European Journal of Nutrition (v.52, #7)

Markers for nutrition studies: review of criteria for the evaluation of markers by Jan de Vries; Jean-Michel Antoine; Tomasz Burzykowski; Alessandro Chiodini; Mike Gibney; Gunter Kuhnle; Agnès Méheust; Loek Pijls; Ian Rowland (1685-1699).
Markers are important tools to assess the nutrition status and effects of nutrition interventions. There is currently insufficient consensus in nutrition sciences on how to evaluate markers, despite the need for properly evaluating them.To identify the criteria for the evaluation of markers related to nutrition, health and disease and to propose generic criteria for evaluation.The report on “Evaluation of Biomarker and Surrogate Endpoints in Chronic Disease” from the Institute of Medicine was the starting point for the literature search. Additionally, specific search strategies were developed for Pubmed.In nutrition, no set of criteria or systematic approach to evaluate markers is currently available. There is a reliance on the medical area where statistical methods have been developed to quantify the evaluation of markers. Even here, a systematic approach is lacking—markers are still evaluated on a case-by-case basis. The review of publications from the literature search resulted in a database with definitions, criteria for validity and the rationale behind the criteria. It was recognized that, in nutrition, a number of methodological aspects differ from medical research.The following criteria were identified as essential elements in the evaluation of markers: (1) the marker has a causal biological link with the endpoint, (2) there is a significant association between marker and endpoint in the target population, (3) marker changes consistently with the endpoint, e.g., in response to an intervention, and (4) change in the marker explains a substantial proportion of the change in the endpoint in response to the intervention.
Keywords: Marker; Criteria; Evaluation; Nutrition research

Do European people with type 1 diabetes consume a high atherogenic diet? 7-year follow-up of the EURODIAB Prospective Complications Study by Sabita S. Soedamah-Muthu; Nish Chaturvedi; John H. Fuller; Monika Toeller (1701-1710).
Individuals with type 1 diabetes have a high risk of developing cardiovascular diseases, and it has been reported that they consume a high atherogenic diet. We examined how nutrient intake and adherence to current European nutritional recommendations evolved in a large cohort of European individuals with type 1 diabetes over a period of 7 years.We analysed data from the EURODIAB Prospective Complications Study, a European multicentre prospective cohort study. Standardized 3-day dietary records were employed in individuals with type 1 diabetes. One thousand one hundred and two patients (553 men, 549 women, baseline age 33 ± 10 years, duration 15 ± 9 years) had complete nutritional data available at baseline and after 7 years. We calculated mean differences in reported nutrients over time and adjusted these for age, gender, HbA1c and BMI with ANOVA models.Compared to baseline, there were minor changes in nutrients. Reported protein (−0.35 % energy (en), fat (−1.07 % en), saturated fat (−0.25 % en) and cholesterol (−7.42 mg/1000 kcal) intakes were lower, whereas carbohydrate (+1.23 % en) and fibre (+0.46 g/1000 kcal) intakes were higher at the 7-year follow-up. European recommendations for adequate nutrient intakes were followed in individuals with type 1 diabetes for protein (76 % at baseline and 78 % at follow-up), moderately for fat (34, 40 %), carbohydrate (34, 41 %) and cholesterol (39, 47 %), but poorly for fibre (1.4, 2.4 %) and saturated fat (11, 13 %).European individuals with type 1 diabetes consume a high atherogenic diet as few patients met recommendations for dietary fibre and saturated fat. This study showed minor changes in dietary nutrients and energy intakes over a period of 7 years. Nutrition education needs particular focus on strategies to increase dietary fibre and reduce saturated fat to exploit their potential benefit.
Keywords: Type 1 diabetes mellitus; Cardiovascular disease; Nutritional intake; Nutrients; Caloric intake; Dietary records; EURODIAB Prospective Complications Study; Dietary recommendations; Re-examination; Follow-up

Iodine status in preschool children and evaluation of major dietary iodine sources: a German experience by Simone A. Johner; Michael Thamm; Ute Nöthlings; Thomas Remer (1711-1719).
Even mild iodine deficiency may negatively affect cognitive performance, especially at a young age. Our aim was to investigate iodine status in very young children and to assess the importance of iodized salt in processed foods of which the use has decreased during the last years in Germany.Twenty-four hours urinary iodine excretion (UIE) as a marker of iodine intake was measured in 378 24 h urine samples collected 2003–2010 by 221 3 to <6 years old participants of the DONALD Study. Parallel 3-d weighed dietary records and measurements of urinary sodium excretion provided data on the daily consumption of the most important iodine sources in the children’s diet (iodized salt, milk, fish, meat and eggs). Time trends of UIE (2003–2010) and contributions of the different food groups were analyzed by using linear mixed-effects regression models.Median UIE of 71 μg/d in boys and 65 μg/d in girls (P = 0.03), corresponding to an iodine intake of 82 and 75 μg/d, respectively (assumption: 15 % non-renal iodine losses), was below the recommended dietary allowance (RDA) of 90 μg/d. Milk, salt and egg intake were significant predictors of UIE; milk and salt together accounted for >80 % of iodine supply. Between 2003 and 2010, UIE decreased significantly by approximately 1 μg/d per year. The contribution of salt intake to UIE decreased from 2003–2006 to 2007–2010.In countries where salt is a major iodine source, already modest decreases in the iodized proportion of salt used in processed foods may relevantly impair iodine status even in preschool children.
Keywords: Preschool children; 24 h Urines; Iodine excretion; Iodized salt; Time trend

Low-volume exercise can prevent sucrose-induced weight gain but has limited impact on metabolic measures in rats by Carling Yan-Yan Chan; Michael Kendig; Robert A. Boakes; Kieron Rooney (1721-1732).
Rats given sugar-sweetened drinks can develop glucose intolerance, insulin resistance and dyslipidaemia. The aim of this study was to investigate whether such metabolic disruptions and also possible weight gain induced by chronic sucrose consumption could be attenuated by low-volume exercise.Using a 2 × 2 factorial design, rats were given free access for 57 days to either a 10 % sucrose solution (Suc and SucEx) or water only (Con and ConEx), while exercise rats (SucEx and ConEx) received 20-min treadmill training every 3 days. Caloric intake and body weight were measured throughout this dietary intervention. Oral glucose tolerance tests were performed on days 29 and 54. Plasma insulin, triglycerides and leptin were also measured, together with post-mortem measures of retroperitoneal fat pads and liver triglycerides.In groups given sucrose, exercise reduced calorie consumption, reduced weight gain and decreased leptin relative to non-exercised controls. Exercise was found to improve glucose tolerance and insulin action at day 29, but not day 54.Low-volume exercise can be effective in preventing weight gain in sucrose-fed rats, probably via reduction of subcutaneous fat, but prevention of the glucose intolerance and dyslipidaemia produced by sucrose consumption may be transient.
Keywords: Metabolic syndrome; Sucrose; Exercise; Body weight; Rat

New perspectives on vitamin D sources in Germany based on a novel mathematical bottom-up model of 25(OH)D serum concentrations by Jonathan Brown; Anita Ignatius; Michael Amling; Florian Barvencik (1733-1742).
Up-to-date knowledge about vitamin D supply and serum concentration in Germany is not sufficient. Our purpose was to compare a novel holistic bottom-up modeling of 25(OH)D concentrations with vitamin D sources such as sunlight, food and supplements for all federal states taking seasonal and geographical variations into account. The second purpose was to update and detail vitamin D supply through food in Germany.To confirm the model of 25(OH)D concentrations, we used the population (1,763 men and 2,267 women, 18–79 years) participated in the representative German National Health Interview and Examination Survey 1998 and the integrated German Nutrition Survey.The maximum model value is 67.5 nmol/L in July and minimum model value is 29.3 nmol/L in January, while the average model value is 45.0 nmol/L. Men have a mean daily intake of 137 IU (3.42 μg) and women of 112 IU (2.79 μg). Correlation between model and actual data is 0.77 (p = 0.003).A comparison of the model data with population-based values showed good agreement. None of the vitamin D sources can provide the German population with enough vitamin D.
Keywords: Vitamin D; Vitamin D deficiency; UVB exposure; Vitamin D supplementation; Vitamin D in natural food

The soluble fiber β-glucan, a natural component of barley, has been shown to lower the postprandial glucose response and is thought to improve insulin resistance.This study examined the effect of chronic consumption of the high β-glucan barley flour on glucose control, liver lipids and markers of muscle fatty acid oxidation in the Zucker diabetic fatty (ZDF) rat. Two groups of ZDF rats were fed diets containing either 6 % β-glucan in the form of barley flour or cellulose as a control for 6 weeks. A group of Zucker lean rats served as a negative control.The barley flour group had an increased small intestinal contents viscosity compared to the obese control group. After 6 weeks, the barley flour group had reduced glycated hemoglobin, lower relative kidney weights and a reduced area under the curve during a glucose tolerance test, indicating improved glucose control. Fasting plasma adiponectin levels increased in the barley flour group and were not different than the lean control group. ZDF rats on the barley flour diet had lower relative epididymal fat pad weights than the obese control and a greater food efficiency ratio. The barley flour group also had reduced liver weights and a decreased concentration of liver lipids. The barley flour group had significantly higher concentrations of muscle acylcarnitines, a metabolite generated during fatty acid oxidation.These results show that chronic consumption of β-glucans can improve glucose control and decrease fatty liver in a model of diabetes with obesity.
Keywords: Acylcarnitines; β-glucan; Dietary fiber; Fatty liver; Insulin resistance; Viscosity

Diverse effects of oats on cholesterol metabolism in C57BL/6 mice correlate with expression of hepatic bile acid-producing enzymes by Kristina E. Andersson; Ulrika Axling; Jie Xu; Karl Swärd; Siv Ahrné; Göran Molin; Cecilia Holm; Per Hellstrand (1755-1769).
We previously reported that two substrains of C57BL/6 mice respond differently to oats with respect to reduction in plasma cholesterol. Analysis of this difference might offer clues to mechanisms behind the cholesterol-lowering effect of oats. Here, we address the possible roles of hepatic steroid metabolism and the intestinal microbiota in this respect.Female C57BL/6 mice were fed an atherogenic diet with oat bran (27 %) or control fibres for 4 weeks.C57BL/6 NCrl mice responded to oat bran with 19 ± 1 % (P < 0.001) lower plasma cholesterol, 40 ± 5 % (P < 0.01) higher excretion of bile acids and increased expression of the bile acid-producing hepatic enzymes CYP7A1 and CYP8B1, but none of these effects were found in C57BL/6JBomTac mice. However, on control diet, C57BL/6JBomTac had tenfold higher expression of CYP7A1 and levels of hepatic cholesterol esters than C57BL/6NCrl mice. Plasma levels of fructosamine indicated improved glycemic control by oat bran in C57BL/6NCrl but not in C57BL/6JBomTac. C57BL/6JBomTac had higher intestinal microbiota diversity, but lower numbers of Enterobacteriaceae, Akkermansia and Bacteroides Fragilis than C57BL/6NCrl mice. Oat bran increased bacterial numbers in both substrains. Microbiota diversity was reduced by oats in C57BL/6JBomTac, but unaffected in C57BL/6NCrl.Our data do not support a connection between altered microbiota diversity and reduced plasma cholesterol, but the bacterial composition in the intestine may influence the effects of added fibres. The cholesterol-lowering properties of oats involve increased production of bile acids via the classical pathway with up-regulation of CYP7A1 and CYP8B1. Altered cholesterol or bile acid metabolism may interfere with the potential of oats to reduce plasma cholesterol.
Keywords: Plasma cholesterol; Oats; Dietary fibre; CYP7A1; Microbiota; β-glucans

A prospective study of plasma vitamin D metabolites, vitamin D receptor gene polymorphisms, and risk of hypertension in men by Lu Wang; Jing Ma; JoAnn E. Manson; Julie E. Buring; J. Michael Gaziano; Howard D. Sesso (1771-1779).
Laboratory studies have suggested that vitamin D inadequacy may be implicated in development of hypertension. Evidence from epidemiologic studies remains limited. We aim to examine the prospective associations of circulating vitamin D metabolites, vitamin D receptor (VDR) gene polymorphisms, and their interaction with risk of hypertension.We conducted prospective analyses among 1,211 US men that were free of baseline hypertension and had baseline plasma 25hydroxy-vitamin D (25(OH)D) or 1,25dihydroxy-vitamin D (1,25(OH)2D) measured and VDR BsmI or FokI polymorphisms genotyped.During 15.3-year follow-up, 695 men developed incident hypertension. After multivariable adjustment, the hazard ratios (HRs) and 95 % CIs for hypertension across increasing quartiles of plasma vitamin D metabolites were 1.00 (ref), 0.94 (0.69–1.27), 0.69 (0.50–0.96), and 0.82 (0.60–1.13) for 25(OH)D (p, trend: 0.43), and 1.00, 0.92 (0.66–1.27), 1.12 (0.82–1.54), and 1.19 (0.86–1.63) for 1,25(OH)2D (p, trend: 0.16). Compared with carriers of VDR BsmI bb, carriers of bB or BB had a HR of 1.25 (1.04–1.51) for hypertension. For VDR FokI polymorphism, compared with carriers of FF and Ff combined, carriers of ff had a HR of 1.32 (1.03–1.70). The relation between plasma 25(OH)D and risk of hypertension did not differ by VDR BsmI and FokI polymorphisms.In a prospective cohort of men, we found suggestive evidence for an inverse association between plasma 25(OH)D and risk of hypertension. We also found associations between VDR BsmI and FokI polymorphisms with hypertension risk. More research is needed to further determine the role of vitamin D in hypertension prevention.
Keywords: Vitamin D; Polymorphisms; Prospective study; Hypertension; Men

Increased gain in bone mineral content of preterm infants fed an isocaloric, protein-, and mineral-enriched postdischarge formula by Monique van de Lagemaat; Joost Rotteveel; Mirjam M. van Weissenbruch; Harrie N. Lafeber (1781-1785).
Preterm infants are at risk for suboptimal bone mineralization. Postnatal bone formation requires optimal nutritional composition. This study evaluated the effect of isocaloric, protein-, and mineral-enriched postdischarge formula (PDF), standard term formula (TF), and human milk (HM) on gain in bone mineral content (BMC) of preterm infants between term age (40 weeks postmenstrual age) and 6 months corrected age (CA).Between term age and 6 months CA, 93 preterm infants were randomized to be fed PDF (n = 52) or TF (n = 41) and 46 preterm infants were fed HM. Weight (g) and length (cm) were measured at birth, term age, and 6 months CA. BMC (g) was measured by whole-body dual-energy x-ray absorptiometry at term age and 6 months CA.Gain in BMC (expressed as median with interquartile range) between term age and 6 months CA was higher in PDF-fed infants (102.3 (32.4) g) compared to TF- and HM-fed infants (91.6 (24.5) and 84.5 (33.3) g, respectively), adjusted for gender, gestational age, birthweight, and gain in weight and length.Between term age and 6 months CA, isocaloric PDF enhances gain in BMC of preterm infants, independent of gain in weight and length. We speculate that higher gain in BMC during infancy may improve adult bone mass in preterm infants.
Keywords: Preterm infants; Nutrition; Bone mineral content; Postdischarge formula; Randomized controlled trial

Attenuation of adjuvant-induced arthritis by dietary sesamol via modulation of inflammatory mediators, extracellular matrix degrading enzymes and antioxidant status by Mahadevappa Hemshekhar; Ram Mohan Thushara; Sadashivaiah Jnaneshwari; Sannaningaiah Devaraja; Kempaiah Kemparaju; Kesturu Subbaiah Girish (1787-1799).
The dietary sesamol is one of the important constituent of sesame seed that has been mainly claimed to combat cardiovascular disease and diabetes, which are the major secondary complications of arthritis. Thus, the present study was designed to evaluate the anti-arthritic, anti-inflammatory and anti-stress potentials of sesamol.Arthritis was induced using Freund’s complete adjuvant to hind paw of experimental rats. The physical and biochemical alterations and its recovery by sesamol were assessed by measuring enzymatic and non-enzymatic mediators. Arthritis-induced inflammation, oxidative stress and their protective by sesamol were measured by determining the levels of pro-inflammatory cytokines and oxidative stress markers.In the present study, sesamol was demonstrated to alleviate arthritis-induced cartilage degeneration by mitigating augmented serum levels of hyaluronidase and matrix metalloproteinases (MMP-13, MMP-3 and MMP-9). It also protected bone resorption by reducing the elevated levels of bone joint exoglycosidases, cathepsin D and tartarate-resistant acid phosphatases. Sesamol also abrogated the non-enzymatic inflammatory markers (TNF, IL-1β, IL-6, COX-2, PGE2, ROS, and H2O2,) effectively. In addition, sesamol neutralizes arthritis-induced oxidative stress by restoring the levels of reactive oxygen species, lipid and hydro peroxides and sustained antioxidant homeostasis by re-establishing altered activities of superoxide dismutase, catalase and glutathione-s-transferase.Taken together, the study demonstrated the anti-arthritic, anti-inflammatory, anti-oxidative stress and chondro-protective potentials of sesamol in vivo. Thus, sesamol could be a single bullet that can fight arthritis as well as the secondary complications of arthritis such as cardio vascular disorders and diabetes.
Keywords: Arthritis; Cartilage degradation; Hyaluronidases; Inflammatory mediators; Oxidative stress; Sesamol

Systemic folate status, rectal mucosal folate concentration and dietary intake in patients at differential risk of bowel cancer (The FAB2 Study) by Elizabeth A. Williams; Mark Welfare; Alison Spiers; Marilyn H. Hill; Wendy Bal; Eileen R. Gibney; Yvonne Duckworth; Hilary J. Powers; John C. Mathers (1801-1810).
Folate has been strongly implicated in the aetiology of colorectal cancer. However, the relationship between dietary folate intake, rectal mucosal folate status and colorectal cancer risk is uncertain. The study aimed to estimate nutrient intakes and measure systemic folate status and rectal mucosal folate concentration in people at differential risk of developing colorectal cancer.Two hundred and twenty-eight individuals were recruited from gastroenterology clinics and subdivided into three patient groups: untreated colorectal cancer (n = 43), adenomatous polyps (n = 90) or normal bowel (n = 95). Biopsies from macroscopically normal rectal mucosa and blood were collected and used for the measurement of rectal mucosal 5-methyltetrahydrofolate (5-MeTHF) and systemic markers of folate status, respectively. Nutrient intake was estimated using a validated food frequency questionnaire.Dietary intake variables, plasma 5-MeTHF and red cell folate and plasma homocysteine concentrations were similar in all three subject groups and 95 % CI fell within normal range for each variable. Rectal mucosal 5-MeTHF concentration was higher in the normal mucosa of adenomatous polyp patients than in normal subjects (P = 0.055). Rectal mucosal 5-MeTHF was associated significantly with plasma folate (P < 0.001, r = 0.294), red cell folate (P = 0.014, r = 0.305), plasma homocysteine (P = 0.017, r = −0.163) and dietary folate intake (P = 0.036, r = 0.152).This study demonstrates adequate folate status of patients attending gastroenterology clinics for the investigation of bowel symptoms, with no significant difference in dietary intakes or systemic folate status indices according to diagnosis. Rectal mucosal 5-MeTHF concentrations were elevated in adenomatous polyp patients, but failed to reach significance. Further studies are required to determine the biological significance of this observation.
Keywords: Folate; Diet; Colorectal cancer; Adenomatous polyps

Supplementation with tocotrienol-rich fraction alters the plasma levels of Apolipoprotein A-I precursor, Apolipoprotein E precursor, and C-reactive protein precursor from young and old individuals by Eng Chee Heng; Saiful Anuar Karsani; Mariati Abdul Rahman; Noor Aini Abdul Hamid; Zalina Hamid; Wan Zurinah Wan Ngah (1811-1820).
Tocotrienol possess beneficial effects not exhibited by tocopherol. In vitro studies using animal models have suggested that these effects are caused via modulation of gene and protein expression. However, human supplementation studies using tocotrienol-rich isomers are limited. This study aims to identify plasma proteins that changed in expression following tocotrienol-rich fraction (TRF) supplementation within two different age groups.Subjects were divided into two age groups—32 ± 2 (young) and 52 ± 2 (old) years old. Four subjects from each group were assigned with TRF (78 % tocotrienol and 22 % tocopherol, 150 mg/day) or placebo capsules for 6 months. Fasting plasma were obtained at 0, 3, and 6 months. Plasma tocopherol and tocotrienol levels were determined. Plasma proteome was resolved by 2DE, and differentially expressed proteins identified by MS. The expressions of three proteins were validated by Western blotting.Six months of TRF supplementation significantly increased plasma levels of tocopherols and tocotrienols. Proteins identified as being differentially expressed were related to cholesterol homeostasis, acute-phase response, protease inhibitor, and immune response. The expressions of Apolipoprotein A-I precursor, Apolipoprotein E precursor, and C-reactive protein precursor were validated. The old groups showed more proteins changing in expression.TRF appears to not only affect plasma levels of tocopherols and tocotrienols, but also the levels of plasma proteins. The identity of these proteins may provide insights into how TRF exerts its beneficial effects. They may also be potentially developed into biomarkers for the study of the effects and effectiveness of TRF supplementation.
Keywords: Tocotrienol-rich fraction; Supplementation; Plasma proteins; Two-dimensional electrophoresis; Matrix-assisted laser desorption/ionization

To assess the effect of high-dose oral thiamine supplements on glucose tolerance in patients with impaired glucose metabolism.Twelve hyperglycemic subjects (10 cases of impaired glucose tolerance and 2 new cases of type 2 diabetes) completed this randomized, double-blind trial, where all participants received both placebo and thiamine capsules (3 × 100 mg/day) for 6 weeks in a cross-over manner. The main endpoint was changes in 2-h plasma glucose. Fasting plasma glucose and insulin, 2-h plasma insulin, the hemostatic model assessment of insulin resistance (HOMA-IR), renal function measurement and thiamin status were also evaluated at the commencement and completion of each treatment period.Thiamine supplementation resulted in significant decrease in 2-h plasma glucose relative to baseline (8.78 ± 2.20 vs. 9.89 ± 2.50 mmol/l, p = 0.004), with no significant change in the placebo arm. Fasting plasma glucose and insulin, and HOMA-IR increased significantly from baseline after 6 weeks in the placebo arm (p = 0.003, p = 0.04 and p = 0.02, respectively). These variables did not change with thiamine supplementation. There were no significant changes in 2-h plasma insulin or renal function marker, within or between arms.Supplementation with high-dose thiamine may prevent deterioration in fasting glucose and insulin, and improve glucose tolerance in patients with hyperglycemia. High-dose thiamine supplementation may prevent or slow the progression of hyperglycemia toward diabetes mellitus in individuals with impaired glucose regulation.
Keywords: Thiamine; Glucose tolerance; Insulin resistance; Hyperglycemia; Type 2 diabetes; Cardiovascular disease