Publications by authors named "Helene McNulty"

112 Publications

Glycated haemoglobin (HbA ), diabetes and neuropsychological performance in community-dwelling older adults.

Diabet Med 2021 Aug 3:e14668. Epub 2021 Aug 3.

Mercer's Institute for Successful Ageing, St James's Hospital, Dublin, Ireland.

Aims: Given that diabetes is associated with cognitive impairment and dementia in later life, we aimed to investigate the relationship between glycated haemoglobin (HbA ), diabetes and domain-specific neuropsychological performance in older adults.

Methods: Cross-sectional cohort study using data from the Trinity-Ulster-Department of Agriculture (TUDA) study. Participants underwent detailed cognitive and neuropsychological assessment using the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Repeatable Assessment for Neuropsychological Status (RBANS). Linear regression was used to assess associations between HbA , diabetes status and neuropsychological performance, with adjustment for important clinical covariates.

Results: Of 4938 older adults (74.1 ± 8.3 years; 66.9% female), 16.3% (n = 803) had diabetes (HbA  ≥ 6.5%; 48 mmol/mol), with prediabetes (HbA  ≥ 5.7%-6.4%; 39-47 mmol/mol) present in 28.3% (n = 1395). Increasing HbA concentration was associated with poorer overall performance on the FAB [β: -0.01 (-0.02, -0.00); p = 0.04 per % increase] and RBANS [β = -0.66 (-1.19, -0.13); p = 0.02 per % increase]. Increasing HbA was also associated with poorer performance on immediate memory, visuo-spatial, language and attention RBANS domains. Diabetes was associated poorer performance on neuropsychological tests of immediate memory, language, visual-spatial and attention.

Conclusions: Both increasing HbA and the presence of diabetes were associated with poorer cognitive and domain-specific performance in older adults. HbA , and not just diabetes status per se, may represent an important target in the promotion of optimal brain health in older adults.
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http://dx.doi.org/10.1111/dme.14668DOI Listing
August 2021

Review of recent innovations in portable child growth measurement devices for use in low- and middle-income countries.

J Med Eng Technol 2021 Jul 26:1-14. Epub 2021 Jul 26.

Nutrition Innovation Centre for Food and Health (NICHE), School of Biomedical Sciences, Ulster University, Coleraine, United Kingdom of Great Britain and Northern Ireland.

Improving nutritional status is fundamental to addressing challenges in child health in low- and middle-income countries (LMICs) and a priority for international organisations such as the United Nations Children's Fund (UNICEF) and the World Health Organisation (WHO). Despite the global consensus that child growth is a key indicator of child nutrition and health, the development of low-cost, accurate and child-friendly growth measurement devices that are fit for purpose in LMICs remains elusive. Recognising these limitations, UNICEF recently published a Target Product Profile (TPP) calling for the development of new state-of-the-art height and length measurement devices. The purpose of this review was to examine current growth measurement devices in relation to this UNICEF TPP requirement and set the stage for the development of new devices. The findings show that there is a gap in the product market for accurate portable length and height measurement devices. In particular, our review indicates that devices in current use generally lack capabilities for automated data recording and transfer of data to a central database, and are often not child-friendly. We conclude that future innovations in length and height measurement devices should focus on addressing these issues.
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http://dx.doi.org/10.1080/03091902.2021.1946181DOI Listing
July 2021

Long-term anticholinergic, benzodiazepine and Z-drug use in community-dwelling older adults: What is the impact on cognitive and neuropsychological performance?

Int J Geriatr Psychiatry 2021 Jul 6. Epub 2021 Jul 6.

Mercer's Institute for Successful Ageing, St James's Hospital, Dublin, Ireland.

Background: Long-term use of anticholinergics, benzodiazepines and related drugs (or "Z-drugs") have been associated with cognitive impairment and dementia. However, the relationship of these medications with cognitive function and domain-specific neuropsychological performance in older adults without dementia, is unclear.

Methods: 5135 older adults (74.0 ± 8.3 years; 67.4% female) without a diagnosis of dementia were recruited in Ireland to the Trinity-Ulster-Department of Agriculture (TUDA) study. Detailed cognitive and neuropsychological assessment was conducted using the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Repeatable Battery for Assessment of Neuropsychological Status (RBANS).

Results: A total of 44% (2259 of 5153) used either a potential or definite anticholinergic medication. Overall, 9.7% (n = 500) used a definite anticholinergic medication. Regular benzodiazepine use was reported by 7% (n = 363), whilst 7.5% (n = 387) used a "Z-drug". Use of definite, but not potential anticholinergic medication was associated with poorer performance on all three assessments (β: -0.09; 95% CI: -0.14, -0.03, p = 0.002 for MMSE; β: -0.04; 95% CI: -0.06, -0.02; p < 0.001 for FAB; β: -4.15; 95% CI: -5.64, -2.66; p < 0.001 for RBANS) in addition to all domains of the RBANS. Regular benzodiazepine use was also associated with poorer neuropsychological test performance, especially in Immediate Memory (β: -4.98; 95% CI: -6.81, -3.15; p < 0.001) and Attention (β: -6.81; 95% CI: -8.60, -5.03; p < 0.001) RBANS domains.

Conclusions: Regular use of definite anticholinergic medications and benzodiazepines, but not potential anticholinergics or "Z-drugs", was associated with poorer overall and domain-specific neuropsychological performance in older adults.
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http://dx.doi.org/10.1002/gps.5598DOI Listing
July 2021

Associations of atrophic gastritis and proton-pump inhibitor drug use with vitamin B-12 status, and the impact of fortified foods, in older adults.

Am J Clin Nutr 2021 Jun 16. Epub 2021 Jun 16.

Nutrition Innovation Centre for Food and Health (NICHE), School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, United Kingdom.

Background: Atrophic gastritis (AG) and use of proton pump inhibitors (PPIs) result in gastric acid suppression that can impair the absorption of vitamin B-12 from foods. The crystalline vitamin B-12 form, found in fortified foods, does not require gastric acid for its absorption and could thus be beneficial for older adults with hypochlorhydria, but evidence is lacking.

Objectives: To investigate associations of AG and PPI use with vitamin B-12 status, and the potential protective role of fortified foods, in older adults.

Methods: Eligible participants (n = 3299) not using vitamin B-12 supplements were drawn from the Trinity-Ulster and Department of Agriculture cohort, a study of noninstitutionalized adults aged ≥60 y and recruited in 2008-2012. Vitamin B-12 status was measured using 4 biomarkers, and vitamin B-12 deficiency was defined as a combined indicator value < -0.5. A pepsinogen I:II ratio <3 was considered indicative of AG.

Results: AG was identified in 15% of participants and associated with significantly lower serum total vitamin B-12 (P < 0.001) and plasma holotranscobalamin (holoTC; P < 0.001), and higher prevalence of vitamin B-12 deficiency (38%), compared with PPI users (21%) and controls (without AG and nonusers of PPIs; 15%; P < 0.001). PPI drugs were used (≥6 mo) by 37% of participants and were associated with lower holoTC concentrations, but only in participants taking higher doses (≥30 mg/d). Regular, compared with nonregular, consumption of fortified foods (i.e., ≥5 and 0-4 portions/wk, respectively) was associated with higher vitamin B-12 biomarkers in all participants, but inadequate to restore normal vitamin B-12 status in those with AG.

Conclusions: Older adults who have AG and/or use higher doses of PPIs are more likely to have indicators of vitamin B-12 deficiency. Fortified foods, if consumed regularly, were associated with enhanced vitamin B-12 status, but higher levels of added vitamin B-12 than currently provided could be warranted to optimize status in people with AG.
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http://dx.doi.org/10.1093/ajcn/nqab193DOI Listing
June 2021

Effects of maternal folic acid supplementation during the second and third trimesters of pregnancy on neurocognitive development in the child: an 11-year follow-up from a randomised controlled trial.

BMC Med 2021 Mar 10;19(1):73. Epub 2021 Mar 10.

Nutrition Innovation Centre for Food and Health (NICHE), School of Biomedical Sciences, Ulster University, Coleraine, BT52 1SA, Northern Ireland, UK.

Background: Maternal folic acid (FA) supplementation before and in early pregnancy prevents neural tube defects (NTD), but it is uncertain whether continuing FA after the first trimester has benefits on offspring health. We aimed to evaluate the effect of FA supplementation throughout pregnancy on cognitive performance and brain function in the child.

Methods: Follow-up investigation of 11-year-old children, residing in Northern Ireland, whose mothers had participated in a randomised trial of Folic Acid Supplementation in the Second and Third Trimesters (FASSTT) in pregnancy and received 400 μg/day FA or placebo from the 14th gestational week. Cognitive performance (Full Scale Intelligence Quotient, Verbal Comprehension, Working Memory, Perceptual Reasoning, and Processing Speed) was assessed using the Wechsler Intelligence Scale for Children. Neuronal function was assessed using magnetoencephalographic (MEG) brain imaging.

Results: Of 119 mother-child pairs in the FASSTT trial, 68 children were assessed for neurocognitive performance at 11-year follow-up (Dec 2017 to Nov 2018). Children of mothers randomised to FA compared with placebo scored significantly higher in two Processing Speed tests, i.e. symbol search (mean difference 2.9 points, 95% CI 0.3 to 5.5, p = 0.03) and cancellation (11.3 points, 2.5 to 20.1, p = 0.04), whereas the positive effect on Verbal Comprehension was significant in girls only (6.5 points, 1.2 to 11.8, p = 0.03). MEG assessment of neuronal responses to a language task showed increased power at the Beta (13-30 Hz, p = 0.01) and High Gamma (49-70 Hz, p = 0.04) bands in children from FA-supplemented mothers, suggesting more efficient semantic processing of language.

Conclusions: Continued FA supplementation in pregnancy beyond the early period currently recommended to prevent NTD can benefit neurocognitive development of the child. MEG provides a non-invasive tool in paediatric research to objectively assess functional brain activity in response to nutrition and other interventions.

Trial Registration: ISRCTN ISRCTN19917787 . Registered on 15 May 2013.
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http://dx.doi.org/10.1186/s12916-021-01914-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945668PMC
March 2021

Vitamin D and Hospital Admission in Older Adults: A Prospective Association.

Nutrients 2021 Feb 14;13(2). Epub 2021 Feb 14.

Department of Gerontology, St James's Hospital, D08 NYH1 Dublin, Ireland.

The health effects of vitamin D are well documented, with increasing evidence of its roles beyond bone. There is, however, little evidence of the effects of vitamin D on hospitalisation among older adults. This study aimed to prospectively determine the relationship of vitamin D status in older adults with hospital admission and emergency department (ED) attendance. Trinity University of Ulster Department of Agriculture (TUDA) is a large cross-sectional study of older adults with a community population from three disease-defined cohorts (cognitive dysfunction, hypertension, and osteoporosis). Participants included in this analysis were recruited between 2008 and 2012. ED and hospital admission data were gathered from the date of TUDA participation until June 2013, with a mean follow up of 3.6 years. Of the 3093 participants, 1577 (50.9%) attended the ED during the period of follow-up. Attendees had lower mean serum 25(OH)D concentrations than non-attendees (59.1 vs. 70.6 nmol/L). Fully adjusted models showed an inverse association between vitamin D and ED attendance (Hazard Ratio (HR) 0.996; 95% Confidence Interval (CI) 0.995-0.998; < 0.001). A total of 1269 participants (41%) were admitted to hospital during the follow-up. Those admitted had lower mean vitamin D concentrations (58.4 vs. 69.3 nmol/L, < 0.001). In fully adjusted models, higher vitamin D was inversely associated with hospital admission (HR 0.996; 95% CI 0.994-0.998; < 0.001) and length of stay (LOS) (β = -0.95, = 0.006). This study showed independent prospective associations between vitamin D deficiency and increased hospitalisation by older adults. The need for further evaluation of current recommendations in relation to vitamin D supplementation, with consideration beyond bone health, is warranted and should focus on randomised controlled trials.
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http://dx.doi.org/10.3390/nu13020616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918803PMC
February 2021

Diets, nutrients, genes and the microbiome: recent advances in personalised nutrition.

Br J Nutr 2021 Jan 29:1-9. Epub 2021 Jan 29.

Nutrition Innovation Center, DSM Nutritional Products Ltd, Kaiseraugst, Switzerland.

As individuals seek increasingly individualised nutrition and lifestyle guidance, numerous apps and nutrition programmes have emerged. However, complex individual variations in dietary behaviours, genotypes, gene expression and composition of the microbiome are increasingly recognised. Advances in digital tools and artificial intelligence can help individuals more easily track nutrient intakes and identify nutritional gaps. However, the influence of these nutrients on health outcomes can vary widely among individuals depending upon life stage, genetics and microbial composition. For example, folate may elicit favourable epigenetic effects on brain development during a critical developmental time window of pregnancy. Genes affecting vitamin B12 metabolism may lead to cardiometabolic traits that play an essential role in the context of obesity. Finally, an individual's gut microbial composition can determine their response to dietary fibre interventions during weight loss. These recent advances in understanding can lead to a more complete and integrated approach to promoting optimal health through personalised nutrition, in clinical practice settings and for individuals in their daily lives. The purpose of this review is to summarise presentations made during the DSM Science and Technology Award Symposium at the 13th European Nutrition Conference, which focused on personalised nutrition and novel technologies for health in the modern world.
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http://dx.doi.org/10.1017/S0007114521000374DOI Listing
January 2021

Impact of the common MTHFR 677C→T polymorphism on blood pressure in adulthood and role of riboflavin in modifying the genetic risk of hypertension: evidence from the JINGO project.

BMC Med 2020 11 11;18(1):318. Epub 2020 Nov 11.

The Nutrition Innovation Centre for Food and Health (NICHE), School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, UK.

Background: Genome-wide and clinical studies have linked the 677C→T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) with hypertension, whilst limited evidence shows that intervention with riboflavin (i.e. the MTHFR co-factor) can lower blood pressure (BP) in hypertensive patients with the variant MTHFR 677TT genotype. We investigated the impact of this common polymorphism on BP throughout adulthood and hypothesised that riboflavin status would modulate the genetic risk of hypertension.

Methods: Observational data on 6076 adults of 18-102 years were drawn from the Joint Irish Nutrigenomics Organisation project, comprising the Trinity-Ulster Department of Agriculture (TUDA; volunteer sample) and the National Adult Nutrition Survey (NANS; population-based sample) cohorts. Participants were recruited from the Republic of Ireland and Northern Ireland (UK) in 2008-2012 using standardised methods.

Results: The variant MTHFR 677TT genotype was identified in 12% of adults. From 18 to 70 years, this genotype was associated with an increased risk of hypertension (i.e. systolic BP ≥ 140 and/or a diastolic BP ≥ 90 mmHg): odds ratio (OR) 1.42, 95% confidence interval (CI) 1.07 to 1.90; P = 0.016, after adjustment for antihypertensive drug use and other significant factors, namely, age, male sex, BMI, alcohol and total cholesterol. Low or deficient biomarker status of riboflavin (observed in 30.2% and 30.0% of participants, respectively) exacerbated the genetic risk of hypertension, with a 3-fold increased risk for the TT genotype in combination with deficient riboflavin status (OR 3.00, 95% CI, 1.34-6.68; P = 0.007) relative to the CC genotype combined with normal riboflavin status. Up to 65 years, we observed poorer BP control rates on antihypertensive treatment in participants with the TT genotype (30%) compared to those without this variant, CT (37%) and CC (45%) genotypes (P < 0.027).

Conclusions: The MTHFR 677TT genotype is associated with higher BP independently of homocysteine and predisposes adults to an increased risk of hypertension and poorer BP control with antihypertensive treatment, whilst better riboflavin status is associated with a reduced genetic risk. Riboflavin intervention may thus offer a personalised approach to prevent the onset of hypertension in adults with the TT genotype; however, this requires confirmation in a randomised trial in non-hypertensive adults.
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http://dx.doi.org/10.1186/s12916-020-01780-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656675PMC
November 2020

Identifying Key Predictors of Cognitive Dysfunction in Older People Using Supervised Machine Learning Techniques: Observational Study.

JMIR Med Inform 2020 Sep 16;8(9):e20995. Epub 2020 Sep 16.

School of Biomedical Sciences, Nutrition Innovation Centre for Food and Health, Ulster University, Coleraine, United Kingdom.

Background: Machine learning techniques, specifically classification algorithms, may be effective to help understand key health, nutritional, and environmental factors associated with cognitive function in aging populations.

Objective: This study aims to use classification techniques to identify the key patient predictors that are considered most important in the classification of poorer cognitive performance, which is an early risk factor for dementia.

Methods: Data were used from the Trinity-Ulster and Department of Agriculture study, which included detailed information on sociodemographic, clinical, biochemical, nutritional, and lifestyle factors in 5186 older adults recruited from the Republic of Ireland and Northern Ireland, a proportion of whom (987/5186, 19.03%) were followed up 5-7 years later for reassessment. Cognitive function at both time points was assessed using a battery of tests, including the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), with a score <70 classed as poorer cognitive performance. This study trained 3 classifiers-decision trees, Naïve Bayes, and random forests-to classify the RBANS score and to identify key health, nutritional, and environmental predictors of cognitive performance and cognitive decline over the follow-up period. It assessed their performance, taking note of the variables that were deemed important for the optimized classifiers for their computational diagnostics.

Results: In the classification of a low RBANS score (<70), our models performed well (F score range 0.73-0.93), all highlighting the individual's score from the Timed Up and Go (TUG) test, the age at which the participant stopped education, and whether or not the participant's family reported memory concerns to be of key importance. The classification models performed well in classifying a greater rate of decline in the RBANS score (F score range 0.66-0.85), also indicating the TUG score to be of key importance, followed by blood indicators: plasma homocysteine, vitamin B6 biomarker (plasma pyridoxal-5-phosphate), and glycated hemoglobin.

Conclusions: The results suggest that it may be possible for a health care professional to make an initial evaluation, with a high level of confidence, of the potential for cognitive dysfunction using only a few short, noninvasive questions, thus providing a quick, efficient, and noninvasive way to help them decide whether or not a patient requires a full cognitive evaluation. This approach has the potential benefits of making time and cost savings for health service providers and avoiding stress created through unnecessary cognitive assessments in low-risk patients.
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http://dx.doi.org/10.2196/20995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527918PMC
September 2020

DNA methylation of hypertension-related genes and effect of riboflavin supplementation in adults stratified by genotype for the MTHFR C677T polymorphism.

Int J Cardiol 2021 01 10;322:233-239. Epub 2020 Sep 10.

Genomic Medicine Research Group, Ulster University, Coleraine BT52 1SA, N. Ireland, UK. Electronic address:

Background: The interaction between genetic, epigenetic and environmental factors plays an important role in the aetiology of hypertension. GWAS and observational studies link the C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR) with hypertension, while riboflavin, the MTHFR cofactor, has been shown to reduce blood pressure and global DNA methylation in homozygous (TT genotype) individuals. It is currently unclear whether riboflavin modulates DNA methylation of other hypertension-related genes.

Objectives: To compare DNA methylation of hypertension-related genes in adults stratified by MTHFR genotype and effect of riboflavin intervention in adults with the variant MTHFR 677TT genotype.

Method: Pyrosequencing was carried out for hypertension-related genes (ACE, AGTR1, GCK, GNA12, IGF2, MMP9 and NOS3) in blood samples from participants in previous trials (CC, n = 40; TT, n = 40). The effect of intervention with riboflavin (1.6 mg/d for16 weeks) or placebo on DNA methylation was investigated in adults with the variant MTHFR 677TT genotype (n = 80).

Results: Individuals with the MTHFR 677TT v CC genotype had significantly higher average DNA methylation at NOS3 (+1.66%, P = 0.044). In response to riboflavin supplementation in TT individuals, there was an increase in average DNA methylation at IGF2 (+1.09%, P = 0.019) and a decrease at ACE (-0.44%, P = 0.021) in females only. Specific CpG sites were hypomethylated in GNA12 and hypermethylated in AGTR1.

Conclusion: This study provides the first RCT evidence that riboflavin alters DNA methylation of hypertension-related genes in adults with the MTHFR 677TT genotype, providing some insight into mechanisms linking hypertension with the genotype-specific response of BP to riboflavin.
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http://dx.doi.org/10.1016/j.ijcard.2020.09.011DOI Listing
January 2021

Riboflavin Is an Important Determinant of Vitamin B-6 Status in Healthy Adults.

J Nutr 2020 10;150(10):2699-2706

Nutrition Innovation Centre for food and Health (NICHE), Ulster University, Coleraine, United Kingdom.

Background: Riboflavin is required to generate the active form of vitamin B-6 (pyridoxal 5'-phosphate; PLP) in tissues, but the relevance of this metabolic interaction for nutritional status of vitamin B-6 is unclear because riboflavin biomarkers are rarely measured in human studies.

Objectives: The purpose of this study was to identify the determinants of biomarkers of vitamin B-6 and riboflavin status and to examine the relationship between these nutrients in healthy adults.

Methods: Multiple linear regression was performed on observational data in 407 healthy adults aged 18-92 y who did not use B-vitamin supplements. Vitamin B-6 status was assessed by plasma PLP concentrations and erythrocyte glutathione reductase activation coefficient (EGRac) was used as a functional indicator of riboflavin status.

Results: Dietary intakes of vitamin B-6 and riboflavin were below the average requirements in 10% and 29% of participants, respectively. Suboptimal status of vitamin B-6 (PLP ≤30.0 nmol/L) was more prevalent in adults aged ≥60 y than in younger participants (i.e., 14% compared with 5%), whereas a high proportion (i.e., overall 37%) of both age groups had deficient riboflavin status (EGRac ≥1.40). In multiple regression analysis, EGRac (P = 0.019) was a significant determinant of plasma PLP, along with dietary vitamin B-6 intake (P = 0.003), age (P < 0.001), BMI (kg/m2) (P = 0.031), and methylenetetrahydrofolate reductase gene (MTHFR) genotype (P < 0.001). Significant determinants of EGRac were dietary riboflavin intake (P < 0.001), age (P < 0.001) and MTHFR genotype (P = 0.020). Plasma PLP showed a stepwise decrease across riboflavin status categories from optimal (EGRac ≤1.26) to low (EGRac 1.27-1.39) to deficient status (P = 0.001), independent of dietary vitamin B-6 intake.

Conclusions: The findings are consistent with the known metabolic dependency of vitamin B-6 on riboflavin status and indicate that riboflavin may be the limiting nutrient, particularly in older people, for maintaining adequate vitamin B-6 status.
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http://dx.doi.org/10.1093/jn/nxaa225DOI Listing
October 2020

Nutritional Epigenomics and Age-Related Disease.

Curr Dev Nutr 2020 Jul 6;4(7):nzaa097. Epub 2020 Jun 6.

Genomic Medicine Research Group , School of Biomedical Sciences, Ulster University, Northern Ireland, United Kingdom. BT52 1SA.

Recent advances in epigenetic research have enabled the development of epigenetic clocks, which have greatly enhanced our ability to investigate molecular processes that contribute to aging and age-related disease. These biomarkers offer the potential to measure the effect of environmental exposures linked to dynamic changes in DNA methylation, including nutrients, as factors in age-related disease. They also offer a compelling insight into how imbalances in the supply of nutrients, particularly B-vitamins, or polymorphisms in regulatory enzymes involved in 1-carbon metabolism, the key pathway that supplies methyl groups for epigenetic reactions, may influence epigenetic age and interindividual disease susceptibility. Evidence from recent studies is critically reviewed, focusing on the significant contribution of the epigenetic clock to nutritional epigenomics and its impact on health outcomes and age-related disease. Further longitudinal studies and randomized nutritional interventions are required to advance the field.
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http://dx.doi.org/10.1093/cdn/nzaa097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335360PMC
July 2020

Health effects of vitamin and mineral supplements.

BMJ 2020 06 29;369:m2511. Epub 2020 Jun 29.

Friedman School of Nutrition Science and Policy, Tufts University, Boston, USA.

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http://dx.doi.org/10.1136/bmj.m2511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322674PMC
June 2020

The Homozygous Hemoglobin EE Variant Is Associated with Poorer Riboflavin Status in Cambodian Women of Reproductive Age.

J Nutr 2020 07;150(7):1943-1950

Department of Food, Nutrition and Health, the University of British Columbia, Vancouver, Canada.

Background: Riboflavin is required for erythropoiesis, which is increased in people with hemoglobinopathies due to increased hemolysis and erythrocyte turnover. Dietary intake and status of riboflavin is poor in Cambodia, where hemoglobinopathies are common.

Objective: We assessed the association between genetic hemoglobin disorders and riboflavin status in women of reproductive age in Cambodia.

Methods: Venous blood samples from 515 Cambodian women of reproductive age, 18-45 y, were analyzed for biomarker status of riboflavin [erythrocyte glutathione reductase activation coefficient (EGRac)], genetic hemoglobin (Hb) disorders, and hematological indices. Linear regression analysis was used to estimate the association between EGRac with Hb, ferritin, and Hb genotypes. EGRac was log transformed in the analyses, and the regression coefficients represent the geometric mean differences.

Results: Genetic Hb disorders were present in 57% of the population, with the homozygous hemoglobin E variant (Hb EE) occurring in ∼10% of women (n = 53). Deficient (EGRac ≥1.40) or marginal riboflavin status (EGRac ≥1.30 and <1.40) was observed in 92% (n = 475) of women. The variant Hb EE genotype was associated with 18% (95% CI: 9%, 28%) higher geometric mean EGRac values than the normal Hb AA genotype (P < 0.001).

Conclusions: Although riboflavin biomarker deficiency or marginal status is widely prevalent in Cambodian women, lower riboflavin status was observed more frequently in women with the Hb EE genotype than in women with normal Hb AA. The relation between genetic Hb disorders and riboflavin warrants further investigation. This trial was registered at clinicaltrials.gov as NCT01593423 and NCT02481375.
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http://dx.doi.org/10.1093/jn/nxaa119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330481PMC
July 2020

Riboflavin supplementation alters global and gene-specific DNA methylation in adults with the MTHFR 677 TT genotype.

Biochimie 2020 Jun 22;173:17-26. Epub 2020 Apr 22.

Genomic Medicine Research Group, Ulster University, Coleraine, Northern Ireland, United Kingdom. Electronic address:

DNA methylation is important in regulating gene expression and genomic stability while aberrant DNA methylation is associated with disease. Riboflavin (FAD) is a cofactor for methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate recycling, which generates methyl groups for homocysteine remethylation to methionine, the pre-cursor to the universal methyl donor S-adenosylmethionine (SAM). A polymorphism (C677T) in MTHFR results in decreased MTHFR activity and increased homocysteine concentration. Previous studies demonstrated that riboflavin modulates this phenotype in homozygous adults (MTHFR 677 TT genotype), however, DNA methylation was not considered. This study examined DNA methylation, globally and at key MTHFR regulatory sites, in adults stratified by MTHFR genotype and the effect of riboflavin supplementation on DNA methylation in individuals with the 677 TT genotype. Samples were accessed from participants, screened for the MTHFR C677T polymorphism, who participated in observational (n = 80) and targeted riboflavin (1.6 mg/day) RCTs (n = 80). DNA methylation at LINE-1 and key regulatory regions of the MTHFR locus were analysed by pyrosequencing in peripheral blood leukocytes. LINE-1 (+1.6%; p = 0.011) and MTHFR south shelf (+4.7%, p < 0.001) were significantly hypermethylated in individuals with the MTHFR 677 TT compared to CC genotype. Riboflavin supplementation resulted in decreased global methylation, albeit only significant at one CpG. A significant reduction in DNA methylation at the MTHFR north shore (-1.2%, p < 0.001) was also observed in TT adults following intervention with riboflavin. This provides the first RCT evidence that DNA methylation may be modulated by riboflavin in adults with the MTHFR 677 TT genotype.
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http://dx.doi.org/10.1016/j.biochi.2020.04.007DOI Listing
June 2020

Impact of the MTHFR C677T polymorphism on one-carbon metabolites: Evidence from a randomised trial of riboflavin supplementation.

Biochimie 2020 Jun 21;173:91-99. Epub 2020 Apr 21.

Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Cromore Rd, Coleraine, BT52 1SA, Northern Ireland, UK. Electronic address:

Homozygosity for the C677T polymorphism in MTHFR (TT genotype) is associated with a 24-87% increased risk of hypertension. Blood pressure (BP) lowering was previously reported in adults with the TT genotype, in response to supplementation with the MTHFR cofactor, riboflavin. Whether the BP phenotype associated with the polymorphism is related to perturbed one-carbon metabolism is unknown. This study investigated one-carbon metabolites and their responsiveness to riboflavin in adults with the TT genotype. Plasma samples from adults (n 115) screened for the MTHFR genotype, who previously participated in RCTs to lower BP, were analysed for methionine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), betaine, choline and cystathionine by liquid chromatography tandem mass spectrometry (LC-MS/MS). The one-carbon metabolite response to riboflavin (1.6 mg/d; n 24) or placebo (n 23) for 16 weeks in adults with the TT genotype was also investigated. Plasma SAM (74.7 ± 21.0 vs 85.2 ± 22.6 nmol/L, P = 0.013) and SAM:SAH ratio (1.66 ± 0.55 vs 1.85 ± 0.51, P = 0.043) were lower and plasma homocysteine was higher (P = 0.043) in TT, compared to CC individuals. In response to riboflavin, SAM (P = 0.008) and cystathionine (P = 0.045) concentrations increased, with no responses in other one-carbon metabolites observed. These findings confirm perturbed one-carbon metabolism in individuals with the MTHFR 677TT genotype, and for the first time demonstrate that SAM, and cystathionine, increase in response to riboflavin supplementation in this genotype group. The genotype-specific, one-carbon metabolite responses to riboflavin intervention observed could offer some insight into the role of this gene-nutrient interaction in blood pressure.
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http://dx.doi.org/10.1016/j.biochi.2020.04.004DOI Listing
June 2020

Critical review of nutrition, blood pressure and risk of hypertension through the lifecycle: do B vitamins play a role?

Biochimie 2020 Jun 11;173:76-90. Epub 2020 Apr 11.

Nutrition Innovation Centre for Food and Health (NICHE), School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, BT52 1SA, United Kingdom. Electronic address:

Hypertension is the leading cause of preventable mortality worldwide, contributing to over 9 million deaths per annum, predominantly owing to cardiovascular disease. The association of obesity, physical inactivity and alcohol with elevated blood pressure (BP) is firmly established. Weight loss or other dietary strategies, such as the Dietary Approaches to Stop Hypertension (DASH) diet, have been shown to be effective in lowering BP. Additionally, specific nutrients are recognised to contribute to BP, with higher sodium intake linked with an increased risk of hypertension, while potassium is associated with a reduced risk of hypertension. Of note, emerging evidence has identified a novel role for one-carbon metabolism and the related B vitamins, particularly riboflavin, in BP. Specifically in adults genetically at risk of developing hypertension, owing to the common C677T polymorphism in MTHFR, supplemental riboflavin (co-factor for MTHFR) was shown in randomised trials to lower systolic BP by up to 13 mmHg. A BP response to intervention of this magnitude could have important clinical impacts, given that a reduction in systolic BP of 10 mmHg is estimated to decrease stroke risk by 40%. This review aims to explore the factors contributing to hypertension across the lifecycle and to critically evaluate the evidence supporting a role for nutrition, particularly folate-related B vitamins, in BP and risk of hypertension. In addition, gaps in our current knowledge that warrant future research in this area, will be identified.
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http://dx.doi.org/10.1016/j.biochi.2020.03.016DOI Listing
June 2020

Influence of nutrients involved in one-carbon metabolism on DNA methylation in adults-a systematic review and meta-analysis.

Nutr Rev 2020 08;78(8):647-666

Nutrition Innovation Centre for Food and Health (NICHE), School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, UK.

Context: Aberrant DNA methylation is linked to various diseases. The supply of methyl groups for methylation reactions is mediated by S-adenosylmethionine, which depends on the availability of folate and related B vitamins.

Objectives: To investigate the influence of key nutrients involved in 1-carbon metabolism on DNA methylation in adults.

Data Sources: Systematic literature searches were conducted in the Cochrane Library, Medline, Embase, Cumulative Index to Nursing and Allied Health Literature Plus, Scopus, and Web of Science databases. Studies that met the inclusion criteria and were published in English were included.

Data Extraction: The first author, study design, sample size, population characteristics, type and duration of intervention, tissue type or cells analyzed, molecular techniques, and DNA methylation outcomes.

Data Synthesis: A meta-analysis of randomized, controlled trials (RCTs) was conducted to investigate the effect of 1-carbon metabolism nutrients on global DNA methylation. Functional analysis and visualization were performed using BioVenn software.

Results: From a total of 2620 papers screened by title, 53 studies met the inclusion criteria. Qualitative analysis indicated significant associations between 1-carbon metabolism nutrients and DNA methylation. In meta-analysis of RCTs stratified by method of laboratory analysis, supplementation with folic acid alone or in combination with vitamin B12 significantly increased global DNA methylation in studies using liquid chromatography-mass spectrometry, which had markedly lower heterogeneity (n = 3; Z = 3.31; P = 0.0009; I2 = 0%) in comparison to other methods. Functional analysis highlighted a subset of 12 differentially methylated regions that were significantly related to folate and vitamin B12 biomarkers.

Conclusion: This study supports significant associations between 1-carbon metabolism nutrients and DNA methylation. However, standardization of DNA methylation techniques is recommended to reduce heterogeneity and facilitate comparison across studies.

Systematic Review Registration: PROSPERO registration number: CRD42018091898.
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http://dx.doi.org/10.1093/nutrit/nuz094DOI Listing
August 2020

Evidence of a Role for One-Carbon Metabolism in Blood Pressure: Can B Vitamin Intervention Address the Genetic Risk of Hypertension Owing to a Common Folate Polymorphism?

Curr Dev Nutr 2020 Jan 16;4(1):nzz102. Epub 2019 Sep 16.

Nutrition Innovation Centre for Food and Health, School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, United Kingdom.

Hypertension in adulthood is recognized as the leading risk factor contributing to mortality worldwide, primarily from cardiovascular disease, whereas hypertension in pregnancy leads to serious adverse fetal and maternal outcomes. This article explores the under-recognized role of one-carbon metabolism in blood pressure (BP) and the potential for folate-related B vitamins to protect against hypertension. Genome-wide association studies and clinical studies provide evidence linking the 677C→T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) with BP and increased risk of hypertension and hypertension in pregnancy. A novel role for riboflavin (the MTHFR cofactor) has recently emerged, however, with evidence from randomized trials that supplemental riboflavin can lower BP specifically in adults with the variant 677TT genotype. Further studies are required to elucidate the biological mechanisms linking one-carbon metabolism with BP and explore the effect of riboflavin in modulating the genetic risk of hypertension in early and later life.
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http://dx.doi.org/10.1093/cdn/nzz102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955829PMC
January 2020

Effect of continued folic acid supplementation beyond the first trimester of pregnancy on cognitive performance in the child: a follow-up study from a randomized controlled trial (FASSTT Offspring Trial).

BMC Med 2019 10 31;17(1):196. Epub 2019 Oct 31.

Nutrition Innovation Centre for Food and Health (NICHE), School of Biomedical Sciences, Ulster University, Coleraine, BT52 1SA, Northern Ireland, UK.

Background: Periconceptional folic acid prevents neural tube defects (NTDs), but it is uncertain whether there are benefits for offspring neurodevelopment arising from continued maternal folic acid supplementation beyond the first trimester. We investigated the effect of folic acid supplementation during trimesters 2 and 3 of pregnancy on cognitive performance in the child.

Methods: We followed up the children of mothers who had participated in a randomized controlled trial in 2006/2007 of Folic Acid Supplementation during the Second and Third Trimesters (FASSTT) and received 400 μg/d folic acid or placebo from the 14th gestational week until the end of pregnancy. Cognitive performance of children at 7 years was evaluated using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) and at 3 years using the Bayley's Scale of Infant and Toddler Development (BSITD-III).

Results: From a total of 119 potential mother-child pairs, 70 children completed the assessment at age 7 years, and 39 at age 3 years. At 7 years, the children of folic acid treated mothers scored significantly higher than the placebo group in word reasoning: mean 13.3 (95% CI 12.4-14.2) versus 11.9 (95% CI 11.0-12.8); p = 0.027; at 3 years, they scored significantly higher in cognition: 10.3 (95% CI 9.3-11.3) versus 9.5 (95% CI 8.8-10.2); p = 0.040. At both time points, greater proportions of children from folic acid treated mothers compared with placebo had cognitive scores above the median values of 10 (girls and boys) for the BSITD-III, and 24.5 (girls) and 21.5 (boys) for the WPPSI-III tests. When compared with a nationally representative sample of British children at 7 years, WPPSI-III test scores were higher in children from folic acid treated mothers for verbal IQ (p < 0.001), performance IQ (p = 0.035), general language (p = 0.002), and full scale IQ (p = 0.001), whereas comparison of the placebo group with British children showed smaller differences in scores for verbal IQ (p = 0.034) and full scale IQ (p = 0.017) and no differences for performance IQ or general language.

Conclusions: Continued folic acid supplementation in pregnancy beyond the early period recommended to prevent NTD may have beneficial effects on child cognitive development. Further randomized trials in pregnancy with follow-up in childhood are warranted.

Trial Registration: ISRCTN ISRCTN19917787 . Registered 15 May 2013.
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http://dx.doi.org/10.1186/s12916-019-1432-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823954PMC
October 2019

Suboptimal Biochemical Riboflavin Status Is Associated with Lower Hemoglobin and Higher Rates of Anemia in a Sample of Canadian and Malaysian Women of Reproductive Age.

J Nutr 2019 11;149(11):1952-1959

Department of Food, Nutrition, and Health, University of British Columbia, Vancouver, British Columbia, Canada.

Background: Riboflavin is required for several redox reactions. Clinical riboflavin deficiency occurs mainly in low-income countries, where it is associated with anemia. The functional significance of suboptimal riboflavin status in different populations and its role in anemia is not well understood.

Objectives: We assessed the biomarker status of riboflavin and its association with hemoglobin concentration and anemia in women living in Vancouver, Canada, and Kuala Lumpur, Malaysia.

Methods: Healthy nonpregnant, nonbreastfeeding women (19-45 y) were recruited from Canada ( n = 206) and Malaysia (n = 210) via convenience sampling. Fasting blood was collected to assess riboflavin status [erythrocyte glutathione reductase activity coefficient (EGRac)], hematological indicators, soluble transferrin receptor (sTfR), ferritin, vitamin A, folate, and vitamin B-12 concentrations. Linear and logistic regression models were used to assess the association of riboflavin status with hemoglobin concentration and anemia.

Results: EGRac (mean ± SD) values were higher, indicating poorer riboflavin status, in Malaysian compared with Canadian women (1.49 ± 0.17 compared with 1.38 ± 0.11). Likewise, riboflavin biomarker deficiency (EGRac ≥1.40) was significantly more prevalent among Malaysians than Canadians (71% compared with 40%). More Malaysian than Canadian women were anemic (hemoglobin <120 g/L; 18% compared with 7%). With use of linear regression (pooled sample; n = 416), EGRac values were negatively associated with hemoglobin concentration (r = -0.18; P < 0.001). This relation remained significant (P = 0.029) after adjusting for age, parity, ethnicity, vitamin B-12, folate, sTfR, ferritin, and vitamin A. Women with riboflavin deficiency (EGRac ≥1.40) were twice as likely to present with anemia (adjusted OR: 2.38; 95% CI: 1.08, 5.27) compared with women with EGRac <1.40.

Conclusions: Biochemical riboflavin deficiency was observed in Canadian and Malaysian women, with higher rates of deficiency among Malaysian women. Deficient biomarker status of riboflavin was a weak but significant predictor of hemoglobin and anemia, suggesting that the correction of riboflavin deficiency may potentially play a small protective role in anemia, but this requires further investigation.
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http://dx.doi.org/10.1093/jn/nxz151DOI Listing
November 2019

Addressing optimal folate and related B-vitamin status through the lifecycle: health impacts and challenges.

Proc Nutr Soc 2019 08 3;78(3):449-462. Epub 2019 Jun 3.

Nutrition Innovation Centre for Food and Health,School of Biomedical Sciences,Ulster University,Coleraine BT52 1SA,Northern Ireland.

The functional effects of folate within C1 metabolism involve interrelationships with vitamin B12, vitamin B6 and riboflavin, and related gene-nutrient interactions. These B vitamins have important roles throughout life, from pregnancy, through childhood, to middle and older age. Achieving optimal nutritional status for preventing folate-related disease is challenging, however, primarily as a result of the poor stability and incomplete bioavailability of folate from natural food sources when compared with the synthetic vitamin form, folic acid. Thus, in European countries, measures to prevent neural tube defects (NTD) have been largely ineffective because of the generally poor compliance of women with folic acid supplementation as recommended before and in early pregnancy. In contrast, countries worldwide with mandatory folic acid fortification policies have experienced marked reductions in NTD. Low vitamin B12 status is associated with increased risk of cognitive dysfunction, CVD and osteoporosis. Achieving optimal B12 status can be problematic for older people, however, primarily owing to food-bound B12 malabsorption which leads to sub-clinical deficiency even with high dietary B12 intakes. Optimising B-vitamin intake may be particularly important for sub-populations with impaired folate metabolism owing to genetic characteristics, most notably the 677C→T variant in the gene encoding the enzyme methylenetetrahydrofolate reductase (MTHFR). This common folate polymorphism is linked with several adverse health outcomes, including stroke, however, recent evidence has identified its novel interaction with riboflavin (the MTHFR cofactor) in relation to blood pressure and risk of developing hypertension. This review addresses why and how the optimal status of folate-related B vitamins should be achieved through the lifecycle.
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http://dx.doi.org/10.1017/S0029665119000661DOI Listing
August 2019

Serum levels of miR-199a-5p correlates with blood pressure in premature cardiovascular disease patients homozygous for the MTHFR 677C > T polymorphism.

Genomics 2020 01 25;112(1):669-676. Epub 2019 Apr 25.

Genomic Medicine Research Group, Biomedical Sciences Research Institute, Ulster University, Cromore Road, Coleraine BT52 1SA, Northern Ireland, UK. Electronic address:

This investigation profiled circulating serum concentrations of microRNAs (miRNAs) in premature cardiovascular disease (CVD) patients screened for the 677C > T polymorphism in methylenetetrahydrofolate reductase (MTHFR), a risk factor for hypertension. Serum samples from 75 premature CVD patients of known MTHFR genotype were analysed for CVD-related miRNA expression, to identify those that were associated with blood pressure. Samples were collected at baseline and following intervention with riboflavin as part of a randomized controlled trial. In patients with the MTHFR 677TT genotype, expression of miR-199a-5p in serum was inversely correlated with hypertension at baseline, and with change in blood pressure in TT genotype patients who responded to riboflavin intervention. These correlations were not observed in MTHFR 677CC genotype patients. In vitro experiments and in silico data analysis provided evidence that miR-199a-5p targets SMAD4. This is the first study to link miR-199a-5p expression with hypertension in a genetically at-risk cohort of premature CVD patients.
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http://dx.doi.org/10.1016/j.ygeno.2019.04.019DOI Listing
January 2020

Hyperglycemia and Metformin Use Are Associated With B Vitamin Deficiency and Cognitive Dysfunction in Older Adults.

J Clin Endocrinol Metab 2019 10;104(10):4837-4847

Nutrition Innovation Centre for Food and Health, Biomedical Sciences Research Institute, Ulster University, Coleraine, Northern Ireland, United Kingdom.

Context: Emerging evidence suggests that deficiencies of folate-related B vitamins can arise with metformin treatment and are independently linked with cognitive dysfunction, a comorbidity of diabetes.

Objective: To determine the impact of hyperglycemia and metformin use on relevant B vitamin biomarkers and cognitive outcomes in older adults.

Setting And Participants: Community-dwelling older adults (74.1 ± 8.3 years, n = 4160) without dementia, recruited to the Trinity, Ulster and Department of Agriculture cohort study in 2008 to 2012, were classified as normoglycemic (n = 1856) or hyperglycemic, based on HbA1c ≥5.7% (39 mmol/mol), either with (n = 318) or without (n = 1986) metformin treatment.

Main Outcome Measures: Biomarkers of folate, vitamin B12, vitamin B6, and riboflavin were measured. Cognitive assessments included the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) and the Frontal Assessment Battery (FAB).

Results: Metformin use was associated with higher risk of deficiency of vitamin B12 (combined B12 index ≤-1; OR 1.45; 95% CI, 1.03 to 2.02) and vitamin B6 (plasma pyridoxal 5-phosphate <30.0 nmol/L; OR 1.48; 95% CI, 1.02 to 2.15). Fortified foods when eaten regularly had a positive impact on all relevant B vitamin biomarkers, even with hyperglycemia. After adjustment for relevant covariates, metformin use was associated with an increased risk of cognitive dysfunction as assessed with the RBANS (OR 1.36; 95% CI, 1.03 to 1.80) and FAB (OR 1.34; 95% CI, 1.03 to 1.74).

Conclusions: Use of metformin by older adults is associated with poorer cognitive performance; B vitamin deficiency may be implicated. Fortified foods can optimize B vitamin status and may be beneficial for maintaining better cognitive health in older people with or at risk for diabetes.
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http://dx.doi.org/10.1210/jc.2018-01791DOI Listing
October 2019

A randomized controlled trial of folic acid intervention in pregnancy highlights a putative methylation-regulated control element at ZFP57.

Clin Epigenetics 2019 02 18;11(1):31. Epub 2019 Feb 18.

Genomic Medicine Research Group, School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UK.

Background: Maternal blood folate concentrations during pregnancy have been previously linked with DNA methylation patterns, but this has been done predominantly through observational studies. We showed recently in an epigenetic analysis of the first randomized controlled trial (RCT) of folic acid supplementation specifically in the second and third trimesters (the EpiFASSTT trial) that methylation at some imprinted genes was altered in cord blood samples in response to treatment. Here, we report on epigenome-wide screening using the Illumina EPIC array (~ 850,000 sites) in these same samples (n = 86).

Results: The top-ranked differentially methylated promoter region (DMR) showed a gain in methylation with folic acid (FA) and was located upstream of the imprint regulator ZFP57. Differences in methylation in cord blood between placebo and folic acid treatment groups at this DMR were verified using pyrosequencing. The DMR also gains methylation in maternal blood in response to FA supplementation. We also found evidence of differential methylation at this region in an independent RCT cohort, the AFAST trial. By altering methylation at this region in two model systems in vitro, we further demonstrated that it was associated with ZFP57 transcription levels.

Conclusions: These results strengthen the link between folic acid supplementation during later pregnancy and epigenetic changes and identify a novel mechanism for regulation of ZFP57. This trial was registered 15 May 2013 at www.isrctn.com as ISRCTN19917787.
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http://dx.doi.org/10.1186/s13148-019-0618-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380035PMC
February 2019

B-vitamins in Relation to Depression in Older Adults Over 60 Years of Age: The Trinity Ulster Department of Agriculture (TUDA) Cohort Study.

J Am Med Dir Assoc 2019 05 25;20(5):551-557.e1. Epub 2019 Jan 25.

Nutrition Innovation Centre for Food and Health (NICHE), School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland, United Kingdom. Electronic address:

Objectives: Mental health disorders are major contributors to disease burden in older people. Deficient status of folate and the metabolically related B vitamins may be implicated in these conditions. This study aimed to investigate folate, vitamin B, vitamin B, and riboflavin in relation to depression and anxiety in aging and also considered the role of fortified foods as a means of optimizing B-vitamin status and potentially reducing the risk of these mental health disorders.

Design: The Trinity Ulster Department of Agriculture (TUDA) aging study was a cross-sectional cohort study.

Setting And Participants: Community-dwelling adults (n = 5186; ≥60 years) recruited from 2 jurisdictions within the island of Ireland from 2008 to 2012.

Measures: Depression and anxiety were assessed using the Centre for Epidemiological Studies Depression (CES-D) and the Hospital Anxiety and Depression (HAD) scales, respectively. The following B-vitamin biomarkers were measured: red blood cell folate, serum total vitamin B, plasma pyridoxal-5-phosphate (PLP; vitamin B), and erythrocyte glutathione reductase activation coefficient (EGRac; riboflavin).

Results: Biomarker values in the lowest 20% of status for folate (odds ratio [OR] 1.79; 95% CI 1.23-2.61), vitamin B (OR 1.45, 95% CI 1.01-2.06), or riboflavin (OR 1.56, 95% CI 1.10-2.00), but not vitamin B, were each associated with an increased risk of depression (CES-D score ≥16). Correspondingly, B vitamin-fortified foods if consumed daily were associated with a reduced risk of depression (OR 0.54, 95% CI 0.41-0.70). A deficient status of vitamin B (OR 1.73, 95% CI 1.07-2.81), but not other vitamins, was associated with increased anxiety.

Conclusions/implications: Better B-vitamin status may have a role in impacting positively on mental health in older adults. Regular intake of fortified foods can provide a means of optimizing B-vitamin status and thus could contribute to reducing depression. If confirmed by a randomized trial, these results may have implications for nutrition and mental health policy, and thus quality of life, in older people.
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http://dx.doi.org/10.1016/j.jamda.2018.11.031DOI Listing
May 2019

Maternal folate nutrition and offspring health: evidence and current controversies.

Proc Nutr Soc 2019 May 26;78(2):208-220. Epub 2018 Dec 26.

Nutrition Innovation Centre for Food and Health, School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland BT52 1SA.

Periconceptional folic acid (FA) is known to have a protective effect in the prevention of neural tube defects (NTD), leading to global recommendations for FA supplementation before and in early pregnancy. Maternal folate throughout pregnancy may have other roles in offspring health, including neurodevelopment and cognitive performance in childhood. Folate is essential for C1 metabolism, a network of pathways involved in several biological processes including nucleotide synthesis, DNA repair and methylation reactions. The evidence reviewed here shows a conclusive role for offspring health of maternal folate nutrition in early pregnancy and probable benefits in later pregnancy. Folate-mediated epigenetic changes in genes related to brain development and function offer a plausible biological basis to link maternal folate with effects in offspring brain, albeit this research is in its infancy. Mandatory FA fortification of food has proven to be highly effective in decreasing NTD cases in populations where it has been implemented, but this policy is controversial owing to concerns related to potential adverse effects of over-exposure to FA. In the absence of population-wide fortification, and given the generally poor compliance with current FA recommendations, optimising folate status of mothers in very early pregnancy for protection against NTD remains challenging. Thus, current policy in the UK, Ireland and elsewhere in Europe for the prevention of NTD (based on periconceptional FA supplementation only), has proven to be largely ineffective. This review addresses the evidence and the controversies that surround this area, as well as identifying the challenges in translating policy into practice.
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http://dx.doi.org/10.1017/S0029665118002689DOI Listing
May 2019

Adequate vitamin B and riboflavin status from menus alone in residential care facilities in the Lower Mainland, British Columbia.

Appl Physiol Nutr Metab 2019 Apr 24;44(4):414-419. Epub 2018 Sep 24.

h Healthy Mothers, Babies and Children Theme, South Australia Health and Medical Research Institute, North Terrace, Adelaide SA 5000, Australia.

Older adults have potential increased risk of nutrient deficiencies because of age-related decreased dietary intake and malabsorption; it is important to ensure nutrient needs are met to avoid adverse health outcomes. B vitamins are of particular interest: vitamin B deficiency can cause irreversible neurodegeneration; there is mandatory folic acid fortification in Canada; and suboptimal riboflavin status has been reported among older adults in the United Kingdom. In this exploratory secondary analysis study we assessed vitamin B and riboflavin biochemical status (via microparticle enzyme immunoassay and erythrocyte glutathione reductase activity coefficient (EGRac), respectively), and the vitamin B, riboflavin, and folate content of menus served to a convenience sample of older adults (≥65 years) from 5 residential care facilities within the Lower Mainland of British Columbia, Canada. Diet was assessed from customized 28-day cycle meal plans. Participants (n = 207; 53 men and 154 women) were aged 86 ± 7 years, largely of European descent (92%), and nonsmokers (95%). The menus served had a low prevalence of inadequacy for vitamin B and riboflavin (only 4% and 1% of menus contained less than the estimated average requirement (EAR), respectively), but 93% contained less than the EAR for folate. Mean ± SD serum total vitamin B concentration was 422 ± 209 pmol/L, and EGRac was 1.30 ± 0.19. The majority of older adults in residential care were provided with adequate vitamin B and riboflavin menu amounts, and only 5% were vitamin B deficient (<148 pmol/L). However, 26% were riboflavin deficient (EGRac ≥ 1.4), which may warrant further investigation.
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http://dx.doi.org/10.1139/apnm-2018-0459DOI Listing
April 2019

Assessment of candidate folate sensitive-differentially methylated regions in a randomised controlled trial of continued folic acid supplementation during the second and third trimesters of pregnancy.

Ann Hum Genet 2019 01 3;83(1):23-33. Epub 2018 Sep 3.

School of Biotechnology, Dublin City University, Dublin, Ireland.

Scope: The aim of this study was to identify if specific regions of the human genome were sensitive to folate status by displaying changes in their DNA methylation patterns in response to continued folic acid supplementation during pregnancy.

Methods And Results: Samples (n = 119) from a previous randomised controlled trial in pregnancy were used to compare the DNA methylation profiles of the same woman pre- versus post-folic acid intervention. Candidate genes were identified from the literature and a pilot genome wide screen of six women (three from each of the folic acid and placebo arms of the trial). We did not observe consistent DNA methylation changes in response to folic acid intervention at any of our candidate genes (RASA4, DHFR, DHFR2, RASSF1A, EIF2C3, ATPF1). We did identify a 40% decrease in DNA methylation at the RASA4 promoter correlating with a 3.5-fold increase in its mRNA abundance in an in vitro cell culture model.

Conclusion: Continued folic acid intervention over a 22-week period did not appear to significantly influence the DNA methylation status of six candidate genes in blood samples of women compared to placebo. However, DNA methylation may play a role in the gene expression control of the RASA4 gene.
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http://dx.doi.org/10.1111/ahg.12281DOI Listing
January 2019

Breakfast Consumption in the UK: Patterns, Nutrient Intake and Diet Quality. A Study from the International Breakfast Research Initiative Group.

Nutrients 2018 Jul 30;10(8). Epub 2018 Jul 30.

Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Cromore Road, Coleraine BT52 1SA, Northern Ireland, UK.

Breakfast consumption is associated with higher overall dietary adequacy; however, there is a lack of quantitative guidelines for optimal nutrient intakes at breakfast in the UK. This study aimed to investigate nutrient and food group intakes at breakfast and examine their relationship to overall Diet Quality (DQ). Data from the most recent National Diet and Nutrition Survey (NDNS, 2008⁻2014) were accessed to provide a representative sample ( = 8174) of the UK population, aged 5⁻96 years, mean age of 33 years. Food intake was measured by a 4-day estimated food diary and DQ was assessed by the Nutrient Rich Food Index 9.3 method. Energy- and socio-economic-adjusted nutrient and food group intakes were compared across age groups and DQ tertiles by ANCOVA. Breakfast contributed 20⁻22% to total energy intake. Breakfast intakes of carbohydrate and non-milk extrinsic sugars (NMES) were higher, and intakes of protein, total fat and saturated fatty acid (SFA) were lower, than relative daily intakes. Breakfast was particularly rich in B vitamins, vitamin D, calcium, iron, iodine and magnesium. From the lowest to the highest DQ tertile decreasing intakes of NMES, SFA and total fat and increasing intakes of carbohydrate, protein, fibre and most micronutrients were found. These findings could help to inform the development of nutrient-based recommendations for a balanced breakfast for the first time in the UK.
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http://dx.doi.org/10.3390/nu10080999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115898PMC
July 2018
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