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 Sep;47(1):70-80. doi: 10.1007/s12020-014-0336-5. Epub 2014 Jun 27.
Sharifi N1, Amani R, Hajiani E, Cheraghian B.
1Department of Nutrition, Faculty of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran, sharifi.nsr at gmail.com.
50,000 IU every two weeks for four months
Vitamin D levels only raised by only 16 ng
A poorly functioning liver processes Vitamin D poorly
Need either more or a different kind of vitamin D to get an acceptable response
See also Vitamin D Life
Liver Inflammation (NAFLD) is prevented by Vitamin D – review May 2015
Poorly functioning livers do not process vitamin D (Calcidiol is needed) – Sept 2014
Many ways to increase Vitamin D - click on chart for details
The aim of this study was to investigate the effects of vitamin D supplementation on serum aminotransferases, insulin resistance, oxidative stress, and inflammatory biomarkers in adult patients with non-alcoholic fatty liver disease (NAFLD).
Fifty-three patients with NAFLD were enrolled in a parallel, double-blind, placebo-controlled study. The patients were randomly allocated to receive either one oral pearl consisting of 50,000 IU vitamin D3 (n = 27) or a placebo (n = 26), every 14 days for 4 months. Serum aminotransferases, high-sensitive C-reactive protein (hs-CRP), tumor necrosis factor α, malondialdehyde (MDA), total antioxidant capacity, transforming growth factor β1, as well as grade of hepatic steatosis and homeostasis model assessment of insulin resistance were assessed pre- and post-intervention. In patients who received vitamin D supplement compared to the controls, the median of serum 25(OH)D3 significantly increased (16.2 vs. 1.6 ng/ml, P < 0.001).
This increase accompanied by significant decrease in serum MDA (-2.09 vs. -1.23 ng/ml, P = 0.03) and near significant changes in serum hs-CRP (-0.25 vs. 0.22 mg/l, P = 0.06).
These between-group differences remained significant even after controlling for baseline covariates. Other variables showed no significant changes. Improved vitamin D status led to amelioration in serum hs-CRP and MDA in patients with NAFLD. This might be considered as an adjunctive therapy to attenuate systemic inflammation and lipid peroxidation alongside other treatments for NAFLD patients.
PMID: 24968737
Publisher wants $40 for the PDF
References
- E.A. Yetley, Assessing the vitamin D status of the US population. Am. J. Clin. Nutr. 88(2), 558S–564S (2008)PubMed
- M.F. Holick, Vitamin D deficiency. N. Engl. J. Med. 357(3), 266–281 2007)PubMedView Article
- J.S. Adams, M. Hewison, Update in vitamin D. J. Clin. Endocrinol. Metab. 95(2), 471–478 (2010)PubMed CentralPubMedView Article
- G. Musso, Non-alcoholic fatty liver, adipose tissue, and the bone: a new triumvirate on the block. Endocrine 42, 237–239 (2012)PubMedView Article
- E. Hyppönen, B.J. Boucher, D.J. Berry, C. Power, 25-hydroxyvitamin D, IGF-1, and metabolic syndrome at 45 years of age. Diabetes 57(2), 298–305 (2008)PubMedView Article
- J.P. Reis, D. von Mühlen, D. Kritz-Silverstein, D.L. Wingard, E. Barrett-Connor, Vitamin D, parathyroid hormone levels, and the prevalence of metabolic syndrome in community-dwelling older adults. Diabetes Care 30(6), 1549–1555 (2007)PubMedView Article
- L.-H. Li, X.-Y. Yin, C.-Y. Yao, X.-C. Zhu, X.-H. Wu, Serum 25-hydroxyvitamin D, parathyroid hormone, and their association with metabolic syndrome in Chinese. Endocrine 44(2), 465–472 (2013)PubMedView Article
- N.C. Bozkurt, E. Cakal, M. Sahin, E.C. Ozkaya, H. Firat, T. Delibasi, The relation of serum 25-hydroxyvitamin-D levels with severity of obstructive sleep apnea and glucose metabolism abnormalities. Endocrine 41(3), 518–525 (2012)PubMedView Article
- G. Targher, L. Bertolini, L. Scala, M. Cigolini, L. Zenari, G. Falezza, G. Arcaro, Associations between serum 25-hydroxyvitamin D3 concentrations and liver histology in patients with non-alcoholic fatty liver disease. Nutr. Metab. Cardiovasc. Dis 17(7), 517–524 (2007)PubMedView Article
- J.M. Clark, F.L. Brancati, A.M. Diehl, Nonalcoholic fatty liver disease. Gastroenterology 122(6), 1649–1657 (2002)PubMedView Article
- I. Barchetta, F. Angelico, M.D. Ben, M.G. Baroni, P. Pozzilli, S. Morini, M.G. Cavallo, 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. 9(1), 85 (2011)PubMed CentralPubMedView Article
- T. Nakano, Y.F. Cheng, C.Y. Lai, L.W. Hsu, Y.C. Chang, J.Y. Deng, Y.Z. Huang, H. Honda, K.D. Chen, C.C. Wang, Impact of artificial sunlight therapy on the progress of non-alcoholic fatty liver disease in rats. J. Hepatol. 55(2), 415–425 (2011)PubMedView Article
- E. Rhee, M. Kim, S. Park, C. Park, K. Baek, W. Lee, M. Kang, S. Park, S. Kim, K. Oh, High serum vitamin D levels reduce the risk for nonalcoholic fatty liver disease in healthy men independent of metabolic syndrome. Endocr. J. 60(6), 743–752 (2013)PubMedView Article
- G. Targher, C. Byrne, Lower 25-hydroxyvitamin D3 levels and increased risk of liver diseases: is there a causal link? Endocrine (2014). doi:10.1007/s12020-014-0220-3 PubMed
- C.L. Roth, C.T. Elfers, D.P. Figlewicz, S.J. Melhorn, G.J. Morton, A. Hoofnagle, M.M. Yeh, J.E. Nelson, K.V. Kowdley, Vitamin D deficiency in obese rats exacerbates nonalcoholic fatty liver disease and increases hepatic resistin and toll-like receptor activation. Hepatology 55(4), 1103–1111 (2012)PubMedView Article
- D. Prati, E. Taioli, A. Zanella, E. Della Torre, S. Butelli, E. Del Vecchio, L. Vianello, F. Zanuso, F. Mozzi, S. Milani, Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann. Intern. Med. 137(1), 1–10 (2002)PubMedView Article
- S. Abu-Mouch, Z. Fireman, J. Jarchovsky, A.R. Zeina, N. Assy, Vitamin D supplementation improves sustained virologic response in chronic hepatitis C (genotype 1)-naïve patients. World J. Gastroenterol. 17(47), 5184–5190 (2011)PubMed CentralPubMedView Article
- C.L. Craig, A.L. Marshall, M. Sjöström, A.E. Bauman, M.L. Booth, B.E. Ainsworth, M. Pratt, U. Ekelund, A. Yngve, J.F. Sallis, International physical activity questionnaire: 12-country reliability and validity. Med. Sci. Sports Exerc. 85(3), 1381–1395 (2003)View Article
- N.A. Botsoglou, D.J. Fletouris, G.E. Papageorgiou, V.N. Vassilopoulos, A.J. Mantis, A.G. Trakatellis, Rapid, sensitive, and specific thiobarbituric acid method for measuring lipid peroxidation in animal tissue, food, and feedstuff samples. J. Agric. Food Chem. 42(9), 1931–1937 (1994)View Article
- A. Khosrowbeygi, N. Zarghami, Y. Deldar, Correlation between sperm quality parameters and seminal plasma antioxidants status. Iran. J. Reprod. Med. 2(2), 58–64 (2012)
- J. Jou, S.S. Choi, A.M. Diehl, Mechanisms of disease progression in nonalcoholic fatty liver disease. Semin. Liver Dis. 28(04), 370–379 (2008)PubMedView Article
- J.W. Haukeland, J.K. Damås, Z. Konopski, E.M. Løberg, T. Haaland, I. Goverud, P.A. Torjesen, K. Birkeland, K. Bjøro, P. Aukrust, Systemic inflammation in nonalcoholic fatty liver disease is characterized by elevated levels of CCL2. J. Hepatol. 44(6), 1167–1174 (2006)PubMedView Article
- G. Targher, Relationship between high-sensitivity C-reactive protein levels and liver histology in subjects with non-alcoholic fatty liver disease. J. Hepatol. 45(6), 879–881 (2006)PubMedView Article
- G. Targher, G. Arcaro, Non-alcoholic fatty liver disease and increased risk of cardiovascular disease. Atherosclerosis 191(2), 235–240 (2007)PubMedView Article
- M.T. Cantorna, Y. Zhu, M. Froicu, A. Wittke, Vitamin D status, 1, 25-dihydroxyvitamin D3, and the immune system. Am. J. Clin. Nutr. 80(6), 1717S–1720S (2004)PubMed
- S. Zúñiga, D. Firrincieli, C. Housset, N. Chignard, Vitamin D and the vitamin D receptor in liver pathophysiology. Clin. Res. Hepatol. Gastroenterol. 35, 295–302 (2011)PubMedView Article
- A. Zittermann, S. Frisch, H.K. Berthold, C. Götting, J. Kuhn, K. Kleesiek, P. Stehle, H. Koertke, R. Koerfer, Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers. Am. J. Clin. Nutr. 89(5), 1321–1327 (2009)PubMedView Article
- S.S. Schleithoff, A. Zittermann, G. Tenderich, H.K. Berthold, P. Stehle, R. Koerfer, Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Am. J. Clin. Nutr. 83(4), 754–759 (2006)PubMed
- J. Beilfuss, V. Berg, M. Sneve, R. Jorde, E. Kamycheva, Effects of a 1-year supplementation with cholecalciferol on interleukin-6, tumor necrosis factor-alpha and insulin resistance in overweight and obese subjects. Cytokine 60(3), 870–874 (2012)PubMedView Article
- Y. Karim, C. Turner, N. Dalton, R. Roplekar, A. Sankaralingam, M. Ewang, I. Fogelman, G. Hampson, The relationship between pro-resorptive inflammatory cytokines and the effect of high dose vitamin D supplementation on their circulating concentrations. Int. Immunopharmacol. 17(3), 693–697 (2013)PubMedView Article
- S. Shab-Bidar, T.R. Neyestani, A. Djazayery, M.R. Eshraghian, A. Houshiarrad, A. Kalayi, N. Shariatzadeh, N. Khalaji, Improvement of vitamin D status resulted in amelioration of biomarkers of systemic inflammation in the subjects with type 2 diabetes. Diabetes Metab. Res. Rev. 28(5), 424–430 (2012)PubMedView Article
- M.J. Czaja, F.R. Weiner, K.C. Flanders, M.-A. Giambrone, R. Wind, L. Biempica, M.A. Zern, In vitro and in vivo association of transforming growth factor-beta 1 with hepatic fibrosis. J. Cell Biol. 108(6), 2477–2482 (1989)PubMedView Article
- F.H. Epstein, G.C. Blobe, W.P. Schiemann, H.F. Lodish, Role of transforming growth factor β in human disease. N. Engl. J. Med. 342(18), 1350–1358 (2000)View Article
- T. Hasegawa, M. Yoneda, K. Nakamura, I. Makino, A. Terano, Plasma transforming growth factor-β1 level and efficacy of α-tocopherol in patients with non-alcoholic steatohepatitis: a pilot study. Aliment Pharmacol. Ther. 15(10), 1667–1672 (2001)PubMedView Article
- S. Isik, U. Ozuguz, Y. Ates Tutuncu, G. Erden, D. Berker, K. Acar, Y. Aydin, G. Akbaba, N. Helvaci, S. Guler, Serum transforming growth factor-beta levels in patients with vitamin D deficiency. Eur. J. Intern. Med. 23(1), 93–97 (2012)PubMedView Article
- A.A. Mahmoud, A.S. Bakir, S.S. Shabana, Serum TGF-β, Serum MMP-1, and HOMA-IR as non-invasive predictors of fibrosis in Egyptian patients with NAFLD. Saudi J. Gastroenterol. 18(5), 327 (2012)PubMed CentralPubMedView Article
- L. Malaguarnera, R. Madeddu, E. Palio, N. Arena, M. Malaguarnera, Heme oxygenase-1 levels and oxidative stress-related parameters in non-alcoholic fatty liver disease patients. J. Hepatol. 42(4), 585–591 (2005)PubMedView Article
- H. Wiseman, Vitamin D is a membrane antioxidant Ability to inhibit iron-dependent lipid peroxidation in liposomes compared to cholesterol, ergosterol and tamoxifen and relevance to anticancer action. FEBS Lett. 326(1), 285–288 (1993)PubMedView Article
- O. Tarcin, D.G. Yavuz, B. Ozben, A. Telli, A.V. Ogunc, M. Yuksel, A. Toprak, D. Yazici, S. Sancak, O. Deyneli, Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects. J. Clin. Endocrinol. Metab. 94(10), 4023–4030 (2009)PubMedView Article
- M.C. Banakar, S.K. Paramasivan, M.B. Chattopadhyay, S. Datta, P. Chakraborty, M. Chatterjee, K. Kannan, E. Thyagarajan, 1,25-Dihydroxyvitamin D3 prevents DNA damage and restores antioxidant enzymes in rat hepatocarcinogenesis induced by diethylnitrosamine and promoted by phenobarbital. World J. Gasteroenterol. 10, 1268–1275 (2004)
- A.G. Pittas, S.S. Harris, P.C. Stark, B. Dawson-Hughes, The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults. Diabetes Care 30(4), 980–986 (2007)PubMedView Article
- P.R. von Hurst, W. Stonehouse, J. Coad, Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient: a randomised, placebo-controlled trial. Br. J. Nutr. 103(4), 549 (2010)View Article
- E. Kamycheva, V. Berg, R. Jorde, Insulin-like growth factor I, growth hormone, and insulin sensitivity: the effects of a one-year cholecalciferol supplementation in middle-aged overweight and obese subjects. Endocrine 43(2), 412–418 (2013)PubMedView Article
- H.R. Ardabili, B.P. Gargari, L. Farzadi, Vitamin D supplementation has no effect on insulin resistance assessment in women with polycystic ovary syndrome and vitamin D deficiency. Nutr. Res. 32(3), 195–201 (2012)PubMedView Article
- I.H. de Boer, L.F. Tinker, S. Connelly, J.D. Curb, B.V. Howard, B. Kestenbaum, J.C. Larson, J.E. Manson, K.L. Margolis, D.S. Siscovick, Calcium plus vitamin D supplementation and the risk of incident diabetes in the Women’s Health Initiative. Diabetes Care 31(4), 701–707 (2008)PubMed CentralPubMedView Article
- R. Jorde, Y. Figenschau, Supplementation with cholecalciferol does not improve glycaemic control in diabetic subjects with normal serum 25-hydroxyvitamin D levels. Eur. J. Nutr. 48(6), 349–354 (2009)PubMedView Article
- A.G. Pittas, B. Dawson-Hughes, Vitamin D and diabetes. J. Steroid Biochem. Mol. Biol. 121(1), 425–429 (2010)PubMed CentralPubMedView Article
- A.G. Pittas, J. Lau, F.B. Hu, B. Dawson-Hughes, The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 92(6), 2017–2029 (2007)PubMed CentralPubMedView Article
- R.A. DeFronzo, J.D. Tobin, R. Andres, Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am. J. Physiol. Endocrinol. Metab. 237(3), E214 (1979)
- S.H. Ipekci, M. Basaranoglu, A. Sonsuz, The fluctuation of serum levels of aminotransferase in patients with nonalcoholic steatohepatitis. J. Clin. Gastroenterol. 36(4), 371 (2003)PubMedView Article
- S. Liangpunsakul, N. Chalasani, Serum vitamin D concentrations and unexplained elevation in ALT among US adults. Dig. Dis. Sci. 56(7), 2124–2129 (2011)PubMed CentralPubMedView Article
- T. Skaaby, L. Husemoen, A. Borglykke, T. Jørgensen, B. Thuesen, C. Pisinger, L. Schmidt, A. Linneberg, Vitamin D status, liver enzymes, and incident liver disease and mortality: a general population study. Endocrine (2013). doi:10.1007/s12020-013-0107-8 H.A. Saleh, A.H. Abu-Rashed, Liver biopsy remains the gold standard for evaluation of chronic hepatitis and fibrosis. J. Gastrointest. Liver. Dis. 16(4), 425 (2007)
- J.F. Cobbold, D. Patel, S.D. Taylor-Robinson, Assessment of inflammation and fibrosis in non-alcoholic fatty liver disease by imaging-based techniques. J. Gastroenterol. Hepatol. 27(8), 1281–1292 (2012)PubMedView Article
- G. Ligabue, G. Besutti, R. Scaglioni, C. Stentarelli, G. Guaraldi, MR quantitative biomarkers of non-alcoholic fatty liver disease: technical evolutions and future trends. Quant. Imaging Med. Surg. 3(4), 192 (2013)PubMed CentralPubMed
- M. Manco, P. Ciampalini, V. Nobili, Low levels of 25-hydroxyvitamin D3 in children with biopsy-proven nonalcoholic fatty liver disease. Hepatology 51(6), 2229 (2010)PubMedView Article
- M. Eliades, E. Spyrou, N. Agrawal, M. Lazo, F. Brancati, J. Potter, A. Koteish, J. Clark, E. Guallar, R. Hernaez, Meta-analysis: vitamin D and non-alcoholic fatty liver disease. Aliment Pharmacol. Ther. 38(3), 246–254 (2013)PubMedView Article
- A. Geier, Shedding new light on vitamin D and fatty liver disease. J. Hepatol. 55(2), 273–275 (2011)PubMedView Article
- G. Targher, E. Scorletti, A. Mantovani, C.D. Byrne, Nonalcoholic fatty liver disease and reduced serum vitamin D3 levels. Metab. Syndr. Relat. Disord. 11(4), 217–228 (2013)PubMedView Article