Search

The aim of this literature review was to identify and provide a summary update on the validity and applicability of the most promising dietary biomarkers reflecting the intake of important foods in the Western diet for application in epidemiological studies. Many dietary biomarker candidates, reflecting intake of common foods and their specific constituents, have been discovered from intervention and observational studies in humans, but few have been validated. The literature search was targeted for biomarker candidates previously reported to reflect intakes of specific food groups or components that are of major importance in health and disease. Their validity was evaluated according to 8 predefined validation criteria and adapted to epidemiological studies; we summarized the findings and listed the most promising food intake biomarkers based on the evaluation. Biomarker candidates for alcohol, cereals, coffee, dairy, fats and oils, fruits, legumes, meat, seafood, sugar, tea, and vegetables were identified. Top candidates for all categories are specific to certain foods, have defined parent compounds, and their concentrations are unaffected by nonfood determinants. The correlations of candidate dietary biomarkers with habitual food intake were moderate to strong and their reproducibility over time ranged from low to high. For many biomarker candidates, critical information regarding dose response, correlation with habitual food intake, and reproducibility over time is yet unknown. The nutritional epidemiology field will benefit from the development of novel methods to combine single biomarkers to generate biomarker panels in combination with self-reported data. The most promising dietary biomarker candidates that reflect commonly consumed foods and food components for application in epidemiological studies were identified, and research required for their full validation was summarized. [ABSTRACT FROM AUTHOR]

Rugulopteryx okamurae is an invasive non-indigenous species (NIS) of marine alga present in the benthic communities of the Strait of Gibraltar, where it has colonized most of the coast triggering ecological, economic and social consequences. The purple sea urchin Paracentrotus lividus is a generalist herbivore with potential to provide resistance to this NIS. Two experiments were carried out to determine if (i) P. lividus consumes R. okamurae under laboratory conditions, (ii) to assess its grazing preferences when this NIS is offered together with the native Ulva sp. and (iii) to find biochemical tissue markers related to R. okamurae ingestion. In the first experiment, sea urchins fed with R. okamurae, Ulva sp. or both diets were evaluated in groups for two months. Ingestion, food preference, growth and survival were assessed. In the second one, the same specimens from the R. okamurae and mixed diets were used to analyse their individual preferences, ingestion rates, growth and fatty acid profiles during another two months. Ingestion rates showed that sea urchins accepted the NIS R. okamurae as food under laboratory conditions, increasing its intake after a long exposure period. The electivity values for R. okamurae also increased when P. lividus was exposed to this alga for a long time. Regarding the fatty acids profile of tissues, the results showed that intestinal arachidonic acid (ARA, 20:4n-6) clearly differentiates sea urchins fed with R. okamurae from those fed with the mixed diet. ARA also appeared to be related to the feeding preferences, highlighting this fatty acid as a reliable marker of R. okamurae ingestion. Further research is needed in order to determine P. lividus feeding behaviour and its role as a biocontrol species in the areas invaded by R. okamurae. Sea urchin Paracentrotus lividus can feed on the alien macroalga Rugulopteryx okamurae. Ingestion rates and electivity increase after long exposure periods. Intestinal arachidonic fatty acid can be used as dietary biomarker. [ABSTRACT FROM AUTHOR]

Metabolomics has been used extensively to capture the exposome. We investigated whether prospectively measured metabolites provided predictive power beyond well-established risk factors among 758 women with adjudicated cancers [n = 577 breast (BC) and n = 181 colorectal (CRC)] and n = 758 controls with available specimens (collected mean 7.2 years prior to diagnosis) in the Women's Health Initiative Bone Mineral Density subcohort. Fasting samples were analyzed by LC-MS/MS and lipidomics in serum, plus GC-MS and NMR in 24 h urine. For feature selection, we applied LASSO regression and Super Learner algorithms. Prediction models were subsequently derived using logistic regression and Super Learner procedures, with performance assessed using cross-validation (CV). For BC, metabolites did not increase predictive performance over established risk factors (CV-AUCs~0.57). For CRC, prediction increased with the addition of metabolites (median CV-AUC across platforms increased from ~0.54 to ~0.60). Metabolites related to energy metabolism: adenosine, 2-hydroxyglutarate, N-acetyl-glycine, taurine, threonine, LPC (FA20:3), acetate, and glycerate; protein metabolism: histidine, leucic acid, isoleucine, N-acetyl-glutamate, allantoin, N-acetyl-neuraminate, hydroxyproline, and uracil; and dietary/microbial metabolites: myo-inositol, trimethylamine-N-oxide, and 7-methylguanine, consistently contributed to CRC prediction. Energy metabolism may play a key role in the development of CRC and may be evident prior to disease development. [ABSTRACT FROM AUTHOR]

Circulating food metabolites could improve dietary assessments by complementing traditional methods. Here, biomarker candidates of food intake were identified in plasma samples from pregnancy (gestational week 29, N = 579), delivery (mothers, N = 532; infants, N = 348), and four months postpartum (mothers, N = 477; breastfed infants, N = 193) and associated to food intake assessed with semi-quantitative food frequency questionnaires. Families from the Swedish birth cohort Nutritional impact on Immunological maturation during Childhood in relation to the Environment (NICE) were included. Samples were analyzed using untargeted liquid chromatography–mass spectrometry (LC-MS)-based metabolomics. Both exposure and outcome were standardized, and relationships were investigated using a linear regression analysis. The intake of fruits and berries and fruit juice were both positively related to proline betaine levels during pregnancy (fruits and berries, β = 0.23, FDR < 0.001; fruit juice, β = 0.27, FDR < 0.001), at delivery (fruit juice, infants: β = 0.19, FDR = 0.028), and postpartum (fruits and berries, mothers: β = 0.27, FDR < 0.001, infants: β = 0.29, FDR < 0.001; fruit juice, mothers: β = 0.37, FDR < 0.001). Lutein levels were positively related to vegetable intake during pregnancy (β = 0.23, FDR < 0.001) and delivery (mothers: β = 0.24, FDR < 0.001; newborns: β = 0.18, FDR = 0.014) and CMPF with fatty fish intake postpartum (mothers: β = 0.20, FDR < 0.001). No clear relationships were observed with the expected food sources of the remaining metabolites (acetylcarnitine, choline, indole-3-lactic acid, pipecolic acid). Our study suggests that plasma lutein could be useful as a more general food group intake biomarker for vegetables and fruits during pregnancy and delivery. Also, our results suggest the application of proline betaine as an intake biomarker of citrus fruit during gestation and lactation. [ABSTRACT FROM AUTHOR]

Metabolomics has been used extensively to capture the exposome. We investigated whether prospectively measured metabolites provided predictive power beyond well-established risk factors among 758 women with adjudicated cancers [n = 577 breast (BC) and n = 181 colorectal (CRC)] and n = 758 controls with available specimens (collected mean 7.2 years prior to diagnosis) in the Women’s Health Initiative Bone Mineral Density subcohort. Fasting samples were analyzed by LC-MS/MS and lipidomics in serum, plus GC-MS and NMR in 24 h urine. For feature selection, we applied LASSO regression and Super Learner algorithms. Prediction models were subsequently derived using logistic regression and Super Learner procedures, with performance assessed using cross-validation (CV). For BC, metabolites did not increase predictive performance over established risk factors (CV-AUCs~0.57). For CRC, prediction increased with the addition of metabolites (median CV-AUC across platforms increased from ~0.54 to ~0.60). Metabolites related to energy metabolism: adenosine, 2-hydroxyglutarate, N-acetyl-glycine, taurine, threonine, LPC (FA20:3), acetate, and glycerate; protein metabolism: histidine, leucic acid, isoleucine, N-acetyl-glutamate, allantoin, N-acetyl-neuraminate, hydroxyproline, and uracil; and dietary/microbial metabolites: myo-inositol, trimethylamine-N-oxide, and 7-methylguanine, consistently contributed to CRC prediction. Energy metabolism may play a key role in the development of CRC and may be evident prior to disease development.

The Omega-3 Index (O3I) reflects eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content in erythrocytes. While the O3I is associated with numerous health outcomes, its widespread use is limited. We investigated whether urinary metabolites could be used to non-invasively monitor the O3I in an exploratory analysis of a previous placebo-controlled, parallel arm randomized clinical trial in males and females (n = 88) who consumed either ~3 g/d olive oil (OO; control), EPA, or DHA for 12 weeks. Fasted blood and first-void urine samples were collected at baseline and following supplementation, and they were analyzed via gas chromatography and multisegment injection–capillary electrophoresis–mass spectrometry (MSI-CE-MS), respectively. We tentatively identified S-carboxypropylcysteamine (CPCA) as a novel urinary biomarker reflecting O3I status, which increased following both EPA and DHA (p < 0.001), but not OO supplementation, and was positively correlated to the O3I (R = 0.30, p < 0.001). Additionally, an unknown dianion increased following DHA supplementation, but not EPA or OO. In ROC curve analyses, CPCA outperformed all other urinary metabolites in distinguishing both between OO and EPA or DHA supplementation groups (AUC > 80.0%), whereas the unknown dianion performed best in discriminating OO from DHA alone (AUC = 93.6%). Candidate urinary biomarkers of the O3I were identified that lay the foundation for a non-invasive assessment of omega-3 status. [ABSTRACT FROM AUTHOR]

Circulating food metabolites could improve dietary assessments by complementing traditional methods. Here, biomarker candidates of food intake were identified in plasma samples from pregnancy (gestational week 29, N = 579), delivery (mothers, N = 532; infants, N = 348), and four months postpartum (mothers, N = 477; breastfed infants, N = 193) and associated to food intake assessed with semi-quantitative food frequency questionnaires. Families from the Swedish birth cohort Nutritional impact on Immunological maturation during Childhood in relation to the Environment (NICE) were included. Samples were analyzed using untargeted liquid chromatography–mass spectrometry (LC-MS)-based metabolomics. Both exposure and outcome were standardized, and relationships were investigated using a linear regression analysis. The intake of fruits and berries and fruit juice were both positively related to proline betaine levels during pregnancy (fruits and berries, β = 0.23, FDR < 0.001; fruit juice, β = 0.27, FDR < 0.001), at delivery (fruit juice, infants: β = 0.19, FDR = 0.028), and postpartum (fruits and berries, mothers: β = 0.27, FDR < 0.001, infants: β = 0.29, FDR < 0.001; fruit juice, mothers: β = 0.37, FDR < 0.001). Lutein levels were positively related to vegetable intake during pregnancy (β = 0.23, FDR < 0.001) and delivery (mothers: β = 0.24, FDR < 0.001; newborns: β = 0.18, FDR = 0.014) and CMPF with fatty fish intake postpartum (mothers: β = 0.20, FDR < 0.001). No clear relationships were observed with the expected food sources of the remaining metabolites (acetylcarnitine, choline, indole-3-lactic acid, pipecolic acid). Our study suggests that plasma lutein could be useful as a more general food group intake biomarker for vegetables and fruits during pregnancy and delivery. Also, our results suggest the application of proline betaine as an intake biomarker of citrus fruit during gestation and lactation.

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.

Wild fish attracted to salmon farms feed on waste feed that presently contain high levels of fatty acids of terrestrial origin. This study examines whether mature Atlantic cod (Gadus morhua) caught at spawning grounds has eaten salmon waste feed. Cod were caught at four spawning grounds around Smøla (Norway), an area with multiple salmon farms, during the spawning season in 2018 (n = 327) and 2019 (n = 488). The fatty acid (FA) profile of their livers, gonads (ovary and testis), and muscles (2019) were determined. Multivariate k-mean cluster analysis of liver FA profiles revealed three main clusters, which could be allocated to trophic niches using known fatty acid trophic markers (FATMs). Of the sampled cod in 2018 and 2019, 13 % and 20 % respectively had high liver concentrations of terrestrial FATMs (18:1n-9, 18:2n-6, and 18:3n-3), indicating waste feed feeding. The remaining cod could be assigned to either the pelagic or benthic food chain. The cod identified as feeding on waste feed had large, fatty livers. The terrestrial FAs were also transferred to the muscle and gonad lipids. It is postulated that the latter may result in gametes with sub-optimal lipid composition, potentially impacting fitness, which warrants further investigation. [ABSTRACT FROM AUTHOR]

Background Molecular stable isotope ratios are a novel type of dietary biomarker with high sensitivity and specificity for certain foods. Among these, fatty acid carbon isotope ratios (CIRs) have strong potential but have not been investigated as dietary biomarkers. Objectives We evaluated whether fatty acid CIRs and mass proportions were associated with meat, fish, and sugar-sweetened beverage (SSB) intake. Methods Thirty-two men [aged 46.2 ± 10.5 y; BMI (kg/m2): 27.2 ± 4.0] underwent a 12-wk inpatient dietary intervention at the National Institute of Diabetes and Digestive and Kidney Diseases in Phoenix, Arizona. Men were randomly assigned to 1 of 8 dietary treatments varying the presence/absence of dietary meat, fish, and SSBs in all combinations. Fatty acid CIRs and mass proportions were measured in fasting blood samples and adipose tissue biopsies that were collected pre- and postintervention. Dietary effects were analyzed using multivariable regression and receiver operating characteristic AUCs were calculated using logistic regression. Results CIRs of the several abundant SFAs, MUFAs and arachidonic acid (20:4n-6) in plasma were strongly associated with meat, as were a subset of these fatty acids in RBCs. Effect sizes in plasma ranged from 1.01‰ to 1.93‰ and were similar but attenuated in RBCs. Mass proportions of those fatty acids were not associated with diet. CIRs of plasma dihomo-γ-linolenic acid (20:3n–6) and adipose palmitic acid (16:0) were weakly associated with SSBs. Mass proportions of plasma odd-chain fatty acids were associated with meat, and mass proportions of plasma EPA and DHA (20:5n–3 and 22:6n–3) were associated with fish. Conclusions CIRs of plasma and RBC fatty acids show promise as sensitive and specific measures of dietary meat. These provide different information from that provided by fatty acid mass proportions, and are informative where mass proportion is not. This trial is registered at www.clinicaltrials.gov as NCT01237093. [ABSTRACT FROM AUTHOR]

The Omega-3 Index (O3I) reflects eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content in erythrocytes. While the O3I is associated with numerous health outcomes, its widespread use is limited. We investigated whether urinary metabolites could be used to non-invasively monitor the O3I in an exploratory analysis of a previous placebo-controlled, parallel arm randomized clinical trial in males and females (n = 88) who consumed either ~3 g/d olive oil (OO; control), EPA, or DHA for 12 weeks. Fasted blood and first-void urine samples were collected at baseline and following supplementation, and they were analyzed via gas chromatography and multisegment injection–capillary electrophoresis–mass spectrometry (MSI-CE-MS), respectively. We tentatively identified S-carboxypropylcysteamine (CPCA) as a novel urinary biomarker reflecting O3I status, which increased following both EPA and DHA (p < 0.001), but not OO supplementation, and was positively correlated to the O3I (R = 0.30, p < 0.001). Additionally, an unknown dianion increased following DHA supplementation, but not EPA or OO. In ROC curve analyses, CPCA outperformed all other urinary metabolites in distinguishing both between OO and EPA or DHA supplementation groups (AUC > 80.0%), whereas the unknown dianion performed best in discriminating OO from DHA alone (AUC = 93.6%). Candidate urinary biomarkers of the O3I were identified that lay the foundation for a non-invasive assessment of omega-3 status.

Previous studies suggest that amino acid carbon stable isotope ratios (CIRAAs) may serve as biomarkers of added sugar (AS) intake, but this has not been tested in a demographically diverse population. We conducted a 15-day feeding study of U.S. adults, recruited across sex, age, and BMI groups. Participants consumed personalized diets that resembled habitual intake, assessed using two consecutive 7-day food records. We measured serum (n = 99) CIRAAs collected at the end of the feeding period and determined correlations with diet. We used forward selection to model AS intake using participant characteristics and 15 CIRAAs. This model was internally validated using bootstrap optimism correction. Median (25th, 75th percentile) AS intake was 65.2 g/day (44.7, 81.4) and 9.5% (7.2%, 12.4%) of energy. The CIR of alanine had the highest, although modest, correlation with AS intake (r = 0.32, p = 0.001). Serum CIRAAs were more highly correlated with animal food intakes, especially the ratio of animal to total protein. The AS model included sex, body weight and 6 CIRAAs. This model had modest explanatory power (multiple R2 = 0.38), and the optimism-corrected R2 was lower (R2 = 0.15). Further investigations in populations with wider ranges of AS intake are warranted. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that components of one‐carbon metabolism, particularly circulating vitamin B6, have an etiological role in renal cell carcinoma (RCC). Vitamin B6 is a cofactor in the transsulfuration pathway. We sought to holistically investigate the role of the transsulfuration pathway in RCC risk. We conducted a nested case‐control study (455 RCC cases and 455 matched controls) within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Plasma samples from the baseline visit were analyzed for metabolites of the transsulfuration pathway, including pyridoxal 5′‐phosphate (PLP, the biologically active form of vitamin B6), homocysteine, serine, cystathionine, and cysteine, in addition to folate. Bayesian conditional logistic regression was used to estimate associations of metabolites with RCC risk as well as interactions with established RCC risk factors. Circulating PLP and cysteine were inversely associated with RCC risk, and these associations were not attenuated after adjustment for other transsulfuration metabolites (odds ratio (OR) and 90% credible interval (CrI) per 1 SD increase in log concentration: 0.76 [0.66, 0.87]; 0.81 [0.66, 0.96], respectively). A comparison of joint metabolite profiles suggested substantially greater RCC risk for the profile representative of low overall transsulfuration function compared to high function (OR 2.70 [90% CrI 1.26, 5.70]). We found some statistical evidence of interactions of cysteine with body mass index, and PLP and homocysteine with smoking status, on their associations with RCC risk. In conclusion, we found evidence suggesting that the transsulfuration pathway may play a role in metabolic dysregulation leading to RCC development. [ABSTRACT FROM AUTHOR]

Background: Circulating dietary biomarkers are not direct proxies for intake, as the biomarkers reflect not only food and supplement consumption but also nutrient absorption, metabolism, and tissue distribution. Therefore, along with nutrient intake, several other upstream factors can impact dietary biomarker concentrations, including demographic, medical history, and genetic factors., Objectives: The aim of this study was to explore the dietary and nondietary determinants of circulating levels of vitamins A, C, D, and E among children aged 6 mo-4 y., Methods: Plasma retinol, β-carotene, ascorbic acid, 25(OH)D, α-tocopherol, and γ-tocopherol were measured in 2887 samples from 1490 children enrolled in The Environmental Determinants of Diabetes in the Young study. Dietary intake was assessed with 3-d food records. Associations of genetic and environmental factors with biomarker concentrations were examined using multivariable linear regression models with random intercepts., Results: All biomarkers except retinol were positively associated with intake of the same nutrient. Inverse associations were identified between recent gastrointestinal infection and β-carotene, ascorbic acid, and α-tocopherol, whereas recent respiratory infection was associated inversely with plasma retinol. Several genetic determinants of biomarker status were identified, validating previously reported findings. For some genetic and environmental exposures, we found evidence of statistical interaction with same-nutrient intake, indicating that the association between intake and biomarker concentration is dependent on the level or status of these other exposures. For example, the association between β-carotene intake and concentration is weaker among children with a recent respiratory infection., Conclusions: Our findings suggest that nondietary exposures including childhood infections can alter micronutrient metabolism. This summary of micronutrient determinants will facilitate improved design of future analyses exploring the role of diet in childhood chronic disease etiology through a better understanding of relevant potential confounders and mediators of the diet-outcome relationships., Competing Interests: Conflict of interest All authors report no conflict of interest., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: High consumption of ultraprocessed foods (UPFs) continues to draw significant public health interest because of the associated negative health outcomes. Metabolomics can contribute to the understanding of the biological mechanisms through which UPFs may influence health., Objectives: To investigate urine and plasma metabolomic biomarkers of UPF intake in adolescents and young adults., Methods: We used data from the Dortmund Nutritional and Anthropometric Longitudinally Designed study to investigate cross-sectional associations of UPF intake with concentrations of urine metabolites in adolescents using 3d weighed dietary records (3d-WDR) and 24-h urine samples (n = 339), and associations of repeatedly assessed UPF intake with concentrations of circulating plasma metabolites in young adults with 3-6 3d-WDRs within 5 y preceding blood measurement (n = 195). Urine and plasma samples were analyzed using mass spectrometry-based metabolomics. Biosample-specific metabolite patterns (MPs) were determined using robust sparse principal components analysis. Multivariable linear regression models were applied to assess the associations of UPF consumption (as a percentage of total food intake in g/d) with concentrations of individual metabolites and MP scores., Results: The median proportion of UPF intake was 22.0% [interquartile range (IQR): 12.3, 32.9] in adolescents and 23.2% (IQR: 16.0, 31.6) in young adults. We identified 42 and 6 UPF intake-associated metabolites in urine and plasma samples, respectively. One urinary MP, "xenobiotics and amino acids" [β = 0.042, 95% confidence interval (CI): 0.014, 0.070] and 1 plasma MP, "lipids, xenobiotics, and amino acids" (β = 0.074, 95% CI: 0.031, 0.117) showed positive association with UPF intake. Both patterns shared 29 metabolites, mostly of xenobiotic metabolism., Conclusions: We identified urine and plasma metabolites associated with UPF intake in adolescents and young adults, which may represent some of the biological mechanisms through which UPFs may influence metabolism and health., Competing Interests: Conflict of interest The authors report no conflicts of interest. Where authors are identified as personnel of the International Agency for Research on Cancer/WHO, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/WHO., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Abstract Background Dietary biomarkers may complement dietary intake assessment made by dietary questionnaires. We developed an a-posteriori dietary biomarkers score based on Mediterranean diet food groups and evaluated its association with mortality. Methods 642 participants (56% female), aged ≥65 years, with complete data on dietary biomarkers were followed during 20 years in the InCHIANTI cohort study (Tuscany, Italy). The main outcomes were all-cause, cardiovascular, and cancer mortality. Dietary biomarkers were selected from literature and from correlation analyses with dietary intakes of Mediterranean diet food groups in the study. The baseline levels of the following dietary biomarkers were chosen: urinary total polyphenols and resveratrol metabolites, and plasma carotenoids, selenium, vitamin B12, linolenic, eicosapentaenoic and docosahexaenoic acids, and the mono-unsaturated/saturated fatty acid ratio. Associations of the Mediterranean diet score using dietary biomarkers and a validated food frequency questionnaire (FFQ) (as tertiles) with mortality were assessed through Cox regression. Results During the 20-year follow-up [median (Q1–Q3), 14 (8–18) years], and 435 deaths occurred (139 from cardiovascular diseases and 89 from cancer-related causes). In the fully adjusted models, the dietary biomarker-Mediterranean diet score was inversely associated with all-cause (HRT3vs.T1 0.72; 95%CI 0.56–0.91) and cardiovascular (HRT3vs.T1 0.60; 95%CI 0.38–0.93), but not with cancer mortality. Associations between the FFQ-Mediterranean diet score and mortality were not statistically significant. Conclusions A greater adherence at baseline to a Mediterranean diet assessed by a dietary biomarker score was associated with a lower risk of mortality in older adults during a 20-year follow-up. The measurement of dietary biomarkers may contribute to guide individualized dietary counseling to older people. Trial registration NCT01331512

The extent to which variation in food-related metabolites are attributable to non-dietary factors remains unclear, which may explain inconsistent food-metabolite associations observed in population studies. This study examined the association between non-dietary factors and the serum concentrations of food-related biomarkers and quantified the amount of variability in metabolite concentrations explained by non-dietary factors. Pregnant women (n = 600) from two Canadian birth cohorts completed a validated semi-quantitative food frequency questionnaire, and serum metabolites were measured by multisegment injection-capillary electrophoresis-mass spectrometry. Hierarchical linear modelling and principal component partial R-square (PC-PR2) were used for data analysis. For proline betaine and DHA (mainly exogenous), citrus foods and fish/fish oil intake, respectively, explained the highest proportion of variability relative to non-dietary factors. The unique contribution of dietary factors was similar (15:0, 17:0, hippuric acid, TMAO) or lower (14:0, tryptophan betaine, 3-methylhistidine, carnitine) compared to non-dietary factors (i.e., ethnicity, maternal age, gestational age, pre-pregnancy BMI, physical activity, and smoking) for metabolites that can either be produced endogenously, biotransformed by gut microbiota, and/or derived from multiple food sources. The results emphasize the importance of adjusting for non-dietary factors in future analyses to improve the accuracy and precision of the measures of food intake and their associations with health and disease. [ABSTRACT FROM AUTHOR]

Subjective reporting of food intake can be unreliable. No objective method is available to distinguish between diets differing in protein type. To address this gap, a secondary analysis of a randomized controlled cross-over feeding trial was conducted. Assessed were fasting plasma metabolite profiles and their associations with cardiometabolic risk factors (CMRFs). Hypercholesterolemic post-menopausal women (N = 11) were provided with diets containing predominantly animal protein (AP) and soy protein (SP). Untargeted metabolomics were used to determine the plasma metabolite profiles at the end of each diet phase. Concentrations of identified metabolites (N = 829) were compared using paired t-tests adjusted for false discovery rate, partial least square-discrimination analysis (PLS-DA) and receiver operating characteristics (ROC). Among the identified metabolites, 58 differed significantly between the AP and SP diets; the majority were phospholipids (n = 36), then amino acids (n = 10), xenobiotics (n = 7), vitamin/vitamin-related (n = 3) and lipids (n = 2). Of the top 10 metabolites, amino acid-derived metabolites, phospholipids and xenobiotics comprised the main categories differing due to dietary protein type. ROC curves confirmed that the top 10 metabolites were potential discriminating biomarkers for AP- and SP-rich diets. In conclusion, amino acid-derived metabolites, phosphatidylethanolamine-derived metabolites and isoflavones were identified as potential metabolite biomarkers distinguishing between dietary protein type. [ABSTRACT FROM AUTHOR]

Background: Dietary biomarkers may complement dietary intake assessment made by dietary questionnaires. We developed an a-posteriori dietary biomarkers score based on Mediterranean diet food groups and evaluated its association with mortality.Methods: 642 participants (56% female), aged ≥65 years, with complete data on dietary biomarkers were followed during 20 years in the InCHIANTI cohort study (Tuscany, Italy). The main outcomes were all-cause, cardiovascular, and cancer mortality. Dietary biomarkers were selected from literature and from correlation analyses with dietary intakes of Mediterranean diet food groups in the study. The baseline levels of the following dietary biomarkers were chosen: urinary total polyphenols and resveratrol metabolites, and plasma carotenoids, selenium, vitamin B12, linolenic, eicosapentaenoic and docosahexaenoic acids, and the mono-unsaturated/saturated fatty acid ratio. Associations of the Mediterranean diet score using dietary biomarkers and a validated food frequency questionnaire (FFQ) (as tertiles) with mortality were assessed through Cox regression.Results: During the 20-year follow-up [median (Q1-Q3), 14 (8-18) years], and 435 deaths occurred (139 from cardiovascular diseases and 89 from cancer-related causes). In the fully adjusted models, the dietary biomarker-Mediterranean diet score was inversely associated with all-cause (HRT3vs.T1 0.72; 95%CI 0.56-0.91) and cardiovascular (HRT3vs.T1 0.60; 95%CI 0.38-0.93), but not with cancer mortality. Associations between the FFQ-Mediterranean diet score and mortality were not statistically significant.Conclusions: A greater adherence at baseline to a Mediterranean diet assessed by a dietary biomarker score was associated with a lower risk of mortality in older adults during a 20-year follow-up. The measurement of dietary biomarkers may contribute to guide individualized dietary counseling to older people.Trial Registration: NCT01331512. [ABSTRACT FROM AUTHOR]

Previous studies suggest that amino acid carbon stable isotope ratios (CIRAAs) may serve as biomarkers of added sugar (AS) intake, but this has not been tested in a demographically diverse population. We conducted a 15-day feeding study of U.S. adults, recruited across sex, age, and BMI groups. Participants consumed personalized diets that resembled habitual intake, assessed using two consecutive 7-day food records. We measured serum (n = 99) CIRAAs collected at the end of the feeding period and determined correlations with diet. We used forward selection to model AS intake using participant characteristics and 15 CIRAAs. This model was internally validated using bootstrap optimism correction. Median (25th, 75th percentile) AS intake was 65.2 g/day (44.7, 81.4) and 9.5% (7.2%, 12.4%) of energy. The CIR of alanine had the highest, although modest, correlation with AS intake (r = 0.32, p = 0.001). Serum CIRAAs were more highly correlated with animal food intakes, especially the ratio of animal to total protein. The AS model included sex, body weight and 6 CIRAAs. This model had modest explanatory power (multiple R2 = 0.38), and the optimism-corrected R2 was lower (R2 = 0.15). Further investigations in populations with wider ranges of AS intake are warranted.

Background Vitamin B6 insufficiency has been linked to increased risk of cancer and other chronic diseases. The circulating concentration of pyridoxal 5′-phosphate (PLP) is a commonly used measure of vitamin B6 status. Ratios of substrates indicating PLP coenzymatic function and metabolism may be useful complementary measures to further explore the role of vitamin B6 in health. Objectives We explored the sensitivity of 5 outcomes, namely PLP concentration, homocysteine:cysteine (Hcy:Cys), cystathionine:cysteine (Cysta:Cys), the 3´-hydroxykynurenine ratio (HKr), and the 4-pyridoxic acid ratio (PAr) to vitamin B6 intake as well as personal and lifestyle characteristics. Medthods Dietary intake and biomarker data were collected from participants from 3 nested case-control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC). Bayesian regression models assessed the associations of the 5 biomarker outcomes with vitamin B6 intake and personal and lifestyle covariates. Analogous models examined the relations of Hcy:Cys, Cysta:Cys, and HKr with PLP. Results In total, 4608 participants were included in the analyses. Vitamin B6 intake was most strongly associated with PLP, moderately associated with Hcy:Cys, Cysta:Cys, and HKr, and not associated with PAr (fold change in marker given a doubling of vitamin B6 intake: PLP 1.60 [95% credible interval (CrI): 1.50, 1.71]; Hcy:Cys 0.87 [95% CrI: 0.84, 0.90]; Cysta:Cys 0.89 [95% CrI: 0.84, 0.94]; HKr 0.88 [95% CrI: 0.85, 0.91]; PAr 1.00 [95% CrI: 0.95, 1.05]). PAr was most sensitive to age, and HKr was least sensitive to BMI and alcohol intake. Sex and menopause status were strongly associated with all 5 markers. Conclusions We found that 5 different markers, capturing different aspects of vitamin B6–related biological processes, varied in their associations with vitamin B6 intake and personal and lifestyle predictors. [ABSTRACT FROM AUTHOR]

Methods to objectively assess fruit and vegetable (FV) intake in young children are needed in order to support rigorous assessments of policies and interventions. Noninvasive skin carotenoid concentration measurements may provide a rapid assessment of toddler carotenoid and carotenoid-rich FV intake. The aim of this study was to evaluate the relationship between pressure-mediated reflection spectroscopy-measured skin carotenoid score (SCS) with proxy-reported carotenoid and FV intake in racially and ethnically diverse US toddlers. This study was a secondary analysis of data obtained from a randomized controlled 10-week study of the effect of an interactive healthy playgroup intervention vs classroom parent education on the diet and physical activity of toddlers. This study collected skin carotenoid and 1-week dietary intake using a 31-item semi-quantitative food frequency questionnaire analyzed by the Nutrient Data System for Research nutrient database. The current study determined dietary predictors of toddler SCS. Participants were racially and ethnically diverse US toddlers (12 to 36 months) and adult guardian dyads (n = 50) recruited from the community in Houston, TX from fall 2018 to spring 2019. At baseline and 10 to 12 weeks after baseline, SCS was measured by means of pressure-mediated reflection spectroscopy (Veggie Meter, Longevity Link Corporation), guardians reported toddler diet using a food frequency questionnaire, and carotenoid intake was estimated from the food frequency questionnaire responses using a nutrient database. The relationship between toddler SCS and intake of total and individual carotenoid species and FV servings was tested using generalized linear mixed models, controlling for body mass index-for-age percentiles, group assignment, and age. SCS was positively and significantly predicted by estimated intakes of total carotenoids (P =.002), β-carotene (P ≤.001), and lutein and zeaxanthin (P =.003). Reported intakes of α-carotene, β-cryptoxanthin, and lycopene were not predictors of SCS. SCS was predicted by estimated total FV intake (P =.047) and vegetable intake (P =.006), but not fruit intake (P =.580). These results showed that reported dietary carotenoid intake is a significant predictor of SCS in an ethnically and racially diverse population of US toddlers. Toddler skin carotenoid measurement holds promise as a rapid, objective, noninvasive biomarker of dietary carotenoid intake. [ABSTRACT FROM AUTHOR]

The extent to which variation in food-related metabolites are attributable to non-dietary factors remains unclear, which may explain inconsistent food-metabolite associations observed in population studies. This study examined the association between non-dietary factors and the serum concentrations of food-related biomarkers and quantified the amount of variability in metabolite concentrations explained by non-dietary factors. Pregnant women (n = 600) from two Canadian birth cohorts completed a validated semi-quantitative food frequency questionnaire, and serum metabolites were measured by multisegment injection-capillary electrophoresis-mass spectrometry. Hierarchical linear modelling and principal component partial R-square (PC-PR2) were used for data analysis. For proline betaine and DHA (mainly exogenous), citrus foods and fish/fish oil intake, respectively, explained the highest proportion of variability relative to non-dietary factors. The unique contribution of dietary factors was similar (15:0, 17:0, hippuric acid, TMAO) or lower (14:0, tryptophan betaine, 3-methylhistidine, carnitine) compared to non-dietary factors (i.e., ethnicity, maternal age, gestational age, pre-pregnancy BMI, physical activity, and smoking) for metabolites that can either be produced endogenously, biotransformed by gut microbiota, and/or derived from multiple food sources. The results emphasize the importance of adjusting for non-dietary factors in future analyses to improve the accuracy and precision of the measures of food intake and their associations with health and disease.

Background Early applications of metabolomics in nutrition and health research identified associations between dietary patterns and metabolomic profiles. Twin studies show that diet-related phenotypes and diet-associated metabolites are influenced by genes. However, studies have not examined whether diet–metabolite associations are explained by genetic or environmental factors and whether these associations are reproducible over multiple time points. Objective This research aims to examine the genetic and environmental factors influencing covariation in diet–metabolite associations that are reproducible over time in healthy twins. Methods The UCD Twin Study is a semi-longitudinal classic twin study that collected repeated dietary, anthropometric, and urinary data over 2 months. Correlation analysis identified associations between diet quality measured using the Healthy Eating Index (HEI) and urinary metabolomic profiles at 3 time points. Diet-associated metabolites were examined using linear regression to identify those significantly influenced by familial factors between twins and those significantly influenced by unique factors. Cholesky decomposition modeling quantified the genetic and environmental path coefficients through associated dietary components onto the metabolites. Results The HEI was associated with 14 urinary metabolites across 3 metabolomic profiles (r: ±0.15–0.49). For 8 diet–metabolite associations, genetic or shared environmental factors influencing HEI component scores significantly influenced variation in metabolites (β: 0.40–0.52). A significant relation was observed between dietary intakes of whole grain and acetoacetate (β: −0.50, P  < 0.001) and β-hydroxybutyrate (β: −0.46, P  < 0.001), as well as intakes of saturated fat and acetoacetate (β: 0.47, P  < 0.001) and β-hydroxybutyrate (β: 0.52, P  < 0.001). For these diet–metabolite associations a common shared environmental factor explained 66–69% of variance in the metabolites. Conclusions This study shows that diet–metabolite associations are reproducible in 3 urinary metabolomic profiles. Components of the HEI covary with metabolites, and covariation is largely due to the shared environment. [ABSTRACT FROM AUTHOR]

Background: Fermented foods are ubiquitous in human diets and often lauded for their sensory, nutritious, and health-promoting qualities. However, precise associations between the intake of fermented foods and health have not been well-established. This is in part due to the limitations of current dietary assessment tools that rely on subjective reporting, making them prone to memory-related errors and reporting bias. The identification of food intake biomarkers (FIBs) bypasses this challenge by providing an objective measure of intake. Despite numerous studies reporting on FIBs for various types of fermented foods and drinks, unique biomarkers associated with the fermentation process ("fermentation-dependent" biomarkers) have not been well documented. We therefore conducted a comprehensive, systematic review of the literature to identify biomarkers of fermented foods commonly consumed in diets across the world. Results: After title, abstract, and full-text screening, extraction of data from 301 articles resulted in an extensive list of compounds that were detected in human biofluids following the consumption of various fermented foods, with the majority of articles focusing on coffee (69), wine (69 articles), cocoa (62), beer (34), and bread (29). The identified compounds from all included papers were consolidated and sorted into FIBs proposed for a specific food, for a food group, or for the fermentation process. Alongside food-specific markers (e.g., trigonelline for coffee), and food-group markers (e.g., pentadecanoic acid for dairy intake), several fermentation-dependent markers were revealed. These comprised compounds related to the fermentation process of a particular food, such as mannitol (wine), 2-ethylmalate (beer), methionine (sourdough bread, cheese), theabrownins (tea), and gallic acid (tea, wine), while others were indicative of more general fermentation processes (e.g., ethanol from alcoholic fermentation, 3-phenyllactic acid from lactic fermentation). Conclusions: Fermented foods comprise a heterogeneous group of foods. While many of the candidate FIBs identified were found to be non-specific, greater specificity may be observed when considering a combination of compounds identified for individual fermented foods, food groups, and from fermentation processes. Future studies that focus on how fermentation impacts the composition and nutritional quality of food substrates could help to identify novel biomarkers of fermented food intake. [ABSTRACT FROM AUTHOR]

Dietary and food intake biomarkers offer the potential of improving the accuracy of dietary assessment. An extensive range of putative intake biomarkers of commonly consumed foods have been identified to date. As the field of food intake biomarkers progresses toward solving the complexities of dietary habits, combining biomarkers associated with single foods or food groups may be required. The objective of this work was to examine the ability of a multi-biomarker panel to classify individuals into categories of fruit intake. Biomarker data was measured using 1H NMR spectroscopy in two studies: (1) An intervention study where varying amounts of fruit was consumed and (2) the National Adult Nutrition Survey (NANS). Using data from an intervention study a biomarker panel (Proline betaine, Hippurate, and Xylose) was constructed from three urinary biomarker concentrations. Biomarker cut-off values for three categories of fruit intake were developed. The biomarker sum cut-offs were ≤ 4.766, 4.766–5.976, >5.976 μM/mOsm/kg for 160 g fruit intake. The ability of the biomarker sum to classify individuals into categories of fruit intake was examined in the cross-sectional study (NANS) (N = 565). Examination of results in the cross-sectional study revealed excellent agreement with self-reported intake: a similar number of participants were ranked into each category of fruit intake. The work illustrates the potential of multi-biomarker panels and paves the way forward for further development in the field. The use of such panels may be key to distinguishing foods and adding specificity to the predictions of food intake.

Purpose: Little is known about the aetiology of renal cell carcinoma (RCC). Components of one-carbon (1C) metabolism, which are required for nucleotide synthesis and methylation reactions, may be related to risk of RCC but existing evidence is inconclusive. We conducted a systematic review and independent exposure-specific meta-analyses of dietary intake and circulating biomarkers of 1C metabolites and RCC risk. Methods: Medline and Embase databases were searched for observational studies investigating RCC or kidney cancer incidence or mortality in relation to components of 1C metabolism and 12 eligible articles were included in the meta-analyses. We used Bayesian meta-analyses to estimate summary relative risks (RRs) and 95% credible intervals (CrIs) comparing the highest versus lowest categories as well as the between-study heterogeneity. Results: We did not find convincing evidence of an association between any exposure (riboflavin, vitamin B6, folate, vitamin B12, methionine, homocysteine, choline, or betaine) and RCC risk. However, vitamin B6 biomarker status did have a protective (RR = 0.62) but imprecise (95% CrI 0.39–1.14) effect estimate and folate intake had a notable association as well (RR = 0.85, 95% CrI 0.71–1.01). Conclusion: There was a lack of precision due largely to the low number of studies. Further investigation is warranted, especially for folate and vitamin B6, which had consistent suggestive evidence of a protective effect for both dietary intake and biomarker status. A unique strength of this review is the use of Bayesian meta-analyses which allowed for robust estimation of between-study heterogeneity. [ABSTRACT FROM AUTHOR]

We examined whether change in added sugar intake is associated with change in δ13C, a novel sugar biomarker, in thirty-nine children aged 5–10 years selected from a Colorado (USA) prospective cohort of children at increased risk for type 1 diabetes. Reported added sugar intake via FFQ and δ13C in erythrocytes were measured at two time points a median of 2 years apart. Change in added sugar intake was associated with change in the δ13C biomarker, where for every 1-g increase in added sugar intake between the two time points, there was an increase in δ13C of 0⋅0082 (P = 0⋅0053), independent of change in HbA1c and δ15N. The δ13C biomarker may be used as a measure of compliance in an intervention study of children under the age of 10 years who are at increased risk for type 1 diabetes, in which the goal was to reduce dietary sugar intake.

Subjective reporting of food intake can be unreliable. No objective method is available to distinguish between diets differing in protein type. To address this gap, a secondary analysis of a randomized controlled cross-over feeding trial was conducted. Assessed were fasting plasma metabolite profiles and their associations with cardiometabolic risk factors (CMRFs). Hypercholesterolemic post-menopausal women (N = 11) were provided with diets containing predominantly animal protein (AP) and soy protein (SP). Untargeted metabolomics were used to determine the plasma metabolite profiles at the end of each diet phase. Concentrations of identified metabolites (N = 829) were compared using paired t-tests adjusted for false discovery rate, partial least square-discrimination analysis (PLS-DA) and receiver operating characteristics (ROC). Among the identified metabolites, 58 differed significantly between the AP and SP diets; the majority were phospholipids (n = 36), then amino acids (n = 10), xenobiotics (n = 7), vitamin/vitamin-related (n = 3) and lipids (n = 2). Of the top 10 metabolites, amino acid-derived metabolites, phospholipids and xenobiotics comprised the main categories differing due to dietary protein type. ROC curves confirmed that the top 10 metabolites were potential discriminating biomarkers for AP- and SP-rich diets. In conclusion, amino acid-derived metabolites, phosphatidylethanolamine-derived metabolites and isoflavones were identified as potential metabolite biomarkers distinguishing between dietary protein type.

Background Advances in metabolomics are anticipated to decipher associations between dietary exposures and health. Replication biomarker studies in different populations are critical to demonstrate generalizability. Objectives To identify and validate robust serum metabolites associated with diet quality and specific foods in a multiethnic cohort of pregnant women. Design In this cross-sectional analysis of 3 multiethnic Canadian birth cohorts, we collected semiquantitative FFQ and serum data from 900 women at the second trimester of pregnancy. We calculated a diet quality score (DQS), defined as daily servings of "healthy" minus "unhealthy" foods. Serum metabolomics was performed by multisegment injection-capillary electrophoresis-mass spectrometry, and specific serum metabolites associated with maternal DQSs were identified. We combined the results across all 3 cohorts using meta-analysis to classify robust dietary biomarkers (r > ± 0.1; P < 0.05). Results Diet quality was higher in the South Asian birth cohort (mean DQS = 7.1) than the 2 white Caucasian birth cohorts (mean DQS <3.2). Sixty-six metabolites were detected with high frequency (>75%) and adequate precision (CV <30%), and 47 were common to all cohorts. Hippuric acid was positively associated with healthy diet score in all cohorts, and with the overall DQS only in the primarily white Caucasian cohorts. We observed robust correlations between: 1) proline betaine—citrus foods; 2) 3-methylhistidine—red meat, chicken, and eggs; 3) hippuric acid—fruits and vegetables; 4) trimethylamine N -oxide (TMAO)—seafood, meat, and eggs; and 5) tryptophan betaine—nuts/legumes. Conclusions Specific serum metabolites reflect intake of citrus fruit/juice, vegetables, animal foods, and nuts/legumes in pregnant women independent of ethnicity, fasting status, and delays to storage across multiple collection centers. Robust biomarkers of overall diet quality varied by cohort. Proline betaine, 3-methylhistidine, hippuric acid, TMAO, and tryptophan betaine were robust dietary biomarkers for investigations of maternal nutrition in diverse populations. [ABSTRACT FROM AUTHOR]

We examined whether change in added sugar intake is associated with change in δ13C, a novel sugar biomarker, in thirty-nine children aged 5–10 years selected from a Colorado (USA) prospective cohort of children at increased risk for type 1 diabetes. Reported added sugar intake via FFQ and δ13C in erythrocytes were measured at two time points a median of 2 years apart. Change in added sugar intake was associated with change in the δ13C biomarker, where for every 1-g increase in added sugar intake between the two time points, there was an increase in δ13C of 0⋅0082 (P = 0⋅0053), independent of change in HbA1c and δ15N. The δ13C biomarker may be used as a measure of compliance in an intervention study of children under the age of 10 years who are at increased risk for type 1 diabetes, in which the goal was to reduce dietary sugar intake. [ABSTRACT FROM AUTHOR]

Background Processed meat intake is associated with a higher risk of colorectal and stomach cancers, coronary artery disease, and type 2 diabetes and with higher mortality, but the estimation of intake of different processed meat products in this heterogeneous food group in epidemiological studies remains challenging. Objective This work aimed at identifying novel biomarkers for processed meat intake using metabolomics. Methods An untargeted, multi-tiered metabolomics approach based on LC-MS was applied to 33 meat products digested in vitro and secondly to urine and plasma samples from a randomized crossover dietary intervention in which 12 volunteers consumed successively 3 processed meat products (bacon, salami, and hot dog) and 2 other foods used as controls, over 3 consecutive days. The putative biomarkers were then measured in urine from 474 subjects from the European Prospective Investigation into Cancer and Nutrition (EPIC) cross-sectional study for which detailed 24-h dietary recalls and FFQs were available. Results Syringol and 4 derivatives of syringol were found to be characteristic of in vitro digests of smoked meat products. The same compounds present as sulfate esters in urine increased at 2 and 12 h after consumption of smoked meat products (hot dog, bacon) in the intervention study. The same syringol sulfates were also positively associated with recent or habitual consumption of smoked meat products in urine samples from participants of the EPIC cross-sectional study. These compounds showed good discriminative ability for smoked meat intake with receiver operator characteristic areas under the curve ranging from 0.78 to 0.86 and 0.74 to 0.79 for short-term and habitual intake, respectively. Conclusions Four novel syringol sulfates were identified as potential biomarkers of smoked meat intake and may be used to improve assessment of smoked meat intake in epidemiological studies. This trial was registered at clinicaltrials.gov as NCT03354130. [ABSTRACT FROM AUTHOR]

Background: The iodine status of the US population is considered adequate, but subpopulations remain at risk for iodine deficiency and a biomarker of individual iodine status has yet to be determined. The purpose of this study was to determine whether a 3 day titration diet, providing known quantities of iodized salt, is reflected in 24 h urinary iodine concentration (UIC), serum iodine, and thyroglobulin (Tg). Methods: A total of 10 participants (31.3 ± 4.0 years, 76.1 ± 6.3 kg) completed three, 3 day iodine titration diets (minimal iodine, US RDA, (United States Recommended Daily Allowance), and 3× RDA). The 24 h UIC, serum iodine, and Tg were measured following each diet. The 24 h UIC and an iodine-specific food frequency questionnaire (FFQ) were completed at baseline. Results: UIC increased an average of 19.3 μg/L for every gram of iodized salt consumed and was different from minimal to RDA (p = 0.001) and RDA to 3× RDA diets (p = 0.04). Serum iodine was different from RDA to 3× RDA (p = 0.006) whereas Tg was not responsive to diet. Baseline UIC was associated with iodine intake from milk (r = 0.688, p = 0.028) and fish/seafood (r = 0.646, p = 0.043). Conclusion: These results suggest that 24 h UIC and serum iodine may be reflective of individual iodine status and may serve as biomarkers of iodine status.

Background: Metabolomics has the potential to enhance dietary assessment by revealing objective measures of many aspects of human food intake. Although metabolomics studies indicate that hundreds of metabolites are associated with dietary intake, correlations have been modest (e.g., r < 0.50), and few have been evaluated in controlled feeding studies., Objectives: The aim of this study was to evaluate associations between metabolites and weighed food and beverage intake in a controlled feeding study of habitual diet., Methods: Healthy postmenopausal females from the Women's Health Initiative (N = 153) were provided with a customized 2-wk controlled diet designed to emulate their usual diet. Metabolites were measured by liquid chromatography tandem mass spectrometry in end-of-study 24-h urine and fasting serum samples (1293 urine metabolites; 1113 serum metabolites). We calculated partial Pearson correlations between these metabolites and intake of 65 food groups, beverages, and supplements during the feeding study. The threshold for significance was Bonferroni-adjusted to account for multiple testing (5.94 × 10 -07 for urine metabolites; 6.91 × 10 -07 for serum metabolites)., Results: Significant diet-metabolite correlations were identified for 23 distinct foods, beverages, and supplements (171 distinct metabolites). Among foods, strong metabolite correlations (r ≥ 0.60) were evident for citrus (highest r = 0.80), dairy (r = 0.65), and broccoli (r = 0.63). Among beverages and supplements, strong correlations were evident for coffee (r = 0.86), alcohol (r = 0.69), multivitamins (r = 0.69), and vitamin E supplements (r = 0.65). Moderate correlations (r = 0.50-0.60) were also observed for avocado, fish, garlic, grains, onion, poultry, and black tea. Correlations were specific; each metabolite correlated with one food, beverage, or supplement, except for metabolites correlated with juice or multivitamins., Conclusions: Metabolite levels had moderate to strong correlations with weighed intake of habitually consumed foods, beverages, and supplements. These findings exceed in magnitude those previously observed in population studies and exemplify the strong potential of metabolomics to contribute to nutrition research. The Women's Health Initiative is registered at clinicaltrials.gov as NCT00000611., (Copyright © 2023. Published by Elsevier Inc.)

Background: Natural abundance stable isotope ratios are candidate biomarkers of dietary intake that have not been evaluated in a controlled feeding study in a US population.Objectives: Our goals were to evaluate dietary associations with serum carbon (CIR), nitrogen (NIR), and sulfur (SIR) isotope ratios in postmenopausal women, and to evaluate whether statistical models of dietary intake that include multiple isotopes and participant characteristics meet criteria for biomarker evaluation.Methods: Postmenopausal women from the Women's Health Initiative (n = 153) were provided a 2-wk controlled diet that approximated each individual's habitual food intake. Dietary intakes of animal protein, fish/seafood, red meat, poultry, egg, dairy, total sugars, added sugars, sugar-sweetened beverages (SSBs), and corn products were characterized during the feeding period with the use of the Nutrition Data System for Research (NDS-R). The CIR, NIR, and SIR were measured in sera collected from fasting women at the beginning and the end of the feeding period. Linear models based on stable isotope ratios and participant characteristics predicted dietary intake. The criterion used for biomarker evaluation was R2 ≥ 0.36, based on the study's power to detect true associations with R2 ≥ 0.50.Results: The NIR was associated with fish/seafood intake and met the criterion for biomarker evaluation (R2 = 0.40). The CIR was moderately associated with intakes of red meat and eggs, but not to the criterion for biomarker evaluation, and was not associated with intake of sugars (total, added, or SSB). A model of animal protein intake based on the NIR, CIR, and participant characteristics met the criterion for biomarker evaluation (R2 = 0.40). Otherwise, multiple isotopes did not improve models of intake, and improvements from including participant characteristics were modest.Conclusion: Serum stable isotope ratios can, with participant characteristics, meet biomarker criteria as measures of fish/seafood and animal protein intake in a sample of postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00000611. [ABSTRACT FROM AUTHOR]

Background: Methods to objectively assess fruit and vegetable (FV) intake in young children are needed in order to support rigorous assessments of policies and interventions. Non-invasive skin carotenoid concentration measurements may provide a rapid assessment of toddler carotenoid and carotenoid-rich FV intake. background OBJECTIVE: The aim of this study was to evaluate the relationship between pressure-mediated reflection spectroscopy-measured skin carotenoid scores (SCSs) with proxy-reported carotenoid and FV intake in racially and ethnically diverse, US toddlers., Design: This study was a secondary analysis of data obtained from a randomized, controlled 10-week study of the effect of an interactive healthy playgroup intervention versus classroom parent education on the diet and physical activity of toddlers. This study collected skin carotenoid and 1-week dietary intake using a 31-item semi-quantitative food frequency questionnaire analyzed by Nutrient Data System for Research nutrient database. The current study determined dietary predictors of toddler SCSs., Participants/setting: Participants were racially and ethnically diverse toddlers (12-36 months) and adult guardian dyads (N=50) recruited from the community in Houston, TX from Fall 2018-Spring 2019., Main Outcome Measures: At baseline and 10-12 weeks after baseline, SCSs were measured by pressure-mediated reflection spectroscopy (Veggie Meter (TM)), guardians reported toddler diet using a food frequency questionnaire (FFQ), and carotenoid intake was estimated from the FFQ responses using a nutrient database., Statistical Analysis: The relationship between toddler SCSs and intake of total and individual carotenoid species, and FV servings was tested using generalized linear mixed models, controlling for BMI-for-age percentiles, group assignment, and age., Results: SCSs were positively and significantly predicted by estimated intakes of total carotenoids (p=0.002), beta-carotene (p=<0.001), and lutein & zeaxanthin (p=0.003). Reported intakes of alpha-carotene, beta-cryptoxanthin, and lycopene were not predictors of SCS. Skin carotenoid scores were predicted by estimated total FV intake (p=0.047) and vegetable intake (p=0.006), but not fruit intake (p=0.580). results CONCLUSION: These results showed that reported dietary carotenoid intake is a significant predictor of SCSs in an ethnically and racially diverse population of toddlers. Toddler skin carotenoid measurement holds promise as a rapid, objective, non-invasive biomarker of dietary carotenoid intake., (Copyright © 2023 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Background: Objective indicators of dietary intake (e.g., biomarkers) are needed to overcome the limitations of self-reported dietary intake assessment methods in adolescents. To our knowledge, no controlled feeding studies to date have evaluated the validity of urinary sodium, nitrogen, or sugar excretion as dietary biomarkers in adolescents.Objective: This investigation aimed to evaluate the validity of urinary sodium, nitrogen, and total sugars (TS) excretion as biomarkers for sodium, protein, and added sugars (AS) intake in nonobese adolescents.Methods: In a crossover controlled feeding study design, 33 adolescents [12-18 y of age, 47 ± 25th percentile (mean ± SD) of body mass index (BMI; in kg/m2) for age] consumed 5% AS [low added sugars (LAS)] and 25% AS [high added sugars (HAS)] isocaloric, macronutrient-matched (55% carbohydrate, 30% fat, and 15% protein) diets for 7 d each, in a randomly assigned order, with a 4-wk washout period between diets. On the final 2 d of each diet period, 24-h urine samples were collected. Thirty-two adolescents completed all measurements (97% retention).Results: Urinary sodium was not different from the expected 90% recovery (mean ± SD: 88% ± 18%, P = 0.50). Urinary nitrogen was correlated with protein intake (r = 0.69, P < 0.001), although it was below the 80% expected recovery (62% ± 7%, P < 0.001). Urinary TS values were correlated with AS intake during the HAS diet (r = 0.77, P < 0.001) and had a higher R2 value of 0.28 than did AS intake (R2 = 0.36). TS excretion differed between LAS (0.226 ± 0.09 mg/d) and HAS (0.365 ± 0.16 mg/d) feeding periods (P < 0.001).Conclusions: Urinary sodium appears to be a valid biomarker for sodium intake in nonobese adolescents. Urinary nitrogen is associated with protein intake, but nitrogen excretion rates were less than previously reported for adults, possibly owing to adolescent growth rates. TS excretion reflects AS at 25% AS intake and was responsive to the change in AS intake. Thus, urinary biomarkers are promising objective indicators of dietary intake in adolescents, although larger-scale feeding trials are needed to confirm these findings. This trial was registered at clinicaltrials.gov as NCT02455388. [ABSTRACT FROM AUTHOR]

Metabolomics is one of the most reliable and widely used approaches to reveal the identity of a variety of bioactive metabolites. It is referred to as 'Foodomics' in food science and as 'Nutrimetabolomics' in nutrition. Nutrimetabolomics has been effectively used in nutritional sciences for intervention studies, identification of dietary biomarkers, and to study the role of metabolomics phenotyping in personalized nutrition for diet-related disorders, such as type 2 diabetes, obesity, metabolic syndrome, and prediabetes. NMR-based nutrimetabolomics has been preferred over the other approaches due to its reliability, sensitivity, reproducibility, and specificity in detecting metabolites relating to human nutrition and metabolic disorders. Clinical samples such as blood, urine, and feces could be analyzed for specific biomarkers involving NMR spectroscopic investigation followed by chemometric analysis. In this review, we have focused on NMR-based nutrimetabolomics strategies and their role in identifying dietary and disease related biomarkers of significance to human nutrition and health. Moreover, this NMR-based metabolomics can play a significant role in determining, understanding, and regulating metabolites involved in the multidimensional and complex area of functional foods and diet-related metabolic diseases. This will disclose the application of NMR nutrimetabolomics in advanced precision and personalized nutrition, food authentication, and diet-oriented disease management system. [Display omitted] • NMR-based approaches to analyze and identify a variety of bioactive metabolites. • Role of metabolomic phenotyping in personalized nutrition for diet-related disorder. • Nutrimetabolomics in detection of human diet related biomarker and disease disorder. • NMR-nutrimetabolomics strategies to identify dietary and disease-related biomarkers. • Advanced precision, personalize nutrition, food authentication and diet-orientation. [ABSTRACT FROM AUTHOR]

Metabolomic and microbiome profiling are promising tools to identify biomarkers of food intake and health status. The individual's genetic makeup plays a significant role on health, metabolism, gut microbes and diet and twin studies provide unique opportunities to untangle gene–environment effects on complex phenotypes. This brief review discusses the value of twin studies in nutrition research with a particular focus on metabolomics and the gut microbiome. Although, the twin model is a powerful tool to segregate the genetic component, to date, very few studies combine the twin design and metabolomics/microbiome in nutritional sciences. Moreover, since the individual's diet has a strong influence on the microbiome composition and the gut microbiome is modifiable (60 % of microbiome diversity is due to the environment), future studies should target the microbiome via dietary interventions. [ABSTRACT FROM PUBLISHER]