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Precision nutrition requires precise tools to monitor dietary habits. Yet current dietary assessment instruments are subjective, limiting our understanding of the causal relationships between diet and health. Biomarkers of food intake (BFIs) hold promise to increase the objectivity and accuracy of dietary assessment, enabling adjustment for compliance and misreporting. Here, we update current concepts and provide a comprehensive overview of BFIs measured in urine and blood. We rank BFIs based on a four-level utility scale to guide selection and identify combinations of BFIs that specifically reflect complex food intakes, making them applicable as dietary instruments. We discuss the main challenges in biomarker development and illustrate key solutions for the application of BFIs in human studies, highlighting different strategies for selecting and combining BFIs to support specific study designs. Finally, we present a roadmap for BFI development and implementation to leverage current knowledge and enable precision in nutrition research., (© 2024. Springer Nature Limited.)

Purpose: Alkylresorcinols (AR) are phenolic lipids present in the bran of wheat and rye. Plasma AR and their urinary metabolites may be suitable biomarkers of whole-grain (WG) wheat and rye consumption. The objective of this study was to examine plasma AR and urinary AR metabolites in response to WG wheat consumption., Methods: In a randomized crossover study, 19 subjects (10 males, 9 females; BMI 22.0 kg/m(2); age 26 years) incorporated either 3 servings (48 g) or 6 servings (96 g) of WG wheat daily into their regular diet for 1 week. Subjects completed a 2-week washout period, abstaining from all WG consumption, before each intervention. Fasting blood and 24-h urine were collected before and after each intervention. Plasma AR homologues (C19:0, C21:0, C23:0) were quantified by GC-MS after diethyl ether and solid phase extraction and derivatization. Urinary AR metabolites [3,5-dihydroxybenzoic acid and 3-(3,5-dihydroxyphenyl)-propanoic acid] were determined using HPLC with electrochemical detection after enzymatic deconjugation and ethyl acetate extraction., Results: Urinary total AR metabolites were significantly higher after 6 compared with 3 servings of WG wheat (56 vs. 32 μmol/day, P < 0.001). This dose-response relationship was independent of age, sex, energy intake, and baseline urinary AR metabolite concentration. Plasma total AR tended to be higher after 6 compared with 3 servings of WG wheat (103.0 vs. 86.9 nmol/L), but this difference was not significant (P = 0.42)., Conclusion: The results suggest that urinary AR metabolites from 24-h urine collections may be useful as biomarkers of compliance in intervention studies of WG wheat.

Scope: Whole grain (WG) intake is associated with decreased risk of developing colorectal cancer, type 2 diabetes, and cardiovascular disease and its comorbidities. However, the role of specific grains is unclear. Moreover, intake of specific WG is challenging to measure accurately with traditional dietary assessment methods. Our aim was to use nontargeted metabolite profiling to discover specific urinary biomarkers for WG rye to objectively reflect intake under free-living conditions., Methods and Results: WG rye intake was estimated by weighed food records, and 24 h urine collections were analyzed by LC-MS. Multivariate modeling was undertaken by repeated double cross-validated partial least squares regression against reported WG rye intake, which correlated well with multivariate prediction estimates (r = 0.67-0.80, p < 0.001), but not with intakes of WG wheat or oats. Hydroxyhydroxyphenyl acetamide sulfate, 3,5-dihydroxyphenylpropionic acid sulfate, caffeic acid sulfate, and hydroxyphenyl acetamide sulfate were among the 20 features that had the greatest potential as intake biomarkers of WG. In addition, three compounds exhibited MS/MS fragmentation of carnitine structures., Conclusion: With this nontargeted approach, we confirmed the specificity of alkylresorcinol metabolites as biomarkers for WG rye intake, but also discovered other compounds that should be evaluated as putative biomarkers in future studies., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: High intake of polyunsaturated fatty acids (PUFAs) may reduce the risk of cardiovascular disease (CVD) and mortality. Large, prospective studies including both sexes and circulating PUFAs as dietary biomarkers are needed. We investigated sex-specific associations of the major dietary PUFAs, eicosapentaenoic acid, docohexaenoic acid, linoleic acid, and α-linolenic acid, with incident CVD and all-cause mortality in a population-based cohort., Methods and Results: PUFAs in serum cholesterol esters were measured at baseline in 60-year-old Swedish women (n=2193) and men (n=2039). With the use of national registers, 484 incident CVD events (294 men and 190 women) and 456 all-cause deaths (265 men and 191 women) were identified during follow-up (median, 14.5 years) in individuals without prior CVD at baseline. Associations of PUFAs with CVD and mortality were evaluated with Cox proportional hazard models. In multivariable-adjusted models, 1-SD increases in eicosapentaenoic acid and docohexaenoic acid were associated with lower risk of incident CVD among women (hazard ratio [HR], 0.79 [95% confidence interval (CI), 0.64-0.97] and 0.74 [95% CI, 0.61-0.89], respectively). α-Linolenic acid was associated with moderately increased CVD risk in women (HR, 1.16; 95% CI, 1.02-1.32). Inverse associations with all-cause mortality were observed for eicosapentaenoic acid and docohexaenoic acid among all participants (HR, 0.81 [95% CI, 0.72-0.91] and 0.80 [95% CI, 0.72-0.89], respectively) and for linoleic acid in men (HR, 0.73; 95% CI, 0.64-0.83)., Conclusions: Serum linoleic acid and very-long-chain n-3 PUFAs, partly reflecting vegetable oil and fish intake, respectively, were inversely associated with all-cause mortality. Inverse associations of eicosapentaenoic acid and docohexaenoic acid with incident CVD were observed only in women., (© 2015 American Heart Association, Inc.)

Assessment of compliance with dietary interventions is necessary to understand the observed magnitude of the health effects of the diet per se. To avoid reporting bias, different dietary biomarkers (DBs) could be used instead of self-reported data. However, few studies investigated a combination of DBs to assess compliance and its influence on cardiometabolic risk factors. The objectives of this study were to use a combination of DBs to assess compliance and to investigate how a healthy Nordic diet (ND) influences cardiometabolic risk factors in participants with high apparent compliance compared with the whole study population. From a recently conducted isocaloric randomized trial, SYSDIET (Systems Biology in Controlled Dietary Interventions and Cohort Studies), in 166 individuals with metabolic syndrome, several DBs were assessed to reflect different key components of the ND: canola oil (serum phospholipid α-linolenic acid), fatty fish [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)], vegetables (plasma β-carotene), and whole grains (plasma alkylresorcinols). High-fat dairy intake (expectedly low in the ND) was reflected by serum pentadecanoic acid. All participants with biomarker data (n = 154) were included in the analyses. Biomarkers were combined by using a biomarker rank score (DB score) and principal component analysis (PCA). The DB score was then used to assess compliance. During the intervention, median concentrations of alkylresorcinols, α-linolenic acid, EPA, and DHA were >25% higher in the ND individuals than in the controls (P < 0.05), whereas median concentrations of pentadecanoic acid were 14% higher in controls (P < 0.05). Median DB score was 57% higher in the ND than in controls (P < 0.001) during the intervention, and participants were ranked similarly by DB score and PCA score. Overall, estimates of group difference in cardiometabolic effects generally appeared to be greater among compliant participants than in the whole study population (e.g., estimates of treatment effects on blood pressure and lipoproteins were ∼1.5- to 2-fold greater in the most compliant participants), suggesting that poor compliance attenuated the dietary effects. With adequate consideration of their limitations, DB combinations (e.g., DB score) could be useful for assessing compliance in intervention studies investigating cardiometabolic effects of healthy dietary patterns. The study was registered at clinicaltrials.gov as NCT00992641., (© 2014 American Society for Nutrition.)

Plasma alkylresorcinols (AR) are useful as dietary biomarkers of wheat and rye whole grain (WG) during interventions but need to be validated in free-living populations. This study estimated the medium-term reproducibility and relative validity of plasma AR as biomarkers of WG and cereal fiber intake. Seventy-two Swedish adults kept 3-d weighed food records on 2 occasions 2-3 mo apart. Of these men and women, 51 provided a fasting blood sample at the end of each occasion. In addition, 18 participants provided 3 fasting and 3 nonfasting samples for 3 consecutive days on the first and second occasions, respectively. Dietary and blood variables did not differ between the 2 occasions. Nonfasting plasma total AR concentration [210 nmol/L (95% CI: 140, 314)] was higher than fasting [99 nmol/L (95% CI: 72, 137)] (P < 0.0001). Mean WG intake was 70 ± 61 g/d (41% from rye) and the intra-class correlation coefficient was 0.44 (95% CI: 0.26, 0.63) for total WG intake and 0.47 (95% CI: 0.27, 0.67) for the fasting plasma total AR concentration, suggesting moderate reproducibility. Fasting plasma total AR moderately correlated with WG rye + wheat (r(s) = 0.53; P < 0.001) and cereal fiber intake (r(s) = 0.32; P < 0.05) when using mean values from both occasions. This suggests that plasma AR concentration in fasting samples can be used as a biomarker of rye + wheat WG intake in free-living populations with a high and consistent WG intake.

Despite many years of research, no biomarkers for stroke are available to use in clinical practice. Progress in high-throughput technologies has provided new opportunities to understand the pathophysiology of this complex disease, and these studies have generated large amounts of data and information at different molecular levels. The integration of these multi-omics data means that thousands of proteins (proteomics), genes (genomics), RNAs (transcriptomics) and metabolites (metabolomics) can be studied simultaneously, revealing interaction networks between the molecular levels. Integrated analysis of multi-omics data will provide useful insight into stroke pathogenesis, identification of therapeutic targets and biomarker discovery. In this Review, we detail current knowledge on the pathology of stroke and the current status of biomarker research in stroke. We summarize how proteomics, metabolomics, transcriptomics and genomics are all contributing to the identification of new candidate biomarkers that could be developed and used in clinical stroke management.

In recent years, the use of electronic cigarettes (e-cigs) has increased. However, their long-term effects on oral health and saliva remain poorly understood. Therefore, this study aimed to evaluate the saliva of e-cig users and investigate possible biomarkers. Participants were divided into two groups: the Electronic Cigarette Group (EG)—25 regular and exclusive e-cig users—and Control Group (CG)—25 non-smokers and non-e-cig users, matched in sex and age to the EG. The clinical analysis included the following parameters: age, sex, heart rate, oximetry, capillary blood glucose, carbon monoxide (CO) concentration in exhaled air, and alcohol use disorder identification test (AUDIT). Qualitative and quantitative analyses of saliva included sialometry, viscosity, pH, and cotinine concentrations. Furthermore, the EG and CG salivary metabolomes were compared using gas chromatography coupled with mass spectrometry (GC-MS). Data were analyzed using the Mann–Whitney test. The MetaboAnalyst 6.0 software was used for statistical analysis and biomarker evaluation. The EG showed high means for exhaled CO concentration and AUDIT but lower means for oximetry and salivary viscosity. Furthermore, 10 metabolites (isoleucine, 2-hydroxyglutaric acid, 3-phenyl-lactic acid, linoleic acid, 3-hydroxybutyric acid, 1,6-anhydroglucose, glucuronic acid, valine, stearic acid, and elaidic acid) were abundant in EG but absent in CG. It was concluded that e-cig users had high rates of alcohol consumption and experienced significant impacts on their general health, including increased cotinine and CO concentration in exhaled air, decreased oximetry, and low salivary viscosity. Furthermore, they showed a notable increase in salivary metabolites, especially those related to inflammation, xenobiotic metabolism, and biomass-burning pathways. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic, immune-mediated skin condition with significant metabolic complications. Although lipid metabolism is linked to its pathogenesis, reliable biomarkers and the impact of modifiable factors remain underexplored. The aim of the present study was to identify potential biomarkers, study the affected metabolic networks, and assess the role of dietary and lifestyle factors in psoriasis. Plasma samples from 56 patients with psoriasis and 49 healthy controls were analyzed, as part of the Metabolic Biomarkers in Hashimoto's Thyroiditis and Psoriasis (METHAP) clinical trial. Using Gas Chromatography-Mass Spectrometry 23 fatty acids and their ratios were quantified, revealing significant changes in psoriasis. Specifically, lower levels of α-linoleic acid (C18:3n3), linoleic acid (C18:2n6), and gamma-linolenic acid (C18:3n6) were observed along with higher levels of eicosatrienoic acid (C20:3n3), eicosapentaenoic acid (C20:5n3), and erucic acid (C22:1n9). Total polyunsaturated fatty acids (PUFA) were significantly decreased, and the ratio of saturated to total fatty acids (SFA/Total) was increased in psoriasis (p-values < 0.0001). Linear regression identified α-linoleic acid, linoleic acid, eicosatrienoic acid, and eicosapentaenoic acid as potential biomarkers for psoriasis, adjusting for demographic, dietary, and lifestyle confounders. Network analysis revealed key contributors in the metabolic reprogramming of psoriasis. These findings highlight the association between psoriasis and fatty acid biomarkers of inflammation, insulin resistance and micronutrients deficiency, suggesting their potency in disease management. [ABSTRACT FROM AUTHOR]

Functional lipids are dietary substances that may have an impact on human health by lowering the risk of chronic illnesses and enhancing the quality of life. Numerous functional lipids have been reported to have potential health benefits in the prevention, management, and treatment of cardiovascular disease, the leading cause of death in the United States. However, there is still insufficient and contradictory information in the literature about their effectiveness and associated mechanisms of action. The objective of this review, therefore, is to evaluate available literature regarding these functional lipids and their health benefits. Various studies have been conducted to understand the links between functional lipids and the prevention and treatment of chronic diseases. Recent studies on phytosterols have reported that CLA, medium-chain triglycerides, and omega-3 and 6 fatty acids have positive effects on human health. Also, eicosanoids, which are the metabolites of these fatty acids, are produced in relation to the ratio of omega-3 to omega-6 polyunsaturated fatty acids and may modulate disease conditions. These functional lipids are available either in dietary or supplement forms and have been proven to be efficient, accessible, and inexpensive to be included in the diet. However, further research is required to properly elucidate the dosages, dietary intake, effectiveness, and their mechanisms of action in addition to the development of valid disease biomarkers and long-term effects in humans. [ABSTRACT FROM AUTHOR]

Oxidative stress plays a significant role in the pathogenesis of cardiovascular diseases, such as myocardial ischemia/reperfusion injury, atherosclerosis, heart failure, and hypertension. This systematic review aims to integrate most relevant studies on oxidative stress management in cardiovascular diseases. We searched relevant literatures in the PubMed database using specific keywords. We put emphasis on those manuscripts that were published more recently and in higher impact journals. We reviewed a total of 200 articles. We examined current oxidative stress managements in cardiovascular diseases, including supplements like resveratrol, vitamins C and E, omega-3 fatty acids, flavonoids, and coenzyme-10, which have shown antioxidative properties and potential cardiovascular benefits. In addition, we reviewed the pharmacological treatments including newly discovered antioxidants and nanoparticles that show potential effects in targeting the specific oxidative stress pathways. Lastly, we examined biomarkers, such as soluble transferrin receptor, transthyretin, and cystatin C in evaluating antioxidant status and identifying cardiovascular risk. By addressing oxidative stress management and mechanisms, this paper emphasizes the importance of maintaining the balance between oxidants and antioxidants in the progression of cardiovascular diseases. This review paper is registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), registration # INPLASY202470064. [ABSTRACT FROM AUTHOR]

Background and Objectives: Sudden cardiac death (SCD) represents a challenge to health systems globally and is met with increased frequency in the population. Over time, multiple screening methods have been proposed, including the analysis of various plasma biomarkers. This article aims to analyze for illustrative purposes the specialized literature in terms of current biomarkers and testing trends, in the case of cardiovascular diseases and implicitly sudden cardiac death. Materials and Methods: In this regard, we searched the PubMed database from 2010 to the present time using the keywords "sudden cardiac death" and "biomarkers". The inclusion criteria were clinical trials that analyzed the effectiveness of screening methods in terms of biomarkers used in stratifying the risk of cardiac distress and/or sudden cardiac death. We excluded reviews, meta-analyses, and studies looking at the effectiveness of treatments. Results: An extended approach was found, through studies that brought to the forefront both classical markers analyzed by new, more performant methods, markers for other pathologies that also determined cardiovascular impact, non-specific molecules with effects on the cardiovascular system, and state-of-the-art markers, such as microRNA. Some molecules were analyzed simultaneously in certain groups of patients. Conclusion: The observed current trend revealed the tendency to define the clinical-biological particularities of the person to be screened. [ABSTRACT FROM AUTHOR]

Context: Disturbances in sleep affects the overall quality of a child's life, with several short- and long-lasting consequences. Hence, early diagnosis and monitoring is crucial in the management of sleep disorders in children. Aims: The aim of this study was to evaluate salivary C-reactive protein (CRP) levels in a group of children with Class II malocclusion and sleep problems before and after twin-block appliance therapy. Settings and Design: The study was a prospective clinical study with a 9-month follow-up period. Subjects and Methods: Eleven children aged 8–12 years with skeletal Class II malocclusion and at least one sleep disorder were enrolled in the study. All children were subjected to a recording of their sleep history and a clinical as well as radiographic examination. Pretreatment levels of salivary CRP were recorded. A twin-block appliance was custom made and delivered to every child. At the end of 9-month follow-up, all children were recalled for a re-evaluation of salivary biomarker levels. Statistical Analysis: Pretreatment and posttreatment changes in biomarker levels were assessed statistically using the students paired t-test. Results: Levels of salivary biomarker CRP were significantly decreased in children following myofunctional therapy using a twin-block appliance (P < 0.001). There was a considerable improvement in the clinical symptoms such as a decrease in snoring and noisy breathing in most children post-twin-block therapy. Conclusion: The measurement of salivary biomarker CRP could be used as an alternative and noninvasive method to evaluate prognosis of oral myofunctional therapy for children with sleep disordered breathing. [ABSTRACT FROM AUTHOR]

Introduction: During adolescence, dairy product intake has shown conflicting associations with metabolic syndrome (MetS) components, which are risk factors for cardiovascular disease (CVD). This study aims to investigate the association between plasma fatty acids (FAs) C15:0, C17:0, and t-C16:1n-7, as biomarkers of dairy intake, with MetS and its components in Mexican adolescents. Methods: A sample of 311 participants from the Early Life Exposure in Mexico City to Environmental Toxicants (ELEMENT) cohort was included in this cross-sectional analysis. FA concentrations were measured in plasma as a percentage of total FA. We used quantile regression models stratified by sex to evaluate the association between FA quantiles and MetS components, adjusting for age, socioeconomic status (SES), sedentary behavior, BMI z-score, pubertal status, and energy intake. Results: We found significant associations between dairy biomarkers and the median of MetS variables. In females, t-C16:1n-7 was associated with a decrease of 2.97 cm in WC (Q4 vs. Q1; 95% CI: −5.79, −0.16). In males, C15:0 was associated with an increase of 5.84 mm/Hg in SBP (Q4 vs. Q1; CI: 1.82, 9.85). For HDL-C, we observed opposite associations by sex. C15:0 in males was associated with decreased HDL-C (Q3 vs. Q1: β = −4.23; 95% CI: −7.98, −0.48), while in females, C15:0 and t-C16:1n-7 were associated with increased HDL-C (Q3 vs. Q1: β = 4.75; 95% CI: 0.68, 8.82 and Q4 vs. Q1: β = 6.54; 95% CI: 2.01, 11.07), respectively. Additionally, in both sexes, different levels of C15:0, C17:0, and t-C16:1n-7 were associated with increased triglycerides (TG). Conclusion: Our results suggest that adolescent dairy intake may be associated in different directions with MetS components and that associations are sex-dependent. [ABSTRACT FROM AUTHOR]

The positive health of a person can be defined as the ability to live long in good health, possibly with no activity limitation. No method is yet available for its objective assessment in individuals, and we propose a framework in this communication that can operationalize this concept. Instead of distal factors, such as diet and lifestyle because these are subjective and difficult to measure, we concentrate on the objectively measurable biomarkers such as immunity level, endorphins, and handgrip strength. The focus is on the major parameters that may protect from diseases and infirmity and can be assessed by noninvasive methods. A combination of such parameters may signify positive health. This may be a novel way to measure positive health at the individual level. In this communication, we briefly review the literature and identify a few major biomarkers that provide a protective shield and could determine the status of positive health at the individual level. This exercise demonstrates that the assessment of the positive health of a person is feasible. A scale based on these and other relevant parameters can be developed later that could quantitatively measure the exact level of positive health. As the exact combination of the parameters that protects from ailments is not fully known yet, a framework such as this may help in identifying the data gaps that require attention in this context. The proposed framework may initiate a discussion on indicators of positive health and characterize the parameters for intervention that could increase a healthy life. [ABSTRACT FROM AUTHOR]

Background: Self-reported adherence to the Mediterranean diet has been modestly inversely associated with incidence of type 2 diabetes (T2D) in cohort studies. There is uncertainty about the validity and magnitude of this association due to subjective reporting of diet. The association has not been evaluated using an objectively measured biomarker of the Mediterranean diet. Methods and findings: We derived a biomarker score based on 5 circulating carotenoids and 24 fatty acids that discriminated between the Mediterranean or habitual diet arms of a parallel design, 6-month partial-feeding randomised controlled trial (RCT) conducted between 2013 and 2014, the MedLey trial (128 participants out of 166 randomised). We applied this biomarker score in an observational study, the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, to assess the association of the score with T2D incidence over an average of 9.7 years of follow-up since the baseline (1991 to 1998). We included 22,202 participants, of whom 9,453 were T2D cases, with relevant biomarkers from an original case-cohort of 27,779 participants sampled from a cohort of 340,234 people. As a secondary measure of the Mediterranean diet, we used a score estimated from dietary-self report. Within the trial, the biomarker score discriminated well between the 2 arms; the cross-validated C-statistic was 0.88 (95% confidence interval (CI) 0.82 to 0.94). The score was inversely associated with incident T2D in EPIC-InterAct: the hazard ratio (HR) per standard deviation of the score was 0.71 (95% CI: 0.65 to 0.77) following adjustment for sociodemographic, lifestyle and medical factors, and adiposity. In comparison, the HR per standard deviation of the self-reported Mediterranean diet was 0.90 (95% CI: 0.86 to 0.95). Assuming the score was causally associated with T2D, higher adherence to the Mediterranean diet in Western European adults by 10 percentiles of the score was estimated to reduce the incidence of T2D by 11% (95% CI: 7% to 14%). The study limitations included potential measurement error in nutritional biomarkers, unclear specificity of the biomarker score to the Mediterranean diet, and possible residual confounding. Conclusions: These findings suggest that objectively assessed adherence to the Mediterranean diet is associated with lower risk of T2D and that even modestly higher adherence may have the potential to reduce the population burden of T2D meaningfully. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12613000602729https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363860. Jakub G Sobiecki and team aim to develop a biomarker score able to discriminate between Mediterranean diet and habitual diet, and test its association with incident type 2 diabetes in a European cohort. Author summary: Why was this study done?: Epidemiological evidence has indicated that greater self-reported adherence to the Mediterranean diet may be associated with lower risk of new onset type 2 diabetes (T2D), but there has been uncertainty about the magnitude of association due to subjective reporting of diet. A combination of nutritional biomarkers could better assess diet–disease associations, but this approach has rarely been considered for overall diet quality, particularly for the association between the Mediterranean diet and T2D. What did the researchers do and find?: Blood carotenoids and fatty acids can be used as an objective measure of adherence to the Mediterranean diet, as indicated by results from a trial (n = 128) of adopting Mediterranean diet with provision of its key foods to study participants. These biomarkers discriminated well between the trial participants under the Mediterranean diet intervention and those randomised to continuation of habitual diet (C-statistic = 0.88). In a study across 8 European countries (n = 22,202), adherence to the Mediterranean diet, estimated using a combination of nutritional biomarkers, was associated with lower risk of new onset T2D, with a stronger relationship compared to that with self-reported Mediterranean diet. The hazard ratios (HRs) (95% confidence interval (CI)) per standard deviation of adherence were 0.71 (0.65 to 0.77) and 0.90 (0.86 to 0.95), respectively. What do these findings mean?: Adherence to the Mediterranean diet may be more beneficial for the primary prevention of T2D than previously estimated from observational dietary studies. Even small upward differences in objectively measured Mediterranean diet may be associated with a sizeable reduction of the risk of T2D at the population level. Causal interpretation of these findings is limited by potential measurement error in nutritional biomarkers, unclear specificity of the biomarker score to the Mediterranean diet, and possible residual confounding. [ABSTRACT FROM AUTHOR]

Purpose: To identify fasting serum metabolites associated with WG intake in a free-living population adjusted for potential confounders. Methods: We selected fasting serum samples at baseline from a subset (n = 364) of the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) cohort. The samples were analyzed using nontargeted metabolomics with liquid chromatography coupled with mass spectrometry (LC–MS). Association with WG intake was investigated using both random forest followed by linear regression adjusted for age, BMI, smoking, physical activity, energy and alcohol consumption, and partial Spearman correlation adjusted for the same covariates. Features selected by any of these models were shortlisted for annotation. We then checked if we could replicate the findings in an independent subset from the same cohort (n = 200). Results: Direct associations were observed between WG intake and pipecolic acid betaine, tetradecanedioic acid, four glucuronidated alkylresorcinols (ARs), and an unknown metabolite both in discovery and replication cohorts. The associations remained significant (FDR<0.05) even after adjustment for the confounders in both cohorts. Sinapyl alcohol was positively correlated with WG intake in both cohorts after adjustment for the confounders but not in linear models in the replication cohort. Some microbial metabolites, such as indolepropionic acid, were positively correlated with WG intake in the discovery cohort, but the correlations were not replicated in the replication cohort. Conclusions: The identified associations between WG intake and the seven metabolites after adjusting for confounders in both discovery and replication cohorts suggest the potential of these metabolites as robust biomarkers of WG consumption. [ABSTRACT FROM AUTHOR]

Context Despite advances in treatments for cardiometabolic disorders such as type 2 diabetes mellitus and obesity, the increasing frequency of these conditions is of major clinical and public health concern. Therefore, primary prevention including diet and lifestyle approaches continues to play a key role in risk reduction. Meta-analyses of prospective cohort studies have documented inverse associations of dairy consumption with the incidence of different cardiometabolic disorders. Dairy is the largest dietary contributor of branched chain fatty acids (BCFAs), which have been suggested to not only serve as biomarkers of dairy consumption but may also have bioactive properties contributing to reducing the risk of cardiometabolic outcomes. To date, however, the literature on this topic has not been systematically reviewed. Objective The aim here was to report the results of a systematic review of the association of BCFAs with cardiometabolic disorders in humans. Data Sources Search terms were developed and run through the Ovid MEDLINE, Ovid Embase, and the Cochrane Library databases. Data Extraction Articles were selected on the basis of prespecified inclusion criteria and assessed for risk of bias by independent reviewers. Results Four studies (n = 2 cross sectional; n = 1 randomized feeding trial and n = 1 pre–post study) were identified. Two studies reported significant inverse associations between serum BCFAs and insulin resistance, triglycerides and/or body mass index. One study identified an inverse association between adipose tissue monomethyl BCFAs and skeletal muscle insulin resistance. In contrast, the randomized feeding trial reported no significant differences to stool BCFA concentrations or body mass index in obese participants following assignment to fruit–vegetable or whole-grain diet groups compared with a refined-grain control group. Conclusions Current evidence suggests beneficial associations of circulating BCFAs with cardiometabolic risk phenotypes, although data in human participants are limited, indicating that additional research is required. PROSPERO registration no CRD42021224975. [ABSTRACT FROM AUTHOR]

Purpose of Review: 'Omics studies provide a comprehensive characterisation of a biological entity, such as the genome, epigenome, transcriptome, proteome, metabolome, or microbiome. This review covers the unique properties of these types of 'omics and their roles as causal mediators in cardiovascular disease. Moreover, applications and challenges of integrating multiple types of 'omics data to increase predictive power, improve causal inference, and elucidate biological mechanisms are discussed. Recent Findings: Multi-omics approaches are growing in adoption as they provide orthogonal evidence and overcome the limitations of individual types of 'omics data. Studies with multiple types of 'omics data have improved the diagnosis and prediction of disease states and afforded a deeper understanding of underlying pathophysiological mechanisms, beyond any single type of 'omics data. For instance, disease-associated loci in the genome can be supplemented with other 'omics to prioritise causal genes and understand the function of non-coding variants. Alternatively, techniques, such as Mendelian randomisation, can leverage genetics to provide evidence supporting a causal role for disease-associated molecules, and elucidate their role in disease pathogenesis. Summary: As technologies improve, costs for 'omics studies will continue to fall and datasets will become increasingly accessible to researchers. The intrinsically unbiased nature of 'omics data is well-suited to exploratory analyses that discover causal mediators of disease, and multi-omics is an emerging discipline that leverages the strengths of each type of 'omics data to provide insights greater than the sum of its parts. [ABSTRACT FROM AUTHOR]

Introduction: Dyslipidemia is a hallmark of T2DM, and as such, analyses of lipid metabolic profiles in affected patients have the potential to permit the development of an integrated lipid metabolite-based biomarker model that can facilitate early patient diagnosis and treatment. Methods: Untargeted and targeted lipidomics approaches were used to analyze serum samples from newly diagnosed 93 Chinese participants in discovery cohort and 440 in validation cohort via UHPLC-MS and UHPLC-MS/MS first. The acid sphingomyelinase protein expression was analyzed by Western blot. Results and Discussion: Through these analyses, we developed a novel integrated biomarker signature composed of LPC 22:6, PC(16:0/20:4), PE(22:6/16:0), Cer (d18:1/24:0)/SM(d18:1/19:0), Cer(d18:1/24:0)/SM(d18:0/16:0), TG(18:1/18:2/18:2), TG(16:0/16:0/20:3), and TG(18:0/16:0/18:2). The area under the curve (AUC) values for this integrated biomarker signature for prediabetes and T2DM patients were 0.841 (cutoff: 0.565) and 0.894 (cutoff: 0.633), respectively. Furthermore, theresults of western blot analysis of frozen adipose tissue from 3 week (prediabetes) and 12 week (T2DM) Goto–Kakizaki (GK) rats also confirmed that acid sphingomyelinase is responsible for significant disruptions in ceramide and sphingomyelin homeostasis. Network analyses of the biomarkers associated with this biosignature suggested that the most profoundly affected lipid metabolism pathways in the context of diabetes include de novo ceramide synthesis, sphingomyelin metabolism, and additional pathways associated with phosphatidylcholine synthesis. Together, these results offer new biological insights regarding the role of serum lipids in the context of insidious T2DM development, and may offer new avenues for future diagnostic and/or therapeutic research. [ABSTRACT FROM AUTHOR]

Simple Summary: Omega-3 fatty acids have known health benefits for humans, but the extent to which these benefits extend to animals is still being discovered. Any benefits derived depend on achieving specific blood omega-3 levels, and the metric often used in human studies is the Omega-3 Index (O3I). It is a valid measure of omega-3 status reflecting the eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content of red blood cell membranes. The O3I is often calculated from an analysis of whole blood dried on filter paper; and how to convert whole blood EPA + DHA into the O3I is well established in humans, but not yet for other species. This study analyzed blood samples from dogs and cats and developed equations to estimate the O3I in both of these species. Having a validated measure of omega-3 status in these animals will facilitate further research to define exactly what blood levels of omega-3 fatty acids are optimal for each species. These levels can then be used by veterinarians and pet owners alike to gauge the amount of supplemental EPA and DHA each animal needs to achieve an optimal O3I. The Omega-3 Index (O3I) is the red blood cell (RBC) eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) content expressed as a percentage of total RBC fatty acids. Although a validated biomarker of omega-3 status in humans, little is known about the O3I status of dogs and cats; species in which omega-3 fatty acids have known health benefits. The purpose of this study was to develop equations to predict the O3I in these species from a dried blood spot (DBS) analysis. Random blood samples from 33 dogs and 10 cats were obtained from a community veterinary clinic. DBS and RBC samples were analyzed for fatty acid composition. For both species, the R2 between the DBS EPA + DHA value and the O3I was >0.96 (p < 0.001). The O3I was roughly 75% lower in dogs and cats than in humans. We conclude that the O3I can be estimated from a DBS sample, and the convenience of DBS collection should facilitate omega-3 research in these companion animals. [ABSTRACT FROM AUTHOR]

In epidemiological studies, dairy food consumption has been associated with minimal effect or decreased risk of some cardiometabolic diseases (CMD). However, current methods of dietary assessment do not provide objective and accurate measures of food intakes. Thus, the identification of valid and reliable biomarkers of dairy product intake is an important challenge to best determine the relationship between dairy consumption and health status. This review investigated potential biomarkers of dairy fat consumption, such as odd-chain, trans- and branched-chain fatty acids (FA), which may improve the assessment of full-fat dairy product consumption. Overall, the current use of serum/plasma FA as biomarkers of dairy fat consumption is mostly based on observational evidence, with a lack of well-controlled, dose–response intervention studies to accurately assess the strength of the relationship. Circulating odd-chain SFA and trans-palmitoleic acid are increasingly studied in relation to CMD risk and seem to be consistently associated with a reduced risk of type 2 diabetes in prospective cohort studies. However, associations with CVD are less clear. Overall, adding less studied FA such as vaccenic and phytanic acids to the current available evidence may provide a more complete assessment of dairy fat intake and minimise potential confounding from endogenous synthesis. Finally, the current evidence base on the direct effect of dairy fatty acids on established biomarkers of CMD risk (e.g. fasting lipid profiles and markers of glycaemic control) mostly derives from cross-sectional, animal and in vitro studies and should be strengthened by well-controlled human intervention studies. [ABSTRACT FROM AUTHOR]

Previous publications reported that around 1.5 million individuals suffer from chronic liver disease. Liver cancer is the sixth most commonly diagnosed cancer and the fourth leading cause of related death worldwide. A recent study in Isfahan province, Iran confirmed a period prevalence (2013-2015) of 18.5 per 100000 persons associated with liver cancer (comprise of 20.9 for males and 16.8 for females). It is well known that different available screening methods could reduce the burden of liver disease and liver cancer. This is a focused literature review with the keywords relevant to; Biomarkers" "Biocatalyst" "Pathology" "Potential History" "Liver Disease" and "Liver Cancer", based on the search associated with the topic of interest in; Pubmed, Scopus, and Web of Science. For hepatocellular carcinoma, early detection ultrasound-based surveillance was reported as 45%. Alpha-fetoprotein-Lens culinaris-agglutinin-reactive and des-gamma-carboxy prothrombin with abdominal ultrasound could increase the sensitivity of early detection in patients with hepatocellular carcinoma. A raised neutrophil-to-lymphocyte ratio is considered a prognostic indicator for patients with cancer. Serum alanine aminotransferase for predicting progression associated with chronic liver disease was reported as a more sensitive and robust marker. For estimating the overall mortality, serum alanine aminotransferase, aspartate transaminase, and γ-glutamyl transpeptidase confirmed clinically economic markers. High-quality imaging, MRI, and in some patients guided biopsy proposed. For early prevention of liver disease, regional anthropometric measures based on the; fat index (arm, hip, and waist circumference) besides body mass index, age, and alanine aminotransferase suggested values. Further evidence-based pharmacotherapy studies are recommended to be advantageous. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the second most common cause of mortality among men. Tumor secretome is a promising strategy for understanding the biology of tumor cells and providing markers for disease progression and patient outcomes. Here, transcriptomic-based secretome analysis was performed on the PCa tumor transcriptome of Genetically Engineered Mouse Model (GEMM) Pb-Cre4/Ptenf/f mice to identify potentially secreted and membrane proteins—PSPs and PMPs. We combined a selection of transcripts from the GSE 94574 dataset and a list of protein-coding genes of the secretome and membrane proteome datasets using the Human Protein Atlas Secretome. Notably, nine deregulated PMPs and PSPs were identified in PCa (DMPK, PLN, KCNQ5, KCNQ4, MYOC, WIF1, BMP7, F3, and MUC1). We verified the gene expression patterns of Differentially Expressed Genes (DEGs) in normal and tumoral human samples using the GEPIA tool. DMPK, KCNQ4, and WIF1 targets were downregulated in PCa samples and in the GSE dataset. A significant association between shorter survival and KCNQ4, PLN, WIF1, and F3 expression was detected in the MSKCC dataset. We further identified six validated miRNAs (mmu-miR-6962-3p, mmu-miR- 6989-3p, mmu-miR-6998-3p, mmu-miR-5627-5p, mmu-miR-15a-3p, and mmu-miR-6922-3p) interactions that target MYOC, KCNQ5, MUC1, and F3. We have characterized the PCa secretome and membrane proteome and have spotted new dysregulated target candidates in PCa. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) ranges from indolent to aggressive tumors that may rapidly progress and metastasize. The switch to aggressive PCa is fostered by reactive stroma infiltrating tumor foci. Therefore, reactive stroma-based biomarkers may potentially improve the early detection of aggressive PCa, ameliorating disease classification. Gene expression profiles of PCa reactive fibroblasts highlighted the up-regulation of genes related to stroma deposition, including periostin and sparc. Here, the potential of periostin as a stromal biomarker has been investigated on PCa prostatectomies by immunohistochemistry. Moreover, circulating levels of periostin and sparc have been assessed in a low-risk PCa patient cohort enrolled in active surveillance (AS) by ELISA. We found that periostin is mainly expressed in the peritumoral stroma of prostatectomies, and its stromal expression correlates with PCa grade and aggressive disease features, such as the cribriform growth. Moreover, stromal periostin staining is associated with a shorter biochemical recurrence-free survival of PCa patients. Interestingly, the integration of periostin and sparc circulating levels into a model based on standard clinico-pathological variables improves its performance in predicting disease reclassification of AS patients. In this study, we provide the first evidence that circulating molecular biomarkers of PCa stroma may refine risk assessment and predict the reclassification of AS patients. [ABSTRACT FROM AUTHOR]

The field of immuno-oncology is now at the forefront of cancer care and is rapidly evolving. The immune checkpoint blockade has been demonstrated to restore antitumor responses in several cancer types. However, durable responses can be observed only in a subset of patients, highlighting the importance of investigating the tumor microenvironment (TME) and cellular heterogeneity to define the phenotypes that contribute to resistance as opposed to those that confer susceptibility to immune surveillance and immunotherapy. In this review, we summarize how some of the most widely used conventional technologies and biomarkers may be useful for the purpose of predicting immunotherapy outcomes in patients, and discuss their shortcomings. We also provide an overview of how emerging single-cell spatial omics may be applied to further advance our understanding of the interactions within the TME, and how these technologies help to deliver important new insights into biomarker discovery to improve the prediction of patient response. [ABSTRACT FROM AUTHOR]

Pregnancy is accompanied by a surge in demand for fatty acids (FAs) in order to support maternal health, as well as fetal growth and development. Of particular demand is essential for long‐chain polyunsaturated FAs. FAs are primarily obtained from dietary sources and are distributed in the body. In comparison with the use of self‐reporting approaches, measuring the FA levels within different blood compartments can present a more accurate image of nutritional, and thus tissue, FA composition. Hence, the FA profile of plasma or serum is commonly used for physiological analyses. Nevertheless, plasma and serum FAs are not yet incorporated into cell membranes, and consequently may not be a suitable reflection of the FA status of body tissues. The evaluation of erythrocyte FA levels offers a superior possibility for the following reasons: the biological fluctuation of erythrocyte FA composition is low, phospholipids account for almost all the lipid content of erythrocytes, and the FA profiles of erythrocytes represent those of tissues. Here, we elaborate on whether the status of maternal erythrocyte FAs can serve as a prognostic biomarker for reproductive health and fetomaternal complications, including embryonic and fetoplacental development, gestational length, and preeclampsia. In addition, factors with the potential of altering the maternal erythrocyte FAs such as maternal diet, lifestyle habits, genetics, and body composition are discussed. [ABSTRACT FROM AUTHOR]

Purpose: Oat supplementation interventions (OSIs) may have a beneficial effect on cardiovascular disease (CVD) risk. However, dietary background can modulate such effect. This systematic review assesses the effects of OSIs on CVD risk markers among adults, accounting for different dietary backgrounds or control arms. Methods: We included randomized clinical trials (RCTs) that assessed the effect of oat, oat beta-glucan-rich extracts or avenanthramides on CVD risk markers. Results: Seventy-four RCTs, including 4937 predominantly hypercholesterolemic, obese subjects, with mild metabolic disturbances, were included in the systematic review. Of these, 59 RCTs contributed to the meta-analyses. Subjects receiving an OSI, compared to control arms without oats, had improved levels of total cholesterol (TC) [weighted mean difference and (95% CI) − 0.42 mmol/L, (− 0.61; − 0.22)], LDL cholesterol [− 0.29 mmol/L, (− 0.37; − 0.20)], glucose [− 0.25 nmol/L, (− 0.36; − 0.14)], body mass index [− 0.13 kg/m2, (− 0.26; − 0.01)], weight [− 0.94 kg, (− 1.84: − 0.05)], and waist circumference [− 1.06 cm, (− 1.85; − 0.27)]. RCTs on inflammation and/or oxidative stress markers were scarce and with inconsistent findings. RCTs comparing an OSI to heterogeneous interventions (e.g., wheat, eggs, rice, etc.), showed lowered levels of glycated haemoglobin, diastolic blood pressure, HDL cholesterol and apolipoprotein B. The majority of included RCTs (81.1%) had some concerns for risk of bias. Conclusion: Dietary OSIs resulted in lowered levels of blood lipids and improvements in anthropometric parameters among participants with predominantly mild metabolic disturbances, regardless of dietary background or control. Further high-quality trials are warranted to establish the role of OSIs on blood pressure, glucose homeostasis and inflammation markers. [ABSTRACT FROM AUTHOR]

Background: Effective targeted prevention of type 2 diabetes (T2D) depends on accurate prediction of disease risk. We assessed the role of metabolomic profiling in improving T2D risk prediction beyond conventional risk factors.Methods: Nuclear magnetic resonance (NMR) metabolomic profiling was undertaken on baseline plasma samples in 65,684 UK Biobank participants without diabetes and not taking lipid-lowering medication. Among a subset of 50,519 participants with data available on all relevant co-variates (sociodemographic characteristics, parental history of diabetes, lifestyle-including dietary-factors, anthropometric measures and fasting time), Cox regression yielded adjusted hazard ratios for the associations of 143 individual metabolic biomarkers (including lipids, lipoproteins, fatty acids, amino acids, ketone bodies and other low molecular weight metabolic biomarkers) and 11 metabolic biomarker principal components (PCs) (accounting for 90% of the total variance in individual biomarkers) with incident T2D. These 11 PCs were added to established models for T2D risk prediction among the full study population, and measures of risk discrimination (c-statistic) and reclassification (continuous net reclassification improvement [NRI], integrated discrimination index [IDI]) were assessed.Results: During median 11.9 (IQR 11.1-12.6) years' follow-up, after accounting for multiple testing, 90 metabolic biomarkers showed independent associations with T2D risk among 50,519 participants (1211 incident T2D cases) and 76 showed associations after additional adjustment for HbA1c (false discovery rate controlled p < 0.01). Overall, 8 metabolic biomarker PCs were independently associated with T2D. Among the full study population of 65,684 participants, of whom 1719 developed T2D, addition of PCs to an established risk prediction model, including age, sex, parental history of diabetes, body mass index and HbA1c, improved T2D risk prediction as assessed by the c-statistic (increased from 0.802 [95% CI 0.791-0.812] to 0.830 [0.822-0.841]), continuous NRI (0.44 [0.38-0.49]) and relative (15.0% [10.5-20.4%]) and absolute (1.5 [1.0-1.9]) IDI. More modest improvements were observed when metabolic biomarker PCs were added to a more comprehensive established T2D risk prediction model additionally including waist circumference, blood pressure and plasma lipid concentrations (c-statistic, 0.829 [0.819-0.838] to 0.837 [0.831-0.848]; continuous NRI, 0.22 [0.17-0.28]; relative IDI, 6.3% [4.1-9.8%]; absolute IDI, 0.7 [0.4-1.1]).Conclusions: When added to conventional risk factors, circulating NMR-based metabolic biomarkers modestly enhanced T2D risk prediction. [ABSTRACT FROM AUTHOR]

BACKGROUND: Alkylresorcinols are phenolic lipids that exclusively present in the outer parts of wheat and rye grains. They have been proposed as specific dietary biomarkers of whole-grain wheat and rye intake. Dietary fibers protective role aganist colorectal cancer has been postulated several decades ago. AIM: To verify the relation of dietary fiber intake and incidence of colorectal cancer using plasma total Alkylresorcinols concentrations as an indicator of whole-grain intake. METHODS: 148 Subjects were enrolled and categorixed into two groups; Group (A): 62 patients with colorectal cancer and Group (B): 86 subjects with normal colonoscopy "control group". Blood samples were withdrawn from the patients after overnight fasting for detection of Alkylresorcinols levels. RESULTS: Detection of the Alkylresorcinols levels; C17, C21 and Total Cs were significantly higher in the control group in comparison to colorectal cancer group, C19 levels showed no significant difference. CONCLUSION: People with high intake of fibers especially cereals probably have a lower risk of developing cancer colon. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is a heterogenous disease in terms of disease aggressiveness and therapy response, leading to dilemmas in treatment decisions. This heterogeneity reflects the multifocal nature of prostate cancer and its diversity in cellular and molecular composition, necessitating spatial molecular approaches. Here in view of the emerging importance of rewired lipid metabolism as a source of biomarkers and therapeutic targets for prostate cancer, we highlight recent advancements in technologies that enable the spatial mapping of lipids and related metabolic pathways associated with prostate cancer development and progression. We also evaluate their potential for future implementation in treatment decision-making in the clinical management of prostate cancer. Due to advances in the detection and management of prostate cancer over the past 20 years, most cases of localised disease are now potentially curable by surgery or radiotherapy, or amenable to active surveillance without treatment. However, this has given rise to a new dilemma for disease management; the inability to distinguish indolent from lethal, aggressive forms of prostate cancer, leading to substantial overtreatment of some patients and delayed intervention for others. Driving this uncertainty is the critical deficit of novel targets for systemic therapy and of validated biomarkers that can inform treatment decision-making and to select and monitor therapy. In part, this lack of progress reflects the inherent challenge of undertaking target and biomarker discovery in clinical prostate tumours, which are cellularly heterogeneous and multifocal, necessitating the use of spatial analytical approaches. In this review, the principles of mass spectrometry-based lipid imaging and complementary gene-based spatial omics technologies, their application to prostate cancer and recent advancements in these technologies are considered. We put in perspective studies that describe spatially-resolved lipid maps and metabolic genes that are associated with prostate tumours compared to benign tissue and increased risk of disease progression, with the aim of evaluating the future implementation of spatial lipidomics and complementary transcriptomics for prognostication, target identification and treatment decision-making for prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. For this reason, it is essential to identify biomarkers for the early detection of T2DM risk and/or for a better prognosis of T2DM. We aimed to identify a plasma fatty acid (FA) profile associated with T2DM development. Methods: We included 462 coronary heart disease patients from the CORDIOPREV study without T2DM at baseline. Of these, 107 patients developed T2DM according to the American Diabetes Association (ADA) diagnosis criteria after a median follow-up of 60 months. We performed a random classification of patients in a training set, used to build a FA Score, and a Validation set, in which we tested the FA Score. Results: FA selection with the highest prediction power was performed by random survival forest in the Training set, which yielded 4 out of the 24 FA: myristic, petroselinic, α-linolenic and arachidonic acids. We built a FA Score with the selected FA and observed that patients with a higher score presented a greater risk of T2DM development, with an HR of 3.15 (95% CI 2.04–3.37) in the Training set, and an HR of 2.14 (95% CI 1.50–2.84) in the Validation set, per standard deviation (SD) increase. Moreover, patients with a higher FA Score presented lower insulin sensitivity and higher hepatic insulin resistance (p < 0.05). Conclusion: Our results suggest that a detrimental FA plasma profile precedes the development of T2DM in patients with coronary heart disease, and that this FA profile can, therefore, be used as a predictive biomarker. Clinical Trials.gov.Identifier: NCT00924937. [ABSTRACT FROM AUTHOR]

Purpose: Information on the association between diet and cardiovascular disease (CVD) in type 1 diabetes (T1D) is scarce. We assessed the association between biomarkers of fatty acid (FA) intake and the presence of carotid plaques (a surrogate marker of future CVD events) in this high-risk population. Methods: Cross-sectional study in 167 consecutive T1D patients without CVD and with at least one of the following: ≥ 40 years, diabetic nephropathy, or ≥ 10 years of T1D duration with another CVD risk factor. The FA profile of erythrocyte membranes was determined by gas chromatography, and the number of carotid plaques (intima-media thickness ≥ 1.5 mm) was assessed by ultrasonography. Regression models were constructed adjusting for classical (age, gender, blood pressure, smoking habit, LDL-cholesterol, body mass index and statins) and T1D-specific risk factors (diabetes duration, HbA1c and chronic complications). Results: A total of 58.7% were men (mean age 48.3 ± 10.3 years, T1D duration 27.2 ± 10.1 years). Sixty-one patients (36.5%) showed carotid plaque. Linoleic acid decreased and all-C18:1trans increased with the number of carotid plaques (none, 1–2, ≥ 3 plaques; p for trend < 0.05). In multivariate regression models, linoleic acid remained inversely associated with the presence of plaque [1% increase of total FAs; OR 0.71 (0.53–0.95), p = 0.021] and ≥ 2 plaques [OR 0.70 (0.51–0.98), p = 0.039]; whereas, all-C18:1trans was positively associated with ≥ 3 plaques (0.1% increase of total FAs; OR 1.51 [1.05–2.16], p = 0.026). Conclusions: Erythrocyte FA composition, as a biomarker of FA intake, was independently associated with preclinical atherosclerosis in T1DM. Our data support the potential role of an unfavorable pattern of fat intake and CVD risk in this population. [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]

The objective was to investigate the effects of substitution (SUB) dietary guidelines (DG) targeted at the prevention of IHD on dietary intake and IHD risk factors in Danish adults with minimum one self-assessed IHD risk factor. A 6-month single-blinded parallel randomised controlled trial with a follow-up at month 12 included 219 subjects (median age 51 years, 59 % female, 73 % overweight or obese) randomised into an SUB DG, an official (OFF) DG or a control group following their habitual diet (HAB). Participants in the DG intervention groups received bi-weekly reminders of their DG and recipes for dishes and the HAB group received a greeting. Dietary intake and fasting blood, anthropometric and blood pressure measurements were obtained at baseline, month 6 and month 12. Linear regression analyses were applied. At month 6, when compared with the HAB, the SUB had a greater impact on the extent of dietary changes with increased intake of whole grains, dietary fibre and low fibre vegetables compared with the OFF DG, and both DG groups had similar decreased percentage of energy (E%) intake from SFA. The extent of dietary changes was similar at month 12. No overall significant changes from baseline were found in blood pressure, anthropometrics and IHD risk markers. In conclusion, both SUB and OFF DG resulted in cardioprotective dietary changes. However, neither the SUB nor the OFF DG resulted in any overall effects on the selected intermediate risk factors for IHD. [ABSTRACT FROM AUTHOR]

Purpose: We investigated risk of myocardial infarction (MI) associated with the content of linoleic acid (LA) in adipose tissue, a biomarker of long-term dietary intake of LA and a marker of endogenous LA exposure. Methods: Between 1993 and 1997, 57,053 middle-aged subjects were included in the Danish Diet, Cancer and Health cohort. We performed a case–cohort study that included a random sample of the full cohort (n = 3167) and all incident MI cases appearing during 16 years of follow-up (n = 2819). Information on incident MI cases was obtained by linkage with Danish nationwide registries. Adipose tissue biopsies were taken from the buttocks of the participants, and their fatty acid composition was determined using gas chromatography. HRs (hazard ratios) with 95% confidence intervals (CIs) were used to describe the associations between content of LA in adipose tissue and the risk of MI. HRs were calculated using weighted Cox proportional hazards regression with robust variance. Results: After adjustment for established risk factors of MI, adipose tissue content of LA was not associated with the risk of MI in men and women combined (quintiles 5 versus 1, HR, 1.03 (95% CI, 0.85–1.25), P-trend = 0.970) or in men and women separately (quintiles 5 versus 1, HR, 1.05 (95% CI, 0.83–1.33), P-trend = 0.871 and quintiles 5 versus 1, HR, 0.99 (95% CI 0.72–1.37), P-trend = 0.928, respectively). Investigating the association between LA and MI with a shorter, 5- or 10-year duration of follow-up provided similar results. Conclusion: Content of LA in adipose tissue was not associated with the risk of MI. [ABSTRACT FROM AUTHOR]

Background: American-style football (ASF) athletes are at risk for cardiovascular disease (CVD) and exhibit elevated levels of serum neurofilament light (Nf-L), a biomarker of axonal injury that is associated with repetitive head impact exposure over the course of a season of competition. Supplementation with the w-3 fatty acid (FA) docosahexaenoic acid (DHA) attenuates serum Nf-L elevations and improves aspects of CVD, such as the omega-3 index (O3I). However, the effect of combining the w-3 FA eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) with DHA on, specifically, serum Nf-L in ASF athletes is unknown. Therefore, this study assessed the effect of supplemental w-3 FA (EPA+DPA+DHA) on serum Nf-L, plasma w-3 FAs, the O3I, and surrogate markers of inflammation over the course of a season. Methods: A multi-site, non-randomized design, utilizing two American football teams was employed. One team (n = 3 1) received supplementation with a highly bioavailablew-3 FA formulation (2000mg DHA, 560mg EPA, 320mg DPA, Mindset®, Struct Nutrition, Missoula, MT) during pre-season and throughout the regular season, while the second team served as the control (n = 35) and did not undergo supplementation. Blood was sampled at specific times throughout pre- and regular season coincident w ith changes in intensity, physical contact, and changes in the incidence and severity of head impacts. Group differences were determined via a mixed-model between-within subjects ANOVA. Effect sizes were calculated using Cohen's dfor all between-group differences. Significance was set a priori at p<.05. Results: Compared to the control group, ASF athletes in the treatment group experienced large increases in plasma EPA (p <.001, d = 1.71) and DHA (p <.001, d = 2.10) which contributed to increases in the O3I (p <.001, d = 2.16) and the EPA:AA ratio (p =.001, d = 0.83) and a reduction in the w-6: w-3 ratio (p <.001, d = 1.80). w-3 FA supplementation attenuated elevations in Nf-L (p =.024). The control group experienced a significant increase in Nf-L compared to baseline at several measurement time points (T2, T3, and T4 [p range <.001 –.005, drange = 0.59-0.85]). Conclusions: These findings suggest a cardio- and neuroprotective effect of combined EPA+DPA+DHA w-3 FA supplementation in American-style football athletes. Trial registration: This trial was registered with the ISRCTN registry (ISRCTN90306741). [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) may lead to increased circulating concentrations of inflammatory biomarkers and treatment may change these. We aimed to assess the effect of oral appliance (OA) therapy on inflammatory biomarkers in a randomised controlled pilot trial. A total of 71 patients with OSA and systemic hypertension were randomly allocated to an active, mandible protruded (OAa) or a passive, mandible non‐protruded device (OAp) treatment. Serum concentrations of the inflammatory biomarkers white blood cells, high‐sensitivity C‐reactive protein, interleukin 6, interleukin 10, and tumour necrosis factor‐α were measured at baseline and after 3 months of OA treatment. The differences between treatment groups in biomarker concentration change during the treatment were presented as the Vargha and Delaney effect size and evaluated with the Wilcoxon–Mann–Whitney test. This effect size expresses the probability of a higher value in a random participant from one group compared with a random patient from the other group, and a value of 0.5 means stochastically equal groups. After 3 months of treatment, there was a significant reduction of the apnea–hypopnea index in the OAa group compared with the OAp group (effect size 0.258, 95% confidence interval 0.146–0.386, p <.001). There were no significant differences between the groups in any of the inflammatory markers' concentration changes during the treatment period (effect sizes between 0.488 and 0.524; all p values ≥.737). Thus, OA treatment for 3 months did not affect circulating concentrations of some common inflammatory markers in patients with OSA and systemic hypertension. [ABSTRACT FROM AUTHOR]

Background: CVD is the leading cause of death in T2DM patients. However, few biomarkers have been identified to detect and diagnose CVD in the early stage of T2DM. The aim of our study was to identify the important mRNAs, micro (mi)RNAs and SNPs (single nucleotide polymorphisms) that are associated with metabolic cardiovascular disease.Materials and Methods: Expression profiles and GWAS data were obtained from Gene Expression Omnibus (GEO) database. MiRNA-sequencing was conducted by Illumina HiSeq 2000 platform in T2DM patients and T2DM with CVD patients. EQTL analysis and gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. MRNA-miRNA co-expression network and mRNA-SNP-miRNA interaction network were established and visualized by Cytoscape 3.7.2.Results: In our study, we identified 56 genes and 16 miRNAs that were significantly differentially expressed. KEGG analyses results indicated that B cell receptor signaling pathway and hematopoietic cell lineage were included in the biological functions of differentially expressed genes. MRNA-miRNA co-expression network and mRNA-SNP-miRNA interaction network illustrated that let-7i-5p, RASGRP3, KRT1 and CEP41 may be potential biomarkers for the early detection and diagnosis of CVD in T2DM patients.Conclusion: Our results suggested that downregulated let-7i-5p, and upregulated RASGRP3, KRT1 and CEP41 may play crucial roles in molecular mechanisms underlying the initiation and development of CVD in T2DM patients. [ABSTRACT FROM AUTHOR]

The n-3 and n-6 polyunsaturated fatty acids (PUFA) are among the most studied nutrients in human metabolism. In the past few decades, prospective studies and controlled trials have supported the view that the effects of these essential fatty acids are clinically relevant. PUFA profiles in different blood compartments are reflections of both diet and metabolism, and their levels may be related to disease risk. Despite widespread interest, there is no consensus regarding which biomarkers best reflect PUFA status in the body. The measurement of PUFA levels is not straight-forward, and a wide variety of indices have been used in clinical studies, producing conflicting results. A major source of heterogeneity among studies is associated with research design, sampling, and laboratory analyses. To date, the n-3 index, n-6/n-3 ratio, and arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio are the most promising biomarkers associated with PUFA metabolism. Although hotly debated, these indices may be considered at least markers, if not risk factors, for several diseases, especially cardiovascular events and brain disorders. Here, we summarize the most updated evidence of n-3 and n-6 PUFA effects on human health, reviewing current controversies on the aforementioned indices and whether they can be considered valuable predictors of clinical outcomes. [ABSTRACT FROM AUTHOR]

Over the past few decades, RNA sequencing has significantly progressed, becoming a paramount approach for transcriptome profiling. The revolution from bulk RNA sequencing to single-molecular, single-cell and spatial transcriptome approaches has enabled increasingly accurate, individual cell resolution incorporated with spatial information. Cancer, a major malignant and heterogeneous lethal disease, remains an enormous challenge in medical research and clinical treatment. As a vital tool, RNA sequencing has been utilized in many aspects of cancer research and therapy, including biomarker discovery and characterization of cancer heterogeneity and evolution, drug resistance, cancer immune microenvironment and immunotherapy, cancer neoantigens and so on. In this review, the latest studies on RNA sequencing technology and their applications in cancer are summarized, and future challenges and opportunities for RNA sequencing technology in cancer applications are discussed. [ABSTRACT FROM AUTHOR]

Objective: Obtaining objective, dietary exposure information from individuals is challenging because of the complexity of food consumption patterns and the limitations of self-reporting tools (e.g., FFQ and diet diaries). This hinders research efforts to associate intakes of specific foods or eating patterns with population health outcomes.Design: Dietary exposure can be assessed by the measurement of food-derived chemicals in urine samples. We aimed to develop methodologies for urine collection that minimised impact on the day-to-day activities of participants but also yielded samples that were data-rich in terms of targeted biomarker measurements.Setting: Urine collection methodologies were developed within home settings.Participants: Different cohorts of free-living volunteers.Results: Home collection of urine samples using vacuum transfer technology was deemed highly acceptable by volunteers. Statistical analysis of both metabolome and selected dietary exposure biomarkers in spot urine collected and stored using this method showed that they were compositionally similar to urine collected using a standard method with immediate sample freezing. Even without chemical preservatives, samples can be stored under different temperature regimes without any significant impact on the overall urine composition or concentration of forty-six exemplar dietary exposure biomarkers. Importantly, the samples could be posted directly to analytical facilities, without the need for refrigerated transport and involvement of clinical professionals.Conclusions: This urine sampling methodology appears to be suitable for routine use and may provide a scalable, cost-effective means to collect urine samples and to assess diet in epidemiological studies. [ABSTRACT FROM AUTHOR]

Lupus is a systemic autoimmune disease typified by uncontrolled inflammation, disruption of immune tolerance, and intermittent flaring – events triggerable by environmental factors. Preclinical and clinical studies reveal that consumption of the marine ω-3 highly unsaturated fatty acids (HUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) might be used as a precision nutrition intervention to lessen lupus symptoms. The anti-inflammatory and pro-resolving effects of ω-3 HUFAs are inextricably linked to their presence in membrane phospholipids. The ω-3 HUFA score, calculated as [100 × (ω-3 HUFAs/(ω-3 HUFAs + ω-6 HUFAs))] in red blood cells (RBCs), and the Omega-3 Index (O3I), calculated as [100 × ((DHA+EPA)/total fatty acids)] in RBCs, are two biomarkers potentially amenable to relating tissue HUFA balance to clinical outcomes in individuals with lupus. Using data from three prior preclinical DHA supplementation studies, we tested the hypothesis that the ω-3 HUFA score and the O3I inversely correlate with indicators of autoimmune pathogenesis in the cSiO2-triggered lupus flaring model. The three studies employed both low and high fat rodent diets, as well as more complex diets emulating the U.S. dietary pattern. The ω-3 HUFA scores in RBCs were comparatively more robust than the O3I at predicting HUFA balances in the kidney, liver, spleen, and lung. Importantly, increases in both the ω-3 HUFA score (>40%) and the O3I (>10%) were strongly associated with suppression of cSiO2-triggered (1) expression of interferon-regulated genes, proinflammatory cytokine production, leukocyte infiltration, and ectopic lymphoid structure development in the lung, (2) pulmonary and systemic autoantibody production, and (3) glomerulonephritis. Collectively, these findings identify achievable ω-3 HUFA scores and O3I thresholds that could be targeted in future human intervention studies querying how ω-3 HUFA consumption influences lupus and other autoimmune diseases. [ABSTRACT FROM AUTHOR]

Rationale: Consumption of whole grains is negatively associated with cardiovascular disease (CVD) risk but quantification of whole‐grain intake is challenging. Alkylresorcinols (ARs) are biomarkers of whole‐grain intake. Current methods for AR quantification involve a time‐consuming multi‐step separation process that hampers applicability in large‐scale studies. Methods: We developed a streamlined method to quantify ARs in human plasma based on protein precipitation and direct injection into an ultra‐high‐performance liquid chromatograph coupled to a quadrupole time‐of‐flight mass spectrometer operating in atmospheric pressure chemical ionization negative ion mode. Results: Separation of five major ARs was achieved, with linearity in the 5 to 550 nmol/L range and a lower limit of detection (LOD) of 0.5 nmol/L and quantification (LOQ) of 5 nmol/L. The within‐run and between‐run precision and accuracy were below 15%, and recoveries above 90%. Once validated, the method was applied to measure concentrations of plasma ARs in subjects who participated in a randomized, crossover trial evaluating the effect of carbohydrate type on CVD risk factors. The unrefined carbohydrate diet with the highest fiber content resulted in the highest plasma AR concentration (93 ± 78 nmol/L), and was significantly different (p <0.01) from lower fiber diets (18 ± 26 nmol/L and 19 ± 26 nmol/L, simple and unrefined carbohydrate, respectively). Conclusions: This method offers a simplified approach to measure concentrations of plasma ARs as an objective biomarker of whole‐grain intake that can be applied to large‐scale cohort studies. [ABSTRACT FROM AUTHOR]

The whole grain intake is closely associated with human health. In this work, three‐phase dynamic hollow‐fiber liquid‐phase microextraction reinforced with 0.10 mg/mL 30 nm zeolitic imidazolate framework‐8 nanoparticles was introduced for purification and enrichment of free urinary metabolite biomarkers of whole grain intake. Eight milliliters of HCl (pH 3.00) and 8 μL of 300 mM NaOH solutions were used as the donor and acceptor phases, respectively. The temperature and stirring rate were kept at 25℃ and 500 rpm, and the extraction time was 40 min. The extraction process required no further desorption, and the resultant extract was directly used for electrophoretic analysis without derivatization. Based on the synergistic effect of hollow‐fiber liquid‐phase microextraction and the electrophoretic stacking, the enrichment factors of 3,5‐dihydroxybenzoic acid and 3‐(3,5‐dihydroxyphenyl)‐1‐propionic acid reached 1018–1034 times, and their limits of detection achieved 0.33–0.67 ng/mL (S/N = 3) in urine matrix. The developed method has been successfully used for urine analysis, and the sample recovery data were in the range of 97.0–103.5%. This developed method provided an attractive alternative for the determination of urinary metabolite biomarkers of whole grain intake due to its sensitive, fast, low‐cost, and environmental‐friendly features. [ABSTRACT FROM AUTHOR]

Dietary intakes are commonly assessed by established methods including food frequency questionnaires, food records, or recalls. These self-report methods have limitations impacting validity and reliability. Dietary biomarkers provide objective verification of self-reported food intakes, and represent a rapidly evolving area. This review aims to summarize the urinary biomarkers of individual foods, food groups, dietary patterns, or nutritional supplements that have been evaluated to date. Six electronic databases were searched. Included studies involved healthy populations, were published from 2000, and compared measured dietary intake with urinary markers. The initial search identified 9985 studies; of these, 616 full texts were retrieved and 109 full texts were included. Of the included studies, 67 foods and food components were studied, and 347 unique urinary biomarkers were identified. The most reliable biomarkers identified were whole grains (alkylresorcinols), soy (isoflavones), and sugar (sucrose and fructose). While numerous novel urinary biomarkers have been identified, further validation studies are warranted to verify the accuracy of self-reported intakes and utility within practice. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is a complex metabolic disease associated with disturbances in metabolism of carbohydrates, lipids and proteins, and largely under the influence of very complex interactions with genetic and environment factors. High prevalence and increasing number of patients with T2D in the world, represent constant challenge for better elucidation of pathogenic mechanisms which contribute to disease development. This paper summarizes a new molecular biomarker that emerged from recent studies in applied genomics, metabolomics and other modern "omics" technologies as powerful tools in diagnosis of T2D. Metabolomics, in this context, has a special potential since it uses newly developed analytical methods in analyses of wide range of metabolites in biological samples. Numbers of prospective studies have shown that changes in the concentration of some individual amino acids, acylcarnitines, hexoses and phospholipids augment or attenuate risk factors for developing T2D. Recently findings shown that polymorphisms in TCF7L2 gene were strongly associated with increasing risk for T2D development while studies of lipidomics, genomics and transcriptomics identified molecular markers for glucose intolerance and other traits. Some specific gene variations were identified which affected de novo lipogenesis and they were significantly associated with concentrations of palmitic, stearic, palmitoleic and oleic acids, the major saturated and unsaturated fatty acids. Development of new trends in analysis and detection of different metabolites, especially fatty acids and amino acids, along with genetic polymorphisms points out new directions in precise diagnosis and therapy of Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Increased attention has been paid to circadian patterns and how predisposition to metabolic disorders can be affected by meal timing. Currently, it is not clear which role can be attributed to the foods selected at meals. On a cross-sectional sub-cohort study (815 adults) within the European Prospective Investigation into Cancer and Nutrition-Potsdam study, we investigated whether the same foods (vegetables, fruits, refined grains, whole grains, red and processed meats) eaten at different meals (breakfast, lunch or dinner) show different associations with biomarkers of cardiometabolic risk. Meal-specific usual intakes were calculated from multiple 24-h dietary recalls. Multivariable-adjusted linear regression models showed that intake of vegetables at breakfast was associated with lower LDL-cholesterol (−0·37 mmol/l per 50 g; 95 % CI −0·61, −0·12) and vegetables at dinner was associated with higher HDL-cholesterol (0·05 mmol/l per 50 g; 95 % CI 0, 0·10). Fruit intake at breakfast was associated with lower glycated Hb (HbA1c) (−0·06 % per 50 g; 95 % CI −0·10, −0·01) and fruits at dinner with lower C-reactive protein (CRP) (−0·21 mg/l per 50 g; 95 % CI −0·42, −0·01). Red and processed meat intake at breakfast was associated with higher HbA1c (0·25 % per 50 g; 95 % CI 0·05, 0·46) and CRP (0·76 mg/l per 50 g; 95 % CI 0·15, 1·36). Our results suggest that by preferring fruits and vegetables and avoiding red and processed meats at specific meals (i.e. breakfast and dinner), cardiometabolic profiles and ultimately chronic disease risk could be improved. Lunch seemed to be a less important meal in terms of food–biomarker associations. [ABSTRACT FROM AUTHOR]

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