# Impact of Heavy Metals on the Antioxidant Activity of Vitamin D: A Metabolic Perspective

## TL;DR

This study explores how heavy metals affect vitamin D's antioxidant activity through metabolic changes, even when vitamin D levels are low.

## Contribution

The study is the first to use metabolomics to examine the effects of heavy metal exposure on vitamin D-related antioxidant pathways under deficiency conditions.

## Key findings

- Heavy metal exposure may stimulate vitamin D-related antioxidant activity through elevated antioxidants like bilirubin, EPA, and DHA.
- DHA levels showed a strong potential as a biomarker for vitamin D activity in response to heavy metal exposure.
- Altered lipid metabolism, including diacylglycerol and phosphatidylcholine levels, was linked to increases in EPA and DHA.

## Abstract

Background/Objectives: Vitamin D (VD) is metabolized in the body and plays a crucial role in regulating the antioxidant system. While exposure to heavy metals (HMs) inhibits VD activity, HMs can also be absorbed following VD stimulation. Despite differing views on the interaction between HM and VD activity, the effects of HM exposure on VD-related pathways have not been examined using metabolomics. This study aimed to investigate the impact of HM exposure on VD-related antioxidant activity under VD deficiency conditions using untargeted metabolic profiling. Methods: In this retrospective cohort study, 46 plasma samples were analyzed using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Metabolic profiling was performed on two groups: individuals with severe VD deficiency and low HM exposure (SVDD–LHM) and those with VD deficiency and high HM exposure (VDD–HHM). Results: As a compensatory response to oxidative stress induced by HMs, VD-related antioxidant pathways may be associated with elevated levels of antioxidants, including bilirubin, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). In-creases in EPA and DHA were also linked to alterations in lipid metabolism, including diacylglycerol and phosphatidylcholine levels. DHA showed an area under the curve (AUC) of 0.850 (95% CI: 0.651–0.990), suggesting that DHA could serve as a potential biomarker for VD activity in response to HM exposure. Conclusions: The identified metabolites and metabolic pathways suggest that HM exposure may stimulate VD-related antioxidant activity, even under VD-deficient conditions.