INDEX

Frankincense (Boswellia serrata)

Indications

Musculoskeletal pain and inflammation, including bursitis, cervical spondylosis, tendonitis, osteoarthritis, and rheumatoid arthritis; and traumatic injuries, strains, sprains, and bruising.

Mechanism of Action

Many of the anti-inflammatory actions of Boswellia are credited to the tetra- and pentacyclic terpenoids called boswellic acids including β-boswellic acid and the triterpene acids acetyl-β-boswellic acid, 11-keto-β-boswellic acid, and acetyl-11-keto-β-boswellic acid (also known as tircuallic, lupeolic, and roburic acids). Out of these four boswellic acids, acetyl-11-keto-β-boswellic acid (AKBA) is the most potent inhibitor of 5-lipoxygenase, an enzyme responsible for inflammation.1 Boswellia gum also contains the essential oils α-thujene and p-cymene.

Boswellia acts by many of the same mechanisms as pharmaceutical nonsteroidal anti-inflammatory drugs (NSAIDs); however, the pharmaceuticals impair glycosaminoglycan synthesis, can induce digestive ulcers, and accelerate joint damage in arthritis, whereas boswellic acids have been shown to significantly reduce glycosaminoglycan degradation.2 Consequently, long-term use of Boswellia does not lead to irritation or ulceration of the stomach. Recent studies also suggest that boswellic acids exert significant anticancer, antimicrobial, and immune-potentiating effects.

Many types of proinflammatory processes are associated with an increase in leukotrienes that contributes to chemotaxis, chemokinesis, and the synthesis and release of superoxide radicals and the release of lysosomal enzymes by phagocytes. Much of the early research on the mechanism of action of Boswellia focused on leukotriene suppression accomplished via lipoxygenase inhibition. Numerous other anti-inflammatory mechanisms have been identified, including effects on prostaglandins, interleukins, tumor necrosis factor, and nuclear factor-κB (NF-κB), among others.3 AKBA was credited with most of these anti-inflammatory effects; however, AKBA is poorly absorbed. Newer research suggests that alternative boswellic acids with better oral bioavailability may be as or more important.3

Or possibly the synergism of the entire plant’s constituents may be more effective than any single isolated compound.

In animal models of diabetes, histological and chemical studies show Boswellia species act to inhibit lymphocyte infiltration into islets, apoptosis of periinsular cells, and shrinking of islet size. It also significantly prevents the increase of inflammatory interleukin (IL)-1A, IL-1B, IL-2, and IL-6; interferon-γ and tumor necrosis factor (TNF)-α.4 Boswellic acids suppress prostaglandin E2 synthase5 and other inflammatory eicosanoids via cyclooxygenase and lipoxygenase inhibition.6 Boswellic acids reduce inflammatory cytokines and exert antioxidant effects in animal models of arthritis, including significant increases of articular elastase, and they significantly reduced levels of inflammatory mediators at doses of 100 and 200 mg/kg.7 Various molecular investigations in animals have shown positive modulation of NF-κB/cyclooxygenase-2 pathways8 and leukotriene and prostaglandin E2 synthesis and ratios9; and inhibition of TNF-α, IL-1β, and TGF-β expression and NF-κB activation.10,11

Evidence-Based Research

Animal studies and pilot clinical trials support the use of Boswellia serrata gum resin extract (BSE) in the treatment of a variety of inflammatory diseases such as inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, and asthma. In 2002 the European Medicines Agency classified BSE as an “orphan drug” for the treatment of peritumoral brain edema.3

Because standard NSAIDs have many gastrointestinal and cardiovascular adverse effects, Boswellia is an important alternative offering anodyne and anti-inflammatory activities without significant side effects. Boswellia extracts and isolated compounds in the oleoresin (the boswellic acids) have been scientifically investigated for >50 years for their analgesic and anti-inflammatory effects. Many commercial products are standardized to contain 10–15 µg/mL AKBA.

The research is fairly extensive and tissue and pathology specific, with Boswellia’s anodyne and anti-inflammatory actions credited with an ability to reduce inflammatory mediators of many types. It protects various tissues including joints, connective tissue, liver, colon, and brain from pathologic changes, degeneration, and loss of function. A randomized controlled trial (RCT) reported topical application of Boswellia to improve psoriatic scales in 70% of subjects compared with 10% in the placebo group.12 Boswellia, boswellic acids or a combination are shown to reduce inflammation and protect the joints,7protect the colon in from progressive pathological changes in adenomatous polyps,8inhibit cancer metastases in animal models of colorectal cancer,11protect the brain after ischemic injury, and reduce reperfusion injury.10It also protects the liver13 and pancreatic islets14 in diabetic rats and the liver from granuloma formation as a result of schistosome infections.9Boswellia may improve the leukocyte infiltration and superficial ulcers typical of ulcerative colitis. Studies in rats show Boswellia protects colonic mucosa cells from acetic acid induced inflammation, and molecular investigations showed Boswellia to prevent tissue injury via increases in lipid peroxidation and nitric oxide, and the expression of inducible nitric-oxide synthase compared with untreated control animals.15

Boswellia has been shown to improve pain and clinical signs in human arthritis patients.

A proprietary Boswellia product patented in India (whole Boswellia extract enriched with additional AKBA) has been shown to significantly improve knee pain and symptoms in osteoarthritis patients in
30 days compared with placebo in an RCT.16 A similar study dosed Boswellia or placebo for 90 days and reported that the treatment offered significant subjective improvements as assessed by pain scores and assessment questionnaires.17 Another RCT reported all patients receiving Boswellia experienced a decrease in knee pain, increased knee flexion and walking distance, and decreased swelling after
8 weeks, compared with the group taking placebo.18 A similar study gave patients 250 mg of a proprietary Boswellia product, and they noted improvements in osteoarthritic pain as soon as 7 days after beginning therapy.19 Osteoarthritis investigations show Boswellia to reduce general inflammatory mediators as well as inhibit cartilage-degrading enzyme MMP-317, thus helping to protect cartilage in osteoarthritis patients.19

Boswellia has been shown to be a safe and effective therapy in ulcerative colitis, chronic colitis, experimental ileitis, Chron’s disease, and all inflammatory bowel conditions. One RCT included patients experiencing chronic diarrhea with histologically proven collagenous colitis. Patients were randomized to receive either oral Boswellia 400 mg three times daily for 6 weeks or placebo. Boswellia was shown to promote remission more frequently than the placebo; however, no histological changes were seen, and one patient withdrew from the study because of unspecified side effects.20 Another RCT on colitis patients evaluated the effects of Boswellia at 300 mg three times a day on reported symptoms compared with sulfasalazine. Fourteen of 20 patients in the Boswellia group went into remission compared with 4 of 10 in the sulfasalazine group. Furthermore, 19 of the 20 patients ( compared to 6 of 10 in the control group) taking Boswellia improved in one or more of the measured outcomes, including stool properties, histopathology, and blood markers such as hemoglobin, serum iron, calcium, phosphorus, proteins, total leukocytes, and eosinophils.21 A similar study gave patients Boswellia at 350 mg three times per day for 6 weeks and reported 82% of Boswellia-treated patients went into remission, compared with 75% of sulfasalazine-treated patients.22

An RCT on asthma patients showed Boswellia at a dose of 300 mg three times per day improved dyspnea, rhonchi, number of asthma attacks, and spirometry readings in 70% of subjects compared with only 27% of controls receiving placebo.23

Safety in Pregnancy and Breastfeeding

Likely safe. Problems have not been reported.

General Safety

No toxic reactions or significant side effects to Boswellia have been reported, and there are no known contraindications with diseases or conditions. A review of 47 clinical trials using Boswellia to treat asthma, rheumatoid arthritis, Crohn’s disease, osteoarthritis, and collagenous colitis reported that no serious safety issues were noted.19,24 One study reported only minor digestive side effects.18

A battery of biochemical parameters in serum, urine, and blood collected during an osteoarthritis clinical trial showed no toxicity or alterations of concern.17

No drug–nutrient–herb interactions have been reported or demonstrated.

Dosage

This herb is generally considered safe at 1000–1500 mg/day.

Isolated and concentrated individual boswellic acids are generally dosed at 100 mg each day in divided doses.

Traditional Uses

Boswellia serrata is a resinous tree native to India, North Africa, and the Middle East. The gummy oleoresin exuded from injured bark is known as salai guggul that has been used in the traditional medicine of India to treat pain and inflammation, particularly arthritic conditions. Boswellia serrata is also referred to as Indian frankincense to differentiate it from the related frankincense species.

Additional traditional uses for Boswellia include pain and arthritis; diarrhea and dysentery; ulcerative colitis and Chron’s disease; lung inflammation including bronchitis, asthma, chronic obstructive pulmonary diseases; and pneumonia and heart disease patients. Boswellia is prepared into paste, plasters, skin washes, and ointments to use topically on wounds, skin fungus, acne, boils, leprosy, to repel insects, and treat tumors.

References

1

Indian J Pharm Sci. 2011;73(3):255–61. Boswellia serrata, a potential antiinflammatory agent: an overview. Siddiqui MZ.

2 Mol Cell Biochem. 2011;354(1–2):189–97. Cellular and molecular mechanisms of anti-inflammatory effect of Aflapin: a novel Boswellia serrata extract. Sengupta K, Kolla JN, Krishnaraju AV, Yalamanchili N, Rao CV, Golakoti T, Raychaudhuri S, Raychaudhuri SP.

3 Clin Pharmacokinet. 2011;50(6):349–69. Boswellia serrata: an overall assessment of in vitro, preclinical, pharmacokinetic and clinical data. Abdel-Tawab M, Werz O, Schubert-Zsilavecz M.

4 Int J Cancer. 2013;132(11):2667–81. Chemoprevention of intestinal adenomatous polyposis by acetyl-11-keto-beta-boswellic acid in APC(Min/+) mice. Liu HP, Gao ZH, Cui SX, Wang Y, Li BY, Lou HX, Qu XJ.

5 J Nat Prod. 2014;77(6):1445–51. Tetra- and pentacyclic triterpene acids from the ancient anti-inflammatory remedy frankincense as inhibitors of microsomal prostaglandin E(2) synthase-1. Verhoff M, Seitz S, Paul M, Noha SM, Jauch J, Schuster D, Werz O.

6 Biochem Pharmacol. 2012;84(5):681–91. A novel C(28)-hydroxylated lupeolic acid suppresses the biosynthesis of eicosanoids through inhibition of cytosolic phospholipase A(2). Verhoff M, Seitz S, Northoff H, Jauch J, Schaible AM, Werz O.

7 Phytomedicine. 2014;21(6):847–56. Boswellia serrata extract attenuates inflammatory mediators and oxidative stress in collagen induced arthritis. Umar S, Umar K, Sarwar AH, Khan A, Ahmad N, Ahmad S, Katiyar CK, Husain SA, Khan HA.

8 Drug Discov Ther. 2014;8(1):25–32. The comparative study of acetyl-11-keto-beta-boswellic acid (AKBA) and aspirin in the prevention of intestinal adenomatous polyposis in APC(Min/+) mice. Wang R, Wang Y, Gao Z, Qu X.

9 Parasitol Res. 2013;112(3):1105–11. A boswellic acid-containing extract attenuates hepatic granuloma in C57BL/6 mice infected with Schistosoma japonicum. Liu M, Chen P, Büchele B, Dong S, Huang D, Ren C, Zhang Y, Hou X, Simmet T, Shen J.

10 Brain Res. 2012;1443:89–97. Protective effects of incensole acetate on cerebral ischemic injury. Moussaieff A, Yu J, Zhu H, Gattoni-Celli S, Shohami E, Kindy MS.

11 Int J Cancer. 2012;130(9):2176–84. Boswellic acid inhibits growth and metastasis of human colorectal cancer in orthotopic mouse model by downregulating inflammatory, proliferative, invasive and angiogenic biomarkers. Yadav VR, Prasad S, Sung B, Gelovani JG, Guha S, Krishnan S, Aggarwal BB.

12 Clin Cosmet Investig Dermatol. 2014;7:321–7. A cosmeceutical formulation based on boswellic acids for the treatment of erythematous eczema and psoriasis. Togni S, Maramaldi G, Di Pierro F, Biondi M.

13 Jundishapur J Nat Pharm Prod. 2012;7(4):168–75. The antioxidant capacity and anti-diabetic effect of Boswellia serrata triana and planch aqueous extract in fertile female diabetic rats and the possible effects on reproduction and histological changes in the liver and kidneys. Azemi ME, Namjoyan F, Khodayar MJ, Ahmadpour F, Darvish Padok A, Panahi M.

14 Phytomedicine. 2011;18(12):1037–44. Prevention of multiple low-dose streptozotocin (MLD-STZ) diabetes in mice by an extract from gum resin of Boswellia serrata (BE). Shehata AM, Quintanilla-Fend L, Bettio S, Singh CB, Ammon HP.

15 Phytother Res. 2014;28(9):1392–8. Boswellia serrata has beneficial anti-inflammatory and antioxidant properties in a model of experimental colitis. Hartmann RM, Fillmann HS, Martins MI, Meurer L, Marroni NP.

16 Int J Med Sci. 2011;8(7):615–22. A double blind, randomized, placebo controlled clinical study evaluates the early efficacy of aflapin in subjects with osteoarthritis of knee. Vishal AA, Mishra A, Raychaudhuri SP.

17 Int J Med Sci. 2010;7(6):366–77. Comparative efficacy and tolerability of 5-Loxin and Aflapin against osteoarthritis of the knee: a double blind, randomized, placebo controlled clinical study. Sengupta K, Krishnaraju AV, Vishal AA, Mishra A, Trimurtulu G, Sarma KV, Raychaudhuri SK, Raychaudhuri SP.

18 Phytomedicine. 2003;10(1):3–7. Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee–a randomized double blind placebo controlled trial. Kimmatkar N, Thawani V, Hingorani L, Khiyani R.

19 Arthritis Res Ther. 2008;10(4):R85. A double blind, randomized, placebo controlled study of the efficacy and safety of 5-Loxin for treatment of osteoarthritis of the knee. Sengupta K, Alluri KV, Satish AR, Mishra S, Golakoti T, Sarma KV, Dey D, Raychaudhuri SP.

20 Int J Colorectal Dis. 2007;22(12):1445–51. Boswellia serrata extract for the treatment of collagenous colitis. A double-blind, randomized, placebo-controlled, multicenter trial. Madisch A, Miehlke S, Eichele O, Mrwa J, Bethke B, Kuhlisch E, Bästlein E, Wilhelms G, Morgner A, Wigginghaus B, Stolte M.

21 Planta Med. 2001;67(5):391–5. Effects of gum resin of Boswellia serrata in patients with chronic colitis. Gupta I, Parihar A, Malhotra P, Gupta S, Lüdtke R, Safayhi H, Ammon HP.

22 Eur J Med Res. 1997;2(1):37–43. Effects of Boswellia serrata gum resin in patients with ulcerative colitis. Gupta I, Parihar A, Malhotra P, Singh GB, Lüdtke R, Safayhi H, Ammon HP.

23 Eur J Med Res. 1998;3(11):511–4. Effects of Boswellia serrata gum resin in patients with bronchial asthma: results of a double-blind, placebo-controlled, 6-week clinical study. Gupta I, Gupta V, Parihar A, Gupta S, Lüdtke R, Safayhi H, Ammon HP.

24 BMJ. 2008;337:a2813. Frankincense: systematic review. Ernst E.