Trace Elements and Depressive Symptoms in Coronary Artery Disease: A Systematic Review of Sparse and Predominantly Indirect Evidence.

Coronary artery disease (CAD), including acute coronary syndromes, frequently co-occurs with depression and is associated with adverse outcomes. Trace elements may influence shared biological pathways, including oxidative stress, inflammation, and neurovascular signaling. This study evaluated the association between trace element status and depressive symptoms in CAD. A systematic review was conducted in accordance with PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420251231129). PubMed, Scopus, and the Cochrane Library were searched from inception to 2 December 2025. Studies assessing trace element concentrations in adults with CAD and depressive symptoms were eligible. Due to limited direct evidence, partially aligned and indirect studies were also included. Data were synthesized narratively. Of 699 records, four studies were included. No studies fulfilled Tier 1 criteria. The available evidence consisted of partially aligned (Tier 2) and indirect (Tier 3) studies. Lower zinc and magnesium levels and higher copper concentrations were suggested to be associated, based exclusively on Tier 2-3, low-certainty, predominantly indirect evidence. Interventional studies reported modest improvements following zinc or combined magnesium and zinc supplementation, although not in CAD-specific populations. Evidence directly addressing trace elements and depression in CAD is extremely limited and largely indirect. Current data do not support causal inference or clinical recommendations. Findings should be considered exploratory and hypothesis-generating.