J J Strain’s research while affiliated with University of Ulster and other places

Background: Telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) variations are linked to age-related diseases and are associated with environmental exposure and nutritional status. Limited data, however, exist on the associations with mercury exposure, particularly early in life. Objective: We examined the association between prenatal mercury (Hg) exposure and TL and mtDNAcn in 1,145 Seychelles children, characterized by a fish-rich diet. Methods: Total mercury (THg) was determined in maternal hair at delivery and cord blood. TL and mtDNAcn were determined relative to a single-copy hemoglobin beta gene in the saliva of 7-y-old children. Linear regression models assessed associations between THg and relative TL (rTL) and relative mtDNAcn (rmtDNAcn) while controlling for maternal and cord serum polyunsaturated fatty acid (PUFA) status and sociodemographic factors. Interactions between THg and child sex, PUFA, and telomerase genotypes were evaluated for rTL and rmtDNAcn. Results: Higher THg concentrations in maternal hair and cord blood were associated with longer rTL [β=0.009; 95% confidence interval (CI): 0.002, 0.016 and β=0.002; 95% CI: 0.001, 0.003, respectively], irrespective of sex, PUFA, or telomerase genotypes. Maternal serum n-6 PUFA and n-6/n-3 ratio were associated with shorter [β=-0.24; 95% CI: -0.33, -0.15 and β=-0.032; 95% CI: -0.048, -0.016, respectively] and n-3 PUFA with longer (β=0.34; 95% CI: 0.032, 0.65) rTL. Cord blood n-6 PUFA was associated with longer (β=0.15; 95% CI: 0.050, 0.26) rTL. Further analyses revealed linoleic acid in maternal blood and arachidonic acid in cord blood as the main drivers of the n-6 PUFA associations. No associations were observed for THg and PUFA with rmtDNAcn. Discussion: Our results indicate that prenatal THg exposure and PUFA status are associated with rTL later in childhood, although not consistently aligned with our initial hypothesis. Subsequent research is needed to confirm this finding, further evaluate the potential confounding of fish intake, and investigate the underlying molecular mechanisms to verify the use of rTL as a true biomarker of THg exposure. https://doi.org/10.1289/EHP14776.

Background Studies investigating associations between prenatal polyunsaturated fatty acid status (PUFAs), in particular the anti‐inflammatory n‐3 PUFAs, and the development of childhood asthma have yielded conflicting results. Objective To determine the associations between maternal fish intake (a rich source of the n‐3 PUFAs), maternal or cord PUFAs with the prevalence of childhood asthma in a high fish‐eating population. Methods We examined these associations between fish intake and PUFA concentrations with childhood asthma prevalence in the Seychelles Child Development Study Nutrition Cohort 2, a large observational study in a high fish‐eating population. Maternal fish intake during pregnancy and child's fish intake at 7 years were assessed by questionnaire, with frequency reported as meals/week. Serum concentrations of PUFAs were quantified in maternal blood collected at 28 weeks' gestation (n = 1448) and in cord blood (n = 1088). Asthma in children at 7 years was assessed using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire (n = 1098). Results A total of 97 children (10.5%) were reported to have asthma. In regression analysis, the odds of childhood asthma were not associated with maternal fish intake or maternal PUFA status. Cord DHA concentrations were associated with increased asthma prevalence when the highest quartile (≥0.123 mg/mL) was compared with the lowest (<0.061 mg/mL). Conclusion The results from this current study add to the growing body of evidence that fish consumption during pregnancy is not associated with asthma development in offspring. The associations between cord blood DHA and asthma prevalence are unexpected and warrant further investigation.

Sub-optimal status of one or more of the interrelated B-vitamins (folate, B12, B6 and riboflavin) is common among older adults ¹ , and considerable observational evidence links low B-vitamin status (and/or elevated concentrations of the related metabolite, homocysteine) with a higher risk of agerelated diseases 2,3 . These nutrients are interlinked though their roles in one-carbon metabolism, but very few studies have investigated the major contributors to status of all four B-vitamins or the trends in B-vitamin biomarkers with advancing age. The aim of this study, therefore, was to investigate the contribution of fortified foods and supplements to dietary intakes and biomarkers of B-vitamins in older adults. From a total sample of community-dwelling older adults (n = 5,186; ≥ 60 years) initially recruited to the Trinity-Ulster-Department of Agriculture (TUDA) study from 2008–2012, an eligible subset (n = 953) was re-investigated between 2016 and 2019. Dietary intake was assessed using a 4-day food diary (over four consecutive days) in combination with a food-frequency questionnaire. Mean daily energy and B-vitamin intakes were calculated using a customised version of the nutritional software package Nutritics (V.4). Non-fasting blood samples were collected at initial sampling and at follow-up to measure corresponding B-vitamin biomarkers. Statistical differences between categories of fortified food consumption and supplement use were assessed using ANCOVA (with adjustment for relevant covariates), while relationships between dietary and corresponding biomarker variables were examined using Pearson correlation coefficients. As dietary intakes of fortified foods increased (from 0 to > 7 portions per week), biomarkers of each B-vitamin improved in a stepwise manner ( P <0.001), and there was a corresponding decrease in plasma homocysteine concentrations ( P <0.001), and the highest B-vitamin biomarkers were observed in those taking B-vitamin supplements. Although mean values for B-vitamin biomarkers generally compared favourably with normal ranges, deficient status of individual B-vitamins at initial sampling (2008 – 2012) was identified in: serum folate (8%), vitamin B12 (8%), vitamin B6 (8%), riboflavin (23%). Non-consumers of fortified food or supplements were at greatest risk of deficiency for each B-vitamin. Dietary intakes from foods were significantly correlated with corresponding biomarkers for serum folate (r = 0.458, P <0.001), plasma pyridoxal-5-phosphate (PLP; r = 0.192, P 0.002) and erythrocyte glutathione reductase activation coefficient (EGRac; r = −0.197, P 0.001), whereas no significant correlation was observed for vitamin B12 intake with status. In conclusion, regular consumption of fortified foods is an effective means to improve intakes and status of folate and related B-vitamins, reduce homocysteine concentrations and lower the prevalence of B-vitamin deficiency. These results emphasise the importance of fortified foods and supplements in contributing to status and highlight potential opportunities for the food industry to develop a wider range of foods fortified with sufficient levels of B-vitamins to optimise status and support healthy ageing.

was presented as the Nutrition and Optimum Life Course Theme Highlight. The n-3 polyunsaturated fatty acids (n-3 PUFA), eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), are known for their beneficial roles in regulating inflammation ⁽¹⁾ . The omega 3 index (O3I) refers to the percentage of EPA+DHA within the erythrocyte membrane with respect to total fatty acids and is a recognised biomarker for cardiovascular disease ⁽²⁾ . An O3I >8% is proposed to confer the greatest level of cardioprotection ⁽²⁾ . Fish is the richest dietary source of n-3 PUFAs and has been noted as one of the main predictors of a higher O3I ⁽³⁾ . Current UK dietary guidelines recommend the consumption of two portions of fish per week; albeit the efficacy of these recommendations in raising the O3I is unknown ⁽⁴⁾ . The aim of this study was to investigate the influence of consuming two portions of fish per week on the O3I amongst low fish consuming women of childbearing age. Data were analysed from the iFish study ⁽⁵⁾ , an 8-week randomised controlled trial where low fish consuming women, were randomly assigned to consume either no fish (n = 18) or 2 portions of tuna (n = 8) or sardines (n = 9) per week. Total n-3 PUFA concentrations of the fish provided in the intervention were 6.47g/100g for sardines and 4.57g/100g for tuna. Fasting blood samples were collected at baseline and post-intervention. The O3I was determined in red blood cells in the control and two portions of fish groups by OmegaQuant Europe. Analysis of covariance, adjusting for age, BMI, and baseline O3I, examined the effect of the fish intervention on the O3I. Chi-square test was used to compare the O3I between groups when categorised as at risk (<4%), intermediate risk (48%) and low risk (>8%). Participants had a mean ± SD age of 25.5 ± 6.4 years. Baseline median (IQR) O3I of the cohort was 5.7 (5.2, 6.7) %. There was no significant difference in the O3I between treatment groups at baseline. Consumption of two portions of fish significantly increased the O3I when compared to the consumption of no fish [6.73 (5.41, 7.38) % vs 5.58 (5.12, 6.49) %, respectively, p = 0.034]. Those consuming two portions of sardines, an oily fish high in n-3 PUFAs, had a significantly greater O3I when compared to those consuming two portions of tuna [7.38 (6.83, 8.37) % vs 5.61 (5.29, 6.79) %, respectively, p <0.001]. Post-intervention, the proportion of participants in the low risk O3I category (>8%) was greater in the two portions of fish group when compared to the control group; albeit this did not reach statistical significance ( p = 0.104). In support of the current dietary guidelines, increasing fish consumption of low consumers to two portions of any fish per week will increase the O3I. Future research should determine the potential cardioprotective properties of a higher O3I as a result of consuming fish.

Dietary intake can influence immune function indirectly by affecting the gut microbiota composition and metabolism ⁽¹⁾ . Fish consumption has been shown to positively regulate the gut microbiota in humans (2,3) ;albeit in those studies fish was consumed in high amounts (500-750g/week) and immune function was not investigated. This study investigated the effect of consuming the UK dietary recommendation for fish ⁽⁴⁾ (2 portions [140-280g/week], one of which is oily) on the gut microbiota alpha diversity. Further, we examined if changes (pre- to post-intervention) in the gut microbiota composition were associated with changes in immune cytokine concentrations. An 8-week randomised controlled trial in low fish consuming women of childbearing age (n = 41; median age 23y) investigated the effect of consuming 1 or 2 portions of fish (tuna or sardines)/week compared to not consuming fish. A blood sample was collected to measure inflammatory cytokines (tumour necrosis factor-a, interleukin [IL]-1b, IL-5, IL-6, IL-17A and IL-22) pre-and post-intervention. Faecal samples were collected at both timepoints and extracted DNA was used to determine gut microbiota compositional profiles using 16S metagenomic sequencing (Illumina, USA). Statistical analysis investigated significant differences in changes in gut microbiota alpha diversity and compositional relative abundances between fish intervention (N = 26) and control (N = 15), then secondary analysis stratified by portion size (1 vs 2 portions) and type of fish (tuna vs sardines). Differences in cytokines between fish intervention and control were assessed by Mann-Whitney U. Spearman rank coefficient assessed associations between the changes in gut microbiota relative abundances with cytokine changes in fish and control groups. Fish consumption increased gut microbiota alpha diversity indices (Chao1 [7.37 ± 41.23], Simpson [0.003 ± 0.163], Shannon [0.07 ± 0.33], phylogenetic diversity [0.35 ± 2.59], observed species [9.00 ± 40.06]), albeit this was not significant compared to the control group (p>0.05). Consumption of fish, specifically sardines, for 8 weeks significantly reduced Bacteroidetes (-4.77 ± 4.88%) when compared to control (+4.15 ± 7.58%) (p<0.01). No significant differences were observed between the change in relative abundances of gut microbiota at genus-level taxa or inflammatory cytokines between the fish intervention and control. In the fish intervention group, increases in IL-17A, IL-22 and IL-6 concentrations were positively correlated with changes in Alistipes, Rhodococcus, Haemophilus, Barnesiella and Akkermansia relative abundances (p<0.05). Although not statistically significant, consistent findings suggest that fish intake, in line with dietary guidelines, may have favourable impact on gut microbiota. Sardines, oily fish rich in n-3 polyunsaturated fatty acids, may have health benefits in disease states where Bacteroidetes is elevated; nevertheless, further research is required in a larger cohort over a longer period.

Findings from animal models suggest early exposure to polyunsaturated fatty acids (PUFAs) during pregnancy may influence developmental plasticity including adiposity ⁽¹⁾ . Birth cohort studies examining associations between offspring weight and maternal n-3 PUFA status or maternal fish intakes, the richest dietary source of n-3 PUFAs have been few and have yielded inconsistent findings. Some have reported lower weight at birth and throughout childhood with increasing maternal fish intakes and n-3 PUFA status ⁽²⁾ , whilst others have observed positive or null associations (3,4) . These have focused on the first few years of life and have been conducted within low fish-consuming populations. Our study provides novel data by examining associations between maternal fish consumption and prenatal PUFA (n-3 & n-6) status and offspring weight at birth and throughout childhood (7 & 13 years) in a high fish-eating population. Pregnant women were enrolled in the Seychelles Child Development Study Nutrition Cohort 2 between 2008-2011. Serum PUFAs were quantified in maternal blood collected at 28-weeks’ gestation and in cord blood collected at delivery using gas-chromatography tandem mass spectrometry. Maternal fish consumption was assessed at 28-weeks’ gestation using a Fish Use Questionnaire. Childbirth weight (kg) was measured at delivery and classified according to WHO growth standards ⁽⁵⁾ (n = 1185). Child height (m), weight (kg), waist and hip circumference (cm) were recorded at 7 (n = 1167) and 13 (n = 878) years. Statistical analysis was conducted using logistic and multiple linear regression adjusting for child sex, gestational age, maternal age, BMI, alcohol use, socioeconomic status, and parity. Models at 7 & 13 years were additionally adjusted for child height and fish intakes. Women were consuming on average 8.49 ± 4.51 fish meals/week during pregnancy. No significant associations were found between maternal fish intakes and anthropometric outcomes at birth, 7 & 13 years. No significant associations were observed between maternal PUFAs and offspring weight at birth. At both 7 & 13 years, however, higher maternal total n-6 PUFAs were associated with increased child weight [7yr; β = 0.070, p = 0.003, 13yr; β = 0.097, p = 0.004], waist circumference [7yr; β = 0.086, p = 0.003, 13yr; β = 0.105, p = 0.004], and hip circumference [7yr; β = 0.062, p = 0.027, 13yr; β = 0.090, p = 0.013]. No significant associations were found between cord n-6 PUFAs and birth weight. In quartile analysis, cord docosahexaenoic acid (DHA; C22:6n-3) concentrations <0.071mg/ml were associated with a higher risk of large for gestational age (LGA; >90 th percentile) when compared to cord DHA concentrations >0.129mg/ml [OR 4.17, p = 0.017]. There were no significant associations between cord PUFAs and anthropometric outcomes at 7 & 13 years. These findings suggest lower cord DHA, an n-3 PUFA, may be associated with higher risk of LGA at birth whilst higher n-6 PUFAs during pregnancy may be associated with adiposity development throughout childhood. Future work is needed to determine the potential long-term metabolic consequences of such associations.

Higher consumption of n-3 polyunsaturated fatty acids (PUFAs) is associated with reduced severity of cardiovascular disease (CVD) and autoimmunity ⁽¹⁾ . The n-3 index (O3I), which correlates to n-3 PUFA habitual intake, is a useful clinical biomarker in determining cardiovascular risk ⁽²⁾ . Individuals with an O3I <4% are considered to have higher cardiovascular risk, with 4-8% characterised as medium risk. The desirable O3I is >8% and deemed low risk for a cardiovascular event ⁽³⁾ . Yet, little is known about O3I in systemic lupus erythematosus (SLE) patients who have a higher risk of CVD associated with their disease. This analysis aimed to determine the O3I of SLE patients, and its associations with disease activity. A non-fasted blood sample was collected from SLE patients (n = 15) and healthy participants (n = 15). Isolated red blood cells were used to determine O3I and expressed as %. Habitual intake of fish, a rich source of n-3 PUFAs was assessed by questionnaire. Disease activity of SLE patients was assessed by a clinician using the British Isle Lupus Assessment Group (BILAG), Systemic Lupus Activity Measure-Revised (SLAM-R) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Mann-Whitney U was used to evaluate O3I differences between SLE patients and healthy participants. Spearman’s rank coefficient assessed associations between O3I and SLE disease activity. SLE patients had an O3I of 4.38% and categorised to have a medium risk of a cardiovascular event, which was significantly lower compared to healthy participants for cardiovascular risk (5.48%; p<0.01). Some 67% SLE patients (n = 10) reported to never/rarely consume fish (≤1 portion per month) whereas 53% healthy participants (n = 8) reported that they consumer >2 portions of fish per month. Correlation analysis showed O3I was negatively associated with BILAG (rho = −0.061), SLAM-R (rho = −0.215) and SLEDAI (rho = −0.122); albeit these associations were not significant (p>0.05). This is the first report of O3I in SLE patients and identified lower O3I compared to healthy participants, suggesting that SLE patients might benefit from increasing fish consumption to reduce their risk of CVD. Further research is required to fully elucidate associations between O3I and SLE disease activity.

Background Loneliness can affect up to 30% of older adults and is associated with increased morbidity and all cause mortality. Loneliness is also a major risk factor for depression. We aimed to explore the predictors of loneliness in older Irish adults and its relationship to depression. Methods Study participants were Irish adults aged >60 years in the Trinity Ulster University Department of Agriculture (TUDA) study. Participants with an MMSE <24 were excluded, to prevent the inclusion of individuals with dementia. Loneliness in the last week was identified from the 'loneliness' question in the Center for Epidemiological Studies Depression Scale (CES-D) and considered present when experienced ≥1-2 days in the last week and absent when experienced rarely or none of the time. Depression was defined as a CES-D ≥16. Predictors of loneliness were explored in multinomial regression models as well as its association with depression. Results There were 4561 participants, 70% female, mean age 70.1 years and 21.6% experienced loneliness. Positive independent predictors of loneliness were living alone (OR 5.2, CI 4.41-6.14, p<0.001), female sex (OR 1.29, CI 1.07-1.56, p=0.009), timed up and go >12 seconds (OR 1.46-2.32, p<0.001) non-driving status (OR 1.37, CI 1.13-1.67, P=0.001) and lower MMSE (OR 0.57, CI 0.41-0.79, p=0.0006). Those who reported loneliness had a higher prevalence of depression (32.1 vs 3.3%, p<0.0001). Conclusion Living alone was, as expected, the greatest predictor of loneliness followed by physical frailty, non-driving status, female sex, and lower cognition. A high proportion (one third) who felt lonely had depression, though low mood may increase the perception of loneliness independent of social engagement. A limitation is that we did not have a specific validated tool to assess loneliness or to distinguish between `emotional' or `social' loneliness.

Background Several studies have shown that vitamin D deficiency may increase the risk of developing type II diabetes and prediabetes. However, the data are inconsistent. Vitamin D may improve insulin sensitivity and pancreatic beta cell function, which could influence diabetes risk. We aimed to examine the relationship between vitamin D deficiency and type II diabetes in older Irish adults. Methods Study participants were from a cross-sectional study of adults aged > 60 years; Trinity Ulster University Department of Agriculture (TUDA) study. Diabetes was defined by self-report, use of diabetic medications or HBA1c ≥ 6.5%. Vitamin D deficiency was defined as 25(OH)D < 30 nmol/l. The relationship between vitamin D deficiency and diabetes was explored in multivariate logistic regression adjusting for age, sex, BMI, waist hip ratio, season, vitamin D supplement use, timed up and go, alcohol intake, current or previous steroid use, smoking, use of statins and socioeconomic status. Results There were 5171 participants (67.2% female, mean age 74.0 years) of whom 19.7% were vitamin D deficient and 15.7% had diabetes. Vitamin D deficiency versus non-deficiency was associated with an increased risk of diabetes both before and after multivariate adjustment (OR 1.46, 1.98-1.79, p<0.0002). Conclusion Vitamin D deficiency was associated with a 46% increased risk of having type II diabetes. However, the results of longitudinal studies and randomised trials have produced inconsistent results, though many had participants with higher baseline 25(OH)D status. A recent review of 46 trials of vitamin D supplementation found that it may reduce Hba1c in diabetics with vitamin D deficiency. Well designed trials to assess the potential effect of vitamin D supplementation on diabetic risk should be conducted.