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

Use of Prescription Medication by Individuals Who Died by Suicide in Northern Ireland

OBJECTIVES/: To understand medication use prior to suicide in relation to patterns, polypharmacy and adherence. METHODS: 1,371 suicide cases were coded and latent class analysis used to identify combinations of medications prescribed prior to death. RESULTS: Two thirds had been prescribed medication with 30.7% prescribed three or more. Latent class analysis revealed three classes: Mixed medication use, primarily mental medication use, and baseline/low medication use. There are potentially high rates of medication non-adherence. CONCLUSIONS: Both medication use but also non-adherence rates were high in this sample of individuals who died by suicide. Potential implications and areas for future research are discussed

The impact of fatty acid desaturase genotype on fatty acid status and cardiovascular health in adults

The aim of this review was to determine the impact of the fatty acid desaturase (FADS) genotype on plasma and tissue concentrations of the long-chain (LC) n-3 PUFA, including EPA and DHA, which are associated with the risk of several diet-related chronic diseases, including CVD. In addition to dietary intakes, which are low for many individuals, tissue EPA and DHA are also influenced by the rate of bioconversion from α-linolenic acid (αLNA). Δ-5 and Δ-6 desaturase enzymes, encoded for by FADS1 and FADS2 genes, are key desaturation enzymes involved in the bioconversion of essential fatty acids (αLNA and linoleic acid (LA)) to longer chained PUFA. In general, carriers of FADS minor alleles tend to have higher habitual plasma and tissue levels of LA and αLNA, and lower levels of arachidonic acid, EPA and also to a lesser extent DHA. In conclusion, available research findings suggest that FADS minor alleles are also associated with reduced inflammation and CVD risk, and that dietary total fat and fatty acid intake have the potential to modify relationships between FADS gene variants and circulating fatty acid levels. However to date, neither the size-effects of FADS variants on fatty acid status, nor the functional SNP in FADS1 and 2 have been identified. Such information could contribute to the refinement and targeting of EPA and DHA recommendations, whereby additional LC n-3 PUFA intakes could be recommended for those carrying FADS minor alleles

Trinity Walton Club: What is its potential for promoting interest in STEM?

Concerns are growing in many countries, including Ireland, regarding an inadequate number of graduates to meet workforce needs in science, technology, engineering and mathematics (STEM) fields. These graduate deficiencies are the result of low student uptake of STEM subjects and courses at post-primary and tertiary level education. Low uptake is partly a consequence of negative student attitudes towards STEM. Many students are losing interest in STEM at an early age due to an inability to see any relevance in their everyday lives. In light of such concerns, a Saturday afternoon club entitled “Trinity Walton Club” (TWC) was established in Trinity College Dublin with the purpose of uniting like-minded students to express, shape, inform and grow their interest in STEM. This club attempted to ‘bring STEM to life’ through thought provoking content, real world problems, contextualised analogies and projects. This paper describes the background to the TWC, reviews the literature around promoting student interest in STEM and examines initial feedback from participants in the pilot year of the club. The findings of this preliminary study indicate that the TWC has the potential to promote interest in STEM. Many of the recommendations from the literature review about promoting interest in STEM were referred to by participants in their responses