Lower 25-hydroxyvitamin D3 levels and increased risk of liver diseases: is there a causal link?

Abstract

Vitamin D deficiency is a highly prevalent condition worldwide, reportedly present in approximately 30-60 % of the general adult population [1,2]. This worldwide pandemic remains generally unrecognized and untreated.Vitamin D is critical for bone mineralization, and numerous observational studies have assessed outcomes for skeletal health [1,2].In the past several years, however, attention has turned to non-skeletal effects of vitamin D deficiency or insufficiency. Indeed, the discovery that many extra-renal tissues also possess the vitamin D receptor(s), and the converting enzyme 1a-hydroxylase has provided new insights into the important physiologic paracrine/autocrine roles of vitamin D in various tissues and organs that are mainly dependent on the availability of serum 25-hydroxyvitamin D [25(OH)D] from the circulating plasma [1,2]. Indeed, the presence of nuclear vitamin D receptors in several cell types, including cardiomyocytes, neurons, immune cells, and hepatocytes, has stimulated considerable scientific interest in understanding the putative pleiotropic properties of vitamin D that may regulate hundreds of different genes and play an important role in regulating cell proliferation, differentiation, and apoptosis in many normal and cancer cells and also have anti-inflammatory and immuno-modulatory effects [1,2]. Evolving data indicate that vitamin D deficiency/insufficiency may be playing a role in the pathophysiology of cardiovascular disease as well as several other acute and chronic diseases, including common cancers, autoimmune diseases, osteoarthritis, mental disorders, infectious diseases, metabolic syndrome, and diabetes mellitus [1,2].To our knowledge, the paper published by Skaaby et al. [3] on this issue of the journal is one of the first prospective studies to demonstrate that lower levels of serum 25(OH)D are significantly associated with a higher incidence of fatal and non-fatal liver diseases (as combined endpoint) in a population-based sample of 2,649 middle-aged Danish individuals, who were followed for a median follow-up period of 16.5 years. Diagnosis of incident liver diseases was based on the Danish National Patient Register. Notably, the association between serum 25(OH)D levels and risk of incident liver diseases remained statistically significant after adjusting for age, sex, season measurement, daily alcohol consumption, body mass index, smoking status, leisure time physical activity, dietary habits, education, and serum alanine aminotransferase level. Notably, the number of patients with chronic viral hepatitis was negligible in this cohort (due to a low prevalence of viral hepatitis in Denmark), and the authors have excluded from analysis subjects with cirrhosis or other established liver diseases at baseline in order to reduce the possibility of reverse causation (i.e., lower serum 25(OH)D levels due to liver failure). Unfortunately, however, the authors did not report measurement of serum 1,25-dihydroxyvitamin D levels as the active moiety of vitamin D, and also did not adjust...

Effect of Vitamin D Deficiency on Liver Cancer Risk: A Systematic Review and Meta-Analysis

“…If the status of vitamin D deficiency is not corrected, it may promote liver cancer growth through β-catenin activation and toll-like receptor 7 signaling pathways (Chen et al, 2016). In the past decade, many studies have demonstrated that vitamin D deficiency is significantly associated with incident liver cancer (Wang et al, 2013;Targher and Byrne, 2014), however, the findings remain controversial. Therefore, based on prospective cohort and case-control studies, we conducted a meta-analysis to systematically assess the relationship of vitamin D levels with the risk of liver cancer.…”

Nutritional issues in patients with obesity and cirrhosis

“…Vitamin D deficiency (VDD, < 50 nmol/L; < 20 ng/mL) is a worldwide pandemic, reported in more than half of the general adult population[ 39 - 42 ]. Specifically, VDD is widespread among patients with chronic liver disease, with prevalence described between 70%-90%[ 40 , 43 - 49 ], while the prevalence of vitamin D insufficiency (< 75 nmol/L; < 30 ng/mL) is almost universal[ 49 ].…”

Does vitamin D improve liver enzymes, oxidative stress, and inflammatory biomarkers in adults with non-alcoholic fatty liver disease? A randomized clinical trial

“…Results of recent cross-sectional studies showed a relationship between vitamin D deficiency and NAFLD [9,[11][12][13]. Study of Targher et al [9,14] for the first time demonstrated that low serum levels of 25(OH)D were independently associated with severity of hepatic injuries such as steatosis, necrosis, and fibrosis in NAFLD patients. The other cross-sectional study also confirmed a significant relationship between VDD and NAFLD [11].…”