An investigation of factors affecting changes in health behaviours during the COVID-19 pandemic in a UK population-based cohort study.

OBJECTIVES: The COVID-19 pandemic has led to changes in behaviours, which may have different health effects in population subgroups. We investigated whether within-individual changes in health behaviours from before to during the pandemic differ by socio-economic deprivation, age or sex. STUDY DESIGN: Prospective cohort study. METHODS: Participants were recruited from the existing UK Fenland cohort study with measurements of health behaviours twice prepandemic (2005 to February 2020) and three times during the pandemic (July 2020 to April 2021). Health behaviours included daily servings of fruit and vegetables, units of alcohol consumed per week, smoking status, sleep duration and total and domain-specific physical activity energy expenditure. Sociodemographic information (English indices of multiple deprivation, education, occupation and ethnicity) and COVID-19 antibody status were also collected. Participants were grouped into three categories based on their English indices of multiple deprivation score: most, middle and least deprived. RESULTS: Participants were included if they had completed at least one measurement during the pandemic and one prepandemic (n = 3212). Fruit and vegetable consumption, total physical activity energy expenditure and smoking prevalence decreased during the pandemic compared with prepandemic, whereas average sleep duration increased and alcohol consumption did not change. Decreases in fruit and vegetable intake and physical activity energy expenditure were most pronounced in the most deprived group compared with the least deprived group and were greater in women than men. CONCLUSIONS: Socio-economic inequalities in health behaviours have worsened during the pandemic. As the country emerges from the COVID-19 pandemic, strategies to reduce health inequalities need to be put at the forefront of recovery plans.

Lipid ratios representing SCD1, FADS1, and FADS2 activities as candidate biomarkers of early growth and adiposity.

BACKGROUND: Altered lipid metabolism in early life has been associated with subsequent weight gain and predicting this could aid in obesity prevention and risk management. Here, a lipidomic approach was used to identify circulating markers for future obesity risk in translational murine models and validate in a human infant cohort. METHODS: Lipidomics was performed on the plasma of APOE*3 Leiden, Ldlr-/-.Leiden, and the wild-type C57BL/6J mice to capture candidate biomarkers predicting subsequent obesity parameters after exposure to high-fat diet. The identified candidate biomarkers were mapped onto corresponding lipid metabolism pathways and were investigated in the Cambridge Baby Growth Study. Infants' growth and adiposity were measured at 0-24 months. Capillary dried blood spots were sampled at 3 months for lipid profiling analysis. FINDINGS: From the mouse models, cholesteryl esters were correlated with subsequent weight gain and other obesity parameters after HFD period (Spearman's r≥0.5, FDR p values <0.05) among APOE*3 Leiden and Ldlr-/-.Leiden mice, but not among the wild-type C57BL/6J. Pathway analysis showed that those identified cholesteryl esters were educts or products of desaturases activities: stearoyl-CoA desaturase-1 (SCD1) and fatty acid desaturase (FADS) 1 and 2. In the human cohort, lipid ratios affected by SCD1 at 3 months was inversely associated with 3-12 months weight gain (B±SE=-0.31±0.14, p=0.027), but positively with 12-24 months weight and adiposity gains (0.17±0.07, p=0.02 and 0.17±0.07, 0.53±0.26, p=0.04, respectively). Lipid ratios affected by SCD1 and FADS2 were inversely associated with adiposity gain but positively with height gain between 3-12 months. INTERPRETATION: From murine models to human setting, the ratios of circulating lipid species indicating key desaturase activities in lipid metabolism were associated with subsequent body size increase, providing a potential tool to predict early life weight gain.

Mobilising vitamin D from adipose tissue: The potential impact of exercise.

Vitamin D is lipophilic and accumulates substantially in adipose tissue. Even without supplementation, the amount of vitamin D in the adipose of a typical adult is equivalent to several months of the daily reference nutrient intake (RNI). Paradoxically, despite the large amounts of vitamin D located in adipose tissue, individuals with obesity are often vitamin D deficient according to consensus measures of vitamin D status (serum 25-hydroxyvitamin D concentrations). Thus, it appears that vitamin D can become 'trapped' in adipose tissue, potentially due to insufficient lipolytic stimulation and/or due to tissue dysfunction/adaptation resulting from adipose expansion. Emerging evidence suggests that exercise may mobilise vitamin D from adipose (even in the absence of weight loss). If exercise helps to mobilise vitamin D from adipose tissue, then this could have important ramifications for practitioners and policymakers regarding the management of low circulating levels of vitamin D, as well as chronically low levels of physical activity, obesity and associated health conditions. This perspective led us to design a study to examine the impact of exercise on vitamin D status, vitamin D turnover and adipose tissue vitamin D content (the VitaDEx project). The VitaDEx project will determine whether increasing physical activity (via exercise) represents a potentially useful strategy to mobilise vitamin D from adipose tissue.

The validation of biomarkers of metabolic efficacy in infant nutrition.

Breastfeeding is regarded as the ideal way to nourish infants. However, feeding with formula milk is also common in much of the West. Despite this, the function of the molecular components of breast and formula milks are not fully understood, less still the relationship between the composition of the milk and the infant's metabolism and how this influences the infant's development. The Biotechnology and Biological Sciences Research Council-funded project 'The validation of biomarkers of metabolic efficacy in infant nutrition' aims to identify lipid biomarkers that can be used to study the effect of diet on growth and development of infants. In this work, we have been able to validate these markers. Here, we present an approach to biomarker discovery that has new depth and will inform research questions about how metabolism is governed, and which species can be used to identify situations where metabolism is becoming defective.

Design and cohort description of the InterAct Project: an examination of the interaction of genetic and lifestyle factors on the incidence of type 2 diabetes in the EPIC Study.

AIMS/HYPOTHESIS: Studying gene-lifestyle interaction may help to identify lifestyle factors that modify genetic susceptibility and uncover genetic loci exerting important subgroup effects. Adequately powered studies with prospective, unbiased, standardised assessment of key behavioural factors for gene-lifestyle studies are lacking. This case-cohort study aims to investigate how genetic and potentially modifiable lifestyle and behavioural factors, particularly diet and physical activity, interact in their influence on the risk of developing type 2 diabetes. METHODS: Incident cases of type 2 diabetes occurring in European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts between 1991 and 2007 from eight of the ten EPIC countries were ascertained and verified. Prentice-weighted Cox regression and random-effects meta-analyses were used to investigate differences in diabetes incidence by age and sex. RESULTS: A total of 12,403 verified incident cases of type 2 diabetes occurred during 3.99 million person-years of follow-up of 340,234 EPIC participants eligible for InterAct. We defined a centre-stratified subcohort of 16,154 individuals for comparative analyses. Individuals with incident diabetes who were randomly selected into the subcohort (n = 778) were included as cases in the analyses. All prevalent diabetes cases were excluded from the study. InterAct cases were followed-up for an average of 6.9 years; 49.7% were men. Mean baseline age and age at diagnosis were 55.6 and 62.5 years, mean BMI and waist circumference values were 29.4 kg/m(2) and 102.7 cm in men, and 30.1 kg/m(2) and 92.8 cm in women, respectively. Risk of type 2 diabetes increased linearly with age, with an overall HR of 1.56 (95% CI 1.48-1.64) for a 10 year age difference, adjusted for sex. A male excess in the risk of incident diabetes was consistently observed across all countries, with a pooled HR of 1.51 (95% CI 1.39-1.64), adjusted for age. CONCLUSIONS/INTERPRETATION: InterAct is a large, well-powered, prospective study that will inform our understanding of the interplay between genes and lifestyle factors on the risk of type 2 diabetes development.

Perspectives for Metabolomics in Human Nutrition: An Overview.

Metabolomics describes the measurement of the full complement of the products of metabolism in a single biological sample and correlating these metabolomic profiles with known physiological or pathological states. The metabolome offers the possibility of finding unique fingerprints responsible for different phenotypes. Analytical techniques such as nuclear magnetic resonance or mass spectrometry measure thousands of compounds within the metabolome simultaneously and appropriate data mining and database tools allow the finding of significant correlations between the measured metabolomes. The first direct outcome of nutritional metabolomics will be the discovery of biomarkers, which can reveal changes in health and disease but also indicate short term and long-term dietary intake. The concerted actions of nutrigenomics and metabolomics will play a crucial role in understanding how specific interactions of single nucleotide polymorphisms (SNP) influence a person's response to a diet. Finally, systems biology approaches to human nutrition combine transcriptomics, proteomics and metabolomics with the aim of understanding how diets interact within the human being.

A fast and simple GC MS method for lignan profiling in Anthriscus sylvestris and biosynthetically related Plant species.

A new GC-MS method for monitoring lignans was developed to study the variation in plants and elucidate the biosynthetic steps. A simple and fast extraction procedure for lyophilised plant material was developed, giving a lignan-rich extract. A GC-MS method was set up using an apolar WCOT fused silica column using a high temperature programme (150 degrees C to 320 degrees C at 15 degrees C min(-1)). This new GC-MS method gave a clear lignan profile of plant material. It was possible to show the large variation in the concentrations of deoxypodophyllotoxin (DOP), yatein and anhydropodorhizol (AHP) in Anthriscus sylvestris (L.) Hoffm. plants growing on different locations using cinchonidin as an internal standard. In contrast with existing GC methods for lignan analysis no derivatisation is needed. It is also possible to use this method for the detection of different classes of lignans in biosynthetically related plant species.

Cytotoxicity of natural ginseng glycosides and semisynthetic analogues.

The cytotoxicity of natural glycosides from Ginseng, semisynthetic analogues and related triterpenes of the dammarane series, isolated from the leaves of the Far-East species of the genus Betula was studied in order to elucidate structure-activity relationships. Some of the compounds studied were active against the human lung carcinoma GLC4 and adenocarcinoma COLO 320 cell lines. The natural glycosides displayed the lowest cytotoxicity. The triterpenes of the dammarane series used as starting aglycones for semisynthetic derivatives were moderately cytotoxic. The dammarane triterpenes possessing keto groups and their semisynthetic glucosides were the most active compounds tested. Cytotoxic effects of the dammarane glucosides were inversely proportional both to the number of sugars attached to the aglycones and to the number of hydroxy groups of the aglycones. The type of side chain and the configuration of the hydroxy group at C-3 in aglycones did not have a significant influence on the cytotoxicity.

Cytotoxicity and mode of action of aeroplysinin-1 and a related dienonefrom the sponge Aplysina aerophoba.

Aeroplysinin-1 (1) and the structurally related dienone 2 were cytotoxic to Ehrlich ascites tumor (EAT) cells and HeLa tumor cells in the microculture tetrazolium (MTT) and clonogenic assays. Both compounds are bromotyrosine derivatives, isolated from the marine spong Aplysina aerophoba. As the effective concentrations in the MTT assay were lower than in the clonogenic assay, 1 and 2 are able to cause growth inhibition as well as actual cell death in these cell lines. With an IC50 value of 8.2 microM (MTT assay, 2-h incubation, EAT cells), 1 was the more toxic compound. When the cells were depleted of glutathione by pretreatment with buthionine sulfoximine, they were significantly more sensitive toward 1 and 2 in the MTT assay. A dose-enhancement factor as high as 11.8 was found in EAT cells after 2-h incubation with 2. Using electron paramagnetic resonance we were able to measure free radical formation of 1 and 2, yielding the semiquinone structures 3 and 4, respectively, in a culture medium with tumor cells. It is concluded that free radicals are, at least in part, responsible for the cytotoxicity of 1 and 2. This conclusion is in line with expectations derived from the chemical structures of both compounds.