Food and Supplementation Benefits and Risks in Carcinogenesis — Part 1

Townsend Letter for Doctors and Patients, Oct, 2001 by Paul Yanick

* Steroid Hormone Pathways and Insulin Modulation of Steroid Hormone and Proinflammatory Pathways: It is well known that many nutrients function as precursors, co-factors, or prohormones in the biochemical pathways of steroid, peptide, and ecosanoid hormones and, as such, modulate anti-inflammatory pathways. [19-21] When steroid hormone pathways are altered with nutrient-dense foods and appropriate nutraceutical supplements, the modulation of steroid hormones may influence gene expression, cell signaling and can regulate the repair and rebalancing of physiological status. Evidence indicates that increasing the competence of DNA repair mechanisms plays a vital role in resisting carcinogenesis. [14-15] Hyperinsulinemia stimulates the detoxification of steroid hormones by upregulating the sulfation and glucuronidation of these hormones, and depletes DHEA and nutrient co-factors and precursors while stimulating the overproduction of androgens. [22-23] In addition, hyperinsulinemia increases proinflammatory ecosa noids and interleukin-6 (IL-6) which, in turn, stimulates the liver's Kupffer cells to release proinflammatory cytokines. Moreover, insulin insensitivity downregulates the expression of genes that regulate steroid hormones and detoxification enzymes, thereby promoting carcinogenesis. [23-24] IL-6 is known to increase brain inflammation and active stress-modulating hormonal pathways through sympathetic nervous system activation. The level of serum amyloid protein increases 1000 fold in response to inflammation and shifts biological pathways toward oxidant stress and an increased calcium uptake which leads to cell death. [26]

* Hexose MonoPhosphate Shunt Pathway: Insulinemia decreases the production of cell-protective phospholipids and lowers glutathione regeneration. Defects in this pathway result in increased oxidative stress and an insufficient supply of ribose, necessary for the polynucleotide synthesis of DNA and RNA. [24-25]

* Nitric Oxide / Homocysteine Mediated Pathways: An overproduction of nitric oxide combined with the uncoupling of mitochondrial energy production and high homocysteine levels results in oxidative-induced damage of vascular and neurologic systems and tumorgenesis. [26-27,32]

The Hidden Dangers of Supplemental Nutrients in Carcinogenesis

Since an imbalanced prooxidative state may increase one's risk of cancer, identifying hidden and common supplemental or dietary triggers of carcinogenesis is a reasonable and important goal. Synthetic vitamins such as the synthetic beta carotene used in the widely publicized New England Journal of Medicine study decreases the levels of other cartenoids in the tissues and increases carcinogenesis as the study noted. [28] This does not happen when natural carotenoid complexes are supplemented as the anticarcinogenic effects of the full spectrum of cartenoids are powerful. [29,30] This hidden danger may be a factor in carcinogenesis because of the indiscriminate use of supplementation by the American public with individual nutrients or multivitamin products that are synthetic and not derived from plant sources and may promote carcinogenesis. For example, feeding a methionine enhanced diet to animals doubled the formation of crypt cell proliferation and aberrant crypt formation and an arginine-enhanced diet incr eased tumor cell growth in mice more than twofold over mice fed control diets. [31-32]