- Boswellia subspecies are branching trees found in Asia and Africa. For medicinal purposes mainly the resin is used.
- No firm conclusions can be drawn on the effect of orally administered Boswellia extracts on peritumoural brain oedema, brain tumours, brain metastases or any other cancer in women, men or children.
- Not enough data are available for topical application of Boswellia-containing creams on radiation dermatitis.
- Boswellic acids might have inhibitory effects on cytochrome P450 isoenzymes and P-glycoprotein.
- Reported adverse effects mainly affect the gastrointestinal system and the skin.
Boswellia subspecies are trees growing in Asia and Africa. Medicinal dry extracts of different Boswellia trees are traded as phytopharmaceuticals for oral and topical administration. Boswellia extracts are claimed to be inhibitors of inflammation processes, with possible efficacy against perifocal oedema in brain tumour patients, radiation-induced dermatitis and other inflammatory skin conditions, and antitumor activity.
In-vitro experiments have found anti-inflammatory, antiproliferative, and apoptotic effects of Boswellic acids.
The results of two clinical studies and two observational studies (case series) suggest beneficial effects of Boswellia extracts on perifocal brain oedema although the evidence is to be considered as low, and no firm conclusions can be drawn about the effect of orally administered Boswellic acids or Boswellia extracts on brain tumours in humans. Topically, Boswellia-based cream may reduce erythema caused by breast radiation based on one clinical trial; these results are however only preliminary.
Pharmacokinetic studies have suggested inhibitory effects of Boswellic acids on cytochrome P450 isoenzymes and P-glycoprotein but provide no assessment of the risk for drug interactions in humans so far.
Adverse effects of Boswellia extracts mainly involve the gastrointestinal system and the skin.
Last updated in September 2018 by Ellen McDonell.
"Is it safe?" part updated in July 2015 by Christoph Ritter and Markus Horneber.
Assessed as up to date in January 2015 by Barbara Wider.
Fully updated and revised in January 2013 by Gabriele Dennert.
Fully updated and revised in October 2011 by Gabriele Dennert.
Fully updated and revised in November 2009 by Gabriele Dennert.
First published in November 2005, authored by Gabriele Dennert.
Ellen McDonell, Gabriele Dennert, CAM-Cancer Consortium. Boswellia spp [online document], http://cam-cancer.org/en/boswellia. September 11, 2018.
Boswellia subspecies are trees (family: Burseraceae) found in India, Northern Africa and the Middle East1. Frankincense is the hardened gum resin extruded from incisions in the trunk of several Boswellia species, including Boswellia carterii (African frankincense) and Boswellia serrata (Indian frankincense). The gummy oleo-resin is also known as olibanum (Boswellia carterii) and Salai Guggal (Boswellia serrata)2.
Medicinal dry extracts from the gummy resin are traded under names such as "H15 Ayurmedica" or "Olibanum" and referred to as “Boswellia extracts” throughout this summary.
Boswellia resin is a mixture containing more than 200 different substances3, for instance: resin, long-chain sugar compounds, essential oils, proteins, and inorganic compounds4. Boswellic acids (BAs) have been identified as the putative active principle of the gum resin. BAs are pentacyclic triterpenes with different functional groups in position 3 and 11 of their carbon rings. The most important BAs are:
- alpha-Boswellic acid
- beta -Boswellic acid
- Acetyl-beta-Boswellic acid
- Acetyl-alpha-Boswellic acid
- 11-Keto-beta-Boswellic acid (KBA)
- Acetyl-11-beta-beta-Boswellic acid (AKBA).
Boswellia preparations vary naturally in terms of their content of the different BAs. Medicinal dry extracts are manufactured following standardised procedures to minimise sources of variation within the production process1.
Application and dosage
Boswellia extracts are administered orally as capsules or tablets usually with a content around 400 mg of Boswellia extract. Providers recommend a daily dosage of 4 to 6 grams per day for adults in the treatment of perifocal brain oedema. Methods to enhance bioavailability have been developed such as lecithin formulations50. Topically, creams containing 0.5%-2% Boswellic acids have been used34-36. Essential oils of Boswellia (frankincense) are used as aromatherapy37,38.
Boswellia preparations have been used in Indian Ayurvedic medicine for the treatment of inflammatory diseases4. It was also occasionally mentioned in European medical traditions from the Middle Ages to modern times7. Current research is being conducted on the anti-inflammatory properties of Boswellia extracts and their use in chronic inflammatory diseases like Morbus Crohn or asthma bronchiale.
Claims of efficacy and alleged indications
Boswellia preparations have been used in Indian Ayurvedic medicine for the treatment of inflammatory diseases4. It was also occasionally mentioned in European medical traditions from the Middle Ages to modern times7. Current research is being conducted on the anti-inflammatory properties of Boswellia extracts and their use in chronic inflammatory diseases such as rheumatoid arthritis, Crohn’s disease, osteoarthritis, and asthma48.
Mechanisms of action
Findings with healthy male volunteers indicated a possible initial fast gastric resorption, followed by intestinal resorption5 depending on concomitant food intake6. Gastrointestinal resorption of BAs was increased when taken with a high-fat meal. The concentration peak was seen after approximately 4.5 hours. Elimination half time was 6 hours in the mean and varied considerably with concomitant food intake. BAs were found to have a high volume of distribution.
A number of in-vitro molecular targets of boswellic acids have been described, such as 5-lipoxygenase (5-LO), leukocyte elastase11, topoisomerase 1 and 224, prostaglandin E247, and NF-kappa B48. The exact mechanisms remain unclear to date.
BAs selectively inhibit the key enzyme of leukotriene synthesis 5-LO4 and reduce leukotriene biosynthesis in a concentration-dependent manner10. Among the investigated BAs, AKBA showed the strongest inhibitory efficacy. When multicomponent extracts that contain several BAs (like all Boswellia gum resin extracts) were tested in in-vitro experiments, the composition and dose of the different Boswellic acids has been found to influence the observed effect. Inhibition of leukotriene synthesis could only be seen at higher concentrations; at lower concentrations an increased synthesis of leukotriens was observed.
Some BAs - especially AKBA48 - have been found to reduce tumour cell proliferation and induce apoptosis in several in-vitro experiments with animal12,13 and human malignant cell lines15,27 including glioma10,40, melanoma12, leukemia14, multiple myeloma25, prostate26, breast and cervical41, and colon42, as well as in vivo animal studies16,43,44. The underlying mechanism of BA-induced apoptosis and inhibition of cell proliferation are still being elucidated, but include interference with epigenetics in tumour cells31, increase in caspase 3/7 mediated apoptosis40,45, increase in Bax/Bcl-2 ratio42, modulation of Wnt/beta-catenin pathway and downregulation of NF-kappaB/COX-2 pathway46, reduction in prostaglandin E2 and its downstream targets47, and PARP cleavage48 among others.
Prevalence of use
There is no data on the prevalence of use of Boswellia products in tumour or brain tumour patients.
Legal issues and providers
Boswellia products are traded as "dietary supplements". H 15 Ayurmedica is a registered Ayurvedic medication in India (Gufic, Mumbay, India). Its manufacturer also holds a partial license for Switzerland, but is not licensed within the EU. However, it can be imported to the EU for use in individual patients under specific circumstances and for use in clinical studies. Additionally, some companies sell Boswellia extracts as “dietary supplements” in the EU.
Cost(s) and expenditures
Costs for Boswellia extracts amount to between €40 to 60 per month (depending on the daily dose) when ordered via the internet (plus shipping).
Two prospective clinical studies, a retrospective and a prospective case series – all involving patients with brain tumours or metastases – as well as a case report of a female patient with brain metastases have been published. One controlled clinical trial of a topical 2% Boswellia cream for women receiving adjuvant breast radiation has been published.
Findings from a randomised clinical pilot trial with 44 patients suggest a positive effect of Boswellia serrata on brain oedema29,30. Patients receiving irradiation of the brain for primary brain tumours or brain metastases of solid tumours were administered either 3 x 1400 mg/d Boswellia extracts during radiotherapy or placebo. In patients with brain metastases, a reduction of brain oedema (evaluated by MRI scans) of > 75% was seen in 60% in the Boswellia group and in 26% in the placebo group at the end of radiotherapy (p=0.023). Reevaluation at 4 weeks after radiotherapy showed no differences between Boswellia and placebo groups, which might be attributable to the termination of Boswellia intake at the end of radiotherapy. No differences could be seen in patients with primary brain tumours (small number of participants).
A prospective clinical study with 29 glioma patients was conducted by Heldt19 and Böker20. Participants were non-randomly allocated to receive three different doses of Boswellia extracts (3 x 1200 mg/d, 3 x 800 mg/d, 3 x 400 mg/d) prior to surgical intervention. After seven days of intervention, the size of perifocal oedema was reduced in the CT scans of participants receiving 3 x 1200 mg/d and – to a lower degree – in participants receiving 3 x 800 mg/d. Improvement in clinical symptoms was found only in the group receiving the highest daily dose. These participants also had a reduced urinary excretion of leukotrien E4 (LTE4) (as a measurement of leukotrien synthesis in the body). No effect on the tumour size was observed. Due to the study design, it is unclear whether changes in oedema size or clinical improvement can be attributed to olibanum intake.
Janssen17 evaluated the use of H15 retrospectively in 17 female and male children (age 0.5 to 18 years) with different progressive or relapsed brain tumours. H15 was administered orally at 40 to 126 mg/kg body weight per day over 1 to 26 months with or without concomitant conventional therapy. Subjective improvement was reported by six patients, clinical regression of neurological symptoms was documented in four patients. In two patients, regression of the peritumoural oedema or reduction of a tumour cyst were documented by MRI. Four children remained in stable disease over 3 to 8 months and two showed tumour regression. However, these effects were more likely attributable to concomitant radio- and chemotherapy than to Boswellia extracts.
Streffer et al.18 published a prospective case series of 12 adult patients with progressive cerebral oedema with or without overt tumour progression (seven with glioblastoma and five with leukencephalopathy after conventional tumour therapy). All study participants had to be taken off steroids or on a stable dosage of steroids. H15 was administered orally at 3 x 1200 mg/d. Three participants with glioblastoma reported a clinical improvement, in two of these three cases a reduction in perifocal oedema could be seen in MRI scan. All five participants with leukencephalopathy reported a clinical benefit. No tumour response was seen in any patient.
Both case series suggest that there might be a beneficial effect for Boswellia extracts on brain oedema in study participants with brain tumours or leukencephalopathy. The applicability of these findings to other patients, however, is limited due to selection of participants and study design.
Flavin22 reported the favourable course of a 39-year old women with newly developed symptomatic multiple brain metastases of a mammacarcinoma, which were documented in a CT scan, one year after initial diagnosis. She received radiation therapy of the brain and capecitabine chemotherapy and also started with Boswellia serrata, 3 x 800 mg/d orally. After 10 weeks of treatment, brain metastases could no longer be seen in the CT scan. The patient was maintained on Boswellia serrata for another 4 years without signs of recurrent cerebral metastases, but newly developed bone metastases after that period.
However, it is not possible to attribute the long-term remission of her brain metastases to Boswellia extracts. Both radiotherapy and capecitabine treatment23 have reportedly induced remission of CNS metastases and may have been the active treatment in this case. Nevertheless, a long-term remission of multiple CNS metastases is rare and all involved possibly beneficial interventions, including Boswellia extracts, deserve consideration in future investigations.
A randomized, placebo-controlled trial evaluated the effect of topical 2% Boswellic acid cream applied twice daily compared to a base cream onradiation dermatitisin 114 women receiving adjuvant breast radiotherapy34. Erythema was evaluated after a total dose of 50 Gy was delivered, and was evaluated with a visual scale (slight, moderate, intense), and a computer-assisted analysis of photos. Secondary endpoints consisted of use of hydrocortisone cream, and adverse effects. There was a statistically significant difference in erythema on the visual scale; of note intense erythema was reported in 49% of placebo cream users versus 22% of Boswellia users, and more people using Boswellia cream had slight or moderate intensity erythema. More patients received hydrocortisone cream in the placebo group than in the Boswellia cream group (63% and 25% respectively, p < 0.0001). Treatment was well tolerated. Authors do not comment on whether the trial was double blinded, or whether unmasking could have occurred due to the smell of Boswellia, which may affect the methodological rigor of the trial.
Boswelliaessential oilalone or in combination with other oils has been used as aromatherapy37-39. No clinical trials exist on the use of frankincense essential oil alone for cancer-related symptoms, however a retrospective audit in a cancer centre37 and one case report38 suggest a potential for quality of life improvements. Future clinical trials should evaluate this further.
Several of the above mentioned clinical investigations reported the presence or absence of side effects of Boswellia extracts4,17-18,20,34. In 134 cancer patients receiving BAs, 11 cases of possible adverse effects were reported: nausea/emesis WHO III (one patient), skin rash WHO II (two patients), diarrhoea WHO I/II (six patients), gastrointestinal pain (two patients), loss of appetite and heartburn (six patients). In the former three patients with nausea/emesis and skin rash, Boswellia administration had to be terminated.
Pregnancy and lactation; nothing is known about teratogenicity and possible effects of Boswellia extracts on breast-fed infants. There is no information available on mutagenic effects of Boswellia extracts in women and men or long-term carcinogenicity.
Further known contraindications are any previous allergic reactions to Boswellia extracts or components of these extracts.
Findings of an in vitro study of extracts of various Boswellia spp. showed minor inhibitory effects on the CYP enzymes 1A2 und 2D5 as well as a moderate inhibition of the enzymes 2C8, 2C9, 2C19, and 3A432. Another in vitro study showed a concentration-dependent modulation of P-glycoprotein function in various cell systems; the degree of P-GP inhibition varied with the type of Boswellic acid studied.
Inhibition of P-GP at the blood brain barrier in humans seems unlikely, as the Boswellian acid plasma levels following oral administration are lower than the concentrations used in vitro. On the other hand, inhibitory effects on the P-GP of the intestinal mucosa are conceivable as a result of the higher intraluminal concentrations of Boswellic acids upon oral application33.
In general, although these results may suggest inhibitory effects of Boswellia components on CYP450 enzymes and P-glycoprotein, they represent merely anecdotal evidence based on cell systems thus precluding any firm conclusions as to the clinical relevance of potential interactions.
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