Reduced plasma homocysteine levels in elderly Australians following mandatory folic acid fortification – A comparison of two cross-sectional cohorts

© 2017 Objective In 2009, Australia implemented mandatory folic acid fortification in wheat flour for bread-making. The primary aim was to improve folate status in reproductive-aged women to reduce neural tube defect incidence. However, folic acid consumption has consequently increased in all demographics. Blood folate is inversely associated with homocysteine levels, a risk factor for multiple diseases. Therefore, we assessed the impact of mandatory folic acid fortification on homocysteine levels in elderly Australians. Methods Homocysteine and blood folate levels were compared between two elderly cross-sectional cohorts (pre-versus post-mandatory folic acid fortification). Importantly, dietary habits were assessed to evaluate the confounding influence of altered dietary patterns not related to fortification. Results Post-fortification, plasma homocysteine levels (10.6 vs. 14.5 μmol/L) and hyperhomocysteinemia incidence (27.2% vs 56.3%) were significantly reduced, relative to the pre-fortification subjects. This was associated with increased blood folate (red cell: 1243 vs 1066 nmol/L, serum 28.0 vs 23.9 nmol/L), and increased intake of synthetic folic acid (366.8 vs 231.0 DFE/day) but not natural folate (332.7 vs 323.6 DFE/day). Limited other differences were detected in dietary intake patterns between groups. The positive relationship between homocysteine levels and age was abrogated post-fortification (p = 0.3 vs p = 0.0003). Conclusions A potential off-target benefit of mandatory folic acid fortification in Australia was demonstrated. With many countries still considering the merits and consequences of mandatory fortification policies, it is important to unravel the off-target effects including dietary context

Relationship between methylation status of Vitamin D-related genes, Vitamin D levels, and methyl-donor biochemistry

© 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

InsuTAG: A novel physiologically relevant predictor for insulin resistance and metabolic syndrome

© 2017 The Author(s). The aim of this study was to investigate whether a novel physiologically relevant marker, InsuTAG (fasting insulin × fasting triglycerides) can predict insulin resistance (IR) and metabolic syndrome (MetS). Data of 618 participants from the Retirement Health and Lifestyle Study (RHLS) were evaluated for the current study. IR was defined by homeostatic model assessment (HOMA-IR) scores. Pearson correlations were used to examine the associations of InsuTAG with HOMA-IR and other markers. Predictions of IR from InsuTAG were evaluated using multiple regression models. Receiver operating characteristic curves (ROC) were constructed to measure the sensitivity and specificity of InsuTAG values and to determine the optimum cut-off point for prediction of IR. InsuTAG was positively correlated with HOMA-IR (r = 0.86; p < 0.0001). InsuTAG is a strong predictor of IR accounting for 65.0% of the variation in HOMA-IR values after adjusting for potential confounders. Areas under the ROC curve showed that InsuTAG (0.93) has higher value than other known lipid markers for predicting IR, with a sensitivity and specificity of 84.15% and 86.88%. Prevalence of MetS was significantly (p < 0.0001) higher in subjects with InsuTAG values greater than optimal cut-off value of 11.2. Thus, InsuTAG appears to be a potential feasible marker of IR and metabolic syndrome

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Sex-dependent association between omega-3 index and body weight status in older Australians

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

Association between erythrocyte omega-3 polyunsaturated fatty acid levels and fatty liver index in older people is sex dependent

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 γ-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

Erythrocyte omega-3 polyunsaturated fatty acid levels are associated with biomarkers of inflammation in older Australians

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 (β = −0.209, p < 0.05) and monocyte cell counts (β = −0.205, p < 0.05), and total n-3PUFA was inversely related to WBC (β = −0.238, p < 0.05), neutrophils (β = −0.212, p < 0.05) and monocytes (β = −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

Sex-dependent association between erythrocyte n-3 PUFA and type 2 diabetes in older overweight people

Copyright © The Authors 2016. The association between n-3 PUFA intake and type 2 diabetes (T2D) is unclear, and studies relating objective biomarkers of n-3 PUFA consumption to diabetic status remain limited. The aim of this study was to determine whether erythrocyte n-3 PUFA levels (n-3 index; n-3I) are associated with T2D in a cohort of older adults (n 608). To achieve this, the n-3I (erythrocyte %EPA+%DHA) was determined by GC and associated with fasting blood glucose; HbA1c; and plasma insulin. Insulin resistance (IR) was assessed using the homeostatic model assessment of insulin resistance (HOMA - IR). OR for T2D were calculated for each quartile of n-3I. In all, eighty-two type 2 diabetic (46.3 % female; 76.7 (sd 5.9) years) and 466 non-diabetic (57.9 % female; 77.8 (sd 7.1) years) individuals were included in the analysis. In overweight/obese (BMI≥27 kg/m 2 ), the prevalence of T2D decreased across ascending n-3I quartiles: 1.0 (reference), 0.82 (95 % CI 0.31, 2.18), 0.56 (95 % CI 0.21, 1.52) and 0.22 (95 % CI 0.06, 0.82) (P trend=0.015). A similar but non-significant trend was seen in overweight men. After adjusting for BMI, no associations were found between n-3I and fasting blood glucose, HbA1c, insulin or HOMA-IR. In conclusion, higher erythrocyte n-3 PUFA status may be protective against the development of T2D in overweight women. Further research is warranted to determine whether dietary interventions that improve n-3 PUFA status can improve measures of IR, and to further elucidate sex-dependent differences