Dietary pattern modifies the risk of MASLD through metabolomic signature

Abstract

Background & Aims

The EAT-Lancet Commission in 2019 advocated a plant-centric diet for health and environmental benefits, but its relation to metabolic dysfunction-associated steatotic liver disease (MASLD) is unclear. We aimed to discover the metabolite profile linked to the EAT-Lancet diet and its association with MASLD risk, considering genetic predisposition.

Methods

We analyzed data from 105,752 UK Biobank participants with detailed dietary and metabolomic information. We constructed an EAT-Lancet diet index and derived a corresponding metabolomic signature through elastic net regression. A weighted polygenic risk score for MASLD was computed from associated risk variants. The Cox proportional hazards model was employed to estimate hazard ratios (HRs) and 95% CIs for the risk of MASLD (defined as hospital admission or death).

Results

During a median follow-up period of 11.6 years, 1,138 cases of MASLD were documented. Participants in the highest group for the EAT-Lancet diet index had a multivariable HR of 0.79 (95% CI 0.66–0.95) for MASLD compared to the lowest group. The diet's impact was unaffected by genetic predisposition to MASLD (p = 0.42). Moreover, a robust correlation was found between the metabolomic signature and the EAT-Lancet diet index (Pearson r = 0.29; p <0.0001). Participants in the highest group for the metabolomic signature had a multivariable HR of 0.46 (95% CI 0.37–0.58) for MASLD, in comparison to those in the lowest group.

Conclusions

Higher intake of the EAT-Lancet diet and its associated metabolite signature are both linked to a reduced risk of MASLD, independently of traditional risk factors.

Impact and implications:

Our analysis leveraging the UK Biobank study showed higher adherence to the EAT-Lancet diet was associated with a reduced risk of metabolic dysfunction-associated steatotic liver disease (MASLD). We identified a unique metabolite signature comprising 81 metabolites associated with the EAT-Lancet diet, potentially underlying the diet's protective mechanism against MASLD. These findings suggest the EAT-Lancet diet may offer substantial protective benefits against MASLD.