Chapter 81: Vitamins

Vitamin A (Retinol) Deficiency

-Because vitamin A is needed for dark adaptation, *night blindness is often the first indication of deficiency*. -With time, vitamin A deficiency may lead to *xerophthalmia* (a dry, thickened condition of the conjunctiva) and *keratomalacia* (degeneration of the cornea with keratinization of the corneal epithelium). -When vitamin A deficiency is *severe, blindness may occur*. In addition to effects on the eye, deficiency can produce *skin lesions and dysfunction of mucous membranes*.

Vitamin A (Retinol) Toxicity

-In high doses, vitamin A can cause *birth defects, liver injury, and bone-related disorders*. To reduce risk, the Food and Nutrition Board has set the UL (Tolerable Upper Intake Level) for vitamin A at *3000 mcg/day*. -Excessive doses can cause a toxic state, referred to as *hypervitaminosis A*. Chronic intoxication affects multiple organ systems, especially the *liver*. Symptoms are diverse and may include *vomiting, jaundice, hepatosplenomegaly, skin changes, hypomenorrhea, and elevation of intracranial pressure*. Most symptoms disappear following vitamin A withdrawal. -Vitamin A excess can *damage bone*. In infants and young children, vitamin A can cause *bulging of the skull at sites where bone has not yet formed*. In adult females, too much vitamin A can increase the *risk of hip fracture*—apparently by blocking the ability of vitamin D to enhance calcium absorption.

Vitamin A (Retinol) Therapeutic Uses

-The only indication for vitamin A is prevention or correction of vitamin A deficiency. -As discussed in Chapter 105, certain derivatives of vitamin A (eg, isotretinoin, etretinate) are used to treat acne and other dermatologic disorders.

Vitamin A (Retinol) Pharmacokinetics

-Under normal conditions, dietary vitamin A is *readily absorbed and then stored in the liver*. -As a rule, liver reserves of vitamin A are large and will last for months if intake of retinol ceases. -Normal plasma levels for retinol range between *30 and 70 mcg/dL*. -In the absence of vitamin A intake, levels are maintained through mobilization of liver reserves. As liver stores approach depletion, plasma levels begin to decline. *Signs and symptoms of deficiency appear when plasma levels fall below 20 mcg/dL.*

We do have solid data supporting the use of three individual vitamins.

-vitamin B12 -folic acid -vitamin D

Vitamin K Requirements

In 2002, The Food and Nutrition Board set the AI for *adult males at 120 mcg*, and the AI for *adult females at 90 mcg*. -For most individuals, vitamin K requirements are readily met through *dietary sources, and through vitamin K synthesized by intestinal bacteria*. Since bacterial colonization of the gut is not complete until several days after birth, levels of vitamin K may be low in newborns.

Vitamin K Pharmacokinetics

Intestinal absorption of the natural forms of vitamin K (phytonadione and vitamin K2) is adequate only in the presence of bile salts. Following absorption, vitamin K is concentrated in the liver. Metabolism and secretion occur rapidly. Very little is stored.

Vitamin E (Alpha-Tocopherol) Sources

Most dietary vitamin E comes from *vegetable oils* (eg, corn oil, olive oil, cottonseed oil, safflower oil, canola oil). The vitamin is also found in *nuts, wheat germ, whole-grain products, and mustard greens*.

Vitamin A (Retinol) Sources

Requirements for vitamin A can be met by: (1) consuming foods that contain preformed vitamin A (retinol) (2) consuming foods that contain provitamin A carotenoids (beta-carotene, alpha-carotene, beta-cryptoxanthin), which are converted to retinol by cells of the intestinal mucosa. Preformed vitamin A is present *only in foods of animal origin*. Good sources are: *dairy products, meat, fish oil, and fish*. Provitamin A carotenoids are found in *darkly colored, carotene-rich fruits and vegetables*. Especially rich sources are carrots, cantaloupe, mangoes, spinach, tomatoes, pumpkins, and sweet potatoes.

Vitamin K Adverse Effects

Severe Hypersensitivity Reactions. Intravenous phytonadione can cause serious reactions (shock, respiratory arrest, cardiac arrest) that resemble anaphylaxis or hypersensitivity reactions. Death has occurred. Consequently, *phytonadione should not be administered IV unless other routes are not feasible*, and then only if the potential benefits clearly outweigh the risks. Hyperbilirubinemia. When administered parenterally to newborns, vitamin K derivatives can elevate plasma levels of bilirubin, thereby posing a risk of *kernicterus*. The incidence of hyperbilirubinemia is greater in premature infants than in full-term infants. Although all forms of vitamin K can raise bilirubin levels, the risk is higher with menadione and menadiol (other types of vitamin K) than with phytonadione.

Vitamin E (Alpha-Tocopherol) Requirements

The RDA for vitamin E, for men and women, is *15 mg/day* (22.5 IU). RDAs *increase for women who are breast-feeding*, but not for those who are pregnant. Taking *more than 200 mg/day increases the risk of hemorrhagic stroke*. Accordingly, this limit should be exceeded only when there is a need to manage a specific disorder (eg, advanced macular degeneration), and only when advised by a healthcare professional.

Vitamin A (Retinol) Requirments

The current RDA for vitamin A for *adult males is 900* RAEs, and the RDA for adult *females is 700 RAEs* (RDA=Recommended Dietary Allowance) (RAE=Retinol Activity Equivalent)

Classification of Vitamins

The vitamins are divided into two major groups: *fat-soluble vitamins* and *water-soluble vitamins* -In the fat-soluble group are *vitamins A, D, E, and K*. -The water-soluble group consists of *vitamin C and members of the vitamin B complex* (thiamine, riboflavin, niacin, pyridoxine, pantothenic acid, biotin, 988folic acid, and cyanocobalamin). *Except for vitamin B12*, water-soluble vitamins undergo minimal storage in the body, and hence frequent ingestion is needed to replenish supplies. -In contrast, fat-soluble vitamins can be stored in massive amounts, which is good news and bad news. The good news is that extensive storage minimizes the risk of deficiency. The bad news is that extensive storage greatly increases the potential for toxicity if intake is excessive.

Vitamin E (Alpha-Tocopherol) Potential Benefits.

There is evidence that 200 IU of vitamin E daily *may reduce the risk of colds in older adults*, and 400 IU daily (in combination with vitamin C, beta-carotene, zinc, and copper) *may delay progression of age-related macular degeneration*.

Vitamin A (Retinol) Actions

Vitamin A, also known as retinol, has multiple functions. -In the *eye*, vitamin A plays an important role in *adaptation to dim light*. -The vitamin also has a role in: `embryogenesis `spermatogenesis `immunity `growth `maintaining the structural and functional integrity of the skin and mucous membranes

Vitamin D

Vitamin D plays a critical role in *calcium metabolism and maintenance of bone health*. The classic effects of deficiency are *rickets* (in children) and *osteomalacia* (in adults).

Vitamin E (Alpha-Tocopherol)

Vitamin E (alpha-tocopherol) is essential to the health of many animal species, but has no clearly established role in human nutrition. Unlike other vitamins, vitamin E has no known role in metabolism. Deficiency, which is rare, can result in neurologic deficits. -Vitamin E helps maintain health primarily through *antioxidant actions*. Specifically, the vitamin helps *protect against peroxidation of lipids*. -Moreover, there is evidence that high-dose vitamin E may actually *increase the risk of heart failure, cancer progression, and all-cause mortality*. -High-dose vitamin E (in combination with vitamin C) can blunt the beneficial effects of exercise on insulin sensitivity. Under normal conditions, exercising enhances cellular responses to insulin. However, among subjects who took vitamin E (400 IU/day) plus vitamin C (500 mg twice daily), exercising failed to yield this benefit.

Vitamin K Deficiency

Vitamin K deficiency *produces bleeding tendencies*. If the deficiency is severe, *spontaneous hemorrhage* may occur. In newborns, intracranial hemorrhage is of particular concern. An important cause of deficiency is *reduced absorption*. Since the natural forms of vitamin K require bile salts for their uptake, any *condition that decreases availability of these salts* (eg, obstructive jaundice) can lead to deficiency. *Malabsorption syndromes* (sprue, celiac disease, cystic fibrosis of the pancreas) can also decrease vitamin K uptake. Other potential causes of impaired absorption are *ulcerative colitis, regional enteritis, and surgical resection of the intestine*. *Disruption of intestinal flora* may result in deficiency by eliminating vitamin K-synthesizing bacteria. Hence, deficiency may occur *secondary to use of antibiotics*. In infants, *diarrhea* may cause bacterial losses sufficient to result in deficiency. The normal infant is born vitamin K deficient. Consequently, to rapidly elevate prothrombin levels and reduce the risk of neonatal hemorrhage, *it is recommended that all infants receive a single injection of phytonadione (vitamin K1) immediately after delivery*. As discussed in Chapter 52, the *anticoagulant warfarin acts as an antagonist of vitamin K*, and thereby decreases synthesis of vitamin K-dependent clotting factors. As a result, warfarin produces a state that is functionally equivalent to vitamin K deficiency. If the dosage of warfarin is excessive, hemorrhage can occur secondary to lack of prothrombin.

Vitamin K Therapeutic Uses and Dosage

Vitamin K has two major applications: (1) correction or prevention of hypoprothrombinemia and bleeding caused by vitamin K deficiency (2) control of hemorrhage caused by warfarin Vitamin K Replacement. As discussed, vitamin K deficiency can result from impaired absorption and from insufficient synthesis of vitamin K by intestinal flora. Rarely, deficiency results from inadequate diet. For children and adults, the usual dosage for correction of vitamin K deficiency ranges between *5 and 15 mg/day*. *As noted, infants are born vitamin K deficient. To prevent hemorrhagic disease in neonates, it is recommended that all newborns be given an injection of phytonadione (0.5 to 1 mg) immediately after delivery.* Warfarin Antidote. Vitamin K reverses hypoprothrombinemia and bleeding caused by excessive dosing with warfarin, an oral anticoagulant. *Bleeding is controlled within hours of vitamin K administration* (see Chapter 52 for dosage).

Vitamin K Actions

Vitamin K is required for synthesis of *prothrombin and clotting factorsVII, IX, and X*. *All of these vitamin K-dependent factors are needed for coagulation of blood.* (phytonadione is the only form of vitamin K available for therapeutic use)

Nutrition experts recommend vitamin B12 for?

all people over age 50

Nutrition experts recommend folic acid for?

all women of child-bearing age

In older people with chronic health problems, too much vitamin E increases the risk of?

death

In people who smoke, too much beta-carotene (a precursor of vitamin A) increases the risk of?

lung cancer

Too much vitamin A increases the risk of?

osteoporosis in postmenopausal women and can cause birth defects when taken early in pregnancy

Nutrition experts recommend vitamin D (plus calcium) for?

postmenopausal women and other people at risk of fractures