Biomarkers Of Whole-grain Intake Research Articles

Zeolitic imidazolate framework-8 reinforced hollow-fiber liquid-phase microextraction of free urinary biomarkers of whole grain intake followed by CE analysis.

The whole grain intake is closely associated with human health. In this work, three-phase dynamic hollow-fiber liquid-phase microextraction reinforced with 0.10mg/mL 30nm zeolitic imidazolate framework-8 nanoparticles was introduced for purification and enrichment of free urinary metabolite biomarkers of whole grain intake. Eightmilliliters of HCl (pH 3.00) and 8 μL of 300mM NaOH solutions were used as the donor and acceptor phases, respectively. The temperature and stirring rate were kept at 25℃ and 500rpm, and the extraction time was 40min. 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 0.33-0.67ng/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.

Personalized Nutrition Recommendations Improve Plasma Metabolite Concentrations Related to Dietary Intake

Abstract Objectives The objectives of our proof-of-concept study was to assess the efficacy of personalized nutrition interventions on diet and chronic disease risk. Methods Fasting plasma samples were collected at day 1 and day 100 of a cohort of 148 adults (aged 23–65y) volunteers with a median (range) BMI of 25.8 (17.2–48.3). At both time points 119 metabolites were quantitated using LC-MS/MS. Based on their metabolite concentrations and dietary preferences, each participant received their own personalized nutrition recommendations through an AI-assisted online platform and were advised to follow the recommendations for 100 days. Plasma metabolite concentrations from Day 1 and Day 100 were compared using a paired t-test with Holm-Bonferroni correction (P < 0.05). Results After 100 days, statistically significant changes in acylcarnitine, phosphatidylcholine and amino acid concentrations indicated participants had increased their intakes of omega-3 fats and whole grains and decreased their intakes of saturated fat. For example, Betaine, a biomarker of whole grain intake, increased significantly in concentration from Day 1 to Day 100 [mean (SD): 34.3 (13.2) to 45.3 (15.6) umol/l]. Overall, 55 of the analyzed 119 metabolites’ (46%) concentrations had previously been linked to dietary intake according to a systematic literature search that was used to generate evidence-based personalized nutrition recommendations. Concentrations of 33 (60%) of these 55 metabolites changed significantly. The majority [26 (79%)] of the metabolite concentrations changed in a predicted manner consistent with the literature, particularly those metabolites associated to chronic disease risk. For example, a significant decrease in asymmetric dimethylarginine concentration [mean (SD): 0.54 (0.15) to 0.48 (0.12) umol/L] which is understood to result in a decreased cardiovascular disease risk. Conclusions Adherence with an evidence-based personalized nutrition plan based on a panel of serum metabolomic data can significantly modify serum metabolite concentrations in a direction that can reduce the risk of chronic disease. Further analysis in how these changes relate to chronic disease risk is warranted. Funding Sources This study was supported by Mitacs and Molecular You.

Whole-Grain Processing and Glycemic Control in Type 2 Diabetes: A Randomized Crossover Trial.

OBJECTIVETo consider the effects of whole-grain processing, specifically milling, on glycemic control in free-living adults with type 2 diabetes.RESEARCH DESIGN AND METHODSParticipants of this crossover trial were randomized to two interventions of 2 weeks, separated by washout. They were advised to replace the grain foods they normally consumed with intervention foods. Intervention foods were nutrient-matched whole-grain products of wheat, oats, and brown rice that differed in their degree of processing. No other lifestyle advice was given. Continuous glucose monitoring systems were worn. Other cardiometabolic risk factors and alkylresorcinols (a biomarker of whole-grain intake) were measured pre- and postintervention.RESULTSThirty-one adults with type 2 diabetes (63 ± 13 years old, BMI 32.4 ± 7 kg/m2, HbA1c 7.5 ± 3.4% [59 ± 14 mmol/mol]) commenced the trial; 28 (90%) completed both interventions. The increase in alkylresorcinols did not differ between interventions, and there was no difference in reported energy intake. Postprandial responses were 9% (95% CI 3–15) lower following breakfast and 6% (1–10) lower following all meals of less-processed whole grains when compared with finely milled grains. Day-long glycemic variability also was reduced when measured by 24-h SD (−0.16 mmol/L [95% CI −0.25 to −0.06]) and mean amplitude of glycemic excursion (−0.36 [95% CI −0.65 to −0.08]). Mean change in body weight differed by 0.81 kg (95% CI 0.62–1.05) between interventions, increasing during the finely milled intervention and decreasing during the less-processed whole-grain intervention. This was not a mediating factor for the glycemic variables considered.CONCLUSIONSConsuming less-processed whole-grain foods over 2 weeks improved measures of glycemia in free-living adults with type 2 diabetes compared with an equivalent amount of whole-grain foods that were finely milled. Dietary advice should promote the consumption of minimally processed whole grains.

Alkylresorcinols (biomarkers of whole grain intake), cereal fibre intake and metabolic profile - results from a European study

AbstractBackground:High intakes of whole-grains and cereal fiber have been consistently associated with lower risk of cardiometabolic diseases in observational studies. Yet, improved understanding about the underlying mechanisms is needed. We hypothesized that cereal fiber and whole-grain are associated with beneficial metabolic marker profiles.Aim:To investigate if cereal fiber intake, estimated by food frequency questionnaires and plasma total alkylresorcinols concentrations as well as the C17:0/C21:0-ratio in plasma as biomarkers of whole-grain wheat and rye intake or the relative whole-grain rye to wheat intake, respectively, were associated with metabolic biomarkers.Design:A cross-sectional study conducted to investigate the associations between alkylresorcinols as biomarker of whole-grain wheat and rye intake, cereal fiber and selected metabolic biomarkers among 954 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cereal fiber intake was assessed by FFQ and whole grain wheat and rye were reflected by biomarkers analyzed in plasma samples, i.e. total alkylresorcinol (AR). Moreover, the ratio of two of the five measured alkylresorcinols (AR C17:0/C21:0 ratio) was used as an indicator of whole-grain source (wheat or rye). Metabolic biomarkers (HbA1c, C-peptide, IGFBP-1, IGFBP-2, total cholesterol, LDL, HDL, triglycerides, apolipoprotein A-I (apoA), apolipoprotein B (ApoB) and CRP) were measured in blood samples. All biomarkers were already measured for nested case-control studies of colorectal cancer matched based on sex, study center, age at blood collection, date and time of blood collection, fasting status. Women were further matched by menopausal status, phase of menstrual cycle, and use of oral contraceptives or hormone replacement therapy at time of blood collection. Multivariable linear regression analysis was used to investigate the relationship between exposure variables metabolic biomarkers adjusted for case-control status and common confounders.Results:No associations were found between cereal fiber intake and the metabolic markers. However, whole-grain wheat and rye intake, reflected by total AR, was associated with a lower concentration of the inflammation marker CRP. The alkylresorcinol C17:0/C21:0 ratio was not associated with any of the measured metabolic markers in this cohort.Conclusion:Overall, we found no support for an association between cereal fibre intake, whole grain wheat and rye intake reflected by biomarkers and metabolic markers in the present cohort. One exception was the finding of an inverse association between whole grain biomarkers and CRP. Prospective studies or RCTs are warranted to confirm our findings.

Biomarkers of Whole-Grain and Cereal-Fiber Intake in Human Studies: A Systematic Review of the Available Evidence and Perspectives.

High whole-grain consumption is related to better health outcomes. The specific physiological effect of these compounds is still unrevealed, partly because the accurate estimation of the intake of whole grains from dietary assessments is difficult and prone to bias, due to the complexity of the estimation of the intake by the consumer. A biomarker of whole-grain intake and type of whole-grain intake would be useful for quantifying the exposure to whole-grain intake. In this review, we aim to review the evidence on the potential biomarkers for whole-grain intake in the literature. We conducted a systematic search in Medline, Embase, Web of Science, and the Cochrane database. In total, 39 papers met the inclusion criteria following the PRISMA guidelines and were included. The relative validity, responsiveness, and reproducibility of these markers were assessed for short-, medium-, and long-term exposure as important criteria for the potential use of these biomarkers from a clinical and research perspective. We found three major groups of biomarkers: (1) alkylresorcinol, as well as its homologs and metabolites, assessed in plasma, adipose tissue biopsies, erythrocyte membranes, and urine; (2) avenacosides, assessed in urine samples; and (3) benzoxazinoid-derived phenylacetamide sulfates, assessed in blood and urine samples. The reviewed biomarkers may be used for improved assessment of associations between whole-grain intake and health outcomes.

Abstract P285: Development of a Simplified Method for the Measurement of Plasma Alkylresorcinols as a Biomarker of Whole Grain Intake and Application to a Human Clinical Trial Evaluating the Effect of Carbohydrate Quality on Cardiometabolic Risk Factors

Introduction: Consumption of whole grains is associated with improvements in cardiometabolic risk factors and decreased CVD risk. Quantification of whole grain intake is challenging due to the limitations of self-reported intake; diversity among and differences in the interpretation of the term “whole grain”. Alkylresorcinols (ARs) are phenolic lipids present in the outer layer of wheat and rye grains that are considered objective biomarkers of whole grain intake. Current methods for ARs quantification involve a multi-step separation, extraction and purification processes that hampers applicability in large-scale studies. Hypothesis: Our aim was to develop a single-step method to measure 5 predominant ARs (C17:0, C19:0, C21:0, C23:0 and C25:0) in human plasma, and to validate this method by measuring plasma ARs levels in subjects who participated in a randomized, cross-over trial evaluating the effect of carbohydrate quality on CVD risk factors. We hypothesized that the direct method would distinguish between low- and high-whole grain intake and be more rapid and cost effective than prior methods. Methods: A dilute-and-shoot strategy based on plasma (20 μL) dilution with methanol for protein precipitation, followed by centrifugation and direct injection into an ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometer (UHPLC/Q-TOF-MS; Agilent Technologies), using negative electrospray ionization. C19:0-D 4 was used as internal standard. Separation was performed using a C18 column. Run time was 11 minutes/sample. Method validation was based on the following criteria: linearity, working range, lowest limit of quantification (LOQ), accuracy and precision. This method was then used to quantify ARs in fasting plasma samples from postmenopausal women and men (N=11, 65±8 years, BMI 29.8±3.2 kg/m 2 , LDL-C ≥2.6 mmol/L) who consumed each of 3 isocaloric diets (60%E carbohydrate, 15%E protein, 25%E fat) enriched in either simple, refined, or unrefined carbohydrate-containing foods for 4.5 weeks in a randomized crossover design, with 2-week washout periods. Results: (1) Analytical: The method showed linearity (>0.999) in the range 2 to 100 ng/mL, and had acceptable values for accuracy and precision with a LOQ of 2 ng/mL. (2) Applicability: Total fiber content of the simple, refined and unrefined carbohydrate diets was 8.6, 9.6 and 19.5g/1000kcal, respectively. This was reflected in plasma AR levels, being significantly higher (p<0.05) after subjects consumed the unrefined (124.8±55.8 pmol/mL) compared to the simple (29.5±10.3 pmol/mL) and refined (26.8±9.0 pmol/mL) diets. C21:0 and C19:0 were the major ARs present in plasma. Conclusion: This simplified method offers a direct and rapid strategy to accurately measure AR in human plasma that can be scaled up for large studies, and provides an objective assessment of whole grain intake.

Biomarkers of Whole Grain Intake

There is growing evidence that whole grain (WG) intake may prevent many chronic diseases. However, there are mixed results on this topic in human studies as a result of a lack of accurate tools to assess the intake of WGs and individual metabolic variation. To better understand the effects of WGs on health maintenance and the risk of chronic disease, there is an urgent need to identify the biomarkers for WG intake. The molecular signatures of WG intake remain undefined. This perspective gives an overview of the current knowledge, challenges, and future directions on the biomarkers of WG intake.

Evaluating Whole Grain Intervention Study Designs and Reporting Practices Using Evidence Mapping Methodology.

Consumption of whole grains have been associated with reduced risk of chronic diseases in many observational studies; yet, results of intervention studies are mixed. We aimed to use evidence mapping to capture the methodological and reporting variability in whole grain intervention studies that may contribute to this inconsistency. We conducted a reproducible search in OVID Medline for whole grain human intervention studies (published 1946 to February 2018). After screening based on a priori criteria, we identified 202 publications describing a total of 213 unique trials. Over half (55%) were acute trials, lasting ≤1 day, 30% were moderate duration studies (up to 6 weeks) and 15% were of longer duration (more than 6 weeks). The majority of acute trials (75%) examined measures of glycaemia and/or insulinemia, while most of the longer trials included measures of cardiometabolic health (71%), appetite/satiety (57%) and weight/adiposity (56%). Among the moderate and long duration trials, there was a wide range of how whole grains were described but only 10 publications referenced an established definition. Only 55% of trials reported the actual amount of whole grains (in grams or servings), while 36% reported the amount of food/product and 9% did not report a dose at all. Of the interventions that provided a mixture of whole grains, less than half (46%) reported the distribution of the different grain types. Reporting of subject compliance also varied and only 22% used independent biomarkers of whole grain intake. This evidence map highlights the need to standardize both study protocols and reporting practices to support effective synthesis of study results and provide a stronger foundation to better inform nutrition scientists and public health policy.

Novel urinary alkylresorcinol metabolites as biomarkers of whole grain intake in free-living Swedish adults.

Most studies on the role of whole grain for health rely on self-reported intake data, which are prone to measurement errors. There is a need for dietary biomarkers that can provide an objective measure of intake. Alkylresorcinols (AR) and their main metabolites 3,5-dihydroxybenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)-propanoic acid (DHPPA) have been proposed as biomarkers for whole grain (WG) wheat and rye intake. The medium-term reproducibility and relative validity of four putative urinary AR metabolites (3,5-dihydroxycinnamic acid (DHCA), 5-(3,5-dihydroxyphenyl) pentanoic acid (DHPPTA), 2-(3,5-dihydroxybenzamido)acetic acid (DHBA-glycine) and 3,5-dihydroxycinnamic acid amide (DHCA-amide)) as biomarkers for WG intake were investigated. Three-day weighed food records and 24-h urine samples from two occasions 2-3 months apart were obtained from 69 Swedish adults. WG intake was calculated and urinary AR metabolites were analyzed. The medium-term reproducibility determined for DHCA, DHPPTA, and DHBA-glycine varied from moderate-to-excellent (intra-class correlation coefficient = 0.63-0.85). Moreover, DHCA and DHPPTA excretion correlated well with self-reported total WG intake (r=0.55, p<0.001 and r=0.42, p<0.001, respectively). DHCA or DHPPTA excretion in 24-h urine might be a suitable medium- to long-term biomarker of WG wheat and rye intake. These findings need to be confirmed in populations with low and infrequent WG intake.

Substituting whole grains for refined grains in a 6-wk randomized trial favorably affects energy-balance metrics in healthy men and postmenopausal women1–3

Background: The effect of whole grains on the regulation of energy balance remains controversial.Objective: We aimed to determine the effects of substituting whole grains for refined grains, independent of body weight changes, on energy-metabolism metrics and glycemic control.Design: The study was a randomized, controlled, parallel-arm controlled-feeding trial that was conducted in 81 men and postmenopausal women [49 men and 32 women; age range: 40–65 y; body mass index (in kg/m2): <35.0]. After a 2-wk run-in period, participants were randomly assigned to consume 1 of 2 weight-maintenance diets for 6 wk. Diets differed in whole-grain and fiber contents [mean ± SDs: whole grain–rich diet: 207 ± 39 g whole grains plus 40 ± 5 g dietary fiber/d; refined grain–based diet: 0 g whole grains plus 21 ± 3 g dietary fiber/d] but were otherwise similar. Energy metabolism and body-composition metrics, appetite, markers of glycemic control, and gut microbiota were measured at 2 and 8 wk.Results: By design, body weight was maintained in both groups. Plasma alkylresorcinols, which are biomarkers of whole-grain intake, increased in the whole grain–rich diet group (WG) but not in the refined grain–based diet group (RG) (P-diet-by-time interaction < 0.0001). Beta ± SE changes (ΔWG compared with ΔRG) in the resting metabolic rate (RMR) (43 ± 25 kcal/d; P = 0.04), stool weight (76 ± 12 g/d; P < 0.0001), and stool energy content (57 ± 17 kcal/d; P = 0.003), but not in stool energy density, were higher in the WG. When combined, the favorable energetic effects in the WG translated into a 92-kcal/d (95% CI: 28, 156-kcal/d) higher net daily energy loss compared with that of the RG (P = 0.005). Prospective consumption (P = 0.07) and glycemia after an oral-glucose-tolerance test (P = 0.10) trended toward being lower in the WG than in the RG. When nonadherent participants were excluded, between-group differences in stool energy content and glucose tolerance increased, and between-group differences in the RMR and prospective consumption were not statistically significant.Conclusion: These findings suggest positive effects of whole grains on the RMR and stool energy excretion that favorably influence energy balance and may help explain epidemiologic associations between whole-grain consumption and reduced body weight and adiposity. This trial was registered at clinicaltrials.gov as NCT01902394.

Alkylresorcinols in adipose tissue biopsies as biomarkers of whole-grain intake: an exploratory study of responsiveness to advised intake over 12 weeks.

Alkylresorcinols (ARs) have been suggested as biomarkers of whole-grain wheat and rye intake. Plasma AR concentrations have a short half-life; hence, long-term biomarkers are needed. This study evaluated the responsiveness of ARs in adipose tissue biopsies as biomarkers after a whole-grain intake intervention. Samples and data of 27 participants from a 12-week randomized parallel-group dietary intervention were available. The participants were replacing their habitual diet with a whole-grain-enriched diet (WGDG) or a refined grain diet (RDG) during the intervention. Blood samples and adipose tissue biopsies were collected at baseline and after 12 weeks, and AR concentrations in the plasma and adipose tissues from the participants were compared against estimated whole-grain intake. AR concentrations in the adipose tissue and plasma did not change after 12 weeks in the WGDG group, as no significant increase in whole-grain intake was observed, but was significantly lower than baseline in the RDG group (P<0.05), owing to decreased whole-grain intake in this group. Plasma and adipose tissue AR concentrations were significantly higher in the WGDG group than in the RDG group (P<0.05), and were highly correlated with average whole-grain intake estimated by food records (Spearman's r=0.60-0.72 (P<0.05, n=16) for total and individual AR homolog concentrations in the plasma; r=0.60--0.84, (P<0.05, n=16) for total and individual AR homolog concentrations in the adipose tissue). In this small pilot study, AR concentrations in adipose tissue responded to reduced intake of whole grain over 12 weeks. Although not significantly different from plasma AR, adipose tissue AR concentrations were highly correlated with whole-grain intake after a 12-week intervention. These results show that adipose tissue AR concentrations have promise as biomarkers of whole-grain wheat and rye intake. Larger studies are needed to evaluate whether they are better long-term biomarkers than AR in the plasma.

Whole grain intake, determined by dietary records and plasma alkylresorcinol concentrations, is low among pregnant women in Singapore.

To quantify whole grain intake in pregnant women in Singapore in order to provide the first detailed analysis of whole grain intake in an Asian country and in pregnant women. Analysis of 24-h diet recalls in a cross-sectional cohort study and analysis of a biomarker of whole grain intake (plasma alkylresorcinols) in a subset of subjects. The Growing Up in Singapore Towards healthy Outcomes-mother offspring cohort study based in Singapore. 998 pregnant mothers with complete 24-h recalls taken during their 26-28th week of gestation. Plasma samples from a randomly select subset of 100 subjects were analysed for plasma alkylresorcinols. Median (IQR) whole grain intake for the cohort and the 30% who reported eating whole grains were 0 (IQR 0, 9) and 23.6 (IQR 14.6, 44.2) g/day respectively. Plasma alkylresorcinol concentrations were very low [median (IQR)=9 (3, 15) nmol/L], suggesting low intake of whole grain wheat in this population. Plasma alkylresorcinols were correlated with whole grain wheat intake (Spearman's r=0.35; p<0.01). Whole grain intake among pregnant mothers in Singapore was well below the 2-3 (60-95 g) servings of whole grains per day recommended by the Singapore Health Promotion Board. Efforts to increase whole grain intake should be supported to encourage people to choose whole grains over refined grains in their diet.

Plasma alkylresorcinols, biomarkers of whole-grain intake, are not associated with progression of coronary artery atherosclerosis in postmenopausal women with coronary artery disease.

The objective of the present study was to examine the relationship between plasma alkyresorcinol (AR) concentrations, which are biomarkers of whole-grain intake, and atherosclerotic progression over 3 years in postmenopausal women with coronary artery disease. Plasma AR concentrations were measured by a validated GC-MS method in fasting plasma samples. Atherosclerosis progression was assessed using change in mean minimal coronary artery diameter (MCAD) and percentage diameter stenosis (%ST), based on mean proximal vessel diameter across up to ten coronary segments. Dietary intake was estimated using a 126-item interviewer-administered FFQ. A prospective study of postmenopausal women participating in the Estrogen Replacement and Atherosclerosis trial. For the analysis of plasma AR concentrations and atherosclerotic progression, plasma samples and follow-up data on angiography were available for 182 women. Mean whole-grain intake was 9·6 (se 0·6) servings per week. After multivariate adjustment, no significant associations were observed between plasma AR concentrations and change in mean MCAD or progression of %ST. Plasma AR concentrations were significantly correlated with dietary whole grains (r=0·35, P<0·001), cereal fibre (r=0·33, P<0·001), bran (r=0·15, P=0·05), total fibre (r=0·22, P=0·003) and legume fibre (r=0·15, P=0·04), but not refined grains, fruit fibre or vegetable fibre. Plasma AR concentrations were not significantly associated with coronary artery progression over a 3-year period in postmenopausal women with coronary artery disease. A moderate association was observed between plasma AR concentrations and dietary whole grains and cereal fibre, suggesting it may be a useful biomarker in observational studies.

Abstract P408: Plasma Alkylresorcinol, A Biomarker of Whole-Grain Intake, Is Not Associated With Progression of Coronary Artery Atherosclerosis In Postmenopausal Women With Coronary Artery Disease

Background: Higher whole-grain intake has been associated with lower risk of cardiovascular disease in prospective observational studies. Few observational studies have incorporated biomarkers of whole-grain intake to confirm self-reported diet-disease associations. Plasma alkylresorcinols (AR) have been used as biomarkers for whole-grain wheat and rye intake. Objective: To assess the relationship between plasma AR concentrations and atherosclerotic progression over a 3-y period. Methods: Plasma AR concentrations were measured by gas chromatography mass spectrometry in baseline samples from 163 post-menopausal women (aged 49-78 y; median BMI: 29.0 kg/m2) with established coronary artery disease (CAD) who participated in the Estrogen Replacement and Atherosclerosis Study (enrolled 1995-1996) and had baseline food frequency questionnaire (FFQ), baseline and follow-up angiography measures, and complete covariate data. Dietary fiber intake was estimated by FFQ and energy-adjusted. Atherosclerosis progression, defined as change in mean minimum coronary artery diameter (MCAD, mm) and change in percent stenosis (%ST), was regressed on plasma AR in mixed models accounting for within-person correlations of coronary segments, and adjusted for the baseline measure, treatment allocation, clinic, age, race, BMI and follow-up time. Results: Median plasma AR was 16.1 nmol/L (interquartile range: 10.9-25.7). Over 3.1±0.7 years of follow-up, MCAD decreased by approximately 0.09±0.02 mm, while %ST increased by approximately 3.2±0.7%. No significant association was observed between AR and change in MCAD or %ST: a 10% increment in AR was associated with a -0.0002±0.0008 mm (P=0.76) change in MCAD and a 0.008±0.03 change in %ST (P=0.79). Further adjustment for lifestyle and risk factors did not materially change these results. As expected, AR correlated with FFQ- derived intake of cereal fiber (Spearman r=0.27, P&lt;0.001) and whole grains (Spearman r=0.28, P&lt;0.001). Of note, this cohort reported low whole-grain and cereal fiber intakes (9.5 servings/wk and 5.3 g/d, respectively). Conclusions: Plasma AR concentrations were not significantly associated with coronary narrowing over a 3-y period in postmenopausal women with CAD. We cannot rule out that large measurement errors in the biomarker, owing to low intake and short half-life may explain the findings.

Plasma Alkylresorcinol Metabolites as Biomarkers for Whole-Grain Intake and Their Association with Prostate Cancer: A Swedish Nested Case–Control Study

Observational studies have mostly found no association between self-reported whole-grain intake and prostate cancer. Plasma alkylresorcinol metabolites have been suggested as biomarkers for whole-grain intake in free-living populations. We investigated the major dietary and lifestyle determinants of plasma alkylresorcinol metabolites in a nested case-control study (1,016 cases and 1,817 controls) in the Malmö Diet and Cancer Study. Multivariate adjusted ORs and 95% confidence intervals (95% CI) were estimated to assess the association between plasma alkylresorcinol metabolites and prostate cancer using logistic regression. Whole-grain intake, waist circumference, educational level, and smoking status were the main determinants of alkylresorcinol metabolites. We observed significant correlations between alkylresorcinol metabolites and whole-grain (r = 0.31) and fiber (r = 0.27) intake. Metabolite concentration was positively associated with prostate cancer risk (Poverall effect = 0.0004) but the association was not linear (P = 0.04). The lowest risk was seen among men with moderate plasma concentrations. The OR for high compared with moderate plasma alkylresorcinol metabolites was 1.41 (95% CI, 1.10-1.80) for prostate cancer. Results suggest that plasma alkylresorcinol metabolites are mainly determined by whole-grain intake in this nested case-control study of Swedish men. The increased risk of prostate cancer seen among men with high plasma alkylresorcinol metabolites requires further study, but residual confounding, detection bias, or competing risks of nonprostate cancer-related deaths are plausible explanations that could not be ruled out. We found no evidence of a protective effect of whole grains on incident prostate cancer. Further validation of alkylresorcinol metabolites as a biomarker for whole-grain intake is needed.

Highlights of This Issue

Few risk factors have been identified for adult glioma. Kitahara and colleagues conducted a pooled analysis of several case–control studies from the US and China. The authors report a 42% reduced risk of glioma for individuals with a history of diabetes. This association does not differ by sex or study design. Future studies will be required to evaluate the associations between type I and type 2 diabetes and glioma.High-risk human papillomavirus (hrHPV) tests have high sensitivity but triage strategies must be carefully developed to follow screen-positive women. Using a cohort of hrHPV-positive women, Dijkstra and colleagues evaluated several triage strategies for the ability to identify cervical intraepithelial neoplasia grade 3 or worse (CIN3+) within four years. The study finds that triaging hrHPV-positive women by cytology after 6 to 12 months combined with HPV16/18 genotyping were effective strategies to follow screen-positive women.The effect of hepatocellular carcinoma (HCC) on circulating metabolites has been widely studied. Xiao and colleagues compared sera levels of two metabolites in HCC cases versus patients with liver cirrhosis. Both metabolites discriminated HCC cases from cirrhotic controls in males and Caucasians but not in females or African Americans. This study demonstrates the potential of these metabolites as candidate biomarkers for HCC.Studies have often failed to find a link between self-reported whole-grain (WG) intake and prostate cancer. Plasma alkylresorcinol metabolites have been suggested as biomarkers for WG intake. Drake and colleagues investigated the dietary determinants of plasma alkylresorcinol metabolites in a nested case–control study. The authors report significant correlations between alkylresorcinol metabolites and WG intake but found no evidence of a protective effect of WG on incident prostate cancer.

Biomarkers of Whole Grain Intake

SUMMARY Biomarkers of dietary intake have been long proposed as alternatives or complementary to questionnaire based forms of dietary assessment. In the case of a food category as diverse as whole grains the application of biomarkers may increase the robustness of estimations of whole grain intake. Currently, alkylresorcinols—phenolic lipids present in the outer layers of wheat, rye, and barley—are promising biomarkers of whole grain cereal intake, meeting most of the suggested criteria for an intake biomarker. Initial studies demonstrate that plasma alkylresorcinols and their metabolites are highly responsive to alkylresorcinol intake and that they reflect whole grain intake. Further studies are required to test their application in observational cohorts and as biomarkers of compliance in intervention studies. There is a need for more biomarkers to cover the other major food cereals such as oats, corn, and rice, and new technological developments will be integral in enabling this.

Intake of Whole-Grain and Fiber-Rich Rye Bread Versus Refined Wheat Bread Does Not Differentiate Intestinal Microbiota Composition in Finnish Adults with Metabolic Syndrome

AbstractWhole-grain (WG) foods rich in indigestible carbohydrates are thought to modulate the composition of the intestinal microbiota. We investigated in a randomized, parallel, 2-arm 12-wk intervention whether consumption of WG and fiber-rich rye breads compared with refined wheat breads affected the microbiota composition in Finnish individuals aged 60 ± 6 y with metabolic syndrome. Fecal samples from 51 participants (25 males, 26 females) before and after the intervention were processed for the microbiota analysis using a phylogenetic microarray and quantitative polymerase chain reactions targeting the 16S rRNA gene. The intake of whole grains calculated from food records was higher in the group consuming rye breads (75 g) than in that consuming refined wheat breads (4 g; P < 0.001), confirmed by fasting plasma alkylrecorsinol concentrations, a biomarker of whole grain intake. The intestinal microbiota composition did not significantly differ between the groups after the intervention. However, we detected a 37% decrease of Bacteroidetes (P < 0.05) in parallel to a 53% decrease in the alkylrecorsinol concentration (P < 0.001) in the group consuming refined wheat breads. In this group, the abundance of bacteria related to Bacteroides vulgatus, B. plebeius, and Prevotella tannerae decreased, whereas that of bacteria related to Collinsella and members of the Clostridium clusters IV and XI increased. In a multivariate regression analysis, the abundance of Bacteroides spp. was best explained by different fat compounds among dietary variables, whereas the main sugar-converting butyrate-producers were mostly associated with the intake of whole- and refined-grain bread and fiber. Our results indicate that the quality of grains has a minor effect on the intestinal microbiota composition in participants with metabolic syndrome and suggest that the dietary influence on the microbiota involves other dietary components such as fat.

Hepatic biotransformation of alkylresorcinols is mediated via cytochrome P450 and β‐oxidation.

Alkylresorcinols (AR) are phenolic lipids present in the bran of whole grains, particularly in wheat and rye kernels. AR may serve as a biomarker of whole grain intake. While AR pharmacokinetics and principal end metabolites have been reported, the metabolic pathways contributing to their relatively rapid elimination from the circulation remain to be established. We investigated whether hepatic ω‐ and β‐oxidation mediate the catabolism of the AR homolog C19:0 to form 3,5‐dihydroxybenzoic acid and 3‐(3,5‐dihydroxyphenyl)‐1‐propanoic acid (DHPPA) using 3 in vitro platforms: human recombinant cytochrome P450 4F2 (CYP4F2), human liver S9 fraction (which includes microsomal and cytosolic enzymes), and HepG2 cells. After incubation with 10 μmol/L C19:0, one hydroxylated metabolite was formed by CYP4F2 and its production appeared to plateau after 1.0 h. After incubation of 10 μmol/L C19:0 with human S9 for up to 4 h, one hydroxylated and one carboxylated metabolite were identified, with their production increasing linearly with time. When HepG2 cells were treated with 5, 10, or 25 μmol/L C19:0 for 48 h, DHPPA was excreted into the media in a dose‐dependent manner. Our results are consistent with a metabolic pathway of absorbed AR to phenolic acids via CYP4F2‐mediated ω‐hydroxylation. Funded by the General Mills Inc. and USDA.

Differential effects of whole and refined grains on abdominal adipose tissue depots in an exploratory subgroup analysis of the GRAIN Study

Abdominal obesity is associated with insulin resistance, specifically having a higher amount of adipose tissue (AT) in visceral (VAT) rather than abdominal subcutaneous (ASAT) depots. We explored the relationship between ASAT, VAT and metabolic and anthropometric variables in a subgroup (n =28/50) of participants from a 12‐week, randomized, parallel arm, weight‐loss study in overweight/obese individuals comparing whole (WG) and refined grains (RG). Abdominal MRI was performed at 0 and 12 weeks. Axial scans at lumbar vertebrae L4–5 to L3 were manually traced to separate the AT depots. Baseline ASAT correlated with BMI, waist circumference, total and central AT (from DXA), C‐reactive protein, interleukin 6, and leptin (Rs&gt;;0.55, P&lt;0.05); VAT correlated with central AT, insulin and HOMA‐IR (Rs&gt;;0.35, P&lt;0.05). VAT % change correlated inversely with alkylresorcinol % change, a biomarker of whole grain intake (L3 only, R=−0.51, P&lt;0.01). While the between group changes in ASAT and VAT were not significant, VAT decreased significantly from baseline in only the WG group (RG: −14 ± 20 g, P=0.08; WG: −18 ± 20 g, P=0.001). These findings suggest that VAT and insulin are strongly associated, whereas ASAT is more highly correlated with body fatness and inflammatory markers. Consumption of WG in the place of RG during weight loss may elicit a greater reduction in VAT, but more research is warranted.Grant Funding Source: General Mills Bell Institute of Health and Nutrition