Chapter 10: The Water-Soluble Vitamins

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

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)

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

Distinction between water-soluble and fat-soluble vitamins

Fat-soluble vitamins Water-soluble vitamins

Absorption Lymph first, then the blood Direct absorption into the blood

Transport Protein carriers used by many Freely transported

Requirements

Periodic doses required Frequent 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

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

Food Sources of Thiamin

Wide variety of food White bread, pork, hot dogs, luncheon meat,

cold cereal Enriched grains/ whole grains

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

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

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”

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

Food Sources of Riboflavin

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

RDA for Riboflavin

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

Deficiency of Riboflavin

Ariboflavinosis Glossitis, cheilosis, seborrheic dermatitis,

stomatitis, eye disorder, throat disorder, nervous system disorder

Niacin

Nicotinic acid (niacin) & nicotinamide (niacinamide)

Coenzyme Nicotinamide adenine dinucleotide (NAD) Nicotinamide adenine dinucleotide phosphate

(NADP) Oxidation-reduction reaction

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

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

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

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?

Pantothenic Acid Part of Coenzyme-A Essential for metabolism of CHO, fat,

protein

Glucose

Fatty acids Acetyl-CoA Amino Acids

Alcohol

Food Sources of Pantothenic Acid

Meat Milk Mushroom Liver Peanut Adequate Intake = 5 mg/day Average intake meets AI

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

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

Biotin Needs

Adequate Intake is 30 ug/day for adults This may overestimate the amount

needed for adults No Upper Limit for biotin

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

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

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

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

Food Sources of Vitamin B-6

Meat, fish, poultry Whole grains (not enriched back) Banana Spinach Avocado Potato Heat and alkaline sensitive

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

Deficiency of Vitamin B-6

Microcytic hypochromic anemia Seborrheic dermatitis Convulsion, depression, confusion Reduced immune response Peripheral nerve damage

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

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

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

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)

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

Food Sources of Folate

Liver Fortified breakfast cereals Grains, legumes Foliage vegetables Susceptible to heat, oxidation, ultraviolet

light

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

Deficiency of Folate

Similar signs and symptoms of vitamin B-12 deficiency

Pregnant women Alcoholics

Interferes with the enterohepatic circulation of bile/folate

Megaloblastic Anemia

Neural Tube Defects

Spina bifida Anencephaly Importance of folate

before and during pregnancy

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

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

Absorption of Vitamin B-12

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

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

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

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

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

Homocysteine and the B Vitamins

Choline

Absorbed from the small intestine All tissues contain choline Excess choline is converted to

betaine

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

Food Sources of Choline

Widely distributed Milk Liver Eggs Peanuts Lecithins added to food Deficiency rare

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)

Deficiency of Choline

Decrease choline stores Liver damage (fatty livers)

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

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

Collagen Synthesis

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

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

Deficiency of Vitamin C

Scurvy Deficient for 20-40 days Fatigue, pinpoint hemorrhages Bleeding gums and joints, hemorrhages Associated with poverty

Vitamin-Like Compounds

Carnitine Inositol Taurine Lipoic acid Synthesized in the body at the expense of

amino acids and other nutrients

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

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

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

Lipoic Acid

Found in meats, liver, and yeast Redox agent Needed in reactions in which CO2 is lost

from a substrate Regenerates vitamin C and glutathione

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

Cancer

Many diseases Formation of tumors (neoplasms)

Benign Malignant

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

Cancer Deaths

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

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

Cancer Initiation, Promotion, and Progression

Cytochrome P-450

Prevents cancer initiation In the liver and intestinal cells Converts dangerous

compounds into harmless water-soluble metabolites

Cancer Initiation

Exposure to carcinogen Alteration of DNA Is relatively short

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

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

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

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

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

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

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