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Abstract Background Epidemiological evidence on weight change and atrial fibrillation (AF) remains limited and inconsistent. Previous studies on body mass index (BMI) in youth and AF rarely considered subsequent BMI. This study aimed to assess the associations of AF with weight change and BMI in youth, as well as modified effect by genetic susceptibility of AF. Methods The study included 21,761 individuals (mean age 57.8 years) from the Malmö Diet and Cancer cohort. Weight information was obtained at three time points, including recalled weight at age 20 years, measured weight at baseline (middle adulthood), and reported weight at 5-year follow-up examination (late middle adulthood). A weighted genetic risk score of AF was created using 134 variants. Results During a median follow-up of 23.2 years, a total of 4038 participants developed AF. The association between weight change from early to middle adulthood and AF risk was modified by sex (P interaction = 0.004); weight loss was associated with a lower AF risk in females, but not in males. Conversely, weight gain was positively associated with AF risk in a linear manner in females, whereas increased AF risk appeared only when weight gain exceeded a threshold in males. Participants with weight gain of > 5 kg from middle to late middle adulthood had a 19% higher risk of AF relative to those with stable weight, whereas weight loss showed a null association. Compared to individuals with a lower BMI at age 20 years, those with a BMI above 25 kg/m2 had an increased risk of AF (HR = 1.14; 95% CI: 1.02–1.28), after controlling for baseline BMI; this association was more pronounced in males or those with a lower genetic risk of AF. Conclusions Weight gain in middle adulthood was associated with higher AF risk. Weight loss from early to middle adulthood, but not from middle to late middle adulthood, was associated with a lower risk of AF only in females. Higher BMI in youth was associated with an increased risk of AF, particularly among males or those with a lower genetic risk of AF.

Summary: Background: Nutri-Score is a scientifically validated 5-color front-of-pack nutrition label reflecting the nutrient profile of foods. It has been implemented in several European countries on a voluntary basis, pending the revision of the European labeling regulation. Hence, scientific evidence is needed regarding the ability of the nutrient profile underlying the Nutri-Score (uNS-NPS, 2023-updated version) to characterize healthier foods. Our objective was therefore to study the prospective association between the nutritional quality of diet characterized by the uNS-NPS and the risk of cardiovascular diseases in a large European population. Methods: Our analyses included 345,533 participants from the European Prospective Investigation into Cancer and Nutrition study (EPIC, 1992–2010, 7 European countries). Food intakes were assessed at baseline using country-specific dietary questionnaires. The uNS-NPS was calculated as a continuous scale for each food, based on its 100 g content of energy, sugars, saturated fatty acids, salt, fibre, and protein and percentage content of fruit, vegetables, and pulses. A dietary index was derived at the individual level (uNS-NPS DI: energy-weighted mean of uNS-NPS scores of all foods consumed by a participant). Cardiovascular events during follow-up were retrieved using country-specific methods (self-report, registry data). Multi-adjusted Cox models were computed. Findings: Overall, 16,214 first cardiovascular events were reported (median follow-up: 12.3 years; 4,103,133 person-years). The consumption of foods with a higher uNS-NPS score (reflecting a lower overall nutritional quality of diet) was associated with higher risks of total cardiovascular events (Hazards Ratio (HR) for an increment of 1 standard deviation: 1.03 (95% Confidence Interval 1.01–1.05)), especially myocardial infarction (HR = 1.03 (1.01–1.07)), and stroke (HR = 1.04 (1.01–1.07)). Interpretation: In this large prospective study among European adults, a higher risk of cardiovascular diseases (total and several subtypes) was observed in individuals consuming a diet with a lower nutritional value, as graded by the uNS-NPS score. This brings new evidence on the relevance of the updated nutrient profile underlying the Nutri-Score to characterize foods with a healthier nutrient profile. Funding: EPIC-CVD was supported by EU FP7, ERC, UK MRC, British Heart Foundation, and UK NIHR.

Background: Coffee, tea, sugar-sweetened beverages (SSBs), and low- and no-calorie sweetened beverages (LNCSBs) are generally frequently consumed in the Nordic and Baltic countries. These beverages have also been related to potential health effects. This scoping review describes the evidence for the role of coffee, tea, SSBs, and LNCSBs for health-related outcomes as a basis for setting and updating food-based dietary guidelines. We used evidence from several qualified systematic reviews (i.e. World Cancer Research Fund, US Dietary Guidelines Advisory Committee, European Food Safety Authority, and World Health Organization) and performed a search for additional systematic reviews. The evidence suggests that moderate coffee and tea consumption do not have long-term adverse health effects. The long-term favorable effects of coffee consumption are related to reduced risk of endometrial and liver cancer, type 2 diabetes, and cardiovascular deaths. However, results from randomized controlled trials (RCTs) suggest that coffee brews that are rich in diterpenes, such as boiled coffee, increase serum cholesterol concentrations. High caffeine intake in pregnancy is associated with higher risk of pregnancy loss, preterm birth, and low birth weight. High consumption of SSBs has been associated with increased risk of obesity, type 2 diabetes, hypertension, and cardiovascular disease, based on data from RCTs and prospective cohort studies. The consumption of LNCSBs may result in a small reduction in body weight in adults, likely mediated through the effect of reduced energy intake, but has neutral effects on other cardiometabolic risk markers using evidence from RCTs. However, evidence from observational studies indicates increased risk of cardiometabolic diseases among high LNCSB consumers. In conclusion, current evidence suggests that moderate coffee and tea consumption have no long-term adverse health effects. The evidence of beneficial effects of coffee consumption on liver and endometrial cancer risk, and some cardiovascular outcomes, comes from observational studies. High consumption of boiled coffee should be avoided due to negative effect on lipid profile. Pregnant women should not exceed the recommended daily dose of caffeine intake of 200 mg set by the European Food Safety Authority as a safe level for the fetus. High consumption of SSBs has consistently been associated with adverse health effects, which is mainly due to excess energy intake, and should be limited. The conflicting results from RCTs and observational studies regarding LNCSBs may be due to revere causation and should be explored further.

The market for artificial sweeteners as substitutes for conventional sugar (sucrose) is growing, despite potential health risks associated with their intake. Estimating population usage of artificial sweeteners is therefore crucial, and wastewater analysis can serve as a complement to existing methods. This study evaluated spatial and temporal usage of artificial sweeteners in five Swedish communities based on wastewater analysis. We further compared their levels measured in wastewater with the restrictions during the COVID-19 pandemic in Sweden and assessed health risks to the Swedish population. Influent wastewater samples (n = 194) collected in March 2019-February 2022 from communities in central and southern Sweden were analyzed for acesulfame, saccharin, and sucralose using liquid-chromatography coupled with tandem mass spectrometry. Spatial differences in loads for individual artificial sweetener were observed, with sucralose being higher in Kalmar (southern Sweden), and acesulfame and saccharin in Enköping and Östhammar (central Sweden). Based on sucrose equivalent doses, all communities showed a consistent prevalence pattern of sucralose > acesulfame > saccharin. Four communities with relatively short monitoring periods showed no apparent temporal changes in usage, but the four-year monitoring in Uppsala revealed a significant (p

Abstract Background About one in ten adults are living with diabetes worldwide. Intake of carbohydrates and carbohydrate-rich foods are often identified as modifiable risk factors for incident type 2 diabetes. However, strong correlation between food variables can make it difficult to identify true associations. The purpose of this study was to identify clusters of carbohydrate-rich foods and analyse their associations with type 2 diabetes incidence in the Malmö Diet and Cancer Study cohort in southern Sweden. Methods Dietary intake of 26 622 participants was assessed using a validated three-part diet history method: a 7-day food diary, a 168-item food frequency questionnaire, and a 60-minute interview. K-means clustering analysis identified five clusters from 21 food variables. The Cox proportional hazard regression model was applied to calculate hazard ratios (HR) and 95% confidence intervals (CI) of the association between clusters and incident type 2 diabetes. Results The cluster analysis resulted in five clusters; high vegetables/low added sugar, high sugar-sweetened beverages, high juice, high fruit, and high refined carbohydrates/low fruit & vegetables (reference). During mean follow-up of 18 years, 4046 type 2 diabetes cases were identified. After adjustment for potential confounding (including lifestyle, body mass index, and diet), a high fruit cluster (HR 0.86; 95% CI 0.78, 0.94) was inversely associated with type 2 diabetes compared to the reference cluster. No other significant associations were identified. Conclusions A dietary pattern defined by a high intake of fruits was associated with a lower incidence of type 2 diabetes. The findings provide additional evidence of a potential protective effect from fruit intake in reducing type 2 diabetes risk. Future studies are needed to explore this association further.

Abstract Background We aim to examine the association between ultra-processed foods (UPF) consumption and cardiovascular disease (CVD) risk and to identify plasma proteins associated with UPF. Methods This prospective cohort study included 26,369 participants from the Swedish Malmö Diet and Cancer Study, established in 1991–1996. Dietary intake was assessed using a modified diet history method, and UPF consumption was estimated using the NOVA classification system. A total of 88 selected CVD-related proteins were measured among 4475 subjects. Incident CVD (coronary heart disease and ischemic stroke) was defined as a hospital admission or death through registers. Cox proportional hazards regression models were performed to analyze the associations of UPF intake with risks of CVD. Linear regression models were used to identify the plasma proteins associated with UPF intake. Results During 24.6 years of median follow-up, 6236 participants developed CVD, of whom 3566 developed coronary heart disease and 3272 developed ischemic stroke. The adjusted hazard ratio (95% confidence interval) in the 4th versus 1st quartile of UPF was 1.18 (1.08, 1.29) for CVD, 1.20 (1.07, 1.35) for coronary heart disease, and 1.17 (1.03, 1.32) for ischemic stroke. Plasma proteins interleukin 18, tumor necrosis factor receptor 2, macrophage colony-stimulating factor 1, thrombomodulin, tumor necrosis factor receptor 1, hepatocyte growth factor, stem cell factor, resistin, C–C motif chemokine 3, and endothelial cell-specific molecule 1 were positively associated with UPF after correcting for multiple testing. Conclusions Our study showed that high UPF intake increased the risk of CVD and was associated with several protein biomarkers. Future studies are warranted to validate these findings and assess the potential pathways between UPF intake and CVD.

Background: Dietary carbohydrates are a major source of energy in the Nordic and Baltic countries. The health effects of different types of carbohydrates vary and there is a need to update the evidence regarding specific carbohydrates and their effects on health-related outcomes. Objective: The aim of this scoping review was to describe the evidence for the role of total carbohydrates (fiber excluded), glycemic index (GI) or glycemic load (GL) and added or free sugars for health-related outcomes as a basis for setting and updating dietary reference values for the Nordic Nutrition Recommendation (NNR) 2023. Method: We included evidence from several qualified systematic reviews (the World Cancer Research Fund, the European Food Safety Authority, the World Health Organization, the United States Dietary Guidelines Advisory Committee, the United Kingdom Scientific Advisory Committee on Nutrition) identified by the NNR project in line with the protocol description. Results: There is limited evidence that total carbohydrate intake (fiber excluded) outside of the current recommended range of 45–60% of energy is associated with health-related outcomes. There were no consistent benefits on clinical outcomes when changing the GI of a diet. High intake of dietary sugars is well known to be associated with dental caries. There was evidence from randomized control trials on surrogate disease endpoints, for a positive and causal relationship between the intake of added and free sugars and risk of some chronic metabolic diseases with moderate level of certainty for obesity and dyslipidaemia. The level of certainty was high for an association between high intake of sugar-sweetened beverages and risk of several chronic metabolic diseases. Conclusion: While there is limited evidence that total carbohydrates and GI and GL of the diet are related to health outcomes, the evidence suggests that high intakes of added and free sugars are related to detrimental health effects. In addition, with increasing intake of added and free sugars, there is less room for healthy foods and micronutrients, which is especially important for those with low energy intake, such as children.

Abstract Background The EAT-Lancet Commission proposed a global reference diet with both human health benefits and environmental sustainability in 2019. However, evidence regarding the association of such a diet with the risk of atrial fibrillation (AF) is lacking. In addition, whether the genetic risk of AF can modify the effect of diet on AF remains unclear. This study aimed to assess the association of the EAT-Lancet diet with the risk of incident AF and examine the interaction between the EAT-Lancet diet and genetic susceptibility of AF. Methods This prospective study included 24,713 Swedish adults who were free of AF, coronary events, and stroke at baseline. Dietary habits were estimated with a modified diet history method, and an EAT-Lancet diet index was constructed to measure the EAT-Lancet reference diet. A weighted genetic risk score was constructed using 134 variants associated with AF. Cox proportional hazards regression models were applied to estimate the hazard ratio (HR) and 95% confidence interval (CI). Results During a median follow-up of 22.9 years, 4617 (18.7%) participants were diagnosed with AF. The multivariable HR (95% CI) of AF for the highest versus the lowest group for the EAT-Lancet diet index was 0.84 (0.73, 0.98) (P for trend

Abstract Background Salivary amylase, encoded by the AMY1 gene, initiate the digestion of starch. Whether starch intake or AMY1 copy number is related to disease risk is currently rather unknown. The aim was to investigate the association between starch intake and AMY1 copy number and risk of cardiovascular disease (CVD) and mortality and whether there is an interaction. In addition, we aim to identify CVD-related plasma proteins associated with starch intake and AMY1 copy number. Methods This prospective cohort study used data from 21,268 participants from the Malmö Diet and Cancer Study. Dietary data were collected through a modified diet history method and incident CVD and mortality were ascertained through registers. AMY1 gene copy number was determined by droplet digital polymerase chain reaction, a risk score of 10 genetic variants in AMY1 was measured, and a total of 88 selected CVD-related proteins were measured. Cox proportional hazards regression was used to analyze the associations of starch intake and AMY1 copy number with disease risk. Linear regression was used to identify plasma proteins associated with starch intake and AMY1 copy number. Results Over a median of 23 years’ follow-up, 4443 individuals developed CVD event and 8125 died. After adjusting for potential confounders, a U-shape association between starch intake and risk of CVD (P-nonlinearity = 0.001) and all-cause mortality (P-nonlinearity = 0.03) was observed. No significant association was found between AMY1 copy number and risk of CVD and mortality, and there were no interactions between starch intake and AMY1 copy number (P interaction > 0.23). Among the 88 plasma proteins, adrenomedullin, interleukin-1 receptor antagonist protein, fatty acid-binding protein, leptin, and C-C motif chemokine 20 were associated with starch intake after adjusting for multiple testing. Conclusions In this large prospective study among Swedish adults, a U-shaped association between starch intake and risk of CVD and all-cause mortality was found. Several plasma proteins were identified which might provide information on potential pathways for such association. AMY1 copy number was not associated with CVD risk or any of the plasma proteins, and there was no interaction between starch intake and AMY1 copy number on disease risk.

Abstract Parkinson’s disease (PD) and cardiovascular disease share many important risk factors, but some associations differ. However, there are no studies that have compared their shared and specific risk factors. The present study aimed to compare risk factors for PD, coronary events, or ischemic stroke. We prospectively analyzed data from 26,210 participants with lifestyle factors aged 45–73 years enrolled between 1991 and 1996. The Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of PD, coronary events, or ischemic stroke in relation to each factor. A modified Lunn-McNeil competing risk analysis was performed to compare the HR strength of the three outcomes. A total of 486 incident PD cases, 3288 coronary events cases and 2,972 ischemic stroke cases occurred during a mean follow-up of 21 years. In multivariable models, age (per additional year: HR = 1.08; 95% CI: 1.06, 1.09), diabetes (HR = 1.52; 95% CI: 1.02, 2.26), neutrophil–lymphocyte ratio (per SD increase: HR = 1.09; 95% CI: 1.00, 1.19), and fasting blood glucose (per SD increase: HR = 1.18; 95% CI: 1.03, 1.36) are the risk factors for PD, whereas female sex (HR = 0.54; 95% CI: 0.43, 0.67), smoking (current smoker [HR = 0.57; 95% CI: 0.43, 0.74] and former smoker [HR = 0.81; 95% CI: 0.66, 0.99]), HDL (per SD increase: HR = 0.74; 95% CI: 0.57, 0.95), and LDL (per SD increase: HR = 0.77; 95% CI: 0.61, 0.96) are the protective factors. A comparison of risk factors for PD, coronary events, and ischemic stroke showed the three outcomes had concordant and discordant risk factors. Our results indicated the risk factor profiles for PD, coronary events, or ischemic stroke had many similarities, but also significant differences.

BackgroundEpidemiological studies have demonstrated an association between the degree of food processing in our diet and the risk of various chronic diseases. Much of this evidence is based on the international Nova classification system, which classifies food into four groups based on the type of processing: (1) Unprocessed and minimally processed foods, (2) Processed culinary ingredients, (3) Processed foods, and (4) “Ultra-processed” foods (UPF). The ability of the Nova classification to accurately characterise the degree of food processing across consumption patterns in various European populations has not been investigated so far. Therefore, we applied the Nova coding to data from the European Prospective Investigation into Cancer and Nutrition (EPIC) in order to characterize the degree of food processing in our diet across European populations with diverse cultural and socio-economic backgrounds and to validate this Nova classification through comparison with objective biomarker measurements.MethodsAfter grouping foods in the EPIC dataset according to the Nova classification, a total of 476,768 participants in the EPIC cohort (71.5% women; mean age 51 [standard deviation (SD) 9.93]; median age 52 [percentile (p)25–p75: 58–66] years) were included in the cross-sectional analysis that characterised consumption patterns based on the Nova classification. The consumption of food products classified as different Nova categories were compared to relevant circulating biomarkers denoting food processing, measured in various subsamples (N between 417 and 9,460) within the EPIC cohort via (partial) correlation analyses (unadjusted and adjusted by sex, age, BMI and country). These biomarkers included an industrial transfatty acid (ITFA) isomer (elaidic acid; exogenous fatty acid generated during oil hydrogenation and heating) and urinary 4-methyl syringol sulfate (an indicator for the consumption of smoked food and a component of liquid smoke used in UPF).ResultsContributions of UPF intake to the overall diet in % grams/day varied across countries from 7% (France) to 23% (Norway) and their contributions to overall % energy intake from 16% (Spain and Italy) to >45% (in the UK and Norway). Differences were also found between sociodemographic groups; participants in the highest fourth of UPF consumption tended to be younger, taller, less educated, current smokers, more physically active, have a higher reported intake of energy and lower reported intake of alcohol. The UPF pattern as defined based on the Nova classification (group 4;% kcal/day) was positively associated with blood levels of industrial elaidic acid (r = 0.54) and 4-methyl syringol sulfate (r = 0.43). Associations for the other 3 Nova groups with these food processing biomarkers were either inverse or non-significant (e.g., for unprocessed and minimally processed foods these correlations were –0.07 and –0.37 for elaidic acid and 4-methyl syringol sulfate, respectively).ConclusionThese results, based on a large pan-European cohort, demonstrate sociodemographic and geographical differences in the consumption of UPF. Furthermore, these results suggest that the Nova classification can accurately capture consumption of UPF, reflected by stronger correlations with circulating levels of industrial elaidic acid and a syringol metabolite compared to diets high in minimally processed foods.

Abstract Background The association between leisure-time physical activity and cardiovascular mortality has been previously studied, but few studies have focused on specific activities and intensities. Methods The association between different leisure-time physical activities and cardiovascular mortality was investigated among 25,876 individuals without diabetes or cardiovascular disease from the population-based Malmö Diet and Cancer Study cohort. The individuals estimated the average duration spent on 17 physical activities at baseline in 1991–1996 and after 5 years. Cardiovascular mortality was obtained from a register during a mean of 20 years of follow-up. Results A total leisure-time physical activity of 15–25 metabolic equivalent task (MET) hours/week was associated with a decreased risk of cardiovascular mortality (HR 15–25 vs

BackgroundDiet and physical activity (PA) are modifiable risk factors thought to influence the risk of ischemic stroke (IS). However, few studies have examined their effect on different subtypes of IS.AimTo examine components of overall diet quality and different types of PA in relation to the risk of atherothrombotic IS (aIS).Materials and methodsThe study population included 23,797 participants (mean age 58 years; 63% women) from the Malmö Diet and Cancer Study cohort. Participants were enrolled between 1991 and 1996 and followed until end of 2016 (median follow-up 21.5 years). Incident aIS events were identified using national registries (total cases 1,937). Measures of PA (total, leisure-time, occupational, and domestic) were assessed using a baseline questionnaire and dietary intakes were estimated using a modified diet history method. Overall diet quality was assessed using a diet quality index. Intake of key food groups and beverages associated with overall diet quality were investigated separately. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using multivariable Cox regression models adjusting for confounders.ResultsA high diet quality with high intake of fruit and vegetables, fish and shellfish and low intake of sugar-sweetened beverages and red and processed meat compared to a low diet quality was associated with lower risk of aIS (HR = 0.82, 95% CI = 0.69–0.97; p = 0.015). Leisure-time PA was associated with reduced risk of aIS (HR = 0.95 per SD increase in MET-hours/week, 95% CI = 0.91–0.99; p = 0.028) with null associations observed for total, occupational and domestic PA level. We observed no significant interaction between diet and PA on the risk of aIS. The standardized 20-year risk of aIS among subjects with low leisure-time PA and low diet quality was 8.1% compared to 6.1% among those with high leisure-time PA and high diet quality.ConclusionSeveral components of a healthy diet and being physically active may reduce the risk of aIS, however, the absolute risk reduction observed was modest. A high diet quality seemed to have a risk reducing effect regardless of level of PA suggesting that individuals with a sedentary lifestyle may still gain some positive health benefits through a healthy diet.

Background: Dioxins and polychlorobiphenyls (PCBs) are persistent organic pollutants that have demonstrated endocrine disrupting properties. Several of these chemicals are carcinogenic and positive associations have been suggested with breast cancer risk. In general population, diet represents the main source of exposure. Methods: Associations between dietary intake of 17 dioxins and 35 PCBs and breast cancer were evaluated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from nine European countries using multivariable Cox regressions. The present study included 318,607 women (mean ± SD age: 50.7 ± 9.7) with 13,241 incident invasive breast cancers and a median follow-up of 14.9 years (IQR = 13.5–16.4). Dietary intake of dioxins and PCBs was assessed combining EPIC food consumption data with food contamination data provided by the European Food Safety Authority. Results: Exposure to dioxins, dioxins + Dioxin-Like-PCBs, Dioxin-Like-PCBs (DL-PCBs), and Non-Dioxin-Like-PCBs (NDL-PCBs) estimated from reported dietary intakes were not associated with breast cancer incidence, with the following hazard ratios (HRs) and 95% confidence intervals for an increment of 1 SD: HRdioxins = 1.00 (0.98 to 1.02), HRdioxins+DL-PCB = 1.01 (0.98 to 1.03), HRDL-PCB = 1.01 (0.98 to 1.03), and HRNDL-PCB = 1.01 (0.99 to 1.03). Results remained unchanged when analyzing intakes as quintile groups, as well as when analyses were run separately per country, or separating breast cancer cases based on estrogen receptor status or after further adjustments on main contributing food groups to PCBs and dioxins intake and nutritional factors. Conclusions: This large European prospective study does not support the hypothesis of an association between dietary intake of dioxins and PCBs and breast cancer risk.

Abstract Background Previous studies have shown that copy number variation (CNV) in the alpha (α)-amylase gene (AMY1A) is associated with body mass index, insulin resistance, and blood glucose levels, factors also shown to increase the risk of Alzheimer’s dementia (AD). We have previously demonstrated the presence of α-amylase in healthy neuronal dendritic spines and a reduction of the same in AD patients. In the current study, we investigate the relationship between AMY1A copy number and AD, memory performance, and brain α-amylase activity. Methods and materials The association between AMY1A copy number and development of AD was analyzed in 5422 individuals (mean age at baseline 57.5 ± 5.9, females 58.2%) from the Malmö diet and cancer study genotyped for AMY1A copy number, whereof 247 where diagnosed with AD during a mean follow-up of 20 years. Associations between AMY1A copy number and cognitive performance where analyzed in 791 individuals (mean age at baseline 54.7 ± 6.3, females 63%), who performed Montreal Cognitive Assessment (MoCA) test. Correlation analysis between α-amylase activity or α-amylase gene expression and AMY1A copy number in post-mortem hippocampal tissue from on demented controls (n = 8) and AD patients (n = 10) was also performed. Results Individuals with very high ( ≥10) AMY1A copy number had a significantly lower hazard ratio of AD (HR = 0.62, 95% CI 0.41–0.94) and performed significantly better on MoCA delayed word recall test, compared to the reference group with AMY1A copy number 6. A trend to lower hazard ratio of AD was also found among individuals with low AMY1A copy number (1–5) (HR = 0.74, 95% CI 0.53–1.02). A tendency towards a positive correlation between brain α-amylase activity and AMY1A copy number was found, and females showed higher brain α-amylase activity compared to males. Conclusion Our study suggests that the degree of α-amylase activity in the brain is affected by AMY1A copy number and gender, in addition to AD pathology. The study further suggests that very high AMY1A copy number is associated with a decreased hazard ratio of AD and we speculate that this effect is mediated via a beneficial impact of AMY1A copy number on episodic memory performance.

Abstract Background The evidence on the impact of high sugar consumption on micronutrient dilution does not yet allow for the establishment of clear thresholds of consumption. To establish upper and lower limit intake thresholds for added sugar, more studies from different countries and multiple populations are needed. The aim of this study was to examine the association between the intakes of added sugar and various micronutrients among the adult Swedish population across almost two decades. Methods The data were obtained from the samples from two populations: 1) Riksmaten Adults, a national dietary survey (n = 1797, 44% male, aged 18–80 years, data collection from 2010 to 11) that assessed dietary intake using a 4-day web-based food diary; and 2) the Malmö Diet and Cancer Study, a population-based cohort study (n = 12,238, 45% male, aged 45–68 years, data collection from 1991 to 1994) that assessed dietary intake via a combination of a 7-day food diary, a food frequency questionnaire and an interview. The mean daily intake of nine micronutrients (calcium, folate, iron, magnesium, potassium, selenium, vitamin C, vitamin D, and zinc), adjusted for age, sex, BMI and energy intake, were examined across six added-sugar-intake groups ( 20%E). Results We observed significant inverse associations between the intake of added sugar and the intake of all micronutrients in both populations. The associations were linear; however, we could not determine the threshold of added sugar intake beyond which the micronutrient intake was clearly compromised. Conclusions These findings suggest that in two Swedish populations the higher the intake of added sugar in the diet, the more likely it is that the intake of micronutrients will be compromised, in two Swedish populations. However, although the trends are significant and consistent with those obtained in other studies on the subject, future studies are needed in order to build the necessary scientific knowledge to establish a threshold of added sugar intake based on micronutrient dilution.

Abstract Background While a dose-response relationship between physical activity and risk of diabetes has been demonstrated, few studies have assessed the relative importance of different measures of physical activity on diabetes risk. The aim was to examine the association between different self-reported measures of physical activity and risk of type 2 diabetes in a prospective cohort study. Methods Out of 26,615 adults (45–74 years, 60% women) in the population-based Swedish Malmö Diet and Cancer Study cohort, 3791 type 2 diabetes cases were identified from registers during 17 years of follow-up. Leisure-time (17 activities), occupational and domestic physical activity were assessed through a questionnaire, and these and total physical activity were investigated in relation to type 2 diabetes risk. Results All physical activity measures showed weak to modest associations with type 2 diabetes risk. The strongest association was found in the lower end of leisure-time physical activity in dose-response analysis at levels approximately below 22 MET-hrs/week (300 min/week) representing around 40% of the population. Compared with the lowest quintile, the moderate leisure-time physical activity category had a 28% (95% CI: 0.71, 0.87) decreased risk of type 2 diabetes. Total physical activity showed a similar, but weaker, association with diabetes risk as to that of leisure-time physical activity. Domestic physical activity was positively and linearly related to diabetes risk, HR = 1.11 (95% CI: 0.99, 1.25) comparing highest to lowest quintile. There was no association between occupational physical activity and diabetes risk. Conclusion A curvilinear association was observed between leisure-time physical activity and risk of diabetes. Beyond a threshold level of approximately 22 MET-hrs/week or 300 min/week, no additional risk reduction was observed with increase in physical activity.

Polyphenols are bioactive compounds from plants with antioxidant properties that may have a protective role against body weight gain, with adipose tissue and systemic oxidative stress as potential targets. We aimed to investigate the dietary intake of individual polyphenols and their association with 5-year body weight change in a sub-cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). This study included 349,165 adult participants from nine European countries. Polyphenol intake was estimated through country-specific validated dietary questionnaires and the Phenol-Explorer database. Body weight was obtained at recruitment and after a mean follow-up time of 5 years. Associations were estimated using multilevel mixed linear regression models. From 91 polyphenols included, the majority (n = 67) were inversely associated with 5-year body weight change after FDR-correction (q < 0.05). The greatest inverse associations were observed for quercetin 3-O-rhamnoside (change in weight for doubling in intake: −0.071 (95% CI: −0.085; −0.056) kg/5 years). Only 13 polyphenols showed positive associations with body weight gain, mainly from the subclass hydroxycinnamic acids (HCAs) with coffee as the main dietary source, such as 4-caffeoylquinic acid (0.029 (95% CI: 0.021; 0.038) kg/5 years). Individual polyphenols with fruit, tea, cocoa and whole grain cereals as the main dietary sources may contribute to body weight maintenance in adults. Individual HCAs may have different roles in body weight change depending on their dietary source.

Background: Whether high dairy consumption is related to longevity is still unclear, and additional studies of prospective cohorts with high-quality dietary data from populations with wide consumption ranges are needed.Objective: To examine the association between dairy consumption and mortality in a Swedish cohort.Design: Among 26,190 participants (62% females, 45–73 years old) without diabetes and cardiovascular disease from the population-based Malmö Diet and Cancer cohort, 7,156 individuals died during a mean follow-up time of 19 years. Data on intake of dairy (non-fermented milk, fermented milk, cheese, cream and butter) were collected from 7 day food records and food questionnaires. A genetic marker (rs4988235) associated with lactase persistence was detected among 22,234 individuals born in Sweden.Results: Higher intakes up to 1,000 g/day of non-fermented milk were associated with only marginal higher mortality rates after adjusting for potential confounders. However, intakes above 1,000 g/day (1.5% of the population) were associated with 34% (95% CI: 14, 59%, p-trend=0.002) higher mortality compared to that with < 200 g/day. Fermented milk and cheese intake were inversely associated with mortality. Cream showed a protective association only among men. Butter was not associated with mortality. CT/TT genotype carriers (i.e., individuals with lactase persistence) had a 27% higher reported consumption of non-fermented milk, and non-significant higher mortality risk (HR = 1.08; 95% CI = 0.96, 1.23; p = 0.20) than CC genotype carriers.Conclusions: Higher mortality rates were mainly observed among participants consuming more than 1,000 g of non-fermented milk per day. In contrast, fermented milk and cheese were associated with lower mortality. Because dairy products differ in composition, it is important to examine them separately in their relation to health and disease. The use of a genetic variant as an objective marker of lactose-containing milk intake should be examined in relation to mortality in a larger population.

Salivary amylase initiates the digestion of starch and it has been hypothesized that salivary amylase may play a role in the development of insulin resistance and type 2 diabetes. The aim was to examine the interaction between copy number variation in the salivary amylase gene AMY1 and starch intake. We studied 3,624 adults without diabetes or elevated blood glucose in the Malmö Diet Cancer cohort. We assessed the associations and interactions between starch intake, AMY1 copies and glucose homeostasis traits (i.e., fasting plasma glucose, insulin and HOMA-IR) and risk of type 2 diabetes over an average of 18 follow-up years. AMY1 copy number was not associated with glucose, insulin or HOMA-IR. We observed a significant interaction between starch intake and AMY1 copies on insulin and HOMA-IR after adjusting for potential confounders (p < 0.05). The inverse association between starch intake and insulin and HOMA-IR was stronger in the group with 10 or more copies (Ptrend < 0.001). In addition, we observed an inverse association between starch intake and type 2 diabetes in the group with 10 or more copies (ptrend = 0.003), but not in the other groups. This cross-sectional observational study suggests that AMY1 copy numbers might interact with starch intake on glucose homeostasis traits. Interventional studies are required to determine whether individuals with high AMY1 copy numbers may benefit from a high starch intake.

Aims: Although diet is one of the main modifiable risk factors of cardiovascular disease, few studies have investigated the association between added sugar intake and cardiovascular disease risk. This study aims to investigate the associations between intake of total added sugar, different sugar-sweetened foods and beverages, and the risks of stroke, coronary events, atrial fibrillation and aortic stenosis.Methods: The study population consists of 25,877 individuals from the Malmö Diet and Cancer Study, a Swedish population-based prospective cohort. Dietary data were collected using a modified diet history method. National registers were used for outcome ascertainment.Results: During the mean follow-up of 19.5 years, there were 2,580 stroke cases, 2,840 coronary events, 4,241 atrial fibrillation cases, and 669 aortic stenosis cases. Added sugar intakes above 20 energy percentage were associated with increased risk of coronary events compared to the lowest intake category (HR: 1.39; 95% CI: 1.09–1.78), and increased stroke risk compared to intakes between 7.5 and 10 energy percentage (HR: 1.31; 95% CI: 1.03 and 1.66). Subjects in the lowest intake group for added sugar had the highest risk of atrial fibrillation and aortic stenosis. More than 8 servings/week of sugar-sweetened beverages were associated with increased stroke risk, while ≤2 servings/week of treats were associated with the highest risks of stroke, coronary events and atrial fibrillation.Conclusion: The results indicate that the associations between different added sugar sources and cardiovascular diseases vary. These findings emphasize the complexity of the studied associations and the importance of considering different added sugar sources when investigating health outcomes.

Studies on sugar intake and its link to cardiometabolic risk show inconsistent results, partly due to dietary misreporting. Cost-effective and easily measured nutritional biomarkers that can complement dietary data are warranted. Measurement of 24-h urinary sugars is a biomarker of sugar intake, but there are knowledge gaps regarding the use of overnight urine samples. We aim to compare (1) overnight urinary sucrose and fructose measured with liquid chromatography-tandem mass spectrometry, (2) self-reported sugar intake measured with web-based 4-day food records, (3) their composite measure, and (4) these different measures' (1–3) cross-sectional associations with cardiometabolic risk factors in 991 adults in the Malmö Offspring Study (18–69 years, 54% women). The correlations between the reported intakes of total sugar, added sugar and sucrose was higher for urinary sucrose than fructose, and the correlations for the sum or urinary sucrose and fructose (U-sugars) varied between r≈0.2–0.3 (P < 0.01) in men and women. Differences in the direction of associations were observed for some cardiometabolic risk factors between U-sugars and reported added sugar intake, as well as between the sexes. In women, U-sugars, but not reported added sugar intake, were positively associated with systolic and diastolic blood pressure and fasting glucose. Both U-sugars and added sugar were positively associated with BMI and waist circumference in women, whereas among men, U-sugars were negatively associated with BMI and waist circumference, and no association was observed for added sugar. The composite measure of added sugars and U-sugars was positively associated with BMI, waist circumference and systolic blood pressure and negatively associated with HDL cholesterol in women (P < 0.05). Conclusively, we demonstrate statistically significant, but not very high, correlations between reported sugar intakes and U-sugars. Results indicate that overnight urinary sugars may be used as a complement to self-reported dietary data when investigating associations between sugar exposure and cardiometabolic risk. However, future studies are highly needed to validate the overnight urinary sugars as a biomarker because its use, instead of 24-h urine, facilitates data collection.

With the rising prevalence of both diabetes mellitus (DM) and peripheral arterial disease (PAD), the aim of this project was to examine the association between dietary intake and lifestyle on the risk of developing PAD among individuals with DM. The Malmö Diet and Cancer study was a prospective cohort study with baseline examinations carried out between 1991 and 1996 in Malmö, Sweden ( n = 30,446). Individuals with prevalent PAD and cardiovascular disease (prior stroke or myocardial infarction) were excluded from the study, resulting in a total study population of 1112 patients with prevalent DM. The diagnosis of incident PAD was validated and confirmed in 98% of patients. Of the 1112 individuals, 136 (12.2%) were diagnosed with PAD during a median follow up of 19.7 years (interquartile range 12.9–22.4). Kaplan–Meier analysis showed that men with DM more often developed incident PAD compared with women (cumulative incidences 15.5% and 8.9%, respectively, p = 0.012). In Cox multivariable regression analysis, smoking (hazard ratio of 1.96, 95% confidence interval of 1.28–3.00) was associated with increased risk of PAD, and there was a trend that a higher intake of fish and shellfish (hazard ratio per additional gram per week of 0.99, 95% confidence interval of 0.99–1.00; p = 0.051) was associated with a decreased risk of PAD. In conclusion, the present study demonstrated a trend towards a protective effect of higher intake of fish and shellfish upon incident symptomatic PAD among individuals with DM.

Despite some epidemiological evidence on the protective effects of polyphenol intake on epithelial ovarian cancer (EOC) risk from case-control studies, the evidence is scarce from prospective studies and non-existent for several polyphenol classes. Therefore, we aimed to investigate the associations between the intake of total, classes and subclasses of polyphenols and EOC risk in a large prospective study. The study was conducted in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which included 309,129 adult women recruited mostly from the general population. Polyphenol intake was assessed through validated country-specific dietary questionnaires and the Phenol-Explorer database. During a mean follow-up of 14 years, 1469 first incident EOC cases (including 806 serous, 129 endometrioid, 102 mucinous, and 67 clear cell tumours) were identified. In multivariable-adjusted Cox regression models, the hazard ratio in the highest quartile of total polyphenol intake compared with the lowest quartile (HRQ4vsQ1) was 1.14 (95% CI 0.94–1.39; p-trend = 0.11). Similarly, the intake of most classes and subclasses of polyphenols were not related to either overall EOC risk or any EOC subtype. A borderline statistically significant positive association was observed between phenolic acid intake (HRQ4vsQ1 = 1.20, 95% CI 1.01–1.43; p-trend = 0.02) and EOC risk, especially for the serous subtype and in women with obesity, although these associations did not exceed the Bonferroni correction threshold. The current results do not support any association between polyphenol intake and EOC in our large European prospective study. Results regarding phenolic acid intake need further investigation

BackgroundHelping consumers make healthier food choices is a key issue for the prevention of cancer and other diseases. In many countries, political authorities are considering the implementation of a simplified labelling system to reflect the nutritional quality of food products. The Nutri-Score, a five-colour nutrition label, is derived from the Nutrient Profiling System of the British Food Standards Agency (modified version) (FSAm-NPS). How the consumption of foods with high/low FSAm-NPS relates to cancer risk has been studied in national/regional cohorts but has not been characterized in diverse European populations.Methods and findingsThis prospective analysis included 471,495 adults from the European Prospective Investigation into Cancer and Nutrition (EPIC, 1992-2014, median follow-up: 15.3 y), among whom there were 49,794 incident cancer cases (main locations: breast, n = 12,063; prostate, n = 6,745; colon-rectum, n = 5,806). Usual food intakes were assessed with standardized country-specific diet assessment methods. The FSAm-NPS was calculated for each food/beverage using their 100-g content in energy, sugar, saturated fatty acid, sodium, fibres, proteins, and fruits/vegetables/legumes/nuts. The FSAm-NPS scores of all food items usually consumed by a participant were averaged to obtain the individual FSAm-NPS Dietary Index (DI) scores. Multi-adjusted Cox proportional hazards models were computed. A higher FSAm-NPS DI score, reflecting a lower nutritional quality of the food consumed, was associated with a higher risk of total cancer (HRQ5 versus Q1 = 1.07; 95% CI 1.03-1.10, P-trend < 0.001). Absolute cancer rates in those with high and low (quintiles 5 and 1) FSAm-NPS DI scores were 81.4 and 69.5 cases/10,000 person-years, respectively. Higher FSAm-NPS DI scores were specifically associated with higher risks of cancers of the colon-rectum, upper aerodigestive tract and stomach, lung for men, and liver and postmenopausal breast for women (all P < 0.05). The main study limitation is that it was based on an observational cohort using self-reported dietary data obtained through a single baseline food frequency questionnaire; thus, exposure misclassification and residual confounding cannot be ruled out.ConclusionsIn this large multinational European cohort, the consumption of food products with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher risk of cancer. This supports the relevance of the FSAm-NPS as underlying nutrient profiling system for front-of-pack nutrition labels, as well as for other public health nutritional measures.

BackgroundThe preference for sweet taste is partially genetically determined. The major allele of the single nucleotide polymorphism rs12033832 in the sweet taste receptor (TAS1R2) has previously been associated with lower sugar sensitivity and higher sugar intake among overweight individuals. The aim of the present study was to examine the association between dietary intake and the TAS1R2 genotype in lean and overweight individuals in the population-based Malmö Diet and Cancer (MDC) cohort using dietary intake data with a high validity.MethodsIn total, 3,602 participants (46–68 years old) from the MDC cohort who underwent baseline examinations between 1991 and 1994, who were non-smokers without diabetes, and for whom information regarding TAS1R2 rs7534618 (a proxy for rs12033832) was available were included in this study. After excluding individuals with potentially misreported and unstable food habits, 2,204 individuals were retained. A modified dietary history method, including a 7-day food diary of prepared meals, which was specifically designed for the MDC study was used.ResultsOnly modest associations were observed between dietary intake and the TAS1R2 genotype. We observed slightly stronger associations after excluding individuals with potentially misreported and unstable food habits. Among the participants with a BMI ≥25, the major (T) allele carriers consumed more carbohydrates [TT = 45.2 percentage of energy intake (E%); TG = 45.2E%; GG = 43.7E%; p = 0.01] and less fat (p = 0.03), but these participants did not consume more sucrose than the G-allele carriers. No association was observed between the genotype and dietary intake among the participants with a BMI

Background: Earlier studies have indicated that the fat mass and obesity-associated gene (FTO) is not only associated with BMI and weight but also with appetite and dietary intake. Objectives: We investigated if the FTO rs9939609 associates with food preferences in healthy adults with no cancer, cardiovascular disease, or diabetes. Additionally, we challenged the question if the associations are modified by obesity status (BMI ≤25 or >25 kg/m2). Design: The analyses are made with 22,799 individuals from the Swedish population-based Malmö Diet and Cancer Cohort Study, who were born between 1923 and 1945. To investigate food preference, 27 food groups conducted from a modified diet history method including a 7-day registration of cooked meals and cold beverages were used in the analyses. Bonferroni correction was used to correct for multiple testing, resulting in a cut-off value for significance level of p

The aim of this study is to review recent data on dietary fiber (DF) and the glycemic index (GI), with special focus on studies from the Nordic countries regarding cardiometabolic risk factors, type 2 diabetes, cardiovascular disease, cancer, and total mortality. In this study, recent guidelines and scientific background papers or updates on older reports on DF and GI published between 2000 and 2011 from the US, EU, WHO, and the World Cancer Research Fund were reviewed, as well as prospective cohort and intervention studies carried out in the Nordic countries. All of the reports support the role for fiber-rich foods and DF as an important part of a healthy diet. All of the five identified Nordic papers found protective associations between high intake of DF and health outcomes; lower risk of cardiovascular disease, type 2 diabetes, colorectal and breast cancer. None of the reports and few of the Nordic papers found clear evidence for the GI in prevention of risk factors or diseases in healthy populations, although association was found in sub-groups, e.g. overweight and obese individuals and suggestive for prevention of type 2 diabetes. It was concluded that DF is associated with decreased risk of different chronic diseases and metabolic conditions. There is not enough evidence that choosing foods with low GI will decrease the risk of chronic diseases in the population overall. However, there is suggestive evidence that ranking food based on their GI might be of use for overweight and obese individuals. Issues regarding methodology, validity and practicality of the GI remain to be clarified.

BackgroundConcerns have been raised about the quality of reporting in nutritional epidemiology. Research reporting guidelines such as the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement can improve quality of reporting in observational studies. Herein, we propose recommendations for reporting nutritional epidemiology and dietary assessment research by extending the STROBE statement into Strengthening the Reporting of Observational Studies in Epidemiology-Nutritional Epidemiology (STROBE-nut).Methods and findingsRecommendations for the reporting of nutritional epidemiology and dietary assessment research were developed following a systematic and consultative process, coordinated by a multidisciplinary group of 21 experts. Consensus on reporting guidelines was reached through a three-round Delphi consultation process with 53 external experts. In total, 24 recommendations for nutritional epidemiology were added to the STROBE checklist.ConclusionWhen used appropriately, reporting guidelines for nutritional epidemiology can contribute to improve reporting of observational studies with a focus on diet and health.

Scores of overall diet quality have received increasing attention in relation to disease aetiology; however, their value in risk prediction has been little examined. The objective was to assess and compare the association and predictive performance of 10 diet quality scores on 10-year risk of all-cause, CVD and cancer mortality in 451,256 healthy participants to the European Prospective Investigation into Cancer and Nutrition, followed-up for a median of 12.8y. All dietary scores studied showed significant inverse associations with all outcomes. The range of HRs (95% CI) in the top vs. lowest quartile of dietary scores in a composite model including non-invasive factors (age, sex, smoking, body mass index, education, physical activity and study centre) was 0.75 (0.72-0.79) to 0.88 (0.84-0.92) for all-cause, 0.76 (0.69-0.83) to 0.84 (0.76-0.92) for CVD and 0.78 (0.73-0.83) to 0.91 (0.85-0.97) for cancer mortality. Models with dietary scores alone showed low discrimination, but composite models also including age, sex and other non-invasive factors showed good discrimination and calibration, which varied little between different diet scores examined. Mean C-statistic of full models was 0.73, 0.80 and 0.71 for all-cause, CVD and cancer mortality. Dietary scores have poor predictive performance for 10-year mortality risk when used in isolation but display good predictive ability in combination with other non-invasive common risk factors.

Consumption of sugar has been relatively high in the Nordic countries; the impact of sugar intake on metabolic risk factors and related diseases has been debated. The objectives were to assess the effect of sugar intake (sugar-sweetened beverages, sucrose and fructose) on association with type 2 diabetes, cardiovascular disease and related metabolic risk factors (impaired glucose tolerance, insulin sensitivity, dyslipidemia, blood pressure, uric acid, inflammation markers), and on all-cause mortality, through a systematic review of prospective cohort studies and randomised controlled intervention studies published between January 2000 and search dates. The methods adopted were as follows: the first search was run in PubMed in October 2010. A second search with uric acid as risk marker was run in April 2011. The total search strategy was rerun in April 2011 in SveMed+. An update was run in PubMed in January 2012. Two authors independently selected studies for inclusion from the 2,743 abstracts according to predefined eligibility criteria. The outcome was that out of the 17 studies extracted, 15 were prospective cohort studies and two were randomised controlled crossover trials. All of the studies included only adults. With respect to incident type 2 diabetes (nine studies), four of six prospective cohort studies found a significant positive association for sugar-sweetened beverage intake. In general, larger cohort studies with longer follow-up more often reported positive associations, and BMI seemed to mediate part of the increased risk. For other metabolic or cardiovascular risk factors or outcomes, too few studies have been published to draw conclusions. In conclusion, data from prospective cohort studies published in the years 2000–2011 suggest that sugar-sweetened beverages probably increase the risk of type 2 diabetes. For related metabolic risk factors, cardiovascular disease or all-cause mortality and other types of sugars, too few studies were available to draw conclusions.

It is still unclear whether carbohydrate consumption is associated with cardiovascular disease (CVD) risk. Genetic susceptibility might modify the associations between dietary intakes and disease risk.The aim was to examine the association between the consumption of carbohydrate-rich foods (vegetables, fruits and berries, juice, potatoes, whole grains, refined grains, cookies and cakes, sugar and sweets, and sugar-sweetened beverages) and the risk of incident ischemic CVD (iCVD; coronary events and ischemic stroke), and whether these associations differ depending on genetic susceptibility to dyslipidemia.Among 26,445 individuals (44-74 years; 62% females) from the Malmö Diet and Cancer Study cohort, 2,921 experienced an iCVD event during a mean follow-up time of 14 years. At baseline, dietary data were collected using a modified diet history method, and clinical risk factors were measured in 4,535 subjects. We combined 80 validated genetic variants associated with triglycerides and HDL-C or LDL-C, into genetic risk scores and examined the interactions between dietary intakes and genetic risk scores on the incidence of iCVD.Subjects in the highest intake quintile for whole grains had a 13% (95% CI: 3-23%; p-trend: 0.002) lower risk for iCVD compared to the lowest quintile. A higher consumption of foods rich in added sugar (sugar and sweets, and sugar-sweetened beverages) had a significant cross-sectional association with higher triglyceride concentrations and lower HDL-C concentrations. A stronger positive association between a high consumption of sugar and sweets on iCVD risk was observed among those with low genetic risk score for triglycerides (p-interaction=0.05).In this prospective cohort study that examined food sources of carbohydrates, individuals with a high consumption of whole grains had a decreased risk of iCVD. No convincing evidence of an interaction between genetic susceptibility for dyslipidemia, measured as genetic risk scores of dyslipidemia-associated variants, and the consumption of carbohydrate-rich foods on iCVD risk was observed.

Recent genome-wide meta-analyses identified 157 loci associated with cross-sectional lipid traits. Here we tested whether these loci associate (singly and in trait-specific genetic risk scores [GRS]) with longitudinal changes in total cholesterol (TC) and triglyceride (TG) levels in a population-based prospective cohort from Northern Sweden (the GLACIER Study). We sought replication in a southern Swedish cohort (the MDC Study; N = 2,943). GLACIER Study participants (N = 6,064) were genotyped with the MetaboChip array. Up to 3,495 participants had 10-yr follow-up data available in the GLACIER Study. The TC- and TG-specific GRSs were strongly associated with change in lipid levels (β = 0.02 mmol/l per effect allele per decade follow-up, P = 2.0 × 10(-11) for TC; β = 0.02 mmol/l per effect allele per decade follow-up, P = 5.0 × 10(-5) for TG). In individual SNP analysis, one TC locus, apolipoprotein E (APOE) rs4420638 (β = 0.12 mmol/l per effect allele per decade follow-up, P = 2.0 × 10(-5)), and two TG loci, tribbles pseudokinase 1 (TRIB1) rs2954029 (β = 0.09 mmol/l per effect allele per decade follow-up, P = 5.1 × 10(-4)) and apolipoprotein A-I (APOA1) rs6589564 (β = 0.31 mmol/l per effect allele per decade follow-up, P = 1.4 × 10(-8)), remained significantly associated with longitudinal changes for the respective traits after correction for multiple testing. An additional 12 loci were nominally associated with TC or TG changes. In replication analyses, the APOE rs4420638, TRIB1 rs2954029, and APOA1 rs6589564 associations were confirmed (P ≤ 0.001). In summary, trait-specific GRSs are robustly associated with 10-yr changes in lipid levels and three individual SNPs were strongly associated with 10-yr changes in lipid levels.

BackgroundThe association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach.Methods and findingsWe used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age- and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p < 0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p < 0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p = 0.001).ConclusionsWe provide novel evidence for a causal relationship between adiposity and heart failure as well as between adiposity and increased liver enzymes.

BACKGROUND:The effect of the macronutrient composition of the usual diet on long term weight maintenance remains controversial. METHODS:373,803 subjects aged 25-70 years were recruited in 10 European countries (1992-2000) in the PANACEA project of the EPIC cohort. Diet was assessed at baseline using country-specific validated questionnaires and weight and height were measured at baseline and self-reported at follow-up in most centers. The association between weight change after 5 years of follow-up and the iso-energetic replacement of 5% of energy from one macronutrient by 5% of energy from another macronutrient was assessed using multivariate linear mixed-models. The risk of becoming overweight or obese after 5 years was investigated using multivariate Poisson regressions stratified according to initial Body Mass Index. RESULTS:A higher proportion of energy from fat at the expense of carbohydrates was not significantly associated with weight change after 5 years. However, a higher proportion of energy from protein at the expense of fat was positively associated with weight gain. A higher proportion of energy from protein at the expense of carbohydrates was also positively associated with weight gain, especially when carbohydrates were rich in fibre. The association between percentage of energy from protein and weight change was slightly stronger in overweight participants, former smokers, participants ≥60 years old, participants underreporting their energy intake and participants with a prudent dietary pattern. Compared to diets with no more than 14% of energy from protein, diets with more than 22% of energy from protein were associated with a 23-24% higher risk of becoming overweight or obese in normal weight and overweight subjects at baseline. CONCLUSION:Our results show that participants consuming an amount of protein above the protein intake recommended by the American Diabetes Association may experience a higher risk of becoming overweight or obese during adult life.

To investigate if diet quality is related to incidence of cardiovascular (CV) events.A diet quality index based on the 2005 Swedish Nutrition Recommendations and the Swedish Dietary Guidelines was created and included six dietary components: saturated fatty acids, polyunsaturated fatty acids, fish and shellfish, dietary fiber, fruit and vegetables, and sucrose. The index ranked 17126 participants (59% women) of the population-based Malmö Diet and Cancer cohort (Sweden) on their dietary intakes. Total index score was categorized as low, medium or high. Cox proportional hazard regression was used to model associations between index score categories and index components with risk of incident CV events, with adjustment for potential confounders. The incidence of first CV events (non-fatal or fatal myocardial infarction or ischemic stroke or death from ischemic heart disease) was monitored from baseline (1991-1996) until December 31, 2008; 703 CV events occurred in women and 1093 in men.A high diet quality was associated with decreased risk of CV events when compared to a low diet quality. In multivariate analysis, the risk reduction was 32% (hazard ratio = 0.68, 95% confidence interval: 0.49-0.73) in men and 27% (hazard ratio = 0.73, 95% confidence interval: 0.59-0.91) in women. When examined separately and mutually adjusted for each other, the individual components were either not associated with CV risk or marginally decreased risks were seen.High quality diets in line with current recommendations may reduce the risk of CV events. This study illustrates the importance of considering a combination of dietary factors when evaluating diet-disease associations.

The evidence that individual dietary and lifestyle factors influence a person's weight and waist circumference is well established; however their combined impact is less well documented. Therefore, we investigated the combined effect of physical activity, nutrition and smoking status on prospective gain in body weight and waist circumference.We used data of the prospective EPIC-PANACEA study. Between 1992 and 2000, 325,537 participants (94,445 men and 231,092 women, aged between 25-70) were recruited from nine European countries. Participants were categorised into two groups (positive or negative health behaviours) for each of the following being physically active, adherent to a healthy (Mediterranean not including alcohol) diet, and never-smoking for a total score ranging from zero to three. Anthropometric measures were taken at baseline and were mainly self-reported after a medium follow-up time of 5 years.Mixed-effects linear regression models adjusted for age, educational level, alcohol consumption, baseline body mass index and follow-up time showed that men and women who reported to be physically active, never-smoking and adherent to the Mediterranean diet gained over a 5-year period 537 (95% CI -706, -368) and 200 (-478, -87) gram less weight and 0.95 (-1.27, -0.639) and 0.99 (-1.29, -0.69) cm less waist circumference, respectively, compared to participants with zero healthy behaviours.The combination of positive health behaviours was associated with significantly lower weight and waist circumference gain.

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.

BACKGROUND: The aim of the study was to examine associations between intake of macronutrients and dietary fiber and incident ischemic cardiovascular disease (iCVD) in men and women. METHODS: We used data from 8,139 male and 12,535 female participants (aged 44-73 y) of the Swedish population-based Malmö Diet and Cancer cohort. The participants were without history of CVD and diabetes mellitus, and had reported stable dietary habits in the study questionnaire. Diet was assessed by a validated modified diet history method, combining a 7-d registration of cooked meals and cold beverages, a 168-item food questionnaire (covering other foods and meal patterns), and a 1-hour diet interview. Sociodemographic and lifestyle data were collected by questionnaire. iCVD cases, which included coronary events (myocardial infarctions or deaths from chronic ischemic heart disease) and ischemic strokes, were ascertained via national and local registries. Nutrient-disease associations were examined by multivariate Cox regressions. RESULTS: During a mean follow-up of 13.5 years, we identified 1,089 male and 687 female iCVD cases. High fiber intakes were associated with lower incidence rates of iCVD in women and of ischemic stroke in men. In post-hoc analysis, we discovered statistically significant interactions between intake of fiber and saturated fat; these interactions also differed between men and women (p

BackgroundThe FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268).Methods and findingsAll studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction) = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents.ConclusionsThe association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.