Vitamins and minerals are needed in correct portions for normal body function. Overuse of vitamins and minerals, particularly fat-soluble vitamins and iron, may lead to vitamin or iron toxicity.

Vitamins

Vitamins are organic chemicals 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 one’s diet. A well-balanced diet has all of the vitamins and minerals needed for body functioning. The intake of vitamins should be increased by those experiencing periods of rapid body growth, those who are pregnant or breastfeeding, those with a debilitating illness, those with malabsorptive issues (e.g., Crohn’s disease), and those with inadequate diets (e.g., alcoholics, some geriatric patients). Children who have poor nutrient intake or 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. Numerous vitamins and herbal medications are available for specialized needs such as cholesterol, memory, menopause, and prostate. Before purchasing these agents, the patient should discuss with the health care provider the health value and use of multiple vitamins and herbal medications. People may take vitamins to relieve tiredness or to improve general overall health; these are inappropriate indications for vitamin therapy. Vitamin supplements are not necessary if the individual is healthy and consumes a well-balanced daily diet on a regular basis; however, patients may take vitamins as a sort of “insurance” to be sure they are getting what they need.

The Food and Nutrition Board of the National Academy of Sciences has established the Dietary Reference Intakes (DRI).

The DRI nutrient recommendations include the following:

1. Adequate intake (AI) is the amount determined to be sufficient in the absence of scientific information. The AI is based on data about the levels of vitamin intake that seem to maintain a healthy status.

2. Estimated average requirement (EAR) is the amount thought to provide a sufficient intake in one half of healthy persons in a defined group.

4. Tolerable upper intake level (UL) is the maximum amount considered not likely to be a risk for healthy persons in a specified group. This is not a recommended level to take.

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 15-1, but vitamins are frequently taken prophylactically rather than therapeutically.

TABLE 15-1

JUSTIFICATION FOR VITAMIN SUPPLEMENTS

CATEGORIES	DEFICIENCIES
Malabsorption, diarrhea, infectious and inflammatory diseases (e.g., Crohn’s disease, celiac disease)
Inability to use vitamins	Liver disease (cirrhosis, hepatitis), renal disease, certain hereditary deficiencies
Increased vitamin losses	Fever from infectious process, hyperthyroidism, hemodialysis, cancer, starvation, crash diets
Increased vitamin requirements	Early childhood, pregnancy, debilitating disease (cancer, alcoholism), gastrointestinal surgery, special diets

With the goal of facilitating better nutrition, the United States Department of Agriculture (USDA) has developed Choose My Plate, part of a communications initiative based on their 2010 Dietary Guidelines for Americans. Available at www.ChooseMyPlate.gov, MyPlate is an interactive tool that helps Americans to eat more healthfully (Figure 15-1), and the SuperTracker assists in the planning, analyzing, and tracking of nutrition and physical activity. This website offers a variety of features, including both consumer and professional information.

FIGURE 15-1 The U.S. Department of Agriculture’s ChooseMyPlate.

The National Academy of Sciences Food and Nutrition Board 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 amount of vitamin content and the proportion of the RDA provided by the vitamin product. Individuals should be encouraged to check the RDA listed on a vitamin container 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, advertised for specific health conditions; these high doses 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. 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.

Table 15-2 lists fat-soluble and water-soluble vitamins, their functions, suggested food sources, and selected deficiency conditions.

TABLE 15-2

VITAMINS: FUNCTIONS, SUGGESTED FOOD SOURCES, AND SELECTED DEFICIENCY CONDITIONS

VITAMIN	FUNCTION	FOOD SOURCES	DEFICIENCY CONDITIONS
A (retinol)	Required for development and maintenance of healthy eyes, gums, teeth, skin, hair, and selected glands. Needed for fat metabolism.	Fortified milk, butter, eggs, leafy green and yellow vegetables and fruits. *Natural vitamin A, found only in animal sources: cod, halibut, shark, tuna	Dry skin, poor tooth development, night blindness
B₁ (thiamine)	Promotes use of sugars (energy). Required for good function of nervous system and heart.	Enriched breads and cereals, yeast, liver, pork, fish, milk, lentils, blackstrap molasses	Sensory disturbances, retarded growth, fatigue, anorexia
B₂ (riboflavin)	Promotes body’s use of carbohydrates, proteins, and fats by releasing energy to cells. Required for tissue integrity.	Milk, enriched breads and cereals, liver, lean meat, eggs, almonds, wheat germ, soy, leafy green vegetables^†	Visual defects such as blurred vision and photophobia; cheilosis; rash on nose; numbness of extremities
B₆ (pyridoxine)	Important in metabolism, protein synthesis, and formation of red blood cells.	Lean meat, leafy green vegetables, whole-grain cereals, yeast, bananas, salmon, soybeans, seeds, nuts, avocados, bananas, carrots	Neuritis, convulsions, dermatitis, anemia, lymphopenia
B₁₂ (cobalamin)	Functions as a building block of nucleic acids and to form red blood cells. Facilitates functioning of nervous system.	Liver, kidney, fish, milk, eggs, chicken, turkey	Gastrointestinal disorders, poor growth, anemias
folic acid (folvite)	Helps in formation of genetic materials and proteins for the cell nucleus. Assists with intestinal functioning. Prevents selected anemias.	Leafy green vegetables, yellow fruits and vegetables, yeast, organ meats, black-eyed peas, lentils	Decreased white blood cell count and clotting factors, anemias, intestinal disturbances, depression
Pantothenic acid	Promotes body’s use of carbohydrates, fats, and proteins. Essential for formation of specific hormones and nerve-regulating substances.	Eggs, leafy green vegetables, nuts, liver, kidney, skim milk, seeds, nuts, wheat germ, salmon	Natural deficiency unknown in humans
Niacin	In all body tissues. Necessary for energy-producing reactions. Assists nervous system.	Eggs, meat, liver, beans, peas, enriched bread and cereals	Retarded growth, pellagra, headache, memory loss, anorexia, insomnia
Biotin	Synthesis of fatty acids and energy production from glucose. Required by body chemical systems.	Eggs, milk, leafy green vegetables, liver, kidney	Natural deficiency unknown in humans
C (ascorbic acid)	Helps tissue repair and growth. Required in formation of collagen.	Citrus fruits, cantaloupe, tomatoes, leafy green vegetables, sweet red peppers, potatoes, strawberries, kiwi	Poor wound healing, bleeding gums, scurvy, predisposition to infection
D (calciferol)	Promotes use of phosphorus and calcium. Important for strong teeth and bones.	Vitamin D–fortified milk, egg yolk, tuna, salmon, liver	Rickets in children; osteomalacia in adults
E (alpha-tocopherol)	Protects fatty acids and promotes formation and functioning of red blood cells, muscle, and other tissues.	Whole-grain cereals, wheat germ, vegetable oils, lettuce, sunflower seeds, milk, eggs, meat, avocados, asparagus	Breakdown of red blood cells
K	Essential for blood clotting.	Leafy green vegetables, liver, cheese, egg yolk, vegetable oil, tomatoes	Increased clotting time, leading to increased bleeding and hemorrhage

*Yellow fruits and vegetables include apricots, cantaloupe, carrots, rutabaga, pumpkin, squash, and sweet potatoes.

^†Leafy green vegetables include brussels sprouts, chard, broccoli, kale, spinach, and turnip and mustard greens.

Fat-Soluble Vitamins

Vitamins fall into two general categories: fat-soluble and water-soluble. The fat-soluble vitaminsare 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). Historically, vitamins E and K were thought to be less toxic than vitamins A and D. Vitamin E was once considered a “wonder” drug, supposedly beneficial for the heart and brain, but it was later determined that vitamin E was an independent risk factor for the development of heart failure.

Foods rich in vitamin A, vitamin D, vitamin E, or vitamin K are shown in Table 15-2.

Vitamin A

Vitamin A is essential for bone growth and the maintenance of epithelial tissues, skin, eyes, and hair. It has been used for the treatment of skin disorders such as acne; however, excess doses can be toxic. During pregnancy, excessive amounts of vitamin A (>6000 international units) might have a teratogenic effect (birth defects) on the fetus. Prototype Drug Chart 15-1 describes the pharmacologic data on vitamin A. IM administration is used only in acutely ill patients or patients refractory to the oral route, such as those with gastrointestinal (GI) malabsorption syndrome.

Prototype Drug Chart 15-1

Vitamin A

Drug Class	Dosage
Fat-soluble vitamin	Severe deficiency:
Trade Names: Acon, Aquasol A, Del-VI-A Pregnancy Category: A (X if doses are above RDA)	A and C >8 y: PO: 100,000-500,000 international units/d × 3 d; then 50,000 international units/d × 14 d (based on severity)
	C: Infant to 8 y: IM: 5000-15,000 international units/d × 10 d Maintenance: C: 4-8 y: IM: 5000-15,000 international units/d × 2 mo C: <4 y 10,000 international units/d × 2 mo
Contraindications	Drug-Lab-Food Interactions
Hypervitaminosis A, pregnancy (massive doses)	Drug: Mineral oil may decrease absorption of vitamin A, cholestyramine
	Lab: May increase BUN, calcium, cholesterol, triglycerides; may lower erythrocyte, leukocyte counts
	Food: None known
Pharmacokinetics	Pharmacodynamics
Absorption: PO: 1 h	PO: Onset: 1-2 h
Distribution: PB: UK	Peak: 4-5 h
Metabolism: : weeks-months	Duration: UK
Excretion: Urine

Therapeutic Effects/Uses

To treat vitamin A deficiency (biliary tract or pancreatic disease, colitis, cirrhosis, celiac disease, sprue), prevent night blindness, treat skin disorders, promote bone development

Mode of Action: Essential for growth, bone and teeth development, vision, integrity of skin and mucous membranes, and reproduction

Side Effects	Adverse Reactions
Headache, fatigue, drowsiness, irritability, anorexia, vomiting, diarrhea, dry skin, visual changes	Evident only with toxicity: leukopenia, aplastic anemia, papilledema, increased intracranial pressure, hypervitaminosis A, bulging fontanelles in infants, jaundice

A, Adult; C, child; d, day; h, hour; IM, intramuscular; PB, protein binding; PO, by mouth; RDA, recommended daily allowance; , half life; UK, unknown; y, year; <, less than; >, greater than.

Pharmacokinetics

When a person is deficient in vitamin A, the vitamin is absorbed faster than when there is no deficiency or intestinal obstruction. A portion of vitamin A is stored in the liver, and this function can be inhibited with liver disease. Massive doses of vitamin A may cause hypervitaminosis A, symptoms of which are hair loss, peeling skin, anorexia, abdominal pain, lethargy, nausea, and vomiting.

The UL for vitamin A is 3000 mcg daily (3000 mcg daily = 10,000 international units). Excess use of vitamin A should be avoided unless warranted because this vitamin is stored in the liver, kidneys, and fat, and it is slowly excreted from the body. Excess vitamin A is stored in the liver for up to 2 years. Vitamin A toxicity affects multiple organs, especially the liver. To prevent the occurrence of vitamin A toxicity, the dose for healthy patients should not be greater than 7500 international units.

Mineral oil, cholestyramine, alcohol, and antilipemic drugs decrease the absorption of vitamin A. Vitamin A is excreted through the kidneys and feces.

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 to blindness.

Vitamin A taken orally begins to take effect in 1 to 2 hours and peaks in 4 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 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 through the skin). Over-the-counter 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.

Calcitriol, the active form of vitamin D, functions as a hormone and, with parathyroid hormone (PTH) and calcitonin, 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.

Excess vitamin D ingestion (>40,000 international units) 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 red blood cells 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.

It has been reported that taking 400 to 800 international units of vitamin E per day reduces the number of nonfatal myocardial infarctions (MIs). Also, it has been stated that taking 200 international units per day for several years can reduce the risk of coronary artery disease (CAD), but the use of vitamin E for CAD is being questioned. However, many still state that this vitamin protects the heart and arteries and aids in the prevention of macular degeneration because of its antioxidant effects (i.e., it inhibits the oxidation of other compounds by blocking a group of harmful chemicals called free radicals). Many patients with Alzheimer’s or Parkinson’s disease take supplemental vitamin E for its antioxidant effects.

Safety

Preventing Medication Errors

Do not confuse…

• Aquasol A or Aquasol E with Anusol, an antiinflammatory generally used to treat hemorrhoids

Side effects of large doses of vitamin E may include fatigue, weakness, nausea, GI upset, headache, and breast tenderness. Vitamin E may prolong the prothrombin time (PT). 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 four forms. Vitamin K₁ (phytonadione) is the most active form; vitamin K₂ (menaquinone) is synthesized by intestinal flora; and vitamin K₃ (menadione) and vitamin K₄ (menadiol) have been produced synthetically. Vitamin K₂ is not commercially available. Vitamins K₁ and K₂ are absorbed in the presence of bile salts. Vitamins K₃ and K₄ do not need bile salts for absorption. 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 one’s diet.

Vitamin K is needed for synthesis of prothrombin and the 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. The commercial drugs available for vitamin K₁ are called Mephyton and AquaMEPHYTON. Vitamin K is used for two reasons: (1) as an antidote for oral anticoagulant overdose and (2) 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 controversial in other countries. This can elevate the bilirubin level and cause hyperbilirubinemia with a risk of kernicterus. There are oral and parenteral forms of phytonadione; 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, cereal, bread, 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 of the vitamin B-complex members. This B-complex group is water-soluble. It 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’s encephalopathy that progresses to Korsakoff’s syndrome, conditions most commonly associated with alcohol abuse. Wernicke-Korsakoff syndrome is a significant central nervous system disorder characterized by confusion, nystagmus, diplopia, ataxia, and loss of recent memory. If not treated, it may 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 46 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 an essential building block of nucleic acids, red blood cell formation, and 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 stored in the liver, muscle, and brain. It is metabolized in the liver and excreted in the urine.

Safety