Human evidence on the effects of early life phthalate exposure on obesity and cardiovascular disease risks, reported by experimental studies, is limited to a few cross-sectional studies.
We evaluated ...the associations between prenatal phthalate exposure and childhood growth and blood pressure in a Spanish birth cohort study.
We assessed exposure using the average of two phthalate metabolite spot-urine concentrations collected from the mothers in the first and third pregnancy trimesters (creatinine-adjusted, n = 391). Study outcomes were the difference in age- and sex-specific z-scores for weight between birth and 6 months of age; and repeated age- and sex-specific z-scores for body mass index (BMI) at 1, 4, and 7 years; waist-to-height ratio at 4 and 7 years; and age- and height-specific z-scores for systolic and diastolic blood pressure at 4 and 7 years.
The sum of five high-molecular-weight phthalate metabolites (ΣHMWPm) was associated with lower weight z-score difference between birth and 6 months (β per doubling of exposure = -0.41; 95% CI: -0.75, -0.06) and BMI z-scores at later ages in boys (β = -0.28; 95% CI: -0.60, 0.03) and with higher weight z-score difference (β = 0.24; 95% CI: -0.16, 0.65) and BMI z-scores in girls (β = 0.30; 95% CI: -0.04, 0.64) (p for sex interaction = 0.01 and 0.05, respectively). The sum of three low-molecular-weight phthalates (ΣLMWPm) was not significantly associated with any of the growth outcomes. ΣHMWPm and ΣLMWPm were associated with lower systolic blood pressure z-scores in girls but not in boys.
This study suggests that prenatal phthalate exposure may be associated with postnatal growth and blood pressure in a sex-specific manner. Inconsistencies with previous cross-sectional findings highlight the necessity for evaluating phthalate health effects in prospective studies.
An association between processed and red meat consumption and total mortality has been reported by epidemiological studies; however, there are many controversial reports regarding the association ...between meat consumption and CVD and IHD mortality. The present meta-analysis was carried out to summarise the evidence from prospective cohort studies on the association between consumption of meat (total, red, white and processed) and all-cause, CVD and IHD mortality. Cohort studies were identified by searching the PubMed and ISI Web of Knowledge databases. Risk estimates for the highest v. the lowest consumption category and dose-response meta-analysis were calculated using a random-effects model. Heterogeneity among the studies was also evaluated. A total of thirteen cohort studies were identified (1 674 272 individuals). Subjects in the highest category of processed meat consumption had 22 and 18 % higher risk of mortality from any cause and CVD, respectively. Red meat consumption was found to be associated with a 16 % higher risk of CVD mortality, while no association was found for total and white meat consumption. In the dose-response meta-analysis, an increase of 50 g/d in processed meat intake was found to be positively associated with all-cause and CVD mortality, while an increase of 100 g/d in red meat intake was found to be positively associated with CVD mortality. No significant associations were observed between consumption of any type of meat and IHD mortality. The results of the present meta-analysis indicate that processed meat consumption could increase the risk of mortality from any cause and CVD, while red meat consumption is positively but weakly associated with CVD mortality. These results should be interpreted with caution due to the high heterogeneity observed in most of the analyses as well as the possibility of residual confounding.
Following the publication of the 2018 World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) Third Expert Report, a collaborative group was formed to develop a ...standardized scoring system and provide guidance for research applications.
The 2018 WCRF/AICR Cancer Prevention Recommendations, goals, and statements of advice were examined to define components of the new Score. Cut-points for scoring were based on quantitative guidance in the 2018 Recommendations and other guidelines, past research that operationalized 2007 WCRF/AICR Recommendations, and advice from the Continuous Update Project Expert Panel.
Eight of the ten 2018 WCRF/AICR Recommendations concerning weight, physical activity, diet, and breastfeeding (optional), were selected for inclusion. Each component is worth one point: 1, 0.5, and 0 points for fully, partially, and not meeting each recommendation, respectively (Score: 0 to 7-8 points). Two recommendations on dietary supplement use and for cancer survivors are not included due to operational redundancy. Additional guidance stresses the importance of accounting for other risk factors (e.g., smoking) in relevant models.
The proposed 2018 WCRF/AICR Score is a practical tool for researchers to examine how adherence to the 2018 WCRF/AICR Recommendations relates to cancer risk and mortality in various adult populations.
The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) current dietary recommendations for cancer prevention include "eating at least five portions/servings of a variety of ...non-starchy vegetables and or fruits every day". The most recent report coordinated by WCRF/AICR (2007) concluded that the evidence of a protective effect of fruits and vegetables on cancer was either "probable"-mouth, pharynx and larynx, oesophagus stomach, lung- or "limited suggestive"-nasopharynx, lung, colorectum, ovary, endometrium, pancreas, liver-. In a previous report published by WCRF/AICR in 1997, the evidence of the association of fruits and vegetables with cancer risk was considered convincing. This judgement was based mainly on the results of case-control studies. The association of fruit and vegetable intake and the risk of colorectal, breast and pancreatic cancer was re-examined in the Continuous Update Project (CUP) and the results were quantitatively summarised in meta-analyses. The CUP, with more data available, has confirmed the conclusion of the WCRF/AICR second expert report that there is no convincing evidence that fruits and vegetables play a role on cancer aetiology. On the other hand, evidence that is more consistent has been collected in the CUP about the role of dietary fibre and colorectal cancer. The evidence on the role of dietary fibre in colorectal cancer aetiology has been recently upgraded by the CUP expert panel from probable to convincing.
Perfluoroalkyl substances (PFAS) may affect body mass index (BMI) and other components of cardiometabolic (CM) risk during childhood, but evidence is scarce and inconsistent.
We estimated ...associations between prenatal PFAS exposures and outcomes relevant to cardiometabolic risk, including a composite CM-risk score.
We measured perfluorohexanesulfonic acid (PFHxS), perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) in maternal plasma (first trimester). We assessed weight gain from birth until 6 mo. At 4 and 7 y, we calculated the age- and sex-specific
-scores for BMI, waist circumference (WC), and blood pressure (BP) (n≈1,000). At age 4, we calculated the age-, sex-, and region-specific
-scores for cholesterol, triglycerides (TGs), high-density (HDL-C), and low-density lipoprotein cholesterol (LDL-C) (n=627). At age 4, we calculated a CM-risk score (n=386) as the sum of the individual age-, sex-, and region-specific
-scores for WC, BP, HDL-C, and TGs. We used the average between the negative of HDL-C
-score and TGs
-score to give similar weight to lipids and the other components in the score. A higher score indicates a higher cardiometabolic risk at age 4.
PFOS and PFOA were the most abundant PFAS (geometric mean: 5.80 and 2.32 ng/mL, respectively). In general, prenatal PFAS concentrations were not associated with individual outcomes or the combined CM-risk score. Exceptions were positive associations between prenatal PFHxS and TGs
-score for a doubling of exposure, β=0.11; 95% confidence interval (CI): 0.01, 0.21, and between PFNA and the CM-risk score (β=0.60; 95% CI: 0.04, 1.16). There was not clear or consistent evidence of modification by sex.
We observed little or no evidence of associations between low prenatal PFAS exposures and outcomes related to cardiometabolic risk in a cohort of Spanish children followed from birth until 7 y. https://doi.org/10.1289/EHP1330.
Peripheral blood mononuclear cells (PBMC) are widely used as a biomarker source in nutrition/obesity studies because they reflect gene expression profiles of internal tissues. In this pilot ...proof-of-concept study we analysed in humans if, as we previously suggested in rodents, PBMC could be a surrogate tissue to study overweight/obesity impact on lipid metabolism. Pre-selected key lipid metabolism genes based in our previous preclinical studies were analysed in PBMC of normoglycemic normal-weight (NW), and overweight-obese (OW-OB) subjects before and after a 6-month weight-loss plan. PBMC mRNA levels of CPT1A, FASN and SREBP-1c increased in the OW-OB group, according with what described in liver and adipose tissue of humans with obesity. This altered expression pattern was related to increased adiposity and early signs of metabolic impairment. Greater weight loss and/or metabolic improvement as result of the intervention was related to lower CPT1A, FASN and SREBP-1c gene expression in an adjusted linear mixed-effects regression analysis, although no gene expression recovery was observed when considering mean comparisons. Thus, human PBMC reflect lipid metabolism expression profile of energy homeostatic tissues, and early obesity-related alterations in metabolic at-risk subjects. Further studies are needed to understand PBMC usefulness for analysis of metabolic recovery in weigh management programs.
Specific lipid molecular changes leading to type 2 diabetes (T2D) are largely unknown. We assessed lipidome factors associated with future occurrence of T2D in a population at high cardiovascular ...risk.
We conducted a case-cohort study nested within the PREDIMED trial, with 250 incident T2D cases diagnosed during 3.8 years of median follow-up, and a random sample of 692 participants (639 noncases and 53 overlapping cases) without T2D at baseline. We repeatedly measured 207 plasma known lipid metabolites at baseline and after 1 year of follow-up. We built combined factors of lipid species using principal component analysis and assessed the association between these lipid factors (or their 1-year changes) and T2D incidence.
Baseline lysophosphatidylcholines and lysophosphatidylethanolamines (lysophospholipids LPs), phosphatidylcholine-plasmalogens (PC-PLs), sphingomyelins (SMs), and cholesterol esters (CEs) were inversely associated with risk of T2D (multivariable-adjusted
for linear trend ≤0.001 for all). Baseline triacylglycerols (TAGs), diacylglycerols (DAGs), and phosphatidylethanolamines (PEs) were positively associated with T2D risk (multivariable-adjusted
for linear trend <0.001 for all). One-year changes in these lipids showed associations in similar directions but were not significant after adjustment for baseline levels. TAGs with odd-chain fatty acids showed inverse associations with T2D after adjusting for total TAGs.
Two plasma lipid profiles made up of different lipid classes were found to be associated with T2D in participants at high cardiovascular risk. A profile including LPs, PC-PLs, SMs, and CEs was associated with lower T2D risk. Another profile composed of TAGs, DAGs, and PEs was associated with higher T2D risk.
Daily eating/fasting cycles synchronise circadian peripheral clocks, involved in the regulation of the cardiovascular system. However, the associations of daily meal and fasting timing with ...cardiovascular disease (CVD) incidence remain unclear. We used data from 103,389 adults in the NutriNet-Santé study. Meal timing and number of eating occasions were estimated from repeated 24 h dietary records. We built multivariable Cox proportional-hazards models to examine their association with the risk of CVD, coronary heart disease and cerebrovascular disease. In this study, having a later first meal (later than 9AM compared to earlier than 8AM) and last meal of the day (later than 9PM compared to earlier than 8PM) was associated with a higher risk of cardiovascular outcomes, especially among women. Our results suggest a potential benefit of adopting earlier eating timing patterns, and coupling a longer nighttime fasting period with an early last meal, rather than breakfast skipping, in CVD prevention.
A higher adherence to a Mediterranean diet has been shown to be protective against obesity in adults, but the evidence is still inconclusive in children at early ages. Our objective was to explore ...the association between adherence to Mediterranean Diet at the age of 4 and the prevalence of overweight, obesity, and abdominal obesity at 4 years of age, and incidence at the age of 8.
We analyzed data from children of the INMA cohort study who attended follow-up visits at age 4 and 8 years (n = 1801 and n = 1527, respectively). Diet was assessed at the age of 4 using a validated food frequency questionnaire. The adherence to MD was evaluated by the relative Mediterranean diet (rMED) score, and categorized as low (0-6), medium (7-10), and high (11-16). Overweight and obesity were defined according to the age-sex specific BMI cutoffs proposed by the International Obesity Task Force, and abdominal obesity as waist circumference >90th percentile. We used Poisson regression models to estimate prevalence ratios at 4 years of age, and Cox regression analysis to estimate hazard ratios (HR) from 4-8 years of age.
In cross-sectional analyses at the age of 4 no association was observed between adherence to MD and overweight, obesity, or abdominal obesity. In longitudinal analyses, a high adherence to MD at age 4 was associated with lower incidence of overweight (HR = 0.38; 95% CI: 0.21-0.67; p = 0.001), obesity (HR = 0.16; 95% CI: 0.05-0.53; p = 0.002), and abdominal obesity (HR = 0.30; 95% CI: 0.12-0.73; p = 0.008) at the age of 8.
This study shows that a high adherence to MD at the age of 4 is associated with a lower risk of developing overweight, obesity, and abdominal obesity at age 8. If these results are confirmed by other studies, MD may be recommended to reduce the incidence of obesity at early ages.
Glycolysis/gluconeogenesis and tricarboxylic acid (TCA) cycle metabolites have been associated with type 2 diabetes (T2D). However, the associations of these metabolites with T2D incidence and the ...potential effect of dietary interventions remain unclear.
We aimed to evaluate the association of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with insulin resistance and T2D incidence, and the potential modifying effect of Mediterranean diet (MedDiet) interventions.
We included 251 incident T2D cases and 638 noncases in a nested case-cohort study within the PREDIMED Study during median follow-up of 3.8 y. Participants were allocated to MedDiet + extra-virgin olive oil, MedDiet + nuts, or control diet. Plasma metabolites were measured using a targeted approach by LC–tandem MS. We tested the associations of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with subsequent T2D risk using weighted Cox regression models and adjusting for potential confounders. We designed a weighted score combining all these metabolites and applying the leave-one-out cross-validation approach.
Baseline circulating concentrations of hexose monophosphate, pyruvate, lactate, alanine, glycerol-3 phosphate, and isocitrate were significantly associated with higher T2D risk (17–44% higher risk for each 1-SD increment). The weighted score including all metabolites was associated with a 30% (95% CI: 1.12, 1.51) higher relative risk of T2D for each 1-SD increment. Baseline lactate and alanine were associated with baseline and 1-y changes of homeostasis model assessment of insulin resistance. One-year increases in most metabolites and in the weighted score were associated with higher relative risk of T2D after 1 y of follow-up. Lower risks were observed in the MedDiet groups than in the control group although no significant interactions were found after adjusting for multiple comparisons.
We identified a panel of glycolysis/gluconeogenesis-related metabolites that was significantly associated with T2D risk in a Mediterranean population at high cardiovascular disease risk. A MedDiet could counteract the detrimental effects of these metabolites. This trial was registered at controlled-trials.com as ISRCTN35739639.
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