Adherence to the EAT-Lancet Diet, plasma proteomics, and risk of venous thromboembolism: a large-scale prospective cohort study

Background
The EAT Lancet diet is increasingly recognized for its simultaneous benefits to human and planetary health. Its key components are known to exert anti-inflammatory and antiplatelet effects; however, the potential association between adherence to the EAT‑Lancet diet and incident venous thromboembolism (VTE), as well as the underlying biological mechanisms, remains unclear.

Methods
This prospective study involved 201,695 UK Biobank participants who were free of VTE at baseline, and integrated large-scale Olink plasma proteomics to identify diet-related molecular signatures. Adherence to the EAT-Lancet diet was quantified using two validated indices. Cox models were employed to evaluate associations between EAT-Lancet diet, plasma proteins, and incident VTE (including deep vein thrombosis [DVT] and pulmonary embolism [PE]). Mediation analyses quantified the role of plasma proteins.

Results
During a median follow-up of 13.77 years, participants in the highest adherence group of the Stubbendorff index showed lower risks of VTE (HR = 0.809, 95% CI: 0.750–0.874), DVT (HR = 0.856, 95% CI: 0.781–0.938), and PE (HR = 0.754, 95% CI: 0.678–0.838). Consistent protective associations were observed with the Knuppel index. Mediation analyses identified 94 shared plasma protein mediators, with mediation proportions ranging from − 4.77% to 8.45% of the association, among which FABP4, LEP, and ENPP6 were the top-ranked mediators. The overall proteomic signature mediated 59.19% (95% CI: 27.02%-92.15%) and 40.10% (95% CI: 14.53%-65.96%) of the associations between the Stubbendorff and Knuppel index and incident VTE, respectively.

Conclusions
Higher adherence to the EAT-Lancet diet is significantly associated with a reduced risk of incident VTE, DVT, and PE, with plasma proteins potentially mediating this effect.