Chapter 10 - The Water-Soluble Vitamins: B Vitamins and Vitamin C

Pellagra

Due to niacin deficiency, produces the symptoms of diarrhea, dermatitis, dementia, and eventually death (referred to as 4 deaths).

If a dietary supplement poses a significant risk of illness to consumers, what agency must prove harm before removing the product from the market?

FDA

Vitamin B6

Family of compounds - pyridoxal, pyridoxine, and pyridoxamine. Primary active coenzyme form in PLP (pyridoxal phosphate), which is active in more than 100 reactions, including carb, fatty acid, and amino acid metabolism. PLP participates in synthesis of heme, nucleic acids, and lecithin. Stored extensively in muscle tissue (unlike other water-solubles). Deficiency leads to diminished syntehsis of key neurotransmitters, abnormal compounds produced in the brain during tryptophan metabolism. Symptoms include depression and confusion, advanced symptoms include abnormal brain waive patterns and convulsions. Low levels can increase risk of some cancers and cardiovascular disease. Alcohol destroys vitamin B6 in body; when alcohol is metabolized, body produces acetaldehyde. When accumulated, it dislodges PLP coenzyme from its enzyme, breaking down and being excreted subsequently. Isoniazid is a medication that is used to inhibit growth of tuberculosis bacterium, but it acts as an antagonist to B6 by binding to and inactivating it. B6 supplements are needed when being treated with this medication. B6 toxicity is possible, leading to neurological damage, so a UL was set. B6 is found in meat, fish, poultry, vegetables and fruit. Loss occurs when food is heated.

Research has shown that the risk for neural tube defects is lowered by taking supplements of

Folate

Which of the following is true regarding B vitamins and homocysteine metabolism?

Folate catabolizes homocysteine

On a per-kcalorie basis, which of the following foods is richest in vitamin B6?

Fruits

Hydrophobic fat-soluble vitamins

Vitamins A, D, E, and K.

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.

Oxidative stress

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

What is a free radical?

A molecule with at least one unpaired electron

Inositol

A nonessential nutrient that can be made in the body from glucose. Inositol is a part of the cell membrane structures.

Carnitine

A nonessential, nonprotein amino acid made in the body from lysine that helps transport fatty acids across the mitochondrial membrane.

Cofactor

A small, inorganic or organic substance that facilitates the action of an enzyme.

Histamine

A substance produced by cells of the immune system as part of a local immune reaction to an antigen.

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.

False negative

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

False positive

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

Free radical

An unstable molecule with one or more unpaired electrons.

Which of the following is a general function of vitamin C?

Antioxidant agent

Vitamin B12

B vitamin characterized by presence of cobalt, active forms of coenzyme B12 are methylcobalamin and deoxyadenosylcobalamin. Closely related to folate, each depending on other for activation. B12 removes methyl group to activate folate coenzyme. When folate gives up its methyl group, B12 coenzyme becomes activated. It first is separated from protein by the HCl in stomach, pepsin, allowing B12 to go from stomach to small intestine, binding with intrinsic factor. That combination travels to end of small intestine, where receptors recognize the complex. Receptors do not recognize B12 without intrinsic factor. B12 is then gradually absorbed into bloodstream as intrinsic factor is degraded, transport of B12 in blood depends on specific binding proteins. Like folate, B12 enters enterohepatic circulation, continuously being secreted into bile and delivered to intestines, reabsorbed. Since B12 is reabsorbed, most healthy people don't have a deficiency. Deficiency is typically due to inadequate absorption, not poor intake. Occurs from either lack of HCl or lack of intrinsic factor. Older adults develop atrophic gastritis, damaging the stomach lining, develops as a response to iron deficiency or infection with Helicobacter pylori. Lacking stomach cells results in less HCl and intrinsic factor, causing inadequate B12 absorption. B12 deficiency due to atrophic gastritis is known as pernicious anemia. Primarily found in foods derived from animals, can take several years for people who stop eating animal products to develop deficiency symptoms due to body recycling its B12. Neurological degeneration appears more rapidly in infants born to mothers with unsupplemented vegan diets or untreated pernicious anemia. Since B12 is required to convert folate to active form, most apparent deficiency symptom is the anemia commonly seen in folate deficiency, characterized by large, immature red blood cells, indicating slow DNA synthesis and inability to divide. If folate is given when B12 is needed, devastating neurological symptoms will occur. B12 maintains the sheath surrounding nerve fibers, so folate "cures" blood symptoms of B12 deficiency, but cannot stop nerve symptoms. Folate then "masks" B12 deficiency. Advanced neurological symptoms include creeping paralysis beginning at extremities and working inwards and up the spine. Early detection and correction is necessary to prevent permanent nerve damage and paralysis. Sufficient folate allows for neurological symptoms of B12 deficiency to develop without evidence of anemia and cognitive decline is especially rapid. That being said, no UL has been set since no toxicity affects have been reported for excess B12. B12 is exclusively in food derived from animals. Greatest bioavailability is in milk and fish. Vegans can rely on B12 fortified soy milk or supplements. Yeast grown on B12 enriched medium and mixed with that medium provides some, but it does not actually contain active B12. Research found that amounts listed on labels of these plant products are inaccurate and misleading because B12 is in an inactive unavailable form. particularly vulnerable to losses in cooking, microwave heating inactivates B12. Preservation requires using oven or stovetop instead of microwave to cook meats and milk products.

Biotin

B vitamin that functions as coenzyme in metabolism to carry activated CO2, critical in TCA cycle because biotin carries carbon to 3-carbon pyruvate, replenishing oxaloacetate, the 4-carbon compound needed to combine with acetyl CoA to keep TCA cycle turning. Biotin coenzyme also participates in gluconeogenesis, fatty acid synthesis, breakdown of certain fatty acids and amino acids. Deficiency is rare, symptomized with skin rash, hair loss, neurological impairment. No adverse effects found from high biotin intake, therefore no UL has been set. Widespread in foods, so eating a variety of foods protects against deficiencies. Some is also synthesized by GI tract bacteria, but the amount is not enough to substantially contribute to biotin absorption.

Riboflavin

B vitamin, coenzyme forms are FMN (flavin mononucleotide) and FAD (flavin adenine dinucleotide). FAD picks up 2 hydrogens during energy metabolism from TCA cycle and delivers them to electron transport chain. Lack of the vitamin causes inflammation of membranes of the mouth, skin, eyes, and GI tract. No UL established, excess appears to cause no harm. Most prevalent milk, but is also in whole-grain/enriched grains, or in dark greens (broccoli, turnip greens, asparagus, spinach). UV light destroys riboflavin, so milk is sold in cardboard or opaque plastic instead of clear bottles. It is stable to heat, cooking won't destroy it.

Niacin

B vitamin, 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. Niacin refers to 2 chemical structures: nicotinic acid and nicotinamide (also known as niacinamide). Nicotinic acid is easily converted into nicotinamide by the body, which is the major form of niacin in the blood. Unique among B vitamins, in that body can make it from amino acid tryptophan. Occurs only after protein synthesis needs have been met. 60mg dietary tryptophan=1mg niacin. Deficiency causes pellagra. Excessive amounts can lead to pharmacological effect in lowering LDL and raising HDL, but can be toxic depending on the patient. Prevalent in meats, poultry, fish, legumes, and enriched grains. Mushrooms, potatoes, tomatoes also very rich source. Niacin is less vulnerable to losses during cooking, fairly heat resistant.

Thiamin

B vitamin, the coenzyme form is TPP (thiamin pyrophosphate). TPP participates in conversion of pyruvate to acetyl CoA. Deficiency can lead to beriberi. There is no UL determined, since no adverse effects have been identified with consuming too much thiamin. Pork is an exceptionally rich source of thiamin.

Folate

B vitamin; also known as folic acid, folacin, or pteroylglutamic acid (PGA). Coenzyme forms are DHF (dihydrofolate) and THF (tetrahydrofolate). GI enzymes hydrolyze polyglutamate to monoglutamate (folate with 1 glutamate attached). Monoglutamate is then attached to methyl group (CH3) and delivered to liver and other body cells. Activation of folate requires methyl group being removed by enzyme requiring the help of B12. Without that help, folate becomes trapped inside cells in methyl form, unavailable to support DNA synthesis and cell growth. Liver incorporate excess folate into bile, travels in same enterohepatic circulation as bile. If GI tract cells are damaged (such as from alcohol abuse) folate is lost. Deficiency develops rapidly and further damages GI tract. Since folate is needed for cell replication, its needs are heightened when pregnant. Folate also breaks down amino acid homocysteine, so without folate, homocysteine would accumulate, potentially increasing the formation of blood clots and atherosclerotic lesions. Folate deficiency is known as macrocytic or megaloblastic anemia, characterized by large, immature red blood cells. Folate deficiency leads to DNA damage destroying many of the red blood cells as they attempt to divide and mature, resulting in fewer but larger red blood cells that cannot carry oxygen or travel through capillaries as efficiently as normal ones can. Folate fortification in food led to this being unlikely in the United States. Deficiency can arise due to inadequate intake, but it can also be due to the amount in need changing due to pregnancy, cancer, skin-destroying diseases (like chicken pox, measles), burns, blood loss, GI tract damage, etc. Folate is most likely to be vulnerable to interactions with drugs, leading to secondary deficiency. Anticancer drugs have a chemical structure similar to folate's structure, displacing vitamin from enzymes and interfering with normal metabolism. Cancer cells need real vitamins to multiply, without it, they die. Anticancer drugs affect both cancerous and healthy cells, creating folate deficiency for all cells. Aspirin inhibits action of folate-requiring enzymes, antacids limit absorption of folate. UL has been established, high enough levels due to supplements can lead to obscuring vitamin B12 deficiency and delay diagnosis of neurological damage.

Hydrophilic water-soluble vitamins

B vitamins (thiamin, riboflavin, niacin, biotin, pantothenic acid, vitamin B6, folate, and vitamin B12), and vitamin C.

Pernicious anemia

Blood disorder reflecting a 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 would be a very good source of vitamin C for the lacto-ovo-vegetarian?

Broccoli

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 HCl and intrinsic factor - 2 substances needed for B12 absorption.

Coenzymes

Complex organic molecules that work with enzymes to facilitate the enzymes' activity. Many coenzymes have B vitamins as part of their structures.

Intrinsic factor

Glycoprotein (a protein with short polysaccharide chains attached) secreted by the stomach cells that bind with B12 in the small intestine to aid in the absorption of B12.

Antioxidants

In the body, substances that significantly decrease the adverse effects of free radicals on normal physiological functions.

Biotin can be synthesized by

Intestinal bacteria

Anemia

Literally "too little blood". Anemia is any condition in which too few red blood cells are present, or the red blood cells are immature (and therefore large) or too small or contain too little hemoglobin to carry the normal amount of oxygen to the tissues. Anemia is not a disease itself but can be a consequence of many different disease conditions, including many nutrient deficiencies, bleeding, excessive red blood cell destruction, and defective red blood cell formation.

Neural tube defects

Malformation of the brain, spinal cord, or both during embryonic development that often results in lifelong disability or death. The two main types of neural tube defects are spina bifida and anencephaly.

Nonvitamins

Mistaken for vitamins but are not essential. Includes inositol and carnitine, both made by the body. Inositol is a part of cell membrane structures, carnitine transports long-chain fatty acids from cytosol to mitochondria for oxidation. Others include PABA (para-aminobenzoic acid, component of folate's chemical structure), bioflavonoids (vitamin P or hesperidin), pyrroloquinoline quinone (methoxatin), orotic acid, lipoic acid, ubiquinone (coenzyme Q10). "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, and is actually potentially dangerous).

Choline

Not defined as a vitamin, but is an essential nutrient commonly grouped with B vitamins. Body uses choline to make acetylcholine and lecithin. Choline supports structure and function of brain and spinal cord during fetal development by supporting neural tube closure and enhancing learning performance. Body can make choline from methionine, but synthesis alone is insufficient for body's needs. Impact of deficiency is not fully understood, UL is based on life-threatening effect in lowering blood pressure. Found in variety of foods like milk, eggs, peanuts.

Ascorbic acid

One of the two active forms of vitamin C. Many people refer to vitamin C by this name.

Vitamins

Organic, essential nutrients required in small amounts by the body for health. Vitamins regulate body processes that support growth and maintain life.

Which vitamin is known to sustain substantial losses during processing of food?

Pantothenic acid

Pantothenic acid

Part of chemical structure of coenzyme A (same CoA that forms acetyl COA, key compound in several metabolic pathways. Deficiency is rare, symptoms involve general failure of all body systems and include fatigue, GI distress, neurological disturbances. "Burning feet" syndrome affected prisoners of war in Asia during WWII thought to have been caused by pantothenic acid deficiency. No toxic effects have been reported for excess intake, so no UL has been established. It is widespread in foods, particularly in beef, poultry, whole grains, potatoes, tomatoes, broccoli. It is readily destroyed by freezing, canning, refining processes.

Vitamin C

Parts company with B vitamins in its mode of action. Can serve as a cofactor helping specific enzyme performance, can also act as antioxidant participating in more general ways. Acts like a bodyguard for water-soluble substances; stands ready to sacrifice itself to save other nutrients. Protects from oxidative stress of free radicals and may play important role in preventing diseases. Enhances iron absorption by protecting iron from oxidation. Helps form fibrous structural protein of connective tissues (collagen). Helps with hydroxylation of carnitine, also participates in conversions of tryptophan and tyrosine to serotonin and norepinephrine, respectively. Also assists in making hormones, like thyroxine. Mostly contained in adrenals. Blood concentrations are unlikely to increase after having about 200 mg (less than 2 cups of orange juice). Smokers will need more due to the oxidants depleting vitamin C. Deficiency is characterized by gum bleeding easily around teeth, and capillaries under the skin breaking spontaneously, resulting in pinpoint hemorrhages. Scurvy symptoms can begin after about a month of lacking vitamin C - including further hemorrhaging, muscular degeneration, skin becoming rough, brown, scaly, wounds fail to heal since scar tissue can't form, bone rebuilding falters, ends of long bones become softened, malformed, fractures develop. Teeth become loose as cartilage around them weakens. Hysteria and depression can also occur. Scurvy is readily resolved by increasing vitamin C intake, with 100mg per day being sufficient, curing it in about 5 days. UL was established due to excess causing GI distress and diarrhea. Can also interfere with medicine, large amounts being taken are excreted in the urine, obscuring results of tests used to detect glucose or ketones in diagnosing diabetes. Excessive vitamin C can result in false positive results, or false negatives. Anticlotting medications might counteract the effect by taking massive doses of vitamin C. Kidney disease, with tendency toward gout, or genetic abnormality altering vitamin C's breakdown to its excretion products are prone to forming kidney stones if taking large doses. Supplements might adversely affect people with iron overload since vitamin C enhances iron absorption and releases iron from body stores, resulting in too much iron causing cellular damage typical of free radicals. Primarily found in fruits and vegetables.

Precursors

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

Tolerable Upper Intake Levels (UL)

The Committee on Dietary References Intakes (DRI) addresses the possibility of adverse effects from high doses of nutrients by establishing the UL, which defines the highest amount of a nutrient that is likely not to cause harm for most healthy people when consumed daily.

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.

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 =1mg niacin or 60mg tryptophan.

Neural tube

The embryonic tissue that forms the brain and spinal cord.

Antiscorbutic factor

The original name for vitamin C.

Bioavailability

The rate at and the extent to which a nutrient is absorbed and used.

Collagen

The structural protein from which connective tissues such as scars, tendons, ligaments, and foundations of bones and teeth are made.

Beriberi

The thiamin-deficiency disease characterized by muscle weakness and/or edema. 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 appear together, with one set of symptoms predominating.

Glossitis

The tongue becomes smooth and swollen due to atrophy of the tissue, indicative of vitamin B deficiency.

Scurvy

The vitamin C deficiency disease.

Why might vitamin C supplements be beneficial in treating the common cold?

They deactivate histamine