Resinous extracts of Boswellia serrata have been used for centuries for medicinal, cosmetic, and ceremonial purposes. Modern clinical research has identified boswellic acids, particularly acetyl-11-keto-beta-boswellic acid (AKBA), as key constituents responsible for the extracts' therapeutic efficacy in treating a variety of inflammatory diseases. The bioavailability may influence efficacy of the individual extracts. The most common contemporaneous use of boswellia extracts is in the treatment of osteoarthritis. This paper reviews the comparative efficacy of different formulations and dosing regimens in the treatment of osteoarthritis.
Frankincense is a resinous extract from the trees of the genus Boswellia, which are native to India and the Arabian peninsula. It has been used since antiquity in religious ceremonies and for perfume production. Its medicinal properties have been recognized and prized for millennia.1 In modern times, the pharmacological characteristics and clinical efficacy of Boswellia serrata have been studied, with research published and systematically reviewed in the medical literature.2
The main active constituents of Boswellia are the boswellic acids, most importantly acetyl-11-keto-beta-boswellic acid (AKBA). AKBA has demonstrated many significant immunomodulatory and inflammation-modulating effects in preclinical research. The best-documented action of boswellic acids is probably the inhibition of the inflammatory mediator 5-lipoxygenase.3 However, other factors such as cytokines (interleukins and TNF-α) and the complement system are likely molecular targets.4,5 AKBA also naturally inhibits NF-kappaB.6
Clinical Applications of Boswellia
A systematic review of data from randomized clinical trials shows boswellia extracts are clinically effective in asthma, rheumatoid arthritis, Crohn’s disease, osteoarthritis, and collagenous colitis.5 However, of the 47 potentially relevant studies considered, only 7 met all inclusion criteria. No serious safety issues were noted. The authors found the totality of the evidence encouraging, but not compelling, mainly due to the prevalence of methodological flaws in many studies. The heterogeneity of materials studied should also be considered. Other clinical conditions treated with oral boswellia extracts include prostatitis,7 cerebral edema,8,9 polyarthritis,10 and ulcerative colitis.11
Modern extracts of boswellia are standardized to AKBA content. The most effective extracts to date employ a standardization level of 20–30% AKBA. Although it is sometimes assumed that a higher percentage of AKBA will equate to a more efficacious product, this is not always the case, possibly due to differences in bioavailability of AKBA.
Three Studies of Boswellia for Osteoarthritis
Boswellia (30% AKBA) 100 mg/day vs 250 mg/day, 90-day study
In a randomized, double-blind, placebo-controlled clinical trial of a 30% AKBA boswellia extract (5-Loxin), researchers found that the extract significantly reduced pain and improved physical functioning in OA patients.12 Seventy-five participants received either 100 mg or 250 mg (delivering 33 mg or 75 mg AKBA, respectively) per day of boswellia extract or a matching placebo for 90 days. Each patient was evaluated for pain and physical function using the visual analog scale (VAS), Lequesne's Functional Index, and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index at baseline and at days 7, 30, 60, and 90. The cartilage-degrading enzyme matrix metalloproteinase-3 was also evaluated in synovial fluid from OA patients. Measurement was also made of several other biochemical parameters in serum and hematological parameters, and urine analyses were performed to evaluate safety of the extract. At the end of the study, both doses of boswellia extract conferred clinically and statistically significant improvements in pain scores and physical function scores in the OA patients. Significant improvements in pain score and functional ability were recorded in the treatment group supplemented with 250 mg as early as 7 days after the start of treatment. The authors also reported a significant reduction in synovial fluid MMP-3 in the treatment groups. Compared with the placebo group, the low-dose (100 mg) and high-dose (250 mg) 5-Loxin® groups showed 31.37% (P=0.002) and 46.4% (P<0.001) reductions in MMP-3 concentration, respectively. The MMP-3 level in the placebo group remained virtually unchanged at day 90 compared with baseline.
Boswellia (30% AKBA vs 20% AKBA) 100 mg/day, 90-day study
A 90-day, double-blind, randomized, placebo-controlled study was conducted to evaluate the comparative efficacy and tolerability of 2 boswellia formulations: 5-Loxin (30% AKBA) and Aflapin (also known as AprèsFlex, 20% AKBA) in patients with knee osteoarthritis.13 Sixty subjects were included in the study. The subjects received either 100 mg (n=20) of 5-Loxin or 100 mg (n=20) of Aflapin or a placebo (n=20) daily for 90 days. Each patient was evaluated for pain and physical function by using the standard tools (VAS, Lequesne's Functional Index, and WOMAC Index) at baseline and at days 7, 30, 60, and 90. A battery of biochemical parameters in serum, urine, and hematological parameters in citrated whole blood were performed to assess the safety of the 2 formulations. Both treatments conferred clinically and statistically significant improvements in pain scores and physical ability scores in OA subjects between baseline and day 90. A comparison test showed statistically significant improvements by 31.6% (P=0.006), 30.3% (P=0.009) and 42.2% (P=0.006) in VAS, WOMAC pain, and WOMAC stiffness scores, respectively, in the 100 mg 5-Loxin treated group in comparison with the placebo group. Improvements by 18.35% (P=0.060) and 21.25% (P=0.078) in LFI and WOMAC functional ability scores, respectively, were also achieved in the 5-Loxin group. In comparison with the placebo group, the Aflapin 100 mg treated group also exhibited statistically significant improvements in all parameters tested. The Aflapin group showed improvements by 47.3% (P<0.0001), 35.8% (P=0.0004), 61.7% (P<0.0001), 60.1% (P=0.0001), and 49.4% (P=0.0001) in VAS, LFI, WOMAC pain, WOMAC stiffness, and WOMAC functional ability scores, respectively. It is worth noting that both treatment groups exhibited improvement in pain scores and physical ability scores as early as 7 days after the start of treatment, and these indices continued to improve throughout the 90 days of treatment.
Boswellia (20% AKBA) 100 mg/day, 30-day study
To validate the clinical efficacy of Aflapin (AprèsFlex) in OA of the knee, a 30-day, double-blind, randomized, placebo-controlled study was conducted.14 Sixty subjects with OA of the knee were included in the study. They received either 100 mg (n=30) of Aflapin or placebo (n=30) daily for 30 days. Each subject was evaluated for pain and physical function by using the standard tools (VAS, Lequesne's Functional Index, and WOMAC Index) at baseline and at days 5, 15, and 30. A series of biochemical tests in serum, urine, and hematological parameters established the safety of the test material. Significant (P<0.05) reduction in all the pain scores was observed in the Aflapin group by day 30, when compared to the placebo group. In comparison with placebo, supplementation of Aflapin for 30 days conferred 37.6%, 32.0%, 40.1%, 41.3%, and 38.8% percent reductions in VAS, LFI, WOMAC pain, WOMAC stiffness, and WOMAC function scores, respectively. Significant (P<0.05) reductions in VAS and LFI scores were also observed in Aflapin group over placebo by day 5. Aflapin supplementation showed 14.8 and 16.3 percent better reduction in VAS and LFI scores respectively over placebo by the 5th day. Compared to the placebo group, however, the reductions in WOMAC scores were not significant after 5 days of treatment. Aflapin supplementation did produce highly significant (P<0.001) reductions in all the pain scores by Day 30, with 49.1%, 34.4%, 49.5%, 48.4%, and 45.2% reductions in VAS, LFI, WOMAC pain, WOMAC stiffness, and WOMAC function scores, respectively, compared to the baseline. Although significant (P<0.05) reductions were observed in VAS, WOMAC pain, and WOMAC function scores in placebo group as well compared to the baseline, the magnitude of the reductions was small compared to Aflapin (17.6%, 12.0%, and 9.24% respectively).
Boswellia is an ancient remedy with numerous modern clinical applications.
Dosing and Formulation
These 3 studies all demonstrate superiority of boswellia extracts standardized for AKBA content over placebo for osteoarthritis of the knee. Each study found that boswellia typically begins to exert noticeable effects within a week. The 20% AKBA formulation known as Aflapin (AprèsFlex) was somewhat faster-acting (5 days in one study) and more efficacious when compared to 30% AKBA (5-Loxin). Although a higher percent AKBA formulation would ordinarily be assumed to be more efficacious, the 20% formulation made use of a proprietary composition intended to improve the bioavailability and bioactivity of the AKBA, so less may have been required to achieve therapeutic results. The studied doses referenced above are 100 mg per day of the 20% formulation (Aflapin, AprèsFlex), or 100 to 250 mg per day of the 30% AKBA preparation (5-Loxin). These formulations appear to be as or more effective than other extracts, which have used doses ranging from 333 mg per day for OA,15 350 mg TID for asthma,16 400 mg TID for collagenous colitis,17 and up to 3.6 grams per day for Crohn’s disease18 and rheumatoid arthritis.19
There are no known major contraindications to the use of boswellia. Safety of boswellia during pregnancy has not been systematically studied and therefore cannot be recommended. Traditionally, boswellia has been used to induce menstruation and may therefore possess potential abortifacient effects.20
Boswellia is generally regarded as safe when used as directed, although there is a lack of systematic research on safety and toxicity in humans. Adverse events were not seen after oral administration of a single 333 mg dose of Boswellia serrata to healthy volunteers21 or in pediatric cancer patients taking 126 mg/kg of H15® daily for a median of 9 months.9
The most common adverse effects in trials have been gastrointestinal, including nausea, epigastric pain, diarrhea, and acid reflux.11,13,16, 22–24
Boswellia is an ancient remedy with numerous modern clinical applications. Extracts of the gum resin with 20% to 30% AKBA represent viable alternative treatments of osteoarthritis. Boswellia extract is also a promising treatment for other inflammatory conditions, including asthma, rheumatoid arthritis, and cerebral edema. Further research is needed to adequately assess its efficacy for these applications.
Conflict of Interest Disclosure
The author is an employee of a company that manufactures products containing ingredients discussed in this article.