Plant-based diets, genetic predisposition and risk of non-alcoholic fatty liver disease

Abstract

Background: Diets rich in plant-based foods are associated with lower risks of non-alcoholic fatty liver disease (NAFLD), while the prospective evidence is limited. We aimed to examine longitudinal associations of plant-based diets and genetic susceptibility with NAFLD risk.

Methods: This longitudinal cohort study included 159,222 participants (58.0 ± 8.0 years old, 55.7% female) free of NAFLD in the UK Biobank. We calculated the overall plant-based diet index (PDI), the healthful plant-based diet index (hPDI), and the unhealthful plant-based diet index (uPDI). New-onset NAFLD was the primary outcome. The weighted polygenic risk score was calculated based on risk variants associated with NAFLD. Hazard ratios (HR) and 95% confidential intervals (CI) were estimated by Cox proportional hazards model. Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) measured liver fat content in a subsample of 20,692 participants (57.5 ± 7.4 years old, 52.6% female) was the secondary outcome. The associations between plant-based diet indices and MRI-PDFF were evaluated using generalized linear models.

Results: During a median follow-up of 9.5 years, 1541 new-onset NAFLD cases were documented. Compared to the lowest quintile, multivariable-adjusted hazard ratios (HRs) of NAFLD in the highest quintile were 0.78 (95% confidential intervals [CI], 0.66-0.93, p-trend =0.02), 0.74 (95% CI, 0.62-0.87, p-trend <0.0001), and 1.24 (95% CI, 1.05-1.46, p-trend = 0.02) for overall PDI, hPDI, and uPDI, respectively. For liver fat content, higher overall PDI and hPDI were associated with lower MRI-PDFF, while higher uPDI was associated with higher liver fat content. We observed a significant interaction between hPDI and PRS (p-interaction =0.03), and the NAFLD risk was lowest among participants with the highest hPDI and low genetic risk.

Conclusions: Higher intake of plant-based diets especially healthful plant-based diets was associated with lower NAFLD risk and liver fat content regardless of genetic susceptibility, whereas an unhealthful plant-based diet was associated with higher NAFLD risk and intrahepatic steatosis. These results suggest that the quality of plant-based foods should be highlighted when adopting a plant-based diet.

Keywords: Genetic risk; NAFLD; Plant-based diet; UK Biobank.

Fig. 1

Restrict cubic spline for associations of overall plant-based diet index, healthful plant-based diet index, and unhealthful plant-based diet index with NAFLD risk. Adjusted for age at the last dietary assessment, sex, education, household income, Townsend deprivation index, assessment centers, smoking, alcohol consumption, physical activity, total energy, BMI, NAFLD-PRS, first 10 principal components of ancestry, and genotype measurement batch. Abbreviations: BMI, body mass index; CI, confidence interval; HR, hazards ratio; NAFLD, non-alcoholic fatty liver disease; PRS, polygenic risk score

Fig. 2

Associations of overall plant-based diet index, healthful plant-based diet index, and unhealthful plant-based diet index with MRI-PDFF. Adjusted for age at the last dietary assessment, age at MRI scan, sex, education, household income, Townsend deprivation index, assessment centers, smoking, alcohol consumption, physical activity, total energy, BMI, NAFLD-PRS, first 10 principal components of ancestry, and genotype measurement batch. Abbreviations: MRI, magnetic resonance imaging; NAFLD, non-alcoholic fatty liver disease; PDFF, proton density fat fraction; PRS, polygenic risk score