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Boswellia species essential oils and extracts as primary, synergistic, and preventative therapies for cancer patients.

Essential oils are extremely concentrated botanical substances that have great potential, when used correctly, to support oncology patients. Recent research suggests that certain essential oils may directly address cancer, while others demonstrate synergistic activity with chemotherapy drugs. This article will review and evaluate research literature on Boswellia species (frankincense) for cancer treatment, comparing preparation methods, study designs, and efficacy for cancer treatment.

Essential oils, because of their potency, should be taken internally only under the supervision of a trained health-care provider. Thankfully, the oils also are quite effective when inhaled or applied dermally (diluted in a polyunsaturated vegetable oil to a 1%-2% dilution). The scope of this article does not include a discussion of essential oil dosing methods but does review research on maximizing boswellic acid absorption.

Boswellia Species and Cancer Treatment

Boswellia species have been used for centuries to treat cancer in India, North Africa, and the Middle East. Researchers are now designing and conducting in vitro (in a test tube or petri dish) experiments to determine which cancer cell types are responsive to Boswellia. The research also aims to discern which species of Boswellia are most cytotoxic and which plant parts are most effective. In this discussion note variations in several different parameters: Boswellia species, the plant part (resin vs. leaf), and the extraction method (essential oil hydrodistillation vs. solvent extraction methods). These considerations are critical in evaluating the literature so that claims about a particular species or extraction method are not mistakenly attributed to another.

Cell studies have already demonstrated that Boswellia serrata has antiproliferative, proapoptotic effects in multiple human cancer cell lines, including meningioma, leukemia, melanoma, fibrosarcoma, colon, prostate, and pancreatic. (1-6)

Boswellia Serrata Essential Oil and Boswellic Acids

Many of the most promising studies have focused on boswellic acids, a group of pentacyclic triterpene constituents of Boswellia. Essential oils have a maximum molecular weight of approximately 300 grams per mole (g/mole). In contrast, boswellic acids (both [alpha] and [beta] forms) have a molecular weight of 456.7 g/mole. (7) Because boswellic acids have a higher molecular weight than an essential oil, essential oils do not contain boswellic acids. Claiming that an essential oil (with a maximum molecular weight of 300) contains boswellic acid (with molecular weight 456) is a physical impossibility.

A 2011 study by Suhail et al. created great excitement (and potentially confusion) about the efficacy of Boswellia essential oil for treating cancer. For this in vitro study, researchers prepared Boswellia sacra essential oil from Omani Hougarigrade resins through hydrodistillation at 78 or 100[degrees]C for 12 hours. Boswellia sacra essential oil-mediated cell viability and death were studied in three established human breast cancer cell lines (T47D, MCF7, MDA-MB-231) and an immortalized normal human breast cell line (MCF10-2A). All three human breast cancer cell lines were sensitive to essential oil treatment with reduced cell viability and elevated cell death. (8) The immortalized normal human breast cell line was more resistant to essential oil treatment.

A closer reading of this study, buried on the third page, reveals this important note: "Briefly, a weighed portion of the sample was diluted in methanol, filtered and then analyzed by high performance liquid chromatography.... Boswellic acids were detected by a photodiode array detector."

Personal correspondence with Hsueh-Kung Lin, a lead researcher on the study, confirmed that the sample referred to here was of Boswellia essential oil. Despite the abovementioned variance in molecular weight, Lin says that boswellic acids may be present in essential oils under two conditions. "First, boswellic acids might be 'coeluted' with other compounds during the 'cooking' process. Second, if a distiller is designed to have a very close distance between water surface and gas phase, high-molecular-weight compounds do not need to travel a long distance and can get into the oil phase." In other words, according to Lin, the boswellic acids likely traveled in water associated with the hydrodistillation process in tandem with the essential oil.

Lin also clarifies, " ... even though we detected boswellic acids in our preparations, the content was very low." Lin notes that although much of the research has focused on boswellic acid, "... we believe other compounds or a combination of different compounds can be useful for anticancer activity," a sentiment shared with a group of pharmacological researchers noted below.

Two of the authors of this study are associated with Young Living Essential Oils, a multilevel marketing company whose 2015 annual sales exceeded $1 billion. Young Living Essential Oils certainly has a vested interest in claiming that Boswellia essential oil has anticancer effects. One author, Gary Young, founded the company; another author, Cole Wooley, PhD (doctorate in chemistry, Brigham Young University), was at the time of publication director of research and development at Young Living Essential Oils.

Research studies cited below compare Boswellia essential oil with other methods of extraction.

Anticancer Effects and Increased Sensitivity to Chemotherapy Drugs

An in vitro study examined the effects, of an ethanol extract of the leaves of Boswellia ovalifoliata on triple negative breast cancer cells. Note that this research employed a different species (ovalifoliata instead of serrata), a different extraction method (ethanol instead of essential oil hydrodistillation), and a different plant part (leaves instead of resin). This in vitro study on triple-negative breast cancer cells demonstrated increased apoptosis; decreased NF-kB activation; and increased sensitivity to chemotherapy, specifically doxorubicin and cisplatin. Several studies have confirmed this last effect, of increasing efficacy of chemotherapy agents, with several types of whole essential oils as well as isolated essential oil constituents utilized in the in vitro experiments. (9)

Another in vitro study utilizing a methanol extract of Boswellia thurifera gum (resin) on human breast cancer cells demonstrated increased p53 activity and cytotoxicity with greater effects at 12 hours than at 6 hours of exposure. (10) Note that the study used yet another species (thurifera), a different solvent (methanol), and the gum or resin of the plant. These studies are included here to demonstrate the wide variety of preparation methods, plant parts, and plant species being utilized in Boswellia research.

Research Comparing Preparation Methods and Anticancer Effects

In the last couple of years as Boswellia research has grown more sophisticated, researchers are comparing different preparation methods within the same trial. In a study, published in 2015, researchers made seven different preparations of Boswellia serrata (11):

* petroleum ether, total extract

* methanol extract, total extract

* fractions I-IV of methanol extract

* essential oil

Each preparation was applied to hepatocellular carcinoma (HCC) and colorectal cancer (CRC) cell lines. The total petroleum and methanol extracts demonstrated the greatest cytotoxicity followed by the methanolic fractions. Although the essential oil did have significant cytotoxic effects on the HCC cell line, it had the least cytotoxicity of the seven preparation methods. The petroleum ether extract's cytotoxic activity exceeded that of doxorubicin (IC50 1.58 and 4.68 respectively). The methanol extract cytotoxicity was comparable to 5-fluorouracil (5-FU).

IC50 (half maximal inhibitory concentration) is a quantitative measure of how much of a particular drug or other substance (inhibitor) is needed to inhibit a given biological process by half. In this case, IC50 measured the concentration needed to kill half of the cancer cells.]

In brief, cytotoxicity of Boswellia serrata for HCC and CRC cell lines: total extracts > fractions > essential oil.

Synergistic Effects of Boswellia and Doxorubicin

Only a handful of essential oil studies have been conducted on humans. The vast majority of the research has been in vitro or animal (murine or rat) studies. The following rat study compared the effects of combining boswellic acid from methanolic extracts with doxorubicin in vitro and in vivo. Both in vitro and in vivo (rat) studies utilized human hepatocellular carcinoma, types HepG2 and Hep3B. (12) Combination of doxorubicin and boswellic acid methanolic extracts demonstrated significant (p < 0.001) activity compared with single agent:

* increased expression of proapoptotic caspase-3

* increased TNF-[alpha] activity, dose dependent

* decreased antiapoptotic protein NF-[kappa]B

* increased IL-6 activity in cancer cells

* decreased SGOT, SGPT, ALP, and bilirubin levels

* reversed acute histopathological changes in DOX-treated livers

These last two effects are particularly exciting because liver damage is one of the side effects of doxorubicin that can cause postponement or cancellation of treatments.

Boswellia to Treat Side Effects of Cancer Therapy

Boswellia serrata also has therapeutic benefits in addressing side effects of cancer treatment, especially radiation therapies. One study examined the anti-inflammatory effect of Boswellia cream vs. placebo for breast cancer radiation patients. (13) The water-based cream contained 2% Bosexil, a lecithin-based phytosome preparation that makes Boswellia serrata more bioavailable. Of 114 subjects, 55 received the 2% Boswellia cream and 59 were given the cream base (placebo). Patients applied the cream twice a day, immediately after radiation treatment and at bedtime; and morning and bedtime on days that they did not have radiation treatment. Erythema was measured by visual grading scale. Fewer patients using the Boswellia cream without concomitant chemotherapy treatment had "intense" erythema (22% in the treated group vs. 49% in the control group). Patients receiving concomitant chemotherapy also had less "intense" erythema rating compared with controls (29% vs. 47%). Patients receiving the Boswellia cream used less corticosteroid creams (25% vs. 63% in the control group).

In a prospective, randomized, placebo-controlled, double-blind pilot study, 44 brain tumor patients receiving radiation therapy were given either 4200 mg/day p.o. Boswellia serrata or placebo. (14) The study group had a marked response: 60% of the patients receiving Boswellia had >75% reduction in brain swelling, as measured by MRI. The difference in the amount of dexamethasone between the study and control groups was not statistically significant. Researchers surmised that the findings may be based on an "additional antitumor effect" of Boswellia. There were no severe adverse events in either group. This pilot study offers great hope for the possibility of reducing dexamethasone dosing for brain tumor patients undergoing radiation therapy.

Boswellia and Cancer Prevention

Boswellia serrata may help reduce the risk of developing breast cancer for women with dense breast tissue. These women have a significantly increased risk of developing breast cancer compared with women with least dense breast tissue; hence, reducing breast density could in turn reduce breast cancer risk. (15,16) In this recent trial of 62 women, the control group of 30 took capsules twice a day containing B2, B6, folic acid, and N-acetylcysteine. The study group took capsules twice a day containing the same nutrients plus boswellic acid, betaine, and myoinositol. In the control group, 22 out of the 30 subjects had extremely dense breast tissue. In the study group, 25 out of 32 were affected by extremely dense breast tissue. At the end of the trial, the control group had no change in breast density. In contrast, the study group had a 60% reduction in breast density as recorded by mammography. Those patients in the study group with decreased tissue compactness also reported reduced breast pain. This study points to the potential role of Boswellia and other supplements to address breast pain and reduce breast density as well as breast cancer risk.

Optimal Dosing of Boswellia

One of the challenges in using Boswellia clinically is its poor bioavailability. A randomized, open, single-dose, two-way crossover study compared taking boswellic acids on an empty stomach with dosing with a standardized high fat meal. Healthy males received three capsules of BSE-018, equivalent to 786 mg dry Boswellia serrata gum resin. Those taking the capsules with a high fat meal had a several-fold increase in plasma concentration time curves as well as peak concentration of beta-boswellic acid, 11-keto-beta-boswellic acid, and acetyl 11-keto-beta-boswellic acid after treatment. Detection of plasma levels of acetyl-alpha-boswellic acid and alphaBA was only possible with administration of a high-fat diet. (17)

Another study aimed to determine the optimal dosing schedule. Researchers gave 12 healthy males 333 mg of oral Boswellia serrata and measured blood levels of 11-keto beta-boswellic acid (KBA). The results suggested that the Boswellia needs to be dosed every 6 hours (calculated half-life) to maintain steady blood levels. (18)

Whole Plant vs. Isolated Constituents

Pharmacology researchers continue to debate the use of whole-plant extracts or whole essential oils versus isolated plant chemical constituents. The same debate has raged for several decades in the natural supplement industry; that is, do standardized extracts of a plant guarantee greater clinical efficacy? And even more to the point: can the elegant, interrelated, complex therapeutic activity of a whole plant be isolated to one or two "active constituents"?

Many pharmacologists advocate research into isolated essential oil constituents: "... the accomplished clinical studies have used the whole plant extract for study, although, not every boswellic acid shows a satisfactory pharmacological performance.... So, the need of the hour is to shift our focus on those active compounds whose mechanistic study has already been accomplished such as AKBA [3-acetyl-11-keto-[beta]-boswellic acid], ..." (19)

Other researchers recognize the complex nature of plants and advocate the use of whole essential oils: "Indeed, [essential oils'] complex chemical composition makes it difficult to envisage a single mechanism underlying the entireness of the biological effect, which is likely the sum and/or synergy of the biological activity of each component. For the same reason, data obtained from single components may not necessarily be, in turn, applied to the whole essential oil." (20)

While both of these differing views on pharmacological research are valid, I am biased toward whole essential oils. At this time we simply lack research methods to understand the synergistic activity of plants. That is the failure of our research models, not the plants.

Summary

Boswellia species offer promise for prevention and possibly treatment of cancer. Researchers continue to explore the most effective species, the optimal plant part, and the best preparation methods. Human clinical trials have been sparse for essential oils in general and that Boswellia in particular. The most promising human research suggests that Boswellia extracts (not the essential oil) offer anti-inflammatory support for radiation patients (breast and brain cancers) and cancer prevention for women with dense breast tissue. For optimal oral absorption, dose boswellic acids (not the essential oil) orally with a high-fat meal every 6 hours.

Notes

(1.) Yong SP, Lee JH, Bondar J, Harwalkar JA, Safayhi H, Golubic M. Cytotoxic action of acetyl-11-keto-[beta]-boswellic acid (AKBA) on meningioma cells. Planta Medica. 2002;68(5):397-401.

(2.) Shao Y, Ho C, Chin C, Badmaev V, Ma W, Huang M. Inhibitory activity of boswellic acids from Boswellia serrata against human leukemia HL-60 cells in culture. Planta Medica. 1998;64(4):328-331.

(3.) Zhao L, Wientjes MG, Au JL. Evaluation of combination chemotherapy: integration of nonlinear regression, curve shift, isobologram, and combination index analyses. Clin Cancer Res. 2004;10(23):7994-8004.

(4.) Liu JJ, Nilsson A, Oredsson S, Badmaev V, Zhao WZ, Duan RD. Boswellic acids trigger apoptosis via a pathway dependent on caspase-8 activation but independent on Fas/Fas ligand interaction in colon cancer HT-29 cells. Carcinogenesis. 2002;23(12):2087-2093.

(5.) Pang X, Yi Z, Zhang X, et al. Acetyl-11-keto-[beta]-boswellic acid inhibits prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis. Cancer Res. 2009;69(14):5893-5900.

(6.) Ni X, Suhail MM, et al. Frankincense essential oil prepared from hydrodistillation of Boswellia sacra gum resins induces human pancreatic cancer cell death in cultures and in a xenograft murine model. BMC Complement Altern Med. 2012; 12: 253. Epub 2012 Dec 13. doi:10.1186/1472-6882-12-253. PMCID: PMC3538159.

(7.) Pappas R. Frankincense and boswellic acid. Int J Prof Holist Aromather. Winter 2012;1(3).

(8.) Suhail MM, Wu W, et al. Boswellia sacra essential oil induces tumor cell specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells. Suhail et al. BMC Complement Altern Med. 2011,11:129.

(9.) Lesgards JF, Baldovini N, et al. Anticancer activities of essential oils constituents and synergy with conventional therapies: a review. Phytother Res. 2014;28:1423-1446.

(10.) Yazdanpanahi N, Behbahani M, et al. Effect of boswellia thurifera gum methanol extract on cytotoxicity and p53 gene expression in human breast cancer cell line. Iran J Pharm Res. 2014 Spring;13(2):719-724.

(11.) Ahmed H, Abd-Rabou A, et al. Phytochemical analysis and anti-cancer investigation of Boswellia serrata bioactive constituents in vitro. Asian Pac J Cancer Prev. 2015;16(16):7179-7188.

(12.) Khan MA et al. Caspase mediated synergistic effect of Boswellia Serrata extract in combination with doxorubicin against human hepatocellular carcinoma. BioMed Res Int. 2014(2014):294143. PMC. Epub 29 Dec. 2015.

(13.) Togni S, Maramaldi G, et al. Clinical evaluation of safety and efficacy of Boswellia-based cream for prevention of adjuvant radiotherapy skin damage in mammary carcinoma: a randomized placebo controlled trial. Eur Rev Med Pharmacol Sci. 2015;19(8):1338-1344.

(14.) Kirste S, Treier M, et al. Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors: a prospective, randomized, placebo-controlled, double-blind pilot trial. Cancer. 2011 Aug 15;117(16):3788-95. doi:10.1002/ cncr.25945. Epub 2011 Feb 1.

(15.) McCormack VA, Burton A, et al. International Consortium on Mammographic Density: methodology and population diversity captured across 22 countries. Cancer Epidemiol. 2016 Feb;40:141-151. doi:10.1016/j.canep.2015.11.015. Epub 2015 Dec 24.

(16.) Tice JA, O'Meara ES, et al. Benign breast disease, mammographic breast density, and the risk of breast cancer. J Natl Cancer Inst. 2013 Jul 17;105(14):1043-1049. doi:10.1093/jnci/djt124. Epub 2013 Jun 6.

(17.) Sterk V, Buchele B, et al. Effect of food intake on the bioavailability of boswellic acids from a herbal preparation in healthy volunteers. Planta Med. 70(2004): 1155-1160.

(18.) Sharma S, Thawani V, et al. Pharmacokinetic study of 11-Keto beta Boswellic acid. Phytomedicine. 11(2004):255-260.

(19.) Roy NK, Deka A, et al. The potential role of boswellic acids in cancer prevention and treatment. Cancer Lett. 2016 Jul 10;377(1):74-86. doi:10.1016/j. canlet.2016.04.017. Epub 2016 Apr 14.

(20.) Russo R, Corasaniti MT, et al. Exploitation of cytotoxicity of some essential oils for translation in cancer therapy. Evid Based Complement Alternat Med. 2015;2015:397821. doi:10.1155/2015/397821. Epub 2015 Feb 4.

by Judith Boice, ND, Lac, FABNO

Dr. Judith Boice, award-winning author, international teacher, naturopathic physician, and acupuncturist, has a special passion for working with wellness and women's health. Dr. Boice conducts seminars throughout North America teaching people how to apply the secrets in her book But My Doctor Never Told Me That I: Secrets for Creating Lifelong Health to achieve their personal life and health goals.

Dr. Boice has also created "The High Level Wellness Program" to support individuals in achieving their personal life and health goals. She designed the High Level Wellness Program for patients who wanted to improve their health but were unsure of where or how to begin.

Other creative passions include photography, music, and gardening. Her photographs have appeared in several magazines and newspapers, Trees for Life calendars, and Sierra Club Books publications. She also has a radio program. A Phi Beta Kappa graduate of Oberlin College, Dr. Boice is the author of several magazine articles and eight books, including But My Doctor Never Told Me That!. Her book Menopause with Science and Soul: A Guidebook for Navigating the Journey (paperback) is a 2009 Nautilus Silver Book Awards Winner. Her most recent book, The Green Medicine Chest: Healthy Treasures for the Whole Family, won two awards in 2011: the Nautilus Silver Award winner for wellness/prevention/vitality and the Living Now Book Awards Bronze medal winner for health/wellness.

Dr. Boice has been interviewed on several radio shows and has a YouTube video. To watch or listen to her, go to her interviews page.
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