B12 Vitamini ve Folik Asidin Adipozite Üzerine Etkisi

Hayvansal kaynaklı besinlerde ve zenginleştirilmiş ürünlerde bulunan B12 vitamini, kobalamin olarak da adlandırılan ve suda çözünen elzem bir vitamindir. Vücutta metilkobalamin ve 5-deoksiadenozil kobalamin olmak üzere iki şekilde kullanılan B12 vitamini metiyonin sentaz enzimi için kofaktör olarak görev yapmaktadır. Buna ek olarak B12 vitamini DNA sentezi, enerji üretimi, eritropoez, nörolojik işlevler, büyüme ve gelişmenin düzenlenmesinde önemli bir role sahiptir. B12 vitaminine bağımlı olan tek karbon metabolizması, hücresel metabolik yolaklarda tek karbon ünitelerinin eklenmesi, taşınması ve çıkarılmasını içeren reaksiyonlardan oluşur. DNA nükleotidlerinin metilasyonu gen ekspresyonunun kontrolünde yer alan en önemli epigenetik mekanizmadır. Bu kontrol mekanizması, özellikle büyüme ve gelişmenin kritik dönemleri boyunca önem taşımaktadır. DNA metilasyonunda görev alan besin ögelerinin maternal dönemde yetersiz ve dengesiz alınması ilerleyen dönemlerde hastalık riskinin artmasına neden olan fetal fenotipler ile ilişkili olabilir. B12 vitamini yetersizliği bozulmuş lipit profili ve metabolik bozukluklarla sonuçlanabilir ve bu süreçler DNA metilasyonundaki değişiklikler ile ilintili olabilir. Folat, metabolik yolaklarda metilasyonu ve nükleotit sentezini kolaylaştıran elzem bir kofaktör olmasından dolayı sağlık ve hastalıklar üzerine geniş bir etki alanına sahiptir. Temel olarak yağ depolanması olarak tanımlanan obezite ile folat düzeyleri ilişkili olabilir. Bu derleme yazıda, B12 vitamini ve folik asidin adipozite üzerine etkisinin değerlendirilmesi amaçlanmıştır

The Effect of Vitamin B12 and Folic Acid on Adiposity

Vitamin B12, also called cobalamin; is a water-soluble essential vitamin found in animal products and fortified food products. Vitamin B12 is used in the body in two forms; methylcobalamin or 5-deoxyadenosly cobalamin. Methylcobalamin is a cofactor for methionine synthase enzyme. Furthermore, vitamin B12 has a fundamental role in DNA synthesis, regulation, energy production, erythropoiesis, neurological function, control of growth and development. One carbon metabolism which is dependent on vitamin B12, includes reactions as the addiction, transfer or removal of 1-C units in cellular metabolic pathways. Methylation of DNA nucleotides is the most important epigenetic mechanism for the control of gene expressions. The control of gene expression is particularly important during critical periods of growth and development and maternal inadequate consumption of nutrients related to DNA methylation may be associated with fetal phenotypes which increase the risk for subsequent diseases. Deficiency of vitamin B12 may result in abnormal lipid profile and metabolic disorders, therefore these processes may be associated with changes on DNA methylation. Folates are essential cofactors in metabolic pathways that facilitate methylation and nucleotide synthesis, and thus have widespread effects on health and diseases. Obesity, simply defined as fat deposition, may be associated with folate status. In this review, we aimed to evaluate the effect of vitamin B12 and folic acid on adiposity

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1. Rébeillé F, Ravanel S, Marquet A, Mendel RR, Smith AG, Warren MJ. Roles of vitamins B5, B8, B9, B12 and molybdenum cofactor at cellular and organismal levels. Nat Prod Rep 2007;24(5):949-962.
2. Stabler SP. Vitamin B12 deficiency. N Engl J Med 2013;368(2):149-160.
3. Pepper MR, Black MM. B12 in fetal development. Semin Cell Dev Biol 2011;22(6):619-623.
4. Patanwala I, King MJ, Barrett DA, Rose J, Jackson R, Hudson M. et al. Folic acid handling by the human gut: implications for food fortification and supplementation. Am J Clin Nutr 2014;100(2):593-599.
5. Huskisson E, Maggini S, Ruf M. The role of vitamins and minerals in energy metabolism and well-being. J Int Med Res 2007;35:277–289.
6. Fernàndez-Roig S, Lai S.-C, Murphy MM, FernandezBallart J, Quadros EV. Vitamin B12 deficiency in the brain leads to DNA hypomethylation in the TCblR/ CD320 knockout mouse. Nutr Metab (Lond) 2012;9:41.
7. Rush E, Katre P,Yajnik C. Vitamin B12: one carbon metabolism, fetal growth and programming for chronic disease. Eur J Clin Nutr 2014;68(1):2-7.
8. De Wals P, Tairou F, Van Allen MI, Uh SH, Lowry RB, Sibbald B, et al. Reduction in neural-tube defects after folic acid fortification in Canada. N Engl J Med 2007;357:135–142.
9. Jiménez-Chillarón JC, Díaz R, Martínez D, Pentinat T, Ramón-Krauel M, Ribó S. et al. The role of nutrition on epigenetic modifications and their implications on health. Biochimie 2012;94(11):2242-2263.
10. Dominguez-Salas P, Cox SE, Prentice AM, Hennig BJ, Moore SE. Maternal nutritional status, C1 metabolism and offspring DNA methylation: a review of current evidence in human subjects. Proc Nutr Soc 2012;71(01):154-165.
11. Sinclair KD, Allegrucci C, Singh R, Gardner DS, Sebastian S, Bispham J, et al. DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. Proc Natl Acad Sci 2007;104(49):19351-19356.
12. Fowden AL, Giussani DA, Forhead AJ. Intrauterine programming of physiological systems: causes and consequences. Physiology 2006;21(1):29-37.
13. Barbosa P, Stabler S, Machado A, Braga R, Hirata R, Hirata M, et al. Association between decreased vitamin levels and MTHFR, MTR and MTRR gene polymorphisms as determinants for elevated total homocysteine concentrations in pregnant women. Eur J Clin Nutr 2008;62(8):1010-1021.
14. Métayer S, Seiliez I, Collin A, Duchêne S, Mercier Y, Geraert P-A, et al. Mechanisms through which sulfur amino acids control protein metabolism and oxidative status. J Nutr Biochem 2008;19(4):207-215.
15. Ingenbleek Y, McCully KS. Vegetarianism produces subclinical malnutrition, hyperhomocysteinemia and atherogenesis. Nutrition 2012;28(2):148-153.
16. Cornier M-A, Després J-P, Davis N, Grossniklaus DA, Klein S, Lamarche B, et al. Assessing adiposity a scientific statement from the American Heart Association. Circulation. 2011;124(18):1996–2019.
17. Samuel VT, Shulman GI. Mechanisms for insulin resistance: common threads and missing links. Cell. 2012;148(5):852–871.
18. Braun KVE, Voortman T, Kiefte-De Jong J, Jaddoe VWV, Hofman A, Franco OH, et al. Dietary intakes of folic acid and methionine in early childhood are associated with body composition at school age. J Nutr 2015;145(9):2123-2129.
19. Krishnaveni G, Hill J, Veena S, Bhat D, Wills A, Karat C, et al. Low plasma vitamin B12 in pregnancy is associated with gestational ‘diabesity’and later diabetes. Diabetologia 2009;52(11):2350-2358.
20. Kumar KA, Lalitha A, Pavithra D, Padmavathi IJ, Ganeshan M, Rao KR, et al. Maternal dietary folate and/or vitamin B 12 restrictions alter body composition (adiposity) and lipid metabolism in Wistar rat offspring. J Nutr Biochem 2013;24(1):25-31.
21. Adaikalakoteswari A, Jayashri R, Sukumar N, Venkataraman H, Pradeepa R, Gokulakrishnan K, et al. Vitamin B12 deficiency is associated with adverse lipid profile in Europeans and Indians with type 2 diabetes. Cardiovasc Diabetol 2014;13:129.
22. Adaikalakoteswari A, Finer S, Voyias PD, McCarthy CM, Vatish M, Moore J, et al. Vitamin B12 insufficiency induces cholesterol biosynthesis by limiting s-adenosylmethionine and modulating the methylation of SREBF1 and LDLR genes. Clin Epigenetics 2015;7:14.
23. Reinstatler L, Qi YP, Williamson RS, Garn JV, Oakley GP. Association of Biochemical B12 Deficiency With Metformin Therapy and Vitamin B12 Supplements The National Health and Nutrition Examination Survey, 1999–2006. Diab Care 2012;35(2):327-333.
24. MacFarlane AJ, Greene-Finestone LS, Shi Y. Vitamin B-12 and homocysteine status in a folate-replete population: results from the Canadian Health Measures Survey. Am J Clin Nutr 2011;94(4):1079-1087.
25. Ho M, Halim JH, Gow ML, El-Haddad N, Marzulli T, Baur LA, et al. Vitamin B12 in Obese Adolescents with Clinical Features of Insulin Resistance. Nutrients 2014;6(12):5611-5618.
26. Dick KJ, Nelson CP, Tsaprouni L, Sandling JK, Aïssi D, Wahl S, et al. DNA methylation and bodymass index: a genome-wide analysis. The Lancet 2014;383(9933):1990-1998.
27. Christensen KE, Mikael LG, Leung KY, Levesque N, Deng L, Wu Q, et al. High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism, and liver injury in mice. Am J Clin Nutr 2015;101:646– 658.
28. Guanti IR, Marks GC, Al-Mamun A, Long KZ. Low serum vitamin B-12 and folate concentrations and low thiamin and riboflavin intakes are inversely associated with greater adiposity in Mexican American children. J Nutr 2014 Dec;144(12):2027-2033.
29. Horan KM, McGowan AC, Gibney RE, Donnelly MJ, McAuliffe MF. The association between maternal dietary micronutrient intake and neonatal anthropometry – secondary analysis from the ROLO study. Nutr J 2015;14:105.
30. Knight BA, Shields BM, Brook A, Dattatray AH, Bhat S, Hattersley TA, et al. Lower circulating B12 Is associated with higher obesity and insulin resistance during pregnancy in a non-diabetic white British population. PLoS ONE 2015;10(8):e0135268.