The effects of whole-diet interactions on vascular health and inflammatory and fatty acid status.
Introduction The proportion of people over 65 years in Europe is predicted to increase from 25 to 40% by 2030. Diet has an important modifiable influence on ageing and it is therefore, important to identify realistic dietary strategies that will contribute to healthy ageing. The NU-AGE project (EU FP7) aims to examine the impact of a year-long whole-diet intervention (including advice on intakes of the n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) on chronic low grade inflammation (primary end-point) in 1250 older adults (aged 65-79 years) in five EU centres. As part of this thesis, the impact of intervention on vascular ‘health’ was established. In addition, a diet score for older adults was designed based on the NU-AGE diet. The intake and status of EPA and DHA is being increasingly recognised as an important modulator of the risk of chronic disease. Potential determinants of fatty acid status, including other dietary components and genotype were investigated and represent the second major component of the thesis. The genotyping focussed on the fatty acid desaturase (FADS) enzymes which are responsible for the desaturation steps in the synthesis of EPA and DHA from α-linolenic acid (αLNA). Methods Diet, vascular and inflammatory health in NU-AGE; the effects of the one year NU-AGE intervention on vascular function and inflammatory and fatty acid status was investigated in 140 participants from the Norwich centre of NU-AGE. Vascular function was clinically measured using EndoPAT, Pulse Wave Velocity (PWV) and Cardio-Ankle Vascular Index (CAVI). The NU-AGE diet score was designed and validated using both the TWIN UK cohort and the NU-AGE baseline data. EPA and DHA status; retrospective analysis of plasma samples from two completed rodent studies and one human clinical trial, which all included polyphenol-rich interventions, were used to investigate the impact of a range of polyphenols on plasma and tissue fatty acid status. In the NU-AGE cohort, the impact of individual FADS gene variants on plasma fatty acid status was examined. 10 tagging single nucleotide polymorphisms (SNPs) were selected and haplotypes were statistically reconstructed. Results There was no significant effect of the NU-AGE intervention on any measured outcomes. However, subgroup analysis showed that the NU-AGE diet ameliorated the significant increase in the stiffness of arteries (as assessed by CAVI) in the control group over the 1 year intervention period in females (p=0.024). A higher NU-AGE diet score was associated with significantly higher CRP in the TWIN UK cohort (p=0.028), but not in the NU-AGE cohort at baseline. In relation to the impact of various polyphenols on LC-PUFA status, we observed no significant differences in any of the three (two rodent and one human) studies. In the NU-AGE cohort, it was observed that participants with the homozygous minor genotype for several of the FADS SNPs had significantly (p<0.05) higher plasma linoleic acid (LA) and significantly lower arachidonic acid (AA), EPA and DHA status, as well as significantly lower desaturase activity (measured by a product-to-precursor ratio of AA/LA) compared with participants with either the homozygous major genotype or the heterozygous genotype. Furthermore, the most common haplotype (containing mostly major alleles and occurring in 26.6% of the cohort) was associated with significantly lower LA plasma levels (up to 9% increase) and significantly higher EPA (up to 38%) and DHA (up to 14%) status compared with haplotypes with a higher frequency of minor alleles. This work also showed that the NU-AGE dietary intervention may be successful in overcoming the negative effect of the minor allele on EPA and DHA status. Conclusion Although there was no significant effect of the NU-AGE intervention on any measured outcomes, the NU-AGE diet did appear to attenuate the expected progression of arterial stiffness in females. This work also suggests that the health benefits of polyphenols are unlikely to be the result of any impact on EPA and DHA status. Furthermore, common FADS genotypes emerged as significant determinants of habitual EPA and DHA status in older adults, the impact of which may be influenced by habitual EPA and DHA intake.
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