Diet, kiwifruit and genotypes : their influence on lipid profiles and CVD-related metabolic markers in hypercholesterolaemic men : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Nutritional Science at Massey University, Albany, New Zealand

Abstract

In New Zealand, cardiovascular disease (CVD) is a major public health concern and a leading cause of death. Lifestyle modification, including dietary change, is a crucial element in the prevention of CVD, with fruit and vegetables key elements of a cardioprotective diet. Kiwifruit is a commonly-consumed, nutrientdense fruit that contains many components individually shown to have positive effects on CVD risk factors. This study investigated the effects on plasma lipid profiles and other CVD-related metabolic markers of consuming kiwifruit daily in conjunction with a healthy diet. Further, plasma lipid responses were examined according to inflammatory status, APOE genotype, and additional high-density lipoprotein cholesterol (HDL-C)-related gene polymorphisms. Eighty-five hypercholesterolaemic men (low-density cholesterol (LDL-C) >3.0 mmol/L and triglycerides (TG) <3 mmol/L) completed a 4-week healthy diet runin before randomisation to a controlled cross-over study of two 4-week interventions of two green kiwifruit/day plus healthy diet (intervention), or healthy diet alone (control). Anthropometric measures, blood pressure (BP), heart rate (HR), stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) and fasting blood samples (lipid profile, insulin, glucose, highsensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, tumour necrosis factor alpha (TNF-α) and IL-10) were taken at baseline, 4 and 8 weeks. An additional blood sample was taken for genetic testing: APOE, CETP Taq1B; APOA1 -75G/A; LIPC-514C→T; LIPG I24582. Subjects were divided into low and medium inflammatory groups, using pre-intervention hs-CRP concentrations (hs-CRP <1 and 1-3 mg/L, respectively). Repeated measures ANOVA was used to examine genotype/inflammatory status x treatment interactions. After the kiwifruit intervention, plasma HDL-C concentrations were significantly higher (mean difference 0.04 [95% CI: 0.01, 0.07] mmol/L [P=0.004]) and the total cholesterol (TC)/HDL-C ratio was significantly lower (-0.15 [-0.24, -0.05] mmol/L [P=0.002]), compared to control. For the total group, there were no significant differences between the interventions for TC, LDL-C, insulin, glucose, hs-CRP, BP, HR, SV, CO and TPR. Lipid responses were modulated according to inflammatory status and APOE and CETP Taq1B genotypes. The medium inflammatory group had a significant improvement in CRP with kiwifruit compared to control. Significant inflammatory group x intervention interactions were seen for TC/HDL-C (P=0.02), TG/HDL-C (P=0.05), and plasma IL-6 (P=0.04). Examined by genotype, APOE4 carriers had significantly decreased TG (-0.18 [-0.34, -0.02] mmol/L [P=0.03]) with kiwifruit compared to control. A significant CETP Taq1B genotype x intervention interaction was seen for the TG/HDL-C ratio (P=0.03), and B1/B1 homozygotes had a significantly lower TG/HDL-C (-0.23±0.58 mmol/L, P=0.03) ratio after the kiwifruit intervention, compared to control. Lipid response was not affected by other polymorphisms. In conclusion, kiwifruit independently of a healthy diet containing fruit improved dyslipidaemic profiles, significantly improving mean HDL-C concentration and TC/HDL-C ratio compared with the control intervention. Effects were even more pronounced in men with phenotypes and genotypes which placed them at higher risk of CVD, with more sizeable improvements in HDL-C and TC/HDL-C ratio, and significant decreases in TG concentrations and TG/HDL-C ratio. Although modest, the improvements suggest that regular inclusion of green kiwifruit as part of a healthy diet could translate into a significant reduction of CVD risk in men with high cholesterol concentrations.