Exploration of the health effects of a high-protein diet have attracted substantial interest during recent years.^1-4 In short-term trials, consumption of high-protein diets have been shown to produce greater weight loss, loss of fat mass, and preservation of lean mass compared with the consumption of normal-protein diets.^5,6 These favorable effects of a high-protein diet in body weight management may be due to the modulation of amino acids in appetitive signaling, leading to increased satiety and hence reduced energy intake.^7,8 High-protein diets are also linked to improvements in cardiovascular risk factors, including blood pressure, blood lipid and lipoprotein profiles, and glycemic regulation.^9,10 Despite these benefits, the health effects of adherence to high dietary protein intake on long-term health and mortality remain to be clarified. Importantly, high consumption of dietary protein is unavoidably linked to a decrease in other foods, usually carbohydrates, and a decrease in carbohydrate foods with high fiber and other micronutrients may have a negative effect. Furthermore, among protein sources, proteins originating from animal and plant sources have different amino acid combinations,¹¹ and the choices of dietary protein source also necessarily influence other macronutrients, micronutrients, and polyphenols in the diet,¹² potentially leading to differential health effects. Thus, clarifying the association between high dietary protein intake and long-term health outcomes is essential; in particular, clarifying the association between specific sources of protein and mortality may help individuals increase longevity by substituting one type of protein for another.

Background & Aims Fish is a rich source of n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). Although consumption of fish and n-3 PUFA has been reported to protect against the development of some types of cancer, little is known about its association with hepatocellular carcinoma (HCC). Methods We investigated the association between fish and n-3 PUFA consumption and HCC incidence (n = 398) in a population-based prospective cohort study of 90,296 Japanese subjects (aged, 45–74 y). Hazard ratios and 95% confidence intervals (CIs) for the highest vs the lowest quintile were estimated from multivariable adjusted Cox proportional hazards regression models. We also conducted subanalyses of subjects with known hepatitis B virus (HBV) or hepatitis C virus (HCV) status, and of subjects who were anti-HCV and/or hepatitis B surface antigen positive. All tests of statistical significance were 2-sided. Results Among all subjects, consumption of n-3 PUFA-rich fish and individual n-3 PUFAs was associated inversely with HCC, in a dose-dependent manner. Hazard ratios for the highest vs lowest quintiles were 0.64 (95% CI, 0.42–0.96) for n-3 PUFA-rich fish, 0.56 (95% CI, 0.36–0.85) for EPA, 0.64 (95% CI, 0.41–0.98) for DPA, and 0.56 (95% CI, 0.35–0.87) for DHA. These inverse associations were similar irrespective of HCV or HBV status. Conclusions Consumption of n-3 PUFA-rich fish or n-3 PUFAs, particularly EPA, DPA, and DHA, appears to protect against the development of HCC, even among subjects with HBV and/or HCV infection.

Human height is a representative phenotype to elucidate genetic architecture. However, the majority of large studies have been performed in European population. To investigate the rare and low-frequency variants associated with height, we construct a reference panel (N = 3,541) for genotype imputation by integrating the whole-genome sequence data from 1,037 Japanese with that of the 1000 Genomes Project, and perform a genome-wide association study in 191,787 Japanese. We report 573 height-associated variants, including 22 rare and 42 low-frequency variants. These 64 variants explain 1.7% of the phenotypic variance. Furthermore, a gene-based analysis identifies two genes with multiple height-increasing rare and low-frequency nonsynonymous variants (SLC27A3 and CYP26B1; P_SKAT-O < 2.5 × 10⁻⁶). Our analysis shows a general tendency of the effect sizes of rare variants towards increasing height, which is contrary to findings among Europeans, suggesting that height-associated rare variants are under different selection pressure in Japanese and European populations.