THE B VITAMINS

You might have wondered why there are so many B vitamins. Initially, the B vitamins were thought to be a single large B vitamin complex, but once the structures and functions were better understood, researchers realized they were actually separate vitamins with distinct functions. To better distinguish the compounds, they retained the title “B vitamin” but gave each vitamin a number, and later, a name. So, the B vitamins include thiamin (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), biotin (B7), cobalamin (B12), and folate (B9). Some are commonly called by their chemical name, while others are identified by their numerical designation, particularly when there are multiple chemical forms of the vitamin.

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In the early twentieth century, corn was cheap and was an important source of dietary energy and protein for poor people, particularly in rural areas. Niacin (and the niacin precursor tryptophan) has limited bioavailability in corn without first processing it with an alkaline substance such as lime. Pellagra is a disease caused by niacin deficiency.
Firma V/Shutterstock

All B vitamins function as coenzymes, with most playing critical roles in energy metabolism. Energy metabolism refers to the chemical reactions that break down carbohydrates, fats, and proteins to release energy, and the chemical reactions that use energy to construct molecules and carry out body processes. Coenzymes are not actually part of the enzyme structure; rather, they assist enzymes by accepting and donating hydrogen ions, electrons, and other molecules during reactions. In other words, the B vitamins do not provide energy to the cells, but they play a critical role in energy transformation. (INFOGRAPHIC 11.4)

INFOGRAPHIC 11.4 B Vitamins Function as Coenzymes Coenzymes associate with enzymes to form an active complex that is capable of catalyzing a chemical reaction.
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Question 11.2

image Describe the basic function of a coenzyme.

The basic function of a coenzyme is to activate an enzyme by binding with it. This allows the desired substrates to also bind to the enzyme and the reaction to take place.

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Beriberi patient on crutches. Beriberi is a disorder of the nervous system caused by a lack of vitamin B1 (thiamin) in the diet. It can cause weight loss, emotional disturbances, and weakness and pain in the limbs, among other symptoms.
Science Source

B vitamins also participate in amino acid metabolism; reactions that build and maintain bones, muscles, and red blood cells; and the synthesis of nucleic acids that are needed for DNA synthesis and cell division.

Many of the B vitamins are interrelated and interdependent, in that the successful functioning of one B vitamin often depends on the successful functioning of others. Likewise, deficiencies of B vitamins rarely occur in isolation, because many B vitamins typically occur together in the same types of foods, and chances are that a diet inadequate in one B vitamin would be low in others. However, a deficiency of a single B vitamin wreaked havoc in the not-too-distant past.

BERIBERI a condition characterized by extreme weakness; caused by thiamin deficiency

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A painful degenerative disease was sweeping East Asia in the closing decades of the 1800s, causing its victims to experience terrible muscle wasting and eventual heart failure. The disease was known as beriberi, and was at one time fairly common among populations whose diet consisted largely of rice.

Technology of the time made it possible to refine white rice cheaply and efficiently. The hulls of the rice were removed and discarded to improve the storage life of the rice—brown rice would spoil faster than white rice. What the people didn’t understand, however, was that removing the rice hull removed many essential nutrients from the rice.

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Rice with and without hulls. The white “polished” rice on the right has been stripped of the nutrients found in the hulls.
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As chance would have it, a Dutch researcher named Christiaan Eijkman noticed that chickens fed a diet of white rice became ill; so ill that they would stumble drunkenly and collapse on their sides. When the brown hulls were added into their diet the chickens recovered. Eijkman surmised incorrectly that there were illness-causing compounds within the white rice, and that something in the rice hulls cured it.

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Polish-born American biochemist Dr. Casimir Funk, who coined the term “vitamin,” is shown in New York City, January 20, 1953.
AP Photo

Many years later a Polish-born American biochemist Casimir Funk was attempting to isolate and identify the exact anti-beriberi factor present in the hulls of brown rice. Funk called the factor vitamine (from vital and amine) and the term was later shortened to “vitamin.” In fact, in 1912, Funk was the first to propose that beriberi, scurvy, rickets, and pellagra were caused by deficiencies of specific vitamin(e)s.

Thiamin

Funk named his first vitamin B1; today, it’s commonly known as thiamin. The coenzyme form of thiamin is needed to provide energy from the breakdown of glucose, fatty acids, and some amino acids—where it participates in reactions that release carbon dioxide (CO2). It is also required for the production of sugars needed for the synthesis of RNA and DNA. Good food sources of thiamin include pork and fortified grain products. (INFOGRAPHIC 11.5)

INFOGRAPHIC 11.5 Food Sources of Thiamin
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NEUROTRANSMITTERS chemical substances involved in transmitting signals between nerve cells

The disruptions in metabolism that occur with a thiamin deficiency alter the production of several neurotransmitters, leading to mental disturbances, such as apathy, irritability, and confusion. Other deficiency symptoms include fatigue and muscle weakness.

Although beriberi is not common in the United States today, another thiamin deficiency, called Wernicke–Korsakoff syndrome, can be found in many developed nations. Alcohol abuse is the leading cause of Wernicke–Korsakoff syndrome, with as many as 80% of chronic alcohol abusers showing signs of deficiency, often resulting in severe neurological disturbances. Alcoholics are at high risk of thiamin deficiency because alcohol consumption displaces the intake of nutrient-rich foods, decreases thiamin absorption, increases its excretion in urine, decreases its storage in the liver, and decreases conversion of thiamin into its coenzyme. In fact, chronic alcohol abuse increases the risk of deficiency for most of the water-soluble vitamins through several of these mechanisms.

Niacin

Recall that pellagra was sweeping the southern United States in the early part of the twentieth century, and that Dr. Goldberger had determined that eating a diet that contained a variety of foods was curative. It wasn’t until 1937, eight years after his death, that the specific curative compound in food was identified. An American biochemist gave a dose of nicotinic acid (niacin) to a dog suffering from a disease known as black tongue, the canine equivalent of pellagra. The dog was cured, and subsequent testing determined that niacin was also an effective treatment for humans with pellagra.

NIACIN EQUIVALENTS (NEs) the total amount of niacin that is provided by a food from both the preformed vitamin and that which can be synthesized in the body from tryptophan in the food

Niacin is rich in meats (especially poultry) and fish, as well as peanuts, mushrooms, and fortified cereals. It can also be synthesized in the body, albeit rather inefficiently, from the amino acid tryptophan found primarily in protein-rich foods. About 1 mg of niacin is made from every 60 mg of tryptophan provided in food, so dietary recommendations are often given in niacin equivalents (NEs). NEs are used to describe the contribution to dietary intake of the preformed niacin and that which can be synthesized from the tryptophan provided by foods.

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Niacin in the ingredients list. Flour loses nutrients in processing; food manufacturers enrich flour by returning some B vitamins and iron to the product.
Martin Shields/Alamy

Therapeutically, doctors sometimes prescribe niacin in high doses to help lower “bad” LDL cholesterol and increase “good” HDL cholesterol. However, as with most vitamins, taking high doses creates side effects and patients must be monitored to ensure the potential benefits outweigh the risks.

Typically, the first sign of pellagra is fatigue, because niacin plays such an important role in the conversion of the macronutrients in food into energy. In addition to being involved in energy metabolism, niacin is also required for the synthesis of glucose, fatty acids, cholesterol, and steroid hormones. It also plays critically important roles in DNA repair, cell signaling, and the regulation of gene expression.

FORTIFICATION the addition of vitamins and/or minerals to a food product

ENRICHMENT a process used to replace some of the B vitamins (and iron) that are extracted from grains when they are refined

To reduce the incidence of pellagra, the U.S. government instituted niacin fortification by adding niacin to grain products in 1938. Although manufacturers today fortify foods for various reasons, the original goal of food fortification was to correct identified nutrient deficiencies by adding specific vitamins and/or minerals to foods. Refined grain products may also be enriched with niacin, meaning that some of the B vitamins (and iron) that were extracted from the grains as part of the refining process were returned. Today, bread products and fortified cereals are a primary source of niacin in our diets, along with protein-rich foods, particularly poultry. Though bread products are not particularly high in niacin, they contribute significantly to our niacin intake because they are so abundant in our diet. (INFOGRAPHIC 11.6)

INFOGRAPHIC 11.6 Food Sources of Niacin
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There is no evidence that consuming too much niacin from food leads to adverse effects. However, people who take high doses of niacin in supplements may suffer side effects such as flushing and gastrointestinal distress. Individuals who are prescribed niacin to control their cholesterol also must be carefully monitored to ensure that excessive amounts of the vitamin do not cause liver problems or glucose intolerance.

Riboflavin

Riboflavin was the second B vitamin to be isolated and its function is similar to that of niacin: It’s important for the metabolism of proteins, lipids, and carbohydrates. Milk and other dairy products are particularly good sources of riboflavin, and it is because riboflavin is destroyed by ultraviolet light that milk is kept in paper cartons or opaque plastic containers. A riboflavin deficiency (known as ariboflavinosis) is characterized by cracks and redness on the lips and corners of the mouth, swelling of tissues in the mouth, and a sore throat. Deficiency may be seen with chronic alcohol abuse or malabsorptive conditions and seldom occurs by itself; it typically occurs along with deficiencies in other B vitamins. No toxicity with riboflavin consumption from food or supplements has been observed. (INFOGRAPHIC 11.7)

INFOGRAPHIC 11.7 Food Sources of Riboflavin
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Vitamin B6

Vitamin B6—sometimes referred to by one of its chemical names, pyridoxine—functions as a coenzyme in the release of glucose from stored glycogen and in amino acid metabolism. It is required for the conversion of the amino acid tryptophan to niacin. The body also uses vitamin B6 for the production of hemoglobin (found in red blood cells) and neurotransmitters.

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Deficiency in vitamin B6 can cause various signs and symptoms, including anemia, impaired immune function, weakness, dermatitis, and neurological disorders such as confusion and convulsions. Poor vitamin B6 status has also been associated with an increased risk of cardiovascular disease. Adverse and sometimes irreversible neurological effects such as pain and numbness in the extremities can occur in people who take vitamin B6 supplements in doses that result from intakes above the UL. (INFOGRAPHIC 11.8)

INFOGRAPHIC 11.8 Food Sources of Vitamin B6 (Pyridoxine)
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Pantothenic acid

Another B vitamin, pantothenic acid, has critical functions in energy metabolism and is also required for the synthesis of fatty acids, cholesterol, steroid hormones, and two neurotransmitters. Named for the Greek word pantothen, meaning “from all sides,” deficiencies of pantothenic acid are rare because of its widespread occurrence in virtually all foods.

Folate

Folate is an important vitamin particularly for developing fetuses. Toward the end of World War II, Nazis blockaded western Netherlands, limiting millions of people’s access to food and causing a terrible six months of starvation known as the Dutch Hunger Winter. The story of the Dutch struggle was featured in Chapter 1 of this book. As tragic as the famine was—it is believed to have killed more than 20,000 Dutch people—the event also gave scientists a rare opportunity to study the biological consequences of nutrient deficiency, particularly during pregnancy. Babies conceived during the famine, when mothers were unable to eat folate-rich foods, were twice as likely as children conceived before or after to have spinal defects like spina bifida (see Chapter 18). Research suggests that folate may be among the most important nutrients for pregnant women during early pregnancy, because the nervous system requires folate to carry out a number of fundamental metabolic processes.

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DIETARY FOLATE EQUIVALENT (DFE) a system established to account for the differences in bioavailability between folic acid in dietary supplements or foods, and folate found naturally in food

Folate—its synthetic form, folic acid, is used in supplements—acts as a coenzyme in the metabolism of certain amino acids and production of nucleic acids that are required for DNA and RNA synthesis, so it is essential for normal cell division and development. A calculation known as the dietary folate equivalent (DFE) is used to consider the difference in bioavailability between the different types of folate. Not only is the folate found naturally in foods absorbed half as well as the folic acid added to foods, it is also degraded much more readily. (INFOGRAPHIC 11.9)

INFOGRAPHIC 11.9 Understanding Folate Equivalents Dietary folate equivalent (DFE) units are used to account for differences in the efficiency of absorption of naturally occurring food folate and synthetic folic acid from dietary supplements or fortified foods.
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Question 11.3

image If a peanut butter sandwich provides 25 mcg of folate and 30 micrograms of folic acid, how many mcg DFE units does this provide? Identify the source of the folic acid and the folate in this sandwich.

The peanut butter sandwich provides 25 mcg DFE + (1.7 mcg DFE x 30 mcg folic acid) = 76 mcg DFE. The folate is from the peanut butter, and the folic acid is from the fortified bread.

Like the Dutch women who were pregnant during the Hunger Winter, expectant mothers today who don’t consume enough folate are at an increased risk of giving birth to children with abnormalities of the spinal cord and brain known as neural tube defects. These children are also more likely to develop schizophrenia, autism, attention problems, and language delays.

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MEGALOBLASTIC ANEMIA a type of anemia characterized by larger-than-normal red blood cells; usually caused by folate or vitamin B12 deficiency

Folate deficiency also causes megaloblastic anemia, a form of blood abnormality characterized by large, immature, and sometimes irregularly shaped red blood cells. Folate deficiencies can also cause poor growth and gastrointestinal tract disturbances because the rate of DNA synthesis is highest during growth or in rapidly dividing cells, such as those found in the brush border of the small intestine. Some research suggests that folate may reduce the risk of heart disease because a high level of the amino acid homocysteine, which folate converts (along with vitamin B12) into another amino acid (methionine), has been linked with an increased risk of heart disease. A 2012 meta-analysis of 14 epidemiologic studies found that for every 200 extra micrograms of folate consumed per day, an individual’s risk of developing heart disease dropped by 12%. However, because randomized controlled trials have not found folic acid supplements to be effective at reducing the risk of heart disease, they are not recommended by the American Heart Association. (INFOGRAPHIC 11.10)

INFOGRAPHIC 11.10 Megaloblastic Anemia A deficiency in either folate or vitamin B12 disrupts DNA synthesis and therefore impairs cell division of red blood cells and other rapidly dividing cells in the body.
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Question 11.4

image Which cellular structure is present in megaloblastic red blood cells that is absent in mature red blood cells?

Megaloblastic red blood cells contain large nuclei. Normal red blood cells have no nuclei.

The RDA for folate for men and women older than 19 years is 400 mcg. The consumption of at least 400 mcg of folic acid daily from supplements, fortified foods, or both, in addition to consuming food folate from a varied diet prior to conception has been shown to prevent approximately two-thirds of all cases of neural tube defects, the most common of all birth defects, in newborns. Once a woman becomes pregnant, her RDA of folate goes up to 600 mcg, which she can get from supplements or fortified foods, such as enriched cereals and bread products, in addition to foods that contain naturally occurring folate. Foods with plentiful naturally occurring folate include green leafy vegetables, avocado, broccoli, and beans. (INFOGRAPHIC 11.11)

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INFOGRAPHIC 11.11 Food Sources of Folate
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People who abuse alcohol, have malabsorptive conditions, or take certain medications (such as high doses of anti-inflammatory drugs or anticonvulsants) are at an increased risk of developing folate deficiencies. The UL for folate applies to synthetic forms found in supplements (folic acid) and is set at 1,000 mcg per day. No adverse effects are known to occur with the amounts of folate found naturally in foods, but getting too much folic acid from fortified foods or supplements can mask vitamin B12 deficiency symptoms.

Vitamin B12

Vitamin B12 is unique among the vitamins for several reasons: It has the largest and most complex structure and it contains a mineral (cobalt; for this reason it is known as cobalamin). Unlike other water-soluble vitamins, it is stored in significant quantities in the liver. Because vitamin B12 found naturally in foods is bound to food proteins, gastric acid from the stomach is required for it to be released from those proteins. It must then bind to a protein produced in the stomach called intrinsic factor. The cobalamin-intrinsic factor complex is then absorbed in the small intestine.

B12 acts as a coenzyme in only two reactions, one of which is important in deriving energy from several amino acids, and the other is the aforementioned reaction involving folate and the conversion of homocysteine to methionine. This last reaction is also indispensable for activating folate; therefore, without B12, folate becomes trapped in an unusable form. For this reason B12 is also required for DNA synthesis and cell division.

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Because the metabolism of folate and vitamin B12 are closely linked, a deficiency in B12 produces the same megaloblastic anemia that is seen with a folate deficiency, causing increased fatigue during physical activity.

As a B12 deficiency continues, it often causes a tingling or lack of sensation in the legs and arms, and may progress to include cognitive impairment and problems with motor control. The risk of developing a deficiency of vitamin B12 increases as we age. Diminished or compromised food intake, sometimes seen in the aging population, decreases the amount of B12 available through the diet. In addition, between 10% and 30% of older people don’t properly absorb the B12 that is found naturally in food because of a common condition that reduces the production of both gastric acid and intrinsic factor by the stomach. For this reason, individuals older than 50 years are advised to mainly meet their B12 RDA by consuming foods fortified with vitamin B12 or by taking supplements containing B12, because this form of B12 is not bound to food proteins and therefore does not rely on gastric acid for absorption. A 2013 study noted that new diagnostic tests have revealed a “surprisingly high prevalence” of a subtle form of subclinical B12 deficiency among the elderly. Low vitamin B12 status is associated with more rapid cognitive decline as we age, adding more importance to adequate B12 intake.

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Get your vitamin B12. Some people don’t consume enough vitamin B12 to meet their needs, while others can’t absorb enough, no matter how much they take in. As a result, vitamin B12 deficiency is relatively common, especially among older people.
laflor/Getty Images

Animal foods such as meat, poultry, fish, and dairy are the only natural sources of vitamin B12; some grain and soy products are fortified with B12. Vegans (those who consume no animal products, including dairy and eggs) must either take supplements or regularly consume fortified food products to meet their RDA. (INFOGRAPHIC 11.12)

INFOGRAPHIC 11.12 Food Sources of Vitamin B12 (Cobalamin)
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PERNICIOUS ANEMIA a condition caused by a failure to produce intrinsic factor, resulting in vitamin B12 malabsorption

Gastric bypass patients are also at risk for B12 deficiency because less intrinsic factor is produced by the stomach after the surgery, and less B12 is released in the stomach as much of the stomach is “bypassed.” Other groups at risk for developing B12 deficiencies include those with pernicious anemia—a condition caused by the failure to produce intrinsic factor (as may often be the case in the elderly), resulting in vitamin B12 malabsorption and megaloblastic anemia. In these cases, treatment may require periodic injections of vitamin B12, or the oral administration of very high daily doses (generally 1 mg per day) of the vitamin. Very high doses can result in absorption by passive diffusion of a small amount in the absence of intrinsic factor.