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Ayurvedic medicine: It is “time” for scientifically sound studies
Ayurvedic Medicine: It Is “Time” for Scientifically Sound Studies Dinesh Khanna, MD, MS
A
yurveda translates into knowledge (Veda) of life (Ayur) (1) and is one of the oldest and still widely practiced medical systems in the Indian subcontinent (2). The concept of Ayurvedic medicine is to promote health, rather than to fight disease, and Ayurveda in daily life aims at maintaining harmony between nature and the “individual” to ensure optimal health (1). Appropriate food, sleep, and sexual activity are three pillars of good health, with emphasis on personal hygiene, massage, and exercise. The disruption of this harmony leads to disease, and reversal of the steps that produce disease is the main therapeutic approach. Individualized treatment regimens include fasting, massages, and/or Ayurvedic medicines (both herbs and mineral compounds) to restore the harmony with nature (1). Most of the Ayurveda practiced outside the Indian subcontinent consists of the use of herbal medications. Use of selfprescribed herbal medications in the US general population is on the rise, from about 2.5% in 1990 to 12.7% in 1997 (3). Use of herbal medicines is much higher in patients with chronic arthritides (44% in a recent survey in the UK) (4) and this may be due to absence of an effective “cure” for chronic diseases using conventional allopathic medications (especially true for autoimmune diseases), perceived safety of the herbs, and potential control over one’s own treatment (5,6). Many modern medications have originated from the plantbased formulations; salicylates, digoxin, and colchicine are a few examples. When tested in a well-designed, randomized controlled trial (RCT), herbs have been found to be both effective (7-10) and ineffective (11,12), results accepted by the physicians in the Western world, and RCTs published in premier medical journals. For example, Maharishi Vedic Medicine, a multimodal, comprehensive Ayurvedic approach, which includes meditation, herbs, and exercise, resulted in significant decrease in the carotid intima-media thickness, a measure of peripheral atherosclerosis compared with physician prescribed dietary, exercise, and multivitamin
Division of Rheumatology, Department of Medicine, David Geffen School of Medicine, Los Angeles, CA. Address correspondence and reprint requests to: Dinesh Khanna, MD, Division of Rheumatology, Department of Medicine, David Geffen School of Medicine, Los Angeles, CA 90085. E-mail: [email protected]
0049-0172/05/$-see front matter © 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.semarthrit.2004.11.002
approach in a 1-year RCT conducted in the US (8). In another RCT in African Americans, stress reduction obtained through Transcendental Meditation, an integral part of Maharishi Vedic Medicine, was compared against a nonpharmacological, cardiovascular disease risk factor prevention education program (13). After an average intervention period of 6.8 ⫾ 1.3 months, the meditation group had a statistically significant decrease in their carotid intima-media thickness compared with the control population. However, claims of effectiveness of herbs are limited to anecdotal reports and personal experiences. These claims do little justice when the “science” of the herb is unknown, and herb use can result in potential toxicity and drug– herb interactions. Appropriate skepticism, hesitancy, and fear regarding prescribing and use of herbs is widespread among physicians (14,15). Samples from different herbal medicines have shown adulteration with toxins and conventional medications causing toxicities (16-18). The same herb marketed by different companies has shown high variability in the content of the herb (19-21). The current publication by Amarasinghe and coworkers in the Seminars reviews the RCTs on the efficacy of Ayurvedic medicine in rheumatoid arthritis (RA). Their meta-analysis is limited to the herbal medicinal aspect of Ayurveda and omits the other aspects of Ayurveda. Their extensive literature search for RA trials evaluating either Ayurvedic medications against placebo or other Ayurvedic medicines yielded 7 RCTs. Of the 7 trials, 3 were placebo controlled, and 4 compared one Ayurvedic medicine against another. Only 1 article (22) was considered of high quality as assessed by the Jaded score and the rest of the 6 were of poor quality. A study by Chopra and coworkers (22) compared a standardized formulation of an Ayurvedic medicine (RA-1) against placebo in double-blind RCT. The primary end points were the proportion of patients achieving American College of Rheumatology (ACR) 20 and 50% improvement response for individual core set variables, and an ACR 20% composite response. At the end of 16 weeks (primary endpoint), the responses for individual core set variables and ACR 20% response were numerically but not statistically higher in the Ayurvedic treatment group. The other 6 studies had flawed study design, analysis, and reporting of the results. 703
704 In conclusion, herbs must undergo the same strict guidelines for drug standardization reserved for conventional medications. Well-designed safety and toxicity studies must be conducted in animal models for arthritis, especially for multicomponent herbs. Well-designed RCT assessing the concept of the Ayurveda including herbal preparations, meditation, and Yoga (an integral part of Ayurveda) (1), not just the herbal aspect, should be conducted. Two recent RCTs have shown a beneficial effect of these modalities over conventional treatment on the carotid intima-media thickness (8,13). In addition to standardization of the herbal formulations, the trials should be conducted in a scientific and ethical manner. For example, all trials in RA should have an anti-rheumatic agent as the background therapy and poor responders can be randomized to either medication or placebo. Radiographs should be a part of these studies to evaluate for any disease-modifying effects of these herbs. Better, trials assessing the “complete” Ayurveda against conventional allopathic treatment for RA should be conducted. As stated by the authors, international collaboration could be one of the avenues to design future methodologically sound clinical trials. Such an effort has already been undertaken by the National Institutes of Health. A double-blind, randomized pilot study comparing Ayurvedic treatment for RA (consisting of specific diet, standardized herbal medications, oil massages, and enemas) with background weekly placebo pills, non-Ayurvedic treatment (consisting of different diet, herbal medications, oil massages, and enemas as compared with Ayurvedic treatment for arthritis) with background weekly methotrexate, and Ayurvedic arthritis treatment with background weekly methotrexate is underway in India. A total of 45 active RA subjects will be randomized into a 1:1:1 ratio for a period of 1 year. This study will have a blinded joint count assessor and ACR 20% improvement response criteria will be the primary outcome (personal communication, Daniel Furst).
References 1. Chopra A, Doiphode VV. Ayurvedic medicine. Core concept, therapeutic principles, and current relevance. Med Clin North Am 2002;86(1): 75-89, vii. 2. Ulrich-Merzenich G, Kraft K, Singh LM. Rheumatic diseases in Ayurveda: a historical perspective. Arthritis Rheum 1999; 42(7):1553-5.
D. Khanna 3. Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M, et al. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA 1998;280(18):1569-75. 4. Walsh N. Mixed herbs and drugs: A dangerous recipe. Int Med News 2004;24. 5. Ernst E, Pittler MH. Herbal medicine. Med Clin North Am 2002;86(1): 149-61. 6. Astin JA. Why patients use alternative medicine: results of a national study. JAMA 1998;279(19):1548-53. 7. Altman RD, Marcussen KC. Effects of a ginger extract on knee pain in patients with osteoarthritis. Arthritis Rheum 2001;44(11):2531-8. 8. Fields JZ, Walton KG, Schneider RH, Nidich S, Pomerantz R, Suchdev P, et al. Effect of a multimodality natural medicine program on carotid atherosclerosis in older subjects: a pilot trial of Maharishi Vedic Medicine. Am J Cardiol 2002;89(8):952-8. 9. Pittler MH, Ernst E. Ginkgo biloba extract for the treatment of intermittent claudication: a meta-analysis of randomized trials. Am J Med 2000;108(4):276-81. 10. Pittler MH, Schmidt K, Ernst E. Hawthorn extract for treating chronic heart failure: meta-analysis of randomized trials. Am J Med 2003;114(8):665-74. 11. Pittler MH, Abbot NC, Harkness EF, Ernst E. Randomized, doubleblind trial of chitosan for body weight reduction. Eur J Clin Nutr 1999;53(5):379-81. 12. Pittler MH, Ernst E. Feverfew for preventing migraine. Cochrane Database Syst Rev 2004;(1):CD002286. 13. Castillo-Richmond A, Schneider RH, Alexander CN, Cook R, Myers H, Nidich S, et al. Effects of stress reduction on carotid atherosclerosis in hypertensive African Americans. Stroke 2000;31(3):568-73. 14. Angell M, Kassirer JP. Alternative medicine—the risks of untested and unregulated remedies. N Engl J Med 1998;339(12):839-41. 15. Talalay P, Talalay P. The importance of using scientific principles in the development of medicinal agents from plants. Acad Med 2001;76(3): 238-47. 16. Hullar TE, Sapers BL, Ridker PM, Jenkins RL, Huth TS, Farraye FA. Herbal toxicity and fatal hepatic failure. Am J Med 1999;106(2): 267-8. 17. Harada T, Ohtaki E, Misu K, Sumiyoshi T, Hosoda S. Congestive heart failure caused by digitalis toxicity in an elderly man taking a licoricecontaining Chinese herbal laxative. Cardiology 2002;98(4):218. 18. Huang WF, Wen KC, Hsiao ML. Adulteration by synthetic therapeutic substances of traditional Chinese medicines in Taiwan. J Clin Pharmacol 1997;37(4):344-50. 19. los Reyes GC, Koda RT. Determining hyperforin and hypericin content in eight brands of St. John’s wort. Am J Health Syst Pharm 2002;59(6): 545-7. 20. Draves AH, Walker SE. Analysis of the hypericin and pseudohypericin content of commercially available St John’s Wort preparations. Can J Clin Pharmacol 2003;10(3):114-8. 21. Nelson MH, Cobb SE, Shelton J. Variations in parthenolide content and daily dose of feverfew products. Am J Health Syst Pharm 2002;59(16): 1527-31. 22. Chopra A, Lavin P, Patwardhan B, Chitre D. Randomized double blind trial of an ayurvedic plant derived formulation for treatment of rheumatoid arthritis. J Rheumatol 2000;27(6):1365-72.
A
yurveda translates into knowledge (Veda) of life (Ayur) (1) and is one of the oldest and still widely practiced medical systems in the Indian subcontinent (2). The concept of Ayurvedic medicine is to promote health, rather than to fight disease, and Ayurveda in daily life aims at maintaining harmony between nature and the “individual” to ensure optimal health (1). Appropriate food, sleep, and sexual activity are three pillars of good health, with emphasis on personal hygiene, massage, and exercise. The disruption of this harmony leads to disease, and reversal of the steps that produce disease is the main therapeutic approach. Individualized treatment regimens include fasting, massages, and/or Ayurvedic medicines (both herbs and mineral compounds) to restore the harmony with nature (1). Most of the Ayurveda practiced outside the Indian subcontinent consists of the use of herbal medications. Use of selfprescribed herbal medications in the US general population is on the rise, from about 2.5% in 1990 to 12.7% in 1997 (3). Use of herbal medicines is much higher in patients with chronic arthritides (44% in a recent survey in the UK) (4) and this may be due to absence of an effective “cure” for chronic diseases using conventional allopathic medications (especially true for autoimmune diseases), perceived safety of the herbs, and potential control over one’s own treatment (5,6). Many modern medications have originated from the plantbased formulations; salicylates, digoxin, and colchicine are a few examples. When tested in a well-designed, randomized controlled trial (RCT), herbs have been found to be both effective (7-10) and ineffective (11,12), results accepted by the physicians in the Western world, and RCTs published in premier medical journals. For example, Maharishi Vedic Medicine, a multimodal, comprehensive Ayurvedic approach, which includes meditation, herbs, and exercise, resulted in significant decrease in the carotid intima-media thickness, a measure of peripheral atherosclerosis compared with physician prescribed dietary, exercise, and multivitamin
Division of Rheumatology, Department of Medicine, David Geffen School of Medicine, Los Angeles, CA. Address correspondence and reprint requests to: Dinesh Khanna, MD, Division of Rheumatology, Department of Medicine, David Geffen School of Medicine, Los Angeles, CA 90085. E-mail: [email protected]
0049-0172/05/$-see front matter © 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.semarthrit.2004.11.002
approach in a 1-year RCT conducted in the US (8). In another RCT in African Americans, stress reduction obtained through Transcendental Meditation, an integral part of Maharishi Vedic Medicine, was compared against a nonpharmacological, cardiovascular disease risk factor prevention education program (13). After an average intervention period of 6.8 ⫾ 1.3 months, the meditation group had a statistically significant decrease in their carotid intima-media thickness compared with the control population. However, claims of effectiveness of herbs are limited to anecdotal reports and personal experiences. These claims do little justice when the “science” of the herb is unknown, and herb use can result in potential toxicity and drug– herb interactions. Appropriate skepticism, hesitancy, and fear regarding prescribing and use of herbs is widespread among physicians (14,15). Samples from different herbal medicines have shown adulteration with toxins and conventional medications causing toxicities (16-18). The same herb marketed by different companies has shown high variability in the content of the herb (19-21). The current publication by Amarasinghe and coworkers in the Seminars reviews the RCTs on the efficacy of Ayurvedic medicine in rheumatoid arthritis (RA). Their meta-analysis is limited to the herbal medicinal aspect of Ayurveda and omits the other aspects of Ayurveda. Their extensive literature search for RA trials evaluating either Ayurvedic medications against placebo or other Ayurvedic medicines yielded 7 RCTs. Of the 7 trials, 3 were placebo controlled, and 4 compared one Ayurvedic medicine against another. Only 1 article (22) was considered of high quality as assessed by the Jaded score and the rest of the 6 were of poor quality. A study by Chopra and coworkers (22) compared a standardized formulation of an Ayurvedic medicine (RA-1) against placebo in double-blind RCT. The primary end points were the proportion of patients achieving American College of Rheumatology (ACR) 20 and 50% improvement response for individual core set variables, and an ACR 20% composite response. At the end of 16 weeks (primary endpoint), the responses for individual core set variables and ACR 20% response were numerically but not statistically higher in the Ayurvedic treatment group. The other 6 studies had flawed study design, analysis, and reporting of the results. 703
704 In conclusion, herbs must undergo the same strict guidelines for drug standardization reserved for conventional medications. Well-designed safety and toxicity studies must be conducted in animal models for arthritis, especially for multicomponent herbs. Well-designed RCT assessing the concept of the Ayurveda including herbal preparations, meditation, and Yoga (an integral part of Ayurveda) (1), not just the herbal aspect, should be conducted. Two recent RCTs have shown a beneficial effect of these modalities over conventional treatment on the carotid intima-media thickness (8,13). In addition to standardization of the herbal formulations, the trials should be conducted in a scientific and ethical manner. For example, all trials in RA should have an anti-rheumatic agent as the background therapy and poor responders can be randomized to either medication or placebo. Radiographs should be a part of these studies to evaluate for any disease-modifying effects of these herbs. Better, trials assessing the “complete” Ayurveda against conventional allopathic treatment for RA should be conducted. As stated by the authors, international collaboration could be one of the avenues to design future methodologically sound clinical trials. Such an effort has already been undertaken by the National Institutes of Health. A double-blind, randomized pilot study comparing Ayurvedic treatment for RA (consisting of specific diet, standardized herbal medications, oil massages, and enemas) with background weekly placebo pills, non-Ayurvedic treatment (consisting of different diet, herbal medications, oil massages, and enemas as compared with Ayurvedic treatment for arthritis) with background weekly methotrexate, and Ayurvedic arthritis treatment with background weekly methotrexate is underway in India. A total of 45 active RA subjects will be randomized into a 1:1:1 ratio for a period of 1 year. This study will have a blinded joint count assessor and ACR 20% improvement response criteria will be the primary outcome (personal communication, Daniel Furst).
References 1. Chopra A, Doiphode VV. Ayurvedic medicine. Core concept, therapeutic principles, and current relevance. Med Clin North Am 2002;86(1): 75-89, vii. 2. Ulrich-Merzenich G, Kraft K, Singh LM. Rheumatic diseases in Ayurveda: a historical perspective. Arthritis Rheum 1999; 42(7):1553-5.
D. Khanna 3. Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M, et al. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA 1998;280(18):1569-75. 4. Walsh N. Mixed herbs and drugs: A dangerous recipe. Int Med News 2004;24. 5. Ernst E, Pittler MH. Herbal medicine. Med Clin North Am 2002;86(1): 149-61. 6. Astin JA. Why patients use alternative medicine: results of a national study. JAMA 1998;279(19):1548-53. 7. Altman RD, Marcussen KC. Effects of a ginger extract on knee pain in patients with osteoarthritis. Arthritis Rheum 2001;44(11):2531-8. 8. Fields JZ, Walton KG, Schneider RH, Nidich S, Pomerantz R, Suchdev P, et al. Effect of a multimodality natural medicine program on carotid atherosclerosis in older subjects: a pilot trial of Maharishi Vedic Medicine. Am J Cardiol 2002;89(8):952-8. 9. Pittler MH, Ernst E. Ginkgo biloba extract for the treatment of intermittent claudication: a meta-analysis of randomized trials. Am J Med 2000;108(4):276-81. 10. Pittler MH, Schmidt K, Ernst E. Hawthorn extract for treating chronic heart failure: meta-analysis of randomized trials. Am J Med 2003;114(8):665-74. 11. Pittler MH, Abbot NC, Harkness EF, Ernst E. Randomized, doubleblind trial of chitosan for body weight reduction. Eur J Clin Nutr 1999;53(5):379-81. 12. Pittler MH, Ernst E. Feverfew for preventing migraine. Cochrane Database Syst Rev 2004;(1):CD002286. 13. Castillo-Richmond A, Schneider RH, Alexander CN, Cook R, Myers H, Nidich S, et al. Effects of stress reduction on carotid atherosclerosis in hypertensive African Americans. Stroke 2000;31(3):568-73. 14. Angell M, Kassirer JP. Alternative medicine—the risks of untested and unregulated remedies. N Engl J Med 1998;339(12):839-41. 15. Talalay P, Talalay P. The importance of using scientific principles in the development of medicinal agents from plants. Acad Med 2001;76(3): 238-47. 16. Hullar TE, Sapers BL, Ridker PM, Jenkins RL, Huth TS, Farraye FA. Herbal toxicity and fatal hepatic failure. Am J Med 1999;106(2): 267-8. 17. Harada T, Ohtaki E, Misu K, Sumiyoshi T, Hosoda S. Congestive heart failure caused by digitalis toxicity in an elderly man taking a licoricecontaining Chinese herbal laxative. Cardiology 2002;98(4):218. 18. Huang WF, Wen KC, Hsiao ML. Adulteration by synthetic therapeutic substances of traditional Chinese medicines in Taiwan. J Clin Pharmacol 1997;37(4):344-50. 19. los Reyes GC, Koda RT. Determining hyperforin and hypericin content in eight brands of St. John’s wort. Am J Health Syst Pharm 2002;59(6): 545-7. 20. Draves AH, Walker SE. Analysis of the hypericin and pseudohypericin content of commercially available St John’s Wort preparations. Can J Clin Pharmacol 2003;10(3):114-8. 21. Nelson MH, Cobb SE, Shelton J. Variations in parthenolide content and daily dose of feverfew products. Am J Health Syst Pharm 2002;59(16): 1527-31. 22. Chopra A, Lavin P, Patwardhan B, Chitre D. Randomized double blind trial of an ayurvedic plant derived formulation for treatment of rheumatoid arthritis. J Rheumatol 2000;27(6):1365-72.