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Toxicities, Adverse Nutrient Interactions, and Safety

July 5th, 2005

The attention of the nutrition community has traditionally focused on obtaining micronutrients in adequate amounts. Much less research information is available to set standards for the upper limits of safe intake. The Food and Nutrition Board was unable to set a UL for five of the first 17 nutrients reviewed, because studies on the presence of adverse effects from large doses of nutrients had not been conducted or were inadequate. It recommended that in the absence of a UL, “extra caution may be warranted in consuming levels above recommended intakes.”

Although suppliers often cite benefits of supplements, consumers must rely on other more objective sources, including dietetics professionals, to learn of possible risks. For instance, the two studies that found increased cancer risk with supplemental beta-carotene tested daily doses of 20mg or 30mg. Supplements containing at least 15mg beta-carotene are sold frequently, and without warnings to smokers. Excess beta-carotene from foods is unlikely, because beta-carotene from foods is less bioavailable than supplemental beta-carotene. While a UL was not set for beta-carotene, the DRI committee concluded, “beta-carotene supplements are not advisable for the general population.”

The toxicities of high doses of nutrients such as vitamins A, B-6, D, niacin, iron, and selenium are well established. Although vitamin A toxicity has occurred from eating the livers of carnivorous animals or large fish, most nutrient toxicities occur through supplementation. Cases of vitamin D toxicity, resulting in hypercalcemia and reduced bone mineral density, have been reported in osteoporosis patients using several nonprescription dietary supplements. Excessively high levels of serum calcium, serum 25 (OH) D and serum creatinine have been reported in individuals taking vitamin D supplements at levels of 50,000 IU for as little as six weeks. Hypervitaminosis D has been reported from inadvertent overfortification of vitamin D in milk. The UL for vitamins and minerals are as low as five times the recommended intake for vitamin D, and as high as 25 to 50 or more times the recommended intakes for vitamins C and E. Although the median amounts of nutrients taken by supplement users in a 1980 national survey were less than three to five times recommended intakes, five percent of supplement users took doses exceeding 25 times the recommended intakes for thiamin, riboflavin, and vitamins B-6, B-12, C, and E . Unfortunately, most recent national survey reports do not provide quantitative information about the use of specific supplements. Such quantitative information is planned for future government nutrition surveys, and will be especially important with current trends for increased self-supplementation as well as increased food fortification.

Large doses of vitamin A may be teratogenic. Because of this risk, the Food and Nutrition Board recommends avoiding supplementation with preformed vitamin A during the first trimester of pregnancy unless there is specific evidence of vitamin A deficiency. A study of 22,748 pregnant women found that women taking more than 10,000 IU preformed vitamin A had a greater risk of giving birth to babies with cranial neural crest defects. Such a risk in early pregnancy raises a need for caution about general vitamin and mineral supplement use by women capable of becoming pregnant. Such women should obtain 400µg of synthetic folic acid daily (in addition to food folate from a varied diet), without taking preformed vitamin A.

Iron supplements intended for other household members are a common cause of pediatric poisoning deaths in the United States. Beyond acute toxicity, iron in moderate doses may have deleterious effects for some people. Unlike childbearing age women, who are more likely at risk of low iron stores or even iron deficiency, adult men and postmenopausal women generally have adequate to high iron stores. The additional iron commonly found in multivitamin and mineral supplements is unlikely to benefit them, and high iron stores may increase the risk of chronic disease in some individuals, especially the 12–14% of the population of Northern European decent who are heterozygous for hemochromatosis, an iron storage disease.

Dietary supplements can cause problems related to nutrient excesses, nutrient imbalances, or adverse interactions with medical care. Many of the problems associated with high doses of a single nutrient may reflect interactions that result in a ‘‘relative deficiency” for another nutrient. High doses of vitamin E can interfere with vitamin K action and enhance the effect of coumarin anticoagulant drugs, and high calcium intakes inhibit the absorption of iron and possibly other trace elements. Folic acid can mask the hematological signs of vitamin B-12 deficiency, and may exacerbate the irreversible neurological damage resulting from untreated vitamin B-12 deficiency. Folic acid can also adversely interact with anticonvulsant medications. Zinc supplementation may reduce copper status, impair immune responses, and decrease plasma HDL cholesterol. Little research has been done to address nutrient interactions and to determine how complex nutrient combinations in supplemental quantities will affect the absorption and utilization of each.

Entry Filed under: General Nutrition

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