Vitamins
Unfolding Case
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Marcus Skinner
Marcus is a 4-year-old boy with autism spectrum disorder who has communication impairments and social difficulties and exhibits repetitive behavior. His treatment includes medical nutrition therapy, speech-language therapy, occupational therapy, and physical therapy. Marcus does not eat a well-balanced eating pattern for several reasons: a feature of his compulsive behavior is that he only accepts a limited variety of foods, he is unable to eat when overstimulated at mealtime, and he has poor fine motor coordination that impairs his ability to feed himself. He is on a gluten-free/casein-free diet because these peptides are believed to cause a variety of effects in the neurotransmitter systems of the brain. Eliminating all foods containing gluten (foods containing wheat, barley, and rye) and casein (the major protein in milk and other dairy products and used as an additive in other foods such as soy products) may improve behaviors in some children with autism, although there is insufficient evidence of benefit.
Check Your Knowledge
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Learning Objectives
Upon completion of this chapter, you will be able to
1 Compare and contrast fat- and water-soluble vitamins.
2 Describe general functions and uses of vitamins.
3 Judge when vitamin supplements may be necessary.
4 Give examples of food sources for individual vitamins.
5 Discuss how Americans can shift their food choices to improve their intake of shortfall vitamins.
6 Identify characteristics to look for when choosing a vitamin supplement.
In 1913, thiamin was discovered as the first vitamin, the “vital amine” necessary to prevent the deficiency disease beriberi. Today, 13 vitamins have been identified as important for human nutrition; vitamin deficiency diseases are generally rare in the United States, and vitamin research focuses on whether consuming various vitamins above the minimum basic requirement can reduce the risk of heart disease, cancer, vision disorders, cognitive decline in the elderly, and other chronic diseases.
This chapter describes vitamins and their uses. Generalizations about fat- and water-soluble vitamins are presented. Unique features of each vitamin are covered individually, and criteria for selecting a vitamin supplement are discussed.
UNDERSTANDING VITAMINS
Vitamins are organic compounds made of carbon, hydrogen, oxygen, and, sometimes, nitrogen or other elements. They differ in their chemistry, biochemistry, function, and availability in foods. Vitamins facilitate biochemical reactions within cells to help regulate body processes such as growth and metabolism. They are essential to life. Unlike the organic compounds covered previously in this unit (carbohydrates, protein, and fat), vitamins
Are individual molecules, not long chains of molecules linked together
Do not provide energy but are needed for the metabolism of energy
Are needed in microgram or milligram quantities, not gram quantities, and so are called micronutrients
Micronutrients nutrients that are needed in very small amounts.
Chemical Substances
Vitamins are extremely complex chemical substances that differ widely in their structures. Because vitamins are defined chemically, the body cannot distinguish between natural vitamins extracted from food and synthetic vitamins produced in a laboratory. However, the absorption rates of natural and synthetic vitamins sometimes differ because of different chemical forms of the same vitamin (e.g., synthetic folic acid is better absorbed than natural folate in foods) or because the synthetic vitamins are “free,” not “bound” to other components in food (e.g., synthetic vitamin B12 is not bound to small peptides as natural vitamin B12 is).
Susceptible to Destruction
As organic substances, vitamins in food are susceptible to destruction and subsequent loss of function. Individual vitamins differ in their vulnerability to heat, light, oxidation, acid, and alkalis. For instance,
Thiamin is heat sensitive and is easily destroyed by high temperatures and long cooking times.
Riboflavin is resistant to heat, acid, and oxidation but is quickly destroyed by light. That is why riboflavin-rich milk is sold in opaque, not transparent, containers.
From 50% to 90% of folate in foods may be lost during preparation, processing, and storage.
Vitamin C is destroyed by heat, air, and alkalis.
Oxidation a chemical reaction in which a substance combines with oxygen; the loss of electrons in an atom.
Multiple Forms
Many vitamins exist in more than one active form. Different forms perform different functions in the body. For instance, vitamin A exists as retinol (important for reproduction), retinal (needed for vision), and retinoic acid (acts as a hormone to regulate growth). Some vitamins have provitamins, an inactive form found in food that the body converts to the active form. Beta-carotene is a provitamin of vitamin A. Dietary Reference Intakes take into account the biologic activity of vitamins as they exist in different forms.
Provitamins precursors of vitamins.
Essentiality
Vitamins are essential in the diet because, with a few exceptions, the body cannot make them. The body can make vitamin A, vitamin D, and niacin if the appropriate precursors are available. Microorganisms in the gastrointestinal (GI) tract synthesize vitamin K and vitamin B12 but not in amounts sufficient to meet the body’s needs.
Coenzymes
Many enzymes cannot function without a coenzyme, and many coenzymes are vitamins. All B vitamins work as coenzymes to facilitate thousands of chemical conversions. For instance, thiamin, riboflavin, niacin, and biotin participate in enzymatic reactions that extract energy from glucose, amino acids, and fat. Folacin facilitates both amino acid metabolism and nucleic acid synthesis; without adequate folacin, protein synthesis and cell division are impaired. An adequate and continuous supply of B vitamins in every cell is vital for normal metabolism.
Enzymes proteins produced by cells that catalyze chemical reactions within the body without undergoing change themselves.
Coenzymes organic molecules that activate an enzyme.
Antioxidants
Free radicals are produced continuously in cells as they burn oxygen during normal metabolism. Ultraviolet radiation, air pollution, ozone, the metabolism of food, and smoking can also generate free radicals in the body. The problem with free radicals is that they oxidize body cells and DNA in their quest to become stable by gaining an electron. These structurally and functionally damaged oxidized cells are believed to contribute to aging and various health problems such as cancer, heart disease, and cataracts. Polyunsaturated fatty acids (PUFAs) in cell membranes are particularly vulnerable to damage by free radicals.
Free Radicals highly unstable, highly reactive molecular fragments with one or more unpaired electrons.
Antioxidants protect body cells from being oxidized (destroyed) by free radicals by undergoing oxidation themselves, which renders free radicals harmless. Vitamins and other substances in fruits, vegetables, and other plant-based food provide dozens, if not hundreds, of antioxidants (Box 5.1). Vitamins that function as major antioxidants are vitamin C, vitamin E, and the provitamin beta-carotene. Each has a slightly different role, so one cannot completely substitute for another. For instance, water-soluble vitamin C works within cells to disable free radicals, and fat-soluble vitamin E functions within fat tissue. Whether high doses of individual antioxidants offer the same health benefits as the package of substances found in food sources is an area of ongoing research.
Antioxidants substances that donate electrons to free radicals to prevent oxidation.
BOX 5.1 Rich Sources of Antioxidants
Beverages: coffee, green and black tea, red wine
Fruits: bilberries, black currants, wild strawberries, blackberries, goji berries, cranberries, dried apples, dried plums, dried apricots, prunes, kiwi, strawberries
Vegetables: green leafy vegetables, pepper, red and green chili, spinach, carrots, tomato, onion, garlic
Spices and herbs: cloves, peppermint, allspice, cinnamon, oregano, thyme, sage, rosemary
Other: dark chocolate, walnuts and pecans with pellicle, sesame oil, canola oil
Food Additives
Some vitamins are used as food additives in certain foods to boost their nutritional content; examples include vitamin C-enriched fruit drinks, vitamin D-fortified milk, and enriched flour and breads. Other foods have certain vitamins added to them to help preserve quality. For instance, vitamin C is added to frozen fish to help prevent rancidity and to luncheon meats to stabilize the red color. Vitamin E helps retard rancidity in vegetable oils, and beta-carotene adds color to margarine.
Food Additives substances added intentionally or unintentionally to food that affect its character.
Enrich to add nutrients back that were lost during processing; for example, white flour is enriched with B vitamins lost when the bran and germ layers are removed.
Fortified to fortify is to add nutrients to a food that were either not originally present or were present in insignificant amounts; for instance, many brands of orange juice are fortified with vitamin D.
Megadoses amounts at least 10 times greater than the Recommended Dietary Allowance (RDA).
Medications
In megadoses, vitamins function like drugs, not nutrients. Large doses of niacin are used to lower cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides in people with hyperlipidemia who do not respond to diet and exercise. Tretinoin (retinoic acid, a form of vitamin A) is used as a topical treatment for acne vulgaris and orally for acute promyelocytic leukemia. Gram quantities of vitamin C promote healing in patients with impaired bone and wound healing.
VITAMIN CLASSIFICATIONS BASED ON SOLUBILITY
Vitamins are classified according to their solubility. Vitamins A, D, E, and K are fat soluble. Vitamin C and the B vitamins (thiamin, riboflavin, niacin, folate, B6, B12, biotin, and pantothenic acid) are water soluble. Solubility determines vitamin absorption, transportation, storage, and excretion.
Fat-Soluble Vitamins
Group characteristics of fat-soluble vitamins are summarized in Table 5.1. Table 5.2 highlights recommended intakes, sources, functions, deficiency symptoms, and toxicity symptoms of each fat-soluble vitamin. The complete table of Dietary Reference Intakes for vitamins appears in Appendix B. Additional features of individual fat-soluble vitamins follow.
Table 5.1 Group Characteristics of Fat-Soluble and Water-Soluble Vitamins | |||||||||||||||||||||
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Table 5.2 Summary of Fat-Soluble Vitamins | |||||||||||||||
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Vitamin A
In its preformed state, vitamin A exists as an alcohol (retinol), aldehyde (retinaldehyde), or acid (retinoic acid). Preformed vitamin A is found only in animal sources such as liver, whole milk, and fish. Low-fat milk, skim milk, margarine, and ready-toeat cereals are fortified with vitamin A.
Preformed Vitamin A the active form of vitamin A.
Carotenoids a group name of retinol precursors found in plants.
The term vitamin A also includes provitamin A carotenoids, natural plant pigments found in deep yellow and orange fruits and vegetables and most dark green leafy vegetables. Although there are over 600 different carotenoids, only a few are considered precursors of retinol. Beta-carotene, lutein, and lycopene are among the most commonly known carotenoids. Carotenoids account for about one-quarter to one-third of the usual intake of vitamin A.
Vitamin A is best known for its roles in normal vision, reproduction, growth, and immune system functioning. It is a relatively poor antioxidant. In contrast, beta-carotene is a major antioxidant in the body, prompting researchers to study whether it can prevent heart disease and cancer. A landmark trial designed to test whether beta-carotene supplements could decrease cancer incidence in people at high risk was prematurely halted when results showed a surprising increase in lung cancer incidence and deaths in smokers and male asbestos workers (Omenn et al., 1996; The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Group, 1994). The U.S. Preventive Services Task Force recommends against beta-carotene supplements for the prevention of cardiovascular disease or cancer (Moyer, 2014).
The body can store up to a year supply of vitamin A, 90% of which is in the liver. Because deficiency symptoms do not develop until body stores are exhausted, it may take 1 to 2 years for them to appear. Although severe vitamin A deficiency is rare in the United States, a large percentage of adults may have suboptimal liver stores of vitamin A even though they are not clinically deficient. Worldwide, vitamin A deficiency is a major health problem; an estimated 250,000 to 500,000 vitamin A-deficient children become blind every year. Half of them die within a year of losing their sight from common infections such as diarrheal disease and measles (World Health Organization, 2012).
Only preformed vitamin A, the form found in animal foods, fortified foods, and supplements, is toxic in high doses. The risk of toxicity is much greater when supplements of vitamin A are consumed. Extremely high doses (at least 30,000 mg/day) consumed over months or years may cause central nervous system (CNS) changes, bone and skin changes, and liver abnormalities that range from reversible to fatal. At high doses during pregnancy, such as three to four times the recommended intake, vitamin A is teratogenic. Supplementation is not recommended during the first trimester of pregnancy unless there is specific evidence of vitamin A deficiency.
Beta-carotene is nontoxic because the body makes vitamin A from it only as needed and the conversion is not rapid enough to cause hypervitaminosis A. Instead, carotene is stored primarily in adipose tissue and may accumulate under the skin to the extent that it causes the skin color to turn yellowish orange, a harmless condition known as hypercarotenemia. The Tolerable Upper Intake Level (UL) for vitamin A does not apply to vitamin A derived from carotenoids.
Vitamin D
Vitamin D is unique in that the body has the potential to make all it needs if exposure to sunlight is optimal and liver and kidney functions are normal. Because vitamin D can be endogenously synthesized, it is not an essential nutrient in the diet.
Essential Nutrient a nutrient that must be supplied by the diet because it is not synthesized in the body. Essentiality does not refer to importance but to the need for a dietary source.
Vitamin D exists in two forms: vitamin D3 or cholecalciferol and vitamin D2 or ergocalciferol. Vitamin D3 is synthesized in the skin when exposed to ultraviolet light. Both forms accumulate in the liver where they are converted to 25-hydroxyvitamin D [25(OH)D], which then enters the circulation. The kidneys convert [25(OH)D] to the biologically active form of vitamin D, 1,25(OH)2D. This conversion is tightly regulated by parathyroid hormone in response to serum calcium and phosphorus levels.
Because vitamin D is synthesized in one part of the body (skin) and stimulates functional activity elsewhere (e.g., GI tract, bones, kidneys), it is actually a prohormone. The most widely known function of vitamin D is to maintain normal blood concentrations of calcium and phosphorus by
Stimulating calcium and phosphorus absorption from the GI tract
Mobilizing calcium and phosphorus from the bone as needed to maintain normal serum levels
Stimulating the kidneys to retain calcium and phosphorus
Overt deficiency of vitamin D causes poor calcium absorption, leading to a calcium deficit in the blood that the body corrects by releasing calcium from bone. In children, the result is rickets, a condition characterized by abnormal bone shape and structure. Fortification of milk was instituted as an effective and inexpensive way to boost vitamin D intake. In adults, vitamin D deficiency can result in osteomalacia, a softening of the bones. Loss of bone mineral density coincides with osteoporosis and increased risk of falls and fractures (Pludowski et al., 2013).
Rickets vitamin D deficiency disease in children, most prominently characterized by bowed legs.
Osteomalacia adult rickets characterized by inadequate bone mineralization due to the lack of vitamin D.
The inverse relationship between sunlight exposure and increased incidence of several chronic diseases such as cancer, autoimmune diseases, diabetes, and cardiovascular disease led researchers to speculate that vitamin D has functions beyond its role in bone health. The discovery that most tissues and cells have vitamin D receptors (e.g., in the skin, pancreas, colon, kidney, parathyroid and pituitary glands, ovaries, and lymphocytes) suggests vitamin D has many diverse roles. Vitamin D may be involved in (Eich & Kline, 2016)
Regulating cell growth and differentiation
Inducing apoptosis
Modulating T and B cells, cell-mediated immunity and cytokines
Decreasing proinflammatory immune cells
Stimulating insulin production.
Low levels of vitamin D have been implicated in autoimmune diseases such as multiple sclerosis (Pender, 2012), hypertension (Witham, Nadir, & Struthers, 2009), cardiovascular diseases (Khaw, Luben, & Wareham, 2014; Muscogiuri et al., 2012), metabolic syndrome (Fung et al., 2012), type 2 diabetes (Lim et al., 2013), several types of cancer (Bolland, Grey, Gamble, & Reid, 2011; Grant, 2011), cognitive decline (Breitling et al., 2012), and depression (Bertone-Johnson et al., 2011). A large cohort study shows vitamin D deficiency is strongly associated with mortality from all causes, including cardiovascular diseases, cancer, and respiratory diseases (Schöttker et al., 2013). There is also evidence that vitamin D plays a role in reducing the risk of respiratory tract infection (Bergman et al., 2012) and sepsis (Watkins, Yamshchikov, Lemonovich, & Salata, 2011).
In 2010, the Institute of Medicine (IOM) established the RDA for vitamin D at 600 IU/day for children and adults through age 70 years and 800 IU/day for adults age 71 years and older (Ross et al., 2011). These levels are based on the assumption of minimal or no sun exposure. The basis for determining the RDA for vitamin D is its cause-and-effect relationship with bone health only; the IOM maintains that evidence linking vitamin D with extraskeletal outcomes, including cancer, cardiovascular disease, diabetes, and autoimmune disorders, is inconsistent, inconclusive, and insufficient to use in determining vitamin D requirements (IOM, 2011).
IU to convert micrograms of vitamin D to IU, multiply micrograms by 40.
Many researchers criticize the RDA for being too conservative. The Endocrine Society agrees that more studies are needed on vitamin D’s extraskeletal roles before those roles are factored into dietary recommendations. However, the Endocrine Society recommends adults consume 1500 to 2000 IU/day to prevent deficiency [25(OH)D <20 ng/mL] or vitamin D insufficiency [25(OH)D levels of 21 to 29 ng/mL] (Holick et al., 2011).
Quick BiteVitamin D content of selected items
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The current UL for vitamin D is set at 4000 IU/day for ages 9 years and older. Factors considered in determining the UL included hypercalcemia, hypercalciuria, vascular and soft tissue calcification, and emerging evidence of a U-shaped relationship for all-cause mortality, cardiovascular disease, certain cancers, falls, and fractures (Ross et al., 2011). Because the body destroys excess vitamin D produced from overexposure to the sun, there has never been a reported case of vitamin D toxicity from too much sun (Food and Nutrition Board, IOM, 1997).
Unfolding Case
Recall Marcus. His gluten-free/casein-free diet restricts many types of grain and milk products and some children following this diet have developed amino acid deficiencies, which is essentially a form of protein malnutrition. Marcus has difficulty chewing meat, which further limits his intake of protein. What foods can provide protein within the context of his dietary restrictions? Should Marcus take amino acid supplements? Which vitamins may he be underconsuming given his restricted intake of grains, milk, and meats? Will vitamin supplements compensate for the lack of variety in his intake?
Vitamin E
Vitamin E is a group name that describes a group of at least eight structurally related, naturally occurring compounds. Alpha-tocopherol is considered the most biologically active form of vitamin E, although other forms also have important roles in maintaining health. As a group, vitamin E functions as the primary fat-soluble antioxidant in the body, protecting PUFAs and other lipid molecules, such as LDL cholesterol, from oxidative damage. By doing so, it helps to maintain the integrity of PUFA-rich cell membranes, protects red blood cells against hemolysis, and protects vitamin A from oxidation. Vitamin E also has several important functions independent of its antioxidant activity, such as inhibiting cell division, enhancing immune system functioning, regulating gene expression, inhibiting platelet aggregation, and promoting blood vessel dilation.
The need for vitamin E increases as the intake of PUFA increases. Fortunately, vitamin E and PUFA share many of the same food sources, particularly nuts, seeds, fortified cereals, vegetable oils and products made from oil such as margarine, salad dressings, and other prepared foods. However, not all oils are rich in alpha-tocopherol, the active form of vitamin E. Soybean oil, the most commonly used oil in food processing, ranks low in alpha-tocopherol content.
Interest in the role of vitamin E in health stems from its antioxidant and anti-inflammatory activity as well as its role in immune system functioning and blood clotting. One hypothesis is that the antioxidant activity of vitamin E could reduce the risk of cancer by protecting cells from damage caused by unchecked free radicals. Unfortunately, most randomized trials find that vitamin E is not beneficial with regard to total or site-specific cancers (Wang et al., 2014). In addition, a study in the posttrial follow-up to the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found that vitamin E supplementation significantly increased the risk of prostate cancer in healthy men (Klein et al., 2011). The U.S. Preventive Services Task Force position states that supplements of vitamin E do not reduce the risk for cancer or cardiovascular disease and recommends they not be taken (Moyer, 2014).
One promising area of research it the role in age-related macular degeneration (ARMD). The Age-Related Eye Disease Study (AREDS), a large randomized clinical trial, and its follow-up study Age-Related Eye Disease Study 2 (AREDS2), showed that a daily supplement containing vitamin E decreased the risk of ARMD by 25% in people at high risk of developing advanced ARMD (Age-Related Eye Disease Study Research Group, 2001; The Age-Related Eye Disease Study 2 Research Group, 2013). However, it is not clear that vitamin E supplements, taken alone or in combination with other antioxidants, reduces the risk of developing ARMD in people who are not at high risk for the disorder.
Vitamin E deficiency is rare and more likely to occur secondary to fat malabsorption syndromes, such as cystic fibrosis and short bowel syndrome, than from an inadequate intake. Premature infants who have not benefited from the transfer of vitamin E from mother to fetus in the last weeks of pregnancy are at risk for red blood cell hemolysis. The breaking of their red blood cell membranes is caused by oxidation; vitamin E corrects red blood cell hemolysis by preventing oxidation. Prolonged vitamin E deficiency symptoms include peripheral neuropathy, ataxia, and impaired vision and speech.
Large amounts of vitamin E are relatively nontoxic but can interfere with vitamin K action (blood clotting) by decreasing platelet aggregation. Large doses may also potentiate the effects of blood-thinning drugs, increasing the risk of hemorrhage. The UL is 66 times higher than the RDA.
Quick BiteOils containing active form of vitamin E (in descending order)
Wheat germ oil
Walnut oil
Sunflower oil
Cottonseed oil
Safflower oil
Palm oil
Canola oil
Sesame oil
Peanut oil
Olive oil
Corn oil
Soybean oil
Vitamin K
Vitamin K occurs naturally in two forms. Phylloquinone is found in plants—spinach, broccoli, iceberg lettuce, and soybean and canola oils are common sources. Menaquinones, the animal form, is found in modest amounts in meat, dairy products, and eggs and is the form of vitamin K synthesized in the intestinal tract by microbiota. It is not known how much vitamin K produced by microbiota are absorbed.
Vitamin K is a coenzyme essential for the synthesis of prothrombin and at least 6 of the other 13 proteins needed for normal blood clotting. Without adequate vitamin K, life is threatened: Even a small wound can cause someone deficient in vitamin K to bleed to death. Vitamin K also activates at least three proteins involved in building and maintaining bone.
Newborns are prone to vitamin K deficiency for a few reasons: Vitamin K transport across the placenta is low, the vitamin K content of breast milk is low, and because newborns have sterile GI tracts that cannot synthesize vitamin K. To prevent hemorrhagic disease, a single intramuscular dose of vitamin K is given prophylactically at birth.
Clinically significant vitamin K deficiency is defined as vitamin K-responsive hypoprothrombinemia and is characterized by an increase in prothrombin time. Vitamin K deficiency does not occur from inadequate intake but may occur secondary to malabsorption syndromes or to the use of certain medications that interfere with vitamin K metabolism or synthesis, such as anticoagulants and antibiotics. Anticoagulants, such as warfarin (Coumadin), interfere with hepatic synthesis of vitamin K-dependent clotting factors. People who take warfarin do not need to avoid vitamin K, but they should try to maintain a consistent intake so that the effect on coagulation time is as constant and as predictable as possible. Antibiotics kill the intestinal bacteria that synthesize vitamin K.
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