Paracelsus to Parascience:
The Environmental Cancer Distraction
N. Ames and Lois
September 7, 1999
3. Errors of Omission: Micronutrient Inadequacy is Genotoxic
Endogenous hormones [43;44], dietary imbalances [45;46], inflammation due to
infection  and genetic factors, none of which involve an exogenous carcinogenic
chemical, are major contributors to human cancer .
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  and 68%
of adults  did not meet the intake recommended by the National Cancer Institute
and the National Research Council: five servings of fruits and vegetables per
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 .
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
. 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) . 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 . Folate
supplementation above the RDA minimized chromosome breakage . 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% . Folate deficiency also damages human sperm , causes neural
tube defects in the fetus and an estimated 10% of U.S. heart disease . 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  had a lower folate level than that
at which chromosome breaks occur . In two small studies of low income (mainly
African-American) elderly  and adolescents  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 .
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 , smoking , and inflammation .
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 . 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 .
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 . 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 , or young adults
, 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 . 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 ), 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 . 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 . 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