Magritt Brustad

Fruit and Vegetable Intake and Overall Cancer Risk in the European Prospective Investigation Into Cancer and Nutrition (EPIC)

BACKGROUND It is widely believed that cancer can be prevented by high intake of fruits and vegetables. However, inconsistent results from many studies have not been able to conclusively establish an inverse association between fruit and vegetable intake and overall cancer risk. METHODS We conducted a prospective analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to assess relationships between intake of total fruits, total vegetables, and total fruits and vegetables combined and cancer risk during 1992-2000. Detailed information on the dietary habit and lifestyle variables of the cohort was obtained. Cancer incidence and mortality data were ascertained, and hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression models. Analyses were also conducted for cancers associated with tobacco and alcohol after stratification for tobacco smoking and alcohol drinking. RESULTS Of the initial 142 605 men and 335 873 women included in the study, 9604 men and 21 000 women were identified with cancer after a median follow-up of 8.7 years. The crude cancer incidence rates were 7.9 per 1000 person-years in men and 7.1 per 1000 person-years in women. Associations between reduced cancer risk and increased intake of total fruits and vegetables combined and total vegetables for the entire cohort were similar (200 g/d increased intake of fruits and vegetables combined, HR = 0.97, 95% CI = 0.96 to 0.99; 100 g/d increased intake of total vegetables, HR = 0.98, 95% CI = 0.97 to 0.99); intake of fruits showed a weaker inverse association (100 g/d increased intake of total fruits, HR = 0.99, 95% CI = 0.98 to 1.00). The reduced risk of cancer associated with high vegetable intake was restricted to women (HR = 0.98, 95% CI = 0.97 to 0.99). Stratification by alcohol intake suggested a stronger reduction in risk in heavy drinkers and was confined to cancers caused by smoking and alcohol. CONCLUSIONS A very small inverse association between intake of total fruits and vegetables and cancer risk was observed in this study. Given the small magnitude of the observed associations, caution should be applied in their interpretation.

Association between Pre-Diagnostic Circulating Vitamin D Concentration and Risk of Colorectal Cancer in European Populations: a Nested Case-Control Study

Objective To examine the association between pre-diagnostic circulating vitamin D concentration, dietary intake of vitamin D and calcium, and the risk of colorectal cancer in European populations. Design Nested case-control study. Setting The study was conducted within the EPIC study, a cohort of more than 520 000 participants from 10 western European countries. Participants 1248 cases of incident colorectal cancer, which developed after enrolment into the cohort, were matched to 1248 controls Main outcome measures Circulating vitamin D concentration (25-hydroxy-vitamin-D, 25-(OH)D) was measured by enzyme immunoassay. Dietary and lifestyle data were obtained from questionnaires. Incidence rate ratios and 95% confidence intervals for the risk of colorectal cancer by 25-(OH)D concentration and levels of dietary calcium and vitamin D intake were estimated from multivariate conditional logistic regression models, with adjustment for potential dietary and other confounders. Results 25-(OH)D concentration showed a strong inverse linear dose-response association with risk of colorectal cancer (P for trend <0.001). Compared with a pre-defined mid-level concentration of 25-(OH)D (50.0-75.0 nmol/l), lower levels were associated with higher colorectal cancer risk (<25.0 nmol/l: incidence rate ratio 1.32 (95% confidence interval 0.87 to 2.01); 25.0-49.9 nmol/l: 1.28 (1.05 to 1.56), and higher concentrations associated with lower risk (75.0-99.9 nmol/l: 0.88 (0.68 to 1.13); ≥100.0 nmol/l: 0.77 (0.56 to 1.06)). In analyses by quintile of 25-(OH)D concentration, patients in the highest quintile had a 40% lower risk of colorectal cancer than did those in the lowest quintile (P<0.001). Subgroup analyses showed a strong association for colon but not rectal cancer (P for heterogeneity=0.048). Greater dietary intake of calcium was associated with a lower colorectal cancer risk. Dietary vitamin D was not associated with disease risk. Findings did not vary by sex and were not altered by corrections for season or month of blood donation. Conclusions The results of this large observational study indicate a strong inverse association between levels of pre-diagnostic 25-(OH)D concentration and risk of colorectal cancer in western European populations. Further randomised trials are needed to assess whether increases in circulating 25-(OH)D concentration can effectively decrease the risk of colorectal cancer.

Variability of fish consumption within the 10 European countries participating in the European Investigation into Cancer and Nutrition (EPIC) study

OBJECTIVE To describe and compare the consumption of total fish (marine foods) and the fish sub-groups - white fish, fatty fish, very fatty fish, fish products and crustacea, in participants from the European Investigation into Cancer and Nutrition (EPIC) study. DESIGN Cross-sectional analysis of dietary intake using a computerised standardised 24-hour recall interview. Crude means, means and standard errors adjusted by age, season and day of the week were calculated, stratified by centre and gender. SETTING Twenty-seven redefined centres in the 10 European countries participating in the EPIC study. SUBJECTS In total, 35 955 subjects (13 031 men and 22 924 women), aged 35-74 years, selected from the main EPIC cohort. RESULTS A six- to sevenfold variation in total fish consumption exists in women and men, between the lowest consumption in Germany and the highest in Spain. Overall, white fish represented 49% and 45% of the intake of total fish in women and men, respectively, with the greatest consumption in centres in Spain and Greece and the least in the German and Dutch centres. Consumption of fatty fish reflected that of total fish. However, the greatest intake of very fatty fish was in the coastal areas of northern Europe (Denmark, Sweden and Norway) and in Germany. Consumption of fish products was greater in northern than in southern Europe, with white fish products predominating in centres in France, Italy, Spain, The Netherlands and Norway. Intake of roe and roe products was low. The highest consumption of crustacea was found in the French, Spanish and Italian centres. The number of fish types consumed was greater in southern than in northern Europe. The greatest variability in consumption by day of the week was found in the countries with the lowest fish intake. CONCLUSIONS Throughout Europe, substantial geographic variation exists in total fish intake, fish sub-groups and the number of types consumed. Day-to-day variability in consumption is also high.

Daily duration of vitamin D synthesis in human skin with relation to latitude, total ozone, altitude, ground cover, aerosols and cloud thickness.

Abstract Vitamin D production in human skin occurs only when incident UV radiation exceeds a certain threshold. From simulations of UV irradiances worldwide and throughout the year, we have studied the dependency of the extent and duration of cutaneous vitamin D production in terms of latitude, time, total ozone, clouds, aerosols, surface reflectivity and altitude. For clear atmospheric conditions, no cutaneous vitamin D production occurs at 51 degrees latitude and higher during some periods of the year. At 70 degrees latitude, vitamin D synthesis can be absent for 5 months. Clouds, aerosols and thick ozone events reduce the duration of vitamin D synthesis considerably, and can suppress vitamin D synthesis completely even at the equator. A web page allowing the computation of the duration of cutaneous vitamin D production worldwide throughout the year, for various atmospheric and surface conditions, is available on the Internet at http://zardoz.nilu.no/~olaeng/fastrt/VitD.html and http://zardoz.nilu.no/~olaeng/fastrt/VitD-ez.html. The computational methodology is outlined here.

Evaluation of under- and overreporting of energy intake in the 24-hour diet recalls in the European Prospective Investigation into Cancer and Nutrition (EPIC)

OBJECTIVE To evaluate under- and overreporting and their determinants in the EPIC 24-hour diet recall (24-HDR) measurements collected in the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN Cross-sectional analysis. 24-HDR measurements were obtained by means of a standardised computerised interview program (EPIC-SOFT). The ratio of reported energy intake (EI) to estimated basal metabolic rate (BMR) was used to ascertain the magnitude, impact and determinants of misreporting. Goldbergs cut-off points were used to identify participants with physiologically extreme low or high energy intake. At the aggregate level the value of 1.55 for physical activity level (PAL) was chosen as reference. At the individual level we used multivariate statistical techniques to identify factors that could explain EI/BMR variability. Analyses were performed by adjusting for weight, height, age at recall, special diet, smoking status, day of recall (weekday vs. weekend day) and physical activity. SETTING Twenty-seven redefined centres in the 10 countries participating in the EPIC project. SUBJECTS In total, 35 955 men and women, aged 35-74 years, participating in the nested EPIC calibration sub-studies. RESULTS While overreporting has only a minor impact, the percentage of subjects identified as extreme underreporters was 13.8% and 10.3% in women and men, respectively. Mean EI/BMR values in men and women were 1.44 and 1.36 including all subjects, and 1.50 and 1.44 after exclusion of misreporters. After exclusion of misreporters, adjusted EI/BMR means were consistently less than 10% different from the expected value of 1.55 for PAL (except for women in Greece and in the UK), with overall differences equal to 4.0% and 7.4% for men and women, respectively. We modelled the probability of being an underreporter in association with several individual characteristics. After adjustment for age, height, special diet, smoking status, day of recall and physical activity at work, logistic regression analyses resulted in an odds ratio (OR) of being an underreporter for the highest vs. the lowest quartile of body mass index (BMI) of 3.52 (95% confidence interval (CI) 2.91-4.26) in men and 4.80 (95% CI 4.11-5.61) in women, indicating that overweight subjects are significantly more likely to underestimate energy intake than subjects in the bottom BMI category. Older people were less likely to underestimate energy intake: ORs were 0.58 (95% CI 0.45-0.77) and 0.74 (95% CI 0.63-0.88) for age (> or =65 years vs. <50 years). Special diet and day of the week showed strong effects. CONCLUSION EI tends to be underestimated in the vast majority of the EPIC centres, although to varying degrees; at the aggregate level most centres were below the expected reference value of 1.55. Underreporting seems to be more prevalent among women than men in the EPIC calibration sample. The hypothesis that BMI (or weight) and age are causally related to underreporting seems to be confirmed in the present work. This introduces further complexity in the within-group (centre or country) and between-group calibration of dietary questionnaire measurements to deattenuate the diet-disease relationship.

Vitamin D status of middle-aged women at 65–71°N in relation to dietary intake and exposure to ultraviolet radiation

Objective: To determine the vitamin D status of middle-aged women living in the Norwegian arctic and its relationship with vitamin D intake and exposure to ultraviolet (UV) radiation. Design: Cross-sectional study. Subjects and setting: This study is based on measurements of 25-hydroxyvitamin D (25(OH)D) levels in a sub-sample of the Norwegian component of the EPIC biological bank, which consists of blood samples from a random selection of participants in the Norwegian Women and Cancer Study. From November 2001 until June 2002, 309 blood samples were collected from a total of 443 invited middle-aged women (44–59 years) in northern Norway (65–718N) (crude response rate, 69.8%). Questionnaire data provided information on dietary sources of vitamin D and UV exposure. Results: Median plasma 25(OH)D concentration for the whole group was 55.0 nmol l 21 (range 8.1–142.8 nmol l 21 ). Vitamin D intake was a significant predictor of 25(OH)D status (P ¼ 0.0003). The time of the year when the blood sample was collected significantly predicted plasma 25(OH)D level (P ¼ 0.005). Levels of 25(OH)D were positively associated (P ¼ 0.0002) with estimated hours per day of exposure to UV-B radiation. Residing in northern Norway during the summer prior to blood sampling was negatively associated with 25(OH)D concentration (P ¼ 0.001). The prevalence of moderate hypovitaminosis D was highest in January–February, when a quarter of the participants had 25(OH)D concentrations #37.5 nmol l 21 . Conclusions: Increased ingestion of marine food items that provide vitamin D should be promoted and further studies should be carried out to investigate vitamin D status in arctic populations in relation to both UV exposure and traditional food sources.

Patterns of alcohol consumption in 10 European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) project

OBJECTIVE The aim of this study was to compare the quantities of alcohol and types of alcoholic beverages consumed, and the timing of consumption, in centres participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). These centres, in 10 European countries, are characterised by widely differing drinking habits and frequencies of alcohol-related diseases. METHODS We collected a single standardised 24-hour dietary recall per subject from a random sample of the EPIC cohort (36 900 persons initially and 35 955 after exclusion of subjects under 35 and over 74 years of age). This provided detailed information on the distribution of alcohol consumption during the day in relation to main meals, and was used to determine weekly consumption patterns. The crude and adjusted (by age, day of week and season) means of total ethanol consumption and consumption according to type of beverage were stratified by centre and sex. RESULTS Sex was a strong determinant of drinking patterns in all 10 countries. The highest total alcohol consumption was observed in the Spanish centres (San Sebastian, 41.4 g day-1) for men and in Danish centres (Copenhagen, 20.9 g day-1) for women. The lowest total alcohol intake was in the Swedish centres (Umeå, 10.2 g day-1) in men and in Greek women (3.4 g day-1). Among men, the main contributor to total alcohol intake was wine in Mediterranean countries and beer in the Dutch, German, Swedish and Danish centres. In most centres, the main source of alcohol for women was wine except for Murcia (Spain), where it was beer. Alcohol consumption, particularly by women, increased markedly during the weekend in nearly all centres. The German, Dutch, UK (general population) and Danish centres were characterised by the highest percentages of alcohol consumption outside mealtimes. CONCLUSIONS The large variation in drinking patterns among the EPIC centres provides an opportunity to better understand the relationship between alcohol and alcohol-related diseases.

Vitamin D – a systematic literature review for the 5th edition of the Nordic Nutrition Recommendations

Background The present literature review is part of the NNR5 project with the aim of reviewing and updating the scientific basis of the 4th edition of the Nordic Nutrition Recommendations (NNR) issued in 2004. Objectives The overall aim was to review recent scientific data on the requirements and health effects of vitamin D and to report it to the NNR5 Working Group, who is responsible for updating the current dietary reference values valid in the Nordic countries. Methods The electronic databases MEDLINE and Swemed were searched. We formulated eight questions which were used for the search. The search terms related to vitamin D status and intake and different health outcomes as well as to the effect of different vitamin D sources on vitamin D status. The search was done in two batches, the first covering January 2000–March 2010 and the second March 2009–February 2011. In the first search, we focused only on systematic literature reviews (SLRs) and in the second on SLRs and randomized control trials (RCTs) published after March 2009. Furthermore, we used snowballing for SLRs and IRCTs published between February 2011 and May 2012. The abstracts as well as the selected full-text papers were evaluated in pairs. Results We found 1,706 studies in the two searches of which 28 studies were included in our review. We found 7 more by snowballing, thus 35 papers were included in total. Of these studies, 31 were SLRs and 4 were RCTs. The SLRs were generally of good or fair quality, whereas that of the included studies varied from good to poor. The heterogeneity of the studies included in the SLRs was large which made it difficult to interpret the results and provide single summary statements. One factor increasing the heterogeneity is the large variation in the assays used for assessing 25-hydroxyvitamin D concentration [25(OH)D], the marker of vitamin D status. The SLRs we have reviewed conclude that the evidence for a protective effect of vitamin D is only conclusive concerning bone health, total mortality and the risk of falling. Moreover, the effect was often only seen in persons with low basal 25(OH)D concentrations. In addition, most intervention studies leading to these conclusions report that intervention with vitamin D combined with calcium and not vitamin D alone gives these benefits. It was difficult to establish an optimal 25(OH)D concentration or vitamin D intake based on the SLRs, but there are evidence that a concentration of ≥50 nmol/l could be optimal. The dose–response studies relating vitamin D intake (fortification and supplementation) to S-25(OH)D suggested that an intake of 1–2.5 µg/day will increase the serum concentration by 1–2 nmol/l but this is dependent on the basal concentration with a response being greater when the basal concentration is low. Conclusion Data show that a S-25(OH)D concentration of 50 nmol/l would reflect a sufficient vitamin D status. Results from this review support that the recommendation in NNR 2004 needs to be re-evaluated and increased for all age groups beyond 2 years of age. We refer to the total intake from food as well as supplements, given minimal sun exposure. Limited sunshine, however, does not reflect the situation for the majority of the Nordic population in the summertime. It should also be emphasized that there are large differences in results depending on assay methods and laboratories measuring 25(OH)D, adding to the uncertainty of determining an appropriate target concentration. Moreover, the dose–response of vitamin D on serum 25(OH)D-concentrations is not well established and is dependent on the basal concentrations, sunshine exposure and dietary intake. We advise that these uncertainties should be taken into account when setting the final Nordic recommendations.

Comparison of telephone vs face-to-face interviews in the assessment of dietary intake by the 24 h recall EPIC SOFT program—the Norwegian calibration study

Objective: To compare food group intakes in grams, total energy and energy contribution from macronutrients between two random samples of women, using a standardized computer program (EPIC SOFT) with either a face-to-face or a telephone 24 h recall interview design.Methods: Two groups of Norwegian women living in Tromsø were drawn at random from the Norwegian Women and Cancer Study (NOWAC) cohort. The EPIC SOFT computer program was used to conduct single 24 h dietary recalls either by telephone or face to face. For the latter, 160 women were invited, of whom 111 responded positively (crude response rate=69.4%) and 102 were interviewed. For the telephone option, 180 were invited to participate, 109 responded positively (crude response rate=60.6%) and 103 were interviewed.Results: The two groups of women were similar with respect to age, body mass index, basal metabolic rate, smoking, education, physical activity and special diet status. No statistically significant difference in dietary intake was found between interviews conducted by telephone and face-to-face, except for ‘egg and egg products’ (P<0.01), for which intake was higher in the telephone group. Total energy intake differed, but the difference was attributable to one interviewer. The distribution of energy-contributing nutrients was not significantly different between groups, except for reported energy percentage from protein (P=0.02), which was significantly higher in the face-to-face group.Conclusion: The telephone vs face-to-face interview design did not influence recalled diet when using the EPIC SOFT program.

Vitamin D: a candidate for the environmental effect in multiple sclerosis - observations from Norway.

Multiple sclerosis (MS) is a chronic disease of the central nervous system, pathologically characterized by inflammation, demyelination, and axonal damage, presumably auto-immune in nature. Complex interactions between genetic susceptibility and environmental factors, such as vitamin D status and primary Epstein-Barr virus infection in adolescence or later in life, probably determine the MS risk. Norway at a latitude 58–71°N is a discrete exception to the hypothesis that solar UV radiation exposure, mediated by vitamin D, coheres with the latitude gradient seen for MS prevalence. Where UV radiation exposure is low in Norway,vitamin D sufficiency is maintained through a traditional diet providing vitamin D as well as marine omega–3 polyunsaturated fatty acids. This observation supports an environmental interaction between diet and latitude, with vitamin D as the common mediator. The potential roles of vitamin D, other environmental exposures, and genes in the complex aetiology of MS are discussed in this review.