The Effect of Vitamin D on Metabolic Profiles in Patients With Fatty Liver Disease

Background. Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. According to various studies, one of the factors contributing to the development and progression of NAFLD is vitamin D deficiency and insufficiency. Objective. To investigate the interrelationships between clinical and laboratory-instrumental markers of fibrosis activity as well as disturbances in lipid and carbohydrate metabolism in patients with NAFLD before and after completing a course of vitamin D supplementation. Materials and Methods. The study included 121 patients with NAFLD who received vitamin D supplements due to diagnosed deficiency or insufficiency. Anthropometric, laboratory, and instrumental indicators were measured before and after the course of vitamin D therapy. Results. After the treatment, most patients demonstrated a statistically significant increase in vitamin D levels (p < 0.001) and improvement in lipid and carbohydrate metabolism. Mean body mass index, waist circumference, triglyceride levels, and insulin levels decreased significantly (p < 0.05). Additionally, correcting vitamin D deficiency and insufficiency contributed to improvements in liver markers, such as ALT, AST, and composite indices. Conclusion. The obtained data confirm a high prevalence of lipid and carbohydrate metabolic disorders among patients with NAFLD. Vitamin D supplementation significantly improves a range of clinical and laboratory parameters (BMI, WC, AST, albumin, glucose, FLI) in NAFLD patients, emphasizing the need for timely correction of vitamin D insufficiency and deficiency as part of comprehensive NAFLD treatment.

non-alcoholic fatty liver disease, NAFLD, vitamin D, metabolic syndrome, obesity, lipid metabolism, carbohydrate metabolism

1. Khalashte A. A., Lyalyukova E. A., Zhachemuk S. K., Beslangurova Z. A., Zhernakova G. N. Eating behavior in patients with metabolically associated fatty liver disease. Experimental and Clinical Gastroenterology. 2024;(5):90-99. (In Russ.) doi: 10.31146/1682-8658-ecg-225-5-90-99.@@ Халаште А. А., Лялюкова Е. А., Жачемук С. К., Беслангурова З. А., Жернакова Г. Н. Пищевое поведение у пациентов с метаболически ассоциированной жировой болезнью печени. Экспериментальная и клиническая гастроэнтерология. 2024;(5):90-99. doi: 10.31146/1682-8658-ecg-225-5-90-99.

2. Park D., Kwon H., Oh S. W. et al. Is Vitamin D an Independent Risk Factor of Nonalcoholic Fatty Liver Disease?: a Cross-Sectional Study of the Healthy Population. J Korean Med Sci. 2017 Jan;32(1):95-101. doi: 10.3346/jkms.2017.32.1.95.

3. Younossi Z., Anstee Q.M, Marietti M. et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018 Jan 20;15(1):11-20.

4. Riazi K., Azhari H., Charette J. H. et al. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2022 Sep;7(9):851-61.

5. Maev I.V., Andreev D. N., Kucheryavy Y. A. et al. Non-alcoholic fatty liver disease from the perspective of modern medicine. - Moscow: Authors’ Collective, 2023. (in Russ.)@@ Маев И. В., Андреев Д. Н., Кучерявый Ю. А. и соавт. Неалкогольная жировая болезнь печени с позиций современной медицины. - Москва: Коллектив авторов, 2023

6. Trukhan D. I. Features hepatoprotectors with prebiotic effect in therapeutic practice. Medical Council. 2016 Jan 1;(9):64-9. (in Russ.)@@ Трухан Д. И. Особенности гепатопротекторов с пребиотическим эффектом в терапевтической практике. Медицинский совет. 2016 Янв 1;(9):64-9.

7. Younossi Z. M. Non-alcoholic fatty liver disease - A global public health perspective. J Hepatol. 2019 Mar;70(3):531-44.

8. Mitra S., De A., Chowdhury A. Epidemiology of non-alcoholic and alcoholic fatty liver diseases. Transl Gastroenterol Hepatol. 2020 Apr;5:16-16.

9. Cotter T.G, Rinella M. Nonalcoholic Fatty Liver Disease 2020: The State of the Disease. Gastroenterology. 2020 May;158(7):1851-64.

10. Lazebnik L.B., Golovanova E. V., Turkina S. V. et al. Non-alcoholic fatty liver disease in adults: clinic, diagnostics, treatment. Guidelines for therapists, third version. Experimental and Clinical Gastroenterology. 2021;1(1):4-52. (In Russ.) doi: 10.31146/1682-8658-ecg-185-1-4-52.@@ Лазебник Л. Б., Голованова Е. В., Туркина С. В. и соавт. Неалкогольная жировая болезнь печени у взрослых: клиника, диагностика, лечение. Рекомендации для терапевтов, третья версия. Экспериментальная и клиническая гастроэнтерология. 2021;1(1):4-52. doi: 10.31146/1682-8658-ecg-185-1-4-52.

11. Ivashkin V.T., Maevskaya M. V., Zharkova M. S. et al. Clinical Recommendations of the Russian Scientific Liver Society and Russian Gastroenterological Association on Diagnosis and Treatment of Liver Fibrosis, Cirrhosis and Their Complications.Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2021;31(6):56-102.@@ Ивашкин В.Т., Маевская М. В., Жаркова М. С. и соавт. Клинические рекомендации Российского научного общества по изучению печени и Российской гастроэнтерологической ассоциации по диагностике и лечению фиброза и цирроза печени и их осложнений. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2021;31(6):56-102.

12. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016 Jun;64(6):1388-402.

13. Vinnitskaya Ye.V., Sandler Yu.G., Bordin D. S. The New Paradigm of Non-Alcoholic Fatty Liver Disease: Phenotypic Diversity of Metabolically Associated Fatty Liver Disease. Effective Pharmacotherapy. 2020 Aug 31;16(24):54-63.

14. Angulo P., Machado M., Diehl A. Fibrosis in Nonalcoholic Fatty Liver Disease: Mechanisms and Clinical Implications. Semin Liver Dis. 2015 May 14;35(02):132-45.

15. Angulo P., Kleiner D. E., Dam-Larsen S. et al. Liver Fibrosis, but No Other Histologic Features, Is Associated With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2015 Aug;149(2):389-397.e10.

16. Parhofer K. G.Interaction between Glucose and Lipid Metabolism: More than Diabetic Dyslipidemia. Diabetes Metab J. 2015;39(5):353.

17. Lu F.B., Hu E. D., Xu L. M. et al. The relationship between obesity and the severity of non-alcoholic fatty liver disease: systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol. 2018 May 4;12(5):491-502.

18. Eslam M, Sanyal A. J., George J.International Consensus Panel. MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease. Gastroenterology. 2020 May;158(7):1999-2014.e1.

19. Klimov L.Y., Zakharova I. N., Kurianinova V. A. et al. Vitamin D deficiency and obesity in children and adolescents: how the two global pandemias are interconnected. Vitamin D role in pathogenesis of obesity and insulin resistance (Part 1). Medical Council. 2017Dec 19;(19):214-20. (in Russ.)@@ Климов Л.Ю., Захарова И. Н., Курьянинова В. А. и соавт. Дефицит витамина D и ожирение у детей и подростков: как взаимосвязаны две глобальные пандемии. Роль витамина D в патогенезе ожирения и инсулинорезистентности (Часть 1). Медицинский совет. 2017 Дек 19;(19):214-20.

20. Savastano S., Barrea L., Savanelli M. C. et al. Low vitamin D status and obesity: Role of nutritionist. Rev Endocr Metab Disord. 2017 Jun;18(2):215-25.

21. Sorokman T.V., Popelyuk N. A. Vitamin D as an independent predictor of obesity in adolescents.International Journal of Endocrinology (Ukraine). 2021 Sep 2;14(5):449-53. (in Ukraine) doi: 10.22141/2224-0721.14.5.2018.142679.

22. Saitov A.R., Biek A.Yu., Dobrynina I.Yu., et al. Vitamin D deficiency in metabolic syndrome and non-alcoholic fatty liver disease. Vestnik SurG U. Medicine. 2022;4(50). (in Russ.)@@ Саитов А. Р., Биек А. Ю., Добрынина И. Ю. и соавт. Дефицит витамина D при метаболическом синдроме и неалкогольной жировой болезни печени. Вестник СурГУ Медицина №. 4(50).

23. Gromova O., Doschanova A., Lokshin V. et al. Vitamin D deficiency in Kazakhstan: Cross-Sectional study. J Steroid Biochem Mol Biol. 2020 May;199:105565.

24. Benedik E. Sources of vitamin D for humans.Int J Vitam Nutr Res. 2022 Mar;92(2):118-25.

25. Abboud M., Rizk R., AlAnouti F. et al. The Health Effects of Vitamin D and Probiotic Co-Supplementation: A Systematic Review of Randomized Controlled Trials. Nutrients. 2020 Dec 30;13(1):111.

26. Clemente M.G., Mandato C., Poeta M., Vajro P. Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions. World J Gastroenterol. 2016;22(36):8078.

27. Di Sessa A., Marzuillo P., Guarino S. et al. When a secondary form of pediatric non-alcoholic fatty liver disease should be suspected? Expert Rev Gastroenterol Hepatol. 2019 Jun 3;13(6):519-21.

28. Friesen C.S., Hosey-Cojocari C., Chan S. S. et al. Efficacy of Weight Reduction on Pediatric Nonalcoholic Fatty Liver Disease: Opportunities to Improve Treatment Outcomes Through Pharmacotherapy. Front Endocrinol (Lausanne). 2021 Apr 13;12.

29. Hourigan S.K., Abrams S., Yates K. et al. Relation between vitamin D status and nonalcoholic fatty liver disease in children. J Pediatr Gastroenterol Nutr. 2015 Mar;60(3):396-404.

30. Barchetta I., Cimini F. A., Cavallo M. G. Vitamin D and Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD): An Update. Nutrients. 2020 Oct 28;12(11):3302.

31. Ospanov O.B., Berkinbaev S. F., Raisova A. M., et al. Clinical protocol of the Ministry of Health of the Republic of Kazakhstan. 2020;(111).@@ Оспанов О. Б., Беркинбаев С. Ф., Раисова А. М. и соавт. Клинический протокол МЗ РК. 2020 (111).

32. Peng L., Wu S., Zhou N. et al. Clinical characteristics and risk factors of nonalcoholic fatty liver disease in children with obesity. BMC Pediatr. 2021 Mar 12;21(1):122.

33. Goldner D., Lavine J. E. Nonalcoholic Fatty Liver Disease in Children: Unique Considerations and Challenges. Gastroenterology. 2020 May;158(7):1967-1983.e1.

34. Liu J., Wang T., Chen J. et al. Efficacy of vitamin D supplement in children with nonalcoholic fatty liver disease: A protocol for systematic review and meta-analysis. Medicine. 2020 Jul 31;99(31): e20960.

35. Chen L.W., Chien C. H., Kuo S. F. Et al. Low vitamin D level was associated with metabolic syndrome and high leptin level in subjects with nonalcoholic fatty liver disease: A community-based study. BMC Gastroenterol. 2019 Jul 16;19(1).

36. Bennouar S., Cherif A. B., Kessira A. et al. Association and interaction between vitamin D level and metabolic syndrome for non-alcoholic fatty liver disease. J Diabetes Metab Disord. 2021 Dec 1;20(2):1309-17.

37. Stepan M.D., Vintilescu Ștefănița B, Streață I. et al. The Role of Vitamin D in Obese Children with Non-Alcoholic Fatty Liver Disease and Associated Metabolic Syndrome. Nutrients. 2023 May 1;15(9).

38. Strange R. C. Metabolic syndrome: A review of the role of vitamin D in mediating susceptibility and outcome. World J Diabetes. 2015;6(7):896.

39. Yang J.D., Abdelmalek M. F., Pang H. et al. Gender and menopause impact severity of fibrosis among patients with nonalcoholic steatohepatitis. Hepatology. 2014 Apr;59(4):1406-14.