Proteomic signature of healthy dietary patterns and risk of cardiovascular disease in the framingham heart study.

Association Between Prudent Dietary Pattern and Cardiometabolic Indicators in a Healthy Qatari Population: Evidence from the Qatar Biobank (QBB)

Background/Objectives: Diet is recognized as an important determinant of cardiometabolic health, yet evidence from Middle Eastern populations remains scarce. This cross-sectional study investigated the association between a Prudent dietary pattern and multiple indicators of obesity, type-2 diabetes, and cardiovascular disease in a metabolically healthy Qatari cohort. Methods: Data were obtained from 6919 Qatari adults from the Qatar Biobank study. Participants with diagnosed metabolic disorders, pregnancy, or non-fasting blood samples were excluded. Anthropometric, biochemical, and clinical measurements were collected using standardized protocols. Dietary intake was assessed using a 102-item food frequency questionnaire, and a Prudent dietary pattern was derived through factor loadings analysis. Participants were categorized into low and high intake groups of the Prudent dietary pattern. Associations between the Prudent dietary pattern and cardiometabolic markers were examined using generalized linear models adjusted for age, sex, adiposity, and physical activity with Bonferroni correction applied for multiple testing. Results: After correction for multiple testing, greater adherence to the Prudent dietary pattern was significantly associated with lower fat mass index (β = −0.02, p = 0.0001), fasting insulin (β = −0.05, p = 0.0021), and higher fat-free mass (β = 0.01, p = 5.7 × 10−5). Conclusions: Overall, in a metabolically healthy Qatari population, greater compliance to a Prudent dietary pattern was favorably associated with fat and muscle mass, and insulin regulation after adjusting for age, sex, BMI and physical activity. These findings support the role of dietary habits in greater cardiometabolic health in Middle Eastern Arab populations.

Ultra-processed food consumption and atherosclerosis risk: a prospective cohort study of UK Biobank

Ultra-processed foods (UPFs) have become dominant in modern diets, yet their relationship with atherosclerosis—the primary pathological basis of cardiovascular disease—remains inadequately characterized. We investigated the association between UPF consumption and incident atherosclerosis risk and explored underlying metabolomic and proteomic molecular signatures. We conducted a prospective analysis of 133,797 UK Biobank participants free of atherosclerosis at baseline. Dietary intake was assessed using 24-h dietary recalls, and UPF consumption was categorized according to the NOVA classification system. Incident atherosclerosis cases were identified through hospital admission records and death registries. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In subset analyses, we performed nuclear magnetic resonance metabolomic profiling and plasma proteomic analysis using the Olink platform to identify molecular signatures associated with UPF-related atherosclerosis risk. During a median follow-up of 10.93 years (interquartile range, 10.83–11.40 years), 654 incident cases of atherosclerosis were documented. After multivariable adjustment, participants in the highest quartile (Q4) of servings/day showed an elevated risk (HR 1.40, 95% CI 1.12–1.75; p  = 0.003) compared to the lowest quartile (Q1). Similarly, participants in Q4 of UPF consumption (g/day) had a 29% increased risk of atherosclerosis compared to those in Q1 (HR 1.29, 95% CI 1.03–1.60; p  = 0.024). Restricted cubic spline analysis revealed higher UPF intake was associated with higher risk. Sparse LASSO identified UPF-related signatures comprising 30 metabolites and 25 proteins, predominantly involving lipoprotein, energy-metabolic, inflammatory, and endocrine pathways. Several biomarkers remained associated with incident atherosclerosis after multivariable adjustment and multiple-testing correction. Higher UPF consumption is associated with increased atherosclerosis risk. Distinct metabolomic and proteomic signatures characterized by systemic inflammation, lipid dysregulation, and enzymatic alterations may reflect potential pathways. These findings support dietary recommendations emphasizing minimally processed foods for cardiovascular disease prevention and highlight candidate molecular correlates requiring independent validation.

Dietary Patterns, Metabolomics, and Incident Gastroesophageal Reflux Disease: A Prospective Cohort Study.

Prospective evidence linking overall diet quality to gastroesophageal reflux disease (GERD) is limited, and metabolic pathways remain unclear. In a cohort of 183,878 adults free of GERD at baseline, we examined nine dietary pattern scores derived from repeated 24-hour dietary recalls and assessed associations with incident GERD over a median follow-up of 13.2 years, during which 15,401 cases occurred. Higher adherence to healthy patterns including MED, MIND, DASH, and DI-GM was associated with lower GERD risk (highest vs lowest tertile HRs 0.87-0.89), whereas a pro-inflammatory pattern (E-DII) was linked to higher risk (HR 1.11). In a metabolomics sub-cohort (N=98,669), diet-related NMR metabolomic signatures, derived from 168 biomarkers using Elastic Net regression, reflected similar associations and mediated 11.1%-32.2% of the diet-GERD relationship. Associations were largely consistent across subgroups and robust in sensitivity analyses, supporting a potential role of systemic metabolic profiles in mediating the effects of diet on GERD and highlighting metabolic mechanisms underlying diet-related disease risk.

Biomarker-calibrated dietary macronutrient densities and their comparative associations with chronic disease risk in a cohort of postmenopausal females.

BACKGROUND Associations between dietary macronutrient composition and the risk of major chronic diseases remain uncertain, partly due to reliance on self-reported dietary intake. OBJECTIVES We make comparisons among biomarker-calibrated dietary macronutrient densities and the risks of cardiovascular diseases (CVDs), cancers, and type-2 diabetes (T2D) over long-term follow-up in Women's Health Initiative (WHI) cohorts of postmenopausal U.S. females. METHODS Biomarker-based intake estimates from serum and 24-hour urine metabolomic profiles were calculated for macronutrient component densities in a WHI Nutrition and Physical Activity Assessment Study (n=436). These values were regressed linearly on corresponding FFQ density estimates and participant characteristics to produce calibration equations that adjust food frequency questionnaire (FFQ) estimates for random and systematic measurement error. Biomarker-calibrated dietary density estimates were calculated in larger WHI cohorts (n=82,121). Hazard ratio methods were used to prospectively relate both biomarker-calibrated intake assessments and, separately, FFQ assessments to chronic disease risk. RESULTS Calibration equations meeting an adjusted R2 criterion could be developed for protein, carbohydrate, saturated (SFA) and polyunsaturated (PUFA) fatty acid densities, and for several specific SFA and PUFA densities, but not for monounsaturated fatty acid density. Hazard ratio (HR) estimates (95% CIs) for 20% increments in biomarker-calibrated SFA density and PUFA density, compared to other macronutrient sources, were respectively 1.13 (1.04, 1.23) and 0.95 (0.87, 1.04) for coronary heart disease (CHD), 1.02 (0.96, 1.08) and 1.10 (1.02, 1.17) for breast cancer, and 1.07 (1.04, 1.11) and 1.07 (1.03, 1.12) for T2D. Protein density also was directly associated with T2D risk. Positive SFA density associations with CVD and T2D risk may be attributable to dietary palmitic acid. CONCLUSIONS Compared to other macronutrient sources, risk may be elevated for CHD at higher SFA density, for breast cancer at higher PUFA density, and for T2D risk at higher SFA, PUFA, and protein densities, among postmenopausal U.S. females. This study is registered with clinicaltrials.gov identifier: NCT00000611 https://clinicaltrials.gov/study/NCT00000611.

The role of genetic variation in apolipoprotein response to diet among Brazilians with cardiovascular disease.

Plasma metabolic signatures of healthy dietary patterns and risk of metabolic dysfunction-associated steatotic liver disease and cirrhosis

The underlying mechanisms of the associations between dietary patterns and liver disease remain unclear. We aimed to identify metabolic signatures (MSs) reflecting adherence to ten healthy dietary patterns and to investigate their associations with metabolic dysfunction-associated steatotic liver disease (MASLD) and cirrhosis. This cohort study included 82,259 participants with detailed dietary and metabolomic data. MSs for each dietary pattern were derived using elastic-net regression. Cox proportional hazards regression, Mendelian randomization, and mediation analyses were employed to explore potential associations and mechanisms. MSs for ten healthy dietary patterns were derived from 31 to 116 metabolites, primarily comprising fatty acids, lipids, and lipoprotein subclasses. Across all patterns, MSs were consistently associated with a lower risk of MASLD, with hazard ratios (HRs) ranging from 0.59 to 0.76. Notably, MSs for MIND, HPDI, rE-DII, and HLCD were associated with reduced cirrhosis risk (HRs: 0.56 to 0.63). Mendelian randomization analysis supported a potential causal relationship between MSs of MED, MIND, HPDI, and EAT-Lancet diets and liver diseases. Mediation analysis revealed that specific MSs accounted for 20.1% to 29.4% of the association between dietary patterns and MASLD, and 25.7% to 27.4% of that with cirrhosis. Metabolites from fatty acid metabolism and lipoprotein subclasses were significantly linked to liver diseases, and substantial mediated effects were observed across these metabolic pathways. Specific MSs linked to healthy dietary patterns are associated with reduced risk of liver disease, potentially underlying the diet's protective mechanism against MASLD and guiding future dietary guidelines in preventing progressive liver disease.