2. Perspectives in Nutrition 5 th ed. Gordon M.Wardlaw, PhD, RD, LD, CNSD PowerPoint Presentation by Dana Wu Wassmer, MS, RD

3. Chapter 10: The Water-Soluble Vitamins

4. Overview of Water-Soluble Vitamins Dissolve in water Generally readily excreted Subject to cooking losses Function as a coenzyme Participate in energy metabolism 50-90% of B vitamins are absorbed Marginal deficiency more common

5. Enrichment Act of 1941 and 1998 Many nutrients lost through milling process of grains Grain/cereal products are enriched Thiamin, riboflavin, niacin, folate, iron Whole grains contain original nutrients Enriched grains still deficient in B-6, magnesium and zinc

6. Thiamin Contains sulfur and nitrogen group Destroyed by alkaline and heat Coenzyme: Thiamin pyrophosphate (TPP)

7. Absorption, Transport, Metabolism of Thiamin Absorbed in the jejunum by a carrier- mediated system Transported by RBC in the blood Excess quickly excreted in the urine

8. Function of Thiamin (Fig. 10-2) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

9. Coenzyme: Thiamin Pyrophosphate (TPP) Synthesis of neurotransmitter Hexose monophosphate shunt Removes CO 2 from some amino acids Convert pyruvate to acetyl-CoA CoA NAD + NADH + H + Glucose Pyruvate Acetyl-CoA Citric CO 2 Acid Cycle

10. Deficiency of Thiamin Occurs where polished rice is the only staple Dry beriberi –Weakness, nerve degeneration, irritability, poor arm/leg coordination, loss of nerve transmission Wet beriberi –Edema, enlarge heart, heart failure

11. Wenicke-Koisakoff Syndrome Mainly in alcoholics –Alcohol diminishes thiamin absorption –Alcohol increases thiamin excretion –Poor quality diet Nystagmus: involuntary eye movement; double vision Ataxia: staggering, poor muscle coo coordination; mental confusion, “drunken stupor”

12. Food Sources of Thiamin Wide variety of food White bread, pork, hot dogs, luncheon meat, cold cereal Enriched grains/ whole grains Thiaminase found in raw fish

13. RDA For Thiamin 1.1 mg/day for women 1.2 mg/day for men Most exceed RDA in diet Surplus is rapidly lost in urine; non toxic

14. Who is at Risk For Deficiency? Poor Alcoholics Elderly Diet consisting of highly processed foods

15. Riboflavin Coenzymes: –Flavin mononucleotide (FMN) –Flavin adenine dinucleotide (FAD) Oxidation-reduction reactions Electron transport chain Citric Acid Cycle Catabolism of fatty acids

16. Absorption, Transport, & Metabolism of Riboflavin HCL in the stomach release riboflavin from its bound forms Absorption –Active or facilitated transport during low to moderate intake –Passive absorption during high intake –Increase with intake Transported by a protein carrier in the blood

17. Functions of Riboflavin Accepts electrons Electron Transport Chain FAD FADH 2 Succinate Fumarate Citric Acid Cycle Participates in beta oxidation FMN shuttles hydrogen ions and electrons to into the electron transport chain Metabolism of oxidized glutathione

18. Deficiency of Riboflavin Ariboflavinosis –Glossitis, cheilosis, seborrheic dermatitis, stomatitis, eye disorder, throat disorder, nervous system disorder Occurs within 2 months Usually in combination with other deficiencies

19. Glossitis (Fig. 10-4) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

20. Who is at Risk For Deficiency? –Rare –Low milk/dairy intake –Alcoholics –Long term phenobarbital use

21. Food Sources of Riboflavin Milk/products Enriched grains Liver Oyster Brewer’s yeast Sensitive to uv radiation (sunlight) Stored in paper, opaque plastic containers

22. RDA for Riboflavin 1.1 mg/day for women 1.3 mg/day for men Average intake is above RDA Toxicity not documented

23. Niacin Nicotinic acid (niacin) & nicotinamide (niacinamide) Coenzyme –Nicotinamide adenine dinucleotide (NAD) –Nicotinamide adenine dinucleotide phosphate (NADP) Oxidation-reduction reaction Metabolic reactions

24. Absorption, Transport and Storage of Niacin Readily absorbed from the stomach and small intestine Absorption: active transport and passive diffusion Transported from the liver to all of the tissues where it is converted to the coenzymes

25. Functions of Niacin NAD and NADP participates in 200+ reactions in the body 2 NAD + 2NADH + H + Glucose Pyruvate NAD + NADH + H + Pyruvate Lactate NAD + NADH + H + Isocitrate Alpha-ketogluterate NAD + NADH + H + Alpha-ketogluterate Succinyl CoA NAD + NADH + H + Malate Oxaloacetate Electron transport chain Citric Acid Cycle

26. Deficiency of Niacin Pellagra –3 Ds –Occurs in 50-60 days –Decrease appetite & weight Prevented with an adequate protein diet Enrichment Act of 1941 Only dietary deficiency disease to reach epidemic proportions in the U.S. Who is at risk? –(Untreated) corn as main staple, poor diet, Hartnup disease, alcoholics

27. Dermatitis of Pellegra (Fig. 10-5) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

28. Food Sources of Niacin Mushroom Enriched grains Beef, chicken, turkey, fish Heat stable; little cooking loss 60mg tryptophan can be converted into 1 mg niacin

29. RDA for Niacin 14 NE/day for women 16 NE/day for men

30. Niacin as a Medicine 75-100 x RDA can lower LDL and TG and increase HDL Slow/ reverse progression of atheroscelerosis with diet and exercise Toxicity effects –Flushing of skin, itching, nausea, liver damage

31. Pantothenic Acid Part of Coenzyme-A Essential for metabolism of CHO, fat, protein Glucose Fatty acids Acetyl-CoA Amino Acids Alcohol

32. Deficiency of Pantothenic Acid Rare Burning foot syndrome, listlessness, fatigue, headache, sleep disturbance, nausea, abdominal distress Alcoholics at risk Usually in combination with other deficiencies

33. Food Sources of Pantothenic acid “From every side” Meat Milk Mushroom Liver Peanut Adequate Intake = 5 mg/day Average intake meets AI

34. Biotin Free and bound form Biocytin (protein bound form) Biotinidase in small intestine Metabolism of CHO, fat, protein (C skeleton) DNA synthesis

35. Functions of Biotin Assists in the addition of CO 2 to substances Carboxylation of acetyl-CoA to form malonyl-CoA for the elongation of a fatty acid chain Addition of CO 2 to pyruvate to yield oxaloacetate Breaks down leucine Allows 3 essential amino acids to be oxidized for energy

36. Food Sources of Biotin Cauliflower, yolk, liver, peanuts, cheese Intestinal synthesis of biotin Biotin content only available for a small number of foods Unsure as to bioavailablity of synthesized biotin We excrete more than we consume Avidin inhibits absorption –> a dozen of raw eggs a day to cause this effect

37. Biotin Needs Adequate Intake is 30 ug/day for adults This may overestimate the amount needed for adults No Upper Limit for biotin

38. Who is at Risk For Deficiency? Rare High intake of raw egg white diet Alcoholics Biotinidase deficiency Anticonvulsant drug use Signs & symptoms: skin rash, hair loss, convulsion, neurological disorders, impaired growth in children

39. Vitamin B-6: Pyridoxal, Pyridoxine, Pyridoxamine Main coenzyme form: pyridoxal phosphate (PLP) Activate enzymes needed for metabolism of CHO, fat, protein Transamination Synthesis of hemoglobin and oxygen binding and white blood cells Synthesis of neurotransmitters

40. Absorption and Metabolism of Vitamin B-6 Absorbed passively All three forms of B-6 are phosphorylated in the liver Binds to albumin for transport in the blood B-6 is stored in the liver and muscle tissue Excess is excreted in urine

41. Functions of Vitamin B-6 Participates in 100+ enzymatic reactions Decarboxylation of amino acid (decarboxylase) Transamination reaction (transaminase) Structural rearrangement of amino acids (racemase) RBC synthesis CHO metabolism Lipid metabolism Neurotransmitter Synthesis Conversion of tryptophan to niacin

42. Other Roles of Vitamin B-6 Homocysteine From the metabolism of methionine Produces toxic effect on arterial walls (atherosclerosis) Metabolized by vitamins B-6, B-12 and folate

43. Deficiency of Vitamin B-6 Microcytic hypochromic anemia Seborrheic dermatitis Convulsion, depression, confusion Reduce immune response Peripheral nerve damage Who is at risk? –Elderly –Alcoholics Alcohol decreases absorption Destroy the coenzyme form

44. Food Sources of Vitamin B-6 Meat, fish, poultry Whole grains (not enriched back) Banana Spinach Avocado Potato Heat and alkaline sensitive

45. RDA for Vitamin B-6 1.3 mg/day for adults 1.7 mg/day for men over 50 1.5 mg/day for women over 50 Daily Value set at 2 mg Average intake is more than the RDA

46. Factors That Affect B-6 Requirement L -DOPA-medication used to treat Parkinson’s disease and Isoniazid-antituberculosis medication Reduce blood concentration of PLP Need extra vitamin B-6 Preeclampsia Reduce blood concentration of PLP Will supplementation will reduce preeclampsia?

47. B-6 As A Medicine? PMS –B-6 to increase the level of serotonin –Improve depression –Not a reliable treatment Carpal tunnel syndrome Toxicity potential Can lead to irreversible nerve damage with > 200 mg/day

48. Folate (Folic acid, Folacin) Consists of pteridine group, para- aminobenzoic acid (PABA), and glutamic acid Coenzyme form: tetrahydorfolic acid (THFA)

49. Absorption, Metabolism of Folate Absorbed in the monoglutamate form with help of folate conjugase Actively absorbed during low to moderate intake Passively absorbed during high intake Delivered to the liver where it is changed back to the polyglutamate form Mostly stored in the liver Excreted in the urine and bile (enterohepatic circulation)

50. Functions of Folate DNA synthesis –Transfer of single carbon units –Synthesis of adenine and guanine –Anticancer drug methotrexate Homocysteine metabolism Neurotransmitter formation

51. Deficiency of Folate Similar signs and symptoms of vitamin B- 12 deficiency Pregnant women Alcoholics –Interferes with the enterohepatic circulation of bile/folate

52. Megaloblastic Anemia (Fig. 10-7) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

53. Neural Tube Defects Spina bifida Anencephaly Importance of folate before and during pregnancy (Fig. 10-8) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

54. Food Sources of Folate Liver Fortified breakfast cereals Grains, legumes Foliage vegetables Susceptible to heat, oxidation, ultraviolet light

55. RDA for Folate 400 ug/day for adults Daily Value is set at 400 ug

56. Toxicity of Folate Epilepsy Skin, respiratory disorder FDA limits nonprescription supplements to 400 ug per tablet for non-pregnant adults OTC Prenatal supplement contains 800 ug Excess can mask vitamin B-12 deficiency

57. Vitamin B-12 Cyanocobalamin. methlcobalamin, 5-deoxyadenosylcobalamin Contains cobalt Folate metabolism Maintenance of the myelin sheaths Rearrange 3-carbon chain fatty acids so can enter the Citric Acid Cycle

58. Absorption of Vitamin B-12 (Fig. 10-10) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

59. Therapy for Ineffective Absorption Many factors can disrupt this process Monthly injections of vitamin B-12 Vitamin B-12 nasal gel Megadoses of vitamin B-12 to allow for passive diffusion

60. Functions of Vitamin B-12 Helps convert methylmalonyl CoA to succinyl CoA (citric acid cycle) RBC formation Nerve functions –Maintains myelin sheath Megalobalstic anemia

61. Vitamin B-12 and Homocysteine (Fig. 10-11) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

62. Deficiency of Vitamin B-12 Pernicious anemia –Never degeneration, weakness –Tingling/numbness in the extremities (parasthesia) –Paralysis and death –Looks like folate deficiency Usually due to decreased absorption ability Achlorhydria especially in elderly Injection of B-12 needed Takes ~20 years on a deficient diet to see nerve destruction

63. Who is at Risk For Deficiency? Vegans Breastfed infants of vegan moms Elderly Individuals with AIDS or HIV

64. Food Sources of Vitamin B-12 Synthesized by bacteria, fungi and algae (Stored primarily in the liver) Animal products Organ meat Seafood Eggs Hot dogs Milk

65. RDA for Vitamin B-12 2.4 ug/ day for adults and elderly adults Average intake exceeds RDA B-12 stored in the liver Non-toxic

66. Choline Absorbed from the small intestine All tissues contain choline Excess choline is converted to betaine Newest essential nutrient

67. Functions of Choline Precursor for acetylecholine (neurotransmitter) Precursor for phospholipids (such as lecithin) Involved in the export of VLDL from the liver Precursor for the methyl donor betaine Assist in the conversion of homocysteine to methionine

68. Food Sources of Choline Widely distributed Milk Liver Eggs Peanuts Lecithins added to food Deficiency rare

69. Deficiency of Choline Decrease choline stores Liver damage (fatty livers)

70. Needs for Choline Adequate Intake is 550 mg/day for adult males Adequate Intake is 425 mg/day for adult females Normal consumption is ~700-1000 mg/day High doses associated with fishy body odor, vomiting, salivation, sweating, hypotension, GI effects Upper Level is set at 3.5 g/day (3500 mg/day)

71. Vitamin C Ascorbic acid (reduced form), dehydroascorbic acid (oxidized form) Synthesized by most animals (not by human) Absorbed by a specific energy dependant transport system Passive transport if intake is high Decrease absorption with high intakes Excess excreted

72. Functions of Vitamin C Reducing agent (antioxidant) Iron absorption Synthesis of carnitine, tryptophan to serotonin, thyroxine, cortiscosteroids, aldosterone, cholesterol to bile acids Immune functions Cancer prevention? Collagen synthesis

73. Collagen Synthesis (Fig. 10-12) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

74. Antioxidant Can donate and accept hydrogen atoms readily Water-soluble intracellular and extracellular antioxidant Must be constantly enzymatically regenerated Needs are higher for smokers

75. Deficiency of Vitamin C Scurvy –Deficient for 20-40 days –Fatigue, pinpoint hemorrhages –Bleeding gums and joints. Hemorrhages –Associated with poverty Rebound scurvy –immediate halt to excess vitamin C supplements Who is at risk? –Infants, elderly men –Alcoholics, smokers

76. Food Sources of Vitamin C Citrus fruits Potatoes Green peppers Cauliflower Broccoli Strawberries Romaine lettuce Spinach Easily lost through cooking Sensitive to heat Sensitive to iron, copper, oxygen

77. RDA for Vitamin C 90 mg/day for male adults 75 mg/day for female adults +35 mg/day for smokers Average intake ~72 mg/day Fairly nontoxic (at <1 gm) Upper Level is 2 g/day Warning to people with hemochromatosis, oxalate kidney stones

78. Vitamin-Like Compounds Choline Carnitine Inositol Taurine Lipoic acid Synthesized in the body at the expense of amino acids and other nutrients

79. Carnitine Found in meat and dairy products Synthesized in the liver from amino acids lysine and methionine Transports fatty acids into the mitochonrida Aids in the removal of excess organic acids

80. Inositol Myo-inositol Found in animal products Synthesized from glucose Precursors to eicosanoids Metabolizes calcium ions Metabolism is altered in people with diabetics, multiple sclerosis, kidney failure, certain cancers

81. Taurine Found only in animal products Synthesized from methionine and cysteine Associated with the photoreceptor in the eye Antioxidant activity in the white blood cell and pulmonary tissue CNS function, platelet aggregation, cardiac contraction, insulin action, cell differentiation and growth

82. Lipoic Acid Found in meats, liver, and yeast Redox agent Needed in reactions in which CO 2 is lost from a substrate Regenerates vitamin C and glutathione

83. Bogus “Vitamins” Para-aminobenzoic acid (PABA) –Part of folate, but not able to make folate –A part of a B-complex family for bacteria Laetrile –“Vitamin B-17” –Contains cyanide, promoted as a cancer cure Bioflavonoids –“Vitamin P” --no nutritional requirement Pangamic Acid –“Vitamin B-15” and is illegal

84. Cancer Many diseases Formation of tumors (neoplasms) –Benign –Malignant

85. Type of Cancers Carcinomas –Cells that covers the body, including the secretory organs Sarcomas –Connective tissues and bones Leukemias –Blood forming tissues Lymphomas –Lymph nodes or lymphoid tissues

86. Cancer Deaths (Fig. 10-15) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

87. Carcinogenesis Protooncogenes –Genes that cause a resting cell to divide Tumor Suppressor Genes –Genes that prevent cells from dividing –P53 gene finds error on the DNA and repairs it Oncogene –The cancer gene –A protoonocogene out of control DNA Repair Mechanism

88. Cell Replication Telomeres –Caps at the ends of chromosomes Telomerase –Enzyme that maintains the length and completeness –Daughter cells are slightly shorter and telomerase activity decreases –Cell undergoes apoptosis Malignant tumor cells, the telomerase activity increases—the cells can live indefinitely

89. Cancer Initiation, Promotion, and Progression (Fig. 10-16) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

90. Cytochrome p-450 Prevents cancer initiation In the liver and intestinal cells Converts dangerous compounds into harmless water-soluble metabolites

91. Cancer Initiation Exposure to carcinogen Alteration of DNA Is relatively short

92. Cancer Promotion May last for months or years Damage is “locked” in Cell division increases –Promoters: estrogen, alcohol, maybe dietary fat Decrease time available for repair

93. Cancer Progression Final stage Cancer cells proliferate and forms a mass Invade surrounding tissue Metastasize to other tissues Heredity can only explain a small percentage of cancers Environment contribute to most of the cancer

94. Role of Diet Excessive intake of calories increases the risk of cancer Excessive body fat affect sex hormone production High intake of fruits and vegetables is associated with lower risk High intake of meats and protein is associated with higher risk Excessive alcohol increases the risk Excessive charcoal broiling increases risk Nitrosamines (from nitrite) increases risk Mycotoxins (from fungi) increases risk

95. Fat and Cancer The National Academy of Sciences recommend 30% of total calories from fat Effects of the type of fat to cancer There are still wide gaps in knowledge linking fat and cancer Excessive intake is a more likely cause

96. Calcium,Vitamin D and Cancer Calcium intake is inversely related to cancer Calcium binds to bile acids in the colon Vitamin D inhibits progression of cancerous polyps Vitamin D inhibits rapid colon/rectal cell growth in patients with ulcerative colitis

97. Recommendations to Reduce the Risk for Cancer Remain physically active Avoid obesity Engage in physical training that promotes lean muscle mass Consume abundance of fruits and vegetables Consume plenty of low-fat/nonfat dairy products Avoid high intakes of red meat and animal fat Avoid excessive alcohol

98. Warning Signs Early detection is critical Unexplained weight loss A change in bowel or bladder habits A sore that does not heal Unusual bleeding or discharge A thickening or lump in the breast or elsewhere Indigestion or difficulty in swallowing An obvious change in a wart or a mole A nagging cough or hoarseness