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Ivana Đuričić, Jelena Kotur-Stevuljević, Milica Miljković, Mirko Kerkez, Vladimir Đorđević, Ljubomir Đurašić and Slađana Šobajić

. Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids. J Am Diet Assoc 2002; 102(11): 1621-30. 21. Beckermann B, Beneke M, Seitz I. Comparative bioavailability of eicosapentaenoic acid and docasahexaenoic acid from triglycerides, free fatty acids and ethyl esters in volunteers. Arzneimittel-Forschung 1990; 40(6): 700-4. 22. Hansen JB, Olsen JO, Wilsgard L, Lyngmo V, Svensson B. Comparative effects of prolonged intake of highly purified fish oils as ethyl ester or triglyceride on

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Giuseppe Lippi, Gian Luca Salvagno, Antonio Fortunato, Mariella Dipalo, Rosalia Aloe, Giorgio Da Rin and Davide Giavarina

References 1. Holick MF. The D-lightful vitamin D for health. J Med Biochem 2013; 32: 1-10. 2. Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium; Ross AC, Taylor CL, Yaktine AL, Del Valle HB, editors. Dietary Reference Intakes for Calcium and Vitamin D. Washin g - ton (DC): National Academies Press (US); 2011. 3. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al; Endocrine Society. Evaluation, treatment, and prevention of vitamin D

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Snežana Jovičić, Svetlana Ignjatović and Nada Majkić-Singh

Summary

Vitamin D is not technically a vitamin, since it is not an essential dietary factor. It is rather a prohormone produced photochemically in the skin from 7-dehydrocholesterol. Vitamin D and its metabolites may be categorized as either cholecalciferols or ergocalciferols. Cholecalciferol (vi - tamin D3) is the parent compound of the naturally occurring family and is produced in the skin from 7-dehydrocholesterol on exposure to the ultraviolet B portion of sunlight. Vitamin D2 (ergocalciferol), the parent compound of the other family, is manufactured by irradiation of ergosterol produced by yeasts and its potency is less than one-third of vitamin D3’s potency. The steps in the vitamin D endocrine system include the following: 1) the photoconversion of 7- dehydrocholesterol to vitamin D3 in the skin or dietary intake of vitamin D3; 2) metabolism of vitamin D3 by the liver to 25-hydroxyvitamin-D3 [25(OH)D3 ], the major form of vitamin D circulating in the blood compartment; 3) conversion of 25(OH)D3 by the kidney (functioning as an endocrine gland) to the hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3 ]; 4) systemic transport of the dihydroxylated metabolite 1,25(OH)2D3 to distal target organs; and 5) binding of 1,25(OH)2D3 to a nuclear receptor (VDR) at target organs, followed by generation of appropriate biological responses. The activation of vitamin D to its hormonal form is mediated by cytochrome P450 enzymes. Six cytochrome P450 (CYP) isoforms have been shown to hydroxylate vitamin D. Four of these, CYP27A1, CYP2R1, CYP3A4 and CYP2J3, are candidates for the enzyme vitamin D 25-hy - droxylase that is involved in the first step of activation. The highly regulated, renal enzyme 25-hydroxyvitamin D-1a-hy - dro xylase contains the component CYP27B1, which completes the activation pathway to the hormonal form 1,25(OH)2D3. A five-step inactivation pathway from 1,25(OH)2D3 to calcitroic acid is attributed to a single multifunctional CYP, CYP24A1, which is transcriptionally in du - ced in vitamin D target cells by the action of 1,25(OH)2D3. An additional key component in the operation of the vitamin D endocrine system is the plasma vitamin D binding protein (DBP), which carries vitamin D3 and its metabolites to their metabolism and target organs. DBP is a specific, high-affinity transport protein. It is synthesized by the liver and circulates in great excess, with fewer than 5% of the binding sites normally occupied. 1,25(OH)2D3, acts as a ligand for a nuclear transcription factor, vitamin D receptor - VDR, which like all other nuclear receptors, regulates gene transcription and cell function. The widespread presence of VDR, and the key activating (1a-hydroxylase, CYP27B1) and inactivating (24-hydroxylase, CYP24A1) en - zy mes in most mammalian cells means that the cells in these tissues have the potential to produce biological res pon ses, depending on the availability of appropriate amounts of vi - tamin D3. Thanks to this widespread presence of elements of vitamin D endocrine system, its biological features are being recognized outside bone tissue, i.e. calcium and pho - sphate metabolism.

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Jolanta Bugajska, Joanna Berska, Diana Hodorowicz-Zaniewska and Krystyna Sztefko

overview. Cancer Detect Prev 2003; 27(1): 55-66. 10. Hodge AM, Simpson JA, Gibson RA, Sinclair AJ, Makrides M, O’Dea K, et al. Plasma phospholipid fatty acid composition as a biomarker of habitual dietary fat intake in an ethnically diverse cohort. Nutr Metab Cardiovasc Dis 2007; 17(6): 415-26. 11. Arab L. Biomarkers of fat and fatty acid intake. J Nutr2003; 133 Suppl: 925S-932S. 12. Saadatian-Elahi M, Slimani N, Chajes V, Jenab M, Goudable J, Biessy C, et al. Plasma phospholipid fatty acid profiles and their association

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David Goldberg

: where do we go from here? Proc Nutr Soc 2003; 62: 63-5. Park Y, Hunter DJ, Spiegelman D, Bergkvist L, Berrino F, Van den Brandt PA, et al. Dietary fiber intake and risk of colorectal cancer. A pooled analysis of prospective cohort studies. JAMA 2005; 294: 2849-57. Uchida K, Kono S, Yin G, Toyomura K, Nagano J, Mizoue T, et al. Dietary fibre, source foods and colorectal cancer risk: the Fukuoka Colorectal Cancer Study. Scand J Gastroenterol 2010; 45: 1223-31. Bravi F, Edefonti V, Bosetti C

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Vesna Škodrić-Trifunović, Ana Blanka, Mihailo I. Stjepanović, Svetlana Ignjatović, Violeta Mihailović-Vučinić, Zorica Šumarac, Ivana Buha and Katarina Ilić

Asians in west London: a case-control study. Lancet 2000; 355: 618–21. 5. Vogeser M, Seger C. Vitamin D–challenges in diagnosing and monitoring of hypovitaminosis D. J Med Biochem 2012; 31(4): 316–25. 6. Institute of Medicine (US) committee to review dietary reference intakes for vitamin D and calcium. Ross AC, Taylor CL, Yaktine AL, Del Valle HB, eds. Dietary re f-erence intakes for calcium and vitamin D. Washington DC: National Academies Press, 2011. 7. Jovičić S, Ignjatović S, Kangrga R, Beletić A, Mirković D, Majkić-Singh N. Comparison of three different

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Anđelo Beletić, Duško Mirković, Aleksandra Dudvarski-Ilić, Branislava Milenković, Ljudmila Nagorni-Obradović, Valentina Đorđević, Svetlana Ignjatović and Nada Majkić-Singh

April 10th, 2014. 7. Jiang B, Ding C, Yao G, Yao C, Zhang Y, Ge J, et al. Intervention effect of folic acid and vitamin B 12 on vascular cognitive impairment complicated with hyperhomocysteinemia. J Med Biochem 2014; 33: 169–74. 8. Guéant JL, Alpers DH. Vitamin B 12 , a fascinating micronutrient, which influences human health in the very early and later stages of life. Biochimie 2013; 95: 967–9. 9. Dhonukshe-Rutten RA, de Vries JH, de Bree A, van der Put N, van Staveren WA, de Groot LC. Dietary intake and status of folate and vitamin B 12 and their

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Michael F. Holick

-18. 4. Hess AF, Unger LJ. The cure of infantile rickets by sunlight. J Am Med Assoc 1921; 77: 39-41. 5. Steenbock H. The induction of growth-prompting and calcifying properties in a ration exposed to light. Science 1924; 60: 224-5. 6. British Pediatric Association. Hypercalcemia in infants and vitamin D. Brit Med J 1956; 2: 149-51. 7. Holick MF. Vitamin D Deficiency. N Engl J Med 2007; 357: 266-81. 8. Holick MF. Vitamin D and Health: Evolution, Biologic Funtions, and Recommended Dietary Intakes for

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David Goldberg and George Soleas

, other carotenoids, and retinol and the risk of cardiovascular disease in men. Am J Clin Nutr 2005; 81: 990-7. Hatzigeorgiou C, Taylor AJ, Feuerstein IM, Bautista L, O'Malley PG. Antioxidant vitamin intake and subclinical coronary atherosclerosis. Prev Cardiol 2006; 9: 75-81. Tavani A, Gallus S, Negri E, Parpinel M, La Vecchia C. Dietary intake of carotenoids and retinol and the risk of acute myocardial infarction in Italy. Free Radic Res 2006; 40: 659-64. Kirmizis D, Chatzidimitriou D

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Tanja Dujić, Tamer Bego, Barbara Mlinar, Sabina Semiz, Maja Malenica, Besim Prnjavorac, Barbara Ostanek, Janja Marc and Adlija Čaušević

Med Genet 2003; 40: 773–80. 40. Tonjes A, Scholz M, Loeffler M, Stumvoll M. Association of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma with Pre-diabetic phenotypes: meta-analysis of 57 studies on nondiabetic individuals. Diabetes Care 2006; 29: 2489–97. 41. Luan J, Browne PO, Harding AH, Halsall DJ, O'Rahilly S, Chatterjee VK, et al. Evidence for gene-nutrient interaction at the PPARgamma locus. Diabetes 2001; 50: 686–9. 42. Lamri A, Abi Khalil C, Jaziri R, Velho G, Lantieri O, Vol S, et al. Dietary fat intake and polymorphisms at