Vitamin toxicity is a condition in which a person develops symptoms as side effects from taking massive doses of vitamins. Vitamins vary in the amounts that are required to cause toxicity and in the specific symptoms that result. Vitamin toxicity, which is also called hypervitaminosis or vitamin poisoning, is becoming more common in developed countries because of the popularity of vitamin supplements.
Overview
Vitamins are organic molecules in food that are needed in small amounts for growth, reproduction, and the maintenance of good health. Some vitamins can be dissolved in oil or melted fat. These fat-soluble vitamins include vitamin D, vitamin E, vitamin A (retinol), and vitamin K. Other vitamins can be dissolved in water. The water-soluble vitamins include folate (folic acid), vitamin B12, biotin, vitamin B6, niacin, thiamin, riboflavin, pantothenic acid, and vitamin C (ascorbic acid). Taking too much of any vitamin can produce a toxic effect. However, megadoses with the fat-soluble vitamins are more likely to become toxic than with water-soluble vitamins because fat-soluble vitamins are often stored in the body while excess water-soluble vitamins are usually excreted in the urine. Vitamins A and D are the most likely to produce hypervitaminosis in large doses, while riboflavin, pantothenic acid, biotin, and vitamin C appear to be the least likely to cause problems.
Vitamins in medical treatment
Vitamin supplements are used for the treatment of various diseases or for reducing the risk of certain diseases. For example, moderate supplements of folic acid appear to reduce the risk for certain birth defects such as neural tube defects, and possibly reduce the risk of cancer. Therapy for diseases brings with it the risk for irreversible vitamin toxicity only in the case of vitamin D. This vitamin is toxic at levels that are only moderately greater than the recommended dietary allowance (RDA). Niacin is commonly used as a drug for the treatment of heart disease, but niacin is far less toxic than vitamin D. Vitamin toxicity is not a risk with medically supervised therapy using any of the other vitamins.
Vitamin megadoses
With the exception of folic acid supplements, the practice of taking vitamin supplements by healthy individuals has little or no relation to good health. Most adults in the United States can obtain enough vitamins by eating a well-balanced diet. It has, however, become increasingly common for people to take vitamins at levels far greater than the RDA. These high levels are sometimes called vitamin megadoses. Megadoses are harmless for most vitamins. But in the cases of a few of the vitamins—specifically, vitamins D, A, and B6—megadoses can be harmful or fatal. Researchers have also started to look more closely at megadoses of vitamins C and E, since indirect evidence suggests that these two vitamins may reduce the risks of cancer, heart disease, and aging. It is not yet clear whether taking megadoses of either vitamin C or vitamin E has any influence on health. Some experts think that megadoses of vitamin C may protect people from cancer. On the other hand, other researchers have gathered indirect evidence that vitamin C megadoses may cause cancer when combined with smoking.
Fat-soluble vitamins
VITAMIN D. Vitamins D and A are the most toxic of the fat-soluble vitamins. The symptoms of vitamin D toxicity are nausea, vomiting, pain in the joints, and loss of appetite. The patient may experience constipation alternating with diarrhea, or have tingling sensations in the mouth. The toxic dose of vitamin D depends on its frequency. In infants, a single dose of 15 milligrams (mg) or greater may be toxic, but it is also the case that daily doses of 1.0 mg over a prolonged period may be toxic. In adults, a daily dose of 1.0 to 2.0 mg of vitamin D is toxic when consumed for a prolonged period. A single dose of about 50 mg or greater is toxic for adults. The immediate effect of an overdose of vitamin D is abdominal cramps, nausea, and vomiting. Toxic doses of vitamin D taken over a prolonged period of time can result in irreversible deposits of calcium crystals in the soft tissues of the body that may damage the heart, lungs, and kidneys. The dietary reference intake (DRI) suggests an upper tolerable limit of 25 micrograms (mcg) per day for children and 50 mcg per day for adults. The DRI is between 5–15 mcg from childhood to adulthood in the absence of adequate sunlight. Older adults have a requirement on the higher end of the scale due to generally reduced sun exposure.
VITAMIN A. Vitamin A toxicity can occur with long-term consumption of 20 mg of retinol or more per day. The symptoms of vitamin A overdosing include accumulation of water in the brain (hydrocephalus), vomiting, tiredness, constipation, bone pain, and severe headaches. The skin may acquire a rough and dry appearance, with hair loss and brittle nails. Vitamin A toxicity is a special issue during pregnancy. Expectant mothers who take 10 mg vitamin A or more on a daily basis may have an infant with birth defects. These birth defects include abnormalities of the face, nervous system, heart, and thymus gland. It is possible to take in toxic levels of vitamin A by eating large quantities of certain foods. For example, about 30 grams of beef liver, 500 grams of eggs, or 2,500 grams of mackerel would supply 10 mg of retinol.
VITAMIN E. Megadoses of vitamin E may produce headaches, tiredness, double vision, and diarrhea in humans. Studies with animals fed large doses of vitamin E have revealed that this vitamin may interfere with the absorption of other fat-soluble vitamins. The term absorption means the transfer of the vitamin from the gut into the bloodstream. Thus, large doses of vitamin E consumed over many weeks or months might result in deficiencies of vitamin D, vitamin A, and vitamin K. The DRI suggests an upper tolerable limit between 200–800 mg per day for children and teenagers, depending on age (younger children have requirements on the lower end of the scale), and 1000 mg per day for adults. The DRI is 15 mg per day for adults and pregnant women.
VITAMIN K. Prolonged consumption of megadoses of vitamin K (menadione) results in anemia, which is a reduced level of red blood cells in the bloodstream. When large doses of menadione are given to infants, they result in the deposit of pigments in the brain, nerve damage, the destruction of red blood cells (hemolysis), and death. A daily injection of 10 mg of menadione into an infant for three days can kill the child. This tragic fact was discovered during the early days of vitamin research, when newborn infants were injected with menadione to prevent a disease known as hemorrhagic disease of the newborn. Today, a different form of vitamin K is used to protect infants against this disease.
Water-soluble vitamins
FOLATE. Folate occurs in various forms in food. There are more than a dozen related forms of folate. The folate in oral vitamin supplements occurs in only one form, however—folic acid. Large doses of folic acid (20 grams/day) can eventually result in kidney damage. Folate is considered, however, to be relatively nontoxic, except in cases where folate supplementation can lead to pernicious anemia. The DRI suggests an upper tolerable limit between 300–800 mcg per day for children and teenagers, depending on age (younger children have requirements on the lower end of the scale), and 1000 mcg per day for adults. The DRI is 400 mcg per day for adults and slightly lower in children; 600 mcg during pregnancy and 500 mcg while lactating.
VITAMIN B12. Vitamin B12 is important in the treatment of pernicious anemia. Pernicious anemia is more common among middle-aged and older adults; it is usually detected in patients between the ages of 40 and 80. The disease affects about 0.1% of all persons in the general population in the United States, and about 3% of the elderly population. Pernicious anemia is treated with large doses of vitamin B12. Typically, 0.1 mg of the vitamin is injected each week until the symptoms of pernicious anemia disappear. Patients then take oral doses of vitamin B12 for the rest of their life. Although vitamin B12 toxicity is not an issue for patients being treated for pernicious anemia, treatment of these patients with folic acid may cause problems. Specifically, pernicious anemia is often first detected because the patient feels weak or tired. If the anemia is not treated, the patient may suffer irreversible nerve damage. The problem with folic acid supplements is that the folic acid treatment prevents the anemia from developing, but allows the eventual nerve damage to occur.
VITAMIN B6. Vitamin B6 is clearly toxic at doses about 1000 times the RDA. Daily doses of 2–5 grams of one specific form of this vitamin can produce difficulty in walking and tingling sensations in the legs and soles of the feet. Continued megadoses of vitamin B6 result in further unsteadiness, difficulty in handling small objects, and numbness in the hands. When the high doses are stopped, recovery begins after two months. Complete recovery may take two to three years. The DRI suggests an upper tolerable limit between 30–80 mg per day for children and teenagers, depending on age (younger children have requirements on the lower end of the scale), and 100 mg per day for adults. The DRI is between1.3–1.7 mg per day for adults, slightly higher during pregnancy, and lower in children.
VITAMIN C. Large doses of vitamin C are considered to be toxic in persons with a family history of or tendency to form kidney stones or gallbladder stones. Kidney and gallbladder stones usually consist of calcium oxalate. Oxalate occurs in high concentrations in foods such as cocoa, chocolate, rhubarb, and spinach. A fraction of the vitamin C in the body is normally broken down to produce oxalate. A daily supplement of 3.0 grams of vitamin C has been found to double the level of oxalate that passes through the kidneys and is excreted into the urine. The DRI suggests an upper tolerable limit between 400–1200 mg per day for children and teenagers, depending on age (younger children have requirements on the lower end of the scale), and 2000 mg per day for adults.
NIACIN. The DRI for niacin is 14–16 mg per day in adults. Niacin comes in two forms, nicotinic acid and nicotinamide. Either form can satisfy the adult requirement for this vitamin. Nicotinic acid, however, is toxic at levels of 100 times the RDA. It can cause flushing of the skin, nausea, diarrhea, and liver damage. Flushing is an increase in blood passing through the veins in the skin, due to the dilation of arteries passing through deeper parts of the face or other parts of the body. In spite of the side effects, however, large doses of nicotinic acid are often used to lower blood cholesterol in order to prevent heart disease. Nicotinic acid results in a lowering of LDL-cholesterol (so-called bad cholesterol), an increase in HDL-cholesterol (so-called good cholesterol), and a decrease in plasma triglycerides. Treatment involves daily doses of 1.5–4.0 grams of nicotinic acid per day. Flushing of the skin occurs as a side effect when nicotinic acid therapy is started, but may disappear with continued therapy. The DRI suggests an upper tolerable limit between 10–30 mg per day for children and teenagers, depending on age (younger children have requirements on the lower end of the scale), and 35 mg per day for adults. The DRI for vitamin C in adults is between 75–90 mg per day, slightly more during pregnancy.
Diagnosis
The diagnosis of vitamin toxicity is usually made on the basis of the patient's dietary or medical history. Questioning the patient about the use of vitamin supplements may shed light on some physical symptoms. The doctor can confirm the diagnosis by ordering blood or urine tests for specific vitamins. When large amounts of the water-soluble vitamins are consumed, a large fraction of the vitamin is absorbed into the bloodstream and promptly excreted into the urine. The fat-soluble vitamins are more likely to be absorbed into the bloodstream and deposited in the fat and other tissues. In the cases of both water-soluble and fat-soluble vitamins, any vitamin not absorbed by the intestines is excreted in the feces. Megadoses of many of the vitamins produce diarrhea, because the non-absorbed nutrient draws water out of the body and into the gut, resulting in the loss of this water from the body.
Treatment
In all cases, treatment of vitamin toxicity requires discontinuing vitamin supplements. Vitamin D toxicity needs additional action to reduce the calcium levels in the bloodstream because it can cause abnormally high levels of plasma calcium (hypercalcemia). Severe hypercalcemia is a medical emergency and is treated by infusing a solution of0.9% sodium chloride into the patient's bloodstream. The infusion consists of 2–3 qt (liters) of salt water given over a period of one to two days.
Prognosis
The prognosis for reversing vitamin toxicity is excellent for most patients. Side effects usually go away as soon as overdoses are stopped. The exceptions are severe vitamin D toxicity, severe vitamin A toxicity, and severe vitamin B6 toxicity. Too much vitamin D leads to deposits of calcium salts in the soft tissue of the body, which cannot be reversed. Birth defects due to vitamin A toxicity cannot be reversed. Damage to the nervous system caused by megadoses of vitamin B6 can be reversed, but complete reversal may require a recovery period of more than a year.
Health care team roles
Health care professionals should familiarize themselves with the symptoms of vitamin toxicities in order to successfully diagnose toxic levels.
Patient education
Health care professionals can direct patients in learning about the recommended requirements for each vitamin so that toxicities do not pose a risk. The DRI can be
referred to for information regarding recommended intakes for individuals, estimated average requirements, and upper tolerable limits. The healthiest way to acquire vitamins is through good nutrition via food. Following the Dietary Guidelines for Americans, published by the U.S. Department of Agriculture and Health and Human Services, can provide a broad overall view of good nutrition. The Food Guide Pyramid was created by the U.S. Department of Agriculture to help Americans choose foods from each food grouping. The food pyramid, developed by nutritionists, provides a visual guide to healthy eating.
Prevention
Vitamin toxicity can be prevented by minimizing the use of vitamin supplements or by only taking a dose within recommended levels of the DRI or RDA. If vitamin D supplements are being used on a doctor's orders, monitoring the levels of plasma calcium help prevent toxicity. The development of hypercalcemia with vitamin D treatment indicates that the patient is at risk for vitamin D toxicity.
KEY TERMS
Absorption—The transfer of a vitamin from the digestive tract to the bloodstream.
Dietary reference intakes (DRI)—These standards explain the daily amounts of energy, protein, minerals, and fat-soluble and water-soluble vitamins needed by healthy males and females, from infancy to old age.
Hypercalcemia—A condition marked by abnormally high levels of calcium in the blood.
Hypervitaminosis—Another name for vitamin toxicity.
Megadose—A very large dose of a vitamin, taken by some people as a form of self-medication.
Menadione—A synthetic form of vitamin K, sometimes called vitamin K3.
Pernicious anemia—A rare disorder in which the body does not absorb enough vitamin B12 from the digestive tract, resulting in an inadequate amount of red blood cells produced.
Food and Nutrition Board. Recommended Dietary Allowances, 10th ed. Washington, DC: National Academy Press, 1989.
Institute of Medicine. Dietary Reference Intakes: Applications in Dietary Assessment. Washington, DC: National Academy Press, 2001.
Institute of Medicine. Dietary Reference Intakes: Risk Assessment (Compass Series). Washington, DC: National Academy Press, 1999.
Larson-Duyff, Roberta. The American Dietetic Association's Complete Food & Nutrition Guide. New York: John Wiley & Sons, 1998.
Mahan, L. Kathleen, and Sylvia Escott-Stump. Krause's Food, Nutrition, & Diet Therapy. London: W. B. Saunders Co.,2000.
Mindell, Earl, and Hester Mundis. Earl Mindell's Vitamin Bible for the 21st Century. London: Warner Books, 1999.
Rodwell-Williams, Sue. Essentials of Nutrition and Diet Therapy. London: Mosby-Year Book, 1999.
PERIODICALS
American Dietetics Association. "Women's Health and Nutrition—Position of ADA and Dietitians of Canada." Journal of the American Dietetic Association (1999): 99: 738-51.
Azais-Braesco, V., and G. Pascal. "Vitamin A in Pregnancy: Requirements and Safety Limits." American Journal of Clinical Nutrition (2000): 71: 1325S-33.
Mills, J. L. "Fortification of Foods with Folic Acid—How Much is Enough?" New England Journal of Medicine (2000): 342: 1442-45.
Traber, Maret G. "Vitamin E: Too Much or Not Enough?" American Journal of Clinical Nutrition 73 (2001): 997-98.
ORGANIZATIONS
American Dietetic Association. 216 W. Jackson Blvd., Chicago, IL 60606-6995. (312) 899-0040. <http://www.eatright.org/>.
Food and Nutrition Information Center Agricultural Research Service, USDA. National Agricultural Library, Room 304, 10301 Baltimore Avenue, Beltsville, MD 20705-2351. (301) 504-5719. (301) 504-6409. <http//www.nal.usda.gov/fnic/.fnic@nal.usda.gov>.
OTHER
Food and Nutrition Professionals Network. <http://nutrition.cos.com>.
