Vitamins

Discovery of Vitamins
Vitamin Vitamin A Vitamin D Vitamin E Vitamin K Thiamin (B1) Riboflavin (B2) Niacin (B3) Year Discovered 1912-1914 (1913?) 1922 1922 1929 1912 1926 1937 Scientists Elmer V. McCollum and M. Davis Edward Mellanby Herbert Evans and Katherine Bishop Henrik Dam Casimir Funk – coined term “Vitamines” but e dropped off in 1920 because not all vitamins are composed of amines D. T. Smith, E. G. Hendrick Conrad Elvehje Richard Kuhn Paul Gyorgy Paul Gyorgy Lucy Wills Karl A. Folkers and Alexander R. Todd A. Hoist and T. Froelich

Pantothenic Acid (B5) 1933 but isolated in 1939 Pyridoxine (B6) Biotin (B7) Folate (B9) Cyanocobalamin (B12) Vitamin C 1941 1934 1933 1926, but isolated in 1948 1912

Fat-soluble Vitamins
Overview of Vitamins
Overview  Are essential organic substances needed in small amounts in the diet for normal function, growth, and maintenance of body tissues  Vitamins A, D, E, and K dissolve in organic solvents whereas the B vitamins and vitamin C dissolve in water  Usually can’t be synthesized in sufficient quantities or synthesized at all  Used in correcting deficiency diseases and some used to treat non-deficiency diseases  Found in plant and animal sources supply vitamins in the diet  Little difference between “natural” vitamins isolated from foods versus “synthesized” Historical  Scurvy in sailors cured by lime juice  Correlation between chemicals factors and cures for deficiencies  Many discovered during the late 19th, early 20th century  As they were discovered were labeled using letters (A, B, C, D, E)  Compounds continually identified as being essential and in the future may be classified as vitamins Storage  Fat-soluble vitamins are not readily excreted and stored in fat cells  Water-soluble vitamins are readily excreted from the body Vitamin Toxicity  Fat-soluble vitamins are not excreted readily and because they are stored in body cells, accumulation may cause toxicity  Vitamin A and D toxicities are observed more often than others Inadequate absorption Preservation of vitamins in food  Vitamins can be lost as a result of: improper storage and excessive cooking Absorption of fat-soluble vitamins  Dependent on fat absorption efficiency – mediated by bile salts and lipase  40-90% of fat-soluble vitamins are absorbed in the small intestine  delivered using chylomicrons and lipoproteins  individuals with cystic fibrosis, celiac disease, and Crohn’s disease have poor ability to absorb fats and fat-soluble vitamins









  

Vitamin A
Vitamin A is a generic term for a class of compounds called retinoids Types of retinoids: retinol, retinal, and retinoic acid Carotenoids: pigment in fruits and vegetables used in forming vitamin A Alpha & Beta-carotene are examples of provitamins converted into vitamin A (retinol) The release of vitamin A from food requires bile, digestive enzymes from the pancreas and intestinal tract, and integration into micelles 90% of vitamin A absorbed in small intestine Retinoids stored in liver and carotenoids stored in liver and adipose Cellular Retinoid-Binding Proteins (CRBP or RBP) - needed for the transport of retinoids into cell Functions:  Visual  Retinal in retina of the eye turns visual light into nerve signals to the brain  Cell differentiation – nuclear retinoid (RAR and RXR) receptors bind to DNA and cause gene expression  Used in growth and differentiation of epithelial, nervous, bone tissues  Immunity – cell differentiation – produce cells involved in specific and nonspecific immunologic defenses Deficiency  Hypovitaminosis  Xerophthalmia  Bitot’s spots (keratin deposited in conjunctiva; associated with night blindness)  Follicular hyperkeratosis (keratin deposited around hair follicle)  Xerosis  Immune suppression  Anemia  Impaired tissue growth Dietary Sources
o 

        





Liver, sweet potato, carrot, spinach, mango, acorn, squash, kale, broccoli, margarine, peaches, apricots, cantaloupes, papaya RAE’s (retinol activity equivalents) versus IU’s Men 900 ug RAE/day, women 700 ug RAE/day Men 3000 IU/day, women 2330 IU/day

RDA
  



Toxicity
  

Hypervitaminosis A Caused by excess dosages (100 times RDA) Can be fatal (13,000 times RDA)

 

Chronic: liver damage, hair loss, bone/muscle pain, loss of appetite, dry skin and mucous membranes, hemorrhages, coma Acute: gastrointestinal upsets/nausea, headaches, dizziness, muscle contraction

Vitamin D
      



 



Two nutritionally important forms: vitamin D2 (ergocalciferol) which is found in plants and vitamin D3 (cholecalciferol) which is synthesized in the body from cholesterol Conversion in skin: provitamin D (a form of cholesterol) is converted to previtamin D3 is converted to vitamin D3 D3 must be metabolized in the liver before becoming the active form of vitamin D 80% of vitamin D is absorbed in small intestine Carried by proteins in blood stream Formation of calcitriol occurs in the liver and kidneys Functions of vitamin D:  Maintains serum calcium and phosphorus concentrations within the range that supports neuromuscular function and bone calcification  Calcitriol causes calcium to be absorbed by kidneys and intestines and also causes calcium to be released from bone Deficiency  Rickets and Osteomalacia  Decreased calcium and phosphorus levels Dietary sources  Fortified milk, margarine, butter, cereals, egg yolks, live, fatty fish AI (adequate intake)  5 ug/day (19-50yrs)  10 ug/day (51-70yrs)  15 ug/day (>70yrs) Toxicity  Hypervitaminosis D  5 times the AI is dangerous for infants, 10 times the AI for adults  calcification of soft tissue, growth retardation, excess calcium excretion via the kidneys (kidney stones), headaches, muscle weakness, fatigue, excessive thirst

Vitamin E
    



  

Family of eight antioxidants, four tocopherols, alpha-, beta-, gamma- and delta-, and four tocotrienols (also alpha-, beta-, gamma- and delta-) Alpha-tocopherol is most active form The release of vitamin E from food requires bile, digestive enzymes from the pancreas and intestinal tract, and integration into micelles Vitamin E is stored in liver and adipose tissue Functions:  Antioxidant  Prevents propagation of free radicals  Protects other substances from oxidation by being oxidized itsel Dietary sources  Polyunsaturated plant oils (margarine, salad dressings, shortenings), leafy green vegetables, wheat germ, whole-grains, liver, egg yolks, nuts (esp. almonds), seeds (esp. sunflower) Deficiencies  Hemolysis of red blood cells, anemia, degeneration of sensory neurons RDA  15mg/day Toxicity  Few symptoms (nausea, fatigue, blurred vision, augmentation of anti-clotting medications)

Vitamin K
   

 



Two forms: Vitamin K1 Phyllaquinones (plant source) and vitamin K2 menaquinone (fish oils and meats) 80% of dietary vitamin K is absorbed The release of vitamin K from food requires bile, digestive enzymes from the pancreas and intestinal tract, and integration into micelles Functions:  Contributes to the synthesis of seven blood clotting factors  Cofactor for enzymes Dietary sources  Liver, green and leafy vegetables, broccoli, peas, and green beans, milk Deficiencies  May occur as a result of inadequate fat absorption and/or antibiotic consumption  Excessive bleeding may occur RDA



Men 120 ug/day Women 90 ug/day Toxicity  May interfere with anti-clotting medication
 

Chapter Objectives After reading chapter nine - A student should be able to... 1. Understand the difference between water soluble and fat soluble vitamins 2. Understand the absorption of vitamins and differences in our ability to absorb each of them 3. Identify different forms of vitamins A D E K 4. Discuss the function(s) of vitamins A D E K 5. Describe signs and symptoms of deficiencies of vitamin A D E K 6. Identify sources of vitamin A D E K 7. List the RDAs or recommendations for vitamin A D E K 8. Describe signs and symptoms of toxicity of vitamin A D E K

U.S. Dietary Reference Intakes


VITAMIN A RDA



Males age 14 and older: 900 mcg/day Females age 14 and older: 700 mcg/day Men 3000 IU/day, women 2330 IU/day 5 ug/day (19-50yrs) 10 ug/day (51-70yrs) 15 ug/day (>70yrs)

PANTOTHENIC ACID (B5) AI



5 mg/day

   

VITAMIN D AI VITAMIN E

BIOTIN (Vitamin H) AI VITAMIN B6



30 ug/day



15mg/day Men 120 ug/day Women 90 ug/day Men 1.2 mg/day and women 1.1 mg/day Men 1.3 mg/day and women 1.1 RDA FOLATE



1.3 mg/day

RDA VITAMIN K RDA THIAMIN (B1) RDA RIBOFLAVIN

  



400 ug/day

RDA VITAMIN B12


2.4 ug/day Men 90



RDA VITAMIN C



(B2) mg/day RDA NIACIN (B3) RDA


RDA Men 16 mg/day and women 14 mg/day CHOLINE AI


mg/day and women 75 mg/day Men 550 mg/day and women 425 mg/day

Water Soluble Vitamins
B Vitamins
Do not provide energy directly Help the body metabolize the nutrients that yield energy (carbohydrates, fat, protein) Some B vitamins are components of coenzymes B vitamins include: thiamin, riboflavin, niacin, pantothenic acid, biotin, vitamin B6, folate, vitamin B12

   

Thiamin (vitamin B1)
  



Absorbed in jejunum by a carrier-mediated system and passive diffusion Transported in the blood and by red blood cells Part of coenzyme thiamin pyrophosphate (TPP) used in energy metabolism of  Carbohydrates (pyruvate  acetyl CoA)  Branched-chain amino acids (alpha-ketogluterate  succinyla-CoA) Thiamin deficiencies: Beriberi and Wernicke-Korsakoff Syndrome  Beriberi  1897, Dr. Christiaan Eijkmann, Indonesian island of Java  Natives suffering from beri beri  Symptoms included muscle weakness, weight loss, nervous disorders and ultimately paralysis and death  Dr. Eijkmann noticed chickens exhibiting some of the same symptoms as the beri beri victims  Natives (victims) ate white rice while (healthy) chickens were fed brown rice but chickens with similar symptoms to natives were fed white rice  Conclusion: something on the brown coat of rice prevented beri beri  Types:  Dry beriberi – peripheral neuropathy, “burning feet syndrome”, abnormal reflexes, and diminished sensation and weakness in the legs

  

Wet beriberi – cardiac manifestations such as rapid heart rate, enlargement of the heart, edema, difficulty breathing, and congestive heart failure  Cerebral beriberi – Wernicke-Korsakoff syndrome  Wernicke-Korsakoff Syndrome  Result of habitual use of alcohol  Wernicke’s disease – damage to multiple nerves in the central and peripheral nervous system  Korsakoff syndrome – impairment of memory and intellect/cognitive skills; confabulation (fabrication) occurs to make up for gaps in memory  Other factors causing thiamine deficiency:  Hemodialysis, diuretics, alcoholism – increases flow of urine and loss of thiamin  Anti-thiamin factors – chemicals found in plants that bind to and/or react with thiamin to render it in a form oxidized in the body; tea and coffee may cause thiamin depletion  Thiaminase – enzyme found in raw shellfish and raw freshwater fish; enzyme breaks down thiamin in food Dietary sources: whole-grain, fortified, or enriched grain products, pork, soy milk, ham, and bacon RDA: men 1.2 mg/day and women 1.1 mg/day Toxicity: none reported but anaphylactic shock can occur in dosages lager than 3 grams


Riboflavin (vitamin B2)
     

  

In stomach, HCl releases riboflavin from its bound from Absorbed actively or passively Transported in the blood via protein carriers Part of coenzyme Flavin adenine dinucleotide (FAD) used in energy metabolism High amounts excreted turn urine the bright yellow color Riboflavin deficiencies: ariboflavinosis  Cracks at the corners of the mouth (cheilosis), painful, redness of tongue (glossitis), skin rash, photophobia (sensitivity to light). Dietary sources: milk products, beef liver, steamed oysters, enriched or whole grains RDA: men 1.3 mg/day and women 1.1 mg/day Toxicity: none reported

Niacin (nicotinic acid, nicotinamide, niacinamide, B3)
   

  

Readily absorbed in the stomach and intestine by active and passive transport Transported to liver to be converted to coenzyme forms, NAD and NADP Nicotinamide adenine dinucleotide (NAD) used in energy metabolism Niacin Deficiencies: Pellagra also “smooth swollen red tongue” o Pellagra – associated with consumption of unfortified maize (corn) as a dietary staple o Diets were low in the amino acid tryptophan, precursor of niacin and/or endogenous niacin was bound and non-bioavailable o Flour now is enriched with niacin o Cultures still relying on maize as a staple presoak maize in alkaline lime prior to cooking to liberate bound niacin Dietary sources: milk, eggs, meat, poultry, fish, whole grain and enriched breads and cereals, nuts RDA: men 16 mg/day and women 14 mg/day Toxicity: o Only observed in individuals who use supplements o Supermegadose levels of nicotinic acid (2000 to 4000 mg). Some patients report “niacin flush” (red skin), itching skin (urticaria), heartburn, nausea, etc.

Pantothenic Acid (B5)
    

Part of coenzyme A (CoA) which is used in metabolism of carbohydrate, protein, alcohol, and fat Pantothenic acid deficiencies: none reported Dietary sources: organ meats, mushrooms, broccoli, avocados, whole grains, sunflower seeds, peanuts Adequate Intake (AI): 5 mg/day Toxicity: none reported

Biotin (B7)
  

  

Found in two forms: free vitamin and the protein bound coenzyme form (boicytin) Used in fat synthesis, amino acid metabolism, and glycogen synthesis Biotin deficiencies: biotinidase in small intestine cleaves the bond between biotin and a protein, releasing the free biotin vitamin – if infants lack the enzyme then levels of free biotin vitamin decrease; may lead to skin rash, hair loss, convulsions, impaired growth Dietary sources: widespread in foods; organ meats, egg yolks, soybeans, fish, whole grains Adequate Intake (AI): 30 ug/day Toxicity: none reported

Vitamin B6
 

   

Three forms (pyridoxine, pyridoxal, pyridoxamine) – all converted into the coenzyme PLP (pyridoxal phosphate) PLP involved in more than 100 enzymatic reactions o Functions as a decarboxylase, an enzyme removing carbon dioxide from amino acids o Catalyzes the first step in synthesis of heme in red blood cells o Part of an enzyme that release glucose from glycogen during glycogenolysis o Catalyzes fatty acid synthesis o Catalyzes synthesis of neurotransmitters (serotonin, dopamine, norepinephrine, histamine, and GABA) o Converts the amino acid tryptophan into the B vitamin niacin Vitamin B6 deficiencies: seborrheic dermatitis, microcytic hypochromic anemia, convulsion, depression, and confusion Dietary sources: meats, fish, poultry, potato, liver, soy products RDA: 1.3 mg/day Toxicity: nerve damage, depression, fatigue, headaches

Folate/Folic acid (B9)
  

  

In body target cells, all forms of folate are converted into the coenzyme form, called tetrahydrofolic acid (THFA or THF) THFA involved in the synthesis of DNA bases’ adenine and guanine Folate deficiencies: megoblastic anemia, smooth red tongue, mental confusion, weakness, fatigue, headache, elevated homocysteine levels (which may increase risk of blood vessel injury and thus heart attack) Dietary sources: fortified grains, asparagus, lentils, orange juice, leafy green vegetables, legumes, seeds, liver RDA: 400 ug/day Toxicity: may mask vitamin B12 deficiency symptoms

Vitamin B12
     

Also called cobalamin Contains the mineral cobalt and is synthesized exclusively by bacteria, fungi, and algae B12 in food is released from proteins by action of HCL and pepsin in gastric juice The free B12 binds to a protein (R-protein) and travels to the small intestines where a protease cleaves the protein from the vitamin Free B12 then is bound to an intrinsic factor and travels to the ileum where B12 is absorbed 50% of B12 absorbed in healthy adult





  

Disruption of absorption can occur as a result of  Absence or defective synthesis of R-protein  Defective binding of intrinsic factor/B12 complex to cells of ileum  Absence of much of the ileum and stomach  Absence or defective synthesis of the intrinsic factor  Bacterial overgrowth of the small intestines  Use of anti-ulcer medications  Chronic mal-absorption syndromes B12 deficiencies: achlorhydria and/or atrophic gastritis causes stomach cells to be damaged and impairs the production of HCL and intrinsic factor – without HCL and the intrinsic factor, B12 cannot be absorbed and may lead to pernicious anemia Dietary sources: meat, poultry, seafood, eggs, milk, and fortified cereals RDA: 2.4 ug/day Toxicity: none reported

Vitamin C (ascorbic acid)
           

Found in all living tissues Most animals (except humans and other primates) can be synthesize it from glucose Absorption occurs in the small intestine by active and passive transport 70-90% is absorbed at daily intakes between 30-180 mg – 50% or less at higher dosages Acts as a reducing agent Functions as an antioxidant Involved in connective tissue biosynthesis Protects white blood cells against oxidative damage Vitamin C deficiencies: Scurvy, fatigue, pinpoint hemorrhages, bleeding gums and joints, impaired wound healing, bone pain, fractures, and diarrhea Dietary sources: orange juice and other citrus fruits, brussels sprouts, bell peppers, broccoli, tomatoes, potatoes, papaya, strawberries RDA: men 90 mg/day and women 75 mg/day Toxicity: nausea, abdominal cramps, diarrhea, fatigue, headache

Vitamin-like Compound Choline

      

Absorbed in the small intestines Found in all tissues Precursor of acetylcholine (a neurotransmitter) and phosphatidylcholine (lecithin) Choline deficiencies: liver damage Dietary sources: milk, liver, eggs, peanuts Adequate Intake (AI): men 550 mg/day and women 425 mg/day Toxicity: body odor, low blood pressure, reduced growth rate, liver damage

Chapter Objectives After reading chapter ten - A student should be able to... 1. 2. 3. 4. 5. 6. Discuss the function(s) of the B vitamins and vitamin C Describe signs and symptoms of deficiencies of the B vitamins and vitamin C Identify sources of the B vitamins and vitamin C List the RDAs or recommendations for the B vitamins and vitamin C Describe signs and symptoms of toxicity of the B vitamins and vitamin C List the various “vitamin-like” compounds and discuss their role in the human body