The cross-sectional study was conducted to examine the association between 25(OH)D concentration and liver enzymes, showing no association with healthy adults, before and after adjustment for potential confounding factors, including age, sex, markers of adiposity, insulin sensitivity, lipids and inflammation. Liver enzymes were related to the metabolic syndrome (MS) factors including FBG and triglycerides. Additionally, GGT, ALT and ALP were positively interacted to each other. Similarly, Ballestri et al. demonstrated that liver histology changes could be predicted significantly using ALT, AST, homeostasis model of assessment-insulin resistance (HOMA-IR), serum uric acid (SUA), MS, total cholesterol (TCH) and serum iron.
Vitamin D can be acquired from the diet, but it is mainly produced by endogenous sun exposure. Transported to the liver, vitamin D is hydroxylated to 25(OH)D by monooxygenase system in microsome. It is generally accepted that serum 25(OH)D concentration could be used to assess status of vitamin D and musculoskeletal growth. What’s more, nutritional guidelines of vitamin D should be based on effects of vitamin D. It is well known that vitamin D is beneficial to calcium and bone metabolism. Studies have confirmed that vitamin D has a series of physiological functions and its deficiency can lead to many diseases. Recent studies have shown that it regulates adaptive immune responses to various inflammatory and autoimmune diseases. Both vitamin D hydroxylase and vitamin D receptor (VDR) were expressed in immune cells, which lay a foundation for vitamin D to play its role in inflammatory diseases. 25(OH)D acts as a ligand for the VDR and participates in diverse physiological processes. Furthermore, increased ALT, GGT and ALP, which were closely associated with liver fat deposition, were considered as indices of liver injury[14–17]. As mentioned earlier, ALT can serve as an index of hepatocyte death and an indirect maker of liver injury[15, 18]. GGT involving in the extracellular catabolism of the antioxidant glutathione was regarded as a marker of oxidative stress and sub-clinical inflammation. ALP was responsible for hydrolysis of phosphate esters. An up to triple improvement of ALP was common to see in hepatocellular diseases, accompanied with elevated aminotransferases. At the same time, ALP was significantly increased in cholestatic hepatobiliary diseases as well, for instance, primary biliary intrahepatic cholestasis. However, the real fact was that AST was a less specific index of liver injury on account of wide secretion from other organs and cells, such as the heart, skeletal muscle, kidney, pancreas, lung, leukocyte, and erythrocyte[18–20].
Similar to our findings, three articles were presented to support our conclusion. The first one from the third National Health and Nutrition Examination Survey (NHANES III) showed no correlation between 25(OH)D concentration and serum ALT levels. The result of this study was consistent with previous irrelevance outcome between ALT and 25(OH)D concentration. However, the study showed that the lower quartile of 25(OH)D had a higher prevalence of unexplained ALT, individuals with elevated ALT levels (n = 308) had a lower concentration of 25(OH)D, compared to BMI-matched controls (n = 976). Notably, individuals with different comorbidities such as diabetes and hypertension were included, and drug use was not adjusted, which may have affected their results. The second study consisted of 654 individuals with risk factors for diabetes(aged ≥ 30 years) reported an inverse association of 25(OH)D concentration and ALT, after adjusting for BMI, waist circumference, and lipids. In contrast, the third study using NHANES III data for 12,155 participants with normal ALT levels, demonstrated a positive association between 25(OH)D concentration and ALT levels, after adjusting for confounding factors, such as gender, race, BMI, diabetes, high blood pressure, smoking and drinking history. One thing to be noted was that all individuals with serum ALT levels > 39 U/L were excluded in their study. However, our study did not require ALT levels and everyone included. Therefore, their findings were not comparable to other conclusions, as higher ALT levels may be related to liver damage and severe comorbidities.
There were some limitations in our study. Firstly, due to the cross-sectional design of our study, we can’t conclude cause and effect relationships and evaluate the impact of vitamin D status over time. Secondly, vitamin D concentration is measured for one time. However, a previous study declared that a single measurement of serum 25(OH)D had reasonable validity over a 5-year period. Multiple measurements of 25(OH)D would estimate the vitamin D status better and reduce the extent of non-differential measurement errors. Thirdly, the status of vitamin D may be confusing because vitamin D concentrations may generally be influenced by a different lifestyles[22, 23]. In our model, we have adjusted other determinants. However, possible residual confusion may not be ruled out. Finally, adverse effects of vitamin D use were not discussed in this article. More deep research for liver injury should be carried out to re-evaluate and determine relationships between 25-hydroxyvitamin D concentration and liver enzymes, using larger sample sizes, longer durations and more sensitive screening tools.