Vitamins (2) PDF

Vitamins (2) Pr. Roberta FORESTI Professor of Biochemistry, Faculty of Health, UPEC [email protected]  What are vitamins? Vitamins are substances which have no energy value but which are vit...

Vitamins (2) Pr. Roberta FORESTI Professor of Biochemistry, Faculty of Health, UPEC [email protected]  What are vitamins? Vitamins are substances which have no energy value but which are vital for the body since they are needed for many physiological processes. Apart from vitamins K and D, the human body cannot synthetise vitamins. Because of this we need to get vitamins though our diet so that our bodies can function correctly. Vitamin (vita=life in Latin) Fat-soluble (liposoluble) vitamins Water-soluble (hydrosoluble) vitamins Vitamin A - Retinoids and carotenoids Vitamin B1 - Thiamin Vitamin D Vitamin B2 - Riboflavin Vitamin E - Tocopherols Vitamin B3 - Niacin Vitamin K Vitamin B5 - Pantothenic acid Vitamin B6 - Pyridoxine Vitamin B8 - Biotin Vitamin B9 - Folate or Folic acid Vitamin B12 - Cobalamin Vitamin C - Ascorbic acid Thiamin (Vitamin B1) Water-soluble Vitamin B1, sometimes also called thiamin(e), is mainly involved in carbohydrate metabolism. The vitamin B1 requirement therefore depends on carbohydrate intake and for this reason it is preferable to express dietary reference values in milligrams per megajoule (mg/MJ) of energy consumed, rather than in mg/d. In chemical terms, thiamin is a pyrimidine ring joined to a thiazole ring. Thiamin pyrophosphate is a direct derivative of thiamin. What is thiamin pyrophosphate? Thiamin pyrophosphate is an essential coenzyme for many metabolic enzymes, including the pyruvate dehydrogenase complex (transforms pyruvate into acetyl-CoA in mitochondria) the α-ketoglutarate dehydrogenase complex (transforms α-ketoglutarate into succynil-CoA in Krebs cycle) a dehydrogenase complex that is involved in the metabolism of branched aminoacids (leucine, isoleucine, valine) Thiamin is also required for enzymes in the pentose phosphate pathway, an alternative pathway for glucose oxidation  Krebs cycle Krebs cycle occurs in the mitochondria matrix Recommended intakes (Anses)  Main dietary sources of thiamin Pork Other meat Potatoes Wheat (wholegrain products) Nuts Seeds Beans  Thiamin deficiency The biological life of thiamin is 10-20 days, so if there is depletion signs of deficiency can develop rapidly. When there is deficiency there is an impaired entry of pyruvate into the Krebs cycle. In the presence of high carbohydrate in the diet there is an increase plasma levels of lactate and pyruvate, which may lead to life-threatening acidosis. The diseases of deficiency are called Beriberi, with neurological and cardiac symptoms such as damage to nerves, muscle weakness, cardiac failure with dilated heart, vasodilation. Or Wernicke-Korsakoff syndrome, typically associated with alcoholism (alcohol inhibits thiamin absorption) but also substance abuse or problems with intestinal absorption due to diseases. Symptoms include confusion and disorientation, involuntary movements, eye muscle paralysis, short or long-term memory loss, unsteady gait. Injections or oral administration of high doses of thiamin can help to improve symptoms. Magnetic resonance imaging (MRI) scans of a healthy male (top) compared to a male of the same age with WK syndrome (bottom). The WK brain has less brain volume and larger cavities within the brain (called ventricles). Riboflavin (Vitamin B2) Water-soluble Vitamin B2 (or riboflavin) is a water-soluble vitamin that is heat-stable but sensitive to light. Riboflavin plays a part in energy metabolism. Its main function is as an electron carrier in a wide variety of oxidation and reduction reactions central to all metabolic processes, including the mitochondrial electron transport chain. Riboflavin in food is found in free form but also as flavin coenzyme, bound to enzymes-FMN and FAD.  Respiratory chain composition Nomber Prosthetic Complexes Names of sub- groups units Complex I NADH 46 FMN, Dehydrogenase Fe-S Complex II Succinate-CoQ 5 FAD, cyt b560, Reductase Fe-S Complex III CoQ-cyt c 11 cyt bH, cyt bL, Reductase cyt c1, Fe-S Complex IV Cytochrome 13 cyt a, cyt a3, Oxidase CuA, CuB Riboflavin has a role in iron absorption, mobilization and storage, with implications for anemia. Riboflavin is involved in the metabolism of niacin and vitamin B6 and FAD is also required by the methylenetetrahydrofolate reductase (MTHFR) in the folate cycle and thereby is involved in homocysteine metabolism. Riboflavin plays a role in determining the circulating levels of homocysteine (still debated). High homocysteine levels are associated with an increased risk of cardiovascular disease, it acts as an irritant in blood vessels and favors the formation of plaques. Recommended intakes (Anses)  Main dietary sources of riboflavin Liver Milk Meat Fish Eggs Green leafy vegetables (spinach) Milk and dairy products are the greatest contributors for its intake in the population. Yellow tinge in cream layer of full fat milk when it sets is riboflavin.  Riboflavin deficiency Cases of deficiency are not very common and the symptoms are aspecific. Riboflavin deficiency is most often accompanied by other nutrient deficiencies, and was reported in populations from both developed and developing countries. Clinical signs of riboflavin deficiency reported in humans include, e.g. sore throat, hyperaemia (increased amount of blood in vessels) and oedema of the pharyngeal and oral mucous membranes, cheilosis (inflammatory condition at the corners of the mouth), glossitis (magenta tongue), seborrhoeic dermatitis, skin lesions including angular stomatitis and normochromicnormocytic anaemia characterised by erythroid hypoplasia and reticulocytopenia Niacin (Vitamin B3) Water-soluble Niacin is a water-soluble vitamin involved as a redox cofactor in the metabolism of glucose, amino acids and fatty acids (see glycolysis, Krebs etc., where it participates in oxidation/reduction reactions). Niacin is a generic term to describe the two compounds that have biological action: nicotinamide and nicotinic acid and are used to produce NAD and NADP. There is a relationship between niacin and dietary tryptophan since this aminoacid can be used to form NAD and NADP. Niacin is being investigated in the protection against diabetes and cardiovascular disease (it affects cholesterol levels).  Recommended intakes Because of the role of vitamin B3 in energy metabolism, the requirements and recommendations are frequently expressed in milligrams of niacin equivalent per megajoule (NE/MJ). (Anses)  Main dietary sources of niacin Meat Liver Fish Nuts Avocado Sweet potato Wholegrain cereals Most of the niacin in cereals is biologically unavailable as it is bound to macromolecules. Corn is a very poor source of niacin (deficiency of niacin in corn-eaters a century ago)  Niacin deficiency Long-term niacin deficiency can lead to the development of pellagra, whose most common symptoms are photosensitive dermatitis, skin lesions, vomiting, diarrhoea, depression and dementia (in advanced state). It was originally described as a disease of malnutrition in corn-eaters. Substituting corn with a mixed cereal diet improved symptoms, inclusion of animal protein also helps. It is also observed in malnourished alcoholic patients. Panthotenic acid (Vitamin B5) Water-soluble Pantothenic acid plays an essential structural role in the synthesis of coenzyme A. It is also required for the synthesis of acyl carrier proteins and several synthases. It is therefore essential for the synthesis and metabolism of carbohydrates, amino acids and fatty acids and has a central role in energy-yielding metabolism. Coenzyme A  Krebs cycle Krebs cycle occurs in the mitochondria matrix Recommended intakes (Anses)  Main dietary sources of panthotenic acid Meat Bread Milk Dairy products Pantothenic acid is found in all foods and deficiency cases are very rare. Pyridoxine (Vitamin B6) Water-soluble Pyridoxine has a central role in the metabolism of aminoacids, is a cofactor in glycogen phosphorylase and modulates the action of steroid hormones. There are six vitamers of pyridoxine and they appear to have all the same biological activity.  Recommended intakes Lowest requiremenst are directly linked to the amount of protein in the diet. (Anses)  Main dietary sources of pyridoxine Poultry Fish Pork Eggs Soya beans Oats Unpolished rice Pyridoxine is widely distributed in food and clinical deficiency is unknown. However, lower levels can have effects on aminoacid metabolism and steroid hormones.  Pyridoxine deficiency Pyridoxine is widely distributed in food and clinical deficiency is unknown. However, lower levels can have effects on aminoacid metabolism and steroid hormones. The effect of pyridoxine deficiency was discovered by chance in the 1950s. By accident, infant milk preparation was severely overheated by the manufacturer rendering the milk deficient in the vitamin (it was not known at the time that the vitamin was important). The affected infants had metabolic abnormalities and they had seizures. They responded to pyridoxine administration. Some deficiencies are also observed in alcoholics (50-80% of alcoholics have low serum levels of pyridoxine or due to drug interaction (ex. anti-inflammatory drug penicillamine). Symptoms: lesions of the lips and corners of the mouth, inflammation of the tongue and peripheral neuropathy-similar to riboflavin deficiency Biotin (Vitamin B8) Water-soluble Biotin has a central role in lipogenesis and gluconeogenesis, as it acts as a coenzyme for carboxylation reactions. It is also important for enzymes in glycolysis. Biotin is an imidazole ring fused to a tetrahydrothiopene ring with a valeric acid side chain. Biotin in food is bound to proteins via its carboxylic group. In uncooked egg white there is avidin, which binds biotin and renders the vitamin unavailable for absorption. Careful in diets with large amounts of uncooked egg whites! Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) derived Dietary Reference Values (DRVs) for biotin. Biotin is a water-soluble vitamin which serves as a co-factor for several carboxylases that play critical roles in the synthesis of fatty acids, the catabolism of branched-chain amino acids and gluconeogenesis. Dietary biotin deficiency is rare. Data on biomarkers of biotin intake or status are insufficient to be used in determining the requirement for biotin. Data available on biotin intakes and health consequences are very limited and cannot be used for deriving DRVs for biotin. As there is insufficient evidence available to derive an Average Requirement and a Population Reference Intake, an Adequate Intake (AI) is proposed. The setting of AIs is based on observed biotin intakes with a mixed diet and the apparent absence of signs of deficiency in the EU, suggesting that current intake levels are adequate. The AI for adults is set at 40 µg/day. The AI for adults also applies to pregnant women. For lactating women, an additional 5 µg biotin/day over and above the AI for adults is proposed, to compensate for biotin losses through breast milk. For infants over six months, an AI of 6 µg/day is proposed by extrapolating from the biotin intake of exclusively breastfed infants aged zero to six months, using allometric scaling and reference body weight for each age group, in order to account for the role of biotin in energy metabolism. The AIs for children aged 1–3 and 4–10 years are set at 20 and 25 µg/day, respectively, and for adolescents at 35 µg/day, based on observed intakes in the EU. (from EFSA)  Main dietary sources of biotin Egg yolk (cooked eggs) Soya flour Cereals Liver Yeast Biotin is tightly bound to avidin in raw egg whites but is freed upon cooking. Fruits and meat are poor sources. It is very difficult to become deficient in biotin. Folate (Vitamin B9) Water-soluble Folate is a generic name for a series of compounds that are present in food. Folate has a central role in the transfer of one carbon groups (CH3) in several reactions, in catabolism and biosynthesis. Folates act as coenzymes and are critical for: Methylation (protein, fat, DNA, RNA) Nucleotide synthesis (purine and pyrimidine) Metabolism of several aminoacids Folic acid is the compound used in food fortification (flour-bread, cereals) while folates are naturally found in food. Folate is involved in homocysteine metabolism and high intake of this vitamin lowers plasma homocysteine levels. Thus it may reduce the risk of cardiovascular disease. There is also evidence that a low folate status is associated with an increase of colorectal cancer and other cancers. Difficult to determine: foods that are rich in folates also contain other protective molecules! Extend food fortification to all? Universal mandatory folic acid supplementation for infants worldwide? Recommended intakes DFE= Dietary Folate Equivalent (Anses)  Main dietary sources of folate Dark green vegetables Orange Liver Bread and wheat germ Beans Fortified breakfast cereals Bread - we eat a lot of it, so even if it is not a good source, it contributes significantly to the intake. Folic acid is much better absorbed than folate. Folic acid is almost entirely absorbed, folates from food ~ 50%  Folate deficiency Folate deficiency is relatively common (8-10% of the population in developed countries). Deficiency results in megaloblastic anemia, whereby there is a failure of maturation of red blood cells in the bone marrow, resulting in the release into the circulation of abnormally large immature red blood cells (due to low synthesis of DNA). Symptoms include depression insomnia forgetfulness irritability Causes of deficiency Inadequate dietary intake Malabsorption (diarrhea) Drug induced (methotrexate, anticancer agent) alcoholism  Folate deficiency and neural tube defects Folate deficiency is associated with the development of neural tube defects and spina bifida/anencephaly in babies (established in the 1960s). Neural tube forms the brain and spinal cord in the first weeks of gestation and the closure occurs around day 21-24 of pregnancy: BEFORE THE WOMAN KNOWS SHE IS PREGNANT! Low folate is accompanied by failure to close the neural tube and bone does not form around unclosed regions. Clinical trials show that supplementation with folic acid reduces of 70% the risk of neural tube defects. It is highly recommended that women planning to have a pregnancy take a folic acid supplement Every year, nearly 5,000 pregnancies in Europe are affected by neural tube defects such as spina bifida and anencephaly (malformations of the brain and skull), with serious consequences for the newborn infants. Taking nutritional supplements containing folic acid (or vitamin B9) before and during early pregnancy may considerably reduce the risk, but studies show that only a minority of women do so. A study published today in The British Medical Journal, and coordinated by Babak Khoshnood, Inserm Research Director (Inserm Unit 1153 “Sorbonne Paris Cité Research Center in Epidemiology and Biostatistics”) concludes that there has been no decrease in neural tube defects over a 20-year period. The researchers urge the decision-makers to consider establishing a policy of mandatory folic acid fortification of some staple foods, such as flour or cereals. (Inserm newsletter 2015) Vitamin B12- Cobalamin Water-soluble Vitamin B12 is a porphyrin ring containing cobalt (cobalamin). It has an important role as a cofactor of 2 enzymes: 1) Methionine synthase (transformation of homocysteine to methionine) 2) Methylmalonyl CoA mutase (for degradation of some aminoacids and odd chain fatty acids) Importantly, vitamin B12 and folate cooperate in the carbon metabolism, so their intake reciprocally affects their action. Vitamin B12  Recommended intakes Vitamin B12 absorption. Very little is absorbed by diffusion and R and the Intrinsic Factor (IF) are necessary for its absorption. (Anses) BMJ 2019;365:l1865  Main dietary sources of vitamin B12 Offal (especially liver) Fish Eggs Meat Milk Dairy products Vitamin B12 is present in animal derived food. No plant sources! Deficiency is particulalry common in vegetarians and especially in vegans. Vitamin B12 is synthesised by micro-organisms, mainly bacteria and archaea, especially those present in the rumen.  Vitamin B12 deficiency Vitamin B12 deficiency happens in 10-15% of the elderly population (> 60 years old) due to malabsorption. It is also common in strict vegans and vegetarians (depending on the intake of animal protein) and this population group has to be very careful about their intake of vitamin B12 (stores in the liver: 3-5 years). Vitamin B12 deficiency leads to pernicious anemia (result of failure to secrete IF), spinal cord degeneration and peripheral neuropathy. High intake of folate prevents the anemia but may also mask vitamin B12 deficiency. Thus, no anemia but neurological damage would still continue undetected until it is irreversible. Symptoms include fatigues weakness numbness tingling of hands and feet difficulty in thinking or reasoning/memory loss Augusta University  Vitamin C Water-soluble Vitamin C is a vitamin only in primates, some birds guinea pigs. In all other species it is synthesized from D-glucose or D-galactose. The physiological important compound is L-ascorbic acid. Its main function are to support the action of hydroxylases, keeping the metals in these enzymes (Cu or Fe) in the reduced form. Vitamin C is also a good antioxidant and has a role in non-heme iron absorption. It is generally thought to suppress cold symptoms (immunological function?) Vitamin C Vitamin C is essential for 1) collagen synthesis (hydroxylation of proline and lysine in healthy collagen fibre). Impaired hydroxylation leads to degradation of collagen; 2) carnithine synthesis. Carnithine has a key role in transporting fatty acids into mitochondria for oxidation and ATP production. 3) noradrenaline synthesis. Important for brain function. Recommended intakes (Anses)  Main dietary sources of vitamin C Oranges and citrus fruits Strawberries Kiwi Spinach Tomato Broccoli Dairy products and meat are poor sources. Unfortified grains and cereals do not contain vitamin C. 85% of dietary intake is absorbed.  Smoking and vitamin C Evidence in humans shows that smokers have low levels of ascorbate WHY? Lower intake of fruit and vegetables, consumption of Vit C by oxidants produced by smoking…….??? Ascorbate is depleted by smoking and repleted by moderate supplementation: a study in male smokers and nonsmokers with matched dietary antioxidant intakes. Lykkesfeldt J, Christen S, Wallock LM, Chang HH, Jacob RA, Ames BN. Am J Clin Nutr. 2000 Feb;71(2):530-6. OBJECTIVE: Our objective was to investigate the effect of smoking on plasma antioxidant status by measuring ascorbic acid, alpha-tocopherol, gamma-tocopherol, beta-carotene, and lycopene, and subsequently, to test the effect of a 3-mo dietary supplementation with a moderate-dose vitamin cocktail. DESIGN: In a double-blind, placebo-controlled design, the effect of a vitamin cocktail containing 272 mg vitamin C, 31 mg all-rac-alpha-tocopheryl acetate, and 400 microg folic acid on plasma antioxidants was determined in a population of smokers (n = 37) and nonsmokers (n = 38). The population was selected for a low intake of fruit and vegetables and recruited from the San Francisco Bay area. RESULTS: Only ascorbic acid was significantly depleted by smoking per se (P < 0.01). After the 3-mo supplementation period, ascorbic acid was efficiently repleted in smokers (P < 0.001). Plasma alpha-tocopherol and the ratio of alpha- to gamma-tocopherol increased significantly in both supplemented groups (P < 0.05). Smokers have lower levels of vitamin C Nutr Rev. 2000 Aug;58(8):239-41. Passive smoking induces oxidant damage preventable by vitamin C. Jacob RA1. 55  Should smokers take vitamin C supplements? The administration of vitamin C megadoses is also controversial due to the fact that ascorbic acid at low concentrations functions primarily as an antioxidant, whereas at higher concentrations, and depending on environmental conditions, it can act as a pro-oxidant that imposes oxidative stress and induces cell death.  Vitamin C deficiency First report of scurvy was reported by Vasco de Gama, who described a disease with symptoms such as swollen legs, bleeding gums, lose teeth and eventually death. Disease of sailors that were at sea for long periods of time and had a poor diet without fruits and vegetables. The major role of vitamin C in the hydroxylation of collagen is directly linked to the development of scurvy. Symptoms include irritability and changes in behavior bleeding gums ulceration tissue hemorrhage and bruises eventually death James Lind is remembered as the man who helped to conquer a killer disease. His reported experiment on board a naval ship in 1747 showed that oranges and lemons were a cure for scurvy (1747). (BBC)