chapter 10 (the water-soluble vitamins) understanding nutrition

Bioavailability Some water-soluble vitamins are synthesized by GI tract bacteria and absorbed by the large intestine, but not in quantities great enough to meet the body's needs; foods must supply these essential nutrients. The amount available from foods depends not only on the quantity provided by a food but also on the vitamin's bioavailability—the amount absorbed and used by the body. The quantity of vitamins in a food can be determined relatively easily. Researchers analyze foods to determine the vitamin contents and publish the results in tables such as the USDA Food Composition Database (https://ndb.nal.usda.gov/). Determining the bioavailability of a vitamin is a more complex task because it depends on many factors, including:

--- Efficiency of digestion and time of transit through the GI tract --- Previous nutrient intake and nutrition status --- Method of food preparation (raw, cooked, or processed) --- Source of the nutrient (synthetic, fortified, or naturally occurring) --- Other foods consumed at the same time (bioavailability: the rate at and the extent to which a nutrient is absorbed and used.)

A person consumes the equivalent of 75 mg of tryptophan from protein alone. How many niacin equivalents does this represent?

1.25

About what percentage of U.S. adults take a multivitamin-mineral supplement regularly?

30

A 35-year-old man consumed the following folate-containing foods for lunch: 2 slices fortified bread = 14 μg food folate, 48 μg synthetic folate 4 tablespoons peanut butter = 47 μg) food folate ½ cup carrot sticks = 12 μg food folate orange = 48 μg food folate 2 graham crackers = 5 μg food folate, 8 μg synthetic folate What percentage of his RDA for folate did his lunch provide?

55

Pantothenic acid is part of the chemical structure of coenzyme A—the same CoA that forms acetyl CoA, a key compound in several metabolic pathways featured in Chapter 7, including the TCA cycle. (Appendix C presents the chemical structures of these two molecules and shows that coenzyme A is made up in part of pantothenic acid.) As such, it is involved in more than 100 different steps in the synthesis of lipids, neurotransmitters, steroid hormones, and hemoglobin.

Pantothenic acid: a B vitamin. The principal active form is part of coenzyme A, called "CoA" throughout Chapter 7.

Keep in mind that the cause of a sign or symptom is not always apparent. The summary tables in this chapter show that deficiencies of riboflavin, niacin, biotin, and vitamin B6 can all cause skin rashes. So can a deficiency of protein, linoleic acid, or vitamin A. Because skin is on the outside and easy to see, it is a useful indicator of "things going wrong inside cells." By itself, a skin condition says nothing about its possible cause. The same is true of anemia. Anemia is often caused by iron deficiency, but it can also be caused by a folate or vitamin B12 deficiency; by digestive tract failure to absorb any of these nutrients; or by such nonnutritional causes as infections, parasites, cancer, or loss of blood. No single nutrient will always cure a given symptom.

A person who feels chronically tired may be tempted to self-diagnose iron-deficiency anemia and self-prescribe an iron supplement. But this will relieve tiredness only if the cause is indeed iron-deficiency anemia. If the cause is a folate deficiency, taking iron will only prolong the fatigue. A person who is better informed may decide to take a multivitamin supplement with iron, covering the possibility of a vitamin deficiency. But the symptom may have a nonnutritional cause. If the cause of the tiredness is actually hidden blood loss due to cancer, the postponement of a diagnosis may be life-threatening. When fatigue is caused by a lack of sleep, of course, no nutrient or combination of nutrients can replace a good night's rest. A person who is chronically tired should see a physician rather than self-prescribe. If the condition is nutrition-related, a registered dietitian nutritionist should be consulted as well.

What is "niacin flush"?

A pharmacological effect that occurs from taking large doses of supplemental or prescription niacin

Bioavailability and Antagonistic Actions antagonist: a competing factor that counteracts the action of another factor. When a drug displaces a vitamin from its site of action, the drug renders the vitamin ineffective and thus acts as a vitamin antagonist. In general, the body absorbs nutrients best from foods in which the nutrients are diluted and dispersed among other substances that may facilitate their absorption. Taken in pure, concentrated form, nutrients are likely to interfere with one another's absorption or with the absorption of nutrients in foods eaten at the same time. Documentation of these effects is particularly extensive for minerals: zinc hinders copper and calcium absorption, iron hinders zinc absorption, calcium hinders magnesium and iron absorption, and magnesium hinders the absorption of calcium and iron. Similarly, binding agents in supplements limit mineral absorption.

Although minerals provide the most-familiar and best-documented examples, interference among vitamins is now being seen as supplement use increases. The vitamin A precursor beta-carotene, long thought to be nontoxic, interferes with vitamin E metabolism when taken over the long term as a dietary supplement. Vitamin E, on the other hand, antagonizes vitamin K activity and so should not be used by people being treated for blood-clotting disorders. Consumers who want the benefits of optimal absorption of nutrients should eat foods selected for nutrient density and variety. Whenever the diet is inadequate, the person should first attempt to improve it so as to obtain the needed nutrients from foods. If that is truly impossible, then the person needs a multivitamin-mineral supplement that supplies between 50 and 150 percent of the Daily Value for each of the nutrients. These amounts reflect the ranges commonly found in foods and therefore are compatible with the body's normal handling of nutrients (its physiological tolerance). The Selection of Supplements provides some pointers to assist in the selection of an appropriate supplement.

The vitamins are a diverse group of essential nutrients that regulate most body processes involved in supporting growth and maintaining life. Notably, the vitamins differ from carbohydrates, fats, and proteins in the following ways: --- Structure. Vitamins are individual units; they are not linked together (as are molecules of glucose or amino acids). Appendix C presents the chemical structure for each of the vitamins. --- Function. Vitamins do not yield energy when metabolized; many of them do, however, assist the enzymes that participate in the release of energy from carbohydrates, fats, and proteins. --- Food contents. Like carbohydrates, fats, and proteins, vitamins are readily available from foods, but the amounts of vitamins people ingest from foods and the amounts they require daily are measured in micrograms (μg) or milligrams (mg), rather than grams (g). For this reason, the vitamins are sometimes described as micronutrients.

Although small in size, the vitamins accomplish giant tasks. Obtaining enough, but not too much, of each vitamin is critical because both deficiencies and toxicities can be harmful. As Chapter 1 described, the Dietary Reference Intakes (DRI) define the amounts of each vitamin that best support health. Research studies help to determine a vitamin's requirement—how much is needed to maintain adequacy. With this information, an Estimated Average Requirement (EAR) is calculated to estimate the average amount that appears sufficient for half of the population. Once an EAR is established, a recommendation can be made that will meet the needs of about 98 percent of the population—the Recommended Dietary Allowance (RDA). If there is insufficient evidence to determine an EAR (which is needed to set an RDA), a recommendation based on the average amount of a nutrient that a group of healthy people consumes—an Adequate Intake (AI)—may be used instead of an RDA. The Tolerable Upper Intake Level (UL) sets the highest amount that appears safe for regular consumption. (See Chapter 1 for more details on the DRI.)

As a Cofactor in Collagen Formation Vitamin C helps to form the fibrous structural protein of connective tissues known as collagen. Collagen serves as the matrix on which bones and teeth are formed. When a person is wounded, collagen glues the separated tissues together, forming scars. Cells are held together largely by collagen; this is especially important in the walls of the blood vessels, which must withstand the pressure of blood surging with each beat of the heart. Chapter 6 described how the body makes proteins by stringing together chains of amino acids. During the synthesis of collagen, each time a proline or lysine is added to the growing protein chain, an enzyme hydroxylates it (adds an OH group), making the amino acid hydroxyproline or hydroxylysine, respectively. These two special amino acids facilitate the binding together of collagen fibers to make strong, ropelike structures. The conversion of proline to hydroxyproline requires both vitamin C and iron. Iron works as a cofactor in the reaction, and vitamin C protects iron from oxidation, thereby allowing iron to perform its job. Without vitamin C and iron, the hydroxylation step does not occur.

As a Cofactor in Other Reactions Vitamin C also serves as a cofactor in the synthesis of several other compounds. As in collagen formation, vitamin C helps in the hydroxylation of carnitine, a compound that transports fatty acids, especially long-chain fatty acids, across the inner membrane of mitochondria in cells. It also participates in the conversions of the amino acids tryptophan and tyrosine to the neurotransmitters serotonin and norepinephrine, respectively. Vitamin C also assists in the making of hormones, including thyroxine, which regulates the metabolic rate; when metabolism speeds up in times of extreme physical stress, the body's use of vitamin C increases.

The requirement—the amount needed to prevent the overt symptoms of scurvy—is only 10 milligrams daily. Consuming 10 milligrams a day does not saturate all the body tissues, however; higher intakes will increase the body's total vitamin C. At about 100 milligrams per day, 95 percent of the population reaches tissue saturation. (For perspective, 1 cup of orange juice provides more than 100 milligrams of vitamin C.) Recommendations are slightly lower, based on the amounts needed to provide antioxidant protection. At about 200 milligrams, absorption reaches a maximum, and there is little, if any, increase in blood concentrations at higher doses. Excess vitamin C is readily excreted.

As mentioned earlier, cigarette smoking increases the need for vitamin C. Cigarette smoke contains oxidants, which greedily deplete this potent antioxidant. Exposure to cigarette smoke, especially when accompanied by low dietary intakes of vitamin C, depletes the body's vitamin C in both active and passive smokers. People who chew tobacco also have low levels of vitamin C. Because people who smoke cigarettes regularly suffer significant oxidative stress, their requirement for vitamin C is increased an additional 35 milligrams; nonsmokers regularly exposed to cigarette smoke should also be sure to meet their RDA for vitamin C. Smokers are among those most likely to suffer vitamin C deficiency.

B Vitamin Toxicities Toxicities of the B vitamins from foods alone are unknown, but they can occur when people overuse dietary supplements. With supplements, the quantities can quickly overwhelm the cells. Consider that one small capsule can easily deliver 2 milligrams of vitamin B6, but it would take more than 3000 bananas, 6600 cups of rice, or 3600 chicken breasts to supply an equivalent amount. When the cells become oversaturated with a vitamin, they must work to eliminate the excess. The cells dispatch water-soluble vitamins to the urine for excretion, but sometimes they cannot keep pace with the onslaught. Homeostasis becomes disturbed and symptoms of toxicity develop.

B Vitamin Food Sources Significantly, deficiency diseases, such as beriberi and pellagra, were resolved by providing foods. Dietary supplements advertise that vitamins are indispensable to life, but human beings obtained their nourishment from foods for centuries before supplements existed. If the diet lacks a vitamin, the first solution is to adjust food intake to obtain that vitamin. The bar graphs of selected foods in this chapter, taken together, sing the praises of a balanced diet. The grains deliver thiamin, riboflavin, niacin, and folate. The fruit and vegetable groups excel in folate. Protein foods serve thiamin, niacin, vitamin B6, and vitamin B12 well. The milk group stands out for riboflavin and vitamin B12. A diet that offers a variety of foods from each group, prepared with reasonable care, serves up ample B vitamins.

fat-soluble vitamins are more likely to reach toxic levels in the body.

Because fat-soluble vitamins tend to remain in fat-storage sites in the body rather than being excreted, they are more likely to reach toxic levels when consumed in excess. Water-soluble vitamins freely circulate in the water-filled compartments of the body, and the kidneys, monitoring the blood flowing through them, will detect and remove small excesses of water-soluble vitamins.

Thiamin Deficiency and Toxicity People who fail to eat enough food to meet energy needs risk nutrient deficiencies, including thiamin deficiency. Inadequate thiamin intakes have been reported among the nation's malnourished and homeless people. Similarly, people who derive most of their energy from empty-kcalorie foods and beverages risk thiamin deficiency. Alcohol provides a good example of how empty kcalories can lead to thiamin deficiency. Alcohol contributes energy but provides few, if any, nutrients and often displaces food. In addition, alcohol impairs thiamin absorption and enhances thiamin excretion in the urine, doubling the risk of deficiency. An estimated four out of five alcoholics are thiamin deficient, which damages the brain's structure and impairs its function. Prolonged thiamin deficiency can result in the disease beriberi, which was first observed in Indonesia when the custom of polishing rice became widespread. Rice provided 80 percent of the energy intake of the people of that area, and the germ and bran of the rice grain was their principal source of thiamin. When the germ and bran were removed in the preparation of white rice, beriberi became rampant.

Beriberi is often described as "dry" or "wet." Dry beriberi reflects damage to the nervous system and is characterized by muscle weakness in the arms and legs. Wet beriberi reflects damage to the cardiovascular system and is characterized by dilated blood vessels, which cause the heart to work harder and the kidneys to retain salt and water, resulting in edema. Typically, both types of beriberi appear together, with one set of symptoms predominating. Figure 10-3 presents the edema of beriberi. No adverse effects have been associated with excesses of thiamin, and no UL has been determined. beriberi: the thiamin-deficiency disease characterized by muscle weakness, edema, or both.

The rate at and the extent to which a nutrient is absorbed and used is known as bioavailability

Bioavailability is the rate at and extent to which a nutrient is absorbed and used by the body. The bioavailability of a vitamin depends on many factors, such as nutrient source, food preparation method, and previous nutrition intake and nutrition status.

Biotin Food Sources Biotin is widespread in foods (including egg yolks), so eating a variety of foods protects against deficiencies. Some biotin is also synthesized by GI tract bacteria, but this amount does not contribute much to the biotin absorbed. The accompanying table provides a summary of biotin.

Biotin AI --- Adults: 30 μg/day Chief Functions in the Body --- Part of a coenzyme used in energy metabolism, fat synthesis, amino acid metabolism, and glycogen synthesis Significant Sources --- Widespread in foods; liver, egg yolks, soybeans, fish, whole grains; also produced by GI bacteria Deficiency Symptoms --- Depression, lethargy, hallucinations, numb or tingling sensation in the arms and legs; red, scaly rash around the eyes, nose, and mouth; hair loss Toxicity Symptoms --- None reported

Biotin Recommendations Biotin is needed in very small amounts. Because there is insufficient research on biotin requirements, an AI has been determined, instead of an RDA.

Biotin Deficiency and Toxicity Biotin deficiencies rarely occur. Researchers can induce a biotin deficiency in animals or human beings by feeding them raw egg whites, which contain a protein that binds biotin and thus prevents its absorption. Biotin-deficiency symptoms include skin rash, hair loss, and neurological impairment. More than two dozen raw egg whites must be consumed daily for several months to produce these effects; cooking eggs denatures the binding protein. Because no adverse effects have been reported from high biotin intakes, a UL has not been set.

Biotin Biotin (BY-oh-tin) plays an important role in metabolism as a coenzyme that carries activated carbon dioxide. This role is critical in the TCA cycle: biotin delivers a carbon to 3-carbon pyruvate, thus replenishing oxaloacetate, the 4-carbon compound needed to combine with acetyl CoA to keep the TCA cycle turning (review Step 6 in Figure 7-15). The biotin coenzyme also participates in gluconeogenesis, fatty acid synthesis, and the breakdown of certain fatty acids and amino acids.

Biotin: a B vitamin that functions as a coenzyme in metabolism.

Figure 10-10 illustrates two forms of folate. It explains that folate in fortified foods and supplements is in its monoglutamate form (containing only one glutamate), whereas naturally occurring folate in foods contains up to six glutamates (known as a polyglutamate). During digestion, enzymes on the intestinal cell walls hydrolyze the polyglutamate to monoglutamate and several single glutamates. The monoglutamate is then attached to a methyl group (CH3), which inactivates folate for storage in the liver and other body cells. To activate folate, the methyl group must be removed by an enzyme that requires the help of vitamin . Without that help, folate remains trapped in its methyl form, unavailable to support DNA synthesis and cell growth. Figure 10-11 summarizes folate's absorption, activation, and relationship with vitamin B12.

Chemically known as pteroylglutamic acid, folate consists of a ring structure (called a pteroyl) and one to six molecules of glutamate (an amino acid). Most naturally occurring folate in foods contains up to six glutamate molecules (polyglutamate) folate occurring in fortified foods and supplements contains one glutamate molecule (monoglutamate)

Choline Although not defined as a vitamin, choline is an essential nutrient that is commonly grouped with the B vitamins. The body uses choline to make the neurotransmitter acetylcholine and the phospholipid lecithin. During pregnancy, choline supports the neurological development of the fetus, and during adulthood, choline may improve cognition. Choline Recommendations The body can make choline from the amino acid methionine, but synthesis alone is insufficient to fully meet the body's needs; dietary choline is also needed. For this reason, the DRI Committee established an AI for choline.

Choline Deficiency and Toxicity Average choline intakes fall below the AI, but the impact of deficiencies are not fully understood. The UL for choline is based on its life-threatening effect in lowering blood pressure. Choline Food Sources Choline is found in a variety of common foods such as milk, eggs, and peanuts and as part of lecithin, a food additive commonly used as an emulsifying agent (review Figure 5-8). The accompanying table provides a summary of choline.

Arguments for Supplements Vitamin-mineral supplements may be appropriate in some circumstances. In some cases, they can prevent or correct deficiencies; in others, they can reduce the risk of certain diseases. Consumers should discuss supplement use with their health-care providers, who can help monitor for adverse effects or nutrient-drug interactions.

Correct Overt Deficiencies In the United States, adults rarely suffer nutrient deficiency diseases such as scurvy, pellagra, and beriberi, but nutrient deficiencies do still occur. To correct an overt deficiency disease, a physician may prescribe therapeutic doses two to ten times the RDA (or AI) of a nutrient. At such high doses, the supplement is having a pharmacological effect and acting as a drug.

best sources per kcalorie: broccoli, tomato juice, pinto beans, lentils, asparagus

Dark green and leafy vegetables (such as spinach and broccoli), legumes (such as black beans, kidney beans, and black-eyed peas), liver, and some fruits (notably citrus fruits and juices) are naturally rich in folate.

Who Needs Supplements? In summary, the following list acknowledges that in these specific conditions, these people may need to take supplements: People with specific nutrient deficiencies may need specific nutrient supplements. People whose energy intakes are particularly low (fewer than 1600 kcalories per day) may need multivitamin-mineral supplements. Vegetarians who eat all-plant diets (vegans) and older adults with atrophic gastritis may need vitamin B12. People who have lactose intolerance or milk allergies or who otherwise do not consume enough milk products to forestall extensive bone loss may need calcium and vitamin D. People in certain stages of the life cycle who have increased nutrient requirements may need specific nutrient supplements. For example, infants may need vitamin D, iron, and fluoride; women of childbearing age and pregnant women may need folate and iron; and the elderly may need vitamin B12 and vitamin D. People who have inadequate intakes of milk or milk products, limited sun exposure, or heavily pigmented skin may need vitamin D. People who have diseases, infections, or injuries or who have undergone surgery that interferes with the intake, absorption, metabolism, or excretion of nutrients may need specific nutrient supplements. People taking medications that interfere with the body's use of specific nutrients may need specific nutrient supplements.

Except for people in these circumstances, most adults can get all the nutrients they need by eating a variety of nutrient-dense foods. Even athletes can meet their nutrient needs without the help of supplements, as Chapter 14 explains.

Regulation of Supplements Dietary supplements are regulated by the FDA (Food and Drug Administration) as foods. Details of supplement regulation are defined in the Dietary Supplement Health and Education Act of 1994, which was intended to enable consumers to make informed choices about dietary supplements. The act subjects supplements to the same general labeling requirements that apply to foods. Specifically: Nutrition labeling for dietary supplements is required. Labels may make nutrient claims (as "high" or "low") according to specific criteria (for example, "an excellent source of vitamin C"). Labels may claim that the lack of a nutrient can cause a deficiency disease, but if they do, they must also include the prevalence of that deficiency disease in the United States. Labels may make health claims that are supported by significant scientific agreement and are not brand specific (for example, "folate protects against neural tube defects"). Labels may claim to diagnose, treat, cure, or relieve common complaints such as menstrual cramps or memory loss, but may not make claims about specific diseases (except as noted previously). Labels may make structure-function claims about the role a nutrient plays in the body, how the nutrient performs its function, and how consuming the nutrient is associated with general well-being (see Photo H10-1). The manufacturer is responsible for ensuring that the claims are truthful and not misleading. Claims must be accompanied by an FDA disclaimer statement: "This statement has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease."

FDA (Food and Drug Administration): an agency within the Department of Health and Human Services that is responsible for ensuring the safety and wholesomeness of all dietary supplements and foods processed and sold in interstate commerce except meat, poultry, and eggs (which are under the jurisdiction of the USDA); inspecting food plants and imported foods; and setting standards for food composition and product labeling. Structure-function claims do not need FDA authorization, but they must be accompanied by a disclaimer.

Unknown Needs Another argument against the use of supplements is that there are no standards and no one knows exactly how to formulate the "ideal" supplement. What nutrients should be included? Which, if any, of the phytochemicals should be included? How much of each? On whose needs should the choices be based? Surveys have repeatedly shown little relationship between the supplements people take and the nutrients they actually need.

False Sense of Security Another argument against supplement use is that it may lull people into a false sense of security. A person might eat irresponsibly, thinking, "My supplement will ensure my needs are met." Or, experiencing a warning symptom of a disease, a person might postpone seeking a diagnosis, thinking, "I probably just need a supplement to make this go away." Such self-diagnosis is potentially dangerous.

Because vitamin B12 is found primarily in foods derived from animals, vegetarians, and especially vegans, are especially likely to develop a vitamin B12 deficiency. It may take several years for people who stop eating animal-derived foods to develop deficiency symptoms because the body recycles much of its vitamin B12, reabsorbing it over and over again and conserving its supply. When deficiency does occur, and vitamin B12 is no longer available, the consequences are dramatic. Neurological degeneration, a sign of vitamin deficiency, appears rapidly in infants born to mothers with unsupplemented vegan diets. Because vitamin B12 is required to convert folate to its active form, one of the most obvious vitamin B12-deficiency symptoms is the anemia commonly seen in folate deficiency. This anemia is characterized by large, immature red blood cells, which indicate slow DNA synthesis and an inability to divide (review Figure 10-12). When folate is trapped in its inactive form (methyl folate) because of vitamin deficiency or is unavailable because of folate deficiency itself, DNA synthesis slows.

First to be affected in a vitamin B12 or folate deficiency are the rapidly growing blood cells. Either vitamin or folate will clear up the anemia, but if folate is given when vitamin B12 is needed, the result is disastrous: devastating neurological symptoms. Remember that vitamin B12, but not folate, maintains the sheath that surrounds and protects nerve fibers and promotes their normal growth. Folate "cures" the blood symptoms of a vitamin deficiency, but cannot stop the nerve symptoms from progressing. By doing so, folate "masks" a vitamin deficiency. Even marginal vitamin deficiency impairs memory and cognition. Advanced neurological symptoms include a creeping paralysis that begins at the extremities and works inward and up the spine. Early detection and correction are necessary to prevent permanent nerve damage and paralysis. With sufficient folate in the diet, the neurological symptoms of vitamin deficiency can develop without evidence of anemia and the cognitive decline is especially rapid. Such interactions between folate and vitamin highlight some of the safety issues surrounding the use of supplements and the fortification of foods. No adverse effects have been reported for excess vitamin B12, and no UL has been set.

Folate Toxicity A UL has been established for folate from fortified foods or supplements (see the insert). Commonly consumed amounts of folate from both natural sources and fortified foods appear to cause no harm. The small percentage of adults who also take high-dose folate supplements, however, can reach levels that are high enough to obscure a vitamin deficiency and delay diagnosis of neurological damage.

Folate Food Sources Figure 10-13 shows that folate is especially abundant in legumes, fruits, and vegetables (see Photo 10-7). The vitamin's name suggests the word foliage, and indeed, dark green, leafy vegetables are outstanding sources. With fortification, grain products also contribute folate. The small red and white bars in Figure 10-13 indicate that meats and milk products are poor folate sources. Heat and oxidation during cooking and storage can destroy as much as half of the folate in foods. The table below provides a summary of folate.

Folate and Heart Disease The FDA's decision to fortify grain products with folate was strengthened by research suggesting a role for folate in protecting against heart disease. One of folate's key roles in the body is to break down the amino acid homocysteine. Without folate, homocysteine accumulates, which seems to enhance formation of blood clots and atherosclerotic lesions. Fortified foods and folate supplements raise blood folate and reduce blood homocysteine, but may not reduce the risk of heart attacks, strokes, or death from cardiovascular causes.

Folate and Cancer Because the synthesis of DNA and the transfer of methyl groups depend on folate, its relationships with cancer are complex, depending on the type of cancer and the timing of folate supplementation. Some research suggests that sufficient folate may protect against the initiation of cancer, whereas other studies report that high intakes may enhance progression once cancer has begun. In general, foods containing folate probably reduce the risk of pancreatic cancer. Limited evidence suggests that folate may also reduce the risk of esophageal and colorectal cancer.

Folate, also known as folacin or folic acid, has a chemical name that would fit a flying dinosaur: pteroylglutamic acid (PGA for short). Its primary coenzyme form, THF (tetrahydrofolate), serves as part of an enzyme complex that transfers 1-carbon compounds that arise during metabolism. This action converts vitamin B6 to one of its coenzyme forms, synthesizes the DNA required for all rapidly growing cells, and regenerates the amino acid methionine from homocysteine.

Folate: a B vitamin; also known as folic acid, folacin, or pteroylglutamic acid (PGA). The coenzyme forms are DHF (dihydrofolate) and THF (tetrahydrofolate).

More than half of the adults in the United States take a dietary supplement regularly, spending $37 billion each year. Most people take supplements as a part of their efforts to live a healthy life. Yet most vitamin and mineral supplements do not prevent chronic disease or delay death. This highlight focuses on vitamin and mineral supplements. (Amino acid and protein supplements are discussed in Chapter 6; weight loss products, in Chapter 9; ergogenic aids for athletes, in Highlight 14; and herbal supplements in Highlight 18.) An estimated 30 percent of US adults take multivitamin-mineral supplements regularly. Others take large doses of single nutrients, most commonly, vitamin D and calcium. In many cases, taking supplements is a costly but harmless practice; sometimes, it is both costly and harmful to health. Every year, more than 7000 emergency department visits in the United States are attributed to adverse effects of vitamin and/or mineral supplements; an additional 16,000 visits are attributed to other herbal and nutritional products. dietary supplement: any pill, capsule, tablet, liquid, or powder that contains vitamins, minerals, herbs, or amino acids intended to increase dietary intake of these substances

For the most part, people self-prescribe supplements, taking them on the advice of friends, advertisements, websites, or books that may or may not be reliable. Sometimes, they take supplements on the recommendation of a physician. When such advice follows a valid nutrition assessment, supplementation may be warranted, but even then the preferred course of action is to improve food choices and eating habits. Without an assessment, the advice to take supplements may be inappropriate. A registered dietitian nutritionist can help with the decision. This highlight asks several questions related to vitamin-mineral supplements. What are the arguments for taking supplements? What are the arguments against taking them? Finally, if people do take supplements, how can they choose the appropriate ones?

Selection of Supplements Whenever a physician or registered dietitian nutritionist recommends a supplement, follow the directions carefully. When selecting a supplement yourself, look for a single, balanced vitamin-mineral supplement. Supplements with a USP verification logo have been tested by the US Pharmacopeia (USP) to ensure that the supplement: Contains the declared ingredients and amounts listed on the label Does not contain harmful levels of contaminants Will disintegrate and release ingredients in the body Was made under safe and sanitary conditions If you decide to take a vitamin-mineral supplement, ignore the eye-catching art and meaningless claims. Pay attention to the form the supplements are in, the list of ingredients, and the price. Here's where the truth lies, and from it you can make a rational decision based on facts. You have two basic questions to answer.

Form The first question: What form do you want—chewable, liquid, or pills? If you'd rather drink your supplements than chew them, fine. If you choose a chewable form, though, be aware that chewable vitamin C can dissolve tooth enamel. If you choose pills, look for statements about the disintegration time. The USP suggests that supplements should completely disintegrate within 30 to 45 minutes. Obviously, supplements that don't dissolve have little chance of entering the bloodstream, so look for a brand that claims to meet USP disintegration standards.

Reduce Disease Risks Few people consume the optimal amounts of all the vitamins and minerals by diet alone. Inadequate intakes have been linked to chronic diseases such as heart disease, some cancers, and osteoporosis. For this reason, some physicians recommend that all adults take vitamin-mineral supplements. Such regular supplementation would provide an optimum intake to enhance metabolic harmony and prevent disease at relatively little cost. Others recognize the lack of conclusive evidence and the potential harm of supplementation and advise against such a recommendation. A statement from the National Institutes of Health acknowledges that evidence is insufficient to recommend either for or against the use of supplements to prevent chronic diseases.

Highlight 11 reviews the relationships between supplement use and disease prevention. It describes some of the accumulating evidence suggesting that intakes of certain nutrients at levels much higher than can be attained from foods alone may be beneficial in reducing some disease risks. It also presents research confirming the associated risks. Clearly, consumers must be cautious in taking supplements to prevent disease.

The multibillion-dollar-a-year supplement industry spends much money and effort influencing these regulations. The net effect of the Dietary Supplement Health and Education Act was a deregulation of the supplement industry. Unlike food additives or drugs, supplements do not need to be proved safe and effective, nor do they need the FDA's approval before being marketed. Furthermore, there are no standards for potency or dosage and no requirements for providing warnings of potential side effects. The FDA can only require good manufacturing practices: that dietary supplements be produced and packaged in a quality manner, do not contain contaminants or impurities, and are accurately labeled to reflect the actual contents. Should a problem arise, the burden falls to the FDA to prove that the supplement poses a "significant or unreasonable risk of illness or injury." Only then would it be removed from the market. When asked, most Americans express support for greater regulation of dietary supplements. Health professionals agree. To learn more about dietary supplements currently on the US market as well as those that have been recalled, consumers can visit the National Institutes of Health website

If all the nutrients we need can come from food, why not just eat food? Foods have so much more to offer than supplements do. Nutrients in foods come in an infinite variety of combinations with a multitude of different carriers and absorption enhancers. They come with water, fiber, and an array of beneficial phytochemicals. Foods stimulate the GI tract to keep it healthy. They provide energy, and as long as you need energy each day, why not have nutritious foods deliver it? Foods offer pleasure, satiety, and opportunities for socializing while eating. Quite simply, foods meet human health needs far better than dietary supplements.

Support Increased Nutrient Needs As Chapters 15, 16 and 17 explain, nutrient needs increase during certain stages of life, making it difficult to meet some of those needs without supplementation. For example, women who lose a lot of blood and therefore a lot of iron during menstruation each month may need an iron supplement. Women of childbearing age need folate supplements to reduce the risks of neural tube defects. Similarly, pregnant women and women who are breastfeeding their infants have exceptionally high nutrient needs and so usually need special supplements. Newborns routinely receive a single dose of vitamin K at birth to prevent abnormal bleeding. Infants may need other supplements as well, depending on whether they are breastfed or receiving formula, and on whether the water they drink contains fluoride. Improve the Body's Defenses Health-care professionals may provide special supplementation to people being treated for addictions to alcohol or other drugs and to people with prolonged illnesses, extensive injuries, or other severe stresses such as surgery. Illnesses and their treatments that interfere with appetite, eating, or nutrient absorption impair nutrition status. For example, the stomach condition atrophic gastritis often creates a vitamin B12 deficiency. In addition, nutrient needs may be heightened by diseases or medications. In all these cases, supplements are appropriate.

Improve Nutrition Status In contrast to the classical deficiencies, which present a multitude of symptoms and are relatively easy to recognize, subclinical deficiencies are subtle and easy to overlook—and they are also more likely to occur. Without fortification or supplementation, many adults in the United States fall short of recommended intakes for several vitamins and minerals. People who do not eat enough food to deliver the needed amounts of nutrients, such as habitual dieters and the elderly, risk developing subclinical deficiencies. Similarly, vegetarians and vegans who restrict their use of entire food groups without appropriate substitutions may fail to fully meet their nutrient needs. If there is no way for these people to eat enough nutritious foods to meet their needs, then vitamin-mineral supplements may be appropriate to help prevent nutrient deficiencies.

In Stress Among the stresses known to increase vitamin C needs are infections; burns; extremely high or low temperatures; intakes of toxic heavy metals such as lead, mercury, and cadmium; the chronic use of certain medications, including aspirin, barbiturates, and oral contraceptives; and cigarette smoking. During stress, the adrenal glands—which contain more vitamin C than any other organ in the body—release vitamin C and hormones into the blood. When immune system cells are called into action, they use a great deal of oxygen and produce free radicals. In this case, free radicals are helpful. They act as ammunition in an "oxidative burst" that demolishes the offending viruses and bacteria and destroys the damaged cells. Vitamin C steps in as an antioxidant to control this oxidative activity. In Disease Prevention Whether vitamin C may help in preventing or treating cancer, heart disease, cataract, and other diseases is still being studied, and findings are presented in Highlight 11's discussion on antioxidants. Conducting research in the United States can be difficult, however, because diets typically contribute enough vitamin C to provide optimal health benefits.

In the Prevention and Treatment of the Common Cold Vitamin C has been a popular option for the prevention and treatment of the common cold for decades, but research supporting such claims has been conflicting and controversial. Some studies find no relationship between vitamin C and the occurrence of the common cold, whereas others report modest benefits—fewer colds, fewer days, and shorter duration of severe symptoms, especially for those exposed to physical and environmental stresses. A review of the research on the treatment and prevention of the common cold reveals a slight reduction in the duration and severity of the common cold in favor of those taking vitamin C supplements. The question for consumers to consider is, "Is it enough to warrant routine daily supplementation?" Discoveries about how vitamin C works in the body provide possible links between the vitamin and the common cold. Anyone who has ever had a cold knows the discomfort of a runny or stuffed-up nose. Nasal congestion develops in response to elevated blood histamine (HISS-tah-mean or HISS-tah-men), and people commonly take antihistamines for relief. Like an antihistamine, vitamin C comes to the rescue and deactivates histamine.

Which type of supplement is particularly toxic and has caused deaths in children?

Iron supplements

Other Invalid Reasons Other invalid reasons people might use for taking supplements include: The belief that the food supply or soil contains inadequate nutrients The belief that supplements can provide energy The belief that supplements can enhance athletic performance or build lean body tissues without physical work or faster than exercise alone (see Highlight 14) The belief that supplements will help a person cope with stress The belief that supplements can prevent, treat, or cure conditions ranging from the common cold to cancer

Ironically, people with health problems are more likely to take supplements than other people, yet today's health problems are more likely to be due to overnutrition and poor lifestyle choices than to nutrient deficiencies. The truth—that most people would benefit from improving their eating and activity patterns—is harder to swallow than a supplement pill.

Which of the following is true of vitamin B6?

It occurs in three forms.

Which of the following is true of niacin?

Large doses of the nicotinic acid form can raise HDL cholesterol.

B Vitamin Deficiencies Now suppose the body's cells lack one of these B vitamins—niacin, for example. Without niacin, the cells cannot make NAD. Without NAD, the enzymes involved in every step of the glucose-to-energy pathway cannot function. Then, because all the body's activities require energy, literally everything begins to grind to a halt. This is no exaggeration. The deadly disease pellagra, caused by niacin deficiency, produces the "devastating four Ds": dermatitis, which reflects a failure of the skin; dementia, a failure of the nervous system; diarrhea, a failure of digestion and absorption; and eventually, as would be the case for any severe nutrient deficiency, death. These symptoms are the obvious ones, but a niacin deficiency affects all other organs, too, because all are dependent on the energy pathways. All the vitamins are as essential as niacin. With any B vitamin deficiency, many body systems become deranged, and similar symptoms may appear. A lack of any of them can have disastrous and far-reaching effects. Deficiencies of single B vitamins seldom show up in isolation, however. After all, people do not eat nutrients singly; they eat foods, which contain mixtures of nutrients. For this reason, B vitamin deficiencies often coexist, and most typically occur among the elderly, vegetarians, and those with alcoholism, heart failure, and recent bariatric surgery. Only in two cases described earlier—beriberi and pellagra—have dietary deficiencies associated with single B vitamins been observed on a large scale in human populations. Even in these cases, several vitamins were lacking even though one vitamin stood out above the rest. When foods containing the vitamin known to be needed were provided, the other vitamins that were in short supply came as part of the package.

Major deficiency diseases of epidemic proportions such as pellagra and beriberi are no longer seen in the United States, but lesser deficiencies of nutrients, including the B vitamins, sometimes occur in people whose food choices are poor because of poverty, ignorance, illness, or poor health habits like alcohol abuse. (Review Highlight 7 to fully appreciate how alcohol induces vitamin deficiencies and interferes with energy metabolism.) Remember from Chapter 1 that deficiencies can arise not only from deficient intakes (primary causes), but also for other (secondary) reasons. In identifying nutrient deficiencies, it is important to realize that a particular sign or symptom may not always have the same cause. The skin and the tongue (shown in Figure 10-15) appear to be especially sensitive to B vitamin deficiencies, but focusing on these body parts gives them undue emphasis. Both the skin and the tongue are readily visible in a physical examination. The physician sees and reports the deficiency's outward signs, but the full impact of a vitamin deficiency occurs inside the cells of the body. If the skin develops a rash or lesions, other tissues beneath it may be degenerating too. Similarly, the mouth and tongue are the visible part of the digestive system; if they are abnormal, most likely the rest of the GI tract is as well.

Life-Threatening Misinformation Another problem arises when people who are ill come to believe that high doses of vitamins or minerals can be therapeutic. Not only can high doses be toxic, but the person may also take them instead of seeking medical help. Furthermore, there are no guarantees that the supplements will be effective. Taking vitamin supplements instead of medication may sound appealing, but they do not protect against the progression of heart disease or cancers. In some cases, supplements may even be harmful. For example, supplements of vitamin E increase the risk of prostate cancer among healthy men.

Marketing materials for supplements often make health statements that are required to be "truthful and not misleading," but they often fall far short of both. Highlight 18 revisits this topic and includes a discussion of herbal preparations and other alternative therapies.

From which amino acid can choline be made?

Methionine

Organic Nature Fresh foods naturally contain vitamins, but because these vitamins are organic, they can be readily destroyed during processing. Therefore, processed foods should be used sparingly, and fresh foods should be handled with care during storage and in cooking (see Photo 10-1). Prolonged heating may destroy much of the thiamin in food. Because riboflavin can be destroyed by the ultraviolet rays of the sun or by fluorescent light, foods stored in transparent glass containers are most likely to lose riboflavin. Oxygen destroys vitamin C, so losses occur when foods are cut, processed, and stored; these losses may be enough to reduce its activity in the body

Minimizing Nutrient Losses To slow the degradation of vitamins, refrigerate (most) fruits and vegetables. To minimize the oxidation of vitamins, store fruits and vegetables that have been cut in airtight wrappers, and store juices that have been opened in closed containers (and refrigerate them). To prevent vitamin losses during washing, rinse fruits and vegetables before cutting (not after). To minimize vitamin losses during cooking, use a microwave oven or steam vegetables in a small amount of water. Add vegetables after water has come to a boil. Use the cooking water in mixed dishes such as casseroles and soups. Avoid high temperatures and long cooking times.

Niacin refers to two chemical structures: nicotinic acid and nicotin-amide (also known as niacinamide). The body can easily convert nicotinic acid to nicotinamide, which is the major form of niacin in the blood. The two coenzyme forms of niacin, NAD (nicotinamide adenine dinucleotide) and NADP (the phosphate form), participate in numerous metabolic reactions. They are central in energy-transfer reactions, especially the metabolism of glucose, fat, and alcohol. NAD is similar to the riboflavin coenzymes in that it carries hydrogens (and their electrons) during metabolic reactions, including the pathway from the TCA cycle to the electron transport chain. NAD also protects against neurological degeneration.

Niacin: a B vitamin. The coenzyme forms are NAD (nicotinamide adenine dinucleotide) and NADP (the phosphate form of NAD). Niacin can be eaten preformed or made in the body from its precursor, tryptophan, an essential amino acid.

Be aware that fake vitamins and preparations that contain items not needed in human nutrition, such as carnitine and inositol, reflect a marketing strategy aimed at your pocket, not at your health. The manufacturer wants you to believe that its pills contain the latest "new" nutrient that other brands omit, but in reality, these substances are not known to be needed by human beings. Realize that the claim that supplements "relieve stress" is another marketing ploy. If you give even passing thought to what people mean by "stress," you'll realize manufacturers could never design a supplement to meet everyone's needs. Is it stressful to take an exam? Well, yes. Is it stressful to survive a major car wreck with third-degree burns and multiple bone fractures? Definitely, yes. The body's responses to these stresses are different. The body does use vitamins and minerals in mounting a stress response, but a body fed a well-balanced diet can meet the needs of most minor stresses. For the major ones, medical intervention is needed. In any case, taking a dietary supplement won't make life any less stressful.

Other marketing tricks to sidestep are "green" pills that contain dehydrated, crushed parsley, alfalfa, and other fruit and vegetable extracts. The nutrients and phytochemicals advertised can be obtained from a serving of vegetables more easily and for less money. Such pills may also provide enzymes, but enzymes are inactivated in the stomach during protein digestion. Recognize the latest nutrition buzzwords. Manufacturers were marketing "antioxidant" supplements before the print had time to dry on the first scientific reports of antioxidant vitamins' action in the body. Remember, too, that high doses can alter a nutrient's action in the body. An antioxidant in physiological quantities may be beneficial, but in pharmacological quantities, it may act as a prooxidant and cause harm. Highlight 11 explores antioxidants and supplement use in more detail.

Pantothenic Acid Food Sources Pantothenic acid is widespread in foods, and typical diets seem to provide adequate intakes. Beef, poultry, whole grains, potatoes, tomatoes, and broccoli are particularly good sources. Losses of pantothenic acid during food production can be substantial because it is readily destroyed by the freezing, canning, and refining processes. The accompanying table provides a summary of pantothenic acid.

Pantothenic Acid AI --- Adults: 5 mg/day Chief Functions in the Body --- Part of coenzyme A, used in energy metabolism Significant Sources --- Widespread in foods; chicken, beef, potatoes, oats, tomatoes, liver, egg yolk, broccoli, whole grains --- Easily destroyed by food processing Deficiency Symptoms --- Vomiting, nausea, stomach cramps; insomnia, fatigue, depression, irritability, restlessness, apathy; hypoglycemia, increased sensitivity to insulin; numbness, muscle cramps, inability to walk Toxicity Symptoms --- None reported

Pantothenic Acid Recommendations An AI for pantothenic acid has been set. It reflects the amount needed to replace daily losses.

Pantothenic Acid Deficiency and Toxicity Pantothenic acid deficiency is rare. Its symptoms involve a general failure of all the body's systems and include fatigue, GI distress, and neurological disturbances. The "burning feet" syndrome that affected prisoners of war in Asia during World War II is thought to have been caused by pantothenic acid deficiency. No toxic effects have been reported, and no UL has been established.

In the early 1900s, pellagra caused widespread misery and some 87,000 deaths in the US South, where many people subsisted on a low-protein diet centered on corn. This diet supplied neither enough niacin nor enough tryptophan. At least 70 percent of the niacin in corn is bound to complex carbohydrates and small peptides, making it unavailable for absorption. Furthermore, corn is high in the amino acid leucine, which interferes with the tryptophan-to-niacin conversion, thus further contributing to the development of pellagra.

Pellagra was originally believed to be caused by an infection. Medical researchers spent many years and much effort searching for infectious microbes until they realized that the problem was not what was present in the food but what was absent from it. That a disease such as pellagra could be caused by diet inadequacies—and not by pathogens—was a groundbreaking discovery. It contradicted commonly held medical opinions that diseases were caused only by infectious agents. By carefully following the scientific method (as Chapter 1 described), researchers advanced the science of nutrition dramatically.

Compounds, like beta-carotene, that can be converted into active vitamins are known as precursors

Precursors are substances that precede others, so, with regard to vitamins, precursors are compounds that can be converted into active vitamins. Precursors also are known as provitamins.

Vitamin C Recommendations How much vitamin C does a person need? As is true of all the vitamins, recommendations are set generously above the minimum requirement to prevent deficiency disease and well below the toxicity level

Recommendations for vitamin C are set generously above the minimum requirement and well below the toxicity level. 10 - prevents scurvy 30 - supports metabolism 75 - RDA for women 90 - RDA for men; daily value on food and supplement labels 100 - saturates tissues 110 - recommendation for female smokers 125 - recommendation for male smokers 200 - limited absorption and little increase in blood concentrations at higher doses 2000 - UL for adults 3000 - adverse consequences may appear at such a high dose

Riboflavin Recommendations Like thiamin's RDA, riboflavin's RDA is based primarily on its role in enzyme activity. Most people in the United States meet or exceed riboflavin recommendations. Riboflavin Deficiency and Toxicity Lack of riboflavin causes inflammation of the membranes of the mouth, skin, eyes, and GI tract. Excesses of riboflavin appear to cause no harm, and no UL has been established. All of these foods are rich in riboflavin, but milk and milk products provide much of the riboflavin in the diets of most people.

Riboflavin Food Sources The greatest contributions of riboflavin come from milk and milk products (see Photo 10-3 and Figure 10-6). Whole-grain or enriched grains are also valuable sources because of the quantities people typically consume. When riboflavin sources are ranked by nutrient density (per kcalorie), many dark green, leafy vegetables (such as broccoli, turnip greens, asparagus, and spinach) appear high on the list. Vegans and others who don't use milk must rely on ample servings of dark greens and enriched grains for riboflavin. Nutritional yeast is another good source.

This chapter has described some of the impressive ways that vitamins work individually, as if their many actions in the body could easily be disentangled. In fact, it is often difficult to tell which vitamin is truly responsible for a given effect because the nutrients are interdependent; the presence or absence of one affects another's absorption, metabolism, and excretion. You have already seen this interdependence with folate and vitamin B12.

Riboflavin and vitamin B6provide another example. One of the riboflavin coenzymes, FMN, assists the enzyme that converts vitamin B6 to its coenzyme form PLP. Consequently, a severe riboflavin deficiency can impair vitamin B6 activity. Thus a deficiency of one nutrient may alter the action of another. Furthermore, a deficiency of one nutrient may create a deficiency of another. For example, both riboflavin and vitamin B6 (as well as iron) are required for the conversion of tryptophan to niacin. Consequently, an inadequate intake of either riboflavin or vitamin B6 can diminish the body's niacin supply. These interdependent relationships are evident in many of the roles B vitamins play in the body.

Which one of these steps can help minimize vitamin losses?

Rinse fruits and vegetables before cutting, not after

Solubility As you may recall, carbohydrates and proteins are hydrophilic and lipids are hydrophobic. The vitamins divide along the same lines—the hydrophilic, water-soluble ones are the B vitamins (thiamin, riboflavin, niacin, biotin, pantothenic acid, vitamin , folate, and vitamin ) and vitamin C; the hydrophobic, fat-soluble ones are vitamins A, D, E, and K. As each vitamin was discovered, it was given a name and sometimes a letter and number as well. Many of the vitamins have multiple names, which has led to some confusion. The summary tables throughout this chapter and the next provide both the standard and the common alternative names.

Solubility is apparent in the food sources of the different vitamins, and it affects their absorption, transport, storage, and excretion by the body. The water-soluble vitamins are found in the watery compartments of foods; the fat-soluble vitamins usually occur together in the fats and oils of foods. On being absorbed, the water-soluble vitamins move directly into the blood. Like fats, the fat-soluble vitamins must first enter the lymph, then the blood. Once in the blood, many of the water-soluble vitamins travel freely, whereas many of the fat-soluble vitamins require transport proteins. Upon reaching the cells, water-soluble vitamins freely circulate in the water-filled compartments whereas fat-soluble vitamins are held in fatty tissues and the liver until needed. The kidneys, monitoring the blood that flows through them, detect and remove small excesses of water-soluble vitamins; large excesses, however, may overwhelm the system, creating adverse effects. Fat-soluble vitamins tend to remain in fat-storage sites in the body rather than being excreted, and so are more likely to reach toxic levels when consumed in excess. Because the body stores fat-soluble vitamins, they can be eaten in large amounts once in a while and still meet the body's needs over time. Water-soluble vitamins are retained in the body for varying lengths of time. The water-soluble vitamins must be eaten more regularly than the fat-soluble vitamins, although a single day's omission from the diet does not create a deficiency.

Toxicity Knowledge about some of the amazing roles of vitamins has prompted many people to take vitamin supplements, assuming that "more is better." Just as an inadequate intake can cause harm, so can an excessive intake. Even some of the water-soluble vitamins have adverse effects when taken in large doses. That a vitamin can be both essential and harmful may seem surprising, but the same is true of most nutrients. The effects of every substance depend on its dose, and this is one reason consumers should not self-prescribe supplements. Figure 10-1 shows three possible relationships between dose levels and effects. The third diagram in Figure 10-1 represents the situation with nutrients—more is better up to a point, but beyond that point, still more can be harmful.

The DRI include Tolerable Upper Intake Levels (UL) to address the possibility of adverse effects from high doses of nutrients. The UL defines the highest amount of a nutrient that is likely not to cause harm for most healthy people when consumed daily. The risk of harm increases as intakes rise above the UL. Of the nutrients discussed in this chapter, niacin, vitamin , folate, choline, and vitamin C have UL, and these values are presented in their respective summary tables. Data are lacking to establish UL for the remaining B vitamins, but this does not mean that excessively high intakes would be without risk. (The insert pages present UL for the vitamins and minerals.)

Vitamin B12 and folate are closely related: each depends on the other for activation. Recall that vitamin B12 removes a methyl group to activate the folate coenzyme. When folate gives up its methyl group, the vitamin B12 coenzyme becomes activated (review Figure 10-11). The regeneration of the amino acid methionine and the synthesis of DNA and RNA depend on both folate and vitamin B12. In addition, vitamin B12 maintains the sheath that surrounds and protects nerve fibers and promotes their normal growth. Bone cell activity and metabolism also depend on vitamin . Vitamin B12: a B vitamin characterized by the presence of cobalt. The active forms of coenzyme are methylcobalamin and deoxyadenosylcobalamin. intrinsic factor: a glycoprotein (a protein with short polysaccharide chains attached) secreted by the stomach cells that binds with vitamin B12 in the small intestine to aid in the absorption of vitamin B12

The digestion and absorption of vitamin B12 depends on several steps. In the stomach, hydrochloric acid and the digestive enzyme pepsin release vitamin B12 from the proteins to which it is attached in foods. Then as vitamin B12 passes from the stomach to the small intestine, it binds with a stomach secretion called intrinsic factor. Bound together, intrinsic factor and vitamin B12 travel to the end of the small intestine, where receptors recognize the complex. Importantly, the receptors do not recognize vitamin B12 without intrinsic factor. The vitamin is gradually absorbed into the bloodstream as the intrinsic factor is degraded. Transport of vitamin B12 in the blood depends on specific binding proteins. Like folate, vitamin B12 enters the enterohepatic circulation—continuously being secreted into bile and delivered to the intestine, where it is reabsorbed. Because most vitamin B12 is reabsorbed, healthy people rarely develop a deficiency even when their intake is minimal.

Niacin is less vulnerable to losses during food preparation and storage than other water-soluble vitamins. Being fairly heat resistant, niacin can withstand reasonable cooking times, but like other water-soluble vitamins, it will leach into cooking water. The accompanying table provides a summary of niacin.

niacin Other Names --- Nicotinic acid, nicotinamide, niacinamide, vitamin ; precursor is dietary tryptophan (an amino acid) RDA --- Men: 16 mg NE/day --- Women: 14 mg NE/day UL --- Adults: 35 mg/day Chief Functions in the Body --- Part of coenzymes NAD (nicotinamide adenine dinucleotide) and NADP (its phosphate form) used in energy metabolism Significant Sources --- Milk, eggs, meat, poultry, fish; whole-grain, fortified, and enriched grain products; nuts and all protein-containing foods Deficiency Disease --- Pellagra Deficiency Symptoms --- Diarrhea, abdominal pain, vomiting; inflamed, swollen, smooth, bright red tongue (glossitis); depression, apathy, fatigue, loss of memory, headache; bilateral symmetrical rash on areas exposed to sunlight Toxicity Symptoms --- Painful flush, hives, and rash ("niacin flush"); nausea and vomiting; liver damage; impaired glucose tolerance

Despite supplement advertisements that claim otherwise, the vitamins do not provide the body with fuel for energy. It is true, though, that without B vitamins the body would lack energy. The energy-yielding nutrients—carbohydrate, fat, and protein—are used for fuel; the B vitamins help the body to use that fuel. Several of the B vitamins—thiamin, riboflavin, niacin, pantothenic acid, and biotin—form part of the coenzymes that assist enzymes in the release of energy from carbohydrate, fat, and protein. Other B vitamins play other indispensable roles in metabolism. Vitamin assists enzymes that metabolize amino acids. Folate and vitamin help cells to multiply. Among these cells are the red blood cells and the cells lining the GI tract—cells that deliver energy to all the others.

The vitamin portion of a coenzyme allows a chemical reaction to occur; the remaining portion of the coenzyme binds to the enzyme. Without its coenzyme, an enzyme cannot function. Thus symptoms of B vitamin deficiencies directly reflect the disturbances of metabolism caused by a lack of coenzymes. Some vitamins form part of the coenzymes that enable enzymes either to synthesize compounds (as illustrated by the lower enzymes in this figure) or to dismantle compounds (as illustrated by the upper enzymes).

Look at the now-familiar pathway of glucose breakdown. To break down glucose to pyruvate, the cells must have certain enzymes. For the enzymes to work, they must have the niacin coenzyme NAD. Cells can make NAD, but only if they have enough niacin (or enough of the amino acid tryptophan to make niacin). The next step is the breakdown of pyruvate to acetyl CoA. The enzymes involved in this step require both NAD and the thiamin and riboflavin coenzymes TPP and FAD, respectively. The cells can manufacture the enzymes they need from the vitamins, if the vitamins are in the diet. Another coenzyme needed for this step is CoA. Predictably, the cells can make CoA except for an essential part that must be obtained in the diet—pantothenic acid. Another coenzyme requiring biotin serves the enzyme complex involved in converting pyruvate to oxaloacetate, the compound that combines with acetyl CoA to start the TCA cycle.

These and other coenzymes participate throughout all the metabolic pathways. Vitamin B6 is an indispensable part of PLP—a coenzyme required for many amino acid conversions, for a crucial step in the making of the iron-containing portion of hemoglobin for red blood cells, and for many other reactions. Folate becomes THF—the coenzyme required for the synthesis of new genetic material and therefore new cells. The vitamin B12 coenzyme, in turn, regenerates THF to its active form; thus vitamin B12 is also necessary for the formation of new cells. Thus each of the B vitamin coenzymes is involved, directly or indirectly, in energy metabolism. Some facilitate the energy-releasing reactions themselves; others help build new cells to deliver the oxygen and nutrients that allow the energy reactions to occur.

B Vitamin Roles Figure 10-14 summarizes the metabolic pathways introduced in Chapter 7 and conveys an impression of the many ways B vitamins assist in metabolic pathways. Metabolism is the body's work, and the B vitamin coenzymes are indispensable to every step. In scanning the pathways of metabolism depicted in the figure, note the many abbreviations for the coenzymes that keep the processes going.

These coenzymes depend on the following vitamins: NAD and NADP: niacin TPP: thiamin CoA: pantothenic acid B12: vitamin B12 FMN and FAD: riboflavin THF: folate PLP: vitamin B6 Biotin Pathways leading toward acetyl CoA and the TCA cycle are catabolic, and those leading toward amino acids, glycogen, and fat are anabolic

Which of the following is true of vitamins in general?

They help enzymes participate in release of energy from carbohydrates, proteins, and fats.

What is the name of the coenzyme form of thiamin?

Thiamin pyrophosphate

Thiamin is the vitamin part of the coenzyme TPP (thiamin pyrophosphate) that assists in energy metabolism. The TPP coenzyme participates in the conversion of pyruvate to acetyl CoA (as Chapter 7 described). Recall how important this step is in allowing carbohydrate metabolism to proceed through the TCA cycle, thus producing much more ATP than during glycolysis alone. The reaction removes 1 carbon from the 3-carbon pyruvate to make the 2-carbon acetyl CoA and carbon dioxide . In a similar step in the TCA cycle, TPP helps convert a 5-carbon compound to a 4-carbon compound. Besides playing these pivotal roles in energy metabolism, thiamin occupies a special site on the membranes of nerve cells. Consequently, nerve activity and muscle activity in response to nerves depend heavily on thiamin.

Thiamin: a B vitamin. The coenzyme form is TPP (thiamin pyrophosphate). TPP (thiamin pyrophosphate): the coenzyme form of thiamin

The liver incorporates excess folate into bile that is then sent to the gallbladder and GI tract. Thus folate travels in the same enterohepatic circulation as bile

This complicated system for handling folate is vulnerable to GI tract injuries. Because folate is actively secreted back into the GI tract with bile, it can be reabsorbed repeatedly. If the GI tract cells are damaged, then folate is lost. Such is the case in alcohol abuse; folate deficiency rapidly develops and, ironically, further damages the GI tract. Remember, folate is active in cell multiplication—and the cells lining the GI tract are among the most rapidly replaced cells in the body. When unable to make new cells, the GI tract deteriorates and not only loses folate, but fails to absorb other nutrients as well.

Why is folate supplementation recommended for women one month before conception and during the first trimester of pregnancy?

To prevent neural tube defects, such as spina bifida, which may occur during the early weeks of pregnancy.

Ultraviolet light destroys riboflavin. For this reason, milk is sold in cardboard or opaque plastic containers, instead of clear glass bottles. In contrast, riboflavin is stable to heat, so cooking does not destroy it. The accompanying table provides a summary of riboflavin.

riboflavin Other Names --- Vitamin B2 RDA --- Men: 1.3 mg/day --- Women: 1.1 mg/day Chief Functions in the Body --- Part of coenzymes FMN (flavin mononucleotide) and FAD (flavin adenine dinucleotide) used in energy metabolism Significant Sources --- Milk products (yogurt, cheese); whole-grain, fortified, or enriched grain products; liver --- Easily destroyed by ultraviolet light and irradiation Deficiency Disease --- Ariboflavinosis Deficiency Symptoms --- Sore throat; cracks and redness at corners of mouth (cheilosis); painful, smooth, purplish red tongue (glossitis); inflammation characterized by skin lesions covered with greasy scales Toxicity Symptoms --- None reported

Toxicity Supplement users may have excessive intakes of certain nutrients. The extent and severity of supplement toxicity remain unclear. Only a few alert health-care professionals can recognize toxicity, even when it is acute. When it is chronic, with the effects developing subtly and progressing slowly, it often goes unrecognized and unreported. In view of the potential hazards, some authorities believe supplements should bear warning labels, advising consumers that large doses may be toxic. At a minimum, manufacturers should be held to the same standards required of the drug industry, which may help to prevent toxicities. Consider that more than 200 people reported symptoms of diarrhea, fatigue, hair loss, and joint pain when the selenium supplements they had taken delivered up to 2.5 times the selenium concentration listed on the label.

Toxic overdoses of vitamins and minerals in children are more readily recognized and, unfortunately, fairly common. Fruit-flavored, chewable vitamins shaped like cartoon characters entice young children to eat them like candy in amounts that can cause poisoning. Iron supplements (30 milligrams of iron or more per tablet) are especially toxic and have caused fatalities among children. Even mild overdoses cause GI distress, nausea, and black diarrhea, which reflects gastric bleeding. Severe overdoses result in bloody diarrhea, shock, liver damage, coma, and death.

Vitamin B12 Food Sources Vitamin B12 is unique among the vitamins in being found almost exclusively in foods derived from animals. Its bioavailability is greatest from milk and fish. Anyone who eats reasonable amounts of animal-derived foods is most likely to have an adequate intake, including vegetarians who use milk products or eggs. Vegans, who restrict all foods derived from animals, need a reliable source, such as vitamin B12-fortified soy milk or vitamin supplements. Yeast grown on a vitamin B12-enriched medium and mixed with that medium provides some vitamin B12, but yeast itself does not contain active vitamin . Similarly, neither fermented soy products such as miso (a soybean paste) nor sea algae such as spirulina provide active vitamin B12. Extensive research shows that the amounts listed on the labels of these plant products are inaccurate and misleading because the vitamin B12 is in an inactive, unavailable form.

VITAMIN b12 Other Names --- Cobalamin (and related forms) RDA --- Adults: 2.4 μg/day Chief Functions in the Body --- Part of coenzymes methylcobalamin and deoxyadenosylcobalamin used in new cell synthesis; helps to maintain nerve cells; reforms folate coenzyme; helps to break down some fatty acids and amino acids Significant Sources --- Foods of animal origin (meat, fish, poultry, shellfish, milk, cheese, eggs), fortified cereals --- Easily destroyed by microwave cooking Deficiency Disease --- Pernicious anemia Deficiency Symptoms Anemia (macrocytic); fatigue, degeneration of peripheral nerves progressing to paralysis; sore tongue, loss of appetite, constipation Toxicity Symptoms --- None reported

Foods lose vitamin B6 when heated. Information is limited, but vitamin B6 bioavailability from plant-derived foods seems to be lower than from animal-derived foods. The accompanying table provides a summary of vitamin B6.

Vitamin B6 Other Names --- Pyridoxine, pyridoxal, pyridoxamine RDA --- Adults (19-50 yr): 1.3 mg/day UL --- Adults: 100 mg/day Chief Functions in the Body --- Part of coenzymes PLP (pyridoxal phosphate) and PMP (pyridoxamine phosphate) used in amino acid and fatty acid metabolism; helps to convert tryptophan to niacin and to serotonin; helps to make red blood cells Significant Sources --- Meats, fish, poultry, potatoes and other starchy vegetables, legumes, noncitrus fruits, fortified cereals, liver, soy products Easily destroyed by heat Deficiency Symptoms --- Scaly dermatitis; microcytic anemia; depression, confusion, convulsions Toxicity Symptoms --- Depression, fatigue, irritability, headaches, nerve damage causing numbness and muscle weakness leading to an inability to walk and convulsions; skin lesions

Vitamin B6 Recommendations The RDA for vitamin B6 is based on the amounts needed to maintain adequate levels of its coenzymes. Unlike other water-soluble vitamins, vitamin B6 is stored extensively in muscle tissue. Research does not support claims, however, that large doses of vitamin B6 enhance muscle strength or physical endurance. Vitamin B6 Deficiency Without adequate vitamin B6, synthesis of key neurotransmitters diminishes, and abnormal compounds produced during tryptophan metabolism accumulate in the brain. Early symptoms of vitamin B6 deficiency include depression and confusion; advanced symptoms include abnormal brain wave patterns and convulsions. Alcohol contributes to the destruction and loss of vitamin B6 from the body. As Highlight 7 described, when the body breaks down alcohol, it produces acetaldehyde. If allowed to accumulate, acetaldehyde dislodges the PLP coenzyme from its enzymes; once loose, PLP breaks down and is excreted.

Vitamin B6 Toxicity The first major report of vitamin B6 toxicity appeared in the early 1980s. Until that time, most researchers and dietitians believed that, like the other water-soluble vitamins, vitamin B6 could not reach toxic concentrations in the body. The report described neurological damage in people who had been taking more than 2 grams of vitamin B6 daily (20 times the current UL of 100 milligrams per day) for 2 months or more.

The potato is an important source of vitamin C, not because one potato by itself meets the daily need, but because potatoes are such a common staple that they make significant contributions. In fact, scurvy was unknown in Ireland until the potato blight of the mid-1840s, when some 2 million people died of malnutrition and infection. The lack of yellow, white, brown, and red bars in Figure 10-19 confirms that grains, milk and milk products (except breast milk), and most protein foods are notoriously poor sources of vitamin C. Organ meats (liver, kidneys, and others) and raw meats contain some vitamin C, but most people don't eat large quantities of these foods. Raw meats and fish contribute enough vitamin C to be significant sources in parts of Alaska, Canada, and Japan, but elsewhere fruits and vegetables are necessary to supply sufficient vitamin C. Because of vitamin C's antioxidant property, food manufacturers sometimes add a variation of vitamin C to some beverages and most cured meats, such as luncheon meats, to prevent oxidation and spoilage. This compound safely preserves these foods, but it does not have vitamin C activity in the body. Simply put, "Ham and bacon cannot replace fruits and vegetables." Vitamin C acts primarily as an antioxidant and a cofactor. Recommendations are set well above the amount needed to prevent the deficiency disease scurvy. A variety of fruits and vegetables—most notably citrus fruits—provide generous amounts of vitamin C.

Vitamin C Other Names Ascorbic acid RDA Men: 90 mg/day Women: 75 mg/day Smokers: RDA + 35 mg/day UL Adults: 2000 mg/day Chief Functions in the Body Collagen synthesis (strengthens blood vessel walls, forms scar tissue, provides matrix for bone growth), antioxidant, thyroxine synthesis, amino acid metabolism, strengthens resistance to infection, helps in absorption of iron Significant Sources Citrus fruits, cabbage-type vegetables (such as brussels sprouts and cauliflower), dark green vegetables (such as bell peppers and broccoli), cantaloupe, strawberries, lettuce, tomatoes, potatoes, papayas, mangoes Easily destroyed by heat and oxygen Deficiency Disease Scurvy Deficiency Symptoms Anemia (microcytic), atherosclerotic plaques, pinpoint hemorrhages; bone fragility, joint pain; poor wound healing, frequent infections; bleeding gums, loosened teeth; muscle degeneration, pain, hysteria, depression; rough skin, blotchy bruises Toxicity Symptoms Nausea, abdominal cramps, diarrhea; headache, fatigue, insomnia; hot flashes; rashes; interference with medical tests, aggravation of gout symptoms, urinary tract problems, kidney stones

Vitamin C Deficiency Early signs of nutrient deficiencies can be difficult to recognize. Two of the most notable signs of a vitamin C deficiency reflect its role in maintaining the integrity of blood vessels. The gums bleed easily around the teeth, and capillaries under the skin break spontaneously, producing pinpoint hemorrhages scorbutic gums pinpoint hemorrhages

When vitamin C concentrations fall to about a fifth of optimal levels (this may take more than a month on a diet lacking vitamin C), scurvy symptoms begin to appear. Inadequate collagen synthesis causes further hemorrhaging. Muscles, including the heart muscle, degenerate. The skin becomes rough, brown, scaly, and dry. Wounds fail to heal because scar tissue will not form. Bone rebuilding falters; the ends of the long bones become softened, malformed, and painful, and fractures develop. The teeth become loose as the cartilage around them weakens. Anemia and infections are common. There are also characteristic psychological signs, including hysteria and depression. Sudden death is likely, caused by massive internal bleeding. Once diagnosed, scurvy is readily resolved by increasing vitamin C intake. Moderate doses of 100 milligrams per day are sufficient, curing the scurvy within about 5 days. Such an intake is easily achieved by including vitamin C-rich foods in the diet.

Arguments against Supplements Foods rarely cause nutrient imbalances or toxicities, but supplements can. The higher the dose, the greater the risk of harm. People's tolerances for high doses of nutrients vary, just as their risks of deficiencies do. Amounts that some can tolerate may be harmful for others, and no one knows who falls where along the spectrum. It is difficult to determine just how much of a nutrient is enough—or too much. The Tolerable Upper Intake Levels (UL) of the DRI answer the question "How much is too much?" by defining the highest amount that appears safe for most healthy people. Table H10-1 presents UL and Daily Values for selected vitamins and minerals.

Who Should Not Take Supplements? The following list recognizes that in certain circumstances, these people may need to avoid specific supplements: Men and postmenopausal women should not take iron supplements given that excess iron is harmful and generally more likely than inadequacies. Smokers should not take beta-carotene supplements given that high doses have been associated with increased lung cancer and mortality. Postmenopausal women should not take vitamin A supplements given that excess retinol has been associated with increased risk of hip fractures and reduced bone density. Surgery patients should not take vitamin E supplements during the week before surgery because vitamin E acts as a blood thinner.

Like thiamin, riboflavin serves as a coenzyme in many reactions, most notably in energy metabolism. The coenzyme forms of riboflavin are FMN (flavin mononucleotide) and FAD (flavin adenine dinucleotide); both can accept and then donate two hydrogens. During energy metabolism, FAD picks up two hydrogens (with their electrons) from the TCA cycle and delivers them to the electron transport chain.

riboflavin: a B vitamin. The coenzyme forms are FMN (flavin mononucleotide) and FAD (flavin adenine dinucleotide).

Folate Deficiency Folate deficiency impairs cell division and protein synthesis—processes critical to growing tissues. In a folate deficiency, the replacement of red blood cells and GI tract cells falters. Not surprisingly, then, two of the first symptoms of a folate deficiency are anemia (ah-NEE-me-ah) and GI tract deterioration. The anemia of folate deficiency is known as macrocytic or megaloblastic anemia and is characterized by large, immature red blood cells (see Figure 10-12). Without folate, DNA damage interferes with the synthesis of the red blood cells as they attempt to divide and mature. The result is fewer, but larger, red blood cells that cannot carry oxygen or travel through the capillaries as efficiently as normal red blood cells. Since the implementation of folate fortification in the United States, the prevalence of macrocytic anemia has decreased dramatically.

anemia: literally, "too little blood"; any condition in which there is reduced delivery of oxygen to the tissues. Anemia is not a disease itself but can be a symptom of many different disease conditions, including some nutrient deficiencies. Of all the vitamins, folate appears to be most vulnerable to interactions with drugs, which can lead to a secondary deficiency. Some medications, notably anticancer drugs, have a chemical structure similar to folate's structure and can displace the vitamin from enzymes and interfere with normal metabolism. Aspirin and antacids also interfere with the body's folate status: aspirin inhibits the action of folate-requiring enzymes, and antacids limit the absorption of folate. Healthy adults who use these drugs to relieve an occasional headache or upset stomach need not be concerned, but people who rely heavily on aspirin or antacids should be aware of the nutrition consequences.

Vitamin B12 Deficiency and Toxicity Most vitamin B12 deficiencies reflect inadequate absorption, not poor intake. Inadequate absorption typically occurs for one of two reasons: a lack of hydrochloric acid or a lack of intrinsic factor. Without hydrochloric acid, the vitamin is not released from the dietary proteins and so is not available for binding with the intrinsic factor. Without the intrinsic factor, the vitamin cannot be absorbed. Vitamin B12 deficiency is common among adults who use heartburn medications to suppress gastric acid production. Deficiency is also common among the elderly. Many older adults develop atrophic gastritis, a condition that damages the cells of the stomach. Atrophic gastritis may also develop in response to iron deficiency or infection with Helicobacter pylori, the bacterium implicated in ulcer formation. Without healthy stomach cells, production of hydrochloric acid and intrinsic factor diminishes. Even with an adequate intake from foods, vitamin B12 status suffers. The vitamin B12 deficiency caused by atrophic gastritis and a lack of intrinsic factor is known as pernicious anemia. Some people inherit a defective gene for the intrinsic factor. In such cases, or when the stomach has been injured and cannot produce enough of the intrinsic factor, vitamin must be given by injection to bypass the need for intestinal absorption. Alternatively, the vitamin may be delivered by nasal spray; absorption is rapid, high, and well tolerated.

atrophic gastritis: chronic inflammation of the stomach accompanied by a diminished size and functioning of the mucous membranes and glands. This condition is also characterized by inadequate hydrochloric acid and intrinsic factor—two substances needed for vitamin B12 absorption. pernicious anemia: a macrocytic anemia that reflects a vitamin B12 deficiency caused by lack of intrinsic factor and characterized by abnormally large and immature red blood cells. Other symptoms include muscle weakness and irreversible neurological damage.

Which of the following is not true of folate? a. It is involved in DNA synthesis. b. Its bioavailability is the same whatever the source. c. It regenerates the amino acid methionine from homocysteine. d. It is involved in converting vitamin B12 to one of its coenzyme forms. e. It comes in two forms.

b. Its bioavailability is the same whatever the source.

Vitamin C Food Sources Fruits and vegetables can easily provide a generous amount of vitamin C. A cup of orange juice at breakfast, a salad for lunch, and a stalk of broccoli and a potato for dinner alone provide more than 300 milligrams. (For perspective, review Figure 10-17.) Clearly, a person making such food choices does not need vitamin C supplements. Figure 10-19 shows the amounts of vitamin C in various common foods. The overwhelming abundance of purple and green bars reveals not only that the citrus fruits are justly famous for being rich in vitamin C, but that other fruits and vegetables are also in the same league (see Photos 10-8 and 10-9). A half cup of broccoli, bell pepper, or strawberries provides more than 50 milligrams of the vitamin (and an array of other nutrients). Because vitamin C is vulnerable to heat, raw fruits and vegetables usually have a higher nutrient density than their cooked counterparts. Similarly, because vitamin C is readily destroyed by oxygen, foods and juices should be stored properly and consumed within a week of opening.

best source per kcalorie: brocoli, strawberries, red bell pepper, kiwi, brussels sprouts When dietitians say "vitamin C," people think "citrus fruits."

Vitamin B6Food Sources As you can see from the colors in Figure 10-9, meats, fish, and poultry (red bars), potatoes and a few other vegetables (green bars), and fruits (purple bars) offer vitamin B6. As is true of most of the other vitamins, fruits and vegetables rank considerably higher when foods are judged by nutrient density (vitamin B6 per kcalorie). Several servings of vitamin B6-rich foods are needed to meet recommended intakes

best sources per kcalore: cornflakes (fortified), broccoli, tomato juice, banana, watermelon Most protein-rich foods such as meat, fish, and poultry provide ample vitamin ; some vegetables and fruits are good sources too.

Niacin Food Sources Tables of food composition typically list preformed niacin only, but as mentioned, niacin can also be made in the body from the amino acid tryptophan. Dietary tryptophan could meet about half the daily niacin requirement for most people, but the average diet easily supplies enough preformed niacin. Figure 10-8 presents niacin in selected foods. Meat, poultry, fish, legumes, and enriched and whole grains contribute about half the niacin people consume (see Photo 10-4). Mushrooms, potatoes, and tomatoes are among the richest vegetable sources, and they can provide abundant niacin when eaten in generous amounts.

best sources per kcalorie: cornflakes (fortified), chicken breast, tuna (canned in water), liver, mushrooms Protein-rich foods such as meat, fish, poultry, and peanut butter contribute much of the niacin in people's diets. Enriched breads and cereals and a few vegetables are also rich in niacin.

Riboflavin is similar to thiamin in that _____.

both serve as coenzymes in energy metabolism.

Which of these essential nutrients is commonly grouped with the B vitamins, even though it is not defined as a vitamin?

choline

Which of these groups has an increased need for vitamin C?

cigarette smokers

Vitamin C Roles Vitamin C parts company with the B vitamins in its mode of action. In some settings, vitamin C serves as a cofactor helping specific enzymes perform their jobs, but in others, it acts as an antioxidant participating in more general ways. As an Antioxidant Vitamin C loses electrons easily, a characteristic that allows it to perform as an antioxidant. In the body, antioxidants defend against free radicals. Free radicals are discussed fully in Highlight 11, but for now, a simple definition will suffice. A free radical is a molecule with one or more unpaired electrons, which makes it unstable and highly reactive. Antioxidants can neutralize free radicals by donating an electron or two. In doing so, antioxidants protect other substances from free radical damage. Figure 10-16 illustrates how vitamin C can give up electrons and then accept them again to become reactivated. This recycling of vitamin C is key to limiting losses and maintaining a reserve of antioxidants in the body. Other key antioxidant nutrients include vitamin E, beta-carotene, and selenium.

cofactor: a small, inorganic or organic substance that facilitates the action of an enzyme. free radical: an unstable molecule with one or more unpaired electrons. The two hydrogens highlighted in yellow give vitamin C its acidity and its ability to act as an antioxidant. (ascorbic acids protects against oxidative damage by donating its two hydrogens with their electrons to free radicals (molecules with unpaired electrons). In doing so, ascorbic acid becomes dehydroascorbic acid) (dehydroascorbic acid can readily accept hydrogens to become ascorbic acid. the reversibility of this reaction is key to vitamin C's role as an antioxidant)

Which of the following is not a role of thiamin? a. Conversion of pyruvate to acetyl CoA b. Energy metabolism c. Participation in the TCA cycle d. DNA synthesis e. ATP production

d. DNA synthesis

Which of the following is not known to increase vitamin C needs? a. chronic use of oral contraceptives b. cigarette smoking c. burns d. physical activity e. infections

d. Physical activity

Which of the following is not true of vitamin B12 a. It converts folate to its active form. b. It depends on intrinsic factor for absorption. c. It is found almost exclusively in animal-derived foods. d. It works closely with thiamin. e. It helps maintain nerve cells.

d. it works closely with thiamin

Folate Recommendations The bioavailability of folate differs depending on the source, and these differences must be considered when establishing folate recommendations. The DRI committee gives naturally occurring folate from foods (polyglutamates) full credit. Synthetic folate from fortified foods and supplements (monoglutamates) is given extra credit because, on average, it is 1.7 times more available than naturally occurring food folate. Thus a person consuming 100 micrograms of folate from foods and 100 micrograms from a supplement (multiplied by 1.7) receives 270 dietary folate equivalents (DFE). The need for folate rises considerably during pregnancy and whenever cells are multiplying, so the recommendations for pregnant women are considerably higher than for other adults.

dietary folate equivalents (DFE): the amount of folate available to the body from naturally occurring sources, fortified foods, and supplements, accounting for differences in the bioavailability from each source. DEF = μg food folate + (1.7 × μg synthetic folate).

Vitamin C Toxicity The availability of vitamin C supplements and the publication of books recommending vitamin C to prevent colds and cancer have led many people to take large doses of vitamin C. Not surprisingly, side effects of vitamin C supplementation such as gastrointestinal distress and diarrhea have been reported. The UL for vitamin C was established based on these symptoms. Several instances of interference with medical regimens are also known. Large amounts of vitamin C excreted in the urine obscure the results of tests used to detect glucose or ketones in the diagnosis of diabetes. In some instances, excess vitamin C gives a false positive result; in others, a false negative. People taking anticlotting medications may unwittingly counteract the effect if they also take massive doses of vitamin C. Those with kidney disease, a tendency toward gout, or a genetic abnormality that alters vitamin C's breakdown to its excretion products are prone to forming kidney stones if they take large doses of vitamin C. Vitamin C supplements may adversely affect people with iron overload. As Chapter 13 explains, vitamin C enhances iron absorption and releases iron from body stores; too much free iron causes the kind of cellular damage typical of free radicals. These adverse consequences illustrate how vitamin C can act as a prooxidant when quantities exceed the body's needs.

false positive: a test result indicating that a condition is present (positive) when in fact it is not present (therefore false). false negative: a test result indicating that a condition is not present (negative) when in fact it is present (therefore false).

Misleading Claims Manufacturers of organic or natural vitamins boast that their pills are purified from real foods rather than synthesized in a laboratory. These supplements are no more effective than others and often cost more. The word synthetic may sound like "fake," but to synthesize just means to put together. Think back on the course of human evolution; it is not natural to take any kind of pill. In reality, the finest, most natural vitamin "supplements" available are whole grains, vegetables, fruits, meat, fish, poultry, eggs, legumes, nuts, and milk and milk products. Avoid products that make "high potency" claims. More is not better (review Figure 10-1). Remember that foods are also providing these nutrients. Nutrients can build up and cause unexpected problems. For example, a man who takes vitamins and begins to lose his hair may think his hair loss means he needs more vitamins, when in fact it may be the early sign of a vitamin A overdose. (Of course, it may be completely unrelated to nutrition as well.)

high potency: 100% or more of the Daily Value for the nutrient in a single supplement and for at least two-thirds of the nutrients in a multinutrient supplement.

Nonvitamins Some substances have been mistaken for vitamins, but they are not essential nutrients. Among them are the compounds inositol and carnitine, which can be made by the body. Inositol is a part of cell membrane structures, and carnitine transports long-chain fatty acids from the cytosol to the mitochondria for oxidation. Other nonvitamins include PABA (para-aminobenzoic acid, a component of folate's chemical structure), the bioflavonoids (vitamin P or hesperidin), pyrroloquinoline quinone (methoxatin), orotic acid, lipoic acid, and ubiquinone (coenzyme Q10). Other names erroneously associated with vitamins are "vitamin O" (oxygenated saltwater), "vitamin B5" (another name for pantothenic acid), "vitamin B15" (also called "pangamic acid," a hoax), and "vitamin B17" (laetrile, an alleged "cancer cure" and not a vitamin or a cure by any stretch of the imagination—in fact, laetrile is a potentially dangerous substance).

inositol: a nonessential nutrient that can be made in the body from glucose. Inositol is a part of cell membrane structures. carnitine: a nonessential nonprotein amino acid made in the body from lysine that helps transport fatty acids across the mitochondrial membrane. As a supplement, carnitine supposedly "burns" fat and spares glycogen during endurance events, but in reality it does neither.

Which of the following is a function of vitamin C?

it helps form collagen

From which of these food groups do most people get their riboflavin?

milk and milk products

Similarly, manufacturers began making dietary supplements using nanotechnology before the FDA had created guidelines defining their use in consumer products. These nanoceuticals promise enhanced nutrient absorption and activity. Such claims may sound good, but again, more does not always mean better. Finally, be aware that advertising on the Internet is cheap and not closely regulated. Promotional e-mails can be sent to millions of people in an instant. Internet messages can easily cite references and provide links to other sites, implying an endorsement when in fact none has been given. Be cautious when examining unsolicited information and search for a balanced perspective. Cost When shopping for supplements, remember that local or store brands may be just as good as nationally advertised brands. If they are less expensive, it may be because the price does not have to cover the cost of national advertising.

nanotechnology: a manufacturing technology that manipulates atoms to change the structure of matter. nanoceuticals: substances with extremely small particles that have been manufactured by nanotechnology.

Folate and Neural Tube Defects The brain and spinal cord develop from the neural tube, and defects in its orderly formation during the early weeks of pregnancy may result in various central nervous system disorders and death. (Figure 15-5 in Chapter 15 includes an illustration of spina bifida, a neural tube defect.) Folate supplements taken 1 month before conception and continued throughout the first trimester of pregnancy can help prevent neural tube defects (see Photo 10-6). For this reason, all women of childbearing age who are capable of becoming pregnant should consume 0.4 milligram (400 micrograms) of folate daily—easily accomplished by eating folate-rich foods, folate-fortified foods, or a multivitamin supplement daily. Because half of the pregnancies each year are unplanned and because neural tube defects occur early in development before most women realize they are pregnant, the Food and Drug Administration (FDA) has mandated that grain products be fortified to deliver folate to the US population. Labels on fortified products may claim that "adequate intake of folate has been shown to reduce the risk of neural tube defects." Fortification has improved folate status in women of childbearing age and dramatically lowered the prevalence rate of neural tube defects.

neural tube: the embryonic tissue that forms the brain and spinal cord. neural tube defects: malformations of the brain, spinal cord, or both during embryonic development that often result in lifelong disability or death. The two main types of neural tube defects are spina bifida (literally "split spine") and anencephaly ("no brain"). Folate helps to protect against spina bifida, a neural tube defect characterized by the incomplete closure of the spinal cord and its bony encasement. Some research suggests that folate taken before and during pregnancy may also prevent congenital heart disease; birth defects, such as cleft lip and cleft palate; and neurodevelopmental disorders, such as autism. Such findings strengthen recommendations for women to pay attention to their folate needs. Folate fortification raises safety concerns as well. Because high intakes of folate can mask a vitamin B12 deficiency, folate consumption should not exceed 1 milligram daily without close medical supervision. The risks and benefits of folate fortification continue to be a topic of current debate, especially given that 5 percent of the US population exceed the UL for folate.

Niacin Recommendations Niacin is unique among the B vitamins in that the body can make it from the amino acid tryptophan. This use of tryptophan occurs only after protein synthesis needs have been met. Approximately 60 milligrams of dietary tryptophan is needed to make 1 milligram of niacin. For this reason, recommended intakes are stated in niacin equivalents (NE). A food containing 1 milligram of niacin and 60 milligrams of tryptophan provides the equivalent of 2 milligrams of niacin, or 2 niacin equivalents. The RDA for niacin allows for this conversion and is stated in niacin equivalents; average niacin intakes in the United States exceed recommendations. Niacin Deficiency The niacin-deficiency disease, pellagra (pell-AY-gra), produces the symptoms of diarrhea, dermatitis, dementia, and eventually death (often called "the four Ds"). Figure 10-7 illustrates the dermatitis of pellagra.

niacin equivalents (NE): the amount of niacin present in food, including the niacin that can theoretically be made from its precursor, tryptophan, present in the food. 1 NE = 1 mg niacin or 60 mg tryptophan. pellagra: the niacin-deficiency disease, characterized by diarrhea, dermatitis, dementia, and eventually death. In the dermatitis of pellagra, the skin darkens and flakes away as if it were sunburned. Skin lesions typically develop only on those parts of the body exposed to the sun.

Pork is the richest source of thiamin, but enriched or whole-grain products typically make the greatest contribution to a day's intake because of the quantities eaten. Legumes such as split peas are also valuable sources of thiamin.

other sources that are the best sources for thiamin per kcalorie: soy milk, squash, acorn, tomato juice, cornflakes (fortified), pork chop (lean)

Vitamin C is like a bodyguard for water-soluble substances; it stands ready to sacrifice its own life to save theirs. In the cells and body fluids, vitamin C protects tissues from the oxidative stress of free radicals and thus may play an important role in preventing diseases. In the small intestine, vitamin C enhances iron absorption by protecting iron from oxidation.

oxidative stress: a condition in which the production of oxidants and free radicals exceeds the body's ability to handle them and prevent damage.

Niacin Toxicity When a normal dose of a nutrient (levels commonly found in foods) provides a normal blood concentration, the nutrient is having a physiological effect. When a large dose (levels commonly available only from supplements) overwhelms the body and raises blood concentrations to abnormally high levels, the nutrient is acting like a drug and having a pharmacological effect. Naturally occurring niacin from foods has a physiological effect that causes no harm. Large doses of nicotinic acid from supplements or drugs, however, produce pharmacological effects, most notably "niacin flush." Niacin flush occurs when nicotinic acid is taken in doses only three to four times the RDA. It dilates the capillaries and causes a tingling sensation that can be painful. The nicotinamide form does not produce this effect. Large doses of nicotinic acid can effectively raise HDL cholesterol, but may not benefit patients with heart disease whose blood lipids are already being controlled with statin drugs. Because of possible side effects (such as liver damage), the use of niacin as a drug must be closely monitored.

physiological effect: the body's response to a normal dose of nutrient (levels commonly found in foods) that provides a normal blood concentration pharmacological effect: the body's response to a large dose of a nutrient (levels commonly available only from supplements) that overwhelms some body system and acts like a drug niacin flush: a temporary burning, tingling, and itching sensation that occurs when a person takes a large dose of nicotinic acid; often accompanied by a headache and reddened face, arms, and chest.

Which of the following is symptom of scurvy?

poor wound healing

Precursors Some vitamins are available from foods in inactive forms known as precursors. Once inside the body, the precursor is converted to an active form of the vitamin. For example, beta-carotene, a red-orange pigment found in fruits and vegetables, is a precursor to vitamin A. Thus, in measuring a person's vitamin intake, it is important to count both the amount of the active vitamin and the potential amount available from its precursors. The discussions and summary tables throughout this chapter and the next indicate which vitamins have precursors.

precursors: substances that precede others; with regard to vitamins, compounds that can be converted into active vitamins; also known as provitamins.

For many centuries, any man who joined the crew of a seagoing ship knew he had at best a 50-50 chance of returning alive—not because he might be slain by pirates or die in a storm, but because he might contract scurvy. As many as two-thirds of a ship's crew could die of scurvy during a long voyage. Only men on short voyages, especially around the Mediterranean Sea, were free of scurvy. No one knew the reason: that on long ocean voyages, the ship's cook used up the fresh fruits and vegetables early and then served only cereals and meats until the return to port. In the mid-1700s, James Lind, a British physician serving in the navy, devised an experiment to find a cure for scurvy. He divided 12 sailors with scurvy into 6 pairs. Each pair received a different supplemental ration: cider, vinegar, sulfuric acid, seawater, oranges and lemons, or a strong laxative. Those receiving the citrus fruits quickly recovered, but sadly, it was almost 50 years before the British navy required all vessels to provide every sailor with lemon or lime juice daily. The tradition of providing British sailors with citrus juice daily to prevent scurvy gave them the nickname "limeys." The antiscurvy "something" in citrus and other foods was dubbed the antiscorbutic factor (AN-tee-skor-BUE-tik). Centuries later, the factor was isolated and found to be a 6-carbon compound similar to glucose; it was named ascorbic acid.

scurvy: the vitamin C-deficiency disease. antiscorbutic factor: the original name for vitamin C. ascorbic acid: one of the two active forms of vitamin C. Many people refer to vitamin C by this name.

How long can it take for the symptoms of vitamin B12 symptoms to develop, if a person, say, a new vegetarian, was to suddenly stop eating animal products?

several years

As mentioned earlier, prolonged cooking can destroy thiamin. Also, like other water-soluble vitamins, thiamin leaches into water when foods are boiled or blanched. Cooking methods that require little or no water such as steaming and microwave heating conserve thiamin and other water-soluble vitamins. The accompanying table provides a summary of thiamin.

thiamin Other Names --- Vitamin B1 RDA --- Men: 1.2 mg/day --- Women: 1.1 mg/day Chief Functions in the Body --- Part of coenzyme TPP (thiamin pyrophosphate) used in energy metabolism Significant Sources --- Whole-grain, fortified, or enriched grain products; moderate amounts in all nutritious food; pork --- Easily destroyed by heat Deficiency Disease --- Beriberi (wet, with edema; dry, with muscle wasting) Deficiency Symptoms --- Enlarged heart, cardiac failure; muscular weakness; apathy, poor short-term memory, confusion, irritability; anorexia, weight loss Toxicity Symptoms --- None reported

Scurvy, the deficiency disease of vitamin C, is _____.

usually cured within five days of beginning treatment with 100 milligrams of vitamin C daily

With which B vitamin does folate have a close relationship?

vitamin B12

Vitamin B6 occurs in three forms—pyridoxal, pyridoxine, and pyridoxamine. All three can be converted to the coenzyme PLP (pyridoxal phosphate), which is active in more than 100 reactions, including carbohydrate, fatty acid, and amino acid metabolism. By using PLP to transfer amino groups from an amino acid to a keto acid, the body can make nonessential amino acids (review Figure 6-11). The ability to add and remove amino groups makes PLP valuable in protein and urea metabolism as well. The conversions of the amino acid tryptophan to niacin or to the neurotransmitter serotonin also depend on PLP. In addition, PLP participates in the synthesis of heme (the nonprotein portion of hemoglobin), nucleic acids (such as DNA and RNA), and lecithin (a phospholipid).

vitamin B6: a family of compounds—pyridoxal, pyridoxine, and pyridoxamine. The primary active coenzyme form is PLP (pyridoxal phosphate).

The vitamins are essential nutrients needed in tiny amounts in the diet both to prevent deficiency diseases and to support optimal health. The water-soluble vitamins are the B vitamins and vitamin C; the fat-soluble vitamins are vitamins A, D, E, and K.

water-soluble vitamins - absorption: directly into blood - transport: travel freely - excretion: kidneys detect and remove excess in urine - toxicity: possible to reach toxic levels when consumed from supplements - requirements: needed in frequent does (perhaps 1 to 3 days) fat-soluble vitamins - absorption: first into the lymph, then the blood - transport: many require transport proteins - storage: stored in the cells associated with fat - excretion: less readily excreted; tend to remain in fat-storage sites - toxicity: likely to reach toxic levels when consumed from supplements - requirements: needed in periodic doses (perhaps weeks or even months)

One difference between water-soluble vitamins and fat-soluble vitamins is that ____.

water-soluble vitamins need to be consumed more frequently than fat-soluble vitamins