Nutritional Studies Research Articles

Chrono-Nutrition, Chrono-Type, and the Prevalence of Type 2 Diabetes Mellitus in a Cross-Sectional Study from the EuroPean Prospective Investigation into Cancer and Nutrition (EPIC) Study.

Background: Previous studies have shown that meal timing, poor sleep quality, and chronotype may play a relevant role in the development of type 2 diabetes mellitus (T2DM). However, its relationship with macronutrients by eating occasions has not been explored deeply. Objective: Our aim was to estimate the association between chrono-nutrition, sleep quality, chronotype, and the prevalence of T2DM. Methods: This cross-sectional study included a subset of 3465 middle-aged Caucasian adults (2068 women) from the European Prospective Investigation into Cancer and Nutrition (EPIC) Spain cohort study. In the 2017-18 follow-up, we assessed chronotype, sleep quality, diet, and sociodemographic data using validated questionnaires. Further, we used blood samples to determine serum levels of glucose. We defined a case of T2DM when serum glucose concentration was ≥126 mg/dL or when participants self-reported diabetes. Results: A higher prevalence of T2DM was associated with poor sleep quality (ORpoorvsgood = 2.90, 95% CI = 1.30, 6.28). Carbohydrate intake at breakfast was inversely associated with the prevalence of T2DM (OR = 0.75, 95% CI = 0.66, 0.85). Finally, lipid intake at breakfast was associated with a 13% higher prevalence of T2DM (OR = 1.13, 95% CI = 1.01, 1.26) for each 1 standard deviation (1-SD) increase. Conclusions: This study concludes that a higher content of carbohydrates at breakfast is correlated with a reduced prevalence of T2DM, while higher lipids intake at breakfast is associated with a higher prevalence of T2DM. Furthermore, poor sleep quality is a potential factor associated with an elevated prevalence of T2DM. Our results emphasize the need for prospective studies to validate and strengthen these observed associations.

Associations of the EAT-Lancet reference diet with metabolic dysfunction-associated steatotic liver disease and its severity: A multicohort study.

The EAT-Lancet Commission devised a globally sustainable dietary pattern to jointly promote human health and sustainability. However, the extent to which this diet supports metabolic dysfunction-associated steatotic liver disease (MASLD) has not yet been assessed. This study aimed to investigate the association between the EAT-Lancet diet and the risk of MASLD and its severity. This prospective multicohort study included 15,263 adults from the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort, 1137 adults from the Guangzhou Nutrition and Health Study (GNHS) cohort, and 175,078 adults from the UK Biobank. In addition, 228 Chinese adults from the Prospective Epidemic Research Specifically of Non-alcoholic Steatohepatitis (PERSONS) with biopsy-proven MASLD were included. An EAT-Lancet diet index was created to reflect adherence to the EAT-Lancet reference diet. The TCLSIH cohort recorded 3010 MASLD cases during 53,575 person-years of follow-up, the GNHS cohort documented 624 MASLD cases during 6454 person-years of follow-up, and the UK Biobank developed 1350 MASLD cases during 1,745,432 person-years of follow-up. In multivariable models, participants in the highest tertiles of the EAT-Lancet diet index had a lower risk of MASLD compared with those in the lowest tertiles (TCLSIH: HR = 0.87, 95% CI: 0.78, 0.96; GNHS: HR = 0.79, 95% CI: 0.64, 0.98; UK Biobank: HR = 0.73, 95% CI: 0.63, 0.85). Moreover, liver-controlled attenuation parameter decreased with increasing the diet index in individuals with biopsy-proven MASLD (β = -5.895; 95% CI: -10.014, -1.775). Adherence to the EAT-Lancet reference diet was inversely associated with the risk of MASLD as well as its severity.

Nutrition users’ guides: systematic reviews part 1 – structured guide for methodological assessment, interpretation and application of systematic reviews and meta-analyses of non-randomised nutritional epidemiology studies

Due to the challenges of conducting randomised controlled trials (randomised trials) of dietary interventions, evidence in nutrition often comes from non-randomised (observational) studies of nutritional exposures—called nutritional epidemiology studies. When...

Is there an "optimal" diet for prevention of inflammatory bowel disease?

Nutritional epidemiological studies have evolved from a focus of single nutrients to diet patterns to capture the protective role of healthy diets on chronic disease development. Similarly, in inflammatory bowel disease (IBD), a healthy diet may be protective against its development in individuals with genetic susceptibility, but the definitions of the optimal diet pattern deserve further exploration. Hence, this review article presents evidence, mainly from prospective cohort studies, for the role of diet quality based on adherence to dietary guidelines, traditional and modern diet patterns in the prevention of IBD. Findings from a limited number of studies on diet quality suggest that high diet quality scores are associated with lower risk of developing Crohn's disease, but the data are inconsistent for ulcerative colitis (UC). There are signals that a Mediterranean diet pattern reduces the risk of Crohn's disease but, again, the data are inconsistent and further studies are much needed. Finally, the evidence is conflicting regarding the role of food additives, with difficulties in the assessment of their intake, namely non-nutritive sweeteners and emulsifiers, precluding accurate assessment of a relationship with IBD risk. In contrast, emerging evidence for a role of ultra-processed food in the development of Crohn's disease but not UC is identified. Given the potential influence of diet quality, a Mediterranean diet and ultra-processed food intake on the risk of Crohn's disease, assessment and implementation of dietary advice for these patients need to be tailored. The search for an optimal diet for UC remains elusive and further research for increasing the evidence in the area is greatly needed.

Diet, Microbiome, and Inflammation Predictors of Fecal and Plasma Short-Chain Fatty Acids in Humans

BackgroundGut microbes produce short-chain fatty acids (SCFAs), which are associated with broad health benefits. However, it is not fully known how diet and/or the gut microbiome could be modulated to improve SCFA production. ObjectivesThe objective of this study was to identify dietary, inflammatory, and/or microbiome predictors of SCFAs in a cohort of healthy adults. MethodsSCFAs were measured in fecal and plasma samples from 359 healthy adults in the United States Department of Agriculture Nutritional Phenotyping Study. Habitual and recent diet was assessed using a food frequency questionnaire and automated self-administered 24-h dietary assessment tool dietary recalls. Markers of systemic and gut inflammation were measured in fecal and plasma samples. The gut microbiome was assessed using shotgun metagenomics. Using statistics and machine learning, we determined how the abundance and composition of SCFAs varied with measures of diet, inflammation, and the gut microbiome. ResultsWe show that fecal pH may be a good proxy for fecal SCFA abundance. A higher healthy eating index for a habitual diet was associated with a compositional increase in fecal butyrate relative to acetate and propionate. SCFAs were associated with markers of subclinical gastrointestinal (GI) inflammation. Fecal SCFA abundance was inversely related to plasma lipopolysaccharide-binding protein. When we analyzed hierarchically organized diet and microbiome data with taxonomy-aware algorithms, we observed that diet and microbiome features were far more predictive of fecal SCFA abundances compared to plasma SCFA abundances. The top diet and microbiome predictors of fecal butyrate included potatoes and the thiamine biosynthesis pathway, respectively. ConclusionsThese results suggest that resistant starch in the form of potatoes and microbially produced thiamine provide a substrate and essential cofactor, respectively, for butyrate synthesis. Thiamine may be a rate-limiting nutrient for butyrate production in adults. Overall, these findings illustrate the complex biology underpinning SCFA production in the gut.This trial was registered at clinicaltrials.gov as NCT02367287.

Fine-Scale Dietary Polyphenol Intake Is Associated with Systemic and Gastrointestinal Inflammation in Healthy Adults

BackgroundPolyphenols are dietary bioactive compounds, many of which have anti-inflammatory properties. However, information on the intake of dietary polyphenols at the class and compound levels and their associations with gastrointestinal (GI) and systemic inflammation is lacking. ObjectivesEstimate dietary polyphenol intake in healthy adults and examine its relationship with GI and systemic inflammation markers. MethodsHealthy adults (n = 350) completed the United States Department of Agriculture Nutritional Phenotyping Study, an observational, cross-sectional study balanced for age, sex, and body mass index. Dietary intake, assessed via multiple 24-h recalls, was ingredientized and mapped to FooDB, a comprehensive food composition database. Dietary polyphenol intake (total, class, compound) was estimated and examined for its relationship to GI and systemic inflammation markers using linear models and random forest regressions. ResultsMean total polyphenol intake was ∼914 mg/1000 kcal/d with flavonoids as the greatest class contributor (495 mg/1000 kcal/d). Tea, coffee, and fruits were among the largest food contributors to polyphenol intake. Total polyphenol intake was negatively associated with the GI inflammation marker, fecal calprotectin (β = −0.004, P = 0.04). At the class level, polyphenols categorized as prenol lipids (β = −0.94, P < 0.01) and phenylpropanoic acids (β = −0.92, P < 0.01) were negatively associated with plasma lipopolysaccharide-binding protein, a proxy for GI permeability. Food sources of these two classes included mainly olive products. We further detected a positive association between C-reactive protein and polyphenols in the “cinnamic acids and derivatives” class using hierarchical feature engineering and random forest modeling. ConclusionsEven in healthy adults, dietary polyphenol intake was negatively associated with GI inflammation and intake of prenol lipids and phenylpropanoic acids was negatively associated with GI permeability. Relationships between polyphenol intake and inflammatory outcomes varied with the resolution—total, class, compound—of polyphenol intake, suggesting a nuanced impact of polyphenols on GI and systemic inflammation.This trial was registered at clinicaltrials.gov as NCT02367287.

Assessing the Susceptibility and Tolerance of Oil Palm Cultivars to Leaf-Bending: A Comparative Physiological and Nutritional Balance Study

Selecting the best oil palm cultivars adapted to specific agro-climatic conditions helps ensure fruit and oil production success. Many biotic and abiotic problems can limit the productivity of the crop, some of which have not yet been described, as well as their symptoms and degree of impact. In oil palm, a disturbance known as leaf-bending occurs, in which the palms present a bending or breakage of the petiole in the leaves, representing a significant challenge for oil palm cultivation. Although leaf-bending in oil palm plantations is known, its effect on the palm’s performance and its possible causes are unknown. Thus, the objectives of the present work were to describe and propose a quantitative way to evaluate leaf-bending in different cultivars (Elaeis guineensis Jacq. and the interspecific O×G hybrid) and to evaluate the disturbance effect on the physiology and nutritional balance of the oil palm. The results showed that most leaves from leaf rings three and four of the palm phyllotaxis have the highest affectation, with 74% leaf-bending. The cultivars with a Deli × La Mé and Coarí × La Mé genetic background were the most tolerant; however, the Deli × AVROS and Deli × Yangambi genetic crosses were the most susceptible. The difference in the affectation between the groups was 60% to 70%. Leaf-bending affected physiological parameters such as photosynthesis, transpiration, and stomatal conductance. Thus, below the second ring of leaves, the affected plants’ physiological parameters decreased between 40% and 50%. The nutritional diagnosis showed that the most sensitive cultivars to leaf-bending were Deli × AVROS, which presented the highest average index of nutritional balance (IBNm), indicating that this genetic cross had the highest nutritional imbalance. On the contrary, the most tolerant cultivars were Deli × La Mé, which presented the lowest IBNm, associated with a better nutritional condition.

Effects of Oral Nutritional Supplement with β-Hydroxy-β-methylbutyrate (HMB) on Biochemical and Hematological Indices in Community-Dwelling Older Adults at Risk of Malnutrition: Findings from the SHIELD Study.

Malnutrition may result in abnormal biochemical and hematological indices. This planned prespecified analysis investigated the effects of a specialized oral nutritional supplement (ONS) on biochemical and hematological indices in community-dwelling older adults at risk of malnutrition. In the Strengthening Health in ELDerly through nutrition (SHIELD) study, 811 older adults aged 65 years and above took part in this randomized, double-blind, placebo-controlled, multi-center study. Participants were randomly allocated to either a complete and balanced specialized ONS (each serving provides 262 kcal, 10.5 g protein, 7.75 µg vitamin D3, and 0.74 g calcium β-hydroxy-β-methylbutyrate) and dietary counselling (intervention group) or a placebo and dietary counselling (placebo group). Both groups consumed study products twice a day for 180 days. Data were collected at baseline, day 90, and day 180. Blood analysis results at follow-up visits were analyzed using repeated measures analysis of covariance with adjustments for confounders. Overall, when compared with the placebo group, the intervention group showed significantly greater urea (6.0 mmol/L vs. 5.4 mmol/L, p < 0.001), urea to creatinine ratio (4.39 vs. 4.26, p < 0.001), prealbumin (24.9 mg/dL vs. 24.0 mg/dL, p < 0.001), vitamin B12 (480.0 pmol/L vs. 420.1 pmol/L, p < 0.001), and globulin levels (26.8 g/L vs. 26.5 g/L, p = 0.032). The intervention group also had a significantly higher absolute reticulocyte count (62.0 × 103/µL vs. 58.2 × 103/µL, overall p < 0.001) and mean platelet volume (10.0 fL vs. 9.9 fL, overall p = 0.003). Furthermore, significant improvements were seen in total protein at day 90 (71.7 g/L vs. 71.1 g/L, p = 0.017) and in absolute monocyte count at day 90 (0.50 × 103/µL vs. 0.47 × 103/µL, p = 0.009) in the intervention group. In conclusion, daily consumption of a specialized ONS for six months led to significant improvements in biochemical and hematological indices in community-dwelling older adults at risk of malnutrition.

Unveiling the epigenetic impact of vegan vs. omnivorous diets on aging: insights from the Twins Nutrition Study (TwiNS)

BackgroundGeroscience focuses on interventions to mitigate molecular changes associated with aging. Lifestyle modifications, medications, and social factors influence the aging process, yet the complex molecular mechanisms require an in-depth exploration of the epigenetic landscape. The specific epigenetic clock and predictor effects of a vegan diet, compared to an omnivorous diet, remain underexplored despite potential impacts on aging-related outcomes.MethodsThis study examined the impact of an entirely plant-based or healthy omnivorous diet over 8 weeks on blood DNA methylation in paired twins. Various measures of epigenetic age acceleration (PC GrimAge, PC PhenoAge, DunedinPACE) were assessed, along with system-specific effects (Inflammation, Heart, Hormone, Liver, and Metabolic). Methylation surrogates of clinical, metabolite, and protein markers were analyzed to observe diet-specific shifts.ResultsDistinct responses were observed, with the vegan cohort exhibiting significant decreases in overall epigenetic age acceleration, aligning with anti-aging effects of plant-based diets. Diet-specific shifts were noted in the analysis of methylation surrogates, demonstrating the influence of diet on complex trait prediction through DNA methylation markers. An epigenome-wide analysis revealed differentially methylated loci specific to each diet, providing insights into the affected pathways.ConclusionsThis study suggests that a short-term vegan diet is associated with epigenetic age benefits and reduced calorie intake. The use of epigenetic biomarker proxies (EBPs) highlights their potential for assessing dietary impacts and facilitating personalized nutrition strategies for healthy aging. Future research should explore the long-term effects of vegan diets on epigenetic health and overall well-being, considering the importance of proper nutrient supplementation.Trial registrationClinicaltrials.gov identifier: NCT05297825

The transcription factors HNF-4α and NF-κB activate the CDO gene to promote taurine biosynthesis in the golden pompano Trachinotus ovatus (Linnaeus 1758)

Cysteine dioxygenase (CDO) is a rate-limiting enzyme in taurine biosynthesis. Taurine synthesis is limited in marine fish, and most taurine is provided by their diet. Although a nutritional study indicated that the transcription of ToCDO was significantly altered by treatment with 10.5 g/kg taurine in food, the regulatory mechanism of this biosynthesis has not been fully elucidated. In the present study, we identified the sequence features of Trachinotus ovatus cysteine dioxygenase (ToCDO), which consists of 201 amino acids. It is characterized by being a member of the cupin superfamily with two conserved cupin motifs located at amino acids 82–102 and 131–145 and with a glutamate residue substituted by a cysteine in its first motif. Moreover, phylogenetic analysis revealed that the similarity of the amino acid sequences between ToCDO and other species ranged from 84.58 % to 91.54 %. Furthermore, a high-performance liquid-phase assay of the activity of recombinantly purified ToCDO protein showed that ToCDO could catalyse the oxidation of cysteine to produce cysteine sulphite. Furthermore, the core promoter region of CDO was identified as −1182–+1 bp. Mutational analysis revealed that the HNF4α and NF-κB sites significantly and actively affected the transcription of CDO. To further investigate the binding of these two loci to the CDO promoter, an electrophoretic shift assay (EMSA) was performed to verify that HNF4α-1 and NF-κB-1 interact with the binding sites of the promoter and promote CDO gene expression, respectively. Additionally, cotransfection experiments showed that HNF4α or both HNF4α and NF-κB can significantly influence CDO promoter activity, and HNF4α was the dominant factor. Thus, HNF4α and NF-κB play important roles in CDO expression and may influence taurine biosynthesis within T. ovatus by regulating CDO expression.

A multi-glycomic platform for the analysis of food carbohydrates.

Carbohydrates comprise the largest fraction of most diets and exert a profound impact on health. Components such as simple sugars and starch supply energy, while indigestible components, deemed dietary fiber, reach the colon to provide food for the tens of trillions of microbes that make up the gut microbiota. The interactions between dietary carbohydrates, our gastrointestinal tracts, the gut microbiome and host health are dictated by their structures. However, current methods for analysis of food glycans lack the sensitivity, specificity and throughput needed to quantify and elucidate these myriad structures. This protocol describes a multi-glycomic approach to food carbohydrate analysis in which the analyte might be any food item or biological material such as fecal and cecal samples. The carbohydrates are extracted by ethanol precipitation, and the resulting samples are subjected to rapid-throughput liquid chromatography (LC)-tandem mass spectrometry (LC-MS/MS) methods. Quantitative analyses of monosaccharides, glycosidic linkages, polysaccharides and alcohol-soluble carbohydrates are performed in 96-well plates at the milligram scale to reduce the biomass of sample required and enhance throughput. Detailed stepwise processes for sample preparation, LC-MS/MS and data analysis are provided. We illustrate the application of the protocol to a diverse set of foods as well as different apple cultivars and various fermented foods. Furthermore, we show the utility of these methods in elucidating glycan-microbe interactions in germ-free and colonized mice. These methods provide a framework for elucidating relationships between dietary fiber, the gut microbiome and human physiology. These structures will further guide nutritional and clinical feeding studies that enhance our understanding of the role of diet in nutrition and health.

Brief instruments for measuring nutrition literacy - the Nutrition Health Literacy Scale and the Self-Perceived Food Literacy Scale Short Form

BackgroundA healthy diet is a critical factor in maintaining long-term health. In addition to a health-promoting food environment, the nutrition health literacy (NHL) and food literacy (FL) of the population are important in this context. This paper describes the development and validation of two short instruments to measure the nutrition literacy of the population, used in the Austrian Nutrition Literacy Survey 2021.MethodsAn instrument to measure NHL (Nutrition Health Literacy Scale; NHLS) has been adapted and further developed. To measure FL, the Self-perceived Food Literacy Scale by Poelman et al. has been modified and shortened (SPFL-SF). Validation of the instruments was based on data from a web survey conducted in Austria in 2021 with almost 3,000 participants aged 18 years and older. Exploratory and confirmatory factor analyses were performed to assess the factorial validity/dimensionality of the instruments. Additionally, internal consistency was assessed using Cronbach’s alpha, ordinal alpha, and McDonald’s omega.ResultsBoth instruments demonstrate excellent data-model fit. The NHLS also shows excellent internal consistency (α = 0.91), while the SPFL-SF displays a sufficient internal consistency for all (α between 0.70 and 0.89) but one sub-dimension (resisting temptation α = 0.61). Furthermore, the distribution of the items indicates that the measures are understandable and suitable, as evidenced by the absence of missing values in the sample. In addition, the items of both instruments differ in their level of difficulty or agreement.ConclusionsThe NHLS and SPFL-SF are reliable and valid instruments for measuring NHL and FL in the general adult population. The brief instruments measuring the different aspects of nutrition literacy can be easily used in nutritional or evaluation studies. Further work is required to investigate other aspects of validity.

Turning Wastes into Resources: Red Grape Pomace-Enriched Biscuits with Potential Health-Promoting Properties.

The life-long adherence to a dietary pattern able to provide a high amount of polyphenols demonstrating beneficial cardiometabolic effects is demanding for the general population. In this study, red grape pomace (GP) was used as an ingredient to increase the daily polyphenols' intake. The incorporation of crude crushed GP at 20 and 30% (w/w) in a control (CTR) biscuit formula improved the nutritional profile by increasing the fiber and reducing lipid and energy content while providing up to 540 mgGAE of polyphenols per 100 g. Besides anthocyanins, GP contains flavonoids and grape-seed procyanidins, contributing to the remarkable antioxidant capacity of 20- and 30-GP biscuits. Upon in vitro gastro-duodenal enzymatic digestion, the concentration of reducing sugars for 20-GP and 30-GP compared to the CTR biscuits dropped significantly, meaning that the combined action of GP fibers and polyphenols could delay the intestinal absorption of glucose. Overall, 60 volatiles were detected in biscuits. All in all, the content of Maillard reaction products was lower in GP than in CTR biscuits, possibly due to the free radical scavenging ability of polyphenols. Despite the high rates of GP utilized, the sensorial attributes and the overall liking of the GP biscuits-especially the 20-GP ones-were not substantially affected. These findings will support nutritional studies to assess the potential role as functional foods of GP biscuits, and, afterwards, the large-scale production of a food mainly based on a waste ingredient turned into a resource.

The International Breakfast Research Initiative—Evaluation and Comparison of Breakfast Nutrient Intakes in Indonesia, Malaysia and the Philippines with a View to Proposing a Harmonised Nutrient-Based Breakfast Recommendation

The International Breakfast Research Initiative is a global study of breakfast nutrition, involving 17 countries in four continents, aiming to derive nutrient-based regional recommendations for breakfast. This study aimed to propose a harmonised recommendation for three South-East Asian countries: Indonesia, Malaysia, and the Philippines. For each country, data from nationally representative dietary surveys on the contribution of breakfast to daily nutrient intakes at both the adult population level and at the level of the upper tertile of daily nutrient density using the Nutrient Rich Food (NRF) Index were collated and examined. Energy intakes at breakfast ranged from 26 to 27% of daily energy intake. In all three countries, breakfast was carbohydrate-rich, providing 52 to 72% of breakfast energy intake, while it was higher in total and saturated fat in Malaysia and Indonesia. Intakes of fibre and vitamin C were low in all countries, while Malaysia tended to have higher intakes of most minerals, including sodium. Daily and breakfast nutrient intakes (at the population level and in the upper tertile of the NRF Index) were compared to the Codex Alimentarius nutrient reference values (NRVs) to assess adequacy. A decision tree was established based on these data to guide the development of recommendations for nutrient intakes at breakfast across the three countries.

Review on the ethnomedicinal and nutritional value of some wild edible plants used by the tribal of Koraput District of Odisha, India

Due to its abundance of plant genetic resources, Odisha is often called a genetic refuge. However, the south Odisha tribal regions, despite their abundance of natural resources, have received scant ethnobotanical research. Human cultural diversity in Koraput is well-known, and the area is also a biodiversity hotspot for several food crops and forest species. The purpose of this study is to consolidate all available information on the ethnomedical uses of wild plants by indigenous peoples in the Koraput district. The reviewed nutritional analysis studies show that numerous species have high nutrient content, some of which are superior to some domesticated varieties. Wild edible plants are used as indigenous food and remarkably improve the nutritional security of several tribal people of Koraput. However, systematic study on the nutritional potential of these wild edible plants is meager. The present study evaluated the Carbohydrate, Fat, Protein, and Fiber content in selected wild edible plants of Koraput. Research shows that several species of tubers are in danger of extinction and hence included on the IUCN Red List of Threatened and Endangered Species. For this reason, the optimal use of this biodiversity is to meet the inhabitant's present and future food. The medicinal needs depend on extensive phytochemical inquiry, safe conservation, and sustainable use of wild tuber, all require strong community participation, which also fulfills the Sustainable Development Goals (SDG) 2 and 3, i.e., zero hunger and good health and well-being.

Correlation between serum trimethylamine-N-oxide and body fat distribution in middle-aged and older adults: a prospective cohort study

BackgroundTrimethylamine-N-oxide (TMAO) is linked with obesity, while limited evidence on its relationship with body fat distribution. Herein, we investigated the associations between serum TMAO and longitudinal change of fat distribution in this prospective cohort study.MethodsData of 1964 participants (40–75y old) from Guangzhou Nutrition and Health Study (GNHS) during 2008–2014 was analyzed. Serum TMAO concentration was quantified by HPLC–MS/MS at baseline. The body composition was assessed by dual-energy X-ray absorptiometry at each 3-y follow-up. Fat distribution parameters were fat-to-lean mass ratio (FLR) and trunk-to-leg fat ratio (TLR). Fat distribution changes were derived from the coefficient of linear regression between their parameters and follow-up duration.ResultsAfter an average of 6.2-y follow-up, analysis of covariance (ANCOVA) and linear regression displayed women with higher serum TMAO level had greater increments in trunk FLR (mean ± SD: 1.47 ± 4.39, P-trend = 0.006) and TLR (mean ± SD: 0.06 ± 0.24, P-trend = 0.011). Meanwhile, for women in the highest TMAO tertile, linear mixed-effects model (LMEM) analysis demonstrated the annual estimated increments (95% CI) were 0.03 (95% CI: 0.003 – 0.06, P = 0.032) in trunk FLR and 1.28 (95% CI: -0.17 – 2.73, P = 0.083) in TLR, respectively. In men, there were no similar significant observations. Sensitivity analysis yielded consistent results.ConclusionSerum TMAO displayed a more profound correlation with increment of FLR and TLR in middle-aged and older community-dwelling women in current study. More and further studies are still warranted in the future.Trial registrationNCT 03179657.

Confounder Selection and Sensitivity Analyses to Unmeasured Confounding from Epidemiological and Statistical Perspectives.

In observational studies, identifying and adjusting for a sufficient set of confounders is crucial for accurately estimating the causal effect of the exposure on the outcome. Even in studies with large sample sizes, which typically benefit from small variances in estimates, there is a risk of producing estimates that are precisely inaccurate if the study suffers from systematic errors or biases, including confounding bias. To date, several approaches have been developed for selecting confounders. In this article, we first summarize the epidemiological and statistical approaches to identify a sufficient set of confounders. Particularly, we introduce the modified disjunctive cause criterion as one of the most useful approaches, which involves controlling for any pre-exposure covariate that affects the exposure, outcome, or both. It then excludes instrumental variables but includes proxies for the shared common cause of exposure and outcome. Statistical confounder selection is also useful when dealing with a large number of covariates, even in studies with small sample sizes. After introducing several approaches, we discuss some pitfalls and considerations in confounder selection, such as the adjustment for instrumental variables, intermediate variables, and baseline outcome variables. Lastly, as it is often difficult to comprehensively measure key confounders, we introduce two statistics, E-value and Robustness value, for assessing sensitivity to unmeasured confounders. Illustrated examples are provided using the National Health and Nutritional Examination Survey Epidemiologic Follow-up Study. Integrating these principles and approaches will enhance our understanding of confounder selection and facilitate better reporting and interpretation of future epidemiological studies.

Simultaneous plasma and interstitial profiles of hormones and metabolites using URHYTHM: a novel ambulatory collection device

Increasing the sampling resolution when examining plasma hormone and metabolite profiles will more accurately describe diurnal/circadian rhythms and expose previously undiscovered ultradian rhythms that underpin metabolic physiology(1). In human research studies this must be tempered by the practical, ethical and safety concerns of repeated cannulation/blood draws. Here we examine the correlation between hormone and metabolite profiles present in interstitial fluid microdialysate(2), and plasma to help solve this dilemma.Hormonal markers of circadian phase (melatonin, cortisol) and metabolites will show similar profiles in plasma and interstitial fluid.Compare time-series hormone and metabolite profiles collected in interstitial fluid using a novel ambulatory microdialysis collection device (U-RHYTHM) with simultaneously drawn plasma samples.All study protocols were reviewed by Health Sciences Faculty Research Ethics Committee, University of Bristol. Fasted healthy male volunteers aged 18-35 (n=3) were fed a standardised breakfast (08:00), lunch (13:00), dinner (19:00) and snack (22:00) (2225kCal [83g protein, 273g carbohydrate, 83g fat, 27g fibre]). Participants remained on the study bed, lights off/sleep occurred between 23:00-07:00 (&lt;4 lux).A 20kDa cutoff 30 mm linear microdialysis membrane was placed in periumbilical subcutaneous tissue, perpendicular to the midline. The membrane was perfused at 1µl/min and the microdialysate collected every 20 minutes for 25 hours into discrete samples using a portable fraction collector (URHYTHM) worn around the waist. Time-matched blood samples were obtained from an antecubital fossa canula.All samples were stored at -80°C prior to analysis. Hormones and metabolites were measured via targeted UPLC-MS/MS metabolomics, for the metabolites the AbsoluteIDQ® p180 kit (Biocrates Life Sciences AG)) was used with 10µL of plasma(3) and 15µL of microdialysate.Simultaneous time-courses of n = 24 metabolites were detected in plasma and interstitial microdialysate: alanine, arginine, asparagine, citrulline, glutamine, glutamate, glycine, histidine, isoleucine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, trans-4-Hydroxyproline, taurine, carnitine and acetylcarnitine.Spearman rank cross correlation identified the time shift that was required to reach highest correlation between the plasma and microdialysate profiles. Excluding taurine, microdialysate profiles were delayed by 32.3 minutes (range 0-130) and 12.9 minutes (range 0-50) for participant 1 and 2, respectively (p &lt;0.05), only 3/20 metabolite profiles were correlated for participant 3. Trans4-hydroxyproline had the strongest correlation (rs 0.890, 0.814 and 0.808), with only participant 3 displaying a time shift (50 minutes). Taurine had the weakest correlation in all 3 participants. (rs 0.096, 0.182, 0.325).These data demonstrate that our novel approach can be used to comprehensively detect hormone and metabolite profiles in interstitial fluid. Thus, the U-RHYTHM would serve as a useful tool, not only to increase sampling resolution in controlled laboratory studies but would prove particularly useful for examining circadian/ultradian profiles for chronobiology and nutrition studies in free-living individuals.

Intersections of Omega-3 Fatty Acids, DNA Methylation and Lung Function: A Nutritional Epigenetic Study in the Genetic Epidemiology of COPD Study

Intersections of Omega-3 Fatty Acids, DNA Methylation and Lung Function: A Nutritional Epigenetic Study in the Genetic Epidemiology of COPD Study

Grilling the Data: Interpreting the Results of Nutritional Epidemiology Studies in the Context of Variation Expected Due to Analytic Flexibility

Grilling the Data: Interpreting the Results of Nutritional Epidemiology Studies in the Context of Variation Expected Due to Analytic Flexibility