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Frankincense, Indian

Scientific Name(s): Boswellia serrata Roxb.
Common Name(s): Dhup, Indian frankincense tree, Indian olibanum, Salai guggal

Medically reviewed by Drugs.com. Last updated on Aug 16, 2024.

Clinical Overview

Use

The oleoresin gum from B. serrata has traditionally been used for its anti-inflammatory effects in conditions such as asthma, osteoarthritis, rheumatoid arthritis, colitis, and irritable bowel syndrome. It has also been used for the management of diabetes, urinary conditions, dermatological ailments, and renal impairment. Boswellic acids have demonstrated immunomodulatory, antiproliferative, cytotoxic, and antimicrobial effects; however, there are no adequate clinical trials to support any of the uses.

Dosing

Administration with high-fat foods may enhance plasma levels of B. serrata. Asthma: 300 to 400 mg of an extract (containing 60% boswellic acids) 3 times daily. In one trial, 300 mg 3 times daily of powdered gum resin capsules (S-Compound), or 400 mg 3 times daily of an extract (standardized to 37.5% boswellic acids per dose) was used. Inflammatory conditions: 300 to 400 mg of a B. serrata extract (containing 60% boswellic acids) 3 times daily was used in a clinical trial of patients with knee osteoarthritis. Two capsules of Articulin-F (contains B. serrata, Withania somnifera, Curcuma longa, zinc complex) 3 times daily; or supplementation with Casperome (150 mg of boswellic acids) 3 times daily has been used for inflammatory conditions such as osteoarthritis and rheumatoid arthritis. Ulcerative colitis: 350 to 400 mg 3 times daily.

Contraindications

Hypersensitivity to B. serrata.

Pregnancy/Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

Substrates of cytochrome P450 (CYP-450) 1A2, 2C8, 2C9, 2C19, 2D6, and 3A4: Upon liquid chromatography mass spectrometry analysis, frankincense derived from B. serrata demonstrated inhibition of CYP1A2, 2C8, 2C9, 2C19, 2D6, and 3A4. Therefore, caution is warranted when using B. serrata with medications that are substrates for these isoenzymes. Substrates for P-glycoprotein (P-gp): Data suggest that B. serrata extract and the major boswellic acids may be potent inhibitors of P-gp via modulation of transport activity at the GI level, but not at the blood-brain barrier. Therefore, medications that depend on P-gp transport across the GI membrane may be impacted with coadministration of B. serrata. Warfarin: According to 2 case reports, coadministration of warfarin and B. serrata may increase international normalized ratio (INR) levels. The interaction may be attributed to inhibition of lipoxygenase and interference with COX-1 by B. serrata. In addition, B. serrata might inhibit CYP2C19, 3A4, and 2C9, which are involved in the metabolism of warfarin. Use of B. serrata in patients receiving warfarin is not recommended.

Adverse Reactions

Diarrhea, abdominal pain, and nausea have been reported.

Toxicology

No data.

Scientific Family

Botany

The Burseraceae family of trees and shrubs consists of 18 genera and more than 540 species that grow mostly in tropical regions of India (B. serrata), North Africa (Boswellia carteri, Boswellia frereana), and the Arabian Peninsula (Boswellia sacra). Most species contain resin ducts in the bark, which yield the products myrrh and frankincense.1, 2 B. serrata is a branching tree that grows on dry, hilly areas throughout most of India and can reach up to 3.7 m in height.3 When the bark is cut, the aromatic balsam, or gum resin, oozes out and is used for medicinal purposes.4 The semi-solid resin is typically harvested each summer and fall and is collected in bamboo baskets, where it remains for approximately 1 month, during which the fluid is drained out. The residue, which is semi-solid to solid, is the part of the gum resin that slowly hardens and is eventually broken into smaller pieces. The tree can produce a quality product for a period of 3 years, after which time the tree should be allowed to rest before being harvested again.5 The oleoresin contains oils, terpenoids, and gum.6

History

The Indian frankincense tree is thought to be related to the tree in the Bible that brought forth the frankincense given by the wise men as a gift to the baby Jesus. In Ayurvedic medicine in India, different parts of the tree have been used for asthma, rheumatism, dysentery, skin ailments, ulcers, blood purification, bronchial conditions, and wound treatment.4 B. serrata is discussed in Ayurvedic texts using the name "Gajabhakshya," meaning it was consumed by elephants.7 Frankincense is also used to perfume clothes, hair, and rooms. It was used in ancient Egypt as an ingredient in embalming liquids for mummification. It has historically been burned in religious and/or spiritual ceremonies and is said to produce a psychoactive substance.8 In 2002, the European Medicine Agency classified the gum resin extract of B. serrata as an orphan drug.9

Chemistry

B. serrata contains oils, terpenoids, sugars, and volatile oils. Four pentacyclic triterpenes are also present: beta-boswellic acid, acetyl-beta-boswellic acid, 11-keto-beta-boswellic acid, and acetyl-11-keto-beta-boswellic acid.3, 6, 10, 11

Uses and Pharmacology

Anticancer effects

Animal and in vitro data

In an in vitro study, acetyl-keto-beta-boswellic acid and keto-beta-boswellic acid exerted antiproliferative and apoptotic effects in human HT-29 colon cancer cells.12 Similarly, apoptotic effects of boswellic acid acetate were observed in myeloid leukemia cells.13 Cytotoxic effects were noted with acetyl-11-keto-beta-boswellic acid in glioblastoma and leukemia cell lines.14

In a murine model, acetyl-11-keto-beta-boswellic acid 50 to 200 mg/kg given orally inhibited the growth of colorectal cancer cells in a dose-dependent manner, with a subsequent reduction in tumor volume; it was also associated with a reduction in ascites and in metastases to the liver, lungs, and spleen.15

An extract of B. serrata caused a loss of viability and inhibited proliferation of 5 leukemia and 2 brain tumor cell lines in a dose-dependent manner.16

Clinical data

In a study of patients with primary or secondary malignant cerebral tumors, a greater than 75% reduction in cerebral edema was observed in 60% of patients receiving radiotherapy plus B. serrata 4,200 mg/day, compared with 26% of patients receiving radiotherapy alone (P=0.023).17

In a case study of a 39-year-old woman with breast cancer brain metastases, a computed tomography scan showed complete disappearance of brain metastases following administration of B. serrata 2,400 mg/day for 10 weeks. The patient continued this regimen for 4 years with no new signs of brain involvement; however, she did develop skeletal metastases.18

In a study of 19 children and adolescents with intracranial tumors, palliative treatment with H15, a phytotherapeutic agent derived from the gum resin of B. serrata, resulted in various improvements in overall health status, neurological symptoms (ataxia, paresis), and muscle strength; one cachectic patient achieved weight gain.19

In a study of 12 patients with brain tumors and associated progressive edema, H15 1,200 mg 3 times daily reduced edema in 2 of 7 patients with glioblastoma and in 3 of 5 patients with leukoencephalopathy. In general, the maximum treatment response was noted within 4 weeks of initiation, and no further reduction was noted with continued treatment.20

Antidiabetic effects

Animal and in vitro data

In a study of diabetic rats, administration of B. serrata (a dose of 200 mg/kg was most effective) significantly reduced blood glucose and hemoglobin A1c levels after 17 days (P≤0.01).21 A B. serrata extract also greatly attenuated effects in a mouse model of induced diabetes.22

Clinical data

In a study of 56 patients with diabetes, B. serrata 250 mg twice daily for 8 weeks did not impact glucose or lipid levels compared with placebo.23 Further investigation of the effects of B. serrata extract on late-onset autoimmune diabetes is needed; one case report noted both clinical improvement and decreased IA2 antibodies in a patient treated with a B. serrata extract.24

Anti-inflammatory effects

In vitro, boswellic acids are specific inhibitors of 5-lipoxygenase (5-LO), the key enzyme of leukotriene biosynthesis. Leukotrienes are biochemicals in the body that maintain inflammation. Of the 4 boswellic acids, acetyl-11-keto-beta-boswellic acid is the most potent 5-LO inhibitor11 and appears to act directly on 5-LO at a selective site for pentacyclic triterpenes.25 Boswellic acids have traditionally been used in treating inflammatory conditions such as arthritis, tendinopathy, and bursitis.4, 10

Animal and in vitro data

Anti-inflammatory activity of B. serrata has been studied in animals.10 The plant extract displays marked anti-inflammatory action and antiarthritic activity in rats, with no significant adverse reactions.26 In one report evaluating boswellic acid inhibition of leukotriene synthesis (via 5-LO), no effect on 12-lipoxygenase, cyclooxygenase, or the peroxidation of arachidonic acid by iron and ascorbate was observed, suggesting that boswellic acids are specific, nonredox inhibitors of leukotriene synthesis.27 Similar results were found in rat peritoneal neutrophils.28, 29

B. serrata was ineffective in the prevention of weight loss or mucosal damage caused by colitis in a study of mice. No improvements in mortality or histology of the colon were noted.30

In a study of rats, boswellic acids demonstrated antiulcerogenic effects in various models of ulceration.31 In addition, B. serrata exerted anti-inflammatory and antioxidant effects in an experimental model of acute colitis in rats.32

Clinical data

GI conditions

B. serrata appears to have benefit in ulcerative colitis due to its ability to inhibit 5-LO. In a clinical trial, patients given B. serrata gum resin preparation (350 mg 3 times daily) for 6 weeks experienced improvement in parameters of ulcerative colitis (eg, stool properties, histopathology, rectal biopsies, blood work) compared with patients receiving sulfasalazine (1 g 3 times daily). Remission was 82% with the resin and 75% with sulfasalazine.33 In a study of patients with ulcerative colitis who were in a minimally symptomatic remission phase, administration of 250 mg/day of Casperome, a lecithin-based delivery system for B. serrata designed to improve bioavailability, had a beneficial effect on parameters of intestinal pain (ie, evident and occult blood in stools, bowel movements, cramping, diarrhea, malaise, anemia, rectal involvement, white blood cell count, need for additional drugs or medical attention).34

A meta-analysis identified 7 placebo-controlled clinical trials that evaluated the efficacy and tolerability of herbal medicines in inflammatory bowel disease. Based on 2 studies (N=113) evaluating B. serrata in patients with Crohn disease or collagenous colitis, a significant result was identified for induction of clinical remission (relative risk, 2.34).35 However, a relevant systematic review of randomized trials found B. serrata to be ineffective for the treatment of collagenous colitis; however, the authors note that the studies reviewed may have been underpowered to detect a difference.36 One trial reviewed (Madisch et al) included 31 patients, 26 of whom were included in the per-protocol analysis. After 6 weeks of receiving oral B. Serrata 400 mg 3 times daily, more patients in the treatment group were in remission compared with those in the placebo group. The difference was significant in the per-protocol group compared with placebo (P=0.04) but not in the intention-to-treat group (P=0.25), indicating a possible flaw in the study design.37, 38

In a randomized controlled trial comparing the efficacy and safety of B. serrata extract (H15) with mesalazine in patients with active Crohn disease, B. serrata was found to be non-inferior to mesalazine.39 In another trial, B. serrata given for 1 year was assessed for use in maintaining remission in patients with Crohn disease. The study was halted early due to a high dropout rate as well as low patient recruitment. The data analyzed did not reveal a difference between treatment and placebo.40

In a study of 30 patients with chronic colitis, patients received either B. serrata 300 mg 3 times daily or sulfasalazine 1 g 3 times daily for 6 weeks. Of the patients receiving B. serrata, 90% reported an improvement in at least one parameter such as stool properties, histopathology, or microscopy, and 70% went into remission. With sulfasalazine, 60% demonstrated improvement and 40% went into remission.41

Gingivitis

In a randomized, double-blind clinical study of high school females with gingivitis, B. serrata extract exerted anti-inflammatory effects.42

Osteoarthritis and other pain

In a double-blind, randomized, crossover trial of healthy adult male volunteers (N=12), pain threshold and tolerance were significantly increased with administration of a single oral dose of B. serrata 125 mg (2 capsules) compared with placebo. Using a mechanical pain model, subjects experienced a significant increase from baseline in mean pain threshold force and time at 2 hours and 3 hours after drug administration compared to placebo (P<0.05); mean pain threshold force and time with B. serrata were also statistically significant at 3 hours compared to baseline (P<0.05). Additionally, mean pain tolerance force and time were significantly increased at all 3 time points (ie, 1, 2, and 3 hours after drug administration) compared with baseline (P<0.05). Mean percentage change from baseline in pain tolerance force and time was also significantly increased at all time points compared with placebo (P≤0.01).43

In a Cochrane review of combined data from 2 high-quality studies in a small number of patients (N=85), a B. serrata 100 mg/day extract administered for 90 days improved symptoms of osteoarthritis. Specifically, B. serrata reduced the mean visual analog scale (VAS) score by 17 points compared with placebo, with a number needed to treat for an additional beneficial outcome of 2. Patients receiving B. serrata reported improvements in physical function (ie, 8-point improvement) compared with placebo.44

In a randomized, double-blind, placebo-controlled crossover study of 42 osteoarthritic patients, B. serrata in an herbomineral combination was compared with placebo. B. serrata decreased pain and disability scores, but radiological assessment showed no change.45 Similarly, in a crossover study of 30 patients with osteoarthritis of the knee, B. serrata 1 g/day for 8 weeks improved knee pain, knee flexion, walking distance, and swelling.46 After 120 days of treatment with a standardized B. serrata extract (Boswellin, equivalent to 87.3 mg of total beta-boswellic acids twice daily), multiple outcomes including pain, ability to walk, quality of life, radiological improvements and the inflammatory biomarker high-sensitivity C-reactive protein were significantly improved compared to placebo in patients with osteoarthritis of the knee in a double-blind, randomized controlled trial.81 When compared with valdecoxib, patients receiving B. serrata extract for osteoarthritis of the knee experienced improvements in pain, stiffness, and difficulty performing activities after 2 months of treatment; these effects persisted until 1 month after discontinuation. While valdecoxib was also successful in improving these parameters after 1 month of therapy, its effects persisted only as long as treatment was continued.47

Novel products produced from B. serrata have been tested in clinical studies. Aflapin, which is derived from the gum resin of B. serrata, improved pain and physical function scores in patients with osteoarthritis of the knee when dosed at 100 mg/day for 30 days.48 Similar results were noted in patients with osteoarthritis of the knee receiving 5-Loxin (a B. serrata extract enriched with 30% 3-O-acetyl-11-keto-beta-boswellic acid) 250 to 500 mg/day for 90 days, with improvement noted as early as 7 days after initiation of treatment.49 In a study of 52 male rugby patients with knee pain without osteoarthritis, Casperome (derived from the extract of B. serrata) dosed at 500 mg/day for 5 days followed by 250 mg/day for 23 days improved local pain on effort, pain-free walking distance, joint effusion, structural damage, thermal imaging, and VAS pain scores.50

An older review of the literature suggests potential benefit of the gum resin of B. serrata in the treatment of rheumatoid arthritis.51 In a small study of 4 patients with chronic cluster headaches receiving B. serrata, long-lasting analgesic effects (mean, 15 months) were noted in 3 patients, and transient analgesic effects (mean, 6 months) were noted in 1 patient.52

Antimicrobial effects

Animal and in vitro data

Acetyl-11-keto-beta-boswellic acid exerted antibacterial effects against Staphylococcus aureus in an in vitro model.53

In an in vitro study, B. serrata was found to exert antiprotozoal activity against Trypanosoma brucei and Plasmodium falciparum.54

In a study evaluating various commercially available essential oils for antimicrobial activity, B. serrata essential oil exerted antimicrobial activity against Trichophyton spp. It was also found to exert a synergistic effect with azoles against azole-resistant Candida albicans. Thus, B. serrata may be useful in the treatment of skin, scalp, and nail infections.55

Asthmatic effects

Boswellic acids may be beneficial in the management of asthma due to inhibition of leukotriene biosynthesis through 5-LO inhibition.56

Clinical data

A systematic review and meta-analysis conducted in 2010 evaluated several complementary alternative products, including boswellic acids, for the management of asthma. Given the small sample sizes, short durations of study, and poor methodologies, among other limitations, it is challenging to make a recommendation regarding use of boswellic acids for the management of asthma. Individual studies determined differences in peak expiratory flow rate and forced vital capacity.57

In a small double-blind, placebo-controlled clinical study, administration of 300 mg of the gum resin of B. serrata 3 times daily for 6 weeks improved physical symptoms such as dyspnea and rhonchi, number of attacks, and spirometry measures in 70% of patients, compared with 27% of those receiving placebo.58

Dermatological effects

Clinical data

In a randomized, double-blind, placebo-controlled study, the effects of a cream containing boswellic acids 0.5% were assessed in 15 women with photoaged skin. Patients were given 2 tubes, one containing boswellic acids and the other containing simply an emollient. Patients were instructed to apply 1 cream to each half of the face once daily for 30 days. The application of boswellic acid cream was associated with improvements in Dover's global score for photoaging, tactile roughness, fine lines, and elasticity, as well as with a reduction in sebum excretion.59, 60

A randomized, placebo-controlled, parallel-group study in 114 women undergoing adjuvant radiotherapy following surgery for breast cancer evaluated the safety and efficacy of a cream containing boswellic acids (Bosexil) compared with base cream for the prevention of radiation-induced dermatological effects. The cream was applied twice daily on radiation days immediately after radiation. Application of the boswellic acid–containing cream was associated with a reduced grade of erythema, with visual intensity rated as "intense" in a larger portion of those receiving base cream (49%) compared with those receiving boswellic acid–containing cream (22%; P=0.009). In addition, the use of topical steroids was reduced with use of boswellic acid–containing cream.61

In a randomized, double-blind, placebo-controlled study in patients with psoriasis, administration of Bosexil twice daily for 30 days improved scales in 70% and erythema in 50% of cases. In patients with eczema, 60% reported improvements in itching, and 60% reported improvements in erythema.62

Immunomodulatory activity

Animal and in vitro data

Mast cell stabilizing activity was demonstrated with an extract of gum resin of B. serrata in a murine model.63 In an immunological study, boswellic acids were shown to possess anticomplementary activity via C3-convertase inhibition.64 C3-convertase is involved in the production of anaphylatoxin.65

Renal effects

Animal data

In a murine model, B. serrata partially protected the kidneys in both acute and chronic renal failure. Arabic gum and ginger had more promising results compared with B. serrata.66

Clinical data

In a study of 16 patients with chronic kidney disease not on dialysis, the combination of B. serrata and C. longa administered for 8 weeks improved levels of interleukin-6; however, no differences were noted in other markers, such as tumor necrosis factor-alpha, glutathione peroxidase, and serum C-reactive protein.67

Urinary effects

B. serrata may be useful for the treatment of stress incontinence because of its astringent properties and ability to tone the muscles.68

Clinical data

In a prospective, single-blind, placebo-controlled, randomized clinical trial of women of reproductive age with stress incontinence, the combination of B. serrata and Cyperus scariosus (1 g of each powder twice daily for 8 weeks) in addition to pelvic floor muscle training was associated with a 23% greater improvement in alleviation of stress incontinence compared with pelvic floor muscle training alone (60% cure rate vs 36.67%; P=0.035).68

In a randomized study of men with chronic prostatitis, antibiotics plus Proxelan suppositories (an herbal blend containing Boswellia) improved patient symptoms but did not change microbiological results compared with antibiotics alone. The exact species of Boswellia used is unclear.69

Other uses

In an in vitro study, beta-boswellic acid exerted protective effects on blood stasis–induced endothelial function by increasing phosphorylation of enzyme nitric oxide synthase.70

In a fully allogenic mouse heart transplantation model, boswellic acid resulted in prolongation of graft survival time.71

Dosing

Administration with high-fat foods may enhance plasma levels of B. serrata.72

Asthma

300 to 400 mg of an extract (containing 60% boswellic acids) 3 times daily.3 In one trial, 300 mg 3 times daily of powdered gum resin capsules (S-Compound), or 400 mg 3 times daily of an extract (standardized to 37.5% boswellic acids per dose) was used.8

Inflammatory conditions

300 to 400 mg of a B. serrata extract (containing 60% boswellic acids) 3 times daily was used in a clinical trial of patients with knee osteoarthritis.3

Two capsules of Articulin-F (contains B. serrata, W. somnifera, C. longa, zinc complex) 3 times daily8; or supplementation with Casperome (150 mg of boswellic acids) 3 times daily has been used for inflammatory conditions such as osteoarthritis and rheumatoid arthritis.40

Ulcerative colitis

350 to 400 mg 3 times daily.8

Pregnancy / Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking. Reports from Indian literature suggest the resin of B. serrata may induce abortion.8

Interactions

Substrates of CYP1A2, 2C8, 2C9, 2C19, 2D6, and 3A4

Upon liquid chromatography mass spectrometry analysis, frankincense derived from B. serrata demonstrated inhibition of CYP1A2, 2C8, 2C9, 2C19, 2D6, and 3A4. Therefore, caution is warranted when using B. serrata with medications that are substrates for these isoenzymes.2

Substrates for P-gp

Data suggest that B. serrata extract and the major boswellic acids may be potent inhibitors of P-gp via modulation of transport activity at the GI level, but not at the blood-brain barrier.73 Therefore, medications that depend on P-gp transport across the GI membrane may be impacted with coadministration of B. serrata.

Warfarin

According to 2 case reports, coadministration of warfarin and B. serrata may increase INR levels. The interaction may be attributed to inhibition of lipoxygenase and interference with COX-1 by B. serrata. In addition, B. serrata might inhibit CYP2C19, 3A4, and 2C9, which are involved in the metabolism of warfarin. Use of B. serrata in patients receiving warfarin is not recommended.74

Adverse Reactions

B. serrata is mostly well tolerated. It has been associated with mild GI disturbances such as nausea, abdominal pain, diarrhea, loss of appetite, and acid reflux.8, 75, 76, 77 Hepatotoxic effects were reported in a study of mice.17 A case report describes development of contact dermatitis in a 28-year-old woman who used a naturopathic cream containing B. serrata for treatment of second-degree burn. Topical and systemic corticosteroids were needed to manage her contact dermatitis, which included a local cutaneous reaction with development of bullae. A patch test produced positive results when B. serrata was tested. Months later, the patient developed contact dermatitis on her hands after applying the same cream on her husband.6

Toxicology

The median lethal dose (LD50) of B. serrata has been determined to be greater than 2 g/kg.3, 7, 40, 78 In rats, the acute oral LD50 of Aflapin, a synergistic composition derived from B. serrata gum resin, was 5 g/kg, and the acute dermal LD50 of Aflapin was 2 g/kg.79 A combination product containing B. serrata, Zingiber officinale, C. longa, and W. somnifera was not associated with any toxicity in rats given one dose of 10 g/kg.80

References

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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