Boswellia species (frankincense) are a genus of trees found in India, Northern Africa, and the Middle East. For medicinal purposes mainly the resin is used, and Boswellia serrata is the most commonly used species. Boswellia extracts have been used orally, topically, and as aromatherapy. Boswellia extracts are claimed to be inhibitors of inflammatory processes, possess anti-cancer actions, and possibly be effective against perifocal oedema in brain cancer, radiation-induced dermatitis, and other inflammatory conditions.
Efficacy
In-vitro experiments have found anti-inflammatory, antiproliferative, and apoptotic effects of Boswellic acids.
Brain tumours: Despite some encouraging preliminary data, no firm conclusions can be drawn on the effect of orally administered Boswellia extracts on peritumoural brain oedema or brain tumours (two controlled and three small uncontrolled studies).
Radiation dermatitis: Not enough data are available (one RCT, n=114) to establish the efficacy of topical Boswellia-containing creams on radiation dermatitis
Safety
Boswellia extracts are generally well tolerated, adverse effects mainly involve the gastrointestinal system and the skin. 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.
Citation
Conte E, CAM Cancer Collaboration. Boswellia spp [online document], Feb 20, 2021.
Document history
Latest update: February 2021
Next update due: February 2024
Description, background and characterisation of the medicinal plant
Boswellia species (frankincense) are a genus of trees from the family Burseraceae found in India, Northern Africription, background and characterisation of the medicinal planta and the Middle East (Ennet 2000, Efferth 2020). 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) (Buvari 2001). The most commonly used and studied species medicinally is Boswellia serrata (Efferth, 2020). Dry extracts from the gummy resin are sold under various trade names such as "H15 Ayurmedica" or "Olibanum", and are referred to as “Boswellia extracts” or “boswellia” throughout this summary. Essential oils of Boswellia are also available but contain different phytochemicals than the resin (Efferth, 2020).
Ingredients and quality requirements
Boswellia resin is a mixture containing more than 200 different substances (Kreck 1999), for instance: resin, long-chain sugar compounds, essential oils, proteins, and inorganic compounds (Ammon 2002). 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 process. (Ennet 2000)
Alleged indications
Boswellia preparations have a long history of use in Indian Ayurvedic medicine for the treatment of inflammatory diseases (Ammon 2002). It was also occasionally mentioned in European medical traditions from the Middle Ages to modern times (Schrott 1998). 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, asthma (Ernst 2008), psoriasis, eczema, osteoarthritis, and multiple sclerosis (Efferth, 2020). Boswellia has been used for cancer to reduce inflammation, treat and prevent cerebral edema, and to exert cytotoxic effects, particularly for brain tumours (Efferth, 2020).
There is no data on the prevalence of use of Boswellia products in patients with cancer.
Application and dosage
Boswellia has been used orally, topically, and as aromatherapy. Boswellia is most often studied and sold as a standardized extract in capsule or tablet form for oral use, with the dose per capsule ranging from 250-500mg. Daily doses used in clinical trials for cancer and inflammatory conditions range from 100mg/day to 4500mg/day, but 1000mg-4000mg/day has been most common (Rossi 2016; Yu 2020, Kirste 2009, De Pierro 2019, Böker 1997). Specifically for perifocal oedema in patients with brain cancer, dosing has ranged from 3200mg-4500mg/day (Kirste 2009, De Pierro 2019, Böker 1997). Boswellia is most often taken in 2-3 divided doses with food.
Topically, creams containing 0.5%-2% Boswellic acids have been used (Togni 2015, Pedretti 2010, Maramaldi 2014). Essential oils of Boswellia (frankincense) are used as aromatherapy (Dyer 2014, Reis 2018).
Mechanisms of action
A variety of mechanisms of action of Boswelia have been evaluated, primarily in vitro, including anti-inflammatory effects via multiple pathways, regulation of the innate and adaptive immune system, and direct cytotoxic effects (Efferth, 2020). A number of in-vitro molecular targets of boswellic acids have been described, such as inhibition of cyclooxygenase 1 and 2 (Efferth, 2020), 5-lipoxygenase (5-LO), leukocyte elastase (Safayhi 1997), topoisomerase 1 and 2 (Syrovets 2000), prostaglandin E2 (Khan 2016), and NF-kappa B (Ernst 2008)
BAs selectively inhibit the key enzyme of leukotriene synthesis 5-LO (Ammon 2002) and reduce leukotriene biosynthesis in a concentration-dependent manner (Glaser 1999). 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 AKBA (Ernst 2008) - have been found to reduce tumour cell proliferation and induce apoptosis in several in-vitro experiments with animal (Zhao 2003, Wang 1991) and human malignant cell lines (Hostanska 2002, Kaur 2011) including glioma (Glaser 1999, Csuk 2015), melanoma (Zhao 2003), leukemia (Shao 1998), multiple myeloma (Kunnumakkara 2009), prostate (Yuan 2008), breast and cervical (Wang 2018), and colon (Conti 2018), as well as in vivo animal studies (Winking 2000, Schmidt 2017, Khan 2014). The underlying mechanism of BA-induced apoptosis and inhibition of cell proliferation are still being elucidated, but include interference with epigenetics in tumour cells (Shen 2012), increase in caspase 3/7 mediated apoptosis (Csuk 2015, Wang 2014), increase in Bax/Bcl-2 ratio (Conti 2018), modulation of Wnt/beta-catenin pathway and downregulation of NF-kappaB/COX-2 pathway (Ranjbarnejad 2017), reduction in prostaglandin E2 and its downstream targets (Khan 2016), and PARP cleavage (Ernst 2008) among others.
Bioavailability of boswellic acids (BA) is a concern as pharmacokinetic studies have found low plasma levels of BAs despite high oral dosing (Abdel-Tawab, 2011). To enhance absorption of the poorly water-soluble BAs, lecithin-formulated extracts (also known as phytosomes) have been developed (Riva 2016). A randomized cross-over study in healthy volunteers confirmed that administration of lecithin-formulated Boswellia extract resulted in significantly higher and more consistent plasma concentrations of all boswellic acids except KBA, compared to standard Boswellia extracts (Riva 2016).
Findings with healthy male volunteers indicated a possible initial fast gastric resorption, followed by intestinal resorption (Sharma 2004) depending on concomitant food intake (Sterk 2004). 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.
There is no information available on mutagenic effects of Boswellia extracts in women and men or long-term carcinogenicity.
Legal issues
Boswellia products are traded as "dietary supplements". H15 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. Many companies sell Boswellia extracts as “dietary supplements” in the EU and North America.
One systematic review of the anti-cancer and anti-inflammatory activities of Boswellia was published in 2020 (Efferth 2020). Seven human studies were identified; one randomized controlled trial (Kirste, 2011), one non-randomized trial (Böker 1997), two uncontrolled observational trials, (Janssen 2000; Streffer 2001), and three case reports (Winking 1996, Flavin 2007, Xia 2017). All studies included patients with primary brain tumors with the exception of one case report of brain metastases from breast cancer (Flavin 2007), and one case report of bladder cancer (Xia, 2017). One additional single-arm trial (De Pierro 2019) was published but not included in the systematic review. One randomized controlled rial of a topical 2% Boswellia cream for women receiving adjuvant breast radiation is also available.
Description of included studies
Antitumour treatment
No studies have focused on objective tumour response or survival outcomes for Boswellia in people with cancer.
Supportive care
Brain oedema
One RCT (Kirste 2011), one prospective non-randomized trial (Böker 1997), one single-arm pilot study (De Pierro 2019), one prospective case series (Streffer 2001), and one retrospective case series (Janssen 2000) have evaluated the effect of boswellia on cerebral oedema.
Findings from a randomised controlled pilot trial with 44 patients suggest a positive effect of Boswellia serrata on brain oedema. (Kirste 2011) 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). Re-evaluation 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).
In a prospective clinical study with 29 glioma patients 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 (Böker 1997). 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.
A single-arm pilot study (n=20) administered a phytosome-formulation of boswellic acids (4500mg/day) to patients receiving adjuvant radiochemotherapy for glioblastoma (GBM). (De Pierro 2019) 22% of participants experienced reduced oedema at T1 (12 weeks post-op) compared to T0 (4-weeks post-op). Steroid use and quality of life scores were relatively stable throughout the study. The study is difficult to interpret given the lack of control group. Adverse events were not reported on.
Two case series (Janssen 2000, Streffer 2001) suggested that there might be a beneficial effect for Boswellia extracts on brain oedema in study participants with brain tumours or leukoencephalopathy. However, without control groups the results are difficult to interpret, and the applicability of these findings to other patients, is limited due to selection of participants and study design.
Radiation dermatitis
A placebo-controlled RCT evaluated the effect of topical 2% Boswellic acid cream applied twice daily compared to a base cream on radiation dermatitis in 114 women receiving adjuvant breast radiotherapy (Togni 2015). 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.
Adverse effects
Boswellia is generally considered safe (Efferth 2020). The maximum tolerated dose has not been established, however doses as high as 4200mg/day resulted in no serious adverse events (Kirste, 2011).
Clinical trials of Boswellia have reported adverse events (AEs) to be uncommon and mild in severity; (Ammon 2002; Janssen 2000; Streffer 2001; Böker 1997; Togni 2015) Reported side effects are mainly gastrointestinal or skin reactions. Clinical trials of use for non-cancer indications have also found Boswellia extracts to be safe (Yu 2020, Efferth 2020).
Contraindications
Pregnancy and lactation - nothing is known about teratogenicity and possible effects of Boswellia extracts on breast-fed infants.
Boswellia is also contraindicated in cases of known allergy to Boswellia or components of these extracts.
Interactions
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 3A4 (Frank 2006). Another in vitro study showed a concentration-dependent modulation of P-glycoprotein (P-GP) 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 application (Weber 2006).
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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