Vitamin and Mineral Replacement

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Vitamins and minerals are needed in the correct portions for normal body function. Most vitamin and mineral nutrients can be safely obtained through the diet. Overuse of vitamins and minerals occurs easily, especially if the nutrients are coming from pills instead of food. It is important to check all supplements with the patient’s provider.

Vitamins

Vitamins are organic substances that are necessary for normal metabolic functions and for tissue growth and healing. The body needs only a small amount of vitamins daily, which can be obtained through the diet. A well-balanced diet has all of the vitamins and minerals needed for body functioning. The intake of vitamins should be increased by people experiencing periods of rapid body growth; those who are pregnant or breastfeeding; patients with debilitating illnesses; those with malabsorptive issues, such as Crohn disease; and those with inadequate diets, which includes alcoholics and some geriatric patients. Children who have poor nutrient intake and are malnourished may need vitamin replacement. People on “fad” or restrictive diets may have vitamin deficiencies, as may those who are unable to afford or do not select a wide variety of foods.
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:
1. Adequate intake (AI) is the consumption and absorption of sufficient food, vitamins, and essential minerals necessary to maintain health.
2. Estimated average requirement (EAR) is the daily intake of a specific nutrient estimated to meet the requirement in 50% of healthy people in an age- and sex-specific group.

TABLE 13.1

Deficiencies That Require Use of Vitamin Supplements

Categories Deficiencies
Inability to metabolize and absorb vitamins Diarrhea, infectious and inflammatory diseases (e.g., Crohn disease, celiac disease)
Inability to use vitamins Liver disease (cirrhosis, hepatitis), renal disease, certain hereditary deficiencies
Increased vitamin losses Fever from infectious processes, hyperthyroidism, hemodialysis, cancer, starvation, crash diets
Increased vitamin requirements Early childhood, pregnancy, debilitating disease (cancer, alcoholism), gastrointestinal surgery, special diets
3. Recommended dietary allowance (RDA) is the amount of vitamins, minerals, or other essential nutrients that should be ingested every day by a normal person engaged in average activities. RDAs are increased for patients who are experiencing increased activity, children who are growing, and women who are pregnant and lactating. RDAs assume a state of wellness and are of little use in patients who are ill.
4. Tolerable upper intake level (UL) is the maximum level of continuing daily nutrient intake that is likely to pose no risk to the health of most of those in the age group for which it has been established.
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.

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FIG. 13.1 The U.S. Department of Agriculture’s ChooseMyPlate.
Table 13.2 lists fat- and water-soluble vitamins, their functions, suggested food sources, and related deficiency conditions.

Fat-Soluble Vitamins

Vitamins fall into two general categories: fat-soluble and water-soluble. The fat-soluble vitamins are A, D, E, and K. They are metabolized slowly; can be stored in fatty tissue, liver, and muscle in significant amounts; and are excreted in the urine at a slow rate. Vitamins A and D are toxic if taken in excessive amounts over time. Current research shows that vitamin D toxicity is quite rare, and its symptoms are fairly nonspecific. Given that many people are found to be vitamin D deficient, it is not uncommon to see high-dose vitamin D therapy (e.g., 50,000 units/week).
Foods rich in vitamins A, D, E, and K are shown in Table 13.2.

Vitamin A

Vitamin A (retinol and beta-carotene) are essential for bone growth and for maintenance of epithelial tissues, skin, eyes, and hair. Vitamin A has antioxidant properties. Studies show that women who take vitamin A have a 20% decrease in breast cancer as opposed to those who do not take vitamin A. However, excessive doses can be toxic. During pregnancy, excessive amounts of vitamin A (>6000 IU) might have a teratogenic effect (i.e., it can cause birth defects) on the fetus. Prototype Drug Chart 13.1 describes the pharmacologic data on vitamin A. Intramuscular administration is used in acutely ill patients.

Pharmacokinetics

Vitamin A is absorbed in the gastrointestinal (GI) tract, and 90% is stored in the liver; however, this function can be inhibited with liver disease. Massive doses of vitamin A can cause hypervitaminosis. Signs and symptoms include hair loss, peeling skin, anorexia, abdominal pain, lethargy, nausea, and vomiting.
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.

TABLE 13.2

Vitamins: Functions, Suggested Food Sources, and Deficiency Conditions

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RBC, Red blood cell; WBC, white blood cell.

Pharmacodynamics

Vitamin A is necessary for many biochemical processes. It aids in the formation of the visual pigment needed for night vision. This vitamin is needed in bone growth and development, and it promotes the integrity of the mucosal and epithelial tissues. An early sign of vitamin A deficiency (hypovitaminosis A) is night blindness. This may progress to dryness and ulceration of the cornea and cause blindness.
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.

Vitamin D

Vitamin D has a major role in regulating calcium and phosphorus metabolism, and it is needed for calcium absorption from the intestines. Dietary vitamin D is absorbed in the small intestine and requires bile salts for absorption. There are two compounds of vitamin D: vitamin D2, ergocalciferol, a synthetic fortified vitamin D, and vitamin D3, cholecalciferol, a natural form of vitamin D influenced by ultraviolet sunlight on the skin. Over-the-counter (OTC) vitamin D supplements usually contain vitamin D3. Once absorbed, vitamin D is converted to calcifediol (also known as 25-hydroxycholecalciferol) in the liver. Calcifediol is then converted to an active form, calcitriol, in the kidneys. Studies have suggested that vitamin D taken with calcium can reduce the incidence of fractures.
 
icon PROTOTYPE DRUG CHART 13.1Vitamin A

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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.

Vitamin E

Vitamin E has antioxidant properties that protect cellular components from being oxidized and protect red blood cells (RBCs) from hemolysis. Vitamin E depends on bile salts, pancreatic secretion, and fat for its absorption. Vitamin E is stored in all tissues, especially the liver, muscle, and fatty tissue. About 75% of vitamin E is excreted in bile.
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

Vitamin K occurs in three forms. Vitamin K1 (phytonadione) is the most active form and is a synthetic type of vitamin K made by plants, and it represents the bulk of dietary vitamin K. Vitamin K2 (menaquinone) is synthesized by probiotic bacteria in the digestive tract. Vitamin K3 (menadione) is another synthetic form of vitamin K. After vitamin K is absorbed, it is stored primarily in the liver and in other tissues. Half of vitamin K comes from the intestinal flora, and the remaining portion comes from the diet. The RDA for an adult male is 120 mcg/day, and for an adult female the RDA is 90 mcg/day. The IOM has not been able to determine a tolerable upper level for vitamin K, so always speak to the health care provider prior to increasing the dose of vitamin K.
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.

Water-Soluble Vitamins

Water-soluble vitamins are the B-complex vitamins and vitamin C. This group of vitamins is not usually toxic unless taken in extremely excessive amounts. Water-soluble vitamins are not stored by the body, so consistent, steady supplementation is required. Water-soluble vitamins are readily excreted in the urine. Protein binding of water-soluble vitamins is minimal. Foods that are high in vitamin B are grains, cereals, breads, and meats. There are reports that B vitamins may promote a sense of well-being and increased energy as well as decreased anger, tension, and irritability. Citrus fruits and green vegetables are high in vitamin C. If the fruits and vegetables are cut or cooked, a large amount of vitamin C is lost.

Vitamin B Complex

Vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (nicotinic acid, or niacin), and vitamin B6 (pyridoxine) are four vitamins in the vitamin B–complex group that are water soluble. This is a common group of vitamins administered in the clinical setting, especially to patients with alcoholism.
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.

Vitamin C

Vitamin C (ascorbic acid) is absorbed from the small intestine. Vitamin C aids in the absorption of iron and in the conversion of folic acid. Vitamin C is not stored in the body and is excreted readily in the urine. A high serum vitamin C level that results from excessive dosing of vitamin C is excreted by the kidneys unchanged. Vitamin C is used in the treatment of scurvy, which is rare in developed countries but seen in individuals who consume few fruits and vegetables. Also, scurvy is seen in people who are on restricted diets or who abuse alcohol or drugs.
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