Dr Katrina King

© 2016 The Authors. Published by Elsevier Inc. Vitamin D is known for its role in the regulation of gene expression via the Vitamin D receptor, a nuclear transcription factor. More recently, a role for Vitamin D in regulating DNA methylation has been identified as an additional mechanism of modulation of gene expression. How methylation status influences Vitamin D metabolism and response pathways is not yet clear. Therefore, we aimed to assess the relationship between plasma 25-hydroxycholecalciferol (25(OH)D) and the methylation status of Vitamin D metabolism enzyme genes (CYP2R1, CYP27B1 and CYP24A1) and the Vitamin D receptor gene (VDR). This analysis was conducted in the context of dietary Vitamin D, and background methyl donor related biochemistry, with adjustment for several dietary and lifestyle variables. Percentage methylation at CpG sites was assessed in peripheral blood cells using methylation sensitive and dependent enzymes and qPCR. Standard analytical techniques were used to determine plasma 25(OH)D and homocysteine, and serum folate and B12, with the relationship to methylation status assessed using multi-variable regression analysis. CYP2R1 and VDR methylation were found to be independent predictors of plasma 25(OH)D, when adjusted for Vitamin D intake and other lifestyle variables. CYP24A1 was related to plasma 25(OH)D directly, but not in the context of Vitamin D intake. Methyl-group donor biochemistry was associated with the methylation status of some genes, but did not alter the relationship between methylation and plasma 25(OH)D. Modulation of methylation status of CYP2R1, CYP24A1 and VDR in response to plasma 25(OH)D may be part of feedback loops involved in maintaining Vitamin D homeostasis, and may explain a portion of the variance in plasma 25(OH)D levels in response to intake and sun exposure. Methyl-group donor biochemistry, while a potential independent modulator, did not alter this effect.

© 2016 The Authors Background/objectives Restricting energy intake for weight management in older adults has potential to adversely affect nutritional status and result in impairment of an already compromised immune system. Investigation of alternative strategies to combat adiposity and sustain lean muscle mass in older adults are warranted to minimise the risk of developing chronic diseases. Long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may play an important role through their impact on increased fat oxidation and reduced inflammation. This study aimed to examine the association between erythrocyte membrane LCn-3PUFA and anthropometric measures in an older population. Subjects/methods A cross-sectional sample of older adults (n¿=¿620; age 65¿95 years; 56.3% females) from the Retirement Health and Lifestyle Study (RHLS) was analysed. Anthropometric measurements, including height, weight, body mass index (BMI), waist (WC) and hip circumference (HC) were taken. The fatty acid composition of erythrocyte membranes was analysed via gas chromatography (GC) to determine the omega-3 index (%EPA plus %DHA). Results An inverse association was detected between the omega-3 index and anthropometric measures, BMI (r¿=¿-0.076, p=0.06), WC (r¿=¿-0.118, p¿<¿0.01) and waist-to-hip ratio (WHR; r¿=¿-0.149, p¿<¿0.001). Stratification of data by sex (females, n¿=¿349; males, n¿=¿271) indicated that these associations were sex-specific. Females displayed an inverse association between the omega-3 index and BMI (r¿=¿-0.146, p¿<¿0.01) and WC (r¿=¿-0.125, p¿<¿0.05). In contrast, no significant association between the omega-3 index and anthropometric measures was detected in males. After correcting for the potentially confounding effects of age, household income, fish oil supplement status, daily dietary energy intake and total physical activity times, the omega-3 index was inversely associated with BMI and WC in females but not males. Conclusions Omega-3 status was associated with weight status, particularly in older women but not in men. These results suggest the need for sex-based intervention trials to examine the role of dietary intake and/or supplementation of LCn-3PUFA in weight management of older adults.

© 2016 The Authors Background/Objectives Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in older people but currently no specific drugs are available for its treatment. Omega-3 polyunsaturated fatty acids (n-3PUFA), known for their lipid-lowering, anti-inflammatory and anti-hypertensive properties, may have therapeutic potential for the management of NAFLD. The aim of this study was to determine whether n-3PUFA levels are associated with the prevalence of NAFLD in older adults. Methods A cross-sectional sample of older adults aged 65¿95 years (n¿=¿620) from the Retirement Health and Lifestyle Study (RHLS) was analysed. Fatty Liver Index (FLI) scores, used as an indicator of NAFLD risk, were calculated using a validated algorithm that incorporates body mass index, waist circumference, plasma triglycerides and ¿-glutamyl transferase. Omega-3 index scores (O3I, %eicosapentaenoic acid plus %docosahexaenoic acid) were determined by analysing the fatty acid composition of erythrocyte membranes by gas chromatography. Results Following application of exclusion criteria, 475 participants were included in the analysis (age 77.9¿±¿7.0 years; 60.4% females). Of these, 216 participants had FLI scores (=60) suggestive of NAFLD (age 77.0¿±¿6.6 years; 49.1% females). O3I was significantly lower in participants with NAFLD compared to those without NAFLD (p¿<¿0.01). A significant inverse relationship was found between O3I and FLI (r¿=¿-0.165; p¿<¿0.001). This relationship was gender specific with women, but not men, showing a significant association (r¿=¿-0.206; p¿<¿0.001). Conclusions The current study demonstrated a sex-dependent inverse relationship between erythrocyte n-3PUFA concentrations and NAFLD in older adults. The finding supports the proposal for sex-stratified n-3PUFA intervention trials in this high-risk age group.

© 2016 The Authors Background Elevated levels of pro-inflammatory mediators heighten the risk of developing or aggravating a spectrum of chronic diseases and are a strong predictor of mortality in elderly cohorts. Omega-3 polyunsaturated fatty acids (n-3PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are known to possess anti-inflammatory properties. However, the relationship between erythrocyte membrane n-3PUFA and inflammation biomarkers has not been well established. Objective This study aimed to determine if n-3PUFA status, together with the omega-3 index (O3I, erythrocyte membrane % EPA plus DHA), is associated with pro-inflammatory mediators in older Australians. Methods The study was a cross-sectional analysis of randomly selected older men and women aged =65 years (n¿=¿620) recruited from the Central Coast of NSW, Australia. Fasted blood samples were analysed for C-reactive protein (CRP), fibrinogen and full blood count using standardised laboratory methods. The fatty acid composition of erythrocyte membranes was analysed via gas chromatography to determine n-3PUFA levels. The relationships between n-3PUFA and inflammatory mediators were evaluated in multivariate regression models after adjusting for known inflammatory confounders. Results After excluding participants who had an inflammatory disease, CRP levels >10¿mg/L, or who were taking anti-inflammatory medications or n-3PUFA supplements, 126 participants (age 77.6¿±¿7.3 years; females, 46%) were included in the analysis. After multivariate adjustments, O3I was inversely associated with CRP (ß¿=¿-0.209, p¿<¿0.05) and monocyte cell counts (ß¿=¿-0.205, p¿<¿0.05), and total n-3PUFA was inversely related to WBC (ß¿=¿-0.238, p¿<¿0.05), neutrophils (ß¿=¿-0.212, p¿<¿0.05) and monocytes (ß¿=¿-0.246, p¿<¿0.05). However no association between fibrinogen and O3I or total n-3PUFA was detected. Conclusions This study demonstrated a negative association between O3I and biomarkers of inflammation in an older population. The findings support a potential role for n-3PUFA supplementation in the management of inflammatory diseases.

© 2015 Elsevier Inc. Management of hyperlipidaemia remains a cornerstone therapy for the prevention of cardiovascular disease (CVD). Dietary supplementation with n-3 polyunsaturated fatty acid (PUFA) has been shown to modulate blood lipid profiles and reduce the risk of developing CVD. However, studies relating objective measures of long-term dietary n-3 PUFA intake and circulating lipid levels in older adults are limited. Thus, we aimed to determine whether there is an association between erythrocyte n-3 PUFA status (omega-3 index, O3I) and blood lipid profiles in older adults. A sample of adults aged 65-95 years who participated in the Retirement Health and Lifestyle Study was evaluated. Outcome measures included O3I (% eicosapentaenoic acid+% docosahexaenoic acid) and fasting blood lipid profiles [total cholesterol (TC), low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol and triglyceride (TG)]. Two hundred and seventy-six subjects were included in the analyses. The mean±SD age was 77.6±7.4 years, and 40.9% were males. O3I was significantly higher in females compared to males. O3I was inversely associated with plasma TG (P<.001) and TC/HDL-cholesterol ratio (P<.05), and positively associated with HDL-cholesterol (P<.05), in all subjects. Associations between O3I and TG were evident in both females (r=-0.250, P<.01) and males (r=-0.225, P<.05). In females only, the odds of being hypertriglyceridaemic were highest in those with lowest O3I (P=006). Trends for hypercholesterolaemia and elevated LDL risk were converse between males and females. Long-term n-3 PUFA status is associated with blood lipid profiles in older Australians. Our findings support the development and implementation of age-specific dietary strategies to reduce the risk of CVD via improving the O3I.

© 2015. Background: Free circulating microRNA (miRNA) in serum may be valuable biomarkers for disease diagnosis and prognosis. miR-21, the archetypal oncogenic miRNA, has been proposed as a biomarker for colorectal cancer and its benign precursor, adenomatous polyps. However, it is now becoming clear that circulating miRNA profiles may be sensitive to lifestyle and environmental influences. Dietary components involved in one-carbon metabolism are particularly well placed to modulate miRNA expression through an influence on DNA methylation pathways. Methods: We investigated the role of methyl group donors (folate, B12, cysteine, homocysteine), polymorphisms of the enzymes of one-carbon metabolism, and serum miR-21 expression in a primary case-control cohort (colonoscopy confirmed adenomatous colon polyps vs controls; n. =. 253) and a secondary cross-sectional cohort (over 65s; n. =. 649). The relationships between these parameters and serum miR-21 levels were assessed, stratified by gender. Conclusions: Serum miR-21 expression was related to occurrence of adenomatous polyps in females, but not males. Folate levels and MTHFR-C677T genotype was associated with miR-21 expression in both genders. Additionally, DHFR-19 del and MSR-A66G were associated with miR-21 expression in females and males, respectively. Stimulation with excess folate increased expression of miR-21 in colon cancer cell lines. General significance: This study demonstrates that serum miR-21 expression correlates with folate status and related genetic status. This may have consequences for the proposed use of miR-21 as a colorectal cancer biomarker.