What is the effect of Vitamin D supplements on liver enzymes?

From the Guidelines

Vitamin D supplements are recommended for patients with chronic liver disease who have vitamin D levels below 20 ng/ml, with the goal of reaching a serum vitamin D level above 30 ng/ml, as this has been shown to have a positive correlation with response to treatment in patients with hepatitis C virus infection, non-alcoholic fatty liver disease, and those who develop hepatocellular carcinoma 1.

Key Considerations

• The prevalence of vitamin D deficiency in patients with chronic liver disease is high, ranging from 64 to 92%, and is often inversely correlated with disease severity and Child-Pugh score 1.
• Assessing plasma vitamin 25 hydroxy-D (25OHD) levels in all patients with chronic liver disease, particularly in those with advanced disease, non-alcoholic fatty liver, and cholestatic disorders, is advisable 1.
• Supplementing patients with vitamin D levels below 20 ng/ml with oral vitamin D until reaching a serum vitamin D level above 30 ng/ml is a reasonable approach, with higher doses potentially necessary in patients with non-alcoholic fatty liver disease 1.

Safety and Monitoring

• While vitamin D supplements are generally safe for liver health when taken at recommended doses, excessive amounts can potentially elevate liver enzymes 1.
• Patients with existing liver disease should consult with their healthcare provider before starting supplements, as they may recommend monitoring liver enzymes periodically.
• Sticking to the recommended dose and avoiding self-prescribing high doses is crucial to minimize the risk of liver problems.

Clinical Implications

• Vitamin D deficiency has been linked to poor outcomes in patients with chronic liver disease, making supplementation a potentially beneficial strategy for improving response to treatment and overall liver health 1.
• Healthcare providers should consider assessing and addressing vitamin D deficiency in patients with chronic liver disease as part of their comprehensive care plan.

From the FDA Drug Label

The in vivo synthesis of the major biologically active metabolites of vitamin D occurs in two steps. The first hydroxylation of ergocalciferol takes place in the liver (to 25-hydroxyvitamin D) and the second in the kidneys (to 1,25-dihydroxyvitamin D) The effect of Vitamin D supplements on liver enzymes is not directly addressed in the provided drug label.

• The label mentions that the first hydroxylation of ergocalciferol takes place in the liver, but it does not provide information on the impact of Vitamin D supplements on liver enzymes. 2

From the Research

Effect of Vitamin D Supplements on Liver Enzymes

• The relationship between vitamin D and liver enzymes is complex and has been studied in various contexts, including chronic liver diseases and non-alcoholic fatty liver disease (NAFLD) 3, 4, 5, 6, 7.
• A 2021 systematic review found that vitamin D supplementation may have uncertain effects on all-cause mortality, liver-related mortality, and serious adverse events in adults with chronic liver diseases, with very low certainty of evidence 3.
• A 2018 cross-sectional and interventional study found no significant relationships between 25-hydroxyvitamin D concentrations and liver enzymes, including γ-glutamyl transferase (GGT), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), in overweight or obese adults 4.
• A 2017 systematic review found that vitamin D supplementation had uncertain effects on all-cause mortality, liver-related mortality, and serious adverse events in adults with chronic liver diseases, with very low quality evidence 5.
• A 2014 general population study found an inverse association between vitamin D status and incident liver disease, with a hazard ratio of 0.88 per 10 nmol/l higher vitamin D status at baseline 6.
• A 2019 study found that high-dose vitamin D supplementation was associated with improvements in serum markers of liver function, including ALT, AST, and GGT, in adolescent girls with abnormal liver function tests 7.

Key Findings

• Vitamin D supplementation may have uncertain effects on liver enzymes and liver function in various populations, including adults with chronic liver diseases and healthy adolescents.
• The relationship between vitamin D and liver enzymes is complex and may be influenced by various factors, including vitamin D status, liver disease severity, and population characteristics.
• Further studies are needed to determine the effects of vitamin D supplementation on liver enzymes and liver function in different populations and to establish the optimal dosage and duration of supplementation.

Liver Enzymes Affected by Vitamin D Supplementation

• Alanine aminotransferase (ALT)
• Aspartate aminotransferase (AST)
• Gamma-glutamyl transferase (GGT)
• Alkaline phosphatase (ALP)
• Lactate dehydrogenase (LDH)
• Total bilirubin
• Direct bilirubin
• Total protein
• Albumin