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Paracelsus to Parascience:
The Environmental Cancer Distraction

by Bruce N. Ames and Lois Swirsky Gold
September 7, 1999

3. Errors of Omission: Micronutrient Inadequacy is Genotoxic

Endogenous hormones [43;44], dietary imbalances [45;46], inflammation due to infection [47] and genetic factors, none of which involve an exogenous carcinogenic chemical, are major contributors to human cancer [46].

High consumption of fruits and vegetables is associated with a lowered risk of degenerative diseases including cancer, cardiovascular disease, cataracts and brain dysfunction [46;48]. More than 200 studies in the epidemiological literature show, with great consistency, an association between low consumption of fruits and vegetables and high cancer incidence [49-51](Table 4). The quarter of the population with the lowest dietary intake of fruits and vegetables has roughly twice the cancer rate of the quarter with the highest intake for most types of cancer (lung, larynx, oral cavity, esophagus, stomach, colorectal, bladder, pancreas, cervix and ovary). 80% of U.S. children and adolescents [52] and 68% of adults [53] did not meet the intake recommended by the National Cancer Institute and the National Research Council: five servings of fruits and vegetables per day.

Publicity about hundreds of minor hypothetical risks, such as pesticide residues, can result in loss of perspective on what is important: half the U.S. public does not know that fruit and vegetable consumption is a protection against cancer [54]. Fruits and vegetables are of major importance for reducing cancer; if they become more expensive because of reduced use of synthetic pesticides, then consumption is likely to decline and cancer to increase. People with low incomes eat fewer fruits and vegetables and spend a higher percentage of their income on food.

Folic acid deficiency, one of the most common vitamin deficiencies in the population consuming few dietary fruits and vegetables, causes chromosome breaks in humans [55]. The mechanism of chromosome breaks has been shown to be deficient methylation of uracil to thymine, and subsequent incorporation of uracil into human DNA (4 million/cell) [55]. Uracil in DNA is excised by a repair glycosylase with the formation of a transient single-strand break in the DNA; two opposing single-strand breaks cause a double-strand chromosome break, which is difficult to repair. Thus, folate deficiency appears to be a radiation mimic. Both high DNA uracil levels and chromosome breaks in humans are reversed by folate administration [55]. Folate supplementation above the RDA minimized chromosome breakage [56]. Folate deficiency has been associated with increased risk of colon cancer [57;58], and the 15 year use of a multivitamin supplement containing folate lowered colon cancer risk by about 75% [59]. Folate deficiency also damages human sperm [60], causes neural tube defects in the fetus and an estimated 10% of U.S. heart disease [61]. Diets low in fruits and vegetables are commonly low in folate, antioxidants, (e.g., vitamin C) and many other micronutrients [46;49;62].

Approximately 10% of the US population [63] had a lower folate level than that at which chromosome breaks occur [55]. In two small studies of low income (mainly African-American) elderly [64] and adolescents [65] done nearly 20 years ago nearly half had folate levels that low; the issue should be reexamined. Recently in the U.S., flour, rice, pasta, and cornmeal have been supplemented with folate [66].

Since radiation causes oxidative damage, insufficiency of dietary antioxidants is likely to be a radiation mimic. Antioxidants such as vitamin C (whose dietary source is fruits and vegetables), vitamin E, and selenium protect against oxidative damage caused by normal metabolism [17], smoking [45], and inflammation [48].

Low intake of any one of nine dietary micronutrients — folic acid, niacin, iron, zinc, selenium, and vitamins B6, B12, C, and E — appears to mimic radiation by breaking DNA and chromosomes or causing oxidative damage to DNA or both [45]. Some of these micronutrients come from fruits and vegetables and could account for much of their protective effect against cancer.

Many other micronutrients whose main dietary sources are not fruits and vegetables, also are likely to play a significant role in the prevention and repair of DNA damage, and thus are important to the maintenance of long term health.

Deficiency of vitamin B12 whose main dietary source is meat, is common. About 4% of the U.S. population consumes less than half of the RDA of vitamin B12 [67]. About 14% of elderly Americans and about 24% of elderly Dutch have mild B12 deficiency, in part accountable by the Americans taking more vitamin supplements [68]. Vitamin B12 would be expected to cause chromosome breaks by the same mechanism as folate deficiency. Both B12 and methyl-THF are required for the methylation of homocysteine to methionine. If either folate or B12 is deficient, then homocysteine, a major risk factor for heart disease [61;69], accumulates. When B12 is deficient, then tetrahydrofolate is trapped as methyl-THF; the methylene-THF pool, which is required for methylation of dUMP to dTMP, is consequently diminished. Therefore, B12 deficiency, like folate deficiency, should cause uracil to accumulate in DNA, and there is accumulating evidence for this [Ingersoll et al., unpublished; 70]. The two deficiencies may act synergistically. In a study of healthy elderly men [71], or young adults [56], increased chromosome breakage was associated with either a deficiency in folate, or B12, or with elevated levels of homocysteine. B12 supplementation above the RDA was necessary to minimize chromosome breakage [56]. B12 deficiency is known to cause neuropathy due to demyelination and loss of peripheral neurons [reviewed in 55].

Niacin, whose main dietary sources are grain and meat, contributes to the repair of DNA breaks [72;73]. As a result, dietary insufficiencies of niacin (2% of the U.S. population ingests <50% of the RDA [67]), folate and antioxidants may act together to increase DNA damage.

Deficiency of zinc, iron, or vitamin B6, can lead to DNA damage and appear to be radiation mimics [45]. Low intake (<50% of the RDA) in the U.S. population is 18% for zinc, 10% for B6, and 19% of menstruating women for iron [45]. We estimate that half of the U.S. population may be low in at least one of these nine micronutrients. Optimizing micronutrient intake (through better diets, fortification of foods or multivitamin-mineral pills) can have a major impact on public health at low cost. More research in this area and educational efforts aimed at increasing micronutrient intake and balanced diets, should be high priorities for public policy.

Article reprinted from Mutation Research Frontiers, 7 September 1999

Revised April 23, 2015