تاثیر مکمل ویتامین D در بهبود کبد چرب غیر الکلی: یک مرور سیستماتیک بر روی مطالعات کارآزمایی بالینی

##plugins.themes.bootstrap3.article.main##

فاطمه سادات ميريعقوبى
مهران نوری
غلامرضا عسکری

چکیده

مقدمه: کبد چرب یک اختلال متابولیکی رایج است که به دلیل تجمع بیش ‌از حد چربی در سلول‌های کبدی منجر به عملکرد غیر طبیعی کبد می‌شود. ویتامین D به دلیل داشتن نقش‌های ضد التهابی، ضد فیبروزی و ایجاد حساسیت به انسولین می‌تواند در بهبود علائم کبد چرب نقش داشته باشد. در این راستا، مطالعه حاضر با هدف خلاصه کردن اطلاعات حاصل از مطالعات کارآزمایی بالینی انجام ‌شده در رابطه با تأثیر مکمل ویتامین D بر پارامترهای مختلف بیماری کبد چرب انجام شد.


روش‌‌ها: مطالعات منتشر شده طی سال‌های 1990 تا 2018 با جستجو در پایگاه‌های علمی PubMed، Google Scholar، Science Direct، Scopus و Web of Science با استفاده از کلیدواژه‌های NAFLD، Nonalcoholic Fatty Liver Disease، Nonalcoholic Steatohepatitis، Vitamin D، Cholecalciferol، 1,25(OH)2D3 و Calcitriol استخراج شدند.


یافته‌ها: به نظر می‌رسد که ویتامین D می‌تواند با کاهش چربی کبد، سطح آنزیم‌های ALT (Alanine Transaminase) و AST (Aspartate Transaminase)، سایتوکاین‌های پیش‌التهابی مانند NF-κB و TNF-α، فاکتور التهابی hs-CRP (high-sensitivity C-reactive protein) و بهبود مقاومت به انسولین، اثر مثبتی بر بهبود علائم کبد چرب غیر الکلی داشته باشد. همچنین می‌تواند با کاهش سطح مالون‌دی‌آلدهید (MDA: Malondialdehyde) و افزایش ظرفیت آنتی‌اکسیدانی، به شکلی مثبت بر استرس اکسیداتیو تأثیر بگذارد.


نتیجه‌گیری: ویتامین D می‌تواند نقش مهمی در روند پیشگیری و بهبود کبد چرب غیر الکلی از طریق مکانیسم‌های مختلف داشته باشد.

##plugins.themes.bootstrap3.article.details##

ارجاع به مقاله
ميريعقوبىف. س., نوریم., & عسکریغ. (2020). تاثیر مکمل ویتامین D در بهبود کبد چرب غیر الکلی: یک مرور سیستماتیک بر روی مطالعات کارآزمایی بالینی. تحقیقات نظام سلامت, 15(3), 169-176. https://doi.org/10.32592/hsr.2020.15.3.100
نوع مقاله
مقاله مروری

مراجع

1. Choi HS, Kim KA, Lim CY, Rhee SY, Hwang YC, Kim KM, et al. Low serum vitamin D is associated with high risk of diabetes in Korean adults. J Nutr 2011; 141: 1524-8. PMID: 21697301.
2. Speliotes EK, Massaro JM, Hoffmann U, Vasan RS, Meigs JB, Sahani DV, et al. Fatty liver is associated with dyslipidemia and dysglycemia independent of visceral fat: the Framingham Heart Study. Hepatology 2010; 51: 1979-87. PMID: 20336705.
3. Zolfaghari H, Askari G, Siassi F, Feizi A, Sotoudeh G. Intake of Nutrients, Fiber, and Sugar in Patients with Nonalcoholic Fatty Liver Disease in Comparison to Healthy Individuals. Int J Prev Med 2016; 7: 98. PMID: 27625763.
4. Hardy T, Oakley F, Anstee QM, Day CP. Nonalcoholic Fatty Liver Disease: Pathogenesis and Disease Spectrum. Annu Rev Pathol 2016; 11: 451-96. PMID: 26980160.
5. Alavian SM, Mohammad-Alizadeh AH, Esna-Ashari F, Ardalan G, Hajarizadeh B. Non-alcoholic fatty liver disease prevalence among school-aged children and adolescents in Iran and its association with biochemical and anthropometric measures. Liver Int 2009; 29: 159-63. PMID: 18492015.
6. Sohrabpour A, Rezvan H, Amini-Kafiabad S, Dayhim M, Merat S, Pourshams A. Prevalence of Nonalcoholic Steatohepatitis in Iran: A Population based Study. Middle East J Dig Dis 2010; 2: 14-9. PMID: 25197507.
7. Crabb DW, Galli A, Fischer M, You M. Molecular mechanisms of alcoholic fatty liver: role of peroxisome proliferator-activated receptor alpha. Alcohol 2004; 34: 35-8. PMID: 15670663.
8. Li H, Wang YJ, Tan K, Zeng L, Liu L, Liu FJ, et al. Prevalence and risk factors of fatty liver disease in Chengdu, Southwest China. Hepatobiliary Pancreat Dis Int 2009; 8: 377-82. PMID: 19666406.
9. Forouhi NG, Luan J, Cooper A, Boucher BJ, Wareham NJ. Baseline serum 25-hydroxy vitamin d is predictive of future glycemic status and insulin resistance: the Medical Research Council Ely Prospective Study 1990-2000. Diabetes 2008; 57: 2619-25. PMID: 18591391.
10. Targher G, Lonardo A, Rossini M. Nonalcoholic fatty liver disease and decreased bone mineral density: is there a link? J Endocrinol Invest 2015; 38: 817-25. PMID: 26003827.
11. Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357: 266-81. PMID: 17634462.
12. DeLuca HF. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr 2004; 80: 1689S-96S. PMID: 15585789.
13. Verstuyf A, Carmeliet G, Bouillon R, Mathieu C. Vitamin D: a pleiotropic hormone. Kidney Int 2010; 78: 140-5. PMID: 20182414.
14. Oosterwerff MM, Eekhoff EM, Van Schoor NM, Boeke AJ, Nanayakkara P, Meijnen R, et al. Effect of moderate-dose vitamin D supplementation on insulin sensitivity in vitamin D-deficient non-Western immigrants in the Netherlands: a randomized placebo-controlled trial. Am J Clin Nutr 2014; 100: 152-60. PMID: 24898240.
15. Sharifi N, Amani R, Hajiani E, Cheraghian B. Does vitamin D improve liver enzymes, oxidative stress, and inflammatory biomarkers in adults with non-alcoholic fatty liver disease? A randomized clinical trial. Endocrine 2014; 47: 70-80. PMID: 24968737.
16. Pham TM, Ekwaru JP, Setayeshgar S, Veugelers PJ. The Effect of Changing Serum 25-Hydroxyvitamin D Concentrations on Metabolic Syndrome: A Longitudinal Analysis of Participants of a Preventive Health Program. Nutrients 2015; 7: 7271-84. PMID: 26343719.
17. Abramovitch S, Sharvit E, Weisman Y, Bentov A, Brazowski E, Cohen G, et al. Vitamin D inhibits development of liver fibrosis in an animal model but cannot ameliorate established cirrhosis. Am J Physiol Gastrointest Liver Physiol 2015; 308: G112-20. PMID: 25214398.
18. Targher G. Relationship between high-sensitivity C-reactive protein levels and liver histology in subjects with non-alcoholic fatty liver disease. J Hepatol 2006; 45: 879-81; author reply 881-2. PMID: 17049665.
19. Della Corte C, Carpino G, De Vito R, De Stefanis C, Alisi A, Cianfarani S, et al. Docosahexanoic Acid Plus Vitamin D Treatment Improves Features of NAFLD in Children with Serum Vitamin D Deficiency: Results from a Single Centre Trial. PLoS One 2016; 11: e0168216. PMID: 27977757.
20. Lorvand Amiri H, Agah S, Tolouei Azar J, Hosseini S, Shidfar F, Mousavi SN. Effect of daily calcitriol supplementation with and without calcium on disease regression in non-alcoholic fatty liver patients following an energy-restricted diet: Randomized, controlled, double-blind trial. Clin Nutr 2017; 36: 1490-1497. PMID: 27720403.
21. Dasarathy J, Varghese R, Feldman A, Khiyami A, McCullough AJ, Dasarathy S. Patients with Nonalcoholic Fatty Liver Disease Have a Low Response Rate to Vitamin D Supplementation. J Nutr 2017; 147: 1938-1946. PMID: 28814531.
22. Barchetta I, Del Ben M, Angelico F, Di Martino M, Fraioli A, La Torre G, et al. No effects of oral vitamin D supplementation on non-alcoholic fatty liver disease in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. BMC Med 2016; 14: 92. PMID: 27353492.
23. Foroughi M, Maghsoudi Z, Ghiasvand R, Iraj B, Askari G. Effect of Vitamin D Supplementation on C-reactive Protein in Patients with Nonalcoholic Fatty Liver. Int J Prev Med 2014; 5: 969-75. PMID: 25489444.
24. Kitson MT, Pham A, Gordon A, Kemp W, Roberts SK. High-dose vitamin D supplementation and liver histology in NASH. Gut 2016 Apr; 65: 717-8. PMID: 26294696.
25. Lorvand Amiri H, Agah S, Mousavi SN, Hosseini AF, Shidfar F. Regression of Non-Alcoholic Fatty Liver by Vitamin D Supplement: A Double-Blind Randomized Controlled Clinical Trial. Arch Iran Med; 19: 631-8. PMID: 27631178.
26. Sharifi N, Amani R, Hajiani E, Cheraghian B. Women may respond different from men to vitamin D supplementation regarding cardiometabolic biomarkers. Exp Biol Med (Maywood) 2016; 241: 830-8. PMID: 26811103.
27. Papapostoli I, Lammert F, Stokes CS. Effect of Short-Term Vitamin D Correction on Hepatic Steatosis as Quantified by Controlled Attenuation Parameter (CAP). J Gastrointestin Liver Dis 2016; 25: 175-81. PMID: 27308648.
28. Foroughi M, Maghsoudi Z, Askari G. The effect of vitamin D supplementation on blood sugar and different indices of insulin resistance in patients with non-alcoholic fatty liver disease (NAFLD). Iran J Nurs Midwifery Res 2016;21: 100-4. PMID: 26985230.
29. Dabbaghmanesh MH, Danafar F, Eshraghian A, Omrani GR. Vitamin D supplementation for the treatment of non-alcoholic fatty liver disease: A randomized double blind placebo controlled trial. Diabetes Metab Syndr 2018; 12: 513-517. PMID: 29588137.
30. Erbaş O, Solmaz V, Aksoy D, Yavaşoğlu A, Sağcan M, Taşkıran D. Cholecalciferol (vitamin D 3) improves cognitive dysfunction and reduces inflammation in a rat fatty liver model of metabolic syndrome. Life Sci 2014; 103: 68-72. PMID: 24727236.
31. Han H, Cui M, You X, Chen M, Piao X, Jin G. A role of 1,25(OH)2D3 supplementation in rats with nonalcoholic steatohepatitis induced by choline-deficient diet. Nutr Metab Cardiovasc Dis 2015; 25: 556-61. PMID: 25843661.
32. Wang H, Zhang Q, Chai Y, Liu Y, Li F, Wang B,et al. 1,25(OH)2D3 downregulates the Toll-like receptor 4-mediated inflammatory pathway and ameliorates liver injury in diabetic rats. J Endocrinol Invest 2015; 38: 1083-91. PMID: 25906757.
33. Shojaei Zarghani S, Soraya H, Alizadeh M. Calcium and vitamin D(3) combinations improve fatty liver disease through AMPK-independent mechanisms. Eur J Nutr 2018; 57: 731-740. PMID: 27988847.
34. Li R, Guo E, Yang J, Li A, Yang Y, Liu S, et al. 1,25(OH)(2) D(3) attenuates hepatic steatosis by inducing autophagy in mice. Obesity (Silver Spring) 2017; 25: 561-571. PMID: 28145056.
35. Zhu CG, Liu YX, Wang H, Wang BP, Qu HQ, Wang BL,et al. Active form of vitamin D ameliorates non-alcoholic fatty liver disease by alleviating oxidative stress in a high-fat diet rat model. Endocr J 2017; 64: 663-673. PMID: 28539530.
36. El-Sherbiny M, Eldosoky M, El-Shafey M, Othman G, Elkattawy HA, Bedir T, et al. Vitamin D nanoemulsion enhances hepatoprotective effect of conventional vitamin D in rats fed with a high-fat diet. Chem Biol Interact 2018; 288: 65-75. PMID: 29653100.
37. Ipekci SH, Basaranoglu M, Sonsuz A. The fluctuation of serum levels of aminotransferase in patients with nonalcoholic steatohepatitis. J Clin Gastroenterol 2003; 36: 371. PMID: 12642751.
38. Liangpunsakul S, Chalasani N. Serum vitamin D concentrations and unexplained elevation in ALT among US adults. Dig Dis Sci 2011; 56: 2124-9. PMID: 21503677.
39. Rhee EJ, Kim MK, Park SE, Park CY, Baek KH, Lee WY, et al. High serum vitamin D levels reduce the risk for nonalcoholic fatty liver disease in healthy men independent of metabolic syndrome. Endocr J 2013; 60: 743-52. PMID: 23411507.
40. Skaaby T, Husemoen LL, Borglykke A, Jørgensen T, Thuesen BH, Pisinger C, et al. Vitamin D status, liver enzymes, and incident liver disease and mortality: a general population study. Endocrine 2014; 47: 213-20. PMID: 24272594.
41. Jou J, Choi SS, Diehl AM. Mechanisms of disease progression in nonalcoholic fatty liver disease. Semin Liver Dis 2008; 28: 370-9. PMID: 18956293.
42. Eslamparast T, Eghtesad S, Poustchi H, Hekmatdoost A. Recent advances in dietary supplementation, in treating non-alcoholic fatty liver disease. World J Hepatol 2015; 7: 204-12. PMID: 25729475.
43. Haukeland JW, Damås JK, Konopski Z, Løberg EM, Haaland T, Goverud I, et al. Systemic inflammation in nonalcoholic fatty liver disease is characterized by elevated levels of CCL2. J Hepatol 2006; 44: 1167-74. PMID: 16618517.
44. Targher G, Arcaro G. Non-alcoholic fatty liver disease and increased risk of cardiovascular disease. Atherosclerosis 2007; 191: 235-40. PMID: 16970951.
45. Cantorna MT, Zhu Y, Froicu M, Wittke A. Vitamin D status, 1,25-dihydroxyvitamin D3, and the immune system. Am J Clin Nutr 2004; 80: 1717S-20S. PMID: 15585793.
46. Boucher BJ, Mannan N, Noonan K, Hales CN, Evans SJ. Glucose intolerance and impairment of insulin secretion in relation to vitamin D deficiency in east London Asians. Diabetologia 1995; 38: 1239-45. PMID: 8690178.
47. Czaja MJ, Weiner FR, Flanders KC, Giambrone MA, Wind R, Biempica L, et al. In vitro and in vivo association of transforming growth factor-beta 1 with hepatic fibrosis. J Cell Biol 1989; 108: 2477-82. PMID: 2500447.
48. Blobe GC, Schiemann WP, Lodish HF. Role of transforming growth factor beta in human disease. N Engl J Med 2000; 342: 1350-8. PMID: 10793168.
49. Targher G, Bertolini L, Rodella S, Zoppini G, Scala L, Zenari L, et al. Associations between plasma adiponectin concentrations and liver histology in patients with nonalcoholic fatty liver disease. Clin Endocrinol (Oxf) 2006; 64: 679-83. PMID: 16712671.
50. Nakano T, Cheng YF, Lai CY, Hsu LW, Chang YC, Deng JY, et al. Impact of artificial sunlight therapy on the progress of non-alcoholic fatty liver disease in rats. J Hepatol 2011; 55: 415-25. PMID: 21184788.
51. Schäffler A, Schölmerich J, Büchler C. Mechanisms of disease: adipocytokines and visceral adipose tissue--emerging role in nonalcoholic fatty liver disease. Nat Clin Pract Gastroenterol Hepatol 2005; 2: 273-80. PMID: 16265231.
52. Song L, Qu D, Zhang Q, Jiang J, Zhou H, Jiang R, et al. Phytosterol esters attenuate hepatic steatosis in rats with non-alcoholic fatty liver disease rats fed a high-fat diet. Sci Rep 2017; 7: 41604. PMID: 28169366.
53. Xie Y, Zhang Y, Guo Z, Zeng H, Zheng B. Effect of Alkaloids from Nelumbinis Plumula against Insulin Resistance of High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease in Mice. J Diabetes Res 2016; 2016: 3965864. PMID: 27761469.
54. Crespo J, Cayón A, Fernández-Gil P, Hernández-Guerra M, Mayorga M, Domínguez-Díez A, et al. Gene expression of tumor necrosis factor alpha and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients. Hepatology 2001; 34: 1158-63. PMID: 11732005.
55. Fon Tacer K, Rozman D. Nonalcoholic Fatty liver disease: focus on lipoprotein and lipid deregulation. J Lipids 2011; 2011: 783976. PMID: 21773052.
56. Yin Y, Yu Z, Xia M, Luo X, Lu X, Ling W. Vitamin D attenuates high fat diet-induced hepatic steatosis in rats by modulating lipid metabolism. Eur J Clin Invest 2012; 42: 1189-96. PMID: 22958216.
57. Barchetta I, Angelico F, Del Ben M, Baroni MG, Pozzilli P, Morini S, et al. Strong association between non alcoholic fatty liver disease (NAFLD) and low 25(OH) vitamin D levels in an adult population with normal serum liver enzymes. BMC Med 2011; 9: 85. PMID: 21749681.
58. Fujita N, Itoh T, Omori H, Fukuda M, Noda T, Yoshimori T. The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy. Mol Biol Cell 2008; 19: 2092-100. PMID: 18321988.
59. Zhang Y, Meng T, Zuo L, Bei Y, Zhang Q, Su Z, et al. Xyloketal B Attenuates Fatty Acid-Induced Lipid Accumulation via the SREBP-1c Pathway in NAFLD Models. Mar Drugs 2017; 15. PMID: 28587208.
60. Lee KC, Hsieh YC, Yang YY, Chan CC, Huang YH, Lin HC. Aliskiren Reduces Hepatic steatosis and Epididymal Fat Mass and Increases Skeletal Muscle Insulin Sensitivity in High-Fat Diet-Fed Mice. Sci Rep 2016; 6: 18899. PMID: 26732252.
61. Heritage M, Jaskowski L, Bridle K, Campbell C, Briskey D, Britton L, et al. Combination curcumin and vitamin E treatment attenuates diet-induced steatosis in Hfe-/- mice. World J Gastrointest Pathophysiol 2017; 8: 67-76. PMID: 28573069.
62. Serra D, Mera P, Malandrino MI, Mir JF, Herrero L. Mitochondrial fatty acid oxidation in obesity. Antioxid Redox Signal 2013; 19: 269-84. PMID: 22900819.
63. Sinha-Hikim I, Sinha-Hikim AP, Shen R, Kim HJ, French SW, Vaziri ND, et al. A novel cystine based antioxidant attenuates oxidative stress and hepatic steatosis in diet-induced obese mice. Exp Mol Pathol 2011; 91: 419-28. PMID: 21570964.
64. Hamden K, Carreau S, Jamoussi K, Miladi S, Lajmi S, Aloulou D, et al. 1Alpha,25 dihydroxyvitamin D3: therapeutic and preventive effects against oxidative stress, hepatic, pancreatic and renal injury in alloxan-induced diabetes in rats. J Nutr Sci Vitaminol (Tokyo) 2009; 55: 215-22. PMID: 19602829.
65. Malaguarnera L, Madeddu R, Palio E, Arena N, Malaguarnera M. Heme oxygenase-1 levels and oxidative stress-related parameters in non-alcoholic fatty liver disease patients. J Hepatol 2005; 42: 585-91. PMID: 15763346.
66. Tarcin O, Yavuz DG, Ozben B, Telli A, Ogunc AV, Yuksel M,et al. Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects. J Clin Endocrinol Metab 2009; 94: 4023-30. PMID: 19584181.
67. Banakar MC, Paramasivan SK, Chattopadhyay MB, Datta S, Chakraborty P, Chatterjee M, et al. 1alpha, 25-dihydroxyvitamin D3 prevents DNA damage and restores antioxidant enzymes in rat hepatocarcinogenesis induced by diethylnitrosamine and promoted by phenobarbital. World J Gastroenterol 2004; 10: 1268-75. PMID: 15112340.
68. Pessayre D. Role of mitochondria in non-alcoholic fatty liver disease. J Gastroenterol Hepatol 2008; 23: 501-2. PMID: 17567459.
69. Hardwick RN, Fisher CD, Canet MJ, Lake AD, Cherrington NJ. Diversity in antioxidant response enzymes in progressive stages of human nonalcoholic fatty liver disease. Drug Metab Dispos 2010; 38: 2293-301. PMID: 20805291.
70. Lee JM, Johnson JA. An important role of Nrf2-ARE pathway in the cellular defense mechanism. J Biochem Mol Biol 2004; 37: 139-43. PMID: 15469687.
71. Nakai K, Fujii H, Kono K, Goto S, Kitazawa R, Kitazawa S, et al. Vitamin D activates the Nrf2-Keap1 antioxidant pathway and ameliorates nephropathy in diabetic rats. Am J Hypertens 2014; 27: 586-95. PMID: 24025724.
72. Xiao J, Guo R, Fung ML, Liong EC, Chang RC, Ching YP, et al. Garlic-Derived S-Allylmercaptocysteine Ameliorates Nonalcoholic Fatty Liver Disease in a Rat Model through Inhibition of Apoptosis and Enhancing Autophagy. Evid Based Complement Alternat Med 2013; 2013: 642920. PMID: 23861709.
73. Alkhouri N, Carter-Kent C, Feldstein AE. Apoptosis in nonalcoholic fatty liver disease: diagnostic and therapeutic implications. Expert Rev Gastroenterol Hepatol 2011; 5: 201-12. PMID: 21476915.
74. Lisakovska O, Shymanskyy I, Mazanova A, Khomenko A, Veliky M. Vitamin D(3) protects against prednisolone-induced liver injury associated with the impairment of the hepatic NF-κB/iNOS/NO pathway. Biochem Cell Biol 2017; 95: 213-222. PMID: 28004974.
75. Browning JD, Horton JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 2004; 114: 147-52. PMID: 15254578.
76. Pacifico L, Anania C, Osborn JF, Ferraro F, Bonci E, Olivero E, et al. Low 25(OH)D3 levels are associated with total adiposity, metabolic syndrome, and hypertension in Caucasian children and adolescents. Eur J Endocrinol 2011; 165: 603-11. PMID: 21753070.
77. Muldowney S, Lucey AJ, Paschos G, Martinez JA, Bandarra N, Thorsdottir I, et al. Relationships between vitamin D status and cardio-metabolic risk factors in young European adults. Ann Nutr Metab 2011; 58: 85-93. PMID: 21474925.
78. Marchesini G, Brizi M, Morselli-Labate AM, Bianchi G, Bugianesi E, McCullough AJ, et al. Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med 1999; 107: 450-5. PMID: 10569299.
79. Seppälä-Lindroos A, Vehkavaara S, Häkkinen AM, Goto T, Westerbacka J, Sovijärvi A, et al. Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. J Clin Endocrinol Metab 2002; 87: 3023-8. PMID: 12107194.
80. Inzucchi SE, Maggs DG, Spollett GR, Page SL, Rife FS, Walton V, et al. Efficacy and metabolic effects of metformin and troglitazone in type II diabetes mellitus. N Engl J Med 1998; 338: 867-72. PMID: 9516221.
81. Lind L, Pollare T, Hvarfner A, Lithell H, Sørensen OH, Ljunghall S. Long-term treatment with active vitamin D (alphacalcidol) in middle-aged men with impaired glucose tolerance. Effects on insulin secretion and sensitivity, glucose tolerance and blood pressure. Diabetes Res 1989; 11: 141-7. PMID: 2697485.
82. Zeitz U, Weber K, Soegiarto DW, Wolf E, Balling R, Erben RG. Impaired insulin secretory capacity in mice lacking a functional vitamin D receptor. FASEB J 2003; 17: 509-11. PMID: 12551842.
83. Nagpal J, Pande JN, Bhartia A. A double-blind, randomized, placebo-controlled trial of the short-term effect of vitamin D3 supplementation on insulin sensitivity in apparently healthy, middle-aged, centrally obese men. Diabet Med 2009; 26: 19-27. PMID: 19125756.
84. Pinelli NR, Jaber LA, Brown MB, Herman WH. Serum 25-hydroxy vitamin d and insulin resistance, metabolic syndrome, and glucose intolerance among Arab Americans. Diabetes Care 2010; 33: 1373-5. PMID: 20332348.