Plant‐Based and Animal‐Based Low‐Carbohydrate Diets and Risk of Hepatocellular Carcinoma Among US Men and Women

Background and Aims Little is known about the role of low‐carbohydrate diets (LCDs) in the development of hepatocellular carcinoma (HCC). We prospectively evaluated the associations between plant‐based and animal‐based LCDs and risk of HCC in the Nurses’ Health Study (NHS) and the Health Professionals Follow‐up Study (HPFS). Approach and Results Dietary intake was assessed every 4 years using validated food frequency questionnaires. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). HRs are shown for a 1‐standard deviation (SD) increment with variables modeled as continuous. During 3,664,769 person‐years of follow‐up, there were 156 incident HCC cases. Although there were no associations between overall or animal‐based LCD score and risk of HCC, plant‐based LCD score was inversely associated with HCC risk (HR, 0.83; 95% CI, 0.70‐0.98; P trend = 0.03). Carbohydrate intake, especially from refined grains (HR, 1.18; 95% CI, 1.00‐1.39; P trend = 0.04), was positively, while plant fat (HR, 0.78; 95% CI, 0.65‐0.95; P trend = 0.01) was inversely associated with HCC risk. Substituting 5% of energy from plant fat and protein for carbohydrate (HR, 0.74; 95% CI, 0.58‐0.93; P trend = 0.01) or refined grains (HR, 0.70; 95% CI, 0.55‐0.90; Ptrend = 0.006) was associated with lower HCC risk. In conclusion, a plant‐based LCD and dietary restriction of carbohydrate from refined grains were associated with a lower risk of HCC. Substituting plant fat and protein for carbohydrate, particularly refined grains, may decrease HCC incidence. Conclusions Our findings support a potential benefit in emphasizing plant sources of fat and protein in the diet for HCC primary prevention; additional studies that carefully consider hepatitis B and C virus infections and chronic liver diseases are needed to confirm our findings.