Casey M Rebholz

Johns Hopkins Bloomberg School of Public Health | JHSPH · Department of Epidemiology

Introduction There is a lack of biomarkers of clinically important diets, such as the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet. Objectives Our study explored serum metabolites associated with adherence to the MIND diet. Methods In 3,908 Atherosclerosis Risk in Communities (ARIC) study participants, we calculated a m...

Our aim was to conduct an umbrella review of evidence from meta-analyses of observational studies investigating the link between sugar-sweetened beverage consumption and human health outcomes. Using predefined evidence classification criteria, we evaluated evidence from 47 meta-analyses encompassing 22,055,269 individuals. Overall, 79% of these ana...

Background Consumption of ultra‐processed food, which is manufactured food that is high in additives and sparse in intact foods, is adversely associated with cardiovascular health, primarily in non‐US study populations. We aimed to estimate the association between ultra‐processed food consumption and incident hypertension in middle‐aged adults in t...

Background Patients with chronic kidney disease (CKD) are encouraged to choose refined grains instead of whole grains as part of the low-phosphorus diet for managing chronic kidney disease-mineral and bone disorders (CKD-MBD). However, there is no direct evidence indicating that limiting whole grains has a beneficial impact on CKD outcomes. Method...

Purpose of review Plant-based diets are associated with a lower risk of hypertension, diabetes, cardiovascular disease, and mortality. Using the most recent evidence, we critically appraised the role of plant-based diets in primary and secondary prevention of chronic kidney disease (CKD) with a focus on key nutritional factors (dietary acid load, p...

Aims/hypothesis Understanding the impact of the overall construct of ultra-processed foods on diabetes risk can inform dietary approaches to diabetes prevention. In this study, we aimed to evaluate the association between ultra-processed food consumption and risk of diabetes in a community-based cohort of middle-aged adults in the USA. We hypothesi...

Background High dietary calcium and phosphorus may accelerate vascular calcification, but epidemiological data are inconsistent. Most of those studies assessed diet at one point and have not been systematically evaluated. Objectives The purpose of this study was to assess the associations of dietary calcium and phosphorus intakes in middle age wit...

Circulating α1-acid glycoprotein (AGP) and C-reactive protein (CRP) are commonly measured to assess inflammation, but these biomarkers fail to reveal the complex molecular biology of inflammation. We mined the maternal plasma proteome to detect proteins that covary with AGP and CRP. In 435 gravida predominantly in <12-week gestation, we correlated...

Key Points We provide an atlas of cross-sectional and longitudinal serum and urine metabolite associations with eGFR and urine albumin-creatinine ratio in an older community-based cohort. Metabolic profiling in serum and urine provides distinct and complementary insights into disease. Background Metabolites represent a read-out of cellular process...

Rationale & Objective Tubulointerstitial damage is a feature of early chronic kidney disease (CKD), but current clinical tests capture it poorly. Urine biomarkers of tubulointerstitial health may identify risk of CKD. Study Design Prospective cohort (Atherosclerosis Risk in Communities [ARIC]) and case-cohort (Multi-Ethnic Study of Atherosclerosis...

Introduction: Understanding the association between low glucose readings (hypoglycemia) detected by CGM and hypoglycemic symptoms experienced by people with diabetes is critically important for diabetes management. However, tools that capture hypoglycemic symptoms in real-time are lacking. Objective: Implement a real-time hypoglycemia symptom repor...

Background: Metabolomics may identify novel biomarkers for predicting, detecting, and managing diabetes. We evaluated the association of novel metabolites with diabetes, prediabetes, and continuous glycemic outcomes (fasting plasma glucose (FPG); hemoglobin A1c (HbA1c)) using data from the Bogalusa Heart Study (BHS) and Atherosclerosis Risk in Comm...

Introduction: Consuming a plant-based diet is associated with a lower risk of cardiometabolic disorders and lower greenhouse gas emissions. Furthermore, a vegetarian diet is considered a healthy dietary pattern according to the U.S. Dietary Guidelines for Americans and strongly aligns with the 2021 AHA Dietary Guidance. Yet, little is known about c...

Background: For individuals with prediabetes and diabetes, the Centers for Disease Control and Prevention recommends consuming more whole foods rather than highly processed foods as part of the everyday diet. Trends in ultra-processed foods (UPFs) consumption among adults with diabetes and prediabetes in the general population are uncharacterized....

Objective To evaluate the existing meta-analytic evidence of associations between exposure to ultra-processed foods, as defined by the Nova food classification system, and adverse health outcomes. Design Systematic umbrella review of existing meta-analyses. Data sources MEDLINE, PsycINFO, Embase, and the Cochrane Database of Systematic Reviews, a...

OBJECTIVE Plant-based dietary patterns emphasize plant foods and minimize animal-derived foods. We investigated the association between plant-based dietary patterns and diabetes in a community-based U.S. sample of Black and White adults. RESEARCH DESIGN AND METHODS We included middle-aged adults from the Atherosclerosis Risk in Communities (ARIC)...

Rationale & Objective While urine excretion of nitrogen estimates the total protein intake, biomarkers of specific dietary protein sources have been sparsely studied. Using untargeted metabolomics, this study aimed to identify serum metabolomic markers of 6 protein-rich foods and to examine whether dietary protein–related metabolites are associated...

Cow’s milk is frequently included in the human diet, but the relationship between milk intake and type 2 diabetes (T2D) remains controversial. Here, using data from the Hispanic Community Health Study/Study of Latinos, we show that in both sexes, higher milk intake is associated with lower risk of T2D in lactase non-persistent (LNP) individuals (de...

BACKGROUND The Dietary Approaches to Stop Hypertension (DASH) diet score lowers blood pressure (BP). We examined interactions between genotype and the DASH diet score in relation to systolic BP. METHODS We analyzed up to 9 420 585 single nucleotide polymorphisms in up to 127 282 individuals of 6 population groups (91% of European population) from...

Objective We examined interactions between genotype and a Dietary Approaches to Stop Hypertension (DASH) diet score in relation to systolic blood pressure (SBP). Methods We analyzed up to 9,420,585 biallelic imputed single nucleotide polymorphisms (SNPs) in up to 127,282 individuals of six population groups (91% of European population) from the Co...

The benefits of plant-based diets may depend on the type of plant. To determine the associations of healthy and unhealthy plant-based diet types on risk of hospitalization with respiratory infections or any infection, we used dietary intake data reported in a food frequency questionnaire from the Atherosclerosis Risk in Communities Study to calcula...

Objective: To evaluate the existing meta-analytic evidence of associations between exposure to ultra-processed foods, as defined by the Nova food classification system, and adverse health outcomes. Design: Systematic umbrella review of existing meta-analyses. Data Sources: MEDLINE, PsycINFO, Embase, and the Cochrane Database of Systematic Reviews,...

Background: Dairy consumption is related to chronic disease risk, yet the measurement of dairy consumption has largely relied upon self-report. Untargeted metabolomics allows for the identification of objective markers of dietary intake. Objectives: We aimed to identify associations between dietary intake of dairy (total dairy, low-fat dairy, an...

Rationale & Objective Biomarkers of kidney disease progression have been identified in individuals with diabetes and underlying chronic kidney disease (CKD). Whether or not these markers are associated with the development of CKD in a general population without diabetes or CKD is not well established. Study Design Prospective observational cohort....

Background Within healthy dietary patterns, manipulation of the proportion of macronutrient can reduce CVD risk. However, the biological pathways underlying healthy diet-disease associations are poorly understood. Using an untargeted, large-scale proteomic profiling, we aimed to (1) identify proteins mediating the association between healthy dietar...

Objective: N-terminal pro-brain-type natriuretic peptide (NT-proBNP) is a marker of cardiac wall stress and is a predictor of cardiovascular disease. Higher diet quality is associated with lower risk of cardiovascular disease. The association between diet quality and subclinical cardiovascular disease assessed by NT-proBNP is uncharacterized. We i...

BACKGROUND The DASH (Dietary Approaches to Stop Hypertension) diets reduced blood pressure (BP) in the DASH and DASH-Sodium trials, but the underlying mechanisms are unclear. We identified metabolites associated with systolic BP or diastolic BP (DBP) changes induced by dietary interventions (DASH versus control arms) in 2 randomized controlled feed...

Background: Dietary consumption has traditionally been studied through food intake questionnaires. Metabolomics can be used to identify blood markers of dietary protein that may complement existing dietary assessment tools. Objectives: We aimed to identify associations between 3 dietary protein sources (total protein, animal protein, and plant p...

Rationale & objective: Ultraprocessed foods are widely consumed in the US and are associated with cardiovascular disease (CVD), mortality, and kidney function decline in the general population. We investigated associations between ultraprocessed food intake and chronic kidney disease (CKD) progression, all-cause mortality, and incident CVD in adul...

Background The Dietary Approaches to Stop Hypertension (DASH) diet is recommended for cardiovascular disease prevention. We aimed to identify protein biomarkers of the DASH diet using data from 2 randomized feeding studies and validate them in an observational study, the ARIC (Atherosclerosis Risk in Communities) study. Methods and Results Large‐s...

Introduction: Older populations have been growing dramatically worldwide. Aging may lead to changes in diet quality. There is a need to better understand dietary intake during late-life and the impact on health outcomes. Hypothesis: We hypothesized that adherence to healthy dietary patterns, i.e., the Dietary Approaches to Stop Hypertension (DASH)...

Introduction: N-terminal pro-brain-type natriuretic peptide (NT-proBNP) is widely used as a diagnostic biomarker for heart failure. Higher diet quality is associated with lower risk of cardiovascular disease. However, the association between diet and subclinical cardiovascular disease, as assessed by biomarker concentrations, is less well-studied....

Introduction: Ultra-processed food (UPF) consumption has an adverse impact on cardiovascular health. Current research is primarily based on non-US study populations. The purpose of our study was to estimate the association between UPF consumption and risk of incident hypertension in a population of middle-aged black and white men and women. Methods...

Background: Numerous studies have shown inverse associations between serum magnesium (Mg) levels and risk of cardiovascular disease (CVD), but studies of dietary Mg have not been consistent. Aim: The association of a Mg-rich diet score with risks of incident CVD, coronary heart disease (CHD), and ischemic stroke in the Atherosclerosis Risk in Commu...

Introduction: The Dietary Approaches to Stop Hypertension (DASH) diet significantly reduced blood pressure (BP) in the DASH and DASH-Sodium trials, but the underlying mechanisms are unclear. Hypothesis: We hypothesized that certain metabolites will be associated with BP reductions. Methods: Metabolomic profiling was conducted at the end of the diet...

Introduction: There is inconsistent evidence on the efficacy of a low-protein diet for patients with chronic kidney disease (CKD) and there is a lack of objective biomarkers of dietary intake. The purpose of this study was to identify plasma metabolites associated with dietary intake of protein among children with CKD and to assess whether protein-...

Background: High dietary calcium and phosphorus intakes may accelerate vascular calcification. A few studies have explored the association of dietary calcium and phosphorus intakes with vascular calcification but reported inconsistent results. Most studies relied on dietary assessment at one time point and evaluated only coronary artery calcificati...

Introduction: There is a lack of objective biomarkers of dietary intake. Untargeted studies can unbiasedly identify dairy biomarkers and inform the creation of robust dietary assessment tools that integrate questionnaire and biospecimen data. Methods: Dairy products from interviewer-administered questionnaires were categorized as either low-fat or...

Objective To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD). Design Pooled analysis. Data sources A...

Background: High ultra-processed food consumption is associated with higher risk of CKD. However, there is no biomarker for ultra-processed food, and the mechanism through which ultra-processed food is associated with CKD is not clear. Metabolomics can provide objective biomarkers of ultra-processed food and provide important insights into the mec...

Nutritional epidemiology seeks to understand nutritional determinants of disease in human populations using experimental and observational study designs. Though randomized controlled trials provide the strongest evidence of causality, the expense and difficulty of sustaining adherence to dietary interventions are substantial barriers to investigati...

Background: Molecular mechanisms underlying the benefits of healthy dietary patterns are poorly understood. Identifying protein biomarkers of dietary patterns can contribute to characterizing biological pathways influenced by food intake. Objectives: This study aimed to identify protein biomarkers associated with four indexes of healthy dietary...

Introduction: We studied the replication and generalization of previously identified metabolites potentially associated with global cognitive function in multiple race/ethnicities and assessed the contribution of diet to these associations. Methods: We tested metabolite-cognitive function associations in U.S.A. Hispanic/Latino adults (n = 2222)...

Background: Metabolomic profiling in individuals with chronic kidney disease (CKD) has the potential to identify novel biomarkers and provide insight into disease pathogenesis. Methods: We examined the association between blood metabolites and CKD progression, defined as the subsequent development of end-stage renal disease (ESRD) or estimated g...

Rationale & Objective Novel metabolite biomarkers of kidney failure with replacement therapy (KFRT) may help identify people at high risk for adverse kidney outcomes, and implicated pathways may aid in developing targeted therapeutics. Study Design Prospective cohort Setting & Participants: 3,799 Atherosclerosis Risk in Communities (ARIC) Study p...

Background and objectives Mitochondrial DNA copy number is a biomarker of mitochondrial function, which has been hypothesized to contribute to pathogenesis of CKD through podocyte injury, tubular epithelial cell damage, and endothelial dysfunction. The prospective association of mitochondrial DNA copy number with CKD progression has not been previo...

Rationale & Objective Ultra-processed foods (UPF) have become readily available in the global food supply in the past few decades. Several adverse health outcomes have been linked with higher consumption of UPF. However, the impact of UPF on chronic kidney disease (CKD) risk remains unknown. Study Design Prospective cohort study. Setting & Partic...

Introduction Coffee is one of the most frequently consumed beverages worldwide and has been shown to have a wide assortment of health benefits. Although habitual coffee consumption is associated with a lower incidence of chronic kidney disease, an association between coffee and acute kidney injury (AKI) has not yet been shown. Methods In the Ather...

Metabolomic signatures of incident diabetes remain largely unclear for US Hispanics/Latinos, a group with high diabetes burden. We evaluated the associations of 624 known serum metabolites (measured by a global, untargeted approach) with incident diabetes in a subsample (n = 2010) of the Hispanic Community Health Study/Study of Latinos without diab...

INTRODUCTION We studied the replication and generalization of previously identified metabolites potentially associated with global cognitive function in multiple race/ethnicities and assessed the contribution of diet to these associations. METHODS We tested metabolite-cognitive function associations in U.S.A. Hispanic/Latino adults (n= 2,222) from...

Introduction: Greater adherence to plant-based diets is associated with a lower risk of incident chronic kidney disease (CKD). Metabolomics can help identify blood biomarkers of plant-based diets and understand the underlying mechanisms. Objectives: Using untargeted metabolomics, we aimed to identify metabolites associated with 4 plant-based diet i...

Introduction: Molecular mechanisms underlying the benefits of healthy dietary patterns on chronic diseases are poorly understood. Identifying protein biomarkers of healthy diets can help us characterize biological pathways influenced by diet quality and confirm the validity of established healthy dietary patterns. Objectives: To identify protein bi...

Background Greater adherence to plant-based diets is associated with a lower risk of incident chronic kidney disease (CKD). Metabolomics can help identify blood biomarkers of plant-based diets and enhance understanding of underlying mechanisms. Objectives Using untargeted metabolomics, we aimed to identify metabolites associated with 4 plant-based...

Background: Glycated albumin may provide complementary information to hemoglobin A1c (HbA1c). We compared cross-sectional associations of HbA1c and glycated albumin with chronic kidney disease (CKD) in US adults. Methods: We included 10 923 adults (9955 without diagnosed diabetes, 968 with a diabetes diagnosis) from the National Health and Nutri...

Scope: Lack of biomarkers is a challenge for the accurate assessment of protein intake and interpretation of observational study data. We aimed to identify biomarkers of a protein-rich dietary pattern. Methods and results: The OmniHeart trial was a randomized cross-over feeding study which tested three dietary patterns with varied macronutrient...

Background Untargeted plasma metabolomic profiling combined with machine learning (ML) may lead to discovery of metabolic profiles that inform our understanding of pediatric CKD causes. We sought to identify metabolomic signatures in pediatric CKD based on diagnosis: FSGS, obstructive uropathy (OU), aplasia/dysplasia/hypoplasia (A/D/H), and reflux...

Background Prior studies have documented lower cardiovascular disease (CVD) risk among people with a higher adherence to a plant-based dietary pattern. Non-Hispanic black Americans are an understudied group with high burden of CVD, yet studies of plant-based diets have been limited in this population. Methods and findings We conducted an analysis...

Background Research examining the role of obesity in cardiovascular disease (CVD) often fails to adequately consider heterogeneity in obesity severity, distribution, and duration. Methods and Results We here use multivariate latent class mixed models in the biracial Atherosclerosis Risk in Communities study (N=14 514; mean age=54 years; 55% female...

Background and objectives Moderate coffee consumption has been associated with lower risk of CKD; however, the exact biologic mechanisms underlying this association are unknown. Metabolomic profiling may identify metabolic pathways that explain the association between coffee and CKD. The goal of this study was to identify serum metabolites associat...

Poor diet quality is strongly associated with elevated risk of cardiovascular disease morbidity and mortality. This scientific statement emphasizes the importance of dietary patterns beyond individual foods or nutrients, underscores the critical role of nutrition early in life, presents elements of heart-healthy dietary patterns, and highlights str...

Background Higher ultra-processed food intake has been linked with several cardiometabolic and cardiovascular diseases. However, prospective evidence from US populations remains scarce. Objectives To test the hypothesis that higher intake of ultra-processed foods is associated with higher risk of coronary artery disease. Methods A total of 13,548...