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Sci 241 Week 5

(©Reinhard/Age Fotostock America, Inc. ) CHAPTER 8 CONCEPTS I I I I I I I I I Thiamin, ribo? avin, niacin, biotin, and pantothenic acid are B vitamins needed to produce ATP from carbohydrate, fat, and protein. Vitamin B6 is important for amino acid metabolism as well as energy production.

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Folate is a coenzyme that is needed for cell division. Vitamin B12, only found in animal foods, is needed for nerve function and to activate folate. Vitamin C is needed to form connective tissue and acts as a watersoluble antioxidant. Vitamin A is essential for vision, and it regulates cell differentiation and growth. Vitamin D is necessary for bone health.

Vitamin E is a fat-soluble antioxidant. Vitamin K is essential for blood clotting. u s t A Ta s t e J Do vitamins give you extra energy? Should everyone take folate supplements? Does eating carrots improve your vision? Can vitamin E protect you from heart disease? The Vitamins Vitamins Are Vital to Your Health Vitamins Provide Many Different Functions in the Body Vitamins Are Found in Almost Everything You Eat We Need Enough but Not Too Much of Each Vitamin Some Vitamins Are Soluble in Water and Others Are Soluble in Fat Many B Vitamins Are Essential for Energy Production Thiamin: Important for Nerve Function Ribo? vin: A Bright Yellow Vitamin Niacin: De? ciency Caused an Epidemic of Mental Illness Biotin: Eggs Contain It but Can Block Its Use Pantothenic Acid: Widely Distributed in Food and Widely Used in the Body Vitamin B6 Is Important for Protein Metabolism Vitamin B6 Is Needed to Synthesize and Break Down Amino Acids Both Animal and Plant Foods Are Good Sources of Vitamin B6 Too Much Vitamin B6 Is Toxic Folate and Vitamin B12 Are Needed for Cell Division Folate: Important for Rapidly Dividing Cells Vitamin B12: Absorption Requires Intrinsic Factor Vitamin C Saved Sailors from Scurvy Vitamin C Is Needed to

Maintain Connective Tissue Vitamin C Is a Water-Soluble Antioxidant Citrus Fruit Is One of the Best Sources of Vitamin C Vitamin C Is the Most Common Vitamin Supplement Choline: Is It a Vitamin? Vitamin A Is Needed for Healthy Eyes Vitamin A Comes in Preformed and Precursor Forms Vitamin A Requires Fat for Absorption and Protein for Transport Vitamin A Is Necessary for Vision Vitamin A Regulates Gene Expression -Carotene Is a Vitamin A Precursor and an Antioxidant Vitamin A Needs Can Be Met with Plant and Animal Sources Vitamin A De? iency Is a World Health Problem Preformed Vitamin A Can Be Toxic Vitamin D Can Be Made in the Skin Vitamin D Is Needed to Maintain Normal Calcium Levels Vitamin D De? ciency Causes Weak Bones Only a Few Foods Are Natural Sources of Vitamin D Too Much Vitamin D Causes Calcium to Deposit in the Wrong Tissues Vitamin E Protects Membranes Vitamin E Is a Fat-Soluble Antioxidant Vitamin E De? ciency Damages Membranes Most of the Vitamin E in Our Diets Comes from Plant Oils Vitamin E Is Relatively Nontoxic Vitamin K Is Needed for Blood Clotting Vitamin K De? iency Causes Bleeding Drugs That Inhibit Vitamin K Prevent Fatal Blood Clots The Requirement for Vitamin K Is Met by Bacterial Synthesis and Food Sources 8 INTRODUCTION Vitamin D Concerns on the Rise By Karen Collins, R. D. Dec. 5, 2003—A lack of vitamin D—thought to be a problem of a bygone era—is showing up in growing numbers of women, children, and the elderly, increasing the risk of bone disease and possibly other health problems. Exposing only the face, hands, and forearms to sunlight for 10 to 30 minutes, just two or three days a week, can usually produce all the vitamin D we need.

Longer exposure doesn’t produce more of this vitamin. Yet today, many people’s lifestyles and locations do not allow them to produce enough, making dietary sources vital. For more information on vitamin D concerns go to www. msnbc. msn. com/id/3660416. A ren’t vitamin de? ciency diseases a thing of the past? After all, the vitamins have been identi? ed, characterized, and puri? ed. We get them from foods that are natural sources and they are added to our breakfast cereal and sold in pill form. For over 100 years scientists have been experimenting with how much of which ones we need to stay healthy and public health of? ials have been providing us with guidelines as to how best to get enough from our diets. How can anyone have a de? ciency? Despite advances in vitamin research over the last century, millions of people around the globe still suffer from vitamin de? ciency diseases. In the United States, the plentiful and 235 236 Chapter 8 The Vitamins varied food supply make severe vitamin de? ciencies unlikely but this doesn’t mean everyone gets enough of everything all the time. Marginal de? ciencies often go unnoticed and can be mistaken for other conditions. Vitamins Are Vital to Your Health

L Vitamins Organic compounds needed * in the diet in small amounts to promote and regulate the chemical reactions and processes needed for growth, reproduction, and the maintenance of health. Vitamins are essential to your health. You only need very small quantities but if you don’t get enough your body cannot function optimally. Severe de? ciencies cause debilitating diseases but even marginal intakes can cause subtle changes that affect your health today and your risk of chronic disease tomorrow. An organic substance is classi? ed as a vitamin if lack of it in the diet causes symptoms that are relieved by adding it back to the diet.

The fact that the vitamins we eat in food are essential to health seems simple and obvious, but it was not always so. For centuries, people knew that some diseases could be cured by certain foods. But it was a long time before we understood why particular foods relieved speci? c ailments. Cures attributed to foods seemed like nothing short of a miracle. People too weak to rise from their beds, those with bleeding wounds that would not heal, those too mentally disturbed to function in society, and those with other serious ailments were cured with changes in diet.

Even before the chemistry of these substances was unraveled, the civilized world was enchanted with the magic of vitamins. They brought hope that incurable diseases could be remedied by simple dietary additions. Today we understand what vitamins do and why they cure de? ciency diseases, but we still hold out hope for more miracles from these small molecules. And we might get a few. Scientists continue to discover important links between vitamins and the risk of developing illnesses such as heart disease, cancer, osteoporosis, and high blood pressure. What is being uncovered is far subtler than the miracle cures of the 19thcentury de? iency diseases, but people cling to the belief that taking more vitamins will cure what ails them. As a result of this “more is always better” attitude vitamin toxicities have become a concern. A toxic reaction can be as devastating as a de? ciency. Trying to get the right amount of each of the vitamins may sound analogous to walking a tightrope between not enough and too much. In reality it is not that hard to get enough of most vitamins from a well-planned diet and most toxicities are not caused by foods but rather by excessive use of supplements. Vitamins provide many different functions in the body

To date, 13 substances have been identi? ed as vitamins essential in the diet (Table 8. 1). They were named alphabetically in approximately the order in which they were identi? ed: A, B, C, D, and E. The B vitamins were ? rst thought to be one chemical substance but were later found to be many different substances, so the alphabetical name was broken down by numbers. Vitamins B6 and B12 are the only ones that are still commonly referred to by their numbers. Thiamin, ribo? avin, and niacin were originally referred to as vitamin B1, B2, and B3, respectively, but today they are not typically called by these names.

Vitamins each have a unique role in the body. For instance, vitamin A is needed for vision, vitamin K is needed for blood clotting, and vitamin C is needed to synthesize connective tissue. Many body processes require the presence of more than one vitamin. For example the B vitamins thiamin, ribo? avin, niacin, biotin, and pantothenic acid are all needed to produce ATP from carbohydrate, fat, and protein. In some cases adequate amounts of one vitamin depend on the presence of another. For example, vitamin B12 is needed to provide the form of folate needed for cell division and vitamin C helps restore vitamin E to its active form.

Vitamins Are Vital to Your Health 237 TABLE 8. 1 Where Does Each Vitamin Fit? Water-Soluble Vitamins B Vitamins • Thiamin (B1) • Ribo? avin (B2) • Niacin (B3) • Biotin • Pantothenic acid • Vitamin B6 • Folate • Vitamin B12 Vitamin C Fat-Soluble Vitamins Vitamin A Vitamin D Vitamin E Vitamin K Vitamins are found in almost everything you eat Almost all foods contain some vitamins (Figure 8. 1). Grain products are good sources of the B vitamins thiamin, niacin, ribo? avin, pantothenic acid, and vitamin B6. Meats, such as beef, pork, and chicken, and ? sh are good sources of all of the B vitamins.

Milk provides ribo? avin and vitamins A and D; leafy greens, such as spinach and kale, provide folate, vitamin A, vitamin E, and vitamin K; citrus fruits like oranges and grapefruit provide vitamin C; and vegetable oils, such as corn and saf? ower oil, are high in vitamin E. FIGURE 8. 1 All the food groups contain choices that are good sources of vitamins. (© Topic Photo Agency) (PhotoDisc, Inc. /Getty Images) Processing affects vitamin content The amount of a vitamin in a food depends on the amount naturally found in that food as well as how the food is cooked, stored, and processed.

The vitamins naturally found in foods can be washed away during preparation, destroyed by cooking, or damaged by exposure to light or oxygen. Thus, processing steps such as canning vegetables, re? ning grains, and drying fruits can cause nutrient losses. However, other processing steps such as forti? cation and enrichment add nutrients to foods. Some nutrients are added to foods to prevent vitamin or mineral de? ciencies and promote health in the population (see Chapter 10). For example, milk is forti? ed with vitamin D to promote bone health, and grains are forti? ed with folic acid to reduce the incidence of birth defects.

Some foods are also forti? ed with nutrients to help increase product sales. Dietary supplements can boost vitamin intake We also get vitamins in dietary supplements. Currently about half of adult Americans take some form of dietary supplement on a daily basis and 80% take them occasionally. 1 While supplements provide speci? c nutrients, they do not provide all the bene? ts of foods. A pill that meets vitamin needs does not provide the energy, protein, minerals, ? ber, or phytochemicals that would have been supplied by food sources of these vitamins (see Chapter 10).

Not all of what you eat can be used by the body The vitamins that we consume in our diets are needed in the cells and ? uids of our body. In order to provide their essential functions, vitamins must get to the target tissues. The amount of a nutrient consumed that can be used by the body is referred to as its bioavailability. Bioavailability is affected by the composition of individual foods, the diet as a whole, and conditions in the body. For example, the thiamin in certain individual foods such as blueberries and red cabbage cannot be used by the body because these foods contain antithiamin factors that destroy the thiamin.

An example of how L Forti? cation A term used generally to * describe the addition of nutrients to foods, such as the addition of vitamin D to milk. L Enrichment The addition of speci? c * nutrients to a food to restore those lost in processing to a level equal to or higher than originally present. L Dietary supplement A product * intended for ingestion in the diet that contains one or more of the following: vitamins, minerals, plant-derived substances, amino acids, or concentrates or extracts. L Bioavailability A general term that * refers to how well a nutrient can be absorbed and used by the body. 38 Chapter 8 The Vitamins Chewing helps break apart fiber and release vitamins Bile produced by the liver helps to absorb fat-soluble vitamins Digestion in the stomach releases vitamins from food Some niacin absorption Liver Stomach Digestive enzymes released by pancreas help to further release vitamins Fat-soluble vitamins absorbed from micelles along with dietary fat Pancreas Water-soluble vitamins (thiamin, riboflavin, niacin, vitamin B6, biotin, pantothenic acid) absorbed by simple diffusion, facilitated diffusion, and active transport Vitamin C absorbed in later portion (ileum) of small intestine

Small Intestine Vitamin B12 absorbed in later portion (ileum) of small intestine Large Intestine Absorption of small amounts of vitamin K, biotin, and pantothenic acid made by bacteria in the large intestine FIGURE 8. 2 An overview of vitamins in the digestive tract. diet composition affects vitamin bioavailability is dietary fat and the absorption of fatsoluble vitamins. Because fat-soluble vitamins are absorbed along with dietary fat, diets very low in fat reduce absorption (Figure 8. 2). Conditions in the body affect bioavailability in several ways.

Some vitamins require speci? c molecules in order to be absorbed. If these aren’t available, the vitamin cannot be absorbed in suf? cient amounts. For example, vitamin B12 must be bound to a protein produced in the stomach before it can be absorbed in the intestine. If this protein is not available, adequate amounts of vitamin B12 cannot be absorbed. Other vitamins require transport molecules to travel in the blood to the tissues that need them. Vitamin A is stored in the liver, but it must be bound to a speci? transport protein to travel in the blood to other tissues; therefore, the amount delivered to the tissues depends on the availability of the transport protein. We need enough but not too much of each vitamin The right amounts and combinations of vitamins and other nutrients are essential to health. Despite our knowledge of what vitamins do and how much of each we need, we don’t all consume the right amounts. In developing countries, vitamin de? ciencies remain a major public health problem. In industrialized countries, a more varied food supply, along with forti? ation, has almost eliminated vitamin-de? ciency diseases in the majority of the population. Concern in these countries now focuses on meeting the needs of high-risk groups such as children and pregnant women, determining the effects of marginal de? ciencies such as the effect of low B vitamin intake on heart disease risk, and evaluating the risk of consuming large amounts. The RDAs and AIs of the Dietary Reference Intakes (DRI) recommend amounts that provide enough of Vitamins Are Vital to Your Health 239 each of the vitamins to prevent a de? ciency and promote health (see Chapter 2).

Because more is not always better when it comes to nutrient intake, the DRIs have also established Tolerable Upper Intake Levels (ULs) as a guide to amounts that are high enough to pose a risk of toxicity (see inside cover). Some vitamins are soluble in water and others are soluble in fat We group vitamins based on their solubility in water or fat, a characteristic that affects how they are absorbed, transported, excreted, and stored in the body. The watersoluble vitamins include the B vitamins and vitamin C. The fat-soluble vitamins include vitamins A, D, E, and K (see Table 8. 1) With he exception of vitamin B12, the water-soluble vitamins are easily excreted from the body in the urine. Because they are not stored to any great extent, supplies of most water-soluble vitamins are rapidly depleted and they must be consumed regularly in the diet. Nevertheless, it takes more than a few days to develop de? ciency symptoms, even when these vitamins are completely eliminated from the diet. Fatsoluble vitamins, on the other hand, are stored in the liver and fatty tissues and cannot be excreted in the urine. In general, because they are stored to a larger extent, it takes longer to develop a de? iency of fat-soluble vitamins when they are no longer provided by the diet. In this chapter the water-soluble vitamins are presented ? rst because many play an important role in the reactions that produce energy from carbohydrate, fat, and protein that have been addressed in Chapters 4 through 7 (Table 8. 2). L Water-soluble vitamins Vitamins that * dissolve in water. L Fat-soluble vitamins Vitamins that * dissolve in fat. TABLE 8. 2 A Quick Guide to the Water-Soluble Vitamins Food Sources Pork, whole and enriched grains, seeds, nuts, legumes Recommended Intake for Adults 1. –1. 2 mg/day Major Functions Coenzyme in glucose metabolism, needed for neurotransmitter synthesis and normal nerve function Coenzyme needed in energy metabolism De? ciency Symptoms Berberi: weakness, apathy, irritability, nerve tingling, poor coordination, paralysis, heart changes In? ammation of mouth and tongue, cracks at corners of the mouth Pellagra: diarrhea, dermatitis on areas exposed to sun, dementia Groups at Risk of De? ciency Alcoholics, those living in poverty Toxicity and UL None reported. No UL Vitamin Thiamin (vitamin B1, thiamin mononitrate) Ribo? vin (vitamin B2) Dairy products, 1. 1–1. 3 mg/day whole and enriched grains, leafy green vegetables, meats Beef, chicken, ? sh, peanuts, legumes, whole and enriched grains. Can be made from tryptophan 14–16 mg NE/day None None reported. No UL Niacin (nicotinamide, nicotinic acid, vitamin B3) Coenzyme needed in energy metabolism and lipid synthesis and breakdown Those consuming a limited diet based on corn, alcoholics Flushing, nausea, rash, tingling extremities. UL is 35 mg from forti? ed foods and supplements (Continued) 240 Chapter 8 The Vitamins TABLE 8. 2 (Continued )

Food Sources Liver, egg yolks, synthesized in the gut Recommended Intake for Adults 30 g/day Major Functions De? ciency Symptoms Groups at Risk of De? ciency Those consuming large amounts of raw egg whites, alcoholics None Toxicity and UL None reported. No UL Vitamin Biotin Coenzyme in Dermatitis, glucose production nausea, and lipid synthesis depression, hallucinations Pantothenic acid (calcium pantothenate) Vitamin B6 (pyridoxine, pyridoxal, pyridoxamine) Meat, legumes, whole grains, widespread in foods Meat, ? sh, poultry, legumes, whole grains, nuts and seeds Leafy green vegetables, legumes, seeds, enriched grains 5 mg/day

Coenzyme in Fatigue, rash energy metabolism and lipid synthesis and breakdown Coenzyme in protein metabolism, neurotransmitter and hemoglobin synthesis Coenzyme in DNA synthesis and amino acid metabolism Headache, numbness, tingling, convulsions, nausea, poor growth, anemia Macrocytic anemia, in? ammation of tongue, diarrhea, poor growth, neural tube defects Pernicious anemia, macrocytic anemia, nerve damage Scurvy: poor wound healing, bleeding gums, loose teeth, bone fragility, joint pain, pinpoint hemorrhages Liver dysfunction None reported. No UL Numbness, nerve damage. UL is 100 mg 1. 3–1. 7 mg/day Women, alcoholics

Folate (folic acid, folacin, pteroyglutamic acid) 400 g DFE/day Pregnant women, alcoholics Masks B12 de? ciency. UL is 1000 g from forti? ed food and supplements None reported. No UL Animal products 2. 4 g/day Vitamin B12 (cobalamin, cyanocobalamin) Coenzyme in folate metabolism, nerve function Vegans, women, those with stomach or intestinal disease Alcoholics, elderly men Vitamin C (ascorbic acid, ascorbate) Citrus fruit, broccoli, strawberries, greens, peppers 75–90 mg/day Collagen (connective tissue) synthesis; hormone and neurotransmitter synthesis, antioxidant Synthesis of cell membranes and neurotransmitters

GI distress, diarrhea. UL is 2000 mg Choline* Egg yolks, organ meats, leafy greens, nuts, body synthesis 425–550 mg/day None Sweating low blood pressure, liver damage. UL is 3500 mg UL, Tolerable Upper Intake Level; NE, niacin equivalent; DFE, dietary folate equivalent. *Choline is technically not a vitamin but recommendations have been made for its intake. Many B Vitamins Are Essential for Energy Production 241 Many B Vitamins Are Essential for Energy Production For many people the term vitamin is synonymous with energy. But vitamins do not actually contain any energy at all.

We get energy from the carbohydrate, fat, and protein in our diet, but we can’t use the energy contained in these nutrients without the help of vitamins. The B vitamins thiamin, ribo? avin, niacin, pantothenic acid, and biotin are directly involved in converting the energy in carbohydrate, fat, and protein into ATP—the form of energy that is used to run the body (Figure 8. 3). Each of these vitamins acts as a coenzyme in one or more of the chemical reactions necessary to generate usable energy from these nutrients (Figure 8. 4). Thiamin: important for nerve function

Thiamin is needed for nerve cells to obtain energy and to synthesize an important neurotransmitter. A de? ciency of thiamin causes beriberi, a condition that has been known for over 1000 years in East Asian countries. In Sri Lanka, the word beriberi literally means “I cannot”; this phrase refers to the extreme weakness that is the earliest symptom of the condition. Beriberi came to the attention of Western medicine in colonial Asia in the 19th century. It became such a problem that the Dutch East India Company sent a team of scientists to ? nd its cause. What they were expecting to ? d was a germ like those that caused cholera and rabies. What they found for a long time was nothing. For over 10 years, a young physician named Christian Eijkman worked C C C C C C Although people often take B vitamins to get more energy these vitamins do not actually provide energy. They are however necessary for the body to produce energy from other nutrients. L Coenzymes Small nonprotein organic * molecules that act as carriers of electrons or atoms in metabolic reactions and are necessary for the proper functioning of many enzymes. L Beriberi The disease resulting from a * de? iency of thiamin. O C C O C C C C C OH C C Glucose Fatty acid Amino acids Niacin Biotin Niacin Riboflavin Biotin Pantothenic acid Niacin Riboflavin Biotin Pantothenic acid O2 Thiamin Riboflavin Niacin Pantothenic acid C C Thiamin Riboflavin Pantothenic acid C C C Niacin Riboflavin H2O CO2 ATP FIGURE 8. 3 Thiamin, ribo? avin, niacin, biotin, and pantothenic acid are needed in the reactions that produce energy from carbohydrate, fat, and protein. If one of these is missing, energy production is disrupted. 242 Chapter 8 The Vitamins Coenzyme Incomplete enzyme

Active enzyme A B A B Enzyme reaction FIGURE 8. 4 The B vitamins serve as coenzymes. This ? gure shows that the coenzyme must bind to form an active enzyme. The enzyme in this example can then join A and B to form a new molecule, shown here as AB. AB to ? nd the cause of beriberi. His success came as a twist of fate. He ran out of food for his experimental chickens and instead of the usual brown rice, he fed them white rice. Shortly thereafter, the chickens came down with beriberi-like symptoms. When he fed them brown rice again, they got well. What did this mean?

To Eijkman it provided evidence that the cause of beriberi was not a poison or a microorganism, but rather something missing from the chicken feed. The incidence of beriberi in East Asia increased dramatically the 1800s due to the rising popularity of polished rice. Polished or white rice is produced by polishing off the bran layer of brown rice creating a more uniform product. However, polishing off the bran also removes the vitamin-rich portion of the grain (Figure 8. 5). Therefore, in populations where white rice was the staple of the diet, beriberi, became a common health problem.

FIGURE 8. 5 Unenriched white rice is a poor source of thiamin. (Charles D. Winters) L Wernicke-Korsakoff syndrome A form * of thiamin de? ciency associated with alcohol abuse that is characterized by mental confusion, disorientation, loss of memory, and a staggering gait. Thiamin is needed to produce energy from glucose The reason thiamin is needed for nerve cells to obtain energy is because it is a coenzyme for some of the important energy-yielding reactions in the body. One of these is essential for the production of energy from glucose, the energy source for nerve cells.

In addition to its role in energy production it is needed for neurotransmitter synthesis and is also essential for the metabolism of other sugars and certain amino acids, and for the synthesis of ribose, a sugar that is part of the structure of RNA (ribonucleic acid). Thiamin de? ciency affects the nervous and cardiovascular systems. Without thiamin, glucose, which is the primary fuel for the brain and nerve cells, cannot be used normally and nerve impulses cannot be transmitted normally. This leads to weakness and depression, which are the ? st symptoms of beriberi; other neurological symptoms include poor coordination, tingling sensations, and paralysis. The reason de? ciency affects the cardiovascular system is not well understood, but symptoms include rapid heartbeat and enlargement of the heart. Overt beriberi is rare in North America today, but a form of thiamin de? ciency called Wernicke-Korsakoff syndrome does occur in alcoholics. People with this condition experience mental confusion, psychosis, memory disturbances, and eventually coma. They are particularly vulnerable because thiamin absorption is decreased due to the effect of alcohol on the gastrointestinal tract.

In addition, thiamin intake is low because alcohol contributes calories to the alcoholic’s diet but brings with it almost no nutrients. Many B Vitamins Are Essential for Energy Production RDA Sunflower seeds (1/4 c) Walnuts (1/4 c) Peanuts (1/4 c) Lentils (1 c) Pork (3 oz) Beef (3 oz) Trout (3 oz) Chicken (3 oz) 2% Milk (1 c) Cheddar cheese (1. 5 oz) Orange juice (1 c) Kiwi (2 med) Apple (1 med) Corn (1/2 c) Asparagus (1/2 c) Spinach, raw (1 c) Oatmeal (1 c) Spaghetti (1 c) Brown rice (1 c) White bread (2 sl) Whole-wheat bread (2 sl) 0 0. 2 0. 4 0. 6 0. 8 Thiamin (mg) 1. 0 1. 2 243

FIGURE 8. 6 Thiamin content of selections from each group of the Food Guide Pyramid. The dashed line represents the RDA for adult men. Pork is a better source of thiamin than other meats. (Randy Mayor/Foodpix/PictureArts Corp. ) The recommended intake for thiamin can be met by eating a varied diet You can meet your needs for thiamin by snacking on sun? ower seeds and having a serving of roast pork for dinner. These foods are exceptionally good sources of thiamin. Together 3 ounces of pork and a quarter cup of sun? ower seeds provide 1. 5 mg of thiamin, well above the RDA, which is 1. mg per day for adult men age 19 and older and 1. 1 mg per day for adult women 19 and older. 2 But even a diet that doesn’t include these foods can meet your thiamin needs as long as you make nutritious choices such as those recommended by the Food Guide Pyramid (Figure 8. 6). Legumes, nuts, and seeds are good sources. Grains are also good sources; thiamin is found in the bran of whole grains and it is added to enriched re? ned grains. A large proportion of the thiamin consumed in the United States comes from enriched grains used in foods such as baked goods. Some breakfast cereals are forti? d with so much additional thiamin that a single bowlful contains more than the RDA. Although it is easy to meet thiamin needs some of the thiamin in foods may be destroyed during cooking or storage because it is sensitive to heat, oxygen, and low-acid conditions. Thiamin availability is also affected by the presence of antithiamin factors that destroy the vitamin. There are enzymes in raw shell? sh and freshwater ? sh that degrade thiamin during food storage and preparation and during passage through the gastrointestinal tract. These enzymes are destroyed by cooking so they are only a concern in foods consumed raw.

Other antithiamin factors that are not inactivated by cooking are found in tea, coffee, betel nuts, blueberries, and red cabbage. Habitual consumption of foods containing antithiamin factors increases the risk of thiamin de? ciency. 2 Despite the fact that intakes of thiamin above the RDA have not been shown to be bene? cial, many supplements contain up to 50 mg of thiamin and promise that they will provide “more energy. ” Although thiamin is needed to produce energy, unless it is de? cient, increasing thiamin intake does not increase the ability to produce energy.

There is no UL for thiamin since no toxicity has been reported when excess is consumed from either food or supplements. 2 Enriched grains have thiamin as well as ribo? avin, niacin, and iron added to them (see Chapter 4). * Remember 244 Chapter 8 The Vitamins Ribo? avin: a bright yellow vitamin Ribo? avin is a water-soluble vitamin that provides a visible indicator when you consume too much of it. Excess is excreted in your urine—turning it a bright ? uorescent yellow. The color may surprise you but it is harmless. No adverse effects have been reported from high doses of ribo? vin from foods or supplements. FIGURE 8. 7 Milk is packaged in opaque or cloudy containers to protect its ribo? avin from destruction by light. (Charles D. Winters) Milk is the best source of ribo? avin in the North American diet Ever wonder why milk comes in opaque cardboard or cloudy plastic containers? The reason is that it is one of the best sources of ribo? avin in our diet and ribo? avin is destroyed by light. If your milk was in a clear glass bottle and sat in a lighted grocery store display case for several days much of the ribo? avin would be destroyed. The most ribo? vin-friendly milk containers are opaque so the ribo? avin is fully protected from light (Figure 8. 7). Other major dietary sources of ribo? avin include other dairy products, liver, red meat, poultry, ? sh, whole grains, and enriched breads and cereals. Vegetable sources include asparagus, broccoli, mushrooms, and leafy green vegetables such as spinach. The RDA for ribo? avin for adult men age 19 and older is 1. 3 mg per day and for adult women 19 and older, 1. 1 mg per day. 3 Two cups of milk provide about half the amount of ribo? avin recommended for a typical adult.

If you do not include milk in your diet you can meet your ribo? avin needs by including two to three servings of meat and four to ? ve servings of enriched grain products and high-ribo? avin vegetables such as spinach (Figure 8. 8). Ribo? avin is needed to produce energy from carbohydrate, fat, and protein Ribo? avin has two active coenzyme forms that function in producing energy from carbohydrate, fat, and protein. Ribo? avin is also involved directly or indirectly in converting a number of other vitamins, including folate, niacin, vitamin B6, and vitamin K, into their active forms. When ribo? vin is de? cient, injuries heal poorly because new cells cannot grow to replace the damaged ones. Tissues that grow most rapidly, such as the skin and the lin- RDA Sunflower seeds (1/4 c) Walnuts (1/4 c) Peanuts (1/4 c) Lentils (1 c) Pork (3 oz) Beef (3 oz) Trout (3 oz) Chicken (3 oz) 2% Milk (1 c) Cheddar cheese (1. 5 oz) Orange juice (1 c) Kiwi (2 med) Apple (1 med) Corn (1/2 c) Asparagus (1/2 c) Spinach, raw (1 c) FIGURE 8. 8 Ribo? avin content of selections from each group of the Food Guide Pyramid. The dashed line represents the RDA for adult men. Milk is an exceptionally good source of ribo? avin. Corbis Images) Oatmeal (1 c) Spaghetti (1 c) Brown rice (1 c) White bread (2 sl) Whole-wheat bread (2 sl) 0 0. 4 0. 8 Riboflavin (mg) 1. 2 Many B Vitamins Are Essential for Energy Production 245 ings of the eyes, mouth, and tongue, are the ? rst to be affected. This causes symptoms such as cracking of the lips and at the corners of the mouth; increased sensitivity to light; burning, tearing, and itching of the eyes; and ? aking of the skin around the nose, eyebrows, and earlobes. A de? ciency of ribo? avin rarely occurs alone; it usually occurs in conjunction with de? ciencies of other B vitamins.

This is because the same foods provide many of the B vitamins. Because ribo? avin is needed to convert other vitamins into their active forms, some of the symptoms seen with ribo? avin de? ciency re? ect de? ciencies of these other nutrients. Niacin: de? ciency caused an epidemic of mental illness In the early 1900’s psychiatric hospitals in the southeastern United States were ? lled with patients with the niacin-de? ciency disease pellagra. At the time, no one knew what caused it but the prime suspects were toxins or microorganisms. The mystery of pellagra was ? nally unraveled by Dr. Joseph Goldberger, who was sent by the U.

S. Public Health Service to investigate the pellagra epidemic. He observed that individuals in institutions such as hospitals, orphanages, and prisons suffered from pellagra, but the staff did not. If pellagra were an infectious disease, both populations would be equally affected. Dr. Goldberger proposed that pellagra was due to a de? ciency in the diet. To test his hypothesis, he added nutritious foods such as fresh meats, milk, and eggs to the diet of children in orphanages. The symptoms of pellagra disappeared, supporting his hypothesis that pellagra is due to a de? ciency of something in the diet.

In another experiment he was able to induce pellagra in healthy prison inmates by feeding them an unhealthy diet. The missing dietary component was later identi? ed as the water-soluble B vitamin niacin. L Pellagra The disease resulting from a * de? ciency of niacin. A niacin de? ciency causes dermatitis, diarrhea, and dementia The need for niacin is so widespread in metabolism that a de? ciency causes major changes throughout the body. The early symptoms of pellagra include fatigue, decreased appetite, and indigestion. These are followed by symptoms that can be remembered as the three D’s: dermatitis, diarrhea, dementia.

If left untreated, niacin de? ciency results in a fourth D—death. Niacin coenzymes function in glucose metabolism and in reactions that synthesize fatty acids and cholesterol (see Figure 8. 3). There are two forms of niacin: nicotinic acid and nicotinamide. Either form can be used by the body to make the active coenzyme forms. Niacin is found in meats, legumes, and grains Meat and ? sh are good sources of niacin (Figure 8. 9). Other sources include legumes, wheat bran, and peanuts. Niacin added to enriched grains provides much of the usable niacin in the North American diet.

Niacin can also be synthesized in the body from the essential amino acid tryptophan. Tryptophan, however, is only used to make niacin if enough is available to ? rst meet the needs of protein synthesis. When the diet is low in tryptophan, it is not used to synthesize niacin. The reason pellagra was prevalent in the South in the early 1900’s is because the local diet among the poor consisted of corn meal, molasses, and fatback or salt pork— all poor sources of both niacin and protein. Corn is low in tryptophan and the niacin found naturally in corn is bound to other molecules and therefore not well absorbed.

Molasses contains essentially no protein or niacin and salt pork is almost pure fat, so it does not contain enough protein to both meet protein needs and synthesize niacin. Although corn-based diets such as this one are historically associated with the appearance of niacin de? ciency it has not been a problem in Mexico and Central American countries. One reason may be because the treatment of corn with lime water, as is done during the making of tortillas, enhances the availability of niacin (Figure 8. 10). The diet in these regions also includes legumes, which provide both niacin and a source of tryptophan for the synthesis of niacin.

In searching for the cause of pellagra, Dr. Goldberger and his coworkers ingested blood, nasal secretions, feces, and urine from patients with the disease—none of them developed pellagra. This helped to disprove the hypothesis that pellagra was an infectious disease. 246 Chapter 8 The Vitamins RDA Sunflower seeds (1/4 c) Walnuts (1/4 c) Peanuts (1/4 c) Lentils (1 c) Pork (3 oz) Beef (3 oz) Trout (3 oz) Chicken (3 oz) 2% Milk (1 c) Cheddar cheese (1. 5 oz) Orange juice (1 c) Kiwi (2 med) Apple (1 med) Corn (1/2 c) Asparagus (1/2 c) Spinach, raw (1 c) FIGURE 8. 9 Niacin content of selections from each group of the Food Guide Pyramid.

The dashed line represents the RDA for adult men. Meat, legumes, and grains are good sources of the vitamin. (PhotoDisc, Inc. /Getty Images) Oatmeal (1 c) Spaghetti (1 c) Brown rice (1 c) White bread (2 sl) Whole-wheat bread (2 sl) 0 2 4 6 8 10 Niacin (mg) 12 14 16 L Niacin equivalents (NEs) The * measure used to express the amount of niacin present in food, including that which can be made from its precursor, tryptophan. One NE is equal to 1 mg of niacin or 60 mg of tryptophan. Today, as a result of the enrichment of grains, including corn meal, with niacin, thiamin, ribo? vin, and iron, pellagra is rare in the United States but it remains common in India and parts of China and Africa. Efforts to eradicate this de? ciency include the development of new varieties of corn that provide more available niacin and more tryptophan than traditional varieties. Because some of the requirement for niacin can be met by the synthesis of niacin from tryptophan, the RDA is expressed as niacin equivalents (NEs). One NE is equal to 1 mg of niacin or 60 mg of tryptophan, the amount needed to make 1 mg of niacin. 3 To estimate the niacin contributed by high-protein foods, protein is considered to be about 1% tryptophan.

The RDA for adult men and women of all ages is 16 and 14 mg NE per day, respectively. A medium chicken breast and a cup of steamed asparagus provide this amount. FIGURE 8. 10 Tortillas, eaten in Mexico and other Latin American countries, provide niacin because the corn is treated with lime water, making the niacin available for absorption. (Jeff Greenberg/Photo Researchers) Many B Vitamins Are Essential for Energy Production 247 High-dose niacin supplements can be toxic There is no evidence of any adverse effects from consumption of niacin naturally occurring in foods, but supplements can be toxic.

The adverse effects of high intakes of niacin include ? ushing of the skin, a tingling sensation in the hands and feet, a red skin rash, nausea, vomiting, diarrhea, high blood sugar levels, abnormalities in liver function, and blurred vision. The UL for adults is 35 mg, but high-dose supplements of one form of niacin (50 mg or greater) are used under medical supervision to treat elevated blood cholesterol (see Chapter 5). Another form is under investigation for its bene? ts in the prevention and treatment of diabetes. When vitamins are taken in large doses to treat diseases that are not due to vitamin de? iencies, they are really being used as drugs rather than vitamins. Biotin: eggs contain it but can block its use You probably know that you shouldn’t eat raw eggs because they can contain harmful bacteria, but did you know that eating raw eggs could cause a biotin de? ciency? Raw egg whites contain a protein called avidin that tightly binds biotin and prevents its absorption. Biotin was discovered when rats fed protein derived from raw egg whites developed a syndrome of hair loss, dermatitis, and neuromuscular dysfunction. Thoroughly cooking eggs kills bacteria and denatures avidin so that it cannot bind biotin (Figure 8. 1). FIGURE 8. 11 Raw eggs are often used to make high-protein health drinks. This is not recommended because raw eggs may contain bacteria that can make you sick, and egg whites contain a protein that makes biotin unavailable. (Charles D. Winters) Biotin is important in energy production and glucose synthesis Biotin is a coenzyme for a group of enzymes that add an acid group to molecules. It functions in energy production and in glucose synthesis. It is also important in the metabolism of fatty acids and amino acids (see Figure 8. 3). Although biotin de? iency is uncommon, it has been observed in those frequently consuming raw egg whites as well as people with malabsorption or protein-energy malnutrition, those receiving intravenous feedings lacking biotin, and those taking certain anticonvulsant drugs for long periods. 3 Biotin de? ciency in humans causes nausea, thinning hair, loss of hair color, a red skin rash, depression, lethargy, hallucinations, and tingling of the extremities. Biotin is consumed in the diet and made by bacteria in the gut Good sources of biotin in the diet include cooked eggs, liver, yogurt, and nuts. Fruit and meat are poor sources.

Biotin is also synthesized by bacteria in the gastrointestinal tract. Some of this is absorbed into the body and contributes to our biotin needs. An AI of 30 mg per day has been established for adults based on the amount of biotin found in a typical North American diet. High doses of biotin have not resulted in toxicity symptoms; there is no UL for biotin. Pantothenic acid: widely distributed in food and widely used in the body Pantothenic acid, which gets its name from the Greek word pantos (meaning “from everywhere”), is widely distributed in foods. It is particularly abundant in meat, eggs, whole grains, and legumes.

It is found in lesser amounts in milk, vegetables, and fruits. In addition to being “from everywhere” in the diet, pantothenic acid seems to be needed everywhere in the body. It is part of a key coenzyme needed for the breakdown of carbohydrates, fatty acids, and amino acids as well as the modi? cation of proteins and the synthesis of neurotransmitters, steroid hormones, and hemoglobin. Pantothenic acid is also part of a coenzyme essential for the synthesis of cholesterol and fatty acids (see Figure 8. 3). The wide distribution of pantothenic acid in foods makes de? ciency rare in humans. It may occur as part of a multiple B vitamin de? iency resulting from malnutrition or chronic alcoholism. The AI is 5 mg per day for adults. Pantothenic acid is relatively nontoxic and there are not suf? cient data to establish a UL. 3 248 Chapter 8 The Vitamins Vitamin B6 Is Important in Protein Metabolism Vitamin B6 is one of only two B vitamins that we still know by its number. The chemical name for vitamin B6 is pyridoxine but we rarely hear it called this. The important role of vitamin B6 in amino acid metabolism distinguishes it from the other B vitamins. Vitamin B6 is needed to synthesize and break down amino acids Vitamin B6 has three forms—pyridoxal, pyridoxine, and pyridoxamine.

These can be converted into the active coenzyme form, pyridoxal phosphate, which is needed for the activity of more than 100 enzymes involved in the metabolism of carbohydrate, fat, and protein. It is particularly important in amino acid synthesis and breakdown; without vitamin B6 the non-essential amino acids cannot be made in the body (Figure 8. 12). Pyridoxal phosphate is needed to synthesize hemoglobin, the oxygen-carrying protein in red blood cells, and is important for the immune system because it is needed to form white blood cells.

It is also needed for the conversion of tryptophan to niacin, the release of glucose from the carbohydrate storage molecule glycogen, the synthesis of certain neurotransmitters, and the synthesis of the lipids that are part of the myelin coating on nerves, which is essential for normal transmission of nerve signals. Vitamin B6 de? ciency causes numbness and tingling Vitamin B6 de? ciency causes neurological symptoms including numbness and tingling in the hands and feet as well as depression, headaches, confusion, and seizures. These symptoms may be related to the role of vitamin B6 in neurotransmitter synthesis and myelin formation.

Anemia also occurs in vitamin B6 de? ciency, because without B6 hemoglobin cannot be synthesized normally. Other de? ciency symptoms such as poor growth, skin lesions, and decreased antibody formation may occur because of the central role vitamin B6 plays in protein and energy metabolism. Since vitamin B6 is needed for amino acid metabolism, the onset of a de? ciency can be hastened by a diet that is low in vitamin B6 but high in protein. H H2N C C O OH Amino acids NH2 C O OH B6 Energy production and glucose synthesis B6 B6 FIGURE 8. 12 Vitamin B6 is essential for many different types of reactions involving amino acids.

It is needed to remove the acid group so neurotransmitters can be synthesized, to remove the amino group so what remains can be used to produce energy or synthesize glucose, and to transfer an amino group to make a new amino acid. Neurotransmitter synthesis NH2 Synthesis of nonessential amino acids Vitamin B6 Is Important in Protein Metabolism Folic acid from food and supplements 249 DNA synthesis Active folate Vitamin B12 Inactive folate Methionine High levels in the FIGURE 8. 13 blood increase cardiovascular The accumulation of homocysteine in the blood is associated with an disease risk

Homocysteine Vitamin B6 increased risk of heart disease. Vitamins B6, B12, and folate, are needed to keep homocysteine levels in the normal range. Vitamin B6 is needed to break down homocysteine. Vitamin B12 and folate are needed to convert homocysteine to methionine. Vitamin B6 status is related to heart disease risk Vitamin B6 is needed to break down the amino acid homocysteine. If B6 levels are low, homocysteine can’t be broken down and levels rise. Even a mild elevation in blood homocysteine levels has been shown to be a risk factor for heart disease (Figure 8. 13). Two other B vitamins, folate and vitamin B12 are also involved in homocysteine metabolism. These are needed to convert homocysteine to the amino acid methionine. If they are unavailable, homocysteine levels will increase. A study that examined the effect of folate and vitamin B6 intake in women found that those with the highest levels in their diets had about half the risk of coronary heart disease as women with the lowest levels. 5 Both animal and plant foods are good sources of vitamin B6 Animal sources of vitamin B6 include chicken, ? sh, pork, and organ meats.

Good plant sources include whole wheat products, brown rice, soybeans, sun? ower seeds, and some fruits and vegetables such as bananas, broccoli, and spinach (Figure 8. 14). Re? ned grains, like white rice and white bread, are not good sources of vitamin B6, because the vitamin is lost in re? ning whole grains but is not added back in enrichment. It is added to many forti? ed breakfast cereals; these make an important contribution to vitamin B6 intake. 6 It is destroyed by heat and light, so it can easily be lost in processing. The RDA for vitamin B6 is 1. 3 mg per day for both adult men and women 19 to 50 years of age. A 3-ounce (85-g) serving of chicken, ? sh, or pork, or half a baked potato, provides about one-fourth of the RDA for an average adult; a banana provides about one-third. Too much vitamin B6 is toxic For years people assumed that because water-soluble vitamins were excreted in the urine they could not cause toxic reactions. However, reports in the 1980’s of severe nerve impairment in individuals taking 2 to 6 g of pyridoxine per day showed these assumptions to be false. 7 The reactions of some supplement users were so severe that they were unable to walk; symptoms improved when the pyridoxine supplements were stopped.

The UL for adults is set at 100 mg per day from food and supplements. 3 Despite the potential for toxicity, high-dose supplements of vitamin B6 containing 100 mg per dose (5000% of the Daily Value) are available over the counter, making it easy to obtain a dose that exceeds the UL. These supplements are taken to reduce the symptoms of premenstrual syndrome (PMS), treat carpal tunnel syndrome, and strengthen immune function. Although studies have not found a relationship between carpal tunnel syndrome and vitamin B6 status, some studies report that low-dose supplements of vitamin B6 may reduce symptoms of PMS and improve immune function. Individuals with an inherited disease called homocysteinuria have extremely high levels of homocysteine in their blood and may have heart attacks and strokes by the age of 2. 250 Chapter 8 The Vitamins RDA Sunflower seeds (1/4 c) Walnuts (1/4 c) Peanuts (1/4 c) Lentils (1 c) Pork (3 oz) Beef (3 oz) Trout (3 oz) Chicken (3 oz) 2% Milk (1 c) Cheddar cheese (1. 5 oz) Orange juice (1 c) Kiwi (2 med) Apple (1 med) Corn (1/2 c) Asparagus (1/2 c) Spinach, raw (1 c) Oatmeal (1 c) Spaghetti (1 c) Brown rice (1 c) White bread (2 sl) Whole-wheat bread (2 sl) 0 0. 0. 8 Vitamin B6 (mg) 1. 2 FIGURE 8. 14 Vitamin B6 content of selections from each group of the Food Guide Pyramid. The dashed line represents the RDA for men and women up to 50 years of age. The best sources are meats, legumes, and whole grains. (David Bishop/Foodpix/PictureArts Corp. ) PMS causes mood swings, food cravings, bloating, tension, depression, headaches, acne, breast tenderness, anxiety, temper outbursts, and over 100 other symptoms. Because vitamin B6 is needed for the synthesis of the neurotransmitters serotonin and dopamine, insuf? ient vitamin B6 has been suggested to cause the anxiety, irritability, and depression associated with PMS by reducing levels of these neurotransmitters. Trials on the effect of vitamin B6 supplements on PMS have had con? icting results— in some cases low-dose supplements appear to be effective in reducing symptoms. 9 Vitamin B6 supplements have been found to improve immune function in older adults, but the reason for the improvement is unclear. 10 Immune function can be impaired by a de? ciency of any nutrient that hinders cell growth and division.

Therefore, one of the most common claims for vitamin supplements in general is that they improve immune function. Vitamin B6 is no exception. Since the elderly frequently have low intakes of vitamin B6, it is unclear whether the bene? cial effects of supplements are due to an improvement in vitamin B6 status or immune system stimulation. Folate and Vitamin B12 Are Needed for Cell Division Inside the nucleus of every cell is the DNA that holds the genetic code. Before a cell can divide it must make a copy of its DNA. The B vitamin folate is needed for the synthesis of DNA and vitamin B12 is needed to keep folate active.

Therefore if either B12 or folate is missing, DNA cannot be copied and new cells cannot be made correctly. As a result of this interdependency, many of the same symptoms are seen when either vitamin B12 or folate are de? cient. Folate: important for rapidly dividing cells A number of different forms of folate are needed for the synthesis of DNA and the metabolism of some amino acids. Because folate is needed for cells to replicate, it is particularly important in tissues where cells are dividing rapidly such the bone marrow, where red blood cells are made, and the developing tissues of an unborn baby.

Folate and Vitamin B12 Are Needed for Cell Division 251 folate adequate folate deficient Normal cell division Red blood cells Red blood cell precursor FIGURE 8. 15 Cells are unable to divide (megaloblast) Macrocyte Megaloblastic or macrocytic anemia occurs when developing blood cells are unable to divide, leaving large immature red blood cells (megaloblasts) and large mature red blood cells (macrocytes). Folate de? ciency results in anemia One of the most notable symptoms of folate de? ciency is anemia. Without folate, developing red blood cells cannot divide. Instead, they just grow bigger (Figure 8. 15).

Fewer mature red cells are produced so the oxygen-carrying capacity of the blood is reduced. This condition is called megaloblastic or macrocytic anemia. Other symptoms of folate de? ciency include poor growth, problems in nerve development and function, diarrhea, and in? ammation of the tongue. Groups most at risk of a folate de? ciency include pregnant women and premature infants because of their rapid rate of cell division and growth; the elderly because of their limited intake of foods high in folate; alcoholics because alcohol inhibits folate absorption; and tobacco smokers because smoke inactivates folate in the cells lining the lungs. Folate intake is related to neural tube defects A low folate intake increases the risk of birth defects that affect the brain and spinal cord called neural tube defects (Figure 8. 16). The exact role of folate in neural tube development is not known, but it is necessary for a critical step called neural tube closure. Neural tube closure occurs very early in pregnancy—only 28 days after conception—when most women may not yet even know they are pregnant. Therefore to reduce the risk of these defects, folate status must be adequate before a pregnancy begins and during the early critical days of pregnancy (see Chapter 12).

However, folate is not the only factor contributing to neural tube defects. Not every pregnant woman with low folate levels gives birth to a child with a neural tube defect. Instead, these birth defects are probably due to a combination of factors that are aggravated by low folate levels. Folate status may affect heart disease and cancer risk Low folate intake may increase the risk of heart disease because of its relation to homocysteine levels (see Figure 8. 13). Low folate status may also increase the risk of developing cancer

L Megaloblastic or macrocytic anemia * A condition in which there are abnormally large immature and mature red blood cells and a reduction in the total number of red blood cells and the oxygen-carrying capacity of the blood. L Neural tube defects Irregularities in * the formation of the portion of the embryo that develops into the brain and spinal cord. These occur early in development and result in brain and spinal cord abnormalities. Vertebrae Spinal cord Vertebrae Spinal cord FIGURE 8. 16 Early in pregnancy, the neural tube develops into the brain and spinal cord.

If folate is inadequate during neural tube closure, neural tube defects such as spina bi? da, shown here, occur more frequently. In spina bi? da the bones that make up the back do not completely surround the spinal cord, allowing membranes, ? uid, and, in severe cases, the nerves of the spinal cord to bulge out where they are unprotected. Normal spine Spine with spina bifida 252 Chapter 8 The Vitamins For more information on folic acid and birth defects, go to the Spina Bifida Association of America at www. sbaa. org of the uterus, cervix, lungs, stomach, esophagus, and colon. Although folate de? iency does not cause cancer, it has been hypothesized that low folate intake enhances an underlying predisposition to cancer. The relation between folate and cancer is strongest for colon cancer. Alcohol consumption greatly increases the cancer risk associated with a low folate diet. 11 L Dietary folate equivalent (DFE) A unit * used to express the amount of folate available to the body that accounts for the higher bioavailability of folic acid in supplements and enriched foods compared to folate found naturally in foods. One DFE is equivalent to 1 g of folate naturally occurring in food, 0. 6 g of synthetic folic acid from forti? d food or supplements consumed with food, or 0. 5 g of synthetic folic acid consumed on an empty stomach. Vegetables, legumes, oranges, and grains are good sources of folate Asparagus, oranges, legumes, liver, and yeast are excellent food sources of folate. Fair sources include grains, corn, snap beans, mustard greens, and broccoli, as well as some nuts. Small amounts are found in meats, cheese, milk, fruits, and other vegetables (Figure 8. 17). Folic acid is added to enriched grain products, including enriched breads, ? ours, corn meal, pasta, grits, and rice. If you look at the label on a bag of enriched ? ur you will see that it is forti? ed with folic acid. Folic acid is a stable form of folate that rarely occurs naturally in food but is used in supplements and forti? ed foods; it is more easily absorbed than natural folate. In the 3-year period after the forti? cation of grain products with folic acid, the incidence of neural tube defects decreased by 25%. 12 Women of childbearing age need extra folate The RDA for folate is set at 400 g dietary folate equivalents (DFEs) per day for adult men and women. Expressing needs in DFEs allows one unit to be used for all the forms of folate; one DFE is equal to 1 g of food folate, 0. g of synthetic folic acid from forti? ed food or supplements consumed with food, or 0. 5 g of synthetic folic acid consumed on an empty stomach. Because supplementing folic acid early in pregnancy has been shown to reduce neural tube defects, a special recommendation is made for women capable of becoming pregnant; 400 g of synthetic folic acid from forti? ed foods and/or supplements is recommended in addition to the food folate consumed in RDA Sunflower seeds (1/4 c) Walnuts (1/4 c) Peanuts (1/4 c) Lentils (1 c) Pork (3 oz) Beef (3 oz) Trout (3 oz) Chicken (3 oz) 2% Milk (1 c) Cheddar cheese (1. oz) Orange juice (1 c) Kiwi (2 med) Apple (1 med) Corn (1/2 c) Asparagus (1/2 c) Spinach, raw (1 c) Oatmeal (1 c) Spaghetti (1 c) Brown rice (1 c) White bread (2 sl) Whole-wheat bread (2 sl) 0 100 200 Folate (µg DFE) 300 400 FIGURE 8. 17 Folate content of selections from each group of the Food Guide Pyramid. The dashed line represents the RDA for adults. Legumes, forti? ed foods, and some fruits and vegetables are good sources. (George Semple) Folate and Vitamin B12 Are Needed for Cell Division 253 PIECE IT TOGETHER Is It Hard to Meet Folate Recommendations?

Marcia would like to have a baby but before she tries to conceive, she wants to be sure she is in the best condition possible. She consults her physician who gives her a clean bill of health but suggests she make sure she is getting enough folate. women who are capable of becoming pregnant should consume 400 g of folic acid from forti? ed foods or supplements each day in addition to the folate found in a varied diet. Folic acid is added to enriched grains, so it can be found in any food that contains enriched grains; you can check the ingredient list to see if the food you have chosen contains added folic acid.

The percent Daily Value includes both the natural folate and added folic acid. W HY IS FOLATE A CONCERN FOR WOMEN CAPABLE OF BECOMING PREGNANT ? M Research shows that consuming extra folic acid can reduce the risk of a type of birth defect called a neural tube defect that affects an unborn child’s brain or spinal cord. For the extra folic acid to be bene? cial, it must be consumed for at least a month before conception and continued for a month after. Since many pregnancies are not planned, it is recommended that all women of childbearing age consume 400 g of folic acid from forti? d foods or supplements. Marcia records her food intake for 1 day to determine her folate intake: Food Breakfast Oatmeal, regular Milk Banana Orange juice Coffee Lunch Hamburger Hamburger bun French fries Coke Apple Dinner Chicken Refried beans White rice Tortilla Salad Salad dressing Milk Cake Total Servings 1 cup 1 cup 1 medium 8 ounces 1 cup 1 1 20 pieces 12 ounces 1 medium 3 ounces 1/2 cup 1 cup 1 1 cup 1 Tbsp 1 cup 1 piece Total Folate ( g) 2 12 22 75 0 11 32 24 0 4 4 106 80 60 64 1 12 32 541 g FOLATE INTAKE MEET THE W HICH FOODS IN M ARCIA’ S DIET ARE HIGHEST IN FOLATE ?

O F THESE , WHICH DO YOU THINK HAVE BEEN FORTIFIED WITH FOLIC ACID ? M Food Rice Orange juice Your answers: Amount 80 g 75 g Natural Forti? ed W HY IS THE OATMEAL LOW IN FOLATE BUT THE OTHER GRAIN PRODUCTS ARE GOOD FOLATE SOURCES ? M Oatmeal is a whole grain, so it has not been forti? ed with folic acid. The other grain products in her diet, such as the white rice, tortilla, and hamburger bun, are re? ned so they contain added folic acid. Even though Marcia is trying to increase her intake of the folic acid form of this vitamin she should not pass up whole grains—they are good sources of most B vitamins, minerals, and ? er. L IST SOME MODIFICATIONS M ARCIA COULD MAKE IN HER DIET TO PROVIDE THE RECOMMENDED AMOUNTS AND FORMS OF FOLATE ? M Your answer: W OULD YOU RECOMMEND M ARCIA TAKE A FOLATE SUPPLEMENT ? D OES M ARCIA’ S RDA? Your answer: M Yes. Marica consumes 541 g of folate, which is greater than the RDA of 400 g DFE, but her doctor told her that M 254 Chapter 8 The Vitamins Not everyone needs a folate supplement. If you are male or a female who is too young or too old to have a baby, the amount of folate you get from a healthy diet will meet your needs.

Even women of childbearing age can get enough folic acid without a supplement if they eat enough folic acid forti? ed foods. a varied diet. The folic acid form is recommended because it is the form that has been shown to reduce birth defects. This recommendation is made for all women of childbearing age because folate is needed very early in a pregnancy—before most women are aware that they are pregnant. To get 400 g of folic acid, you would need to eat 4 to 6 servings of forti? ed grain products each day or take a supplement containing folic acid.

Excess folate can mask anemia caused by vitamin B12 de? ciency Although extra folate is recommended for pregnant women, too much is a concern for some groups. There is no known folate toxicity, but a high intake may mask the early symptoms of vitamin B12 de? ciency, allowing it to go untreated so irreversible nerve damage can occur. The UL for adults is set at 1000 g per day of folate from supplements and/or forti? ed foods. This value was determined based on the progression of neurological symptoms seen in patients who are de? cient in vitamin B12 and taking folate supplements.

L Pernicious anemia An anemia * resulting from vitamin B de? ciency that 12 Vitamin B12: absorption requires intrinsic factor If you lived in the early 1900’s and developed a condition called pernicious anemia, it was a death sentence. There was no cure. In the 1920’s researchers George Minot and William Murphy pursued their belief that pernicious anemia could be cured by something in the diet. Their experiments were able to restore good health to patients by feeding them about 4 to 8 ounces of slightly cooked liver at every meal. Today we know that liver contains high levels of vitamin B12.

We also know that pernicious anemia is not actually caused by a lack of the vitamin in the diet, but rather an inability to absorb the vitamin. Vitamin B12 absorption requires a protein called intrinsic factor that is produced by cells in the stomach lining. With the help of stomach acid, intrinsic factor binds to vitamin B12 and this vitamin B12-intrinsic factor complex is then absorbed in the small intestine. When very large amounts of the vitamin are consumed, some can be absorbed without intrinsic factor. This is why Minot and Murphy were able to cure pernicious anemia with extremely high dietary doses of the vitamin.

Today, pernicious anemia is treated with injections of vitamin B12 rather than plates full of liver. occurs due to a lack of a protein called intrinsic factor needed to absorb dietary vitamin B12. L Intrinsic factor A protein produced * in the stomach that is needed for the absorption of adequate amounts of vitamin B12. L Cobalamin The chemical term for * vitamin B . 12 Vitamin B12 is needed for nerve function Vitamin B12, also known as cobalamin, is necessary for the maintenance of myelin, which is the coating that insulates nerves and is essential for nerve transmission.

Vitamin B12 is also needed for the production of energy from certain fatty acids and to convert homocysteine to methionine (see Figure 8. 13). This reaction also converts folate from an inactive form to a form that functions in DNA synthesis. Because of the need for vitamin B12 in folate metabolism, a de? ciency can cause a secondary folate de? ciency and, consequently, macrocytic anemia. Symptoms of vitamin B12 de? ciency include an increase in blood homocysteine levels and anemia that is indistinguishable from that seen in folate de? ciency. Other symptoms include numbness and tingling, bnormalities in gait, memory loss, and disorientation due to degeneration of the myelin that coats the nerves, spinal cord, and brain. If not treated, this eventually causes paralysis and death. Consuming extra folate can mask a vitamin B12 de? ciency When the diet is de? cient in vitamin B12, consuming extra folate can mask the vitamin B12 de? ciency by preventing the appearance of anemia. If the de? ciency is not treated, the other symptoms of B12 de? ciency, such as nerve damage, progress and can be irreversible. This connection between folate and vitamin B12 has raised concerns that our folate-forti? d food supply may allow B12 de? ciencies to go unnoticed. So far, this