New research underscores need of folate intake
New data strengthen case of chemoprotection
Folates have long been recognized as essential to fetal health, but a new body of research suggests the importance of folates may be chemoprotective as well.
Several recent studies offer the following food for thought:
- High folate intake from food sources may reduce the risk of pancreatic cancer among smokers.1
- Increased folate intake may reduce the risk of breast cancer in alcohol drinkers.2
- DNA damage from low folate intake may pose an increased risk of all types of cancers.3
The National Cancer Institute (NCI) in Bethesda, MD, reports 80% of American children and 68% of American adults do not eat five portions of fruits and vegetables a day, which means there is a shortfall of micronutrients — and especially folate — in the vast majority of the American population.
The National Health and Nutrition Examination Study (NHANES II) showed folate deficiency is present in 10% of the American population and in 25% of the country’s poor; however, recent regulations requiring folate enrichment of packaged grain products may have changed those figures.
A study from the University of California at Berkeley showed that micronutrient deficiencies, including the low intake of folates, break DNA strands, mimicking the effects of radiation.
"Micronutrient deficiency may explain, in good part, why the quarter of the population that eats the fewest fruits and vegetables [five portions a day is advised] has about double the cancer rate for all types of cancer compared to the quarter with the highest intake," says Bruce Ames, PhD, professor of biochemistry and molecular biology at the University of California at Berkeley. Ames is the author of the study on DNA damage and micronutrient deficiency.
"The evidence is very clear. Adequate folate intake keeps chromosome breakage from occurring and cell mutations from taking place," he explains. "Tell your patients this: If you don’t eat enough fruits and vegetables, you might as well be irradiating yourself. You’ll get the same kind of chromosome damage."
Some background on folates
Folate and folic acid are forms of a water-soluble B vitamin. Folate occurs naturally in food and folic acid is the synthetic form of this nutrient that is found in supplements and fortified foods as required under U.S. law since 1998. Folate is necessary for the production and maintenance of new cells, and it is therefore especially important during periods of rapid cell division and growth such as infancy and pregnancy. It is also needed to produce DNA and RNA, and helps prevent changes to DNA that may lead to cancer.
NHANES III (1988-91) and the Continuing Survey of Food Intakes by Individuals (1994-96) indicated that most adults did not consume adequate folate. However, the folic acid fortification program has increased folic acid content of commonly eaten foods such as cereals and grains, and as a result, the diets of most adults now provide recommended amounts of folate equivalents.
| Folates: Recommended Intake | |
| Ages 19 and older: (men and women) |
400 mcg |
| Pregnant women: | 600 mcg |
| Lactating women: | 500 mcg |
| Source: National Institutes of Health, Bethesda, MD. | |
Folates and cancer
A NCI study of older male smokers shows that taking in more folates in food rather than as supplements appears to reduce the risk of pancreatic cancer. Past studies indicate that cigarette smoke may reduce folate and vitamin B6 status and interfere with B12 metabolism.
"Baseline energy-adjusted dietary folate was significantly inversely associated with pancreatic cancer with those in the highest quintile having approximately half the risk compared to those in the lowest quintile," wrote lead author Rachael Stolzenberg-Solomon, a cancer prevention fellow at NCI. "So we decided to take a look at pancreatic cancer because, outside of lung cancer, it is one type of cancer that has been associated with smoking.
Stolzenberg-Solomon hypothesizes that the mechanism at hand is increased gene mutation or less efficient DNA production due to low folate intake. Folate deficiency also has been observed in alcoholics.
A 1997 review of the nutritional status of chronic alcoholics found low folate status in more than 50% of those surveyed. Alcohol interferes with the absorption of folate and increases excretion of folate by the kidney. In addition, many alcohol abusers have poor-quality diets that do not provide the recommended intake of folate. Increasing folate intake through diet, or folic acid intake through fortified foods or supplements, may be beneficial to the health of alcoholics.
Folates and breast cancer
Low intakes of folate also may increase breast cancer risk, especially among women who drink alcohol, according to a Mayo Clinic study to be published next month in the journal Epidemiology. Biochemical data suggest that low vitamin B intake may increase the risk of breast cancer through decreased DNA repair capacity, in much the same manner low folate intake was associated with higher risk of pancreatic cancer in the NCI study.
Harvard researchers reported three years ago, based on data from the Nurses Health Study, that women who were relatively heavy drinkers, consuming two to five alcoholic drinks each day, were 41% more likely to develop breast cancer than nondrinkers. But for moderate drinkers who consumed three-fourths to one drink, or 10 g of alcohol, a day, the risk was only 9% higher than among nondrinkers.4
In an effort to add to this growing body of data, the Mayo researchers reviewed findings from the Iowa Women’s Health Study, a prospective cohort study of cancer occurrence among 41,836 postmenopausal women. In 1986, participants completed questionnaires that assessed breast cancer risk (such as body measurements and history of pregnancy) and food and nutrient intake (including vitamin supplements). After 12 years of follow-up, the researchers found that 1,586 women had developed breast cancer.
Low intake of B vitamins did not influence the risk of breast cancer. However, low folate intake — below 173 mcg a day — among women who regularly consumed alcohol (more than 4 g, or less than half of one drink a day) significantly increased the risk of breast cancer. A 59% increased risk was noted among women with low folate intakes and alcohol intakes above 4 g per day, compared to nondrinkers and participants who consumed higher amounts of folate.
The researchers suggest that "folate supplementation may attenuate the risks of breast cancer associated with alcohol-containing beverages." They also note that "the fact that our food supply is now being supplemented with folate as a means to reduce birth defects may have unintended additional benefits on breast cancer."
The bottom line: "Everyone should take a multivitamin," says Ames. "They’re cheap and available everywhere. It doesn’t matter what you get. I just bought a year’s supply of multivitamins at Costco for $8. Think of it as a cheap insurance policy against cancer."
| Table: Food High in Folates | ||
% DV * |
||
mcg
100 Ready-to-eat cereal, fortified with 100% of the DV, 3/4 cup 400 45 Beef liver, cooked, braised, 3 ounces 185 25 Cowpeas (blackeyes), immature, cooked, boiled, 1/2 cup 105 25 Breakfast cereals, fortified with 25% of the DV, 3/4 cup 100 25 Spinach, frozen, cooked, boiled, 1/2 cup 100 25 Great Northern beans, boiled, 1/2 cup 90 20 Asparagus, boiled, 4 spears 85 20 Wheat germ, toasted, 1/4 cup 80 20 Orange juice, chilled, includes concentrate, 3/4 cup 70 20 Turnip greens, frozen, cooked, boiled, 1/2 cup 65 15 Vegetarian baked beans, canned, 1 cup 60 15 Spinach, raw, 1 cup 60 15 Green peas, boiled, 1/2 cup 50 15 Broccoli, chopped, frozen, cooked, 1/2 cup 50 15 Egg noodles, cooked, enriched, 1/2 cup 50 15 Rice, white, long-grain, parboiled, cooked, enriched, 1/2 cup 45
* DV = Daily Value. DVs are reference numbers based on the Daily Reference Intake. They were developed to help consumers determine if a food contains a lot or a little of a specific nutrient. The DV for folic acid is 400 mcg. The percent DV (% DV) listed on the nutrition facts panel of food labels tells adults what percentage of the DV is provided by one serving. Percent DVs are based on a 2,000-calorie diet. DVs may be higher or lower depending on calorie needs. Foods that provide lower percentages of the DV also contribute to a healthful diet.
Source: National Institutes of Health, Bethesda, MD.
Beware of the interaction between vitamin B12 and folic acid, says the NCI. Folic acid supplements can correct the anemia associated with vitamin B12 deficiency. Unfortunately, folic acid will not correct changes in the nervous system that result from vitamin B12 deficiency. Permanent nerve damage can occur if vitamin B12 deficiency is not treated. Intake of supplemental folic acid should not exceed 1,000 mcg per day to prevent folic acid from masking symptoms of vitamin B12 deficiency.
Clinicians should be aware of the relationship between folic acid and vitamin B12, especially in older adults, because they are at greater risk of having a vitamin B12 deficiency. If a patient is 50 or older, determine B12 status before prescribing a supplement that contains folic acid. Clinicians also should check for prescription medications commonly used by people with diabetes and heart disease that might effect folate utilization as noted in the table. (See table, below.)
| Medications that Can Interfere with Folate Utilization |
| Anticonvulsant medications (such as dilantin, phenytoin, and primidone) |
| Metformin |
| Sulfasalazine |
| Triamterene |
| Methotrexate |
| Source: National Institutes of Health, Bethesda, MD. |
References
1. Stolzenberg-Solomon RZ, Pietinen P, Barrett MJ, et al. Dietary and other methyl-group availability factors and pancreatic cancer risk in a cohort of male smokers. Am J Epidemiol 2001; 153:680-687.
2. Sellers TA, Kushi LH, Cerhan JR, et al. Dietary folate intake, alcohol, and risk of breast cancer in a prospective study of postmenopausal women. Epidemiology 2001; 12(4):in press.
Ames BN. DNA damage from micronutrient deficiencies is likely to be a major cause of cancer. Mutation Res 2001; 475:7-20.
4. Smith-Warner SA, Spiegelman D, Yaun SS, et al. Alcohol and breast cancer in women: A pooled analysis of cohort studies. JAMA 1998; 279:535-540.
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