2. Chapter 10: The Water- Soluble Vitamins

3. Overview of Water-Soluble Vitamins Dissolve in water Easily destroyed or washed out during food storage and preparation. Are easily absorbed and excreted Not stored in the body tissues and must be replaced each day. Seldom reach toxic levels

4. Overview of Water-Soluble Vitamins Many B-complex vitamins needed for energy metabolism and form an integral part of coenzymes Help the body metabolize CHO, lipids and amino acids Thiamin pyrophosphate – TPP (thiamin) Flavin Adenine Dinucleotide (FAD), Flavin Mononucleotide (FMN)(riboflavin) Nicotinamide Adenine Dinucleotide (NAD), Nicotinamide adenine dinucleotide phosphate (NADP)( niacin ) Coenzyme A ( pantothenic acid ) Pyridoxal phosphate (PLP) ( Vitamin B-6 ) Tetrahydrofolic acid ( folate ) Cofactor (biotin)

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

6. Distinction between water-soluble and fat-soluble vitamins Fat-soluble vitaminsWater-soluble vitamins Absorption Lymph first, then the bloodDirect absorption into the blood Transport Protein carriers used by manyFreely transported Requireme nts Periodic doses requiredFrequent doses required Storage Stored in cells associated with fat Circulate in water- filled parts of the body Excretion Less readily excreted, tend to remain in fat-storage sites Excreted in urine by kidneys Toxicity Toxic levels likely when consuming supplements Toxic levels possible when consuming supplements

7. Thiamin Functions as a coenzyme: Thiamin pyrophosphate (TPP) In metabolism of CHO; & amino acids Decarboxylation of alpha keto acids (page 227) Enzyme is Transketolase: coverts glucose to a 5- carbon sugar

8. Food Sources of Thiamin Wide variety of food White bread, pork, hot dogs, luncheon meat, cold cereal Enriched grains/ whole grains

9. 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

10. Deficiency of Thiamin Beriberi first observed in the Far East where polished rice replaced rice where bran remained intact. characterized by loss of sensation in the hands and feet, muscular weakness, advancing paralysis,and abnormal heart action. Peripheral neuropathy 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 Involuntary eye movement; double vision Ataxia: staggering, poor muscle coordination Mental confusion, “drunken stupor”

12. Riboflavin Coenzymes: Flavin mononucleotide (FMN) Flavin adenine dinucleotide (FAD) Oxidation-reduction reactions Electron transport chain Citric Acid Cycle Catabolism of fatty acids: beta oxidation FMN shuttles hydrogen ions and electrons to into the electron transport chain

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

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

15. Deficiency of Riboflavin Ariboflavinosis Glossitis, cheilosis, seborrheic dermatitis, stomatitis, eye disorder, throat disorder, nervous system disorder

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

17. Food Sources of Niacin Mushroom Enriched grains Beef, chicken, turkey, fish, eggs,milk Amino acid tryptophan can be converted to niacin Heat stable; little cooking loss 60mg tryptophan can be converted into 1 mg niacin Estimate by dividing the total gram of protein by 6

18. Deficiency of Niacin Pellagra 3 Ds: Dermatitis, dementia, diarrhea appeared in Europe in early 1700s when corn became staple food corn lacks niacin and tryptophan

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

20. Content Review How are water-soluble vitamins different from fat- soluble vitamins? Many of the B vitamins all function as a coenzyme, what is a coenzyme? What disease is associated with a deficiency of niacin? What disease is associated with a deficiency of thiamin? What is the Enrichment Act? What nutrients are involved?

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

22. Food Sources of Pantothenic Acid Meat Milk Mushroom Liver Peanut Adequate Intake = 5 mg/day Average intake meets AI

23. Biotin Free and bound form Biocytin (protein bound form) Freed by Biotinidase in small intestine Infant with genetic defect : low levels of biotinidase Metabolism of CHO, fat, protein (C skeleton) DNA synthesis

24. Functions of Biotin Required to convert pyruvate to oxaloacetate (TCA cycle) and thus ATP production. Required for fatty acid synthesis Breaks down leucine Sources Widely distributed in foods and is produced by intestinal bacteria Liver, egg yolk, whole grains, cauliflower are good food sources Avidin in raw egg whites bind biotin

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

26. Biotin 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

27. Vitamin B-6 family: 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

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

29. Other Role 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

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

31. RDA for Vitamin B-6 1.3 - 1.7 mg/day for adults Daily Value set at 2 mg Average intake is more than the RDA

32. Deficiency of Vitamin B-6 Microcytic hypochromic anemia Seborrheic dermatitis Convulsion, depression, confusion Reduced immune response Peripheral nerve damage

33. Factors That Affect B-6 Requirement Alcohol reduces PLP formation L -DOPA-medication used to treat Parkinson’s disease and Isoniazid-antituberculosis medication Reduce blood concentration of PLP Need extra vitamin B-6

34. B-6 As A Medicine? PMS B-6 to increase the level of serotonin Improve depression Not a reliable treatment Toxicity potential Can lead to irreversible nerve damage with > 200 mg/day Upper level set at 100 mg/day

35. Folate (Folic acid, Folacin) Consists of pteridine group, para-aminobenzoic acid (PABA), and glutamic acid Coenzyme form: tetrahydorfolic acid (THFA) Produce many identical deficiency signs and symptoms as vitamin B-12 Vitamin B-12 is needed to recycle folate coenzyme

36. Absorption, Metabolism of Folate Absorbed in the monoglutamate form with the 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)

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

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

39. RDA for Folate 400 ug/day for adults Daily Value is set at 400 ug Dietary folate equivalents (DFE) are units to express folate needs throughout life except during child bearing years DFE = [(total synthetic folate) x 1.7] + total food folate intake

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

41. Megaloblastic Anemia

42. Neural Tube Defects Spina bifida Anencephaly Importance of folate before and during pregnancy

43. 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 Upper Level for synthetic folate is 1 mg Excess can mask vitamin B-12 deficiency

44. Vitamin B-12 Cyanocobalamin, methlcobalamin, 5-deoxyadenosylcobalamin Contains cobalt Folate metabolism Synthesized exclusively by bacteria, fungi, and algae Maintenance of the myelin sheaths Rearrange 3-carbon chain fatty acids so can enter the Citric Acid Cycle

45. Absorption of Vitamin B-12

46. 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

47. 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

48. RDA for Vitamin B-12 2.4 ug/ day for adults and elderly adults Average intake exceeds RDA B-12 stored in the liver; little is lost Non-toxic

49. Functions of Vitamin B-12 Helps convert methylmalonyl CoA to succinyl CoA (citric acid cycle) Recycles folate coenzymes Nerve functions Maintains myelin sheath Megalobalstic anemia

50. Deficiency of Vitamin B-12 Pernicious anemia Nerve 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

51. Homocysteine and the B Vitamins

52. Choline Absorbed from the small intestine All tissues contain choline Excess choline is converted to betaine

53. 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

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

55. 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)

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

57. 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

58. Functions of Vitamin C Reducing agent (antioxidant) Iron absorption Synthesis of carnitine, tryptophan to serotonin, thyroxine, cortiscosteroids, aldosterone, cholesterol to bile acids Immune functions Synthesis of other compounds Questionable as to vitamin C’s role as an antioxidant in people

59. Collagen Synthesis

60. 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

61. 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 gm/day Excess intake will not cure the common cold

62. Deficiency of Vitamin C Scurvy Deficient for 20-40 days Fatigue, pinpoint hemorrhages Bleeding gums and joints, hemorrhages Associated with poverty

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

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

65. 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

66. 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

67. 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

68. 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

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

70. Types 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

71. Cancer Deaths

72. 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

73. 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

74. Cancer Initiation, Promotion, and Progression

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

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

77. 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

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

79. Role of Diet Excessive intake of calories increases the risk of cancer Excessive body fat affects 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

80. Fat and Cancer The National Academy of Sciences recommends 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

81. 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

82. 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

83. Warning Signs (CAUTION) 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