreases were recorded in the overall WOMAC scale (22.9%), as well as for specific subscales (24% pain, 22% stiffness, 23% physical function) as compared to baseline. The VAS scale also showed a similar decrease in patient-reported pain (26% actual pain and 25% average pain). The physicians noted improvement in the physical exam of patients using DC, with 45% noting less pain on palpation, 35% less limitation in mobility, and 25% less joint crepitus. The treatment was well-tolerated with only two minor adverse gastrointestinal events reported.
The main limitation of this study is its design. Open label studies provide good information about adverse events, but the efficacy of treatments may be exaggerated as none of the participants are blinded. However, these moderate effects are achieved in a relatively short trial and are accompanied by some improvement in physical signs as well as symptoms. Given the apparent safety of this product, a therapeutic trial with DC would be reasonable for OA patients who either did not want to use or could not tolerate conventional therapy.
Our second study concerns the use of bromelain, an enzyme isolated from pineapple.8 Again, in an open-label design, 70 patients with acute knee pain (71% female) were randomly assigned to be given either low-dose (200 mg/d) or high-dose (400 mg/d) bromelain for 30 days. The bromelain used was supplied by Lichtwer Pharma, but otherwise was not characterized. Outcomes were measured by using the WOMAC scale and the Psychological General Well-Being Index (PGWB), both patient-reported scales. There was no assessment made by providers in this study. Results suggested that bromelain could provide symptomatic relief for knee pain. The WOMAC score decreased significantly in both groups, although the high-dose group showed a better response (41% vs. 59%). Likewise, scores for all three WOMAC subscales (pain, stiffness, physical function) were better in the high-dose group as compared to the low-dose group. Results on the PGWB scale paralleled the results of the WOMAC. Both groups significantly improved their scores over baseline, but the high-dose group did much better than the low-dose group (P = 0.01 vs. P = 0.0003), respectively. Only minor adverse events, such as headache, flatulence, nausea, fatigue, and minor skin rash, were reported in a minority of patients.
This study is limited by its design. The observational design does not control for observer bias in reporting efficacy and therefore may exaggerate the benefits of treatment. In addition, this trial had about a 25% dropout rate, suggesting that a number of non-responders quit the trial early and therefore were not included in the analysis. There may be some limitations imposed by patient selection as well. Patients had acute, not chronic, knee pain; thus, these results may not fully predict response in OA sufferers. Despite these limitations, a useful clinical effect is suspected because of the dose-response relationship observed in this trial (i.e., the patients with a greater dose of medication reported a greater effect). The markedly positive results on psychological well-being were especially intriguing.
Clinically, how can we use these studies to guide our patients? For chronic conditions such as OA, which limit function and impair well-being, all well-tolerated therapies should be considered for patients. Along with more well-known products, such as glucosamine and chondroitin, practitioners could consider recommending DC and perhaps bromelain. For acute pain, bromelain especially should be considered. Both of these products are becoming more available in the U.S. market, and reputable suppliers have made standardized supplements that should be in local stores. Caution patients to look out for the minor side effects as noted in both groups, and if they decide to try these products, a 12-week trial is recommended at the doses mentioned in the studies.
Dr. Hardy, Associate Director, UCLA Center for Dietary Supplement Research: Botanicals Medical Director Cedars-Sinai Integrative Medicine Program Los Angeles, CA, is on the Editorial Advisory Board of Alternative Therapies in Women’s Health.
1. National Center for Health Statistics. Fast Stats: A to Z. Arthritis. Available at: www.cdc.gov/nccdphp/arthritis/index.htm. Accessed May 17, 2004.
2. MMWR reports. Prevalence of Self-Reported Arthritis or Chronic Joint Symptoms Among Adults—United States, 2001. Available at: www.cdc.gov/mmwr/preview/mmwrhtml/mm5142a2.htm. Accessed May 18, 2004.
3. MMWR reports. Public Health and Aging; Projected Prevalence of Self-Reported Arthritis of Chronic Joint Symptoms Among Persons Aged > 65 Years —United States, 2005—2030. Available at: www.cdc.gov/mmwr/preview/mmwrhtml/mm5221a1.htm. Accessed May 18, 2004.
4. Zochling J, et al. Use of complementary medicines for osteoarthritis—A prospective study. Ann Rheum Dis 2004;63:540-554.
5. Rao JK, et al. Rheumatology patients’ use of complementary therapies: Results from a one-year longitudinal study. Arthritis Rheum 2003;49:619-625.
6. Fautrel B, et al. Use of complementary and alternative therapies by patients self-reporting arthritis or rheumatism: Results from a nationwide Canadian survey J Rheumatol 2002;29:2435-2441.
7. Wegener T, Lupke NP. Treatment of patients with arthrosis of hip or knee with an aqueous extract of devil’s claw (Harpagophytum procumbens DC.). Phytother Res 2003;17:1165-1172.
8. Walker AF, et al. Bromelain reduces mild acute knee pain and improves well-being in a dose-dependent fashion in an open study of otherwise healthy adults. Phytomedicine 2002;9:681-686.