The effects of vitamin B12 supplementation on metabolic profile of patients with non-alcoholic fatty liver disease: a randomized controlled trial

Clinical Trials & Research
  • Clark, J. M. The epidemiology of nonalcoholic fatty liver disease in adults. J. Clin. Gastroenterol. 40(Suppl 1), S5–S10 (2006).

    PubMed 

    Google Scholar
     

  • Targher, G. & Arcaro, G. Non-alcoholic fatty liver disease and increased risk of cardiovascular disease. Atherosclerosis 191, 235–240 (2007).

    CAS 
    PubMed 

    Google Scholar
     

  • Noureddin, M., Mato, J. M. & Lu, S. C. Nonalcoholic fatty liver disease: Update on pathogenesis, diagnosis, treatment and the role of S-adenosylmethionine. Exp. Biol. Med. (Maywood) 240, 809–820 (2015).

    CAS 

    Google Scholar
     

  • Mato, J. M. & Lu, S. C. Role of S-adenosyl-L-methionine in liver health and injury. Hepatology 45, 1306–1312 (2007).

    CAS 
    PubMed 

    Google Scholar
     

  • Bottiglieri, T. S-Adenosyl-L-methionine (SAMe): From the bench to the bedside—Molecular basis of a pleiotrophic molecule. Am. J. Clin. Nutr. 76, 1151s–1157s (2002).

    CAS 
    PubMed 

    Google Scholar
     

  • Halsted, C. H. et al. Folate deficiency disturbs hepatic methionine metabolism and promotes liver injury in the ethanol-fed micropig. Proc. Natl. Acad. Sci. U.S.A. 99, 10072–10077 (2002).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hirsch, S. et al. Serum folate and homocysteine levels in obese females with non-alcoholic fatty liver. Nutrition 21, 137–141 (2005).

    CAS 
    PubMed 

    Google Scholar
     

  • Koplay, M., Gulcan, E. & Ozkan, F. Association between serum vitamin B12 levels and the degree of steatosis in patients with nonalcoholic fatty liver disease. J. Investig. Med. 59, 1137–1140 (2011).

    CAS 
    PubMed 

    Google Scholar
     

  • Polyzos, S. A. et al. Serum vitamin B12 and folate levels in patients with non-alcoholic fatty liver disease. Int. J. Food Sci. Nutr. 63, 659–666 (2012).

    CAS 
    PubMed 

    Google Scholar
     

  • Prati, D. et al. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann. Intern. Med. 137, 1–10 (2002).

    CAS 
    PubMed 

    Google Scholar
     

  • Kwok, T. et al. A randomized placebo controlled trial of vitamin B12 supplementation to prevent cognitive decline in older diabetic people with borderline low serum vitamin B12. Clin. Nutr. 36, 1509–1515 (2017).

    CAS 
    PubMed 

    Google Scholar
     

  • Romero-Gómez, M., Zelber-Sagi, S. & Trenell, M. Treatment of NAFLD with diet, physical activity and exercise. J. Hepatol. 67, 829–846 (2017).

    PubMed 

    Google Scholar
     

  • European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J. Hepatol. 64, 1388–1402 (2016).


    Google Scholar
     

  • Craig, C. L. et al. International physical activity questionnaire: 12-country reliability and validity. Med. Sci. Sports Exerc. 35, 1381–1395 (2003).

    PubMed 

    Google Scholar
     

  • Chimoriya, R., Piya, M. K., Simmons, D., Ahlenstiel, G. & Ho, V. The use of two-dimensional shear wave elastography in people with obesity for the assessment of liver fibrosis in non-alcoholic fatty liver disease. J. Clin. Med. 10, 95 (2020).

    PubMed Central 

    Google Scholar
     

  • Lee, D. H. et al. Accuracy of two-dimensional shear wave elastography and attenuation imaging for evaluation of patients with nonalcoholic steatohepatitis. Clin. Gastroenterol. Hepatol. 19, 797–805 (2021).

    PubMed 

    Google Scholar
     

  • Zaleska-Dorobisz, U. et al. The evaluation of liver fibrosis in the real-time shear wave elastography technique in chronic hepatitis B and C patients: How many measurements are necessary to assign patients to METAVIR score properly? Hepat. Mon. 18, e61189 (2018).


    Google Scholar
     

  • Botsoglou, N. A. et al. Rapid, sensitive, and specific thiobarbituric acid method for measuring lipid peroxidation in animal tissue, food, and feedstuff samples. J. Agric. Food Chem. 42, 1931–1937 (1994).

    CAS 

    Google Scholar
     

  • Xu, Y., Guan, Y., Yang, X., Xia, Z. & Wu, J. Association of serum homocysteine levels with histological severity of NAFLD. J. Gastrointest. Liver Dis. 29, 51–58 (2020).


    Google Scholar
     

  • de Carvalho, S. C. et al. Plasmatic higher levels of homocysteine in non-alcoholic fatty liver disease (NAFLD). Nutr. J. 12, 37 (2013).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gulsen, M. et al. Elevated plasma homocysteine concentrations as a predictor of steatohepatitis in patients with non-alcoholic fatty liver disease. J. Gastroenterol. Hepatol. 20, 1448–1455 (2005).

    CAS 
    PubMed 

    Google Scholar
     

  • Ai, Y. et al. Homocysteine induces hepatic steatosis involving ER stress response in high methionine diet-fed mice. Nutrients 9, 346 (2017).

    PubMed Central 

    Google Scholar
     

  • Polyzos, S. A. et al. Serum homocysteine levels in patients with nonalcoholic fatty liver disease. Ann. Hepatol. 11, 68–76 (2012).

    CAS 
    PubMed 

    Google Scholar
     

  • Dai, Y., Zhu, J., Meng, D., Yu, C. & Li, Y. Association of homocysteine level with biopsy-proven non-alcoholic fatty liver disease: a meta-analysis. J. Clin. Biochem. Nutr. 58, 76–83 (2016).

    CAS 
    PubMed 

    Google Scholar
     

  • Werstuck, G. H. et al. Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways. J. Clin. Investig. 107, 1263–1273 (2001).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Werge, M. P. et al. The role of the transsulfuration pathway in non-alcoholic fatty liver disease. J. Clin. Med. 10, 1081 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cordero, P., Gomez-Uriz, A. M., Campion, J., Milagro, F. I. & Martinez, J. A. Dietary supplementation with methyl donors reduces fatty liver and modifies the fatty acid synthase DNA methylation profile in rats fed an obesogenic diet. Genes Nutr. 8, 105–113 (2013).

    CAS 
    PubMed 

    Google Scholar
     

  • Pooya, S. et al. Methyl donor deficiency impairs fatty acid oxidation through PGC-1alpha hypomethylation and decreased ER-alpha, ERR-alpha, and HNF-4alpha in the rat liver. J. Hepatol. 57, 344–351 (2012).

    CAS 
    PubMed 

    Google Scholar
     

  • Jacobs, R. L., Lingrell, S., Zhao, Y., Francis, G. A. & Vance, D. E. Hepatic CTP: Phosphocholine cytidylyltransferase-alpha is a critical predictor of plasma high density lipoprotein and very low density lipoprotein. J. Biol. Chem. 283, 2147–2155 (2008).

    CAS 
    PubMed 

    Google Scholar
     

  • Zhao, Y. et al. Lack of phosphatidylethanolamine N-methyltransferase alters plasma VLDL phospholipids and attenuates atherosclerosis in mice. Arterioscler. Thromb. Vasc. Biol. 29, 1349–1355 (2009).

    CAS 
    PubMed 

    Google Scholar
     

  • Abdulkhaleq, F. M. et al. Antioxidative stress effects of vitamins C, E, and B(12), and their combination can protect the liver against acetaminophen-induced hepatotoxicity in rats. Drug Des. Dev. Ther. 12, 3525–3533 (2018).

    CAS 

    Google Scholar
     

  • Monserrat-Mesquida, M. et al. Oxidative stress and pro-inflammatory status in patients with non-alcoholic fatty liver disease. Antioxidants (Basel) 9, 759 (2020).

    CAS 

    Google Scholar
     

  • Zelber-Sagi, S. et al. Serum malondialdehyde is associated with non-alcoholic fatty liver and related liver damage differentially in men and women. Antioxidants (Basel) 9, 759 (2020).


    Google Scholar
     

  • Bayés, B., Pastor, M. C., Bonal, J., Juncà, J. & Romero, R. Homocysteine and lipid peroxidation in haemodialysis: Role of folinic acid and vitamin E. Nephrol. Dial. Transplant. 16, 2172–2175 (2001).

    PubMed 

    Google Scholar
     

  • Racek, J., Rusnáková, H., Trefil, L. & Siala, K. K. The influence of folate and antioxidants on homocysteine levels and oxidative stress in patients with hyperlipidemia and hyperhomocysteinemia. Physiol. Res. 54, 87–95 (2005).

    CAS 
    PubMed 

    Google Scholar
     

  • Aghamohammadi, V., Gargari, B. P. & Aliasgharzadeh, A. Effect of folic acid supplementation on homocysteine, serum total antioxidant capacity, and malondialdehyde in patients with type 2 diabetes mellitus. J. Am. Coll. Nutr. 30, 210–215 (2011).

    CAS 
    PubMed 

    Google Scholar
     

  • Armandi, A., Rosso, C., Caviglia, G. P. & Bugianesi, E. Insulin resistance across the spectrum of nonalcoholic fatty liver disease. Metabolites 11, 155 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, Z. et al. Folate and vitamin B12 status is associated with insulin resistance and metabolic syndrome in morbid obesity. Clin. Nutr. 37, 1700–1706 (2018).

    CAS 
    PubMed 

    Google Scholar
     

  • Iglesia, I. et al. Associations between insulin resistance and three B-vitamins in European adolescents: The HELENA study. Nutr. Hosp. 34, 568–577 (2017).

    CAS 
    PubMed 

    Google Scholar
     

  • Al-Daghri, N. M. et al. Association of vitamin B12 with pro-inflammatory cytokines and biochemical markers related to cardiometabolic risk in Saudi subjects. Nutrients 8, 460 (2016).

    PubMed Central 

    Google Scholar
     

  • Kurt, R. et al. Folic Acid and vitamin B12 supplementation improves coronary flow reserve in elderly subjects with vitamin B12 deficiency. Arch. Med. Res. 41, 369–372 (2010).

    CAS 
    PubMed 

    Google Scholar
     

  • Setola, E. et al. Insulin resistance and endothelial function are improved after folate and vitamin B12 therapy in patients with metabolic syndrome: Relationship between homocysteine levels and hyperinsulinemia. Eur. J. Endocrinol. 151, 483–489 (2004).

    CAS 
    PubMed 

    Google Scholar
     

  • Satapathy, S., Bandyopadhyay, D., Patro, B. K., Khan, S. & Naik, S. Folic acid and vitamin B12 supplementation in subjects with type 2 diabetes mellitus: A multi-arm randomized controlled clinical trial. Complement Ther. Med. 53, 102526 (2020).

    PubMed 

    Google Scholar
     

  • Najib, S. & Sánchez-Margalet, V. Homocysteine thiolactone inhibits insulin signaling, and glutathione has a protective effect. J. Mol. Endocrinol. 27, 85–91 (2001).

    CAS 
    PubMed 

    Google Scholar
     

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