Publications by authors named "Rune Blomhoff"

162 Publications

Emotional Eating in Relation to Worries and Psychological Distress Amid the COVID-19 Pandemic: A Population-Based Survey on Adults in Norway.

Int J Environ Res Public Health 2020 12 27;18(1). Epub 2020 Dec 27.

Department of Global Public Health and Primary Care, Faculty of Medicine, University of Bergen, 5020 Bergen, Norway.

Population-based studies have revealed a high occurrence of self-reported psychological distress symptoms during the early phases of the coronavirus disease 2019 (COVID-19) pandemic. Stress and negative affect can lead to emotional eating, which in turn can have negative outcomes on health. In this population-based study, 24,968 Norwegian inhabitants participated in an electronic questionnaire including structured questions on dietary habits, emotional eating, psychological distress symptoms, and COVID-19-related worries. The study took place during April 2020 after around six weeks of interventions to tackle the first wave of the COVID-19 pandemic. Overall, emotional eating was reported in 54% of the population and was markedly more frequent in female participants. Worries related to consequences of the pandemic were associated with increased emotional eating, and the association was stronger for worries related to personal economy-odds ratios (OR) 1.7 (95% confidence interval (CI95%) 1.5-1.9)-compared to worries related to health-OR 1.3 (CI95% 1.2-1.5). Psychological distress had a strong association with emotional eating-OR 4.2 (CI95% 3.9-4.4). Correspondingly, the intake of high-sugar foods and beverages was higher for those with substantial COVID-19-related worries and those with psychological distress compared to the overall population.
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http://dx.doi.org/10.3390/ijerph18010130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795972PMC
December 2020

Dietary Adjustments to Altitude Training in Elite Endurance Athletes; Impact of a Randomized Clinical Trial With Antioxidant-Rich Foods.

Front Sports Act Living 2020 26;2:106. Epub 2020 Aug 26.

Faculty of Chemistry, Biotechnology and Food Sciences, Norwegian University of Life Sciences, Ås, Norway.

Altitude training stresses several physiological and metabolic processes and alters the dietary needs of the athletes. International Olympic Committee (IOC)'s Nutrition Expert Group suggests that athletes should increase intake of energy, carbohydrate, iron, fluid, and antioxidant-rich foods while training at altitude. We investigated whether athletes adjust their dietary intake according to the IOC's altitude-specific dietary recommendations, and whether an in-between meal intervention with antioxidant-rich foods altered the athletes' dietary composition and nutrition-related blood parameters (mineral, vitamin, carotenoid, and hormone concentrations). The dietary adjustments to altitude training (3 weeks at 2,320 m) were determined for 31 elite endurance athletes (23 ± 5 years, 23 males, 8 females) by six interviewer-administered 24-h dietary recalls on non-consecutive days; three before and during the altitude camp. The additional effect of in -between meal intervention with eucaloric antioxidant-rich or control snacks (1,000 kcal/day) was tested in a randomized controlled trial with parallel design. At altitude the athletes increased their energy intake by 35% (1,430 ± 630 kcal/day, < 0.001), the provided snacks accounting for 70% of this increase. Carbohydrate intake increased from 6.5 ± 1.8 g/kg body weight (BW) (50 E%) to 9.3 ± 2.1 g/kg BW (53 E%) ( < 0.001), with no difference between the antioxidant and control group. Dietary iron, fluid, and antioxidant-rich food intake increased by 37, 38, and 104%, respectively, in the whole cohort. The intervention group had larger increases in polyunsaturated fatty acids (PUFA), ω3 PUFA (n-3 fatty acids), ω6 PUFA (n-6 fatty acids), fiber, vitamin C, folic acid, and copper intake, while protein intake increased more among the controls, reflecting the nutritional content of the snacks. Changes in the measured blood minerals, vitamins, and hormones were not differentially affected by the intervention except for the carotenoid; zeaxanthin, which increased more in the intervention group ( < 0.001). Experienced elite endurance athletes increased their daily energy, carbohydrate, iron, fluid, and antioxidant-rich food intake during a 3-week training camp at moderate altitude meeting most of the altitude-specific dietary recommendations. The intervention with antioxidant-rich snacks improved the composition of the athletes' diets but had minimal impact on the measured nutrition-related blood parameters. NCT03088891 (www.clinicaltrials.gov), Norwegian registry number: 626539 (https://rekportalen.no/).
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http://dx.doi.org/10.3389/fspor.2020.00106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739752PMC
August 2020

Use of bioelectrical impedance analysis to monitor changes in fat-free mass during recovery from colorectal cancer- a validation study.

Clin Nutr ESPEN 2020 Dec 3;40:201-207. Epub 2020 Oct 3.

Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; Division of Cancer Medicine, Oslo University Hospital, Oslo, Norway.

Background & Aims: Although previous research show high correlation between fat-free mass (FFM) measured by bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA), the validity of BIA to track longitudinal changes in FFM is uncertain. Thus, the aim of this study was to validate the ability of BIA to assess changes in FFM during 6 months of recovery from non-metastatic colorectal cancer (CRC).

Methods: A total of 136 women and men (50-80 years) with stage I-III CRC and a wide range of baseline FFM (35.7-73.5 kg) were included in the study. Body composition was measured at study baseline within 2-9 months of surgery and again 6 months later. Whole-body BIA FFM estimates (FFM) were calculated using three different equations (manufacturer's, Schols' and Gray's) before comparison to FFM estimates obtained by DXA (FFM).

Results: Correlation between changes in FFM and FFM was intermediate regardless of equation (r ≈ 0.6). The difference in change of FFM was significant compared to FFM, using all three equations and BIA overestimated both loss and gain. However, BIA showed 100% sensitivity and about 90% specificity to identify individuals with ≥5% loss in FFM, using all three equations. Sensitivity of FFM to detect a smaller loss of FFM (60-76%) or a gain in FFM of ≥5% (33-62%) was poor.

Conclusion: In a well-nourished population of non-metastatic CRC patients, a single-frequency whole-body BIA device yielded imprecise data on changes in FFM, regardless of equation. BIA is thus not a valid option for quantifying changes in FFM in individuals. However, BIA could be used to identify patients with loss in FFM ≥5% in this population. The validity of BIA to monitor changes in FFM warrants further investigation before implementation in clinical praxis.
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http://dx.doi.org/10.1016/j.clnesp.2020.09.021DOI Listing
December 2020

The Nordic Nutrition Recommendations 2022 - handbook for qualified systematic reviews.

Food Nutr Res 2020 18;64. Epub 2020 Jun 18.

Department of Nutrition, University of Oslo, Oslo, Norway.

Background: Systematic reviews (SRs) constitute a major part of the Nordic Nutrition Recommendations (NNRs). The step-by-step procedure used to develop SRs has evolved considerably over time and is often tailored to fit the exposure and outcomes in focus.

Objective: To describe a detailed procedure for developing qualified SRs commissioned by the NNR2022 project.

Design: Scrutinizing procedures of recent SRs commissioned by leading national food and health authorities or international food and health organizations.

Results: The following eight steps must be included when developing qualified SRs for the NNR2022 project: 1) define research question, 2) protocol development, 3) literature search, 4) screening and selection of studies, 5) data extraction, 6) assessing risk of bias, 7) synthesis and grading of total strength of evidence, and 8) reporting according to certain standards.

Discussion: This guide is based on the guidelines developed for the fifth edition of NNR but includes some important new domains in order to adhere to more recent, authoritative standards.

Conclusion: All qualified SRs in the NNR2022 project will follow the protocol described here.
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http://dx.doi.org/10.29219/fnr.v64.4404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307435PMC
June 2020

The Nordic Nutrition Recommendations 2022 - principles and methodologies.

Food Nutr Res 2020 18;64. Epub 2020 Jun 18.

Department of Nutrition, University of Oslo, Oslo, Norway.

Background: The Nordic Nutrition Recommendations (NNRs) constitute the scientific basis for national dietary reference values (DRVs) and food-based dietary guidelines (FBDGs) in the Nordic and Baltic countries.

Objective: To define principles and methodologies for the sixth edition of NNR to be published in 2022 (NNR2022).

Design: The principles and methodologies of the previous edition of NNR were used as a starting point. Recent nutrition recommendations commissioned by other national food and health authorities or international food and health organizations were examined and dissected. Updated principles and methodologies were agreed by the NNR2022 Committee in a consensus-driven process.

Results: An organizational model with 'checks and balances' was developed to minimize the influence of subjective biases of the committee members and experts. Individual chapters on all included nutrients and food groups will be updated as scoping reviews. Systematic reviews (SRs), which are the main basis for evaluating causal effects of nutrients or food groups on health outcomes, will be embedded in each chapter. A NNR SR Centre will be established for performing SRs on prioritized topics. To avoid duplication and optimize the use of resources, qualified SRs commissioned by other national and international organizations and health authorities will also inform DRVs and FBDGs in NNR2022.

Discussion: The evidence-based methods defined in the NNR2022 project are compatible with most contemporary methods used by leading national food and health authorities. Global harmonization of methodological approaches to nutrition recommendations is strongly encouraged.

Conclusion: Evidence-informed principles and methodologies underpinned by SRs will ensure that DRVs and FBDGs defined in the NNR2022 project are based on the best available evidence and as far as possible free from overt bias.
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http://dx.doi.org/10.29219/fnr.v64.4402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307430PMC
June 2020

The Nordic Nutrition Recommendations 2022 - structure and rationale of qualified systematic reviews.

Food Nutr Res 2020 18;64. Epub 2020 Jun 18.

Department of Nutrition, University of Oslo, Oslo, Norway.

Background: Qualified systematic reviews (SRs) will form the main basis for evaluating causal effects of nutrients or food groups on health outcomes in the sixth edition of Nordic Nutrition Recommendations to be published in 2022 (NNR2022).

Objective: To describe rationale and structure of SRs used in NNR2022.

Design: The SR methodologies of the previous edition of NNR were used as a starting point. Methodologies of recent SRs commissioned by leading national food and health authorities or international food and health organizations were examined and scrutinized. Methodologies for developing SRs were agreed by the NNR2022 Committee in a consensus-driven process.

Results: Qualified SRs will be developed by a cross-disciplinary group of experts and reported according to the requirements of the EQUATOR network. A number of additional requirements must also be fulfilled, including 1) a clearly stated set of objectives and research questions with pre-defined eligibility criteria for the studies, 2) an explicit, reproducible methodology, 3) a systematic search that attempts to identify all studies that would meet the eligibility criteria, 4) an assessment of the validity of the findings of the included studies through an assessment of 'risk of bias' of the studies, 5) a systematic presentation and synthesis of the characteristics and findings of the included studies, and 6) a grading of the overall evidence. The complete definition and requirements of a qualified SR are described.

Discussion: Most SRs published in scientific journals do not fulfill all criteria of the qualified SRs in the NNR2022 project. This article discusses the structure and rationale for requirements of qualified SRs in NNR2022. National food and health authorities have only recently begun to use qualified SRs as a basis for nutrition recommendations.

Conclusion: Qualified SRs will be used to inform dietary reference values (DRVs) and food-based dietary guidelines (FBDGs) in the NNR2022 project.
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http://dx.doi.org/10.29219/fnr.v64.4403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307429PMC
June 2020

Should calculation of chemotherapy dosage for bowel cancer be based on body composition?

Tidsskr Nor Laegeforen 2020 May 19;140(8). Epub 2020 May 19.

Background: Dosage of chemotherapy for colon cancer is currently based on the patient's body surface area. Several studies have identified an association between low fat-free mass and chemotherapy toxicity among patients with metastatic colorectal cancer. This has been less widely studied for localised disease. This review aims to summarise studies that have investigated the association between clinical signs of disease-related malnutrition (low body mass index, weight loss and low muscle mass) and tolerance of chemotherapy in patients with localised colon cancer.

Material And Method: We conducted a systematic search in PubMed with various synonyms of the terms 'colorectal cancer', 'adjuvant chemotherapy', 'nutritional status' and 'toxicity'. The search was concluded in May 2019. Of 553 articles, 39 were considered relevant and read in full text. Ten of these fulfilled the inclusion criteria for this review.

Results: Nine of the ten studies indicate an association between clinical signs of disease-related malnutrition and dose-limiting toxicity. The association appears to be especially pronounced in patients with low fat-free mass.

Interpretation: The results support the hypothesis that there is an association between disease-related malnutrition and the prevalence of toxicity and modification of the course of adjuvant chemotherapy in patients with localised colon cancer. The potential benefits of basing chemotherapy dosage on body composition in addition to body surface area should be investigated in clinical trials.
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http://dx.doi.org/10.4045/tidsskr.19.0769DOI Listing
May 2020

Retinol, Retinoic Acid, and Retinol-Binding Protein 4 are Differentially Associated with Cardiovascular Disease, Type 2 Diabetes, and Obesity: An Overview of Human Studies.

Adv Nutr 2020 05;11(3):644-666

Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.

Vitamin A is a fat-soluble essential nutrient obtained from plant- and animal-based sources that has roles in growth, vision, and metabolism. Vitamin A circulates mainly as retinol bound to retinol-binding protein 4 (RBP4), and is delivered to tissues and converted to retinoic acid, which is a ligand for several nuclear receptors. In recent years, aspects of vitamin A metabolism have been under scrutiny with regards to the development of metabolic and lifestyle diseases including cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), and overweight and obesity in humans. Studies have mainly focused on RBP4 in this context, whereas the major circulating form, retinol, and the major bioactive form, retinoic acid, have been overlooked in this regard until recently. As one of the main roles of RBP4 is to deliver retinol to tissues for biological action, the associations of retinol and retinoic acid with these diseases must also be considered. In this review, we summarize and discuss recent and available evidence from human studies with focus on retinol, retinoic acid, and RBP4 and provide an overview of these crucial components of vitamin A metabolism in CVD, T2DM, and obesity. In summary, retinol was found to be both inversely and positively associated with CVD whereas the associations with T2DM and obesity were less clear. Although only a few studies have been published on retinoic acid, it was inversely associated with CVD. In contrast, serum RBP4 was mostly found to be positively associated with CVD, T2DM, and obesity. At present, it is difficult to ascertain why the reported associations differ depending on the compound under study, but there is a clear imbalance in the literature in disfavor of retinol and retinoic acid, which needs to be considered in future human studies.
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http://dx.doi.org/10.1093/advances/nmz131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231588PMC
May 2020

Creatinine, total cysteine and uric acid are associated with serum retinol in patients with cardiovascular disease.

Eur J Nutr 2020 Sep 9;59(6):2383-2393. Epub 2019 Sep 9.

Centre for Nutrition, Department of Clinical Science, University of Bergen, Haukelandsbakken, 5009, Bergen, Norway.

Purpose: We hypothesized that biomarkers and dietary factors related to cardiovascular disease risk were associated with serum retinol and evaluated these potential associations in patients with suspected coronary artery disease (CAD).

Methods: We used cross-sectional data from 4116 patients hospitalised for suspected CAD. Dietary data were obtained from a subgroup of 1962 patients using a food frequency questionnaire. Potential biomarkers and dietary factors were explored using linear regression modelling adjusted for age and sex. Regression coefficients and corresponding confidence intervals (CI) are given as  % change in serum retinol per unit change in the predictors. Analyses were performed in the total population and in strata of serum retinol tertiles.

Results: In age- and sex-adjusted models, serum creatinine (standardized β: 0.38, 95% CI [0.35, 0.42]), plasma total cysteine (0.26, [0.23, 0.29]), serum uric acid (0.30, [0.26, 0.33]) and plasma neopterin (0.22, [0.18, 0.25]) were positively associated, whereas plasma serine (- 0.15, [- 0.18, - 0.12]) and serum C-reactive protein (- 0.15, [- 0.18, - 0.12]) were inversely associated with serum retinol. When we included the significant biomarkers in a multivariate model, the model explained 33% of the variability (R = 0.33) in serum retinol. The results were similar in the lower and upper tertiles of serum retinol. Weak or no associations were observed for dietary factors.

Conclusions: In patients with suspected CAD, concentrations of creatinine, cysteine and uric acid were positively associated with serum retinol. Future studies should assess whether retinol concentrations are influenced by metabolic alterations in patients at risk of cardiovascular disease.
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http://dx.doi.org/10.1007/s00394-019-02086-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413901PMC
September 2020

Effects of antioxidant-rich foods on altitude-induced oxidative stress and inflammation in elite endurance athletes: A randomized controlled trial.

PLoS One 2019 13;14(6):e0217895. Epub 2019 Jun 13.

Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.

Background: Various altitude training regimes, systematically used to improve oxygen carrying capacity and sports performance, have been associated with increased oxidative stress and inflammation. We investigated whether increased intake of common antioxidant-rich foods attenuates these processes.

Methods: In a randomized controlled trial, 31 elite endurance athletes (23 ± 5 years), ingested antioxidant-rich foods (n = 16), (> doubling their usual intake), or eucaloric control foods (n = 15) during a 3-week altitude training camp (2320 m). Fasting blood and urine samples were collected 7 days pre-altitude, after 5 and 18 days at altitude, and 7 days post-altitude. Change over time was compared between the groups using mixed models for antioxidant capacity [uric acid-free (ferric reducing ability of plasma (FRAP)], oxidative stress (8-epi-PGF2α) and inflammatory biomarkers (IFNγ, IL1α, IL1RA, IL1β, IL2, IL5, IL6, IL7, IL10, IL12p70, IL13, IL17, TNFα, MCP-1 and micro-CRP). The cytokine response to a stress-test (VO2max ramp test or 100 m swimming) was assessed at pre- and post-altitude.

Results: FRAP increased more in the antioxidant compared to the control group (p = 0.034). IL13 decreased in the antioxidant group, while increasing in the controls (p = 0.006). A similar trend was seen for IL6 (p = 0.062). A larger decrease in micro-CRP was detected in the antioxidant group compared to controls (β: -0.62, p = 0.02). We found no group differences for the remaining cytokines. 8-epi-PGF2α increased significantly in the whole population (p = 0.033), regardless group allocation. The stress response was significantly larger post-altitude compared with pre-altitude for IL1β, IL6, IL7, IL13, IL12p70 and TNFα, but we found no group differences.

Conclusions: Increased intake of antioxidant-rich foods elevated the antioxidant capacity and attenuated some of the altitude-induced systemic inflammatory biomarkers in elite athletes. The antioxidant intervention had no impact on the altitude-induced oxidative stress or changes in acute cytokine responses to exercise stress-tests.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0217895PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563980PMC
February 2020

A Collaborative Analysis of Individual Participant Data from 19 Prospective Studies Assesses Circulating Vitamin D and Prostate Cancer Risk.

Cancer Res 2019 01 13;79(1):274-285. Epub 2018 Nov 13.

Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.

Previous prospective studies assessing the relationship between circulating concentrations of vitamin D and prostate cancer risk have shown inconclusive results, particularly for risk of aggressive disease. In this study, we examine the association between prediagnostic concentrations of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)D] and the risk of prostate cancer overall and by tumor characteristics. Principal investigators of 19 prospective studies provided individual participant data on circulating 25(OH)D and 1,25(OH)D for up to 13,462 men with incident prostate cancer and 20,261 control participants. ORs for prostate cancer by study-specific fifths of season-standardized vitamin D concentration were estimated using multivariable-adjusted conditional logistic regression. 25(OH)D concentration was positively associated with risk for total prostate cancer (multivariable-adjusted OR comparing highest vs. lowest study-specific fifth was 1.22; 95% confidence interval, 1.13-1.31; trend < 0.001). However, this association varied by disease aggressiveness ( = 0.014); higher circulating 25(OH)D was associated with a higher risk of nonaggressive disease (OR per 80 percentile increase = 1.24, 1.13-1.36) but not with aggressive disease (defined as stage 4, metastases, or prostate cancer death, 0.95, 0.78-1.15). 1,25(OH)D concentration was not associated with risk for prostate cancer overall or by tumor characteristics. The absence of an association of vitamin D with aggressive disease does not support the hypothesis that vitamin D deficiency increases prostate cancer risk. Rather, the association of high circulating 25(OH)D concentration with a higher risk of nonaggressive prostate cancer may be influenced by detection bias. SIGNIFICANCE: This international collaboration comprises the largest prospective study on blood vitamin D and prostate cancer risk and shows no association with aggressive disease but some evidence of a higher risk of nonaggressive disease.
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http://dx.doi.org/10.1158/0008-5472.CAN-18-2318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330070PMC
January 2019

Agreement between PG-SGA category and fat-free mass in colorectal cancer patients.

Clin Nutr ESPEN 2018 10 7;27:24-31. Epub 2018 Aug 7.

Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway; Division of Cancer Medicine, Oslo University Hospital, Oslo, Norway. Electronic address:

Background And Aims: Low fat-free mass (FFM) is associated with adverse outcomes in colorectal cancer (CRC) patients. Patient-Generated Subjective Global Assessment (PG-SGA) is a widely used tool developed to detect patients with malnutrition or at risk of malnutrition. The aim of this study was to investigate the agreement between PG-SGA category and FFM in patients with non-metastatic CRC.

Methods: Ninety-seven patients were included and categorized as well nourished (PG-SGA:A, n = 67) or malnourished (PG-SGA:B, n = 30). No patients were severely malnourished (PG-SGA: C). Bioelectrical impedance analysis (BIA) was used to assess FFM. Low FFM was defined as low fat-free mass index (FFMI) according to cut-off values recently proposed by The European Society for Clinical Nutrition and Metabolism (ESPEN).

Results: Twenty-nine percent of the patients were identified with low FFMI. The proportion with low FFMI was significantly higher among patients classified as malnourished by PG-SGA compared to well nourished (p = 0.015). The sensitivity was however low, as the PG-SGA categorization classified only 50.0% of the patients with low FFMI as malnourished (PG-SGA B). Using the PG-SGA scores (cut-off point > 4), the sensitivity increased to 60.7%. Physical examination in the PG-SGA identified only 64.3% of the patients with low FFMI as muscle depleted.

Conclusion: Our results indicate a low agreement between PG-SGA category and low FFMI among patients with non-metastatic CRC. In clinical practice, PG-SGA should be supplemented by muscle mass assessments by BIA or other methods in order to detect low FFM in this patient group.
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http://dx.doi.org/10.1016/j.clnesp.2018.07.005DOI Listing
October 2018

The risk association of plasma total homocysteine with acute myocardial infarction is modified by serum vitamin A.

Eur J Prev Cardiol 2018 10 17;25(15):1612-1620. Epub 2018 Jul 17.

2 Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.

Background Plasma total homocysteine (tHcy) has been implicated in the development of cardiovascular disease, but the mechanisms remain unclear. Vitamin A (Vit-A) is involved in homocysteine metabolism and we therefore explored the potential interaction between plasma tHcy and serum Vit-A in relation to incident acute myocardial infarction. Methods Cox proportional hazards models were used to assess the prospective relationships between tHcy and acute myocardial infarction in 2205 patients from Western Norway undergoing elective coronary angiography for suspected stable angina pectoris. Results are reported as hazard ratio per standard deviation increase in log-transformed tHcy. An interaction term for tHcy × Vit-A was added to multivariate models including age, sex, smoking, apolipoprotein B fasting, statin and aspirin prescription and estimated glomerular filtration rate. Results Geometric mean (geometric standard deviation) age of the participants (64.3% men) was 62.3 (1.24) years. Plasma tHcy was higher among participants in the upper versus lower Vit-A tertile. During 7 (2.4) years of follow-up, 15.1% suffered an AMI. A significant association of plasma tHcy with AMI in the total study population was observed. When we stratified the population according to Vit-A tertiles, plasma tHcy was associated with acute myocardial infarction only in the upper Vit-A tertile (hazard ratio per SD: 1.25, 95% confidence interval: 1.04-1.53, p = 0.03). Conclusions The risk relationship between plasma tHcy and acute myocardial infarction was modified by serum concentrations of Vit-A in patients with suspected stable angina pectoris. This finding may clarify the relationship between tHcy and cardiovascular disease.
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http://dx.doi.org/10.1177/2047487318788587DOI Listing
October 2018

Placental release of taurine to both the maternal and fetal circulations in human term pregnancies.

Amino Acids 2018 Sep 1;50(9):1205-1214. Epub 2018 Jun 1.

Division of Obstetrics and Gynecology, Department of Obstetrics, Oslo University Hospital, PO BOKS 4950, 0424, Oslo, Norway.

Taurine is regarded as an essential amino acid in utero, and fetal taurine supply is believed to rely solely on placental transfer from maternal plasma. Despite its potential role in intrauterine growth restriction and other developmental disturbances, human in vivo studies of taurine transfer between the maternal, placental, and fetal compartments are scarce. We studied placental transfer of taurine in uncomplicated human term pregnancies in vivo in a cross-sectional study of 179 mother-fetus pairs. During cesarean section, we obtained placental tissue and plasma from incoming and outgoing vessels on the maternal and fetal sides of the placenta. Taurine was measured by liquid chromatography-tandem mass spectrometry. We calculated paired arteriovenous differences, and measured placental expression of the taurine biosynthetic enzyme cysteine sulfinic acid decarboxylase (CSAD) with quantitative real-time polymerase chain reaction and western blot. We observed a fetal uptake (p < 0.001), an uteroplacental release (p < 0.001), and a negative placental consumption of taurine (p = 0.001), demonstrating a bilateral placental release to the maternal and fetal compartments. Increasing umbilical vein concentrations and fetal uptake was associated with the uteroplacental release to the maternal circulation (r = - 0.19, p = 0.01/r = - 0.24, p = 0.003), but not with taurine concentrations in placental tissue. CSAD-mRNA was expressed in placental tissue, suggesting a potential for placental taurine synthesis. Our observations show that the placenta has the capacity to a bilateral taurine release, indicating a fundamental role of taurine in the human placental homeostasis beyond the supply to the fetus.
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http://dx.doi.org/10.1007/s00726-018-2576-9DOI Listing
September 2018

Validation of two short questionnaires assessing physical activity in colorectal cancer patients.

BMC Sports Sci Med Rehabil 2018 29;10. Epub 2018 May 29.

1Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.

Background: In order to investigate the impact of adherence to recommendations of physical activity and sedentary time on health outcomes in clinical trials, there is a need for feasible tools such as questionnaires that can give representative estimates of these measures. The primary aim of the present study was to validate two such questionnaires and their ability to estimate adherence to the recommendations of physical activity defined as moderate-to- vigorous physical activity or moderate physical activity of at least 150 min/week in colorectal cancer patients. Secondarily, self-reported sedentary time from the HUNT-PAQ was also evaluated.

Methods: Participants from 'The Norwegian dietary guidelines and colorectal cancer survival-study' (CRC-NORDIET study) completed two short questionnaires; the NORDIET-FFQ ( = 78) and the HUNT-PAQ ( = 77). The physical activity monitor SenseWear Armband Mini was used as the reference method during seven consecutive days.

Results: The NORDIET-FFQ provided better estimates of time in moderate-to- vigorous physical activity and moderate physical activity than the HUNT-PAQ. The NORDIET-FFQ was unable to rank individual time in moderate-to- vigorous physical activity and moderate physical activity (Spearman's rho = 0.08,  = 0.509 and Spearman's rho rho = 0.01,  = 0.402, respectively). All intensities were under-reported by the HUNT-PAQ, but ranking of individual time in moderate physical activity and sedentary time were acceptable among women only (Spearman's rho = 0.37,  = 0.027 and Spearman's rho = 0.36,  = 0.035, respectively). The HUNT-PAQ correctly classified 71% of those not meeting the recommendations (sensitivity), and the NORDIET-FFQ correctly classified 63% of those who met the recommendations (specificity). About 67% and 33% reported to meet the recommendation of moderate-to- vigorous physical activity with the NORDIET-FFQ and HUNT-PAQ, respectively, whereas 55% actually met the moderate-to- vigorous physical activity according to the SenseWear Armband Mini.

Conclusions: The NORDIET-FFQ provided better specificity and better estimates of PA than the HUNT-PAQ. The HUNT-PAQ provided better sensitivity, and provided better ranking of PA and sedentary time among women than NORDIET-FFQ. It is important to be aware of the limitations documented in the present study.

Trial Registration: The study is registered on the National Institutes of Health Clinical Trials (Identifier: NCT01570010). Registered 4 April 2012.
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http://dx.doi.org/10.1186/s13102-018-0096-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5975662PMC
May 2018

Relative validity of a short food frequency questionnaire assessing adherence to the Norwegian dietary guidelines among colorectal cancer patients.

Food Nutr Res 2018 22;62. Epub 2018 Feb 22.

Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.

Background: The Norwegian food-based dietary guidelines (FBDG) aim at reducing the risk of developing chronic diseases and promote overall health. We studied the effect of the Norwegian FBDG in colorectal cancer (CRC) patients. There is a need for a time-efficient dietary assessment tool measuring adherence to these guidelines in patients treated for dietary dependent cancer, such as CRC patients.

Objective: To evaluate a new short food frequency questionnaire (NORDIET-FFQ), developed to estimate adherence to the Norwegian FBDG among CRC patients.

Design: Eighty-one CRC patients from both study groups in the Norwegian Dietary Guidelines and Colorectal Cancer Survival study, an ongoing dietary intervention, completed both the short 63-item NORDIET-FFQ and a 7-day weighed food record.

Results: The NORDIET-FFQ was on group level able to estimate intakes of fruits, vegetables, unsalted nuts, fish, fatty fish, high fat dairy products, unprocessed meat, processed meat, red meat, water, sugar-rich beverages, alcoholic drinks, and sugar- and fat-rich foods. Ranking of individuals according to intake was good ( = 0.31-0.74) for fruits and vegetables, fruits, unsalted nuts, whole grain products, sugar-rich cereals, fish, fatty fish, dairy products, red meat, water, sugar-rich beverages, alcoholic beverages, and sugar- and fat-rich foods. The NORDIET-FFQ was able to identify the individuals who did not fulfil the recommendations of fruits, vegetables, unsalted nuts, whole grains, low-fat dairy products, processed meat, water, alcoholic beverages, and sugar- and fat-rich foods (sensitivity: 67-93%).

Conclusions: The NORDIET-FFQ showed good ability in to estimate intakes of plant-based foods, fish, dairy products, meat, and energy-dense foods; adequate ranking of individuals according to intake of most recommendations except for unprocessed meat, processed meat, and vegetables; and importantly a good ability to identify those patients in need of dietary counselling for foods that are known to modulate the risk of CRC.

Trial Registration: National Institutes of Health ClinicalTrials.gov; Identifier: NCT01570010.
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http://dx.doi.org/10.29219/fnr.v62.1306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5846207PMC
February 2018

DNA damage in blood cells in relation to chemotherapy and nutritional status in colorectal cancer patients-A pilot study.

DNA Repair (Amst) 2018 03 11;63:16-24. Epub 2018 Jan 11.

Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. Electronic address:

DNA damage can be considered as a biomarker for toxicity and response to chemotherapy. It is not known whether the chemotherapy-induced genotoxicity is associated with malnutrition. In this pilot study, we assess genotoxicity by means of DNA damage in patients with lymph-node positive colorectal cancer (CRC) and explore associations with chemotherapy treatment and nutritional status. DNA damage was compared between patients receiving chemotherapy (n = 24) and those not receiving chemotherapy (n = 20). DNA damage was measured in frozen whole blood by the comet assay. Associations between DNA damage and various indicators of malnutrition were also explored, including Patient-Generated Subjective Global Assessment (PG-SGA), bioelectrical impedance analysis (BIA) and anthropometric measurements, using multiple linear regression models. Patients on chemotherapy have higher levels of DNA damage in blood cells than patients not receiving chemotherapy (median of 16.9 and 7.9% tail DNA respectively, p = 0.001). The moderately malnourished patients (PG-SGA category B), representing 41% of the patients, have higher levels of cellular DNA damage than patients with good nutritional status (mean difference of 7.5% tail DNA, p = 0.033). In conclusion, adjuvant chemotherapy and malnutrition are both associated with increased levels of DNA damage in blood cells of CRC patients. Carefully controlled longitudinal studies or randomized controlled trials should be performed to determine whether good nutritional status may protect against chemotherapy-induced genotoxicity and enhance compliance to therapy in CRC patients.
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http://dx.doi.org/10.1016/j.dnarep.2018.01.005DOI Listing
March 2018

Uptake and release of amino acids in the fetal-placental unit in human pregnancies.

PLoS One 2017 5;12(10):e0185760. Epub 2017 Oct 5.

Department of Obstetrics, Division of Obstetrics and Gynecology, Oslo University Hospital, Oslo, Norway.

Objectives: The current concepts of human fetal-placental amino acid exchange and metabolism are mainly based on animal-, in vitro- and ex vivo models. We aimed to determine and assess the paired relationships between concentrations and arteriovenous differences of 19 amino acids on the maternal and fetal sides of the human placenta in a large study sample.

Methods: This cross-sectional in vivo study included 179 healthy women with uncomplicated term pregnancies. During planned cesarean section, we sampled blood from incoming and outgoing vessels on the maternal (radial artery and uterine vein) and fetal (umbilical vein and artery) sides of the placenta. Amino acid concentrations were measured by liquid chromatography-tandem mass spectrometry. We calculated paired arteriovenous differences and performed Wilcoxon signed-rank tests and Spearman's correlations.

Results: In the umbilical circulation, we observed a positive venoarterial difference (fetal uptake) for 14 amino acids and a negative venoarterial difference (fetal release) for glutamic acid (p<0.001). In the maternal circulation, we observed a positive arteriovenous difference (uteroplacental uptake) for leucine (p = 0.005), isoleucine (p = 0.01), glutamic acid (p<0.001) and arginine (p = 0.04) and a negative arteriovenous difference (uteroplacental release) for tyrosine (p = 0.002), glycine (p = 0.01) and glutamine (p = 0.02). The concentrations in the maternal artery and umbilical vein were correlated for all amino acids except tryptophan, but we observed no correlations between the uteroplacental uptake and the fetal uptake or the umbilical vein concentration. Two amino acids showed a correlation between the maternal artery concentration and the fetal uptake.

Conclusions: Our human in vivo study expands the current insight into fetal-placental amino acid exchange, and discloses some differences from what has been previously described in animals. Our findings are consistent with the concept that the fetal supply of amino acids in the human is the result of a dynamic interplay between fetal and placental amino acid metabolism and interconversions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0185760PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628923PMC
October 2017

Cardiovascular disease risk associated with serum apolipoprotein B is modified by serum vitamin A.

Atherosclerosis 2017 10 21;265:325-330. Epub 2017 Jul 21.

Department of Heart Disease, Haukeland University Hospital, 5021 Bergen, Norway; KG Jebsen Centre for Diabetes Research, University of Bergen, 5009 Bergen, Norway; Department of Clinical Science, Faculty of Medicine, University of Bergen, 5021 Bergen, Norway.

Background And Aims: Apolipoproteins B (apoB) and A1 (apoA1) are major protein constituents of low-density and high-density lipoproteins, respectively, and serum concentrations of these apolipoproteins are associated with risk of atherosclerosis. Vitamin A (VA) has been implicated in lipoprotein metabolism. We evaluated the associations of serum apoB, apoA1 and their ratio (apoBAR) with risk of incident acute myocardial infarction (AMI) and the possible modification by serum VA.

Methods: Risk associations were assessed by Cox regression, and presented as hazard ratios (HRs) per standard deviation (SD) increment in log-transformed values of the lipid parameters, among 4117 patients with suspected stable angina pectoris, located in Western Norway. Interactions with VA were evaluated by including interaction terms in the models. The multivariate model included age, sex, smoking, hypertension, number of stenotic coronary arteries, left ventricular ejection fraction, C-reactive protein, estimated glomerular filtration rate and statin treatment at discharge.

Results: Median (25th, 75th percentile) age of the 4117 patients (72% male) was 62 (55, 70) years. ApoB and apoA1 were higher among patients in the upper versus lower tertiles of VA. During a median of 4.6 (3.6, 5.7) years of follow-up, 8.2% of patients experienced an AMI. Overall, we observed no significant associations between lipid parameters and AMI after multivariate adjustment. However, apoB and apoBAR were associated with AMI among patients in the upper tertile of VA (HR per SD 1.35, (95% CI: 1.11-1.65), and 1.42 (1.16-1.74), respectively, p for interactions ≤0.003).

Conclusions: The associations of apoB and apoBAR with incident AMI were confined to patients with elevated VA.
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http://dx.doi.org/10.1016/j.atherosclerosis.2017.07.020DOI Listing
October 2017

The Norwegian dietary guidelines and colorectal cancer survival (CRC-NORDIET) study: a food-based multicentre randomized controlled trial.

BMC Cancer 2017 01 30;17(1):83. Epub 2017 Jan 30.

Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.

Background: Colorectal cancer survivors are not only at risk for recurrent disease but also at increased risk of comorbidities such as other cancers, cardiovascular disease, diabetes, hypertension and functional decline. In this trial, we aim at investigating whether a diet in accordance with the Norwegian food-based dietary guidelines and focusing at dampening inflammation and oxidative stress will improve long-term disease outcomes and survival in colorectal cancer patients.

Methods/design: This paper presents the study protocol of the Norwegian Dietary Guidelines and Colorectal Cancer Survival study. Men and women aged 50-80 years diagnosed with primary invasive colorectal cancer (Stage I-III) are invited to this randomized controlled, parallel two-arm trial 2-9 months after curative surgery. The intervention group (n = 250) receives an intensive dietary intervention lasting for 12 months and a subsequent maintenance intervention for 14 years. The control group (n = 250) receives no dietary intervention other than standard clinical care. Both groups are offered equal general advice of physical activity. Patients are followed-up at 6 months and 1, 3, 5, 7, 10 and 15 years after baseline. The study center is located at the Department of Nutrition, University of Oslo, and patients are recruited from two hospitals within the South-Eastern Norway Regional Health Authority. Primary outcomes are disease-free survival and overall survival. Secondary outcomes are time to recurrence, cardiovascular disease-free survival, compliance to the dietary recommendations and the effects of the intervention on new comorbidities, intermediate biomarkers, nutrition status, physical activity, physical function and quality of life.

Discussion: The current study is designed to gain a better understanding of the role of a healthy diet aimed at dampening inflammation and oxidative stress on long-term disease outcomes and survival in colorectal cancer patients. Since previous research on the role of diet for colorectal cancer survivors is limited, the study may be of great importance for this cancer population.

Trial Registration: ClinicalTrials.gov Identifier: NCT01570010 .
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http://dx.doi.org/10.1186/s12885-017-3072-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5282711PMC
January 2017

Validity of bioelectrical impedance analysis in estimation of fat-free mass in colorectal cancer patients.

Clin Nutr 2018 02 12;37(1):292-300. Epub 2017 Jan 12.

Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway; Division of Cancer Medicine, Oslo University Hospital, Oslo, Norway. Electronic address:

Background & Aims: Bioelectrical impedance analysis (BIA) is an accessible and cheap method to measure fat-free mass (FFM). However, BIA estimates are subject to uncertainty in patient populations with altered body composition and hydration. The aim of the current study was to validate a whole-body and a segmental BIA device against dual-energy X-ray absorptiometry (DXA) in colorectal cancer (CRC) patients, and to investigate the ability of different empiric equations for BIA to predict DXA FFM (FFM).

Methods: Forty-three non-metastatic CRC patients (aged 50-80 years) were enrolled in this study. Whole-body and segmental BIA FFM estimates (FFM, FFM) were calculated using 14 empiric equations, including the equations from the manufacturers, before comparison to FFM estimates.

Results: Strong linear relationships were observed between FFM and FFM estimates for all equations (R = 0.94-0.98 for both devices). However, there were large discrepancies in FFM estimates depending on the equations used with mean differences in the ranges -6.5-6.8 kg and -11.0-3.4 kg for whole-body and segmental BIA, respectively. For whole-body BIA, 77% of BIA derived FFM estimates were significantly different from FFM, whereas for segmental BIA, 85% were significantly different. For whole-body BIA, the Schols* equation gave the highest agreement with FFM with mean difference ±SD of -0.16 ± 1.94 kg (p = 0.582). The manufacturer's equation gave a small overestimation of FFM with 1.46 ± 2.16 kg (p < 0.001) with a tendency towards proportional bias (r = 0.28, p = 0.066). For segmental BIA, the Heitmann* equation gave the highest agreement with FFM (0.17 ± 1.83 kg (p = 0.546)). Using the manufacturer's equation, no difference in FFM estimates was observed (-0.34 ± 2.06 kg (p = 0.292)), however, a clear proportional bias was detected (r = 0.69, p < 0.001). Both devices demonstrated acceptable ability to detect low FFM compared to DXA using the optimal equation.

Conclusion: In a population of non-metastatic CRC patients, mostly consisting of Caucasian adults and with a wide range of body composition measures, both the whole-body BIA and segmental BIA device provide FFM estimates that are comparable to FFM on a group level when the appropriate equations are applied. At the individual level (i.e. in clinical practice) BIA may be a valuable tool to identify patients with low FFM as part of a malnutrition diagnosis.
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http://dx.doi.org/10.1016/j.clnu.2016.12.028DOI Listing
February 2018

Tomato-based randomized controlled trial in prostate cancer patients: Effect on PSA.

Clin Nutr 2017 06 30;36(3):672-679. Epub 2016 Jun 30.

Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, PO Box 1046, Blindern, 0316 Oslo, Norway; Division of Cancer Medicine, Transplantation and Surgery, Oslo University Hospital, PO Box 4950, Nydalen, 0424 Oslo, Norway. Electronic address:

Background & Aims: The effect of lycopene-containing foods in prostate cancer development remains undetermined. We tested whether a lycopene-rich tomato intervention could reduce the levels of prostate specific antigen (PSA) in prostate cancer patients.

Methods: Prior to their curative treatment, 79 patients with prostate cancer were randomized to a nutritional intervention with either 1) tomato products containing 30 mg lycopene per day; 2) tomato products plus selenium, omega-3 fatty acids, soy isoflavones, grape/pomegranate juice, and green/black tea (tomato-plus); or 3) control diet for 3 weeks.

Results: The main analysis, which included patients in all risk categories, did not reveal differences in changes of PSA-values between the intervention and control groups. Post-hoc, exploratory analyses within intermediate risk (n = 41) patients based on tumor classification and Gleason score post-surgery, revealed that median PSA decreased significantly in the tomato group as compared to controls (-2.9% and +6.5% respectively, p = 0.016). In separate post-hoc analyses, we observed that median PSA-values decreased by 1% in patients with the highest increases in plasma lycopene, selenium and C20:5 n-3 fatty acid, compared to an 8.5% increase in the patients with the lowest increase in lycopene, selenium and C20:5 n-3 fatty acid (p = 0.003). Also, PSA decreased in patients with the highest increase in lycopene alone (p = 0.009).

Conclusions: Three week nutritional interventions with tomato-products alone or in combination with selenium and n-3 fatty acids lower PSA in patients with non-metastatic prostate cancer. Our observation suggests that the effect may depend on both aggressiveness of the disease and the blood levels of lycopene, selenium and omega-3 fatty acids.
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http://dx.doi.org/10.1016/j.clnu.2016.06.014DOI Listing
June 2017

Total antioxidant intake and prostate cancer in the Cancer of the Prostate in Sweden (CAPS) study. A case control study.

BMC Cancer 2016 07 11;16:438. Epub 2016 Jul 11.

Department of Medical Epidemiology and Biostatistics, Karolinska Institute, 17177, Stockholm, Sweden.

Background: The total intake of dietary antioxidants may reduce prostate cancer risk but available data are sparse and the possible role of supplements unclear. We investigated the potential association between total and dietary antioxidant intake and prostate cancer in a Swedish population.

Methods: We used FFQ data from 1499 cases and 1112 controls in the population based case-control study Cancer of the Prostate in Sweden (CAPS). The ferric reducing antioxidant potential (FRAP) assay was used to assess the total antioxidant capacity (TAC) of diet and supplements. We calculated odds ratios (ORs) for the risk of prostate cancer across quintiles of antioxidant intake from all foods, from fruit and vegetables only, and from dietary supplements using unconditional logistic regression.

Results: Coffee comprised 62 % of the dietary antioxidant intake, tea 4 %, berries 4 %, chocolate 2 %, and boiled potatoes 2 %. In total 19 % and 13 % of the population took multivitamins and supplemental Vitamin C respectively, on a regular basis. Antioxidant intake from all foods and from fruits and vegetables separately measured by the FRAP assay was not associated with prostate cancer risk. For antioxidant intake from supplements we found a positive association with total, advanced, localized, high grade and low grade prostate cancer in those above median supplemental TAC intake of users compared to non-users (Adjusted ORs for total prostate cancer: 1.37, 95 % CI 1.08-1.73, advanced: 1.51, 95 % CI 1.11-2.06, localized: 1.36. 95 % CI 1.06-1.76, high grade 1.60, 95 % CI 1.06-2.40, low grade 1.36, 95 % CI 1.03-1.81). A high intake of coffee (≥6 cups/day) was associated with a possible risk reduction of fatal and significantly with reduced risk for high grade prostate cancer, adjusted OR: 0.45 (95 % CI: 0.22-0.90), whereas a high intake of chocolate was positively associated with risk of total, advanced, localized and low grade disease (adjusted OR for total: 1.43, 95 % CI 1.12-1.82, advanced: 1.40, 95 % CI 1.01-1.96, localized: 1.43, 95 % CI 1.08-1.88, low-grade: 1.41, 95 % CI 1.03-1.93).

Conclusions: Total antioxidant intake from diet was not associated with prostate cancer risk. Supplement use may be associated with greater risk of disease.
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http://dx.doi.org/10.1186/s12885-016-2486-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4939657PMC
July 2016

Long Term Association between Serum 25-Hydroxyvitamin D and Mortality in a Cohort of 4379 Men.

PLoS One 2016 17;11(3):e0151441. Epub 2016 Mar 17.

The Cancer Registry of Norway, Institute of Population-based Cancer Research, Oslo, Norway.

Objective: A number of observational studies have shown an inverse association between circulating 25-hydroxyvitamin D and total mortality, but a reverse J-shaped association has also been reported. In a large nested case-control study, serum-25-hydroxyvitamin D (s-25(OH)D) was positively associated with incident prostate cancer. Based on the same study population, the primary aim of the present study was to investigate the association between s-25(OH)D and total mortality.

Methods: Men participating in population based health screenings during 1981-1991 and enrolled in a nested case-control study were followed throughout 2007 with respect to all-cause and cause-specific mortality. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox proportional hazards regression.

Results: In men with prostate cancer (n = 2282), there was a significant inverse association between s-25(OH)D and total mortality after controlling for potential confounders (HR = 1.25 (95% CI 1.05-1.50), s-25(OH)D <50 nmol/l versus s-25(OH)D ≥ 50 nmol/l). The corresponding figure among controls (n = 2147) was HR = 1.15 (95% CI 0.88-1.50) and in the total study population HR = 1.19 (95% CI 1.03-1.38). For cause-specific deaths, we found no significant associations.

Conclusions: In this study population, s-25(OH)D was inversely associated with total mortality during more than two decades of follow-up, despite, as previous reported, high s-25(OH)D was associated with increased risk of prostate cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0151441PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795600PMC
August 2016

Effect of Omega-3 and Vitamins E + C Supplements on the Concentration of Serum B-Vitamins and Plasma Redox Aminothiol Antioxidant Status in Elderly Men after Strength Training for Three Months.

Ann Nutr Metab 2016 6;68(2):145-55. Epub 2016 Feb 6.

Department of Public Health, Sport and Nutrition, University of Agder, Kristiansand, Norway.

Background: Data on redox plasma aminothiol status in individuals on strength training are very limited. Therefore, we studied the effect of omega-3 and vitamins E + C supplementation on the concentration of B-vitamins and redox aminothiol status in elderly men after strength training for 3 months.

Methods: Healthy men, age 60 ± 6 (mean ± SD) were randomly divided into 3 groups: group I received placebo (n = 17), group II consumed omega-3 (700 mg, n = 17), and group III consumed vitamins E + C (235 mg +1 g, n = 16) daily for 3 months. All participants completed a strength training program for the same period.

Results: The concentration of serum vitamin B12 decreased and the concentration of serum folate increased in group I after the intervention (p = 0.01, p = 0.009). The concentration of plasma 5-pyridoxal phosphate decreased in groups II and III (p = 0.03 and p = 0.01), whereas the concentration of serum uric acid decreased only in group II (p = 0.02). We detected an increase in the concentration of reduced form of aminothiols in all groups (p < 0.001). The red/ox plasma aminothiol status was significantly changed in all groups after the intervention (p < 0.05).

Conclusion: Omega-3 and vitamins E + C supplementation affect the concentrations of serum B-vitamins and redox plasma aminothiol status in healthy elderly men on strength training.
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http://dx.doi.org/10.1159/000443847DOI Listing
October 2016

Coffee inhibits nuclear factor-kappa B in prostate cancer cells and xenografts.

J Nutr Biochem 2016 Jan 3;27:153-63. Epub 2015 Sep 3.

Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, P.O. Box 1046, 0317 Oslo, Norway. Electronic address:

Chronic inflammation contributes to prostate cancer and the transcription factor Nuclear Factor-kappa B (NF-κB) is constitutively active in most such cancers. We examine the effects of coffee on NF-κB and on the regulation of selected genes in human-derived prostate cancer cells (PC3) and in PC3 xenografts in athymic nude mice. PC3 cells stably transduced with an NF-κB-luciferase reporter were used both in vitro and for xenografts. NF-κB activity was measured by reporter assays, DNA binding and in vivo imaging. Gene expression was measured in PC3 cells, xenografts and tumor microenvironment by low-density arrays. Western blotting of activated caspases was used to quantify apoptosis. Coffee inhibited TNFα-induced NF-κB activity and DNA-binding in PC3 cells. Furthermore, coffee increased apoptosis and modulated expression of a number of inflammation- and cancer-related genes in TNFα-treated PC3 cells. In vivo imaging revealed a 31% lower NF-κB-luciferase activation in the xenografts of the mice receiving 5% coffee compared to control mice. Interestingly, we observed major changes in gene expression in the PC3 cells in xenografts as compared to PC3 cells in vitro. In PC3 xenografts, genes related to inflammation, apoptosis and cytoprotection were down-regulated in mice receiving coffee, and coffee also affected the gene expression in the xenograft microenvironment. Our data demonstrate that coffee inhibits NF-κB activity in PC3 cells in vitro and in xenografts. Furthermore, coffee modulates transcription of genes related to prostate cancer and inflammation. Our results are the first to suggest mechanistic links between coffee consumption and prostate cancer in an experimental mouse model.
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http://dx.doi.org/10.1016/j.jnutbio.2015.08.028DOI Listing
January 2016

No increase in risk of hip fracture at high serum retinol concentrations in community-dwelling older Norwegians: the Norwegian Epidemiologic Osteoporosis Studies.

Am J Clin Nutr 2015 Nov 16;102(5):1289-96. Epub 2015 Sep 16.

Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway; Institute of Health and Society, University of Oslo, Oslo, Norway; and.

Background: Norway has the highest hip fracture rates worldwide and a relatively high vitamin A intake. Increased fracture risk at high intakes and serum concentrations of retinol (s-retinol) have been observed in epidemiologic studies.

Objective: We aimed to study the association between s-retinol and hip fracture and whether high s-retinol may counteract a preventive effect of vitamin D.

Design: We conducted the largest prospective analysis of serum retinol and hip fracture to date in 21,774 men and women aged 65-79 y (mean age: 72 y) who attended 4 community-based health studies during 1994-2001. Incident hip fractures occurring up to 10.7 y after baseline were retrieved from electronic hospital discharge registers. Retinol determined by high-pressure liquid chromatography with ultraviolet detection in stored serum was available in 1154 incident hip fracture cases with valid body mass index (BMI) data and in a subcohort defined as a sex-stratified random sample (n = 1418). Cox proportional hazards regression weighted according to the stratified case-cohort design was performed.

Results: There was a modest increased risk of hip fracture in the lowest compared with the middle quintile of s-retinol (HR: 1.41; 95% CI: 1.09, 1.82) adjusted for sex and study center. The association was attenuated after adjustment for BMI and serum concentrations of α-tocopherol (HR: 1.16; 95% CI: 0.88, 1.51). We found no increased risk in the upper compared with the middle quintile. No significant interaction between serum concentrations of 25-hydroxyvitamin D and s-retinol on hip fracture was observed (P = 0.68).

Conclusions: We found no evidence of an adverse effect of high serum retinol on hip fracture or any interaction between retinol and 25-hydroxyvitamin D. If anything, there tended to be an increased risk at low retinol concentrations, which was attenuated after control for confounders. We propose that cod liver oil, a commonly used food supplement in Norway, should not be discouraged as a natural source of vitamin D for fracture prevention.
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http://dx.doi.org/10.3945/ajcn.115.110528DOI Listing
November 2015

IRF4 Is a Critical Gene in Retinoic Acid-Mediated Plasma Cell Formation and Is Deregulated in Common Variable Immunodeficiency-Derived B Cells.

J Immunol 2015 Sep 14;195(6):2601-11. Epub 2015 Aug 14.

Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, N-0317 Oslo, Norway;

In the present study, we aimed at identifying the mechanisms whereby the vitamin A metabolite all-trans retinoic acid (RA) promotes the formation of plasma cells upon stimulation of B cells via the innate immunity receptors TLR9 and RP105. Most often, differentiation of B cells involves the sequential events of class switch recombination and somatic hypermutations characteristic of germinal center reactions, followed by plasma cell formation. By studying the regulatory networks known to drive these reactions, we revealed that RA enhances the expression of the plasma cell-generating transcription factors IFN regulatory factor (IRF)4 and Blimp1, and paradoxically also activation-induced deaminase (AID) involved in somatic hypermutations/class switch recombination, in primary human B cells. IRF4 was identified as a particularly important protein involved in the RA-mediated production of IgG in TLR9/RP105-stimulated B cells. Based on kinetic studies, we present a model suggesting that the initial induction of IRF4 by RA favors AID expression. According to this model, the higher level of IRF4 that eventually arises results in sustained elevated levels of Blimp1. Regarded as a master regulator of plasma cell development, Blimp1 will in turn suppress AID expression and drive the formation of IgG-secreting plasma cells. Notably, we demonstrated IRF4 to be deregulated in B cells from common variable immunodeficiency patients, contributing to the observed aberrant expression of AID in these patients. Taken together, the present study both provides new insight into the mechanisms whereby RA induces differentiation of B cells and identifies IRF4 as a key to understand the defective functions of B cells in common variable immunodeficiency patients.
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http://dx.doi.org/10.4049/jimmunol.1500250DOI Listing
September 2015

Polyphenol-rich juices reduce blood pressure measures in a randomised controlled trial in high normal and hypertensive volunteers.

Br J Nutr 2015 Oct 31;114(7):1054-63. Epub 2015 Jul 31.

Department of Nutrition,Institute of Basic Medical Sciences, University of Oslo,Sognsvannsveien 9, PO Box 1046, Blindern,0317Oslo,Norway.

Intake of fruits and berries may lower blood pressure (BP), most probably due to the high content of polyphenols. In the present study, we tested whether consumption of two polyphenol-rich juices could lower BP. In a randomised, double-blinded, placebo-controlled trial of 12 weeks, 134 healthy individuals, aged 50-70 years, with high normal range BP (130/85-139/89 mmHg, seventy-two subjects) or stage 1-2 hypertension (140/90-179/109 mmHg, sixty-two subjects), were included. They consumed 500 ml/d of one of either (1) a commercially available polyphenol-rich juice based on red grapes, cherries, chokeberries and bilberries; (2) a juice similar to (1) but enriched with polyphenol-rich extracts from blackcurrant press-residue or (3) a placebo juice (polyphenol contents 245·5, 305·2 and 76 mg/100 g, respectively). Resting BP was measured three times, with a 1 min interval, at baseline and after 6 and 12 weeks of intervention. Systolic BP significantly reduced over time (6 and 12 weeks, respectively) in the pooled juice group compared with the placebo group in the first of the three measurements, both for the whole study group (6·9 and 3·4 mmHg; P= 0·01) and even more pronounced in the hypertensive subjects when analysed separately (7·3 and 6·8 mmHg; P= 0·04). The variation in the BP measurements was significantly reduced in the pooled juice group compared with the placebo group (1·4 and 1·7 mmHg; P= 0·03). In conclusion, the present findings suggest that polyphenol-rich berry juice may contribute to a BP- and BP variability lowering effect, being more pronounced in hypertensive than in normotensive subjects.
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http://dx.doi.org/10.1017/S0007114515000562DOI Listing
October 2015

Feasibility of self-sampled dried blood spot and saliva samples sent by mail in a population-based study.

BMC Cancer 2015 Apr 11;15:265. Epub 2015 Apr 11.

Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0316, Oslo, Norway.

Background: In large epidemiological studies it is often challenging to obtain biological samples. Self-sampling by study participants using dried blood spots (DBS) technique has been suggested to overcome this challenge. DBS is a type of biosampling where blood samples are obtained by a finger-prick lancet, blotted and dried on filter paper. However, the feasibility and efficacy of collecting DBS samples from study participants in large-scale epidemiological studies is not known. The aim of the present study was to test the feasibility and response rate of collecting self-sampled DBS and saliva samples in a population-based study of women above 50 years of age.

Methods: We determined response proportions, number of phone calls to the study center with questions about sampling, and quality of the DBS. We recruited women through a study conducted within the Norwegian Breast Cancer Screening Program. Invitations, instructions and materials were sent to 4,597 women. The data collection took place over a 3 month period in the spring of 2009.

Results: Response proportions for the collection of DBS and saliva samples were 71.0% (3,263) and 70.9% (3,258), respectively. We received 312 phone calls (7% of the 4,597 women) with questions regarding sampling. Of the 3,263 individuals that returned DBS cards, 3,038 (93.1%) had been packaged and shipped according to instructions. A total of 3,032 DBS samples were sufficient for at least one biomarker analysis (i.e. 92.9% of DBS samples received by the laboratory). 2,418 (74.1%) of the DBS cards received by the laboratory were filled with blood according to the instructions (i.e. 10 completely filled spots with up to 7 punches per spot for up to 70 separate analyses). To assess the quality of the samples, we selected and measured two biomarkers (carotenoids and vitamin D). The biomarker levels were consistent with previous reports.

Conclusion: Collecting self-sampled DBS and saliva samples through the postal services provides a low cost, effective and feasible alternative in epidemiological studies.
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http://dx.doi.org/10.1186/s12885-015-1275-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428002PMC
April 2015