Inflammation is an important protective mechanism in the human organism. It plays together with the activation of the various components of the immune system and allows suitable reactions to a range of conditions such as injuries or contact with microorganisms. However, if the regulation of inflammation is not properly controlled, the typical inflammatory disorders such as rheumatic diseases or allergies result. Cardiovascular disease, osteoporosis and other conditions typically occurring in the second half of life are likewise related to inflammatory mechanisms. Even cancer shares certain specific pathways with inflammation on the cellular level.
All conditions where inflammation plays a role feature common factors such as the formation of mediators which support the inflammatory process. Typical mediators of inflammation on the level of cellular turnover are certain prostaglandins, leukotrienes, interleukins, enzymes such as the endothelial and inducible nitrogen oxide synthethases (eNOS and iNOS), the cyclooxygenases COX I and II, lipoxygenase, matrixmetalloproteases (MMPs) or the C-reactive protein (CRP), or nuclear factors such as tumour necrosis factor alpha (TNFα) or nuclear factor κB (NFκB). They all coordinate the inflammatory process in a very complex manner.
Antiinflammatory drugs act on the formation or function of such mediators, factors and enzymes, and thus inhibit the inflammation reaction. Isoflavones have been demonstrated to act on various of these inflammation mediators.
The formation of interleukin 6 (IL-6) is increased when the hormonal levels drop during menopause. Elevated levels of IL-6 are related to the formation of tumours, osteoporosis, arthritis and neurodegenerative diseases. Isoflavones have been shown to suppress IL-6 formation (Dijsselbloem et al. 2004; Vanden Berghe et al. 2006) – an effect also demonstrated in animal models of artificially induced inflammation (Paradkar et al. 2004).
Another important mediatior of inflammation, osteoporosis and cancer is TNFα, for which the increased formation also correlates with decreasing estrogen levels. This correlation was impressively demonstrated in postmenopausal women, where in addition the supplementation of isoflavones reduced the formation of TNFα. Upon discontinuation the levels increased again (Huang et al. 2005). Isoflavones likewise inhibit the formation of the inflammation marker CRP in postmenopausal women (Vafeiadou et al. 2006).
Isoflavones are known to be activators of the estrogen-beta receptor (ER-β), and thus of a protective system with multiple tasks in the organism. Until menopause the estrogens contribute to the control of inflammatory disorders (Zänker 2006). This effect is obviously transmitted through ER-β, and thus through a receptor system also reacting to isoflavones. The activation of ER-β-related protective systems is, however, only one aspect of isoflavone effects in inflammatory disorders. Isoflavones most likely also directly affect the formation of inflammation mediators, and can therefore probably also provide beneficial effects when there is no or only little ER-β present. Such a situation is found in certain forms of breast cancer, where isoflavones and their synthetic derivatives such as phenoxodiol still have an effect (Vanden Berghe et al. 2006).
References
Dijsselbloem, N., Vanden Berghe, W., De Naeyer, A., and Haegeman, G. (2004). Soy isoflavone phyto-pharmaceuticals in interleukin-6 affections. Multi-purpose nutraceuticals at the crossroad of hormone replacement, anti-cancer and anti-inflammatory therapy. Biochem. Pharmacol. 68 (6): 1171-1185.
Huang, Y., Cao, S., Nagamani, M., Anderson, K. E., Grady, J. J., and Lu, L. J. (2005). Decreased circulating levels of tumor necrosis factor-alpha in postmenopausal women during consumption of soy-containing isoflavones. J. Clin Endocrinol. Metab 90 (7): 3956-3962.
Paradkar, P. N., Blum, P. S., Berhow, M. A., Baumann, H., and Kuo, S. M. (2004). Dietary isoflavones suppress endotoxin-induced inflammatory reaction in liver and intestine. Cancer Lett. 215 (1): 21-28.
Vafeiadou, K., Hall, W. L., and Williams, C. M. (2006). Does genotype and equol-production status affect response to isoflavones? Data from a pan-European study on the effects of isoflavones on cardiovascular risk markers in post-menopausal women. Proc Nutr. Soc. 65 (1): 106-115.
Vanden Berghe, W., Dijsselbloem, N., Vermeulen, L., Ndlovu, N., Boone, E., and Haegeman, G. (2006). Attenuation of mitogen- and stress-activated protein kinase-1-driven nuclear factor-kappaB gene expression by soy isoflavones does not require estrogenic activity. Cancer Res. 66 (9): 4852-4862.
Zänker, K. S. (2006). Prävention von Alterserkrankungen der Frauen. I. Die Bedeutung von Entzündungen auf zellulärer Ebene für das Altern. Gyne (1): 4-5.
Clinical effects 