Vitamin and Mineral Replacement

The sale of vitamins in the United States is a multibillion-dollar business. About 73% of the population uses a variety of nutritional supplements. Older women and people with higher education are typical users of nutritional supplements. Numerous vitamins and herbal medications are available for specialized needs such as cholesterol, memory, menopause, and prostate support. Before purchasing these agents, the patient should discuss with their health care provider the use and health benefits of multiple vitamins and herbal medications. Vitamin supplements are not necessary if the individual is healthy and consumes a well-balanced daily diet on a regular basis.

The Food and Nutrition Board of the Institute of Medicine (IOM) has established the Dietary Reference Intakes (DRIs).

The DRI nutrient recommendations include these components:

Vitamin deficiencies can cause cellular and organ dysfunction that may result in slow recovery from illness. Vitamin supplements are necessary for the vitamin deficiencies described in Table 13.1, but vitamins are frequently taken prophylactically rather than therapeutically.

With the goal of facilitating better nutrition, the U.S. Department of Agriculture (USDA) has developed Choose My Plate, part of a communications initiative based on its 2010 Dietary Guidelines for Americans. Available at www.ChooseMyPlate.gov, Choose My Plate is an interactive tool that helps Americans to eat more healthfully (Fig. 13.1). This website offers a variety of features, including both consumer and professional information.

The Food and Nutrition Board at the IOM publishes the U.S. RDA for daily dose requirements of each vitamin. The U.S. Food and Drug Administration (FDA) requires that all vitamin products be labeled according to the vitamin content and the proportion of the RDA provided by the vitamin product. Individuals should be encouraged to check the RDA listed on the vitamin label to determine whether the product provides the RDA dose requirements. The RDA may need to be modified for patients who are ill.

Megadoses of vitamins are available and are advertised for specific health conditions, but high doses of some vitamins can be toxic. Patients should be advised to contact their health care provider before taking these products. Megadoses of fat-soluble vitamins (A, D, E, and K) may cause toxic effects, whereas megadoses of water-soluble vitamins are eliminated via the urine and thus are generally not toxic. Adverse reactions—kidney stones and nerve damage, respectively—have been reported from vitamin C and vitamin B6. However, it is also claimed that B vitamins may positively influence metabolism in older adults.

Foods rich in vitamins A, D, E, and K are shown in Table 13.2.

The upper limit (UL) for vitamin A is 3000 mcg/daily = 10,000 IU). Vitamin A toxicity affects multiple organs, especially the liver. Mineral oil, cholestyramine, alcohol, and antihyperlipidemic drugs decrease the absorption of vitamin A. Vitamin A is excreted through the kidneys and feces.

Vitamin A taken orally is readily absorbed from the GI tract and peaks in 3 to 5 hours. Its duration of action is unknown. Because vitamin A is stored in the liver, the vitamin may be available to the body for days, weeks, or months.

Calcitriol, the active form of vitamin D, functions as a hormone, and along with parathyroid hormone (PTH) and calcitonin, it regulates calcium and phosphorus metabolism. Calcitriol and PTH stimulate bone reabsorption of calcium and phosphorus. Excretion of vitamin D is primarily in bile; only a small amount is excreted in the urine. If serum calcium levels are low, more vitamin D is activated; when serum calcium levels are normal, activation of vitamin D is decreased. The normal adult RDA of vitamin D is 1000 mg daily (600 IU/day).

Excess vitamin D ingestion (>4000 IU/day) results in hypervitaminosis D and may cause hypercalcemia (an elevated serum calcium level). Anorexia, nausea, and vomiting are early symptoms of vitamin D toxicity.

Although early evidence had suggested the potential for vitamin E to reduce cardiovascular disease (CVD), more recent outcome studies have not shown benefits with vitamin E. Currently, the American Heart Association guidelines do not recommend vitamin E therapy for women as a preventative measure for CVD. Vitamin E has been of interest for its antioxidant properties, and it has been used off label for various conditions, including Alzheimer disease.

The RDA of vitamin E in adults is 30 IU daily and should not exceed the upper limit (UL) of 1000 mg/day in oral intake. The dosage is determined by nutritional intake or degree of deficiency by the health care provider. Side effects of large doses of vitamin E may include fatigue, weakness, nausea, GI upset, headache, bleeding, and breast tenderness. Vitamin E may prolong the prothrombin time (PT), and patients taking warfarin should have their PT monitored closely. Iron and vitamin E should not be taken together because iron can interfere with the body’s absorption and use of vitamin E.

Vitamin K is needed for synthesis of prothrombin and clotting factors VII, IX, and X. For oral anticoagulant overdose, vitamin K1 (phytonadione) is the only vitamin K form available for therapeutic use and is most effective in preventing hemorrhage. Vitamin K is used for two purposes: as an antidote for oral anticoagulant overdose and to prevent and treat the hypoprothrombinemia of vitamin K deficiency. Spontaneous hemorrhage may occur with vitamin K deficiency due to lack of bile salts and malabsorption syndromes that interfere with vitamin K uptake (e.g., celiac disease). Newborns are vitamin K deficient, thus a single dose of phytonadione is recommended immediately after delivery. This practice is common in the United States but is controversial in other countries because it can elevate the bilirubin level and can cause hyperbilirubinemia with a risk of kernicterus. Oral and parenteral forms of phytonadione are available; intravenous (IV) administration is dangerous and may cause death.

Thiamine deficiency can lead to the polyneuritis and cardiac pathology seen in beriberi or to Wernicke encephalopathy that progresses to Korsakoff syndrome, conditions most commonly associated with alcohol abuse. Wernicke-Korsakoff syndrome is a significant central nervous system (CNS) disorder characterized by confusion, nystagmus, diplopia, ataxia, and loss of recent memory. If not treated, it can cause irreversible brain damage. IV administration of thiamine is recommended for treatment of Wernicke-Korsakoff syndrome. Thiamine must be given before giving any glucose to avoid aggravation of symptoms.

Riboflavin may be given to manage dermatologic problems such as scaly dermatitis, cracked corners of the mouth, and inflammation of the skin and tongue. To treat migraine headache, riboflavin is given in larger doses than for dermatologic concerns.

Niacin is given to alleviate pellagra and hyperlipidemia, for which large doses are required. Chapter 41 offers a discussion of niacin use to reduce cholesterol levels. However, large doses may cause GI irritation and vasodilation, resulting in a flushing sensation.

Pyridoxine is administered to correct vitamin B6 deficiency. It may also help alleviate the symptoms of neuritis caused by isoniazid (INH) therapy for tuberculosis. Vitamin B6 is essential as a building block of nucleic acids, in RBC formation, and in synthesis of hemoglobin. Pyridoxine is used to treat vitamin B6 deficiency caused by lack of adequate diet, inborn errors of metabolism, or drug-induced deficiencies secondary to INH, penicillamine, or cyclosporine (or hydralazine) therapy. It is also used to treat neonates with seizures refractive to traditional therapy. Vitamin B6 deficiencies may occur in alcoholics along with deficiencies of other B-complex vitamins. Patients with diabetes or alcoholism may benefit from daily supplementation. Pyridoxine is readily absorbed in the jejunum and is stored in the liver, muscle, and brain. It is metabolized in the liver and excreted in the urine.

The recommended daily allowance of vitamin C (adult dose) is 75 mg/day for women and 90 mg/day for men to prevent deficiency. Some individuals take greater amounts. Massive doses of vitamin C can cause GI upset. Prototype Drug Chart 13.2 details pharmacologic data on vitamin C.

The use of large doses of vitamin C is questionable. Large doses of any vitamin can cause toxicity. Most authorities believe that vitamin C does not prevent the common cold, cure advanced cancer, or treat schizophrenia. Moreover, large doses of vitamin C can cause nausea, abdominal cramps, and diarrhea. If taken with aspirin or sulfonamides, it may cause crystal formation in the urine. Vitamin C directly irritates the intestinal mucosa in the GI tract. This is why the Food and Nutrition Board has set 2 g/day as the adult UL for vitamin C. Large doses of vitamin C can decrease the effect of oral anticoagulants. If large doses of any vitamin are to be discontinued, a gradual reduction of the dosage is necessary to avoid vitamin deficiency.

Folic acid is essential for body growth. It is needed for DNA synthesis, and without folic acid, cellular division is disrupted. Chronic alcoholism, poor nutritional intake, malabsorption syndromes, pregnancy, and drugs that cause inadequate absorption (phenytoin, barbiturates) or folic acid antagonism (methotrexate, triamterene, trimethoprim) are causes of folic acid deficiencies. Symptoms of folic acid deficiencies include anorexia, nausea, stomatitis, diarrhea, fatigue, alopecia, and blood dyscrasias (megaloblastic anemia, leukopenia, thrombocytopenia). These symptoms are usually not noted until 2 to 4 months after folic acid storage is depleted.

Folic acid deficiency during the first trimester of pregnancy can affect the development of the CNS of the fetus. This may cause neural tube defects (NTDs) such as spina bifida, defective closure of the bony structure of the spinal cord, or anencephaly, lack of brain mass formation. The U.S. Public Health Services recommends that all women who may become pregnant consume 400 mcg of supplemental folic acid each day in addition to the folate they get with food. Synthetic folate is more stable than folic acid obtained from food: bioavailability is greater than 85% with synthetic folate and less than 59% for food-sourced folic acid. Some evidence suggests that 400 to 500 mcg (0.4 to 0.5 mg) of folic acid per day can decrease the incidence of coronary artery disease (CAD). It is thought that folic acid decreases the amino acid homocysteine in the blood, which may contribute to heart disease.

Excessive doses of folic acid may mask signs of vitamin B12 deficiency, which is a risk in older adults. Patients taking phenytoin to control seizures should be cautious about taking folic acid. This vitamin can lower the serum phenytoin level, which could increase the risk of seizures; the phenytoin dose would need to be adjusted in such patients. This is a complex interaction that is not fully understood, but it is thought that 1 mg or less per day of folic acid is safe in patients with controlled epilepsy.

The gastric parietal cells produce an intrinsic factor that is necessary for the absorption of vitamin B12 through the intestinal wall. Without the intrinsic factor, little or no vitamin B12 is absorbed. After absorption, vitamin B12 binds to the protein transcobalamin II and is transferred to the tissues. Most vitamin B12 is stored in the liver and is slowly excreted, and it can take 2 to 3 years for stored vitamin B12 to be depleted and for a deficit to be noticed.

Vitamin B12 deficiency is uncommon unless there is a disturbance of the intrinsic factor and intestinal absorption. Pernicious anemia (lack of the intrinsic factor) is the major cause of vitamin B12 deficiency, but deficiency can also develop in strict vegetarians who do not consume meat, fish, or dairy products. Other possible causes of vitamin B12 deficiency include malabsorption syndromes (cancer, celiac disease, and certain drugs), gastrectomy, Crohn disease, and liver and kidney diseases. Vitamin B12 deficiency is commonly seen with the use of metformin and proton pump inhibitors (e.g., omeprazole). Symptoms may include numbness and tingling in the lower extremities, weakness, fatigue, anorexia, loss of taste, diarrhea, memory loss, mood changes, dementia, psychosis, megaloblastic anemia with macrocytes (overenlarged erythrocytes [RBCs]) in the blood, and megaloblasts (overenlarged erythroblasts) in the bone marrow.

To correct vitamin B12 deficiency, cyanocobalamin in crystalline form can be given intramuscularly for severe deficits. It cannot be given intravenously because of possible hypersensitive reactions. Cyanocobalamin can be given orally and is commonly found in multivitamin preparations. It can also be given as a subcutaneous injection.

During pregnancy, iron requirements increase due to the expansion of maternal blood volume and production of RBCs by the fetus. The iron needs of pregnant women are too great to be met through their diet, therefore supplementation is needed. About 27 mg/day are recommended during pregnancy and for 2 to 3 months after delivery.

The dose of iron for infants up to 12 months old is 11 mg/day, and for children from 1 to 8 years of age, it is 7 to 10 mg/day. Males from 9 to 50 years of age require 8 to 11 mg/day. Females 9 to 13 years of age require 8 mg/day; 14 to 18 years of age, 15 mg/day; 19 to 50 years of age, 18 mg/day; and women over 50 years of age require 8 mg/day. Prototype Drug Chart 13.3 describes the pharmacologic data on iron.

The onset of action for iron therapy takes days, and its peak action does not occur for days or weeks; therefore the patient’s symptoms are slow to improve. Increased hemoglobin and hematocrit levels occur within 3 to 7 days.

About 30% to 50% of adults on parenteral nutrition have been shown to have iron deficiency. Pediatric patients are at a 40% to 84% risk of developing an iron deficiency.

Iron toxicity is a serious cause of poisoning in children. As few as 10 tablets of ferrous sulfate (3 g) taken at one time can be fatal within 12 to 48 hours; hemorrhage from the ulcerogenic effects of unbound iron leads to shock, therefore parents should be strongly cautioned against leaving iron tablets that look like candy (M&Ms) within a child’s reach. (Most iron products are distributed in bubble packs.) There is also danger of children overdosing on adult or children’s multivitamins that contain iron.

A prolonged copper deficiency may result in anemia that cannot be corrected by taking iron supplements. Abnormal blood and skin changes caused by a copper deficiency include a decrease in white blood cell count, glucose intolerance, and a decrease in skin and hair pigmentation. Mental retardation may also occur in the young. Copper deficiency in patients receiving parenteral nutrition ranges from 30% to 56% and includes both adults and children.

The RDA for copper is 900 mcg/day. Most adults consume about 1 mg/day. Foods rich in copper are shellfish (crab, oysters), liver, nuts, seeds (sunflower, sesame), legumes, and cocoa.

Large doses, more than 150 mg, may cause a copper deficiency, a decrease in high-density lipoprotein (HDL) cholesterol (“good” cholesterol), and a weakened immune response. Zinc can inhibit tetracycline absorption. Patients taking zinc and an antibiotic should not take them together; zinc should be taken at least 2 hours after taking an antibiotic. About 10% of adults on long-term parenteral nutrition develop a zinc deficiency. Infants and children have a much higher rate of deficiency (20% to 30%). Zinc is the most common deficiency likely to occur in parenteral nutrition because zinc is lost in the patient’s stool.

There is no RDA for chromium; however, 25 to 35 mcg/day is considered within the normal range for adults and children older than 9 years of age. Foods rich in chromium include meats, whole-grain cereals, and brewer’s yeast.

The RDA for selenium is 40 to 75 mcg (the lower dose is recommended for women, higher dose for men). Foods rich in selenium include meats, especially liver; seafood; eggs; and dairy products.