Ulrika Ericson

Fat and carbohydrate intake modify the association between genetic variation in the FTO genotype and obesity

BACKGROUND The fat mass and obesity-associated gene (FTO) has been shown to be associated with obesity and to influence appetite regulation. OBJECTIVE The aim was to examine whether dietary factors (macronutrient and fiber intakes) and leisure-time physical activity modify the association between genetic variation in FTO and body mass index (BMI; in kg/m(2)). DESIGN A cross-sectional study examined 4839 subjects in the population-based Malmö Diet and Cancer study with dietary data (from a modified diet history method) and information on the genetic variant FTO (rs9939609). Direct anthropometric measures were made, and leisure-time physical activity was determined from the duration participants spent on 18 different physical activities. RESULTS Significant interactions between energy-adjusted fat intake and FTO genotype (P = 0.04) and between carbohydrate intake and FTO genotype (P = 0.001) on BMI were observed. The observed increase in BMI across FTO genotypes was restricted to those who reported a high-fat diet, with a mean BMI of 25.3 (95% CI: 24.9, 25.6) among TT carriers and of 26.3 (95% CI: 25.8, 26.8) among AA carriers (P = 0.0001). The FTO variant was not associated with a higher BMI among subjects with lower fat intakes (BMI = 25.7 and 25.9 in TT carriers and AA carriers, respectively; P = 0.42). Among individuals with a low-carbohydrate intake, we observed a mean BMI of 25.4 for TT carriers and of 26.8 for AA carriers. The increase in BMI across genotypes was mainly restricted to individuals who reported low leisure-time physical activity (P for trend = 0.004, P for interaction = 0.05). CONCLUSION Our results indicate that high-fat diets and low physical activity levels may accentuate the susceptibility to obesity by the FTO variant.

Dietary Fibre Intake and Risks of Cancers of the Colon and Rectum in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Background Earlier analyses within the EPIC study showed that dietary fibre intake was inversely associated with colorectal cancer risk, but results from some large cohort studies do not support this finding. We explored whether the association remained after longer follow-up with a near threefold increase in colorectal cancer cases, and if the association varied by gender and tumour location. Methodology/Principal Findings After a mean follow-up of 11.0 years, 4,517 incident cases of colorectal cancer were documented. Total, cereal, fruit, and vegetable fibre intakes were estimated from dietary questionnaires at baseline. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models stratified by age, sex, and centre, and adjusted for total energy intake, body mass index, physical activity, smoking, education, menopausal status, hormone replacement therapy, oral contraceptive use, and intakes of alcohol, folate, red and processed meats, and calcium. After multivariable adjustments, total dietary fibre was inversely associated with colorectal cancer (HR per 10 g/day increase in fibre 0.87, 95% CI: 0.79–0.96). Similar linear associations were observed for colon and rectal cancers. The association between total dietary fibre and risk of colorectal cancer risk did not differ by age, sex, or anthropometric, lifestyle, and dietary variables. Fibre from cereals and fibre from fruit and vegetables were similarly associated with colon cancer; but for rectal cancer, the inverse association was only evident for fibre from cereals. Conclusions/Significance Our results strengthen the evidence for the role of high dietary fibre intake in colorectal cancer prevention.

A diabetes-predictive amino acid score and future cardiovascular disease

AIMS We recently identified a metabolic signature of three amino acids (tyrosine, phenylalanine, and isoleucine) that strongly predicts diabetes development. As novel modifiable targets for intervention are needed to meet the expected increase of cardiovascular disease (CVD) caused by the diabetes epidemic, we investigated whether this diabetes-predictive amino acid score (DM-AA score) predicts development of CVD and its functional consequences. METHODS AND RESULTS We performed a matched case-control study derived from the population-based Malmö Diet and Cancer Cardiovascular Cohort (MDC-CC), all free of CVD. During 12 years of follow-up, 253 individuals developed CVD and were matched for age, sex, and Framingham risk score with 253 controls. Amino acids were profiled in baseline plasma samples, using liquid chromatography-tandem mass spectrometry, and relationship to incident CVD was assessed using conditional logistic regression. We further examined whether the amino acid score also correlated with anatomical [intima-media thickness (IMT) and plaque formation] and functional (exercise-induced myocardial ischaemia) abnormalities. Compared with the lowest quartile of the DM-AA score, the odds ratio (95% confidence interval) for incident CVD in subjects belonging to quartiles 2, 3, and 4 was 1.27 (0.72-2.22), 1.96 (1.07-3.60), and 2.20 (1.12-4.31) (Ptrend = 0.010), respectively, after multivariate adjustment. Increasing quartile of the DM-AA score was cross-sectionally related to carotid IMT (Ptrend = 0.037) and with the presence of at least one plaque larger than 10 mm(2) (Ptrend = 0.001). Compared with the lowest quartile of the DM-AA score, the odds ratio (95% confidence interval) for inducible ischaemia in subjects belonging to quartiles 2, 3, and 4 was 3.31 (1.05-10.4), 4.24 (1.36-13.3), and 4.86 (1.47-16.1) (Ptrend = 0.011), respectively. CONCLUSION This study identifies branched-chain and aromatic amino acids as novel markers of CVD development and as an early link between diabetes and CVD susceptibility.

Gene × Physical Activity Interactions in Obesity: Combined Analysis of 111,421 Individuals of European Ancestry

Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age2, sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS × physical activity interaction effect estimate (Pinteraction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, Pinteraction = 0.014 vs. n = 71,611, Pinteraction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (Pinteraction = 0.003) and the SEC16B rs10913469 (Pinteraction = 0.025) variants showed evidence of SNP × physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.

Fruit and Vegetable Consumption and Mortality European Prospective Investigation Into Cancer and Nutrition

In this study, the relation between fruit and vegetable consumption and mortality was investigated within the European Prospective Investigation Into Cancer and Nutrition. Survival analyses were performed, including 451,151 participants from 10 European countries, recruited between 1992 and 2000 and followed until 2010. Hazard ratios, rate advancement periods, and preventable proportions to respectively compare risk of death between quartiles of consumption, to estimate the period by which the risk of death was postponed among high consumers, and to estimate proportions of deaths that could be prevented if all participants would shift their consumption 1 quartile upward. Consumption of fruits and vegetables was inversely associated with all-cause mortality (for the highest quartile, hazard ratio = 0.90, 95% confidence interval (CI): 0.86, 0.94), with a rate advancement period of 1.12 years (95% CI: 0.70, 1.54), and with a preventable proportion of 2.95%. This association was driven mainly by cardiovascular disease mortality (for the highest quartile, hazard ratio = 0.85, 95% CI: 0.77, 0.93). Stronger inverse associations were observed for participants with high alcohol consumption or high body mass index and suggested in smokers. Inverse associations were stronger for raw than for cooked vegetable consumption. These results support the evidence that fruit and vegetable consumption is associated with a lower risk of death.

Differences in dietary intakes, food sources and determinants of total flavonoids between Mediterranean and non-Mediterranean countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

A greater adherence to the traditional Mediterranean (MED) diet is associated with a reduced risk of developing chronic diseases. This dietary pattern is based on higher consumption of plant products that are rich in flavonoids. We compared the total flavonoid dietary intakes, their food sources and various lifestyle factors between MED and non-MED countries participating in the EPIC study. Flavonoid intakes and their food sources for 35,628 subjects, aged 35-74 years and recruited between 1992 and 2000, in twenty-six study centres were estimated using standardised 24 h dietary recall software (EPIC-Soft®). An ad hoc food composition database on flavonoids was compiled using analytical data from the United States Department of Agriculture and Phenol-Explorer databases. Moreover, it was expanded to include using recipes, estimations of missing values and flavonoid retention factors. No significant differences in total flavonoid mean intake between non-MED countries (373·7 mg/d) and MED countries (370·2 mg/d) were observed. In the non-MED region, the main contributors were proanthocyanidins (48·2%) and flavan-3-ol monomers (24·9%) and the principal food sources were tea (25·7%) and fruits (32·8%). In the MED region, proanthocyanidins (59·0%) were by far the most abundant contributor and fruits (55·1%), wines (16·7%) and tea (6·8%) were the main food sources. The present study shows similar results for total dietary flavonoid intakes, but significant differences in flavonoid class intakes, food sources and some characteristics between MED and non-MED countries. These differences should be considered in studies about the relationships between flavonoid intake and chronic diseases.

Plasma folate, related genetic variants and colorectal cancer risk in EPIC

Background: A potential dual role of folate in colorectal cancer (CRC) is currently subject to debate. We investigate the associations between plasma folate, several relevant folate-related polymorphisms, and CRC risk within the large European Prospective Investigation into Cancer and Nutrition cohort. Methods: In this nested case-control study, 1,367 incident CRC cases were matched to 2,325 controls for study center, age, and sex. Risk ratios (RR) were estimated with conditional logistic regression and adjusted for smoking, education, physical activity, and intake of alcohol and fiber. Results: Overall analyses did not reveal associations of plasma folate with CRC. The RR (95% confidence interval; Ptrend) for the fifth versus the first quintile of folate status was 0.94 (0.74-1.20; 0.44). The polymorphisms MTHFR677C→T, MTHFR1298A→C, MTR2756A→G, MTRR66A→G, and MTHFD11958G→A were not associated with CRC risk. However, in individuals with the lowest plasma folate concentrations, the MTHFR 677TT genotype showed a statistically nonsignificant increased CRC risk [RR (95% CI; Ptrend) TT versus CC = 1.39 (0.87-2.21); 0.12], whereas those with the highest folate concentrations showed a nonsignificant decreased CRC risk [RR TT versus CC = 0.74 (0.39-1.37); 0.34]. The SLC19A180G→A showed a positive association with CRC risk [RR AA versus GG 1.30 (1.06-1.59); <0.01]. Conclusions: This large European prospective multicenter study did not show an association of CRC risk with plasma folate status nor with MTHFR polymorphisms. Impact: Findings of the present study tend to weaken the evidence that folate plays an important role in CRC carcinogenesis. However, larger sample sizes are needed to adequately address potential gene-environment interactions. Cancer Epidemiol Biomarkers Prev; 19(5); 1328–40. ©2010 AACR.

Variation in intakes of calcium, phosphorus, magnesium, iron and potassium in 10 countries in the European Prospective Investigation into Cancer and Nutrition study.

Background/objectives:Adequate mineral intake is important for the maintenance of bone health, cellular function and general metabolism, and possibly in the aetiology of cancer and other chronic diseases. This study aimed at investigating variation in intakes of selected minerals across 10 European countries participating in the EPIC (European Prospective Investigation into Cancer and Nutrition) study.Methods:Nutrient intakes for 36 034 subjects, aged between 35 and 74 years, in 27 centres were obtained using standardized 24-h dietary recall software (EPIC-SOFT). Mean intakes of calcium, phosphorus, magnesium, iron and potassium were calculated by centre and weighted by season and day of the week and were also stratified by age group. The contribution of food groups to total nutrient intake was calculated.Results:There was clear geographical variability in intakes, with differences ranging from 35% for magnesium to 90% for iron in men and 36% for potassium to 75% for calcium in women, and a twofold difference in sources of haem iron (meat and fish). There was a geographical gradient in iron intake, with higher intakes in Southern than in Northern Europe and also around a twofold north–south gradient in the contribution of fruits and vegetables to potassium intake. Compared with reference intakes, the majority of age groups and centres had intakes above the recommended levels. Dairy foods and products contributed the most to calcium and phosphorus intake in almost all centres. Cereals and cereal products contributed the most to magnesium and iron intakes, except in Greece and Germany.Conclusions:Intakes of minerals vary substantially throughout Europe, with some geographical variability in their food sources.

Eating out of home: energy, macro- and micronutrient intakes in 10 European countries. The European Prospective Investigation into Cancer and Nutrition

Objectives:To assess the contribution of out-of-home (OH) energy and nutrient intake to total dietary intake, and to compare out- versus in-home nutrient patterns among 27 centres in 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Methods:Between 1995 and 2000, 36 034 participants aged between 35–74 years completed a standardized 24-h dietary recall using a software programme (EPIC-Soft) that recorded the place of food/drink consumption. Eating OH was defined as the consumption of foods and beverages anywhere other than in household premises, irrespective of the place of purchase/preparation. Nutrient intakes were estimated using a standardized nutrient database. Mean intakes were adjusted for age and weighted by season and day of recall.Results:Among women, OH eating contributed more to total fat intake than to intakes of protein and carbohydrates. Among both genders, and particularly in southern Europe, OH eating contributed more to sugar and starch intakes and less to total fibre intake. The contribution of OH eating was also lower for calcium and vitamin C intakes. The composition of diet at home was different from that consumed out of home in southern countries, but was relatively similar in the north.Conclusions:In northern Europe, OH and in-home eating are homogeneous, whereas southern Europeans consider OH eating as a distinctive occasion. In most centres, women selected more fat-rich items when eating out.

Food sources of fat may clarify the inconsistent role of dietary fat intake for incidence of type 2 diabetes

BACKGROUND Dietary fats could affect glucose metabolism and obesity development and, thereby, may have a crucial role in the cause of type 2 diabetes (T2D). Studies indicated that replacing saturated with unsaturated fats might be favorable, and plant foods might be a better choice than animal foods. Nevertheless, epidemiologic studies suggested that dairy foods are protective. OBJECTIVE We hypothesized that, by examining dietary fat and its food sources classified according to fat type and fat content, some clarification regarding the role of dietary fat in T2D incidence could be provided. DESIGN A total of 26,930 individuals (61% women), aged 45-74 y, from the Malmö Diet and Cancer cohort were included in the study. Dietary data were collected by using a modified diet-history method. During 14 y of follow-up, 2860 incident T2D cases were identified. RESULTS Total intake of high-fat dairy products (regular-fat alternatives) was inversely associated with incident T2D (HR for highest compared with lowest quintiles: 0.77; 95% CI: 0.68, 0.87; P-trend < 0.001). Most robust inverse associations were seen for intakes of cream and high-fat fermented milk (P-trend < 0.01) and for cheese in women (P-trend = 0.02). High intake of low-fat dairy products was associated with increased risk, but this association disappeared when low- and high-fat dairy were mutually adjusted (P-trend = 0.18). Intakes of both high-fat meat (P-trend = 0.04) and low-fat meat (P-trend < 0.001) were associated with increased risk. Finally, we did not observe significant association between total dietary fat content and T2D (P-trend = 0.24), but intakes of saturated fatty acids with 4-10 carbons, lauric acid (12:0), and myristic acid (14:0) were associated with decreased risk (P-trend < 0.01). CONCLUSIONS Decreased T2D risk at high intake of high- but not of low-fat dairy products suggests that dairy fat partly could have contributed to previously observed protective associations between dairy intake and T2D. Meat intake was associated with increased risk independently of the fat content.