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How well does Boswellia work?

Inflammatory processes are associated with increased formation of leucotriens from arachidonic acid. Leukotriens act as mediators in inflammation causing chemotaxis, chemokinesis and release of phagocyte enzymes. The key enzyme for the biosynthesis of leukotriens is the 5-lipoxygenase (5-LO). BAs have been found to interfere with leukotrien biosynthesis by a selective antagonism to the 5-LO5 and reduce leukotrien biosynthesis in a concentration-dependent manner (ref 11). Among the investigated BAs, AKBA showed the strongest inhibitory efficacy. Additionally, AKBA has been found to inhibit human leukocyte elastase in-vitro, an enzyme also involved in inflammation (ref 12).

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. An inhibitory effect could only be seen at higher concentrations; at lower concentrations an increased synthesis of leukotriens was observed.

Can Boswellia extracts have a direct effect on malignant cells and tumours? BAs have shown to reduce tumour cell proliferation and to induce apoptosis in several in-vitro experiments with animal (ref 13, 14) and human (ref 11, 13, 15, 16) malignant cell lines. However, in one study (ref 16) low concentrations of Boswellia extract resulted in an increased growth of human malignant cells. Growth of brain tumours in rats was reduced and survival time of animals significantly prolonged by administration of BAs (ref 17).

Clinical data

A retrospective case series, a prospective case series and one prospective clinical study – all involving brain tumour patients – have been published to date.

Janssen (ref 18) et al. evaluated the use of the Boswellia extract H15 retrospectively in 8 female and 11 male children (age 0.5 to 18 years). Results were presented for 17 children who were being treated for 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. Six patients received concomitant conventional therapy (3 radiation, 2 chemotherapy, 1 dexamethasone).

Six patients reported an improvement of their clinical condition and subjective relief of symptoms. In two of these patients, and in two additional patients with no subjective changes, regression of prior neurological symptoms like pareses and ataxia was documented. Radiological findings during the treatment period were reported for 11 patients: Regression of the peritumoural edema in one case and reduction of a tumour cyst in another case were documented by MRI. Under Boswellic acids, 4 children with malignant brain tumours in progression remained in stable disease over 3 to 8 months. In two additional patients an anti-tumoural treatment effect was seen, however, this was more likely to be the result of concomitant radio- and chemotherapy than of Boswellia extracts. In one case a partial remission over 26 months with administration of H15 as monotherapy was considered questionable by study authors, as tumour relapse had only been documented radiologically without histological re-evaluation.

Streffer (ref 19) et al. published a prospective case series of 12 adult patients with progressive cerebral edema with or without overt tumour progression. Seven patients were treated for glioblastoma and five patients for leukencephalopathy (after conventional tumour therapy). All study participants had to be taken off steroids or on a stable dosage of steroids for at least four weeks. H15 was administered orally at 3 x 1200mg/d and follow-up included MRI and clinical examination. Three (of seven) patients with glioblastoma reported a clinical improvement, in two of these three cases a reduction in perifocal edema could be seen in MRI scan. All five (of five) patients with leukencephalopathy reported a clinical benefit. No tumour response was seen in any patient.

A prospective clinical study with brain tumour patients was conducted by Heldt (ref 20, Böker (ref 21) et al. Twenty-nine patients with gliomas were allocated to three treatment arms with different doses of Boswellia extracts (3 x1200mg/d, 3 x 800 mg/d, 3 x 400 mg/d) prior to surgical intervention. After seven days of treatment, a reduction in size of perifocal edema as seen in CT scan could be found in the group with the highest daily intake (3 x 1200mg/d olibanum extracts) and also to a lower extent in the group receiving 3 x 800 mg/d. No effect on perifocal edema was seen in the group at 3 x 400 mg/d. Improvement in clinical symptoms was found only in the group at the highest daily dose (1200 mg/d). Patients who received 3 x 1200 mg/d olibanum also had a lower urinary excretion of leukotrien E4 (LTE4) (as a measurement of leukotrien synthesis in the body) after seven days of intervention compared to their LTE4 excretion prior to treatment. No effect on the tumour size in CT scan could be seen after seven days of intervention.

Both case series (Oxford level of evidence IV) suggest that there might be a beneficial effect for Boswellia extracts on brain edema 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. Both case series involved highly pre-selected small groups of brain tumour patients in differing treatment situations and clinical conditions and with different (malign and benign) tumours. There was no control group without Boswellia treatment and only Streffer evaluated the intervention prospectively. In the case series by Janssen, H15 was administered at different dosages for varying intervals.

The only clinical study (Oxford level of evidence IV) compared three different dosages of Boswellia extracts. Allocation to intervention groups was neither randomised nor concealed and there was no control group (without intervention or with placebo). The number of patients in this study is rather small and no further information is available on possible intervening factors like co-morbidity. It remains unclear how the clinical status of patients and the claimed improvement of clinical status was assessed. The radiologic method (CT scan) to evaluate edema size was criticised as unreliable (ref 22) and no information was available as to whether outcome assessors were blinded to treatment status of patients. Therefore, it remains unclear whether there was a significant reduction of brain edema at all and whether the reported reduction could be attributed to the Boswellia extracts. The hypothesis that the observed clinical improvement and a possible radiologically diagnosed reduction of brain edema was attributable to the intervention, was supported by a putative dose-response relationship and a reduction of LTE4 in urine.

References

11. Glaser T, Winter S, Groscurth P, Safayhi H, Sailer ER, Ammon HP, Schabet M, Weller M: Boswellic acids and malignant glioma: induction of apoptosis but no modulation of drug sensitivity. Br J Cancer 1999;80:756-65.

12. afayhi H, Rall B, Sailer ER, Ammon HPT: Inhibition by boswellic acids of human leukocyte elastase. J Pharmacol Experiment Therapeutics 1997; 281(1): 460-463

13. Zhao W, Entschladen F, Liu H, Niggemann B, Fang Q, Zaenker KS, Han R: Boswellic acid acetate induces differentiation and apoptosis in highly metastatic melanoma and fibrosarcoma cells. Cancer Detect Prev 2003;27:67-75.

14. Wang L-G, Liu X-M, Ji X-J: Determination of DNA topoisomerase II activity from L1210 cells - a target for screening antitumor agents. Acta Pharmacol Sinica 1991;12:114.

15. Shao Y, Ho CT, Chin CK, Badmaev V, Ma W, Huang MT: Inhibitory activity of Boswellic acids from Boswellia serrata against human leukemia HL-60 cells in culture. Planta Med 1998;64:328-31.

16. Hostanska K, Daum G, Saller R: Cytostatic and apoptosis-inducing activity of Boswellic acids toward malignant cell lines in vitro. Anticancer Res 2002;22:2853-62.

17. Winking M, Sarikaya S, Rahmanian A, Jödicke A, Böker DK: Boswellic acids inhibit glioma growth: a new treatment option? J Neurooncol 2000;46:97-103.

18. Janssen G, Bode U, Breu H, Dohrn B, Engelbrecht V, Gobel U: Boswellic acids in the palliative therapy of children with progressive or relapsed brain tumors. Klin Padiatr 2000;212:189-95.

19. Streffer JR, Bitzer M, Schabet M, Dichgans J, Weller,M: Response of radiochemotherapy-associated cerebral edema to a phytotherapeutic agent, H15. Neurology 2001;56:1219-21.

20. Heldt MR, Winking M, Simmet T: Cysteinyl-leukotrienes as potential mediators of the peritumoral brain oedema in astrocytoma patients. J Neurooncol 30[2]. 1996.

21. Böker DK, Winking M: Die Rolle von Boswellia-Säuren in der Therapie maligner Gliome. Deutsches Ärzteblatt 1997;94:A-1197.

22. Warnke PC, Kopitzki K, Ostertag CB: Die Rolle von Boswellia-Säuren in der Therapie maligner Gliome - Methodische Mängel. Deutsches Ärzteblatt 1998;95:220-2.

23. http://www.intelihealth.com (accessed 13.06.2005)