Food and Supplementation Benefits and Risks in Carcinogenesis — Part 1

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:

* 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]

Even though free radicals occur as normal by-products' of metabolism, they get "out of control" when the body is deficient in antioxidants or patients are given too much of a certain antioxidant. The antioxidant power of fruits and vegetables is awesome and beyond the power of isolated unnatural, unbalanced and narrow-minded "bullet" treatments. [33-35] For example, studies have shown that the bioavailability of individual tocopherols and tocotrientols is best when all subtypes of tocopherols and tocotrienols are given and that a high intake of polyunsaturated oils without a concomitant increase in vitamin E may cause neurological disorders. [36,37] There is growing evidence that whole food concentrates packed with powerful phytochemicals are far superior to the fragmented use of synthetic or isolated vitamin and mineral supplements. [6,12] Plant phytonutrients have been documented to inhibit oncogene activation, P53 mutation, angiogenesis, suppress COX-2 activation, protect DNA, stimulate natural killer (NK ) cell activity and T-helper cell proliferation and inhibit many enzymes and signal transducers used by cancer cells for growth, proliferation, and metastasis. [44-50]

A continuous battle is waged between free radicals and antioxidants every day in the body. Runaway free radical chain reactions can sabotage cells -- the building blocks of all organs and tissues. The ability of the body to produce natural antioxidants decreases with advancing age. Nutraceutical support that is targeted to meridian-organ sites carrying appropriate plant phytochemicals and nutrients is necessary to fortify the cellular environment with the essential biological weapons to reduce oxidative stress. [51-54] These organ-specific nutraceuticals contribute significantly to defenses against oxidative damage and protect the bddy by:

1. Intercepting and absorbing free radicals after they are formed and improving Krebs cycle function.

2. Shielding the cell's DNA and mitochondrial membranes from free radical bombardment.

3. Reducing oxidative transcription factors and neutralizing oxygen breakdown products before they can damage the body.

4. Supplementing electrons to compensate for the process of oxidation -- the robbing of electrons from substances -- thereby stabilizing the electron transport chain.

5. Upregulating hormone pathways. and optimizing neurotransmitter synthesis to maintain and stabilize neurohormonal regulation and repair routines.

Tissue/Organ and Cell Specificity

There appears to be a selective uptake by the various tissues of the body for pytochemicals. For example, lung tissue has a high concentration of lutien, phytofluene and betacryptoxanthin and breast tissue is high in phytofluene and zeta-carotene. The cervix and prostate gland have high levels of lycopene [54] In addition, a tissue-specific protective effect against chemotherapy toxicity has been noted for quercitin in renal tubular cells, glutatbione on cardiac and skeletal muscle, and curcumin on cardiac tissue. [55-57]

Protein kinase C, a vital step in carcinogenesis, can be inhibited by fisetin, quercetin, luteolin, apigenin, myricetin, morin, and curcumin. [58] The enzyme tyrosine kinase which promotes tumor spread via growth factors can be inhibited by quercetin, luteolin, apigenin, and kaempferaol. [59] These powerful plant compounds have anticarcinogenic effects and growth inhibitory effects on a variety of tumors. [60'61]

The N-3 oils inhibit tumor growth in breast and colon cancers by targeting and damping down COX-2 inflammatory activity, reported to be abnormally high in tumors, and prernalignant growths of the esophagus, stomach, breast, prostate, lung, bladder, pancreas, skin, cervix, head/neck, and colon. [62,63] Research on natural plant-derived COX-2 inhibitors has been reported in more detail in another publication by the authorfr. [64]

At the cellular level, NK cell activity can be. enhanced by ascorbic acid which also protects normal cells against apoptosis, reduces oxidative damage, and enhances immune function. [65,66] Oral doses of vitamin C (60mg/kg body weight) enhanced NK cell activity up to ten-fold in 78% of patients tested in one study. [65] In another study, doses of 500, 1000mg reduced apoptosis by more than 50% in individuals with moderately elevated baseline apoptosisfr. [66] Since oxidative stress is a mediator of apoptosis, targeting cells with NK modulators such as mushroom extracts combined with carrier proteins will provide extraordinary action against hidden viral activity and deep-rooted fungal and yeast infections. [51"52]

Observational data (cross-sectional analysis, migration patterns, and retrospective and prospective longitudinal cohort studies) and experimental studies (case study methods and clinical studies) have established dietary guidelines for reducing the risk of cancer. [7] Prolonged consumption of adverse diets combined with exposure to water and air pollution and adverse lifestyle and social habits have advanced the carcinogenic potential of the average American. For example, the widespread consumption of refined flour (enriched with iron) has been associated with increased cancer induction, accelerated tumor growth, and metastasis, [68] while the common dietary practice of using margarines and refined oils (high in trans fatty acids) enhances tumor growth and carcinogenesis. [62,62] Unless these dietary practices are halted along with other common dietary errors, carcinogenesis will continue in the American population unabated.

Dietary and Nutritional Goals for the Treatment of Carcinogenesis, Not Cancer

New research has heightened long-standing concerns about the dangers of common food additives, preservatives, packaging and processing methods used by the food and nutritional industry. The increasing level of toxicity in supplements have documented that over 90% of natural supplements contain one or more toxic or carcinogenic ingredients that may silentlysuppress immunity and increase oxidative stress [72] When oncologists think more about treating the causes of carcinogenesis rather than only treating cancer in advanced stages, they will be in a position to halt the decades-long progression toward malignancy. Powerful COX2 specific phytochemicals and antioxidants are now, available to provide superior anti-inflammatory and anti-carcinogenic activity that are much safer than NSAIDs. [51-52 64]

A diet rich in fresh fruits and vegetables (preferably organic or biogenic) has been shown in 128 out of 156 dietary (epidemiological) studies to be protective against cancer.6 According to Jerome Block, M.D. of UCLA Medical Center and Steven Evans, MS ". . .there is 'sufficient pertinent scientific clinical data to indicate that certain antioxidant and other nutrient supplements reduce cancer risk, clinical cancer occurrence, and/or interrupt the carcinogenic process in appropriately-defined populations." [7] As for reducing the toxic effects of chemotherapy, Mark C. Houston, MD and John A. Strupp, MD of Vanderbilt University School of Medicine state "Ajudicious, scientifically-based use of supplements Would not only make the patient feel better subjectively, but would reduce complications, promote surgical healing, reduce infections, possibly reduce the growth of a tumor, prevent metastasis, and allow the oncologist to use higher doses chemotherapy and radiation when needed, without increasing complication rates." [6]

Rather then waiting to begin treatment before the final pathology report, physicians need to identify molecular biomarkers as described by Dr. Aristo Vojdani that are capable of signaling a greater risk of cancer. Furthermore, as Dr. Vojdani has noted, identifying the early precancerous stages of carcinogenesis before invasive disease begins is the key for intervention and prevention of the fatal diseases. [68]

In summary, carcinogenesis involves the prolonged accumulation of injuries at multiple biological levels. Biologic markers of molecular and immune system function along with Quantum Medicine [TM] protocols can help to define dysfunction early giving the Physician a chance to prevent malignancy

An antioxidant vitamin or flavonoid should not be taken alone for extended periods of time. Individualized testing of nutraceutical supplements and the targeting of specific tissues and organs will yield the best clinical response and this is especially true if the supplements tested contain grade 10 superior quality ingredients and are free of solvents, glues, lubricants, asbestos, binders, fillers, and other toxic chemicals. [51-52,64] Teamwork and synergism with combinations of appropriate antioxidants has been reported.[69-70] Since chemical binding implies strong interaction between nuclei and electrons, assessing the human energy system via quantum medicine TM techniques and targeting muscle-organ connections with low level light/laser therapies may help to enhance proprioceptive feedback mechanisms of the brain, thus allowing the practitioner to target "functionally weak" organs, thereby increasing the absorption of nutrients needed by deficient organs. Scientists have documented that photoassociative ionization causes molecular bond formation and creates order in the body's molecular and sub-molecular world. [73] The multi-electron redox capability of the right combinations of antioxidants combined with the versatility of new Qtiantum Medicine [TM] energy balancing techniques and organ-specific nutraceuticals offers new possibilities for addressing the quantum forces of oxidative stress.

Part II of this article will discuss the benefits of functional foods and highlight the food supplements that may prevent, slow down, or halt carcinogenesis.

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