Food and Supplementation Benefits and Risks in Carcinogenesis — Part 1

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

Whole food, grown on organic, nutrient-rich and chemical-free soil in a clean environment, provides the body with a synergistic array of thousands of known and unknown antioxidants, nutrients and powerful nutraceutical compounds. These exogenous antioxidants (carotenoids, flavonoids, vitamins, trace minerals, etc) help the body counteract oxidative stress. Assuming that these foods are pesticide-free and harvested at the right time, they provide the best avenue of full-spectrum protection against reactive oxygen, species (ROS) that initiate various growth factors, cytokines, and other chemical mediators that increase inflammation and a proliferative carcinogenic response. The unfortunate truth however is that foods of this quality are in short supply in the Standard American Diet (SAD). Today's foods are not only depleted of vital antioxidants, trace minerals, and phytochemicals but contain harmful levels of pesticides and other toxic chemicals. Studies have documented that antioxidant levels in foods have d ecreased by 50% over the past 25 years in the US. [1,2]

The progressive depletion of antioxidants in food has created an imbalanced prooxidative state that may increase one's risk of cancer. Indeed, studies have shown that diet accounts for 35 to 80% of cancers. [3-6] Recently, valuable controlled scientific data supporting cancer risk reduction with antioxidants has been presented by Block and Evans. [7] The danger is that antioxidant levels in the SAD are too low to protect the body from the increasing levels of chemical carcinogens in the environment. The result: instead of winning the war against cancer, statistics since 1970 show a dramatic rise in the incidence of cancer and other chronic degenerative diseases in the US.

Addressing Disturbed Mitochondrial Energetics and Carcinogenesis

The cytoplasm and its organelles, particularly the mitochondria, allow the cell to generate energy that it uses to synthesize structural and enzymatic molecules that give it the functional properties by which it contributes to the overall operation of the organism. [8-9] Energy formation depends on nutrient intake, electron flow and oxygen transport to the body tissue. Acidification of the extracellular matrix, due to increasing environmental pollution, strees, and dietary deficiencies of nutrients, leads to a reduction O2 transport to the tissues and high levels of oxidative stress. [11-12] Many cellular processes require O2 and the optimum blood-carrying capacity for O2 is closely correlated to an anabolic pH of around 7.4. However, sometimes oxygen and other small molecules become electron deficient. These oxygen radicals (also called radical oxygen species, ROS), can react with DNA to cause:

* A distortion in the shape of the DNA molecule, potentially causing mistranslations,

* Mutations when the DNA reproduces itself (replicates), an adducted base can be misread causing a mutation in the new strand.

* Mutations or deletions of genetic material from the bulky adducts which, in turn, cause breakages in the DNA strand. If these adducts are not repaired, they may induce extensive mutations that lead to carcinogenesis.

Chemical carcinogens can cause direct DNA damage because they are electron-deficient molecules after transformation by normal human metabolic enzymes causing them to react readily with electron-rich molecules such as protein and DNA. Oxidative damage to DNA occurs at a daily rate of about [10.sup.4] hits per cell in humans and has been shown to play a significant role in carcinogenesis. [13-15] Nutrition and diet provides the primary way to decrease and repair oxidative DNA damage. [16] It is well known that DNA damage repair is accomplished by internal surveillance and repair systems involving antioxidant nutrients that function as electron donors. They specifically protect DNA and cell membranes against oxidative damage, including that induced by carcinogenic agents. Because the mitochondria is the site in the cell where the majority of oxidative chemistry occurs, mitochondrial DNA is some 2000 times more susceptible to oxidative damage than nuclear DNA. [17] Nutritional deficiency states lead to disturbed mitochondrial energetics, genetic alteration of mitochondrial DNA, and increased exposure to mitochondrial carcinogens. [18]

Altered Biological and Energetic Pathways

Undernutrition, related to the down-regulation of nutrient uptake with advancing age and/or poor dietary choices may reduce the functional capacity of many organs and glands of the body. Accelerated molecular and tissue aging is a mismatch of genes with one's energetic and nutritional status, lifestyle, diet, and environment. In turn, these altered energetic and biological pathways contribute to post-translational modifications of protein and Advanced Glycosylation End Products (AGEs) that increase proinflammatory cytokines, inhibit B cell function, and decrease hormone and neurotransmitter action; transport, and reception.

The identification of nutrients and dietary factors that trigger carcinogenesis is of paramount importance in preventing carcinogenesis. In addition, the novel use of whole food concentrates, phytochemicals and nutritional factors that are metabolically active and organ-targeted may provide novel ways to treat a wide range of inflammatory disorders. [12] By altering the specificity of action of nutraceutical complexes, nutrients can be used to target tissues and organs, and modulate anti-inflammatory bioactivity by reducing toxicity, endobiosis, and oxidative stress. The following are examples of three biochemical pathways deplete nutrients and promote carcinogenesis: