Search

Background Red meat is a nutrient‐dense source of protein fundamental for older adults; however, red meat is also high in detrimental components, including saturated fat. It is unclear whether habitual red meat consumption is associated with risk of frailty. This study aimed to examine the prospective association between the consumption of total, unprocessed, and processed red meat and the risk of frailty in older adults. Methods We analysed data from 85 871 women aged ≥60 participating in the Nurses' Health Study. Consumption of total, unprocessed, and processed red meat was obtained from repeated food frequency questionnaires administered between 1980 and 2010. Frailty was defined as having at least three of the following five criteria from the FRAIL scale: fatigue, low strength, reduced aerobic capacity, having ≥5 chronic illnesses, and unintentional weight loss ≥5%. The occurrence of frailty was assessed every four years from 1992 to 2014. Results During 22 years of follow‐up (median follow‐up 14 years), we identified 13 279 incident cases of frailty. Women with a higher intake of red meat showed an increased risk of frailty after adjustment for lifestyle factors, medication use, and dietary factors. The relative risk (95% confidence interval) for one serving/day increment in consumption was 1.13 (1.08, 1.18) for total red meat, 1.08 (1.02, 1.15) for unprocessed red meat, and 1.26 (1.15, 1.39) for processed red meat. When each component of the frailty syndrome was individually examined, each of them was positively associated with total red meat consumption, except for the weight loss criterion. Replacing one serving/day of unprocessed red meat with other protein sources was associated with significantly lower risk of frailty; the risk reduction estimates were 22% for fish and 14% for nuts, while for replacement of processed red meat, the percentages were 33% for fish, 26% for nuts, 13% for legumes, and 16% for low‐fat dairy. Conclusions Habitual consumption of unprocessed and processed red meat was associated with a higher risk of frailty. Replacement of red meat by other protein sources might reduce the risk of frailty. These findings are in line with dietary guidelines promoting diets that emphasize plant‐based sources of protein.

Background and ObjectivesWomen have higher lifetime risk of stroke than men, and metabolic factors seem more strongly associated with stroke for women than men. However, few studies in either men or women have evaluated metabolomic profiles and incident stroke.MethodsWe applied liquid chromatography–tandem mass spectrometry to measure 519 plasma metabolites in a discovery set of women in the Nurses' Health Study (NHS; 454 incident ischemic stroke cases, 454 controls) with validation in 2 independent, prospective cohorts: Prevención con Dieta Mediterránea (PREDIMED; 118 stroke cases, 791 controls) and Nurses' Health Study 2 (NHS2; 49 ischemic stroke cases, 49 controls). We applied logistic regression models with stroke as the outcome to adjust for multiple risk factors; the false discovery rate was controlled through the q value method.ResultsTwenty-three metabolites were significantly associated with incident stroke in NHS after adjustment for traditional risk factors (q < 0.05). Of these, 14 metabolites were available in PREDIMED and 3 were significantly associated with incident stroke: methionine sulfoxide, N6-acetyllysine, and sucrose (q < 0.05). In NHS2, one of the 23 metabolites (glucuronate) was significantly associated with incident stroke (q < 0.05). For all 4 metabolites, higher levels were associated with increased risk. These 4 metabolites were used to create a stroke metabolite score (SMS) in the NHS and tested in PREDIMED. Per unit of standard deviation of SMS, the odds ratio for incident stroke was 4.12 (95% confidence interval [CI] 2.26–7.51) in PREDIMED, after adjustment for risk factors. In PREDIMED, the area under the receiver operating characteristic curve (AUC) for the model including SMS and traditional risk factors was 0.70 (95% CI 0.75–0.79) vs the AUC for the model including the traditional risk factors only of 0.65 (95% CI 0.70–0.75), corresponding to a 5% improvement in risk prediction with SMS (p < 0.005).DiscussionMetabolites associated with stroke included 2 amino acids, a carboxylic acid, and sucrose. A composite SMS including these metabolites was associated with ischemic stroke and showed improvement in risk prediction beyond traditional risk factors.Classification of EvidenceThis study provides Class II evidence that a SMS accurately predicts incident ischemic stroke risk.

Context The interrelationships among the gut microbiome, the Mediterranean diet (MedDiet), and a clinical endpoint of diabetes is unknown. Objective To identify gut microbial features of a MedDiet and examine whether the association between MedDiet and diabetes varies across individuals with different gut microbial profiles. Methods This study included 543 diabetic, 805 prediabetic, and 394 normoglycemic participants from a cohort study of USA Hispanic/Latino men and women. Fecal samples were profiled using 16S rRNA gene sequencing. Adherence to MedDiet was evaluated by an index based on 2 24-hour dietary recalls. Results A greater MedDiet adherence was associated with higher abundances of major dietary fiber metabolizers (e.g., Faecalibacterium prausnitzii, false-discovery-rate–adjusted P [q] = 0.01), and lower abundances of biochemical specialists (e.g., Parabacteroides, q = 0.04). The gut microbiomes of participants with greater MedDiet adherence were enriched for functions involved in dietary fiber degradation but depleted for those related to sulfur reduction and lactose and galactose degradation. The associations between MedDiet adherence and diabetes prevalence were significantly stronger among participants with depleted abundance of Prevotella (pinteraction = 0.03 for diabetes, 0.02 for prediabetes/diabetes, and 0.02 for prediabetes). A 1-SD deviation increment in the MedDiet index was associated with 24% (odds ratio [OR] 0.76; 95% CI, 0.59-0.98) and 7% (OR 0.93; 95% CI, 0.72-1.20) lower odds of diabetes in Prevotella noncarriers and carriers, respectively. Conclusion Adherence to MedDiet is associated with diverse gut microorganisms and microbial functions. The inverse association between the MedDiet and diabetes prevalence varies significantly depending on gut microbial composition.

Summary Background & aims Unrestrained eating behavior has been thought to be a proxy for diet frequency, timing, and caloric intake. We investigated the association of unrestrained eating with mortality risk in the Nurses’ Health Study prospectively. Methods During follow-up (1994–2016), 21,953 deaths were documented among 63,999 eligible participants in analyses of eating anything at any time, 22,120 deaths were documented among 65,839 participants in analyses of no concern with figure change. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Results Eating anything at any time was associated with an increased mortality from cancer (overall HR, 95%CI: 1.07, 1.00–1.13; driven by gastrointestinal tract cancer: 1.30, 1.10–1.54) and respiratory disease (1.16, 1.05–1.29), and decreased cardiovascular disease-specific mortality (0.92, 0.86–0.99), compared to those without this behavior; however, no association was observed between this behavior and all-cause mortality (1.02, 0.99–1.05). Women who reported having no concern with figure change experienced higher risk of mortality from all-cause (1.08, 1.05–1.11), cancer (1.08, 1.02–1.14), and respiratory disease (1.18, 1.08–1.30), compared to those not reporting this behavior. Their combined effect was associated with a higher all-cause (1.09, 1.04–1.14), cancer-specific (overall: 1.18, 1.09–1.28; gastrointestinal tract cancer: 1.36, 1.08–1.71; lung cancer: 1.09; 1.04–1.14), and respiratory disease-specific (1.30, 1.13–1.50) mortality, and was inversely associated with cardiovascular disease-specific mortality (0.88, 0.80–0.98), compared to those exhibiting the opposite. Conclusions Unrestrained eating was associated with increased risk of all-cause, cancer-specific (particularly for gastrointestinal tract cancer and lung cancer), and respiratory disease-specific mortality, and decreased risk of cardiovascular disease-specific mortality.

Background Unrestrained eating behavior, as a potential proxy for diet frequency, timing, and caloric intake, has been questioned as a plausible risk factor for digestive system cancers, but epidemiological evidence remains sparse. Objectives We investigated prospectively the associations between unrestrained eating behavior and digestive system cancer risk. Methods Participants in the Nurses' Health Study who were free of cancer and reported dietary information in 1994 were followed for ≤18 y. Cox models were used to estimate HRs and 95% CIs for unrestrained eating (eating anything at any time, no concern with figure change, or both) and risk of digestive system cancers. Results During follow-up, 2064 digestive system cancer cases were documented among 70,450 eligible participants in analyses of eating anything at any time, In total, 2081 digestive system cancer cases were documented among 72,468 eligible participants in analyses of no concern with figure change. In fully adjusted analyses, women with the behavior of eating anything at any time had a higher risk of overall digestive system cancer (HR: 1.22; 95% CI: 1.10, 1.35), overall gastrointestinal tract cancer ((HR: 1.33; 95% CI: 1.18, 1.50), buccal cavity and pharynx cancer (HR: 1.50; 95% CI: 1.02, 2.21), esophageal cancer (HR: 1.62; 95% CI: 1.01, 2.62), small intestine cancer (HR: 1.92; 95% CI: 1.02,3. 59), and colorectal cancer (HR: 1.20; 95% CI: 1.04, 1.38), and a non-statistically significant increased risk of stomach cancer (HR: 1.54; 95% CI: 0.96,2.48), compared with women without this behavior. No statistically significant association was observed for pancreatic cancer and liver and gallbladder cancer. The combined effect of eating anything at any time and having no concern with figure change was associated with a significantly increased risk of overall digestive system cancer (HR: 1.27; 95% CI: 1.10, 1.46), overall gastrointestinal tract cancer (HR: 1.45; 95% CI: 1.23, 1.71), and colorectal cancer (HR: 1.34; 95% CI: 1.11, 1.63), compared with women exhibiting the opposite. Conclusions Unrestrained eating behavior was independently associated with increased risk of gastrointestinal tract cancers. The potential importance of unrestrained eating behavior modification in preventing gastrointestinal tract cancers should be noted.

The association between religion, spirituality, and body weight is controversial, given the methodological limitations of existing studies. Using the Nurses’ Health Study II cohort, follow-up occurred from 2001 to 2015, with up to 35,547 participants assessed for the religious or spiritual coping and religious service attendance analyses. Cox regression and generalized estimating equations evaluated associations with obesity and weight change, respectively. Religious or spiritual coping and religious service attendance had little evidence of an association with obesity. Compared with not using religious or spiritual coping at all, the fully adjusted hazard ratios (HRs) were minimally different across categories: a little bit (HR = 1.05, 95% CI: 0.92–1.18), a medium amount (HR = 1.09, 95% CI: 0.96–1.24), and a lot (HR = 1.10; 95% CI: 0.96–1.25) (Ptrend = 0.17). Compared with participants who never or almost never attend religious meetings or services, there was little evidence of an association between those attending less than once/month (HR = 1.08, 95% CI: 0.97–1.10), 1–3 times/month (HR = 1.01, 95% CI: 0.90–1.13), once/week (HR = 0.92, 95% CI: 0.83–1.02), and more than once/week (HR = 0.94, 95% CI: 0.82–1.07) (Ptrend = 0.06). Findings were similar for weight change. There was no significant association between religious or spiritual coping, religious service attendance, obesity, and weight change. While religion and spirituality are prominent in American society, they are not important psychosocial factors influencing body weight in this sample.

Background We have developed a simple and globally applicable tool, the Global Diet Quality Score (GDQS), to measure diet quality. Objectives To test the utility of the GDQS, we examined the associations of the GDQS with weight change and risk of obesity in US women. Methods Health, lifestyle, and diet information were collected from women (n = 68,336) in the Nurses’ Health Study II (aged 27–44 y in 1991) through repeated questionnaires (1991–2015). The GDQS has 25 food groups (maximum = 49 points) and scoring higher points reflects a healthier diet. The association between GDQS change in 4-y intervals and concurrent weight change was computed with linear models adjusted for confounders. Results Mean ± SD weight gain across 4-y periods was 1.68 ± 6.26 kg. A >5-point improvement in GDQS was associated with −1.13 kg (95% CI: −1.19, −0.77 kg) weight gain compared with a score change of 5-point score decrease was associated with 1.13 kg (95% CI: 1.04, 1.22 kg) more weight gain in women aged 5-point increase and 1.32 (95% CI: 1.26, 1.37) for a >5-point decrease. Risk of obesity did not differ by age. Compared with other diet quality scores, the Alternate Healthy Eating Index-2010 had somewhat stronger associations than the GDQS (P

Background The double burdens of under- and overnutrition are changing the health of individuals and the economic and disease burdens in China. Poor diet plays an important role; however, a valid and easily operationalized metric that could capture the full range of characteristics of the diet that are relevant to both under- and overnutrition is lacking in China. Objectives We aimed to examine the application of the Global Diet Quality Score (GDQS) to evaluate nutrient inadequacy and metabolic syndrome in different demographic groups of Chinese adults. Methods A total of 35,146 individuals (men 14,978, women 20,168) aged >18 y from the 2010–2012 China National Nutrition and Health Survey were included. We scored the GDQS using average intakes of 25 food groups from 3 d of 24-h dietary recalls. Double burden was defined as coexisting metabolic syndrome and nutrient inadequacy. Results Diet quality assessed by GDQS was significantly higher in urban than in rural residents (20.8 compared with 18.7), and increased with both educational level and household income (P-trends < 0.0001). A higher GDQS score was inversely associated with metabolic syndrome and nutrient inadequacy, or both (P-trends < 0.0001): multivariate adjusted ORs comparing extreme quintiles of GDQS were 0.79 (95% CI: 0.69, 0.91) for metabolic syndrome, 0.17 (95% CI: 0.14, 0.20) for nutrient inadequacy, and 0.59 (95% CI: 0.50, 0.69) for the double burden. These associations were consistent across different household income levels (P-interaction = 0.26), suggestively stronger in younger (

Background We have developed a diet quality metric intended for global use. To assess its utility in high-income settings, an evaluation of its ability to predict chronic disease is needed. Objectives We aimed to prospectively examine the ability of the Global Diet Quality Score (GDQS) to predict the risk of type 2 diabetes in the United States, examine potential differences of association by age, and compare the GDQS with other diet quality scores. Methods Health, lifestyle, and diet information was collected from women (n = 88,520) in the Nurses’ Health Study II aged 27–44 y at baseline through repeated questionnaires between 1991 and 2017. The overall GDQS consists of 25 food groups. Points are awarded for higher intake of healthy groups and lower intake of unhealthy groups (maximum of 49 points). Multivariable HRs were computed for confirmed type 2 diabetes using proportional hazards models. We also compared the GDQS with the Minimum Diet Diversity score for Women (MDD-W) and the Alternate Healthy Eating Index-2010 (AHEI-2010). Results We ascertained 6305 incident cases of type 2 diabetes during follow-up. We observed a lower risk of diabetes with higher GDQS; the multivariable HR comparing extreme quintiles of the GDQS was 0.83 (95% CI: 0.76, 0.91; P-trend

Background: Emerging evidence suggests beneficial impacts of plant-based diets on glucose metabolism among generally healthy individuals. Whether adherence to these diets is related to risk of gestational diabetes mellitus (GDM) is unknown. Objectives: We aimed to examine associations between plant-based diets and GDM in a large prospective study. Methods: We included 14,926 women from the Nurses' Health Study II (1991-2001), who reported ≥1 singleton pregnancy and without previous GDM before the index pregnancy. Prepregnancy adherence to plant-based diets was measured by an overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI) as assessed by FFQs every 4 y. Incident first-Time GDM was ascertained from a self-reported physician diagnosis, which was previously validated by review of medical records. We used log-binomial models with generalized estimating equations to calculate RRs and 95% CIs for associations of PDIs with GDM. Results: We documented 846 incident GDM cases over the 10-y follow-up among 20,707 pregnancies. Greater adherence to the PDI and hPDI was associated with lower GDM risk. For the PDI, the multivariable-Adjusted RR (95% CI) comparing the highest and lowest quintiles (Q5 compared with Q1) was 0.70 (0.56, 0.87) (Ptrend = 0.0004), and for each 10-point increment was 0.80 (0.71, 0.90). For the hPDI, the RR (95% CI) of Q5 compared with Q1 was 0.75 (0.59, 0.94) (Ptrend = 0.009) and for each 10-point increment was 0.86 (0.77, 0.95). After further adjustment for prepregnancy BMI, the associations were attenuated but remained significant: for the PDI, the RR (95% CI) for each 10-point increment was 0.89 (0.79, 1.00) and the corresponding RR (95% CI) was 0.89 (0.80, 0.99) for the hPDI. The uPDI was not associated with GDM. Conclusions: Our study suggests that greater prepregnancy adherence to a healthful plant-based diet was associated with lower risk of GDM, whereas an unhealthful plant-based diet was not related to GDM risk.

Background: Plant-based diets have been associated with lower risk of various diseases, including type 2 diabetes, cardiovascular disease, and other cardiometabolic risk factors. However, the association between plant-based diet quality and breast cancer remains unclear. Methods: We prospectively followed 76,690 women from the Nurses' Health Study (NHS, 1984–2016) and 93,295 women from the NHSII (1991–2017). Adherence to an overall plant-based diet index (PDI), a healthful PDI (hPDI), and an unhealthful PDI (uPDI) was assessed using previously developed indices. Cox proportional hazards models were used to estimate HR and 95% confidence intervals (CI) for incident invasive breast cancer. Results: Over 4,841,083 person-years of follow-up, we documented 12,482 incident invasive breast cancer cases. Women with greater adherence to PDI and hPDI were at modestly lower risk of breast cancer [(HRQ5 vs. Q1, 0.89; 95% CI, 0.84–0.95); (HRQ5 vs. Q1, 0.89; 95% CI, 0.83–0.94)]. We observed significant heterogeneity by estrogen receptor (ER) status, with the strongest inverse association between hPDI and breast cancer observed with ER-negative tumors [HRQ5 vs. Q1, 0.77; 95% CI, 0.65–0.90; Ptrend < 0.01]. We also found an inverse association between extreme quintiles of healthy plant foods and ER-negative breast cancer [HR, 0.74; 95% CI, 0.61–0.88; Ptrend < 0.01]. Conclusions: This study provides evidence that adherence to a healthful plant-based diet may reduce the risk of breast cancer, especially those that are more likely to be aggressive tumors. Impact: This is the first prospective study investigating the relation between healthful and unhealthful plant-based dietary indices and risk of total and subtype-specific breast cancer.

Objective To examine the association of long-term weight change with RA risk in a large prospective cohort study. Methods The Nurses’ Health Study II started in 1989 (baseline); after exclusions, we studied 108 505 women 25–42 years old without RA. Incident RA was reported by participants and confirmed by medical record review. Body weight was reported biennially through 2015. We investigated two time-varying exposures: weight changes from baseline and from age 18; change was divided into five categories. We used a marginal structural model approach to account for time-varying weight change and covariates. Results Over 2 583 266 person-years, with a median follow-up time of 25.3 years, 541 women developed RA. Compared with women with stable weight from baseline, weight change was significantly associated with increased RA risk [weight gain 2–2 kg: RR = 2.05 (95% CI 1.28, 3.28)]. Weight gain of 10 kg or more from age 18 compared with stable weight was also associated with increased RA risk [10–< 20 kg: RR = 2.12 (95% CI 1.37, 3.27), ≥20 kg: RR = 2.31 (95% CI 1.50, 3.56)]. Consistent findings were observed for seropositive and seronegative RA. Conclusion Long-term weight gain was strongly associated with increased RA risk in women, with weight gain of ≥20 kg associated with more than a three-fold increased RA risk. Maintenance of healthy weight may be a strategy to prevent or delay RA.

Summary In this study, we integrated large-scale GWAS summary data and used the predicted transcriptome-wide association study method to discover novel genes associated with osteoporosis. We identified 204 candidate genes, which provide novel clues for understanding the genetic mechanism of osteoporosis and indicate potential therapeutic targets. Introduction Osteoporosis is a highly polygenetic disease characterized by low bone mass and deterioration of the bone microarchitecture. Our objective was to discover novel candidate genes associated with osteoporosis. Methods To identify potential causal genes of the associated loci, we investigated trait-gene expression associations using the transcriptome-wide association study (TWAS) method. This method directly imputes gene expression effects from genome-wide association study (GWAS) data using a statistical prediction model trained on GTEx reference transcriptome data. We then performed a colocalization analysis to evaluate the posterior probability of biological patterns: associations characterized by a single causal variant or multiple distinct causal variants. Finally, a functional enrichment analysis of gene sets was performed using the VarElect and CluePedia tools, which assess the causal relationships between genes and a disease and search for potential gene’s functional pathways. The osteoporosis-associated genes were further confirmed based on the differentially expressed genes profiled from mRNA expression data of bone tissue. Results Our analysis identified 204 candidate genes, including 154 genes that have been previously associated with osteoporosis, 50 genes that have not been previously discovered. A biological function analysis found that 20 of the candidate genes were directly associated with osteoporosis. Further analysis of multiple gene expression profiles showed that 15 genes were differentially expressed in patients with osteoporosis. Among these, SLC11A2, MAP2K5, NFATC4, and HSP90B1 were enriched in four pathways, namely, mineral absorption pathway, MAPK signaling pathway, Wnt signaling pathway, and PI3K-Akt signaling pathway, which indicates a causal relationship with the occurrence of osteoporosis. Conclusions We demonstrated that transcriptome fine-mapping identifies more osteoporosis-related genes and provides key insight into the development of novel targeted therapeutics for the treatment of osteoporosis. Supplementary Information The online version contains supplementary material available at 10.1007/s00198-021-06024-z.

Shangzhi Gao,1 Corbin Quick,2 Marta Guasch-Ferre,3 Zhu Zhuo,2 John M Hutchinson,2 Li Su,1 Frank Hu,3 Xihong Lin,2 David Christiani1,4 1Environmental Health, Harvard University T H Chan School of Public Health, Boston, MA, USA; 2Biostatistics, Harvard University T H Chan School of Public Health, Boston, MA, USA; 3Nutrition, Harvard University T H Chan School of Public Health, Boston, MA, USA; 4Pulmonary and Critical Care Division, Department of Medicine, MA General Hospital, Boston, Massachusetts, USACorrespondence: David ChristianiEnvironmental Health, Harvard University T H Chan School of Public Health, Boston, MA, 02115, USAEmail dchris@hsph.harvard.eduIntroduction: Human metabolism and inflammation are closely related modulators of homeostasis and immunity. Metabolic profiling is a useful tool to understand the association between metabolism and inflammation at a systemic level.Objective: To investigate the longitudinal associations between the concentration of plasma metabolites and biomarkers related to inflammation and oxidative stress.Methods: We conducted a repeated cross-sectional analysis consisting of 8 short-term panels that included 88 healthy adult male welders in Massachusetts, USA. In each panel, we collected 1– 6 repeated measurements of blood and urine. We used a human vascular injury panel assay and custom cytokine/chemokine assay to quantify inflammatory biomarker plasma levels, liquid chromatography-mass spectrometry to quantify the concentrations of 665 plasma metabolites, and a competitive enzyme-linked immunoassay to quantify urinary 8-OHdG and 8-isoprostane levels. We used linear mixed effects models to estimate the longitudinal association between each inflammatory and oxidative stress biomarker and each metabolite.Results: At a 5% FDR threshold, we detected ≥ 1metabolite association for 8 unique inflammatory and oxidative stress biomarkers: urinary 8-isoprostane, plasma C-reactive protein (CRP), serum amyloid A (SAA), intercellular adhesion molecule 1, circulating vascular cell adhesion molecule-1, interleukin 8 (IL-8), interleukin 10 (IL-10) and vascular endothelial growth factor. Specifically, 3 metabolites in the androgenic steroids pathway were negatively associated with SAA; 3 dihydrosphingomyelins metabolites were positively associated with 1 or more of CRP, SAA, IL-8 and IL-10; 4 metabolites in acyl choline metabolism pathways were negatively associated with IL-8; 7 lysophospholipid metabolites were negatively associated with 1 or more of CRP, SAA and IL-8; 4 sphingomyelins were positively associated with CRP and/or SAA; and 10 metabolites in the xanthine pathway were positively associated with urinary 8-isoprostane.Conclusion: We found that metabolites in phospholipid groups had strong associations with multiple inflammatory biomarkers, especially CRP, SAA and IL-8. The mechanism of these associations warrants further investigation.Keywords: metabolism, inflammation, phospholipids, metals, particulates, metabolomics, occupational health

Human microbiome science has advanced rapidly and reached a scale at which basic biology, clinical translation and population health are increasingly integrated. It is thus now possible for public health researchers, practitioners and policymakers to take specific action leveraging current and future microbiome-based opportunities and best practices. Here we provide an outline of considerations for research, education, interpretation and scientific communication concerning the human microbiome and public health. This includes guidelines for population-scale microbiome study design; necessary physical platforms and analysis methods; integration into public health areas such as epidemiology, nutrition, chronic disease, and global and environmental health; entrepreneurship and technology transfer; and educational curricula. Particularly in the near future, there are both opportunities for the incorporation of microbiome-based technologies into public health practice, and a growing need for policymaking and regulation around related areas such as prebiotic and probiotic supplements, novel live-cell therapies and fecal microbiota transplants.

To address how the microbiome might modify the interaction between diet and cardiometabolic health, we analyzed longitudinal microbiome data from 307 male participants in the Health Professionals Follow-Up Study, together with long-term dietary information and measurements of biomarkers of glucose homeostasis, lipid metabolism and inflammation from blood samples. Here, we demonstrate that a healthy Mediterranean-style dietary pattern is associated with specific functional and taxonomic components of the gut microbiome, and that its protective associations with cardiometabolic health vary depending on microbial composition. In particular, the protective association between adherence to the Mediterranean diet and cardiometabolic disease risk was significantly stronger among participants with decreased abundance of Prevotella copri. Our findings advance the concept of precision nutrition and have the potential to inform more effective and precise dietary approaches for the prevention of cardiometabolic disease mediated through alterations in the gut microbiome. The beneficial effects of a Mediterranean diet on cardiometabolic health are associated with specific changes in the gut microbiome, suggesting a personalized approach towards cardiometabolic disease prevention.

BACKGROUND: Walnut consumption is associated with lower risk of type 2 diabetes (T2D) and cardiovascular disease (CVD). However, it is unknown whether plasma metabolites related to walnut consumption are also associated with lower risk of cardiometabolic diseases. OBJECTIVES: The study aimed to identify plasma metabolites associated with walnut consumption and evaluate the prospective associations between the identified profile and risk of T2D and CVD. METHODS: The discovery population included 1833 participants at high cardiovascular risk from the PREvención con DIeta MEDiterránea (PREDIMED) study with available metabolomics data at baseline. The study population included 57% women (baseline mean BMI (in kg/m(2)): 29.9; mean age: 67 y). A total of 1522 participants also had available metabolomics data at year 1 and were used as the internal validation population. Plasma metabolomics analyses were performed using LC-MS. Cross-sectional associations between 385 known metabolites and walnut consumption were assessed using elastic net continuous regression analysis. A 10-cross-validation (CV) procedure was used, and Pearson correlation coefficients were assessed between metabolite weighted models and self-reported walnut consumption in each pair of training–validation data sets within the discovery population. We further estimated the prospective associations between the identified metabolite profile and incident T2D and CVD using multivariable Cox regression models. RESULTS: A total of 19 metabolites were significantly associated with walnut consumption, including lipids, purines, acylcarnitines, and amino acids. Ten-CV Pearson correlation coefficients between self-reported walnut consumption and the plasma metabolite profile were 0.16 (95% CI: 0.11, 0.20) in the discovery population and 0.15 (95% CI: 0.10, 0.20) in the validation population. The metabolite profile was inversely associated with T2D incidence (HR per 1 SD: 0.83; 95% CI: 0.71, 0.97; P = 0.02). For CVD incidence, the HR per 1-SD was 0.71 (95% CI: 0.60, 0.85; P

BACKGROUND: Dietary recommendations and policies should be guided by rigorous systematic reviews. Reviews that are of poor methodological quality may be ineffective or misleading. Most of the evidence in nutrition comes from nonrandomized studies of nutritional exposures (usually referred to as nutritional epidemiology studies), but to date methodological evaluations of the quality of systematic reviews of such studies have been sparse and inconsistent. OBJECTIVES: We aimed to investigate the quality of recently published systematic reviews and meta-analyses of nutritional epidemiology studies and to propose guidance addressing major limitations. METHODS: We searched MEDLINE (January 2018–August 2019), EMBASE (January 2018–August 2019), and the Cochrane Database of Systematic Reviews (January 2018–February 2019) for systematic reviews of nutritional epidemiology studies. We included a random sample of 150 reviews. RESULTS: Most reviews were published by authors from Asia (n = 49; 32.7%) or Europe (n = 43; 28.7%) and investigated foods or beverages (n = 60; 40.0%) and cancer morbidity and mortality (n = 54; 36%). Reviews often had important limitations: less than one-quarter (n = 30; 20.0%) reported preregistration of a protocol and almost one-third (n = 42; 28.0%) did not report a replicable search strategy. Suboptimal practices and errors in the synthesis of results were common: one-quarter of meta-analyses (n = 30; 26.1%) selected the meta-analytic model based on statistical indicators of heterogeneity and almost half of meta-analyses (n = 50; 43.5%) did not consider dose–response associations even when it was appropriate to do so. Only 16 (10.7%) reviews used an established system to evaluate the certainty of evidence. CONCLUSIONS: Systematic reviews of nutritional epidemiology studies often have serious limitations. Authors can improve future reviews by involving statisticians, methodologists, and researchers with substantive knowledge in the specific area of nutrition being studied and using a rigorous and transparent system to evaluate the certainty of evidence.

Exhaled carbon monoxide (COex) level has been proposed as a noninvasive and easily-obtainable cardiovascular risk marker, however, with limited prospective evidence, and its association with stroke risk has been rarely explored. Measurements of COex were performed during 2004–2008 baseline examinations in the China Kadoorie Biobank study among 512,891 adults aged 30–79 years from 10 diverse study areas. After excluding participants with baseline cardiopulmonary diseases, stroke and cancer, 178,485 men and 267,202 women remained. Cox regression yielded hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of cardio-cerebral-vascular disease (CCVD) associated with COex levels, with sequential addition of adjustment for proxy variables for CO exposure, including study area indexing ambient CO variations at large, and smoking and solid fuel use, apart from adjusting for traditional cardiovascular risk factors. During 7-year follow-up, we documented 1744 and 1430 major coronary events (myocardial infarction plus fatal ischemic heart disease), 8849 and 10,922 ischemic strokes, and 2492 and 2363 hemorrhagic strokes among men and women, respectively. The HRs with 95% CIs comparing the highest with lowest COex quintile were 2.15 [1.72, 2.69] for major coronary events, 1.65 [1.50, 1.80] for ischemic stroke, and 1.35 [1.13, 1.61] for hemorrhagic stroke among men, while among women higher associated risk was only observed for major coronary events (1.64 [1.35, 2.00]) and ischemic stroke (1.87 [1.73, 2.01]). The elevated risks were consistent when COex level was over 3 ppm. However, these associations were all attenuated until null by sequential addition of stratification by study areas, and adjustments of smoking and solid fuel use. Nevertheless, the association with ischemic stroke was maintained among the subgroup of male smokers even with adjustment for the depth and amount of cigarette smoking (HR [95% CI]: 1.37 [1.06, 1.77]), while a negative association with hemorrhagic stroke also appeared within this subgroup. Higher COex level (over 3 ppm) was associated with elevated risk of ischemic CCVD, but not independently of CO exposure. Our finding suggests that, though not an independent risk factor, COex could potentially provide a cost-effective biomarker for ischemic cardio-cerebral-vascular risk, given that CO exposure is ubiquitous.

Background and aim The aim of this study was to assess the association between body shape trajectories and all-cause mortality in a Mediterranean cohort. Methods and results Using a group-based modeling approach to fit body shape trajectories from the age of 5–40 years, among 11,423 participants from the Spanish SUN cohort, we assessed the subsequent risk of all-cause mortality. To create the trajectories, we used a censored normal model as a polynomial function of age. Cox regression models adjusted for sex, age, years of university education, marital status, smoking status, package-years of smoking, and recruitment period were used to estimate the hazard ratios (HR) for mortality according to each assigned trajectory. Overall, five distinct trajectories were identified: “lean-moderate increase,” “medium-moderate increase,” “medium-stable,” “heavy-medium,” and “heavy-moderate increase.” During 106,657 person-years of follow-up, we observed 240 deaths. Compared with those who maintained a medium body shape in early and middle life (“medium-stable” trajectory), those who were heavy and had a moderate increase (“heavy-moderate increase” trajectory) showed higher mortality risk [HR = 1.91 (95% confidence interval: 1.14–3.21)]. In contrast, participants who were heavy in early life, and then decreased their body shape during early adulthood, and maintained a medium body shape throughout middle adulthood (“heavy-medium”), tend to exhibit lower mortality risk [HR = 0.60 (0.34–1.05)], similarly to those who were lean at childhood and had a moderate increase during adulthood (“lean-moderate increase”) [HR = 0.82 (0.58–1.15)]. Conclusion A moderate increase in body shape among subjects who were already heavy at early life was associated with higher risk of mortality in a Mediterranean cohort of university graduates.

Background Whether egg consumption is associated with the risk of type 2 diabetes (T2D) remains unsettled. Objectives We evaluated the association between egg consumption and T2D risk in 3 large US prospective cohorts, and performed a systematic review and meta-analysis of prospective cohort studies. Methods We followed 82,750 women from the Nurses' Health Study (NHS; 1980-2012), 89,636 women from the NHS II (1991-2017), and 41,412 men from the Health Professionals Follow-up Study (HPFS; 1986-2016) who were free of T2D, cardiovascular disease, and cancer at baseline. Egg consumption was assessed every 2-4 y using a validated FFQ. We used Cox proportional hazard models to estimate HRs and 95% CIs. Results During a total of 5,529,959 person-years of follow-up, we documented 20,514 incident cases of T2D in the NHS, NHS II, and HPFS. In the pooled multivariable model adjusted for updated BMI, lifestyle, and dietary confounders, a 1-egg/d increase was associated with a 14% (95% CI: 7%, 20%) higher T2D risk. In random-effects meta-analysis of 16 prospective cohort studies (589,559 participants; 41,248 incident T2D cases), for each 1 egg/d, the pooled RR of T2D was 1.07 (95% CI: 0.99, 1.15; I2 = 69.8%). There were, however, significant differences by geographic region (P for interaction = 0.01). Each 1 egg/d was associated with higher T2D risk among US studies (RR: 1.18; 95% CI: 1.10, 1.27; I2 = 51.3%), but not among European (RR: 0.99; 95% CI: 0.85, 1.15; I2 = 73.5%) or Asian (RR: 0.82; 95% CI: 0.62, 1.09; I2 = 59.1%) studies. Conclusions Results from the updated meta-analysis show no overall association between moderate egg consumption and risk of T2D. Whether the heterogeneity of the associations among US, European, and Asian cohorts reflects differences in egg consumption habits warrants further investigation.This systematic review was registered at www.crd.york.ac.uk/prospero as CRD42019127860.

Coffee, Caffeine, and Health In many countries, a large majority of adults consume caffeine daily. This review summarizes the evidence about the varied physiological effects of caffeine and coffee ...

BACKGROUND: Plant-based dietary patterns may be related to better cardiovascular profiles. Whether a healthy plant-based dietary index is predictive of future cardiovascular disease (CVD) across people with different genetic susceptibility remains uncertain. OBJECTIVE: We investigated associations of adherence to healthy plant-based diets with the incidence of CVD considering the genetic susceptibility. METHODS: This prospective cohort study included a total of 156,148 adults initially free of CVD and cancer. We calculated a healthful plant-based diet index (healthful-PDI) in which healthy plant foods received positive scores, and less healthy plant foods and animal foods received reverse scores. Genetic risk scores (GRSs) for myocardial infarction (MI) and stroke were calculated to assess interactions between healthful-PDI and GRSs. RESULTS: During 5 y of follow-up, we observed 1812 incident cases of CVD. Higher healthful-PDI was associated with a lower CVD risk [HR per 10-unit increment: 0.87 (95% CI: 0.81, 0.93) after adjusting for demographic, lifestyle, and other dietary factors (model 1); HR 0.90 (0.84, 0.97) after further adjusting for obesity and metabolic factors (model 2)]. The risk of CVD was gradually decreased in association with higher adherence to healthful-PDI, regardless of genetic susceptibility. The inverse associations of healthful-PDI with CVD were consistently observed in people with low GRS-MI [HR 0.85 (95% CI: 0.76, 0.94) in model 1; HR 0.88 (0.79, 0.97) in model 2] and those with high GRS-MI [HR 0.91 (0.82, 0.99) in model 1; HR 0.94 (0.86, 1.04) in model 2], without significant interactions (P(interaction) = 0.59 in model 1; P(interaction) = 0.66 in model 2). Similarly, higher healthful-PDI was related to a lower risk of CVD, regardless of low/high GRS-stroke. CONCLUSION: Adherence to healthy plant-based diets may be associated with a decreased incidence of CVD in the entire population, suggesting that plant-based dietary patterns may modify the risk of CVD, regardless of genetic susceptibility.

Summary Background & aims Drinking water and food are the major sources of strontium in human. Strontium is essential for bone metabolism, while its role in glucose and lipid metabolism is largely unknown. We aimed to investigate the association of strontium, a bone-seeking element, with type 2 diabetes mellitus (T2DM) and impaired glucose regulation (IGR) and to further explore the potential mechanisms. Methods The case-control study included 1448 newly diagnosed T2DM patients, 782 IGR patients, and 2230 matched controls with normal glucose tolerance. Plasma strontium and other plasma minerals were quantified via inductively coupled plasma mass spectrometry. Multivariable logistic regression analysis was used to evaluate the independent associations between plasma strontium and T2DM and IGR. Results Plasma strontium was inversely associated with T2DM and IGR. After adjustment for sociodemographic, lifestyle factors, and multiple plasma metals, the odds ratios (95% confidence intervals) of T2DM and IGR were 0.45 (0.35–0.57) and 0.55 (0.43–0.71), respectively, comparing the highest to the lowest quartile of plasma strontium levels. In spline analysis, the odds of T2DM and IGR decreased remarkably with increasing strontium concentration and followed by a plateau. Additionally, plasma strontium was negatively associated with total cholesterol, low density lipoprotein cholesterol, and lipid peroxidation (plasma malondialdehyde level). Conclusions The current study indicated that higher plasma strontium concentration was associated with lower odds of T2DM and IGR. Further studies are warranted to confirm these findings and to clarify the underlying mechanisms.

BACKGROUND: Current evidence on associations between intakes of linoleic acid (LA), the predominant n–6 (ω-6) fatty acid, and mortality is inconsistent and has not been summarized by a systematic review and meta-analysis. OBJECTIVE: The aim was to perform a systematic review and meta-analysis of prospective cohort studies to examine associations between LA intake and mortality. METHODS: We conducted a comprehensive search of MEDLINE and EMBASE databases through 31 July 2019 for prospective cohort studies reporting associations of LA (assessed by dietary surveys and/or LA concentrations in adipose tissue or blood compartments) with mortality from all causes, cardiovascular disease (CVD), and cancer. Multivariable-adjusted RRs were pooled using random-effects meta-analysis. RESULTS: Thirty-eight studies reporting 44 prospective cohorts were identified; these included 811,069 participants with dietary intake assessment (170,076 all-cause, 50,786 CVD, and 59,684 cancer deaths) and 65,411 participants with biomarker measurements (9758 all-cause, 6492 CVD, and 1719 cancer deaths). Pooled RRs comparing extreme categories of dietary LA intake (high vs low) were 0.87 (95% CI: 0.81, 0.94; I(2) = 67.9%) for total mortality, 0.87 (95% CI: 0.82, 0.92; I(2) = 3.7%) for CVD mortality, and 0.89 (95% CI: 0.85, 0.93; I(2) = 0%) for cancer mortality. Pooled RRs for each SD increment in LA concentrations in adipose tissue/blood compartments were 0.91 (95% CI: 0.87, 0.95; I(2) = 64.1%) for total mortality, 0.89 (95% CI: 0.85, 0.94; I(2) = 28.9%) for CVD mortality, and 0.91 (95% CI: 0.84, 0.98; I(2) = 26.3%) for cancer mortality. Meta-regressions suggested baseline age and dietary assessment methods as potential sources of heterogeneity for the association between LA and total mortality. CONCLUSIONS: In prospective cohort studies, higher LA intake, assessed by dietary surveys or biomarkers, was associated with a modestly lower risk of mortality from all causes, CVD, and cancer. These data support the potential long-term benefits of PUFA intake in lowering the risk of CVD and premature death.

Background De novo lipogenesis (DNL) is the primary metabolic pathway synthesizing fatty acids from carbohydrates, protein, or alcohol. Our aim was to examine associations of in vivo levels of selected fatty acids (16:0, 16:1n7, 18:0, 18:1n9) in DNL with incidence of type 2 diabetes (T2D). Methods and findings Seventeen cohorts from 12 countries (7 from Europe, 7 from the United States, 1 from Australia, 1 from Taiwan; baseline years = 1970–1973 to 2006–2010) conducted harmonized individual-level analyses of associations of DNL-related fatty acids with incident T2D. In total, we evaluated 65,225 participants (mean ages = 52.3–75.5 years; % women = 20.4%–62.3% in 12 cohorts recruiting both sexes) and 15,383 incident cases of T2D over the 9-year follow-up on average. Cohort-specific association of each of 16:0, 16:1n7, 18:0, and 18:1n9 with incident T2D was estimated, adjusted for demographic factors, socioeconomic characteristics, alcohol, smoking, physical activity, dyslipidemia, hypertension, menopausal status, and adiposity. Cohort-specific associations were meta-analyzed with an inverse-variance-weighted approach. Each of the 4 fatty acids positively related to incident T2D. Relative risks (RRs) per cohort-specific range between midpoints of the top and bottom quintiles of fatty acid concentrations were 1.53 (1.41–1.66; p < 0.001) for 16:0, 1.40 (1.33–1.48; p < 0.001) for 16:1n-7, 1.14 (1.05–1.22; p = 0.001) for 18:0, and 1.16 (1.07–1.25; p < 0.001) for 18:1n9. Heterogeneity was seen across cohorts (I2 = 51.1%–73.1% for each fatty acid) but not explained by lipid fractions and global geographical regions. Further adjusted for triglycerides (and 16:0 when appropriate) to evaluate associations independent of overall DNL, the associations remained significant for 16:0, 16:1n7, and 18:0 but were attenuated for 18:1n9 (RR = 1.03, 95% confidence interval (CI) = 0.94–1.13). These findings had limitations in potential reverse causation and residual confounding by imprecisely measured or unmeasured factors. Conclusions Concentrations of fatty acids in the DNL were positively associated with T2D incidence. Our findings support further work to investigate a possible role of DNL and individual fatty acids in the development of T2D., Fumiaki Imamura and colleagues investigate the association between concentrations of fatty acid involved in de-novo lipogensis and incidence of Type 2 diabetes., Author summary Why was this study done? De novo lipogenesis (DNL) is a metabolic pathway involved in the endogenous synthesis of specific fatty acids, such as 16:0, 16:1n7, 18:0, and 18:1n9, and it is linked to the pathophysiology of cardiometabolic diseases, including type 2 diabetes (T2D). Circulating or tissue concentrations of these fatty acids have been investigated for the associations with T2D incidence in epidemiological research. However, published studies reported inconsistent associations inconsistently and were subject to publication bias. Summary evidence is not available to date for the associations between these fatty acids and T2D incidence. An integration of available cohort studies would increase statistical power and allow assessment of generalizability, standardization of analytical strategies, and evidence synthesis with the potential publication bias minimized. What did the researchers do and find? As a part of the Fatty Acids and Outcomes Research Consortium (FORCE), we conducted new individual-participant data analyses of 17 cohort studies of a total of 65,225 adults free of T2D at baseline, among whom 15,383 developed incident T2D over up to 20 years of follow-up. The cohort studies analyzed the associations between fatty acids (16:0, 16:1n7, 18:0, and 18:1n9) and the risk of developing T2D with standardized analytic strategy. In pooled analyses, each of the fatty acids was positively associated with a higher risk of developing T2D. The associations were independent of major risk factors for T2D, such as age, sex, race/ethnicity, socioeconomic characteristics, smoking status, physical activity, and obesity. What do these findings mean? The findings provide the first summary evidence to date for the positive relationships of concentrations of the DNL-related fatty acids with a risk of T2D, indicating the strong relevance of DNL and its determinants to the development of T2D. These fatty acids potentially reflect the status of DNL activity, which may be stimulated or suppressed by a combination of carbohydrate intake, alcohol intake, polyunsaturated fatty acid intake, and other lifestyle and clinical factors. Therefore, the current findings indicate the need for investigation into determinants and consequences of elevated concentrations of these fatty acids. Despite several advantages of our individual-level data analysis in this pooling project, the results cannot establish whether elevated concentrations of these fatty acids caused the development of T2D or whether underlying peripheral or hepatic insulin resistance, for example, may elevate both the fatty acid concentrations and the risk of T2D independently.

Salivary amylase, encoded by the AMY1 gene, is responsible for the digestion of carbohydrates. We investigated associations of AMY1 genetic variations with general and central adiposity changes considering dietary carbohydrate intake among 32,054 adults from four prospective cohort studies. A genetic risk score (GRS) was calculated based on nine AMY1 single-nucleotide polymorphisms, with higher AMY1-GRS indicating higher activity of salivary amylase. We meta-analyzed interactions between AMY1-GRS and dietary intake for changes in general and central adiposity over 5.5–10 years. We found that carbohydrate food intake significantly altered associations of AMY1-GRS with changes in BMI (Pinteraction = 0.001) and waist circumference (Pinteraction < 0.001). Results were consistent and significant in female cohorts rather than in male cohorts. Among women, higher AMY1-GRS was associated with more increases in adiposity if dietary carbohydrate food intake was high, while higher AMY1-GRS was associated with less gains in adiposity when the dietary intake was low. Also, in a 2-year randomized dietary intervention trial, associations of AMY1-GRS with changes in weight (Pinteraction = 0.023) and waist circumference (Pinteraction = 0.037) were significantly modified by carbohydrate intake. Our results suggest the importance of precision nutrition strategies considering participants’ genetic adaptation to carbohydrate-rich diets in regulating general and central adiposity.

PURPOSE: The purpose of this study is to explore the preference and acceptance of white rice substitution with brown and black rice among young adults in Indonesia to prevent diabetes. METHODS: This study used a qualitative design. Rice preference deeply explored using focus group discussion as a case-study. 85 informants with an average of ages 20 years old were divided into several groups. Several topics to discuss include the reasons to accept or reject brown and black rice, knowledge, attitude, motivation, and potency to substitute white rice. RESULTS: Price was the main barrier to substitute white rice to brown and black rice. The participants have known brown rice from parents, mass media, and friends. Most of them were still unfamiliar with black rice. Culture also affected the preferences of the participants. To motivate people to change their white rice diet, creative packaging and segmentation of the sale were recommended. CONCLUSION: Substituting white to brown and black rice is still a challenge for young adults in Indonesia. Several barriers such as culture, accessibility, and affordability need to be considered. Further efforts are important to manage a program to increase brown and black rice consumption.

Background & aims Sedentariness and physical inactiveness are associated with deleterious health outcomes, but their associations with liver enzyme elevations remain uncertain. Methods In 10 385 US Hispanics/Latinos from the Hispanic Community Health Study/Study of Latinos, we examined associations of sedentary time and moderate-to-vigorous physical activity (MVPA) measured by accelerometers with liver enzyme elevations. Elevated alanine aminotransferase (ALT), aspartate aminotransferase and γ-glutamyltransferase (GGT) were defined as the highest gender-specific deciles. Prevalence ratios (PRs) and 95% confidence intervals (CIs) were calculated using weighted Poisson regressions. Results After adjusting for demographical/socioeconomic factors and MVPA, increasing quartiles of sedentary time were associated with a higher prevalence of elevated ALT (PRs [95% CI] = 1.0, 1.17 [0.92-1.47], 1.21 [0.96, 1.53] and 1.51 [1.13-2.02]; P-trend = .007) and elevated GGT (PRs [95% CI] = 1.0, 1.06 [0.82-1.36], 1.35 [1.06-1.73] and 1.66 [1.27-2.16]; P-trend = .0001). These associations were attenuated but remained significant after further adjustment for cardiometabolic traits including body-mass index, waist-hip-ratio, lipids and homeostatic model assessment of insulin resistance. In contrast, increasing quartiles of MVPA were associated with a lower prevalence of elevated ALT (PRs [95% CI] =1.0, 0.97 [0.77-1.23], 0.84 [0.66-1.06] and 0.72 [0.54-0.96]; P-trend = .01) after adjusting for demographical/socioeconomic factors and sedentary time, but this association became non-significant after further adjustment for cardiometabolic traits. Notably, the association of sedentary time with GGT elevation was significant both in individuals meeting the US Physical Activity Guidelines for Americans (MVPA ≥150 minutes/week) and in those who did not (both P-trend ≤ .003). Conclusions Our findings suggest that objectively measured sedentary time is independently associated with elevated ALT and GGT in US Hispanics/Latinos.

Objective The objective of this study was to evaluate the effect of skipping breakfast on body composition and cardiometabolic risk factors. Methods This study conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating breakfast skipping compared with breakfast consumption. Inclusion criteria included age ≥ 18, intervention duration ≥ 4 weeks, ≥ 7 participants per group, and ≥ 1 body composition measure. Random-effects meta-analyses of the effect of breakfast skipping on body composition and cardiometabolic risk factors were performed. Results Seven RCTs (n = 425 participants) with an average duration of 8.6 weeks were included. Compared with breakfast consumption, breakfast skipping significantly reduced body weight (weighted mean difference [WMD] = -0.54 kg [95% CI: -1.05 to -0.03], P = 0.04, I2 = 21.4%). Percent body fat was reported in 5 studies and was not significantly different between breakfast skippers and consumers. Three studies reported on low-density lipoprotein cholesterol (LDL), which was increased in breakfast skippers as compared with breakfast consumers (WMD = 9.24 mg/dL [95% CI: 2.18 to 16.30], P = 0.01). Breakfast skipping did not lead to significant differences in blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, C-reactive protein, insulin, fasting glucose, leptin, homeostatic model assessment of insulin resistance, or ghrelin. Conclusions Breakfast skipping may have a modest impact on weight loss and may increase LDL in the short term. Further studies are needed to provide additional insight into the effects of breakfast skipping.

Background Olive oil intake has been associated with lower risk of cardiovascular disease (CVD) in Mediterranean populations, but little is known about these associations in the U.S population. Objectives This study sought to examine whether olive oil intake is associated with total CVD, coronary heart disease (CHD), and stroke risk. Methods This study included 61,181 women from the Nurses’ Health Study (1990 to 2014) and 31,797 men from the Health Professionals Follow-up Study (1990 to 2014) who were free of cancer, heart disease, and stroke at baseline. Diet was assessed using food frequency questionnaires at baseline and then every 4 years. Cox proportional hazards regressions were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results During 24 years of follow-up, this study documented 9,797 incident cases of CVD, including 6,034 CHD cases and 3,802 stroke cases. After adjusting for major diet and lifestyle factors, compared with nonconsumers, those with higher olive oil intake (>0.5 tablespoon/day or >7 g/day) had 14% lower risk of CVD (pooled HR: 0.86; 95% CI: 0.79 to 0.94) and 18% lower risk of CHD (pooled HR: 0.82; 95% CI: 0.73 to 0.91). No significant associations were observed for total or ischemic stroke. Replacing 5 g/day of margarine, butter, mayonnaise, or dairy fat with the equivalent amount of olive oil was associated with 5% to 7% lower risk of total CVD and CHD. No significant associations were observed when olive oil was compared with other plant oils combined. In a subset of participants, higher olive oil intake was associated with lower levels of circulating inflammatory biomarkers and a better lipid profile. Conclusions Higher olive oil intake was associated with lower risk of CHD and total CVD in 2 large prospective cohorts of U.S. men and women. The substitution of margarine, butter, mayonnaise, and dairy fat with olive oil could lead to lower risk of CHD and CVD.

BACKGROUND: The frailty syndrome is associated with higher risk of disability and death after accounting for multimorbidity. Therefore, the determinants of frailty need to be identified to ensure older adults live not only longer but also healthier lives. However, the effect of diet quality on frailty is mostly unknown. OBJECTIVES: We aimed to evaluate the alternate Mediterranean diet (AMED), the Dietary Approaches to Stop Hypertension (DASH) diet, and the alternate Healthy Eating Index-2010 (AHEI-2010) in association with frailty risk among older women. METHODS: We analyzed data from 71,941 women aged ≥60 y participating in the Nurses’ Health Study. The AMED, DASH, and AHEI-2010 were computed from validated FFQs in 1990 and repeated every 4 y until 2010. Frailty was defined as having ≥3 of the following 5 criteria from the FRAIL scale: fatigue, reduced resistance, reduced aerobic capacity, having ≥5 illnesses, and weight loss ≥5%. The occurrence of frailty was assessed every 4 y. RESULTS: During follow-up we identified 11,564 incident cases of frailty. After adjusting for potential confounders, the RRs (95% CIs) of frailty per 1-SD increase in the AMED, DASH, and AHEI-2010 scores were 0.87 (0.85, 0.90), 0.93 (0.91, 0.95), and 0.90 (0.88, 0.92), respectively. All diet quality scores were associated with lower risk of the individual frailty criteria fatigue, reduced resistance, reduced aerobic capacity, and weight loss. Lower consumption of red and processed meat, a lower sodium intake, a higher ratio of monounsaturated to saturated fat, vegetables, and moderate alcohol intake were components of the diet quality scores independently associated with lower risk of frailty. CONCLUSIONS: Adherence to a healthy diet, as defined by the AMED, DASH, and AHEI-2010 scores, was associated with reduced risk of frailty in older women.

OBJECTIVE To identify sleep duration trajectories from early to middle adulthood and their associations with incident type 2 diabetes. RESEARCH DESIGN AND METHODS Using a group-based modeling approach, we identified sleep duration trajectories based on sleep duration in ages 20–25, 26–35, 36–45, and 46+ years, which were retrospectively assessed in 2009 among 60,068 women from the Nurses’ Health Study II (median age 54.9 years) who were free of diabetes, cardiovascular disease, and cancer. We investigated the prospective associations between sleep duration trajectories and diabetes risk (2009–2017) using multivariable Cox proportional hazards models. RESULTS We documented 1,797 incident diabetes cases over a median follow-up of 7.8 years (442,437 person-years). Six sleep duration trajectories were identified: persistent 5-, 6-, 7-, or 8-h sleep duration and increased or decreased sleep duration. After multivariable adjustment for diabetes risk factors, compared with the persistent 7-h sleep duration group, the hazard ratio was 1.43 (95% CI 1.10, 1.84) for the 5-h group, 1.17 (1.04, 1.33) for the 6-h group, 0.96 (0.84, 1.10) for the 8-h group, 1.33 (1.09, 1.61) for the increased sleep duration group, and 1.32 (1.10, 1.59) for the decreased sleep duration group. Additional adjustment for time-updated comorbidities and BMI attenuated these associations, although a significantly higher risk remained in the decreased sleep duration group (1.24 [1.03, 1.50]). CONCLUSIONS Persistent short sleep duration or changes in sleep duration from early to middle adulthood were associated with higher risk of type 2 diabetes in later life. These associations were weaker after obesity and metabolic comorbidities were accounted for.

Background The association between circulating folate concentrations and risk of coronary artery disease (CAD) has been evaluated in Western populations with inconsistent results; however, the observational and causal associations in Chinese populations with relatively low folate concentrations remain unclear. Objectives We aimed to examine the association of circulating folate concentrations with incident CAD in Chinese adults, and further evaluated the causal relation using Mendelian randomization (MR) analysis. Methods We measured baseline serum folate in 1605 incident CAD cases and 1605 age- and sex-matched controls nested within the Dongfeng-Tongji (DFTJ) cohort, which recruited 27,009 individuals with a mean age of 63.6 y in 2008-2010 and followed up until the end of 2013 (mean: 4.4 y). We quantified the observational association between folate and incident CAD using conditional logistic regression models. A 2-sample MR analysis was performed using summary statistics obtained for genetic variants identified from a genome-wide association study (GWAS) of circulating folate concentrations in participants of European ancestry (n = 37,341) and from the CardiogramplusC4D 1000 genomes-based GWAS meta-analysis (n = 184,305). We also conducted 1-sample MR among 1545 incident CAD cases and 1444 controls with genotyping data in the DFTJ cohort. Results In the DFTJ cohort, higher serum folate concentrations were associated with a lower risk of CAD: the OR (95% CI) across sex-specific quartiles of folate (from lowest to highest concentrations) was 1.00 (reference), 0.78 (0.63, 0.97), 0.77 (0.61, 0.97), and 0.75 (0.60, 0.95), respectively (P-trend = 0.01). In the MR analysis, the OR of CAD per SD increase in genetically predicted serum folate was 0.99 (0.82, 1.20) and 0.88 (0.59, 1.32) for European and Chinese populations, respectively. Conclusions We found an inverse association between circulating folate concentrations and incident CAD among Chinese populations. However, we confirmed that there was no genetic evidence to support the causal relation in both European and Chinese populations.

While conventional nutrition research has yielded biomarkers such as doubly labeled water for energy metabolism and 24-h urinary nitrogen for protein intake, a critical need exists for additional, equally robust biomarkers that allow for objective assessment of specific food intake and dietary exposure. Recent advances in high-throughput MS combined with improved metabolomics techniques and bioinformatic tools provide new opportunities for dietary biomarker development. In September 2018, the NIH organized a 2-d workshop to engage nutrition and omics researchers and explore the potential of multiomics approaches in nutritional biomarker research. The current Perspective summarizes key gaps and challenges identified, as well as the recommendations from the workshop that could serve as a guide for scientists interested in dietary biomarkers research. Topics addressed included study designs for biomarker development, analytical and bioinformatic considerations, and integration of dietary biomarkers with other omics techniques. Several clear needs were identified, including larger controlled feeding studies, testing a variety of foods and dietary patterns across diverse populations, improved reporting standards to support study replication, more chemical standards covering a broader range of food constituents and human metabolites, standardized approaches for biomarker validation, comprehensive and accessible food composition databases, a common ontology for dietary biomarker literature, and methodologic work on statistical procedures for intake biomarker discovery. Multidisciplinary research teams with appropriate expertise are critical to moving forward the field of dietary biomarkers and producing robust, reproducible biomarkers that can be used in public health and clinical research.

Background A gut-microbial metabolite, trimethylamine N-oxide (TMAO), has been associated with coronary atherosclerotic burden. No previous prospective study has addressed associations of long-term changes in TMAO with coronary heart disease (CHD) incidence. Objectives The purpose of this study was to investigate whether 10-year changes in plasma TMAO levels were significantly associated with CHD incidence. Methods This prospective nested case-control study included 760 healthy women at baseline. Plasma TMAO levels were measured both at the first (1989 to 1990) and the second (2000 to 2002) blood collections; 10-year changes (Δ) in TMAO were calculated. Incident cases of CHD (n = 380) were identified after the second blood collection through 2016 and were matched to controls (n = 380). Results Regardless of the initial TMAO levels, 10-year increases in TMAO from the first to second blood collection were significantly associated with an increased risk of CHD (relative risk [RR] in the top tertile: 1.58 [95% confidence interval (CI): 1.05 to 2.38]; RR per 1-SD increment: 1.33 [95% CI: 1.06 to 1.67]). Participants with elevated TMAO levels (the top tertile) at both time points showed the highest RR of 1.79 (95% CI: 1.08 to 2.96) for CHD as compared with those with consistently low TMAO levels. Further, we found that the ΔTMAO-CHD relationship was strengthened by unhealthy dietary patterns (assessed by the Alternate Healthy Eating Index) and was attenuated by healthy dietary patterns (p interaction = 0.008). Conclusions Long-term increases in TMAO were associated with higher CHD risk, and repeated assessment of TMAO over 10 years improved the identification of people with a higher risk of CHD. Diet may modify the associations of ΔTMAO with CHD risk.

Summary Background To reduce their overall substantially increased risk of cardiovascular disease and premature mortality, smoking cessation is especially important for people with diabetes. However, the effect of weight change after quitting smoking on the long-term health consequences of smoking cessation is unclear. We aimed to examine smoking cessation and subsequent weight change in relation to incident cardiovascular disease events and mortality among adults with type 2 diabetes. Methods In this population-based cohort study, we analysed data from people with type 2 diabetes from two prospective cohorts in the USA: the Nurses' Health Study (1976–2014) and the Health Professionals Follow-Up Study (1986–2014). We included participants from both cohorts who either had prevalent type 2 diabetes or were diagnosed during the study, and who were either current smokers or never smokers without cardiovascular disease or cancer at diagnosis of diabetes. Information on demographics, newly diagnosed diseases, medical history, and lifestyle factors, including smoking status and weight change, was updated every 2 years through validated questionnaires. We assessed the incidence of cardiovascular disease and all-cause and cause-specific mortality among recent quitters (within 6 years of stopping) and long-term quitters (>6 years) associated with weight change within 6 years of smoking cessation among people with type 2 diabetes. We did a multivariable-adjusted Cox proportional hazard models to estimate hazard ratios (HRs) for the associations of smoking cessation and weight change on the outcomes. Findings Of 173 229 total cohort participants (121 700 from the Nurses' Health Study and 51 529 from the Health Professionals Follow-Up Study), 10 809 people with type 2 diabetes were included in the incident cardiovascular disease analysis and 9688 were included in the mortality analysis. 2580 incident cases of cardiovascular disease occurred during 153 166 person-years of follow-up, and 3827 deaths occurred during 152 811 person-years of follow-up. Recent quitters (2–6 consecutive years since smoking cessation) without weight gain within the first 6 years of quitting had a significantly lower risk of cardiovascular disease than people who continued to smoke (multivariable-adjusted HR 0·83 [95% CI 0·70–0·99] among all recent quitters, 0·77 [0·62–0·95] among recent quitters without weight gain, 0·99 [0·70–1·41] among recent quitters with weight gain of 0·1–5·0 kg, 0·89 [0·65–1·23] among recent quitters with weight gain of >5·0 kg, and 0·72 [0·61–0·84] among longer-term quitters [>6 consecutive years since smoking cessation]). Weight gain within 6 years after smoking cessation did not attenuate the inverse relation between long-term cessation and all-cause mortality (multivariable-adjusted HR 0·69 [95% CI 0·58–0·82] among long-term quitters without weight gain, 0·57 [0·45–0·71] among long-term quitters with weight gain of 0·1–5·0 kg, and 0·51 [0·42–0·62] among long-term quitters with weight gain of >5·0 kg), with similar results observed for cardiovascular disease and cancer mortality. Interpretation Smoking cessation without subsequent weight gain is associated with a reduced risk of cardiovascular disease and mortality among smokers with type 2 diabetes. Weight gain after smoking cessation attenuates the reduction in risk of developing cardiovascular disease, but does not attenuate the beneficial effect of smoking cessation with respect to mortality. These findings confirm the overall health benefits of quitting smoking among people with type 2 diabetes, but also emphasise the importance of weight management after smoking cessation to maximise its health benefits. Funding US National Institutes of Health.

Background Clinical and epidemiologic studies have shown that obesity is associated with asthma and that these associations differ by asthma subtype. Little is known about the shared genetic components between obesity and asthma. Objective We sought to identify shared genetic associations between obesity-related traits and asthma subtypes in adults. Methods A cross-trait genome-wide association study (GWAS) was performed using 457,822 subjects of European ancestry from the UK Biobank. Experimental evidence to support the role of genes significantly associated with both obesity-related traits and asthma through a GWAS was sought by using results from obese versus lean mouse RNA sequencing and RT-PCR experiments. Results We found a substantial positive genetic correlation between body mass index and later-onset asthma defined by asthma age of onset at 16 years or greater (Rg = 0.25, P = 9.56 × 10−22). Mendelian randomization analysis provided strong evidence in support of body mass index causally increasing asthma risk. Cross-trait meta-analysis identified 34 shared loci among 3 obesity-related traits and 2 asthma subtypes. GWAS functional analyses identified potential causal relationships between the shared loci and Genotype-Tissue Expression (GTEx) quantitative trait loci and shared immune- and cell differentiation–related pathways between obesity and asthma. Finally, RNA sequencing data from lungs of obese versus control mice found that 2 genes (acyl-coenzyme A oxidase-like [ACOXL] and myosin light chain 6 [MYL6]) from the cross-trait meta-analysis were differentially expressed, and these findings were validated by using RT-PCR in an independent set of mice. Conclusions Our work identified shared genetic components between obesity-related traits and specific asthma subtypes, reinforcing the hypothesis that obesity causally increases the risk of asthma and identifying molecular pathways that might underlie both obesity and asthma.