Boswellia serrata for Inflammatory Conditions
By Robert Alan Bonakdar, MD, DAAPM, David C. Leopold, MD, DAAPM, and Danielle Weiss, MD Dr. Bonakdar is Director of Pain Management and Dr. Leopold is Director of Integrative Medical Education, Scripps Center for Integrative Medicine; and Dr. Weiss is in the Scripps Mercy Hospital Residency Program, San Diego, CA; they report no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study.
Botanicals with anti-inflammatory properties in the form of polysaccharides, terpenes, curcuminoids, and alkaloids are becoming increasingly prevalent in today's tumultuous nonsteroidal anti-inflammatory drug (NSAID) market. With increasing concern regarding the safety and availability of NSAIDs, greater attention is being placed on these unique anti-inflammatories derived from various plant sources.1 The use of such anti-inflammatory compounds as Boswellia serrata has been a mainstay of several medical systems for hundred of years in the treatment of inflammatory conditions. Because of this renewed interest, boswellia has been the focus of recent basic and clinical research in an attempt to ascertain its anti-inflammatory actions and role in modern therapeutic interventions.
Historically, the boswellia trees of Asia have been utilized within Ayurvedic and Chinese medicine for various conditions, typically employed for their anti-inflammatory and antimicrobial properties. The most common form of boswellia, Boswellia serrata (also known as sallai guggal, boswellin, and Indian frankincense) has been harvested for its sap, or oleoresin. The oleoresin is purified to the herbal preparation containing boswellic acid (BA) and utilized within Ayurvedic medicine to treat a number of conditions including arthritis, asthma, and colitis.
The form of boswellia utilized varies considerably and depends on its intended use. The most dilute form of boswellia oils, known as olibanum and typically containing < 1% BA, is used as a food fixative, fragrance, and in cosmetic applications including lotions and skin toners. Other topical applications containing higher levels of BA have been used for the treatment of acne, skin infections, and wounds. Oral formulations, including powders, tablets, and teas are most commonly used for pain and inflammatory disorders including dysmenorrhea, colitis, and rheumatic conditions. In its ceremonial role, boswellia has been burned as incense during religious rituals to increase spiritual awareness and consciousness.
Constituents and Mechanism of Action
The gum oleoresin of boswellia contains essential oils, gums, and terpenoids. The terpenoid portion contains the boswellic acids that have been shown to be the most active constituents. Today, extracts are typically standardized to contain 30-65% boswellic acids and dosed at 100-400 mg orally per day. Fractionation of the oleogum resin of boswellia has resulted in the isolation and identification of terpenoids including lupeol, beta-boswellic acid, 11-keto-beta-boswellic acid (KBA), acetyl beta-boswellic acid, acetyl 11-keto-beta-boswellic acid (AKBA), acetyl-alpha-boswellic acid, 3-oxo-tirucallic acid, and 3-hydroxy-tirucallic acid. Of note, the unfractionated resin has been found to be more bioactive than any of the individual purified compounds.2 The KBAs and AKBAs are typically thought of as the most potent anti-inflammatory constituents, although this has not been definitively demonstrated. The half-life of boswellia has been shown in one study to be approximately six hours. With ideal dosing at this interval, the plasma concentration reaches steady state after approximately 30 hours.3
Boswellia's anti-inflammatory properties have been the most extensive area of mechanistic study. The gum resin-derived boswellic acids inhibit leukotriene biosynthesis in neutrophils and human platelets by a non-redox, noncompetitive inhibition of 5-lipoxygenase.4 This is of key importance with our knowledge of chronic inflammatory diseases perpetuated by leukotriene upregulation. A recent study found that inflammation caused by TNF-alpha induction of metalloproteinases and adhesion molecules (VCAM-1 and ICAM-1) is significantly inhibited by boswellia.5
Boswellia also possesses certain properties that may make it a potential therapeutic agent in the setting of autoimmune disorders, cancer, asthma, and organ transplant. Boswellia's disease-modifying effects are exemplified by a decrease in glycosaminoglycan degradation in the animal model.6 In vitro immunomodulatory activities have been noted, including a decrease in the production of mast cells, antibodies, and cell-mediated immunity.7 Prevention of organ transplant rejection has been demonstrated by a reduction of ischemia and reperfusion injury similar in extent to steroid therapy.8 Lastly, boswellic acids, particularly AKBA and KBA, have demonstrated antiproliferative and apoptotic effects in human colon cancer cells.9
Clinical Studies
Boswellia has been studied most rigorously for its action in asthma as well as rheumatic and inflammatory bowel conditions including rheumatoid arthritis (RA), osteoarthritis (OA), Crohn's disease, and ulcerative colitis.
Asthma. Gupta et al performed a randomized, controlled trial of 80 patients with chronic stable asthma.10 Following six weeks of therapy there were significant improvements in 70% of patients on active therapy. Specifically, the boswellia group demonstrated significant improvements in several diagnostic parameters, including forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). In addition, there were improvements noted in asthma symptomatology including wheezing and dyspnea as well as the number of asthma exacerbations (P < 0.0001) vs. placebo. Of note, there were significant differences at baseline noted between groups, making some of the results difficult to interpret.
Joint Disease. For treatment of OA, two randomized double-blind placebo-controlled cross-over trials have been performed. Kulkarni et al randomized 42 patients with OA to three months of placebo or a combination product (Articulin F) containing 50 mg of Boswellia serrata as well as turmeric (Curcuma longa), ashwagandha (Withania somnifera), and zinc.11 Active treatment with the boswellia complex led to statistically significant improvements in overall disability and level of pain. However, trends for improvement in other areas including joint scores and morning stiffness did not reach significance.
The second study by Kimmatkar et al randomized 30 patients with knee OA to eight weeks of a Boswellia serrata extract and found significant improvements in knee pain, knee mobility, and walking distance compared to placebo.12 Although both trials are promising, because of the use of combination products in the first and lack of discussion of randomization process in both, it is difficult to reach firm conclusions regarding the benefit of boswellia in OA.
Regarding treatment of RA, several trials have attempted to elucidate boswellia's effects as a therapeutic agent. Sander et al randomized 37 patients to a standardized boswellia extract (H15) at 3600 mg/d vs. placebo.13 The trial, which lasted l2 weeks, failed to demonstrate any significant difference in pain or functional ability. Unfortunately, this trial suffered from a large drop-out rate and lack of discussion of the population size or its effect on the power calculation, thus making it difficult to discern whether lack of benefit was true or due to the small sample size.
Etzel attempted to summarize the results of 11 unpublished trials on the use of boswellia for RA between 1985 and 1990.14 These trials, which included more than 260 patients, varied greatly from open to randomized trials. The results demonstrated a trend toward reduction in joint swelling and stiffness as well as NSAID intake with no significance in other areas. However, because of minimal descriptors regarding the population and parameter's measured, the importance of these trialsother than demonstrating a minimal side effect profile in trials of 1-6 months durationis unclear.
Two additional placebo-controlled trials for treatment of RA, both utilizing combination products, have been published. In a small double-blind placebo-controlled crossover trial of 20 patients by Kulkarni, Articulin F (described above) was utilized for 12 weeks vs. placebo.15 Results of this trial were impressive in that the active group reported improvement in all areas of disability and pain measured vs. placebo. In addition, a significantly smaller number of patients on active treatment required rescue NSAID therapy. Benefit in this trial began after two weeks, which is important to keep in mind when discussing treatment with boswellia with patients. A second trial by Chopra et al, and likely the best quality study performed on boswellia, examined RA-1 (Boswellia serrata, turmeric [Curcuma longa], ashwagandha [Withania somnifera], and ginger [Zingiber officinale]) in 182 patients for 16 weeks.16 In this trial, there were statistically significant improvements seen in the majority of parameters measured, including the numbers of swollen joints, rheumatoid factor improvement, and improvement in the American College of Rheumatology joint assessment score (ACR-20). Of note, this trial suffered from a high placebo response, which may have diminished potential benefits seen with active therapy. Also, both of these trials demonstrated a significant decrease in rheumatoid factor vs. placebo. Again, because of the use of combination products, the exact contribution of boswellia in these trials cannot be estimated.
Gastrointestinal disease. Gerhardt et al examined a standardized Boswellia serrata extract (H15) vs. mesalazine in 102 patients with active Crohn's disease.17 The trial was eight weeks long and examined 1200 mg of H15 vs. 1.5 g of mesalazine taken three times daily and examined improvement in symptoms as noted on the Crohn's disease Activity Index (CDAI). At trial's end, improvements were identified in both groups with no significant difference noted between groups on the CDAI, with the authors concluding relative equivalence between therapies. There were several weaknesses in the trial including lack of an intent-to-treat analysis and a drop-out rate of 20%.
For the treatment of ulcerative colitis (UC), Gupta et al examined boswellia extract (n = 20) and sulfasalazine (n = 10).18 Although a greater percentage of boswellia-treated patients improved in comparison to sulfasalazine, it is difficult to interpret these results due to non-blinding. Sigmoidoscopy examination demonstrated histological benefit in a significantly greater percentage of boswellia subjects at the end of the trial. A second trial on ulcerative colitis treated 42 patients with boswellia vs. sulfasalazine.19 The results of this non-blinded trial demonstrated similar benefit in both groups with a conclusion of bioequivalence between the therapies. These results include an approximate 75% improvement on histological biopsy obtained on sigmoidoscopy. However, comparisons between groups in this study are nearly possible to make as there was no randomization and subjects were able to decide their treatment group at enrollment.
Safety
Boswellia's safety has been established in animal studies in doses up to 2g/kg.20 In humans, boswellia appears safe in most clinical scenarios and, unlike NSAIDS, has not been linked to any serious side effects including gastrointestinal bleeding or ulceration, kidney function impairment, or cardiovascular sequelae in studies up to six months in length. However, no long-term studies specifically focusing on these issues have been carried out. Boswellia is well-tolerated with the most common side effect reported as gastrointestinal upset including epigastric pain, heartburn, nausea, and diarrhea. Dermatitis, a rare side effect, has been reported.21 Although boswellia is used in dilute doses as an additive, it should not be used during pregnancy because of the potential to induce menstruation or abortion.22 Use during breast feeding or in pediatrics has not been studied systematically. Because of boswellia's actions in decreasing glucosaminoglycan degradation, its potential synergistic role in the treatment of degenerative arthritis with supplements typically utilized in this scenario, such as glucosamine or chondroitin, is intriguing and deserves further study.
Conclusion
Debate over the use and side effect profile of available prescription and over-the-counter NSAIDs will continue to complicate clinical decision-making regarding such therapy. In addition, this debate has created greater interest in the potential use of various phyto-anti-inflammatories which may work adjunctively with or as a replacement for NSAIDs. Among the most popular choices currently available is boswellia, which has a long tradition of use for the treatment of inflammatory conditions.
Boswellia's mechanistic background as an inhibitor of a number of key inflammatory markers (most importantly leukotrienes) provides a strong theoretic rationale for potential incorporation in the treatment of several inflammatory conditions. From a safety standpoint, boswellia has a benign side effect profile, which provides additional support for use, especially in populations that cannot tolerate NSAID therapy or require adjunctive support. From a clinical perspective, the available data range from poorly controlled observational data to an occasional well-controlled clinical trial. These studies provide supportive subjective trends and in some cases statistically significant objective data, namely, decreased rheumatoid factor (RA) and tissue improvement on biopsy (UC). Overall, boswellia therapy appears promising and may prove to be an attractive adjunct or alternative for the treatment of selected inflammatory conditions while awaiting future trials.
Recommendation
Additional studies are warranted to examine the long-term safety and benefit of boswellia for the conditions noted above. Of note, studies comparing the efficacy of boswellia vs. combination therapy and conventional therapy are needed to better understand boswellia's role in treatment of inflammatory conditions. Because of boswellia's synergistic role with glucosaminoglycan-based therapies (i.e., glucosamine), clinical trials that examine their potential effects in combination are desired. Future trials should also be explicit in their discussion of the type of boswellia used, standardization and parameters of use. Additional trials with adequate power calculations and appropriate subject size are needed to make definitive conclusions regarding efficacy and equivalence to conventional therapy.
Because of boswellia's low side effect profile and potential anti-inflammatory properties, clinicians are advised to discuss its potential incorporation in the treatment of inflammatory conditions mentioned above. Attention should be especially focused on patients with refractory conditions or those who would benefit from medication reduction due to side effects. Clinicians should be familiar with available brands and, whenever possible, recommend those that have been clinically tested. Use should be monitored on a regular basis, similar to other anti-inflammatories, to ensure tolerability and to check for potential clinical improvement based on standardized subjective and objective measures.
References
1. Darshan S, Doreswamy R. Patented antiinflammatory plant drug development from traditional medicine. Phytother Res 2004;18:343-357.
2. Badria FA, et al. Immunomodulatory triterpenoids from the oleogum resin of Boswellia carterii Birdwood. Z Naturforsch [C] 2003;58:505-516.
3. Sharma S, et al. Pharmacokinetic study of 11-Keto beta-Boswellic acid. Phytomedicine 2004;11:255-260.
4. Ammon HP. Boswellic acids (components of frankincense) as the active principle in treatment of chronic inflammatory diseases. Wien Med Wochenschr 2002; 152:373-378.
5. Roy S, et al. Human genome screen to identify the genetic basis of the anti-inflammatory effects of Boswellia in microvascular endothelial cells. DNA Cell Biol 2005;24:244-255.
6. Reddy GK, et al. Studies on the metabolism of glycosaminoglycans under the influence of new herbal anti-inflammatory agents. Biochem Pharmacol 1989; 38:3527-3534.
7. Pungle P, et al. Immunomodulatory activity of boswellic acids of
Boswellia serrata Roxb. Indian
J Exp Biol 2003;41:1460-1462.
8. Dahmen U, et al. Boswellic acid, a potent antiinflammatory drug, inhibits rejection to the same extent as high dose steroids. Transplant Proc 2001;33:539-541.
9. Liu JJ, et al. Boswellic acids trigger apoptosis via a pathway dependent on caspase-8 activation but independent on Fas/Fas ligand interaction in colon cancer HT-29 cells. Carcinogenesis 2002;23:2087-2093.
10. Gupta I, et al. Effects of Boswellia serrata gum resin in patients with bronchial asthma: Results of a double-blind, placebo-controlled, 6-week clinical study. Eur J Med Res 1998;3:511-514.
11. Kulkarni RR, et al. Treatment of osteoarthritis with herbomineral formulation: A double-blind, placebo-controlled, cross-over study. J Ethnopharmacol 1991; 33:91-95.
12. Kimmatkar N, et al. Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of kneea randomized double blind placebo controlled trial. Phytomedicine 2003;10:3-7
13. Sander O, et al. Is H15 (resin extract of Boswellia serrata, "incense") a useful supplement to established drug therapy of chronic polyarthritis? Results of a double-blind pilot study. Z Rheumatol 1998;57:11-16.
14. Etzel R. Special extract of Boswellia serrata (H15) in the treatment of rheumatoid arthritis. Phytomedicine 1996;3:91-94.
15. Kulkarni RR, et al. Efficacy of an Ayurvedic formulation in rheumatoid arthritis: A double-blind, placebo-controlled, cross-over study. Indian J Pharm 1992;24:98-101.
16. Chopra A, et al. Randomized double blind trial of an ayurvedic plant derived formulation for treatment of rheumatoid arthritis. J Rheumatol 2000;27:1365-1372.
17. Gerhardt H, et al. Therapy of active Crohn disease with Boswellia serrata extract H 15. Z Gastroenterol 2001;39:11-17.
18. Gupta I, et al. Effects of gum resin of Boswellia serrata in patients with chronic colitis. Planta Med 2001;67: 391-395.
19. Gupta I, et al. Effects of Boswellia serrata gum resin in patients with ulcerative colitis. Eur J Med Res 1997;2:37-43.
20. Singh GB, et al. Toxicity and safety evaluation of boswellic acids. Phytomedicine 1996;3:87-90.
21. Acebo E, et al. Allergic contact dermatitis from Boswellia serrata extract in a naturopathic cream. Contact Dermatitis 2004;51:91-2.
22. Kamboj VP. A review of Indian medicinal plants with interceptive activity. Indian J Med Res 1988; 87:336-355.
Bonakdar RA, Leopold DC, Weiss D. Bosewllia serrata for inflammatory conditions. Altern Med Alert 2005;8(10):114-118.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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