Sufficient Vitamin D Levels Reduces Risk for All-Cause and Cardiovascular Mortality in Subjects with Non-Alcoholic Fatty Liver Disease

by | Dec 1, 2022 | 2022, Cardiovascular Health, Liver Health, Vitamin D - Mortality

Written by Taylor Woosley, Staff Writer. Results of this prospective cohort study using data from the 2001-2006 NHANES shows that each 1-unit increase in serum 25(OH)D concentration was related to a 41% lower risk of all-cause mortality and a 65% lower risk of cardiovascular mortality in the fully adjusted model. 

liver scanOver the past two decades, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease in the world, with around 25% of the world’s population currently thought to have NAFLD1. The spectrum of NAFLD encompasses different abnormalities, ranging from a simple increase in intrahepatic lipid content to nonalcoholic steatohepatitis with various degrees of necrotic inflammation, fibrosis, and ultimately, cirrhosis2. The pathogenesis of NAFLD involves chronic inflammation and oxidative stress3. In NAFLD, an increase in liver fat leads to inflammation, causing mitochondrial dysfunction with oxidative stress and endoplasmic reticulum stress-associated mechanisms being activated4.

Vitamin D (25(OH)D) is a pleiotropic hormone with functions that extend far beyond the regulation of calcium homeostasis and bone mineralization; evidence has proven the involvement of vitamin D in mediating several immune-inflammatory and metabolic processes5. Vitamin D plays an important role in reducing insulin resistance, cardiovascular risk, and metabolic syndrome6. Studies have increasingly found that vitamin D can affect the development of NAFLD by regulating insulin resistance, immune inflammation, lipid metabolism and target gene expression7.

Chen Y et al. conducted a retrospective cohort study to assess the impact of serum 25(OH)D levels on mortality in adults with NAFLD. Data used was from the 2001-2006 National Health and Nutrition Examination Survey (NHANES), with 4512 subjects with NAFLD and 6517 participants without NAFLD being included in the final analysis. NAFLD was defined in individuals using the US fatty liver index (USFLI) with USFLI values ≥30. 25(OH)D concentrations were measured using the DiaSorin kit and mortality status was determined based on the National Death Index. Information on demographics, lifestyle factors, and medical history were obtained through questionnaires. Subjects had physical examinations and gave blood samples to collect data regarding height, weight, and blood pressure. Covariates such as race/ethnicity, smoking status, education levels, physical activity, and alcohol consumption were also included in analysis.

Serum 25(OH)D levels were categorized into four categories: <25.0 nmol/L, 25.0–49.9 nmol/L, 50.0–74.9 nmol/L, and ≥75.0 nmol/L. Chi-square test for categorical variables and ANOVA for continuous variables were used to compare differences among groups. Weighted Cox proportional hazards models were utilized to estimate the association between serum 25(OH)D levels and mortality. Subgroup analyses were also performed by age, sex, race/ethnicity, smoking status, BMI, and physical activity. Of the 4512 individuals with NAFLD, the average age was 54.12 year and 43.23% were female. Around one-third of individuals were in the severe to moderate deficiency group (<50.0 nmol/L) and about a quarter of individuals were in the sufficiency group (≥75.0 nmol/L). Over a median follow-up of 8.7 years, 898 all-cause deaths and 305 CVD deaths were documented in NAFLD subjects. Significant findings of the study are as follows:

  • Compared with individuals in the severe deficiency group (<25.0 nmol/L), the multivariable‐adjusted HRs and 95% CIs were 0.55 (0.35, 0.86), 0.40 (0.25, 0.65) and 0.36 (0.22, 0.60), respectively, for all‐cause mortality (P for trend <0.001); 0.28 (0.15, 0.52), 0.16 (0.08, 0.32), and 0.14 (0.07, 0.29), respectively, for cardiovascular mortality (p for trend < 0.001) in the other three groups from lower to higher serum 25(OH)D categories (25.0–49.9, 50.0–74.9, and ≥75.0 nmol/L) in the fully adjusted model.
  • Among individuals without NAFLD, the impacts of the highest serum 25(OH)D group (≥75.0 nmol/L) compared with the lowest group (<25.0 nmol/L) on all‐cause (HR = 0.50, 95% CI: 0.24–1.07) and cardiovascular mortality (HR = 0.38, 95% CI: 0.15–1.01) were insignificant in the fully adjusted model.

Results of the prospective cohort study using NHANES 2001-2006 data show that increased serum 25(OH)D concentrations were significantly associated with decreased mortality from cardiovascular diseases and all causes in NAFLD subjects. Further research including large-scale prospective studies and clinical designs should continue to explore whether serum 25(OH)D levels may help prevent mortality in individuals with NAFLD. Study limitations include only collecting serum 25(OH)D concentrations at enrollment with no further repeated measurements, the lack of NAFLD diagnosis by liver biopsy, and the inability to include residual confounders in analysis.

Source: Chen, Yuxiong, Siqin Feng, Zhen’ge Chang, Yakun Zhao, Yanbo Liu, Jia Fu, Yijie Liu et al. “Higher Serum 25-Hydroxyvitamin D Is Associated with Lower All-Cause and Cardiovascular Mortality among US Adults with Nonalcoholic Fatty Liver Disease.” Nutrients 14, no. 19 (2022): 4013.

© 2022 by the authors. Li‐ censee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and con‐ ditions of the Creative Commons At‐ tribution (CC BY) license (https://cre‐ ativecommons.org/licenses/by/4.0/).

Click here to read the full text study.

Posted December 1, 2022.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

References:

  1. Younossi Z, Tacke F, Arrese M, et al. Global Perspectives on Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. Hepatology. Jun 2019;69(6):2672-2682. doi:10.1002/hep.30251
  2. Pafili K, Roden M. Nonalcoholic fatty liver disease (NAFLD) from pathogenesis to treatment concepts in humans. Mol Metab. Aug 2021;50:101122. doi:10.1016/j.molmet.2020.101122
  3. Castera L, Friedrich-Rust M, Loomba R. Noninvasive Assessment of Liver Disease in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. Apr 2019;156(5):1264-1281.e4. doi:10.1053/j.gastro.2018.12.036
  4. Anania C, Perla FM, Olivero F, Pacifico L, Chiesa C. Mediterranean diet and nonalcoholic fatty liver disease. World J Gastroenterol. May 21 2018;24(19):2083-2094. doi:10.3748/wjg.v24.i19.2083
  5. Barchetta I, Cimini FA, Cavallo MG. Vitamin D and Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD): An Update. Nutrients. Oct 28 2020;12(11)doi:10.3390/nu12113302
  6. Rezaei S, Tabrizi R, Nowrouzi-Sohrabi P, et al. The Effects of Vitamin D Supplementation on Anthropometric and Biochemical Indices in Patients With Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis. Front Pharmacol. 2021;12:732496. doi:10.3389/fphar.2021.732496
  7. Zhang R, Wang M, Wang M, et al. Vitamin D Level and Vitamin D Receptor Genetic Variation Were Involved in the Risk of Non-Alcoholic Fatty Liver Disease: A Case-Control Study. Front Endocrinol (Lausanne). 2021;12:648844. doi:10.3389/fendo.2021.648844