Unsaturated fatty acids are ligands of PPAR-γ, which up-regulates genes involved in fatty acid transport and TAG synthesis and the insulin-sensitising adipokine adiponectin, which activates fatty acid β-oxidation via PPAR-α action in liver. We investigated the effect of dietary fatty acid interaction with PPARG, PPARA and ADIPOQ gene variants on plasma lipid and adiponectin concentrations in the Reading Imperial Surrey Cambridge King's study, a five-centre, parallel design, randomised controlled trial of 466 subjects at increased cardiometabolic risk. After a 4-week run-in to baseline, SFA was replaced by MUFA or carbohydrate (low fat) in isoenergetic diets for 24 weeks. Habitual dietary PUFA:SFA ratio×PPARG Pro12Ala genotype interaction influenced plasma total cholesterol (P=0·02), LDL-cholesterol (P=0·002) and TAG (P=0·02) concentrations in White subjects. PPARA Val162Leu×PPARG Pro12Ala genotype interaction influenced total cholesterol (P=0·04) and TAG (P=0·03) concentrations at baseline. After high-MUFA and low-fat diets, total cholesterol and LDL-cholesterol were reduced (P<0·001) and gene×gene interaction determined LDL-cholesterol (P=0·003) and small dense LDL as a proportion of LDL (P=0·012). At baseline, ADIPOQ −10066 G/A A-allele was associated with lower serum adiponectin (n 360; P=0·03) in White subjects. After the high-MUFA diet, serum adiponectin increased in GG subjects and decreased in A-allele carriers (P=0·006 for difference). In GG, adiponectin increased with age after the high MUFA and decreased after the low-fat diet (P=0·003 for difference at 60 years). In conclusion, in Whites, high dietary PUFA:SFA would help to reduce plasma cholesterol and TAG in PPARG Ala12 carriers. In ADIPOQ −10066 GG homozygotes, a high-MUFA diet may help to increase adiponectin with advancing age.

The increase in CVD incidence following the menopause is associated with oestrogen loss. Dietary isoflavones are thought to be cardioprotective via their oestrogenic and oestrogen receptor-independent effects, but evidence to support this role is scarce. Individual variation in response to diet may be considerable and can obscure potential beneficial effects in a sample population; in particular, the response to isoflavone treatment may vary according to genotype and equol-production status. The effects of isoflavone supplementation (50 mg/d) on a range of established and novel biomarkers of CVD, including markers of lipid and glucose metabolism and inflammatory biomarkers, have been investigated in a placebo-controlled 2×8-week randomised cross-over study in 117 healthy post-menopausal women. Responsiveness to isoflavone supplementation according to (1) single nucleotide polymorphisms in a range of key CVD genes, including oestrogen receptor (ER) α and β and (2) equol-production status has been examined. Isoflavones supplementation was found to have no effect on markers of lipids and glucose metabolism. Isoflavones improve C-reactive protein concentrations but do not affect other plasma inflammatory markers. There are no differences in response to isoflavones according to equol-production status. However, differences in HDL-cholesterol and vascular cell adhesion molecule 1 response to isoflavones v. placebo are evident with specific ERβ genotypes. In conclusion, isoflavones have beneficial effects on C-reactive protein, but not other cardiovascular risk markers. However, specific ERβ gene polymorphic subgroups may benefit from isoflavone supplementation.