Content of nitrate and nitrite in commercial and self-made beetroot juices and the effect of storage temperature.

Popularity of beetroot juice (BJ) is growing due to its high inorganic nitrate content NO3- and its potential physiological benefits. However, the content of NO3- is not indicated in most commercial BJs and it can be affected by seasonal changes and storage conditions. This study analyzed the content of NO3- and nitrite NO2- in five and two commercial and self-made BJs, respectively, that were purchased in the summer and winter periods. The effect of storage temperature (20°C, 4°C, and -20°C) and pH was also analyzed. In nonconcentrated BJs, the NO3- content was 34 ± 20% (p = .075) in the winter than in the summer. NO3- was fully degraded in self-made BJ after 3 days at 20°C. This effect was attenuated by 78% and 82% when it was kept at 4°C and -20°C, respectively. The addition of lemon juice (5%) to self-made BJ was another useful approach to avoid NO3- degradation for 3 days when it was kept at 20°C. Regarding NO2-, self-made BJ had higher concentration (0.097 ± 0.01 mg/mL) compared to commercial BJs (<0.1 mg/mL; p = .001). The pH of self-made BJ was higher (6.3 ± 0.1) compared to commercial BJs (4.5 ± 0.3; p = .001). These results suggest that the content of NO3- in nonconcentrated BJs can substantially differ across the year and this is an important factor to take into account when recommending BJs to promote some of its potential physiological benefits.

Effect of supplementation with leucine alone, with other nutrients or with physical exercise in older people with sarcopenia: a systematic review.

BACKGROUND: Older adults are at a greater risk of developing sarcopenia as a result of reduced mobility, malnutrition, dietary changes and certain diseases. There are no systematic reviews in the literature analysing the effects of supplementation with leucine alone or as part of a supplement, and with or without physical exercise in older people with sarcopenia. We aimed to systematically review the evidence in intervention studies on the effects of supplementation with leucine, either alone, combined with other supplements, or combined with other supplements and physical exercise in older people with sarcopenia. MATERIALS AND METHODS: Literature searches related to the topic were conducted in three databases (Pubmed/Medline, Cochrane and SciELO) looking for articles published prior to December 2020. This review includes intervention studies in older adults over 60 years of age with a history of sarcopenia where researchers reported on the effects of leucine supplementation, with or without physical exercise, related to the disease's treatments or outcomes. RESULTS: The systematic review identified three intervention studies examining the effect of leucine without physical exercise, one on leucine with physical exercise, seven on leucine paired with another nutrient and without physical exercise, and twelve on leucine paired with another nutrient and physical exercise. The results revealed that leucine supplementation alone and without physical exercise did not improve markers of sarcopenia, whereas interventions pairing leucine with supplements, particularly leucine-enriched protein supplements, are a promising treatment for the improvement of sarcopenic markers, whether with or without physical exercise. CONCLUSIONS: Leucine supplementation, specifically paired with protein supplements, both with and without physical exercise, was found to be an effective dietary intervention for the improvement of sarcopenia. Further dietary interventions are necessary to calculate effective dosage quantities for both leucine and nutrient supplementation as an integral part of the treatment.

Edible Insect Consumption for Human and Planetary Health: A Systematic Review.

This systematic review aimed to examine the health outcomes and environmental impact of edible insect consumption. Following PRISMA-P guidelines, PubMed, Medline ProQuest, and Cochrane Library databases were searched until February 2021. Twenty-five articles met inclusion criteria: twelve animal and six human studies (randomized, non-randomized, and crossover control trials), and seven studies on sustainability outcomes. In animal studies, a supplement (in powdered form) of 0.5 g/kg of glycosaminoglycans significantly reduced abdominal and epididymal fat weight (5-40% and 5-24%, respectively), blood glucose (10-22%), and total cholesterol levels (9-10%), and a supplement of 5 mg/kg chitin/chitosan reduced body weight (1-4%) and abdominal fat accumulation (4%) versus control diets. In other animal studies, doses up to 7-15% of edible insect inclusion level significantly improved the live weight (9-33%), reduced levels of triglycerides (44%), cholesterol (14%), and blood glucose (8%), and increased microbiota diversity (2%) versus control diet. In human studies, doses up to 7% of edible insect inclusion level produced a significant improvement in gut health (6%) and reduction in systemic inflammation (2%) versus control diets and a significant increase in blood concentrations of essential and branched-chain amino acids and slowing of digestion (40%) versus whey treatment. Environmental indicators (land use, water footprint, and greenhouse gas emissions) were 40-60% lower for the feed and food of edible insects than for traditional animal livestock. More research is warranted on the edible insect dose responsible for health effects and on environmental indicators of edible insects for human nutrition. This research demonstrates how edible insects can be an alternative protein source not only to improve human and animal nutrition but also to exert positive effects on planetary health.

Assessing Adherence to Healthy Dietary Habits Through the Urinary Food Metabolome: Results From a European Two-Center Study.

Background: Diet is one of the most important modifiable lifestyle factors in human health and in chronic disease prevention. Thus, accurate dietary assessment is essential for reliably evaluating adherence to healthy habits. Objectives: The aim of this study was to identify urinary metabolites that could serve as robust biomarkers of diet quality, as assessed through the Alternative Healthy Eating Index (AHEI-2010). Design: We set up two-center samples of 160 healthy volunteers, aged between 25 and 50, living as a couple or family, with repeated urine sampling and dietary assessment at baseline, and 6 and 12 months over a year. Urine samples were subjected to large-scale metabolomics analysis for comprehensive quantitative characterization of the food-related metabolome. Then, lasso regularized regression analysis and limma univariate analysis were applied to identify those metabolites associated with the AHEI-2010, and to investigate the reproducibility of these associations over time. Results: Several polyphenol microbial metabolites were found to be positively associated with the AHEI-2010 score; urinary enterolactone glucuronide showed a reproducible association at the three study time points [false discovery rate (FDR): 0.016, 0.014, 0.016]. Furthermore, other associations were found between the AHEI-2010 and various metabolites related to the intake of coffee, red meat and fish, whereas other polyphenol phase II metabolites were associated with higher AHEI-2010 scores at one of the three time points investigated (FDR < 0.05 or ß ≠ 0). Conclusion: We have demonstrated that urinary metabolites, and particularly microbiota-derived metabolites, could serve as reliable indicators of adherence to healthy dietary habits. Clinical Trail Registration: www.ClinicalTrials.gov, Identifier: NCT03169088.

Effects of chlorhexidine mouthwash on the oral microbiome.

INTRODUCTION/OBJECTIVES: Chlorhexidine (CHX) is a commonly used mouthwash with potent anti-microbial effects useful for the management of oral disease. However, we are moving away from the view of simply 'killing' bacteria, towards managing oral microbial ecosystems (oral microbiome), as an integrated system, to promote oral and systemic health. Here, we aimed to review the effects of CHX mouthwash on the balance of microbial communities in the mouth in vivo in oral health and disease. SOURCES AND STUDY SECTION: The hierarchy of evidence was applied, with systematic reviews and randomised controlled trials consulted where available and case controlled studies being described thereafter. Search terms for each subject category were entered into MEDLINE, PubMed, Google Scholar and the Cochrane database. Focussing on metagenomics studies provides unique overview of the oral microbiome as an integrated system. DATA: Evidence was limited, but several next generation sequencing case-controlled studies suggested that in an integrated system, CHX may cause a shift towards lower bacterial diversity and abundance, in particular nitrate-reducing bacteria in vivo. CHX also appeared to alter salivary pH, lactate, nitrate and nitrite concentrations in saliva. Evidence regarding the effects of CHX on the oral microbiome during oral disease is still emerging. CONCLUSIONS: CHX alters the composition the oral microbiome. However, as CHX use remains widespread in dentistry to manage oral disease, urgent research using metagenomics studies of microbial communities in vivo are still needed to determine CHX mouthwash is 'good', 'bad' or otherwise for bacteria, in the context of oral and systemic health.

Visceral Adipose Tissue Phospholipid Signature of Insulin Sensitivity and Obesity.

Alterations in visceral adipose tissue (VAT) are closely linked to cardiometabolic abnormalities. The aim of this work is to define a metabolic signature in VAT of insulin resistance (IR) dependent on, and independent of, obesity. An untargeted UPLC-Q-Exactive metabolomic approach was carried out on the VAT of obese insulin-sensitive (IS) and insulin-resistant subjects (N = 11 and N = 25, respectively) and nonobese IS and IR subjects (N = 25 and N = 10, respectively). The VAT metabolome in obesity was defined among other things by changes in the metabolism of lipids, nucleotides, carbohydrates, and amino acids, whereas when combined with high IR, it affected the metabolism of 18 carbon fatty acyl-containing phospholipid species. A multimetabolite model created by glycerophosphatidylinositol (18:0); glycerophosphatidylethanolamine (18:2); glycerophosphatidylserine (18:0); and glycerophosphatidylcholine (18:0/18:1), (18:2/18:2), and (18:2/18:3) exhibited a highly predictive performance to identify the metabotype of "insulin-sensitive obesity" among obese individuals [area under the curve (AUC) 96.7% (91.9-100)] and within the entire study population [AUC 87.6% (79.0-96.2)]. We demonstrated that IR has a unique and shared metabolic signature dependent on, and independent of, obesity. For it to be used in clinical practice, these findings need to be validated in a more accessible sample, such as blood.

Economic benefit of dietetic-nutritional treatment in the multidisciplinary primary care team / Beneficio económico del tratamiento dietético-nutricional en el equipo multidisciplinario de atención primaria

Chronic diseases and aging are placing an ever increasing burden on healthcare services worldwide. Nutritional counselling is a priority for primary care because it has shown substantial cost savings. This review aims to evaluate the evidence of the cost-effectiveness of nutritional care in primary care provided by health professionals. A literature search was conducted using PubMed/MEDLINE between January 2000 and February 2019. The review included thirty-six randomized controlled trials (RCTs) and systematic reviews conducted in healthy people and people with obesity, type-2 diabetes mellitus, cardiovascular risk or malnutrition. All the RCTs and reviews showed that nutritional intervention led by dietitians-nutritionists in people with obesity or cardiovascular risk factors was cost-effective. Dietary interventions led by nurses were cost-effective in people who needed to lose weight but not in people at high cardiovascular risk. Some dietary changes led by a primary care team in people with diabetes were cost-effective. Incorporating dietitians-nutritionists into primary care settings, or increasing their presence, would give people access to the healthcare professionals who are best qualified to carry out nutritional treatment, and may be the most cost-effective intervention in terms of health expenditure. Notwithstanding the limitations described, this review suggests that incorporating dietitians-nutritionists into primary health care as part of the multidisciplinary team could be regarded as an investment in health. Even so, more research is required to confirm the conclusions

Las enfermedades crónicas y el envejecimiento suponen una carga cada vez mayor para los servicios de salud en todo el mundo. El asesoramiento nutricional es una prioridad para la atención primaria porque ha demostrado ahorros sustanciales de costes. Esta revisión tiene como objetivo evaluar la evidencia de la relación coste-efectividad de la atención nutricional en la atención primaria proporcionada por profesionales de la salud. Se realizó una búsqueda bibliográfica utilizando PubMed/MEDLINE entre enero de 2000 y febrero de 2019. La revisión incluyó 36 ensayos controlados aleatorios (ECA) y revisiones sistemáticas realizadas en personas sanas y personas con obesidad, diabetes mellitus de tipo 2, riesgo cardiovascular o desnutrición. Todos los ECA y las revisiones mostraron que la intervención nutricional dirigida por dietistas-nutricionistas en personas con obesidad o factores de riesgo cardiovascular fue coste-efectiva. Las intervenciones dietéticas dirigidas por enfermeras fueron coste-efectivas en personas que necesitaban perder peso pero no en personas con alto riesgo cardiovascular. Algunos de los cambios en la dieta dirigidos por un equipo de atención primaria en personas con diabetes también fueron coste-efectivos. La incorporación de dietistas-nutricionistas en entornos de atención primaria, o aumentar su presencia, daría a las personas acceso a los profesionales de la salud mejor calificados para llevar a cabo el tratamiento nutricional, y resultaría más rentable en términos de gasto en salud. A pesar de las limitaciones descritas, esta revisión sugiere que incorporar dietistas-nutricionistas en atención primaria como parte del equipo multidisciplinario podría considerarse una inversión en salud. Aun así, se requiere más investigación para confirmar las conclusiones

Exercise dose affects the circulating microRNA profile in response to acute endurance exercise in male amateur runners.

The systemic response to exercise is dose-dependent and involves a complex gene expression regulation and cross-talk between tissues. This context ARISES the need for analyzing the influence of exercise dose on the profile of circulating microRNAs (c-miRNAs), as emerging posttranscriptional regulators and intercellular communicators. Thus, we hypothesized that different exercise doses will determine specific c-miRNA signatures that will highlight its potential as exercise dose biomarker. Nine active middle-aged males completed a 10-km race (10K), a half-marathon (HM), and a marathon (M). Blood samples were collected immediately before and after races. Plasma RNA was extracted, and a global screening of 752 microRNAs was analyzed using RT-qPCR. Three different c-miRNA profiles were defined according to the three doses. In 10K, 14 c-miRNAs were found to be differentially expressed between pre- and post-exercise, 13 upregulated and 1 downregulated. Regarding HM, 13 c-miRNAs were found to be differentially modulated, in all the cases upregulated. A total of 28 c-miRNAs were found to be differentially expressed in M, 21 overexpressed and 7 repressed after this race. We had also found 3 common c-miRNAs between 10K and M and 2 common c-miRNAs between 10K and HM. In silico analysis supported a close association between exercise dose c-miRNA profiles and cellular pathways linked to energy metabolism and cell cycle. In conclusion, we have observed that different exercise doses induced specific c-miRNA profiles. So, our results point to c-miRNAs as emerging exercise dose biomarkers and as one of regulatory mechanisms modulating the response to endurance exercise.

Economic benefit of dietetic-nutritional treatment in the multidisciplinary primary care team.

INTRODUCTION: Chronic diseases and aging are placing an ever increasing burden on healthcare services worldwide. Nutritional counselling is a priority for primary care because it has shown substantial cost savings. This review aims to evaluate the evidence of the cost-effectiveness of nutritional care in primary care provided by health professionals. A literature search was conducted using PubMed/MEDLINE between January 2000 and February 2019. The review included thirty-six randomized controlled trials (RCTs) and systematic reviews conducted in healthy people and people with obesity, type-2 diabetes mellitus, cardiovascular risk or malnutrition. All the RCTs and reviews showed that nutritional intervention led by dietitians-nutritionists in people with obesity or cardiovascular risk factors was cost-effective. Dietary interventions led by nurses were cost-effective in people who needed to lose weight but not in people at high cardiovascular risk. Some dietary changes led by a primary care team in people with diabetes were cost-effective. Incorporating dietitians-nutritionists into primary care settings, or increasing their presence, would give people access to the healthcare professionals who are best qualified to carry out nutritional treatment, and may be the most cost-effective intervention in terms of health expenditure. Notwithstanding the limitations described, this review suggests that incorporating dietitians-nutritionists into primary health care as part of the multidisciplinary team could be regarded as an investment in health. Even so, more research is required to confirm the conclusions.

INTRODUCCIÓN: Las enfermedades crónicas y el envejecimiento suponen una carga cada vez mayor para los servicios de salud en todo el mundo. El asesoramiento nutricional es una prioridad para la atención primaria porque ha demostrado ahorros sustanciales de costes. Esta revisión tiene como objetivo evaluar la evidencia de la relación coste-efectividad de la atención nutricional en la atención primaria proporcionada por profesionales de la salud. se realizó una búsqueda bibliográfica utilizando PubMed/MEDLINE entre enero de 2000 y febrero de 2019. La revisión incluyó 36 ensayos controlados aleatorios (ECA) y revisiones sistemáticas realizadas en personas sanas y personas con obesidad, diabetes mellitus de tipo 2, riesgo cardiovascular o desnutrición. Todos los ECA y las revisiones mostraron que la intervención nutricional dirigida por dietistas-nutricionistas en personas con obesidad o factores de riesgo cardiovascular fue coste-efectiva. Las intervenciones dietéticas dirigidas por enfermeras fueron coste-efectivas en personas que necesitaban perder peso pero no en personas con alto riesgo cardiovascular. Algunos de los cambios en la dieta dirigidos por un equipo de atención primaria en personas con diabetes también fueron coste-efectivos. La incorporación de dietistas-nutricionistas en entornos de atención primaria, o aumentar su presencia, daría a las personas acceso a los profesionales de la salud mejor calificados para llevar a cabo el tratamiento nutricional, y resultaría más rentable en términos de gasto en salud. A pesar de las limitaciones descritas, esta revisión sugiere que incorporar dietistas-nutricionistas en atención primaria como parte del equipo multidisciplinario podría considerarse una inversión en salud. Aun así, se requiere más investigación para confirmar las conclusiones.

Effects of Chlorhexidine mouthwash on the oral microbiome.

Following a single blind, cross-over and non-randomized design we investigated the effect of 7-day use of chlorhexidine (CHX) mouthwash on the salivary microbiome as well as several saliva and plasma biomarkers in 36 healthy individuals. They rinsed their mouth (for 1 min) twice a day for seven days with a placebo mouthwash and then repeated this protocol with CHX mouthwash for a further seven days. Saliva and blood samples were taken at the end of each treatment to analyse the abundance and diversity of oral bacteria, and pH, lactate, glucose, nitrate and nitrite concentrations. CHX significantly increased the abundance of Firmicutes and Proteobacteria, and reduced the content of Bacteroidetes, TM7, SR1 and Fusobacteria. This shift was associated with a significant decrease in saliva pH and buffering capacity, accompanied by an increase in saliva lactate and glucose levels. Lower saliva and plasma nitrite concentrations were found after using CHX, followed by a trend of increased systolic blood pressure. Overall, this study demonstrates that mouthwash containing CHX is associated with a major shift in the salivary microbiome, leading to more acidic conditions and lower nitrite availability in healthy individuals.

Lipids and physical function in older adults.

PURPOSE OF REVIEW: Healthy aging is a public health priority. The maintenance of adequate physical function is recognized as a key element of healthy aging. In recent years, scientific evidence has increased concerning the ability of lipids, in particular omega 3 polyunsaturated fatty acids (n-3 PUFAs), to positively influence muscle and overall physical function in older patients. The article will critically review observational as well as intervention studies on this topic, and it will elucidate the potential biological mechanisms underlying the beneficial effects of n-3 PUFA on physical function. RECENT FINDINGS: Observational studies and clinical trials performed in healthy older patients and in older patients with chronic diseases mostly found positive effects of n-3 PUFA on muscle metabolism, muscle strength and in general physical function. SUMMARY: Although the use of n-3 PUFA might represent an important intervention to preserve physical function in older adults, several key questions still need to be answered. Above all, large randomized controlled trials should be performed to confirm the utility of n-3 PUFA as therapeutic agents to prevent and treat physical function decline in old age.

Mother's nutritional miRNA legacy: Nutrition during pregnancy and its possible implications to develop cardiometabolic disease in later life.

Maternal nutrition during pregnancy and lactation influences the offspring's health in the long-term. Indeed, human epidemiological studies and animal model experiments suggest that either an excess or a deficit in maternal nutrition influence offspring development and susceptibility to metabolic disorders. Different epigenetic mechanisms may explain in part the way by which dietary factors in early critical developmental steps might be able to affect the susceptibility to develop metabolic diseases in adulthood. microRNAs are versatile regulators of gene expression and play a major role during tissue homeostasis and disease. Dietary factors have also been shown to modify microRNA expression. However, the role of microRNAs in fetal programming remains largely unstudied. This review evaluates in vivo studies conducted to analyze the effect of maternal diet on the modulation of the microRNA expression in the offspring and their influence to develop metabolic and cardiovascular disease in later life. In overall, the available evidence suggests that nutritional status during pregnancy influence offspring susceptibility to the development of cardiometabolic risk factors, partly through microRNA action. Thus, therapeutic modulation of microRNAs can open up new strategies to combat - later in life - the effects of nutritional insult during critical points of development.

MicroRNAs expression in normal and malignant colon tissues as biomarkers of colorectal cancer and in response to pomegranate extracts consumption: Critical issues to discern between modulatory effects and potential artefacts.

SCOPE: MicroRNAs (miRs) are proposed as colorectal cancer (CRC) biomarkers. Pomegranate ellagic acid and their microbiota metabolites urolithins exert anticancer effects in preclinical CRC models, and target normal and malignant colon tissues in CRC patients. Herein, we investigated whether the intake of pomegranate extract (PE) modified miRs expression in surgical colon tissues versus biopsies from CRC patients. METHODS AND RESULTS: We conducted a randomized, double-blind, controlled trial. Thirty-five CRC patients consumed 900 mg PE daily before surgery. Control CRC patients (no PE intake, n = 10) were included. Our results revealed: (1) significant differences for specific miRs between malignant and normal tissues modifiable by the surgical protocols; (2) opposed trends between -5p and -3p isomolecules; (3) general induction of miRs attributable to the surgery; (4) moderate modulation of various miRs following the PE intake, and (5) no association between tissue urolithins and the observed miRs changes. CONCLUSION: PE consumption appears to affect specific colon tissue miRs but surgery critically alters miRs levels hindering the discrimination of significant changes caused by dietary factors and the establishment of genuine differences between malignant and normal tissues as biomarkers. The components responsible for the PE effects and the clinical relevance of these observations deserve further research.

Circulating inflammatory miRNA signature in response to different doses of aerobic exercise.

While moderate acute exercise has been associated with strong anti-inflammatory mechanisms, strenuous exercise has been linked to deleterious inflammatory perturbations. It is therefore fundamental to elucidate the mechanisms that regulate the exercise-induced inflammatory cascade. Information on novel regulators such as circulating inflammatory microRNAs (c-inflammamiRs) is incomplete. In this study, we evaluated the response of a panel of c-inflammamiRs to different doses of acute aerobic exercise. We first studied the exercise-induced inflammatory cascade in serum samples of nine active middle-aged males immediately before and after (0 h, 24 h, 72 h) 10-km, half-marathon, and marathon races. Next, we analyzed the circulating profile of 106 specific c-inflammamiRs immediately before) and after (0 h, 24 h) 10-km (low inflammatory response) and marathon (high inflammatory response) races. Analysis of classical inflammatory parameters revealed a dose-dependent effect of aerobic exercise on systemic inflammation, with higher levels detected after marathon. We observed an increase in miR-150-5p immediately after the 10-km race. Levels of 12 c-inflammamiRs were increased immediately after the marathon (let-7d-3p, let-7f-2-3p, miR-125b-5p, miR-132-3p, miR-143-3p, miR-148a-3p, miR-223-3p, miR-223-5p, miR-29a-3p, miR-34a-5p, miR-424-3p, and miR-424-5p). c-inflammamiRs returned to basal levels after 24 h. Correlation and in silico analyses supported a close association between the observed c-inflammamiR pattern and regulation of the inflammatory process. In conclusion, we found that different doses of acute aerobic exercise induced a distinct and specific c-inflammamiR response, which may be associated with control of the exercise-induced inflammatory cascade. Our findings point to c-inflammamiRs as potential biomarkers of exercise-induced inflammation, and hence, exercise dose.

Consumption of distinct dietary lipids during early pregnancy differentially modulates the expression of microRNAs in mothers and offspring.

Diet during pregnancy and lactation influences the offspring's health in the long-term. Indeed, human epidemiological studies and animal experiments suggest that different type of fatty acids consumption during pregnancy affect offspring development and susceptibility to metabolic disorders. Epigenetic changes are thought to be elicited by dietary factors during critical timing of development. microRNAs (miRNAs) are versatile regulators of gene expression. Thus, we aimed to determine the influence of different fatty acids on miRNA expression in offspring when given during early pregnancy. We fed pregnant either soybean (SO), olive (OO), fish (FO), linseed (LO), or palm-oil (PO) diets from conception to day 12 of gestation; and standard diet thereafter. miRNA expression was assessed in liver an adipose tissue of pregnant rats and their virgin counterparts. While liver concentrations of fatty acids in pregnant or virgin rats replicated those of the diets consumed during early pregnancy, their pups' liver tissue marginally reflected those of the respective experimental feeds. By contrast, the liver fatty acid profile of adult offsprings was similar, regardless of the diet fed during gestation. Different parental miRNAs were modulated by the different type of fatty acid: in adult offspring, miR-215, miR-10b, miR-26, miR-377-3p, miR-21, and miR-192 among others, were differentially modulated by the different fatty acids fed during early pregnancy. Overall, our results show that maternal consumption of different types of fatty acids during early pregnancy influences miRNA expression in both maternal and offspring tissues, which may epigenetically explain the long-term phenotypic changes of the offspring.

Genome-wide interaction of genotype by erythrocyte n-3 fatty acids contributes to phenotypic variance of diabetes-related traits.

BACKGROUND: Little is known about the interplay between n-3 fatty acids and genetic variants for diabetes-related traits at the genome-wide level. The present study aimed to examine variance contributions of genotype by environment (GxE) interactions for different erythrocyte n-3 fatty acids and genetic variants for diabetes-related traits at the genome-wide level in a non-Hispanic white population living in the U.S.A. (n = 820). A tool for Genome-wide Complex Trait Analysis (GCTA) was used to estimate the genome-wide GxE variance contribution of four diabetes-related traits: HOMA-Insulin Resistance (HOMA-IR), fasting plasma insulin, glucose and adiponectin. A GxE genome-wide association study (GWAS) was conducted to further elucidate the GCTA results. Replication was conducted in the participants of the Boston Puerto Rican Health Study (BPRHS) without diabetes (n = 716). RESULTS: In GOLDN, docosapentaenoic acid (DPA) contributed the most significant GxE variance to the total phenotypic variance of both HOMA-IR (26.5%, P-nominal = 0.034) and fasting insulin (24.3%, P-nominal = 0.042). The ratio of arachidonic acid to eicosapentaenoic acid + docosahexaenoic acid contributed the most significant GxE variance to the total variance of fasting glucose (27.0%, P-nominal = 0.023). GxE variance of the arachidonic acid/eicosapentaenoic acid ratio showed a marginally significant contribution to the adiponectin variance (16.0%, P-nominal = 0.058). None of the GCTA results were significant after Bonferroni correction (P < 0.001). For each trait, the GxE GWAS identified a far larger number of significant single-nucleotide polymorphisms (P-interaction ≤ 10E-5) for the significant E factor (significant GxE variance contributor) than a control E factor (non-significant GxE variance contributor). In the BPRHS, DPA contributed a marginally significant GxE variance to the phenotypic variance of HOMA-IR (12.9%, P-nominal = 0.068) and fasting insulin (18.0%, P-nominal = 0.033). CONCLUSION: Erythrocyte n-3 fatty acids contributed a significant GxE variance to diabetes-related traits at the genome-wide level.

A genetic variant of PPARA modulates cardiovascular risk biomarkers after milk consumption.

OBJECTIVE: The association of dairy food consumption with the risk for developing cardiovascular disease (CVD) has been investigated in many studies, but results often have been contradictory. The aim of the present study was to determine whether genetic polymorphisms are associated with interindividual variation in the response of CVD risk biomarker values after milk consumption. METHODS: Fourteen single nucleotide polymorphisms (SNPs) in nine genes related to lipid metabolism were examined in 161 volunteers randomly allocated to consume either 500 mL/d of skimmed (S) or semi-skimmed (SS) milk for 1 year in addition to their usual diets. Total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) and low-density lipoprotein/HDL-C ratios were used as biomarkers of CVD risk. Three-way repeated-measures analysis of variance was used to examine the effect of time, treatment (S or SS), and genotype on these biomarkers. RESULTS: A TT genotype for the proliferator-activated receptor alpha polymorphism (PPARA rs135549 SNP) was significantly associated with a reduction in the TC/HDL and LDL/HDL ratios after 12 mo of S milk intake (mean reduction -0.29, 95% confidence interval [CI], -0.63 to 0.05; P = 0.0015 and -0.31, 95% CI, -0.58 to -0.03; P = 0.0005, respectively). However, no differences were observed after consuming either S or SS milk in the C allele carriers. CONCLUSIONS: Saturated fatty acid consumption has long been linked to an increased risk for CVD; indeed, the consumption of saturated fat-free products is recommended as a means of reducing this risk. However, the present results suggest that many individuals might not benefit from such general recommendations. Genetic analysis of PPARA rs135549 might help identify those individuals who are more likely to benefit from reducing the saturated fatty acid content of their diet.

Saturated fat intake modulates the association between an obesity genetic risk score and body mass index in two US populations.

Combining multiple genetic variants related to obesity into a genetic risk score (GRS) might improve identification of individuals at risk of developing obesity. Moreover, characterizing gene-diet interactions is a research challenge to establish dietary recommendations to individuals with higher predisposition to obesity. Our objective was to analyze the association between an obesity GRS and body mass index (BMI) in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) population, focusing on gene-diet interactions with total fat and saturated fatty acid (SFA) intake, and to replicate findings in the Multi-Ethnic Study of Atherosclerosis (MESA) population. Cross-sectional analyses included 783 white US participants from GOLDN and 2,035 from MESA. Dietary intakes were estimated with validated food frequency questionnaires. Height and weight were measured. A weighted GRS was calculated on the basis of 63 obesity-associated variants. Multiple linear regression models adjusted by potential confounders were used to examine gene-diet interactions between dietary intake (total fat and SFA) and the obesity GRS in determining BMI. Significant interactions were found between total fat intake and the obesity GRS using these variables as continuous for BMI (P for interaction=0.010, 0.046, and 0.002 in GOLDN, MESA, and meta-analysis, respectively). These association terms were stronger when assessing interactions between SFA intake and GRS for BMI (P for interaction=0.005, 0.018, and <0.001 in GOLDN, MESA, and meta-analysis, respectively). SFA intake interacts with an obesity GRS in modulating BMI in two US populations. Although determining the causal direction requires further investigation, these findings suggest that potential dietary recommendations to reduce BMI effectively in populations with high obesity GRS would be to reduce total fat intake mainly by limiting SFAs.

How Gene Networks Can Uncover Novel CVD Players.

Cardiovascular diseases (CVD) are complex, involving numerous biological entities from genes and small molecules to organ function. Placing these entities in networks where the functional relationships among the constituents are drawn can aid in our understanding of disease onset, progression and prevention. While networks, or interactomes, are often classified by a general term, say lipids or inflammation, it is a more encompassing class of network that is more informative in showing connections among the active entities and allowing better hypotheses of novel CVD players to be formulated. A range of networks will be presented whereby the potential to bring new objects into the CVD milieu will be exemplified.

Effects of plant sterol esters in skimmed milk and vegetable-fat-enriched milk on serum lipids and non-cholesterol sterols in hypercholesterolaemic subjects: a randomised, placebo-controlled, crossover study.

Plant sterol (PS)-supplemented foods are recommended to help in lowering serum LDL-cholesterol (LDL-C). Few studies have examined the efficacy of PS-enriched skimmed milk (SM) or semi-SM enriched with vegetable fat (PS-VFM). There is also insufficient information on factors predictive of LDL-C responses to PS. We examined the effects of PS-SM (0·1 % dairy fat) and PS-VFM (0·1 % dairy fat plus 1·5 % vegetable fat) on serum lipids and non-cholesterol sterols in hypercholesterolaemic individuals. In a placebo-controlled, crossover study, forty-three subjects with LDL-C>1300 mg/l were randomly assigned to three 4-week treatment periods: control SM, PS-SM and PS-VFM, with 500 ml milk with or without 3·4 g PS esters (2 g free PS). Serum concentrations of lipids and non-cholesterol sterols were measured. Compared to control, LDL-C decreased by 8·0 and 7·4 % (P < 0·015, both) in the PS-SM and PS-VFM periods, respectively. Serum lathosterol:cholesterol (C) ratios increased by 11-25 %, while sitosterol:C and campesterol:C ratios increased by 70-120 % with both the PS-fortified milk. Adjusted LDL-C reductions were variably enhanced in participants with basal low serum lathosterol/C or conversely high sitosterol/C and campesterol/C. Subjects with post-treatment serum PS:C ratios above the median showed mean LDL-C changes of - 5·9 to - 10·4 %, compared with 1·7 to - 2·9 % below the median. In conclusion, consumption of 2 g/d of PS as PS-SM and PS-VFM lowered LDL-C in hypercholesterolaemic subjects to a similar extent. Basal and post-treatment changes in markers of cholesterol metabolism indicating low cholesterol synthesis and high cholesterol absorption predicted improved LDL-C responses to PS.