Publications by authors named "Kim Overvad"

944 Publications

Polyphenol Intake and Epithelial Ovarian Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study.

Antioxidants (Basel) 2021 Aug 4;10(8). Epub 2021 Aug 4.

Institut Gustave Roussy, 94805 Villejuif, France.

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 (HR) was 1.14 (95% CI 0.94-1.39; -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 (HR = 1.20, 95% CI 1.01-1.43; -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.
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http://dx.doi.org/10.3390/antiox10081249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389235PMC
August 2021

Vitamin K Intake and Atherosclerotic Cardiovascular Disease in the Danish Diet Cancer and Health Study.

J Am Heart Assoc 2021 Aug 7;10(16):e020551. Epub 2021 Aug 7.

Institute for Nutrition Research School of Medical and Health Sciences Edith Cowan University Perth Australia.

Background Dietary vitamin K (K and K) may reduce atherosclerotic cardiovascular disease (ASCVD) risk via several mechanisms. However, studies linking vitamin K intake with incident ASCVD are limited. We aimed to determine the relationship between dietary vitamin K intake and ASCVD hospitalizations. Methods and Results In this prospective cohort study, participants from the Danish Diet, Cancer, and Health Study, with no prior ASCVD, completed a food-frequency questionnaire at baseline and were followed up for hospital admissions of ASCVD; ischemic heart disease, ischemic stroke, or peripheral artery disease. Intakes of vitamin K and vitamin K were estimated from the food-frequency questionnaire, and their relationship with ASCVD hospitalizations was determined using Cox proportional hazards models. Among 53 372 Danish citizens with a median (interquartile range) age of 56 (52-60) years, 8726 individuals were hospitalized for any ASCVD during 21 (17-22) years of follow-up. Compared with participants with the lowest vitamin K intakes, participants with the highest intakes had a 21% lower risk of an ASCVD-related hospitalization (hazard ratio, 0.79; 95% CI: 0.74-0.84), after multivariable adjustments for relevant demographic covariates. Likewise for vitamin K, the risk of an ASCVD-related hospitalization for participants with the highest intakes was 14% lower than participants with the lowest vitamin K intake (hazard ratio, 0.86; 95% CI, 0.81-0.91). Conclusions Risk of ASCVD was inversely associated with diets high in vitamin K or K. The similar inverse associations with both vitamin K and K, despite very different dietary sources, highlight the potential importance of vitamin K for ASCVD prevention.
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http://dx.doi.org/10.1161/JAHA.120.020551DOI Listing
August 2021

Theoretical substitutions between dairy products and all-cause and cause-specific mortality. Results from the Danish diet, cancer and health cohort.

Br J Nutr 2021 Jul 22:1-10. Epub 2021 Jul 22.

National Food Institute, Division for Diet, Disease Prevention and Toxicology, Technical University of Denmark, Kongens Lyngby, Denmark.

A daily intake of dairy products is recommended in many countries in order to maintain optimal health throughout life. However, evidence regarding the association between intake of individual dairy products and mortality is limited. We therfore, explored associations between intake of different dairy products and all-cause and cause-specific mortality using specified theoretical substitution analyses. We analysed data from 55 775 Danish men and women aged 50-64 years between 1993 and 1997. Information about dairy product intake at baseline was collected using a validated food frequency questionnaire. Information about vital status and causes of death was obtained through national registers. Measures of associations were calculated using Cox proportional hazards regression. During a median follow-up of 19·0 years, 11 586 participants died. For all-cause mortality, we observed that the intake of low-fat milk, whole-fat milk or low-fat yogurt products in place of cheese was associated with a higher rate of death (hazard ratios between 1·03 and 1·12 per serving/d substituted). The same pattern was present for CVD mortality. For cancer mortality, whole-fat milk and low-fat yogurt products in place of cheese were also associated with a higher rate of death for men while for women, whole-fat milk in place of buttermilk was associated with a higher cancer mortality rate. The results appeared robust in several sensitivity analyses. Our results suggest that intake of low-fat milk, whole-fat milk or low-fat yogurt products in place of cheese is associated with a higher rate of all-cause and cause-specific mortality.
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http://dx.doi.org/10.1017/S0007114521002464DOI Listing
July 2021

Association of Cycling With All-Cause and Cardiovascular Disease Mortality Among Persons With Diabetes: The European Prospective Investigation Into Cancer and Nutrition (EPIC) Study.

JAMA Intern Med 2021 Sep;181(9):1196-1205

University of Southern Denmark, Odense, Denmark.

Importance: Premature death from all causes and cardiovascular disease (CVD) causes is higher among persons with diabetes.

Objective: To investigate the association between time spent cycling and all-cause and CVD mortality among persons with diabetes, as well as to evaluate the association between change in time spent cycling and risk of all-cause and CVD mortality.

Design, Setting, And Participants: This prospective cohort study included 7459 adults with diabetes from the European Prospective Investigation into Cancer and Nutrition study. Questionnaires regarding medical history, sociodemographic, and lifestyle information were administered in 10 Western European countries from 1992 through 2000 (baseline examination) and at a second examination 5 years after baseline. A total of 5423 participants with diabetes completed both examinations. The final updated primary analysis was conducted on November 13, 2020.

Exposures: The primary exposure was self-reported time spent cycling per week at the baseline examination. The secondary exposure was change in cycling status from baseline to the second examination.

Main Outcomes And Measures: The primary and secondary outcomes were all-cause and CVD mortality, respectively, adjusted for other physical activity modalities, diabetes duration, and sociodemographic and lifestyle factors.

Results: Of the 7459 adults with diabetes included in the analysis, the mean (SD) age was 55.9 (7.7) years, and 3924 (52.6%) were female. During 110 944 person-years of follow-up, 1673 deaths from all causes were registered. Compared with the reference group of people who reported no cycling at baseline (0 min/wk), the multivariable-adjusted hazard ratios for all-cause mortality were 0.78 (95% CI, 0.61-0.99), 0.76 (95% CI, 0.65-0.88), 0.68 (95% CI, 0.57-0.82), and 0.76 (95% CI, 0.63-0.91) for cycling 1 to 59, 60 to 149, 150 to 299, and 300 or more min/wk, respectively. In an analysis of change in time spent cycling with 57 802 person-years of follow-up, a total of 975 deaths from all causes were recorded. Compared with people who reported no cycling at both examinations, the multivariable-adjusted hazard ratios for all-cause mortality were 0.90 (95% CI, 0.71-1.14) in those who cycled and then stopped, 0.65 (95% CI, 0.46-0.92) in initial noncyclists who started cycling, and 0.65 (95% CI, 0.53-0.80) for people who reported cycling at both examinations. Similar results were observed for CVD mortality.

Conclusion And Relevance: In this cohort study, cycling was associated with lower all-cause and CVD mortality risk among people with diabetes independent of practicing other types of physical activity. Participants who took up cycling between the baseline and second examination had a considerably lower risk of both all-cause and CVD mortality compared with consistent noncyclists.
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http://dx.doi.org/10.1001/jamainternmed.2021.3836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290339PMC
September 2021

Plasma concentrations of persistent organic pollutants and pancreatic cancer risk.

Int J Epidemiol 2021 Jul 14. Epub 2021 Jul 14.

Cancer Registry and Histopathology Department, "Civic-M.P. Arezzo" Hospital, ASP Ragusa, Ragusa, Italy.

Background: Findings and limitations of previous studies on persistent organic pollutants (POPs) and pancreatic cancer risk support conducting further research in prospective cohorts.

Methods: We conducted a prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Participants were 513 pancreatic cancer cases and 1020 matched controls. Concentrations of 22 POPs were measured in plasma collected at baseline.

Results: Some associations were observed at higher concentrations of p, p'-DDT, trans-nonachlor, β-hexachlorocyclohexane and the sum of six organochlorine pesticides and of 16 POPs. The odds ratio (OR) for the upper quartile of trans-nonachlor was 1.55 (95% confidence interval 1.06-2.26; P for trend = 0.025). Associations were stronger in the groups predefined as most valid (participants having fasted >6 h, with microscopic diagnostic confirmation, normal weight, and never smokers), and as most relevant (follow-up ≥10 years). Among participants having fasted >6 h, the ORs were relevant for 10 of 11 exposures. Higher ORs were also observed among cases with microscopic confirmation than in cases with a clinical diagnosis, and among normal-weight participants than in the rest of participants. Among participants with a follow-up ≥10 years, estimates were higher than in participants with a shorter follow-up (for trans-nonachlor: OR = 2.14, 1.01 to 4.53, P for trend = 0.035). Overall, trans-nonachlor, three PCBs and the two sums of POPs were the exposures most clearly associated with pancreatic cancer risk.

Conclusions: Individually or in combination, most of the 22 POPs analysed did not or only moderately increased the risk of pancreatic cancer.
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http://dx.doi.org/10.1093/ije/dyab115DOI Listing
July 2021

Omega-3 fatty acids in adipose tissue and risk of atrial fibrillation.

Eur J Clin Invest 2021 Jul 7:e13649. Epub 2021 Jul 7.

Aalborg AF Study Group, Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.

Background: The aim of the present study was to examine the relation between adipose tissue content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the risk of incident atrial fibrillation (AF).

Methods: In this case-cohort study based on data from the Danish Diet, Cancer and Health cohort, a total of 5255 incident cases of AF was identified during 16.9 years of follow-up. Adipose tissue biopsies collected at baseline from all cases and from a randomly drawn subcohort of 3440 participants were determined by gas chromatography. Data were analysed using weighted Cox regression.

Results: Data were available for 4741 incident cases of AF (2920 men and 1821 women). Participants in the highest vs. the lowest quintile of EPA experienced a 45% lower risk of AF (men HR 0.55 (95% CI 0.41-0.69); women HR 0.55 (0.41-0.72)). For DHA, no clear association was found in men, whereas in women, participants in the highest quintile of DHA in adipose tissue had a 30% lower risk of incident AF (HR 0.70 (0.54-0.91)) compared to participants in the lowest quintile.

Conclusions: A monotonous inverse association was found for the content of EPA in adipose tissue and risk of AF in both men and women. The content of DHA was inversely associated with the risk of AF in women, whereas no clear association was found for men.
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http://dx.doi.org/10.1111/eci.13649DOI Listing
July 2021

Dietary Methyl-Group Donor Intake and Breast Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Nutrients 2021 May 28;13(6). Epub 2021 May 28.

Office of the Director, International Agency for Research on Cancer, CEDEX 08, 69372 Lyon, France.

(1) Background: Methyl-group donors (MGDs), including folate, choline, betaine, and methionine, may influence breast cancer (BC) risk through their role in one-carbon metabolism; (2) Methods: We studied the relationship between dietary intakes of MGDs and BC risk, adopting data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort; (3) Results: 318,686 pre- and postmenopausal women were followed between enrolment in 1992-2000 and December 2013-December 2015. Dietary MGD intakes were estimated at baseline through food-frequency questionnaires. Multivariable Cox proportional hazards regression models were used to quantify the association between dietary intake of MGDs, measured both as a calculated score based on their sum and individually, and BC risk. Subgroup analyses were performed by hormone receptor status, menopausal status, and level of alcohol intake. During a mean follow-up time of 14.1 years, 13,320 women with malignant BC were identified. No associations were found between dietary intakes of the MGD score or individual MGDs and BC risk. However, a potential U-shaped relationship was observed between dietary folate intake and overall BC risk, suggesting an inverse association for intakes up to 350 µg/day compared to a reference intake of 205 µg/day. No statistically significant differences in the associations were observed by hormone receptor status, menopausal status, or level of alcohol intake; (4) Conclusions: There was no strong evidence for an association between MGDs involved in one-carbon metabolism and BC risk. However, a potential U-shaped trend was suggested for dietary folate intake and BC risk. Further research is needed to clarify this association.
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http://dx.doi.org/10.3390/nu13061843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228096PMC
May 2021

Urinary cadmium and stroke - a case-cohort study in Danish never-smokers.

Environ Res 2021 09 29;200:111394. Epub 2021 May 29.

Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Environmental Science, Aarhus University, Roskilde, Denmark.

Background: and Purpose: Cadmium has been associated with risk of cardiovascular events, including stroke. Human cadmium exposure occurs primarily through diet and tobacco smoke. Recent cohort studies have found an association with stroke, but residual confounding from smoking, could not be ruled out. We therefore conducted a case-cohort study to evaluate whether cadmium is associated with stroke in never-smokers.

Methods: The Danish Diet Cancer and Health cohort consists of Danes 50-64 years old, recruited in 1993-1997. From never-smoking cohort members without previous cancer or stroke we sampled a sub-cohort of 1200 persons. We also identified all (n = 534) cases in the cohort with a validated stroke diagnosis between baseline and 2009. We quantified cadmium and creatinine concentrations from baseline urine samples and used cadmium per creatinine as our main exposure metric. We used Cox proportional hazards models to estimate hazard ratios (HRs) with age as time scale and adjusting for BMI, education and urinary cotinine with and without stratification by sex.

Results: The median urinary cadmium concentration was 0.21 μg cadmium/g creatinine in cases and 0.19 μg/g in the sub-cohort. The majority (83%) of stroke cases were diagnosed with ischemic stroke. The HR for stroke in the highest quartile of exposure (median 0.44 μg/g creatinine) was 1.11 (95% CI: 0.79-1.54) compared with the lowest quartile (median 0.10 μg/g creatinine). The HR per inter quartile range (IQR, 0.19 μg/g creatinine) was 1.02 (95% CI: 0.92-1.12). Among men, the HR per IQR higher levels of cadmium (0.16 μg/g creatinine) was 1.18 (95% CI: 0.92-1.52), and 1.00 (95% CI: 0.89-1.12) among women. Adjusting for creatinine or using osmolality instead of creatinine standardization generally attenuated observed relationships.

Conclusions: Our results do not support that low levels of cadmium exposure among never-smokers are strongly associated with risk of stroke, although results varied somewhat by sex and method of accounting for urinary dilution.
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http://dx.doi.org/10.1016/j.envres.2021.111394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403651PMC
September 2021

Flavonoid intake and incident dementia in the Danish Diet, Cancer, and Health cohort.

Alzheimers Dement (N Y) 2021 13;7(1):e12175. Epub 2021 May 13.

School of Medical and Health Sciences Edith Cowan University Perth Australia.

Introduction: Prospective studies investigating flavonoid intake and dementia risk are scarce. The aims of this study were to examine associations between flavonoid intake and the risk of incident dementia and to investigate whether this association differs in the presence of lifestyle risk factors for dementia.

Methods: We examined associations in 55,985 participants of the Danish Diet, Cancer, and Health Study followed for 23 years. The Phenol-Explorer database was used to estimate flavonoid intakes. Information on incident dementia and dementia subtypes was obtained using Danish patient and prescription registries. Hazard ratios (HRs) were calculated using restricted cubic splines in multivariable-adjusted Cox proportional hazards models.

Results: For incident dementia, moderate compared to low intakes of flavonols (HR: 0.90 [0.82, 0.99]), flavanol oligo+polymers (HR: 0.87 [0.79, 0.96]), anthocyanins (HR: 0.84 [0.76, 0.93]), flavanones (HR: 0.89 [0.80, 0.99]), and flavones (HR: 0.85 [0.77, 0.95]) were associated with a lower risk. For vascular dementia, moderate intakes of flavonols (HR: 0.69 [0.53, 0.89]) and flavanol oligo + polymers (HR: 0.65 [0.51, 0.83]) were associated with lower risk. Flavonoid intakes were not significantly associated with Alzheimer's disease or unspecified dementia. The inverse association between total flavonoid intake and incident dementia was stronger in "ever" smokers than in "never" smokers and in those without hypercholesterolemia versus those with hypercholesteremia. Furthermore, the inverse association of vascular dementia with a moderate total flavonoid intake was stronger in "ever" smokers and those who were "normal" to "overweight" versus "never" smokers or those who were "obese," respectively.

Conclusion: A moderate intake of flavonoid-rich foods may help to reduce dementia risk.
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http://dx.doi.org/10.1002/trc2.12175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118115PMC
May 2021

Plant n-3 PUFA intake may lower the risk of atherosclerotic cardiovascular disease only among subjects with a low intake of marine n-3 PUFAs.

Eur J Nutr 2021 May 7. Epub 2021 May 7.

Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.

The role of the major plant-derived n-3 PUFA, alpha-linolenic acid (ALA), on the risk of atherosclerotic cardiovascular (ASCVD) remains unclear, but most studies have reported no association. However, the association between intake of ALA and the risk of ASCVD may depend on the intake of marine n-3 PUFAs. We investigated this hypothesis among more than 53,909 middle-aged, Danish men and women followed for a median of 13.4 years. We found a statistically significant inverse association between ALA intake modelled as a restricted cubic spline and the rate of ASCVD in subjects with a low intake of marine n-3 PUFAs, while no association was observed among subjects with a higher intake of marine n-3 PUFAs. Our findings suggest that the intake of ALA may be associated with a lower risk of total ASCVD, but only among subjects with a low intake of marine n-3 PUFAs.
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http://dx.doi.org/10.1007/s00394-021-02581-5DOI Listing
May 2021

Vegetable nitrate intake, blood pressure and incident cardiovascular disease: Danish Diet, Cancer, and Health Study.

Eur J Epidemiol 2021 Aug 21;36(8):813-825. Epub 2021 Apr 21.

Institute for Nutrition Research, School of Medical and Health Sciences, Edith Cowan University, Level 3, Royal Perth Hospital Research Foundation, Rear 50 Murray St, Perth, WA, 6000, Australia.

Whether the vascular effects of inorganic nitrate, observed in clinical trials, translate to a reduction in cardiovascular disease (CVD) with habitual dietary nitrate intake in prospective studies warrants investigation. We aimed to determine if vegetable nitrate, the major dietary nitrate source, is associated with lower blood pressure (BP) and lower risk of incident CVD. Among 53,150 participants of the Danish Diet, Cancer, and Health Study, without CVD at baseline, vegetable nitrate intake was assessed using a comprehensive vegetable nitrate database. Hazard ratios (HRs) were calculated using restricted cubic splines based on multivariable-adjusted Cox proportional hazards models. During 23 years of follow-up, 14,088 cases of incident CVD were recorded. Participants in the highest vegetable nitrate intake quintile (median, 141 mg/day) had 2.58 mmHg lower baseline systolic BP (95%CI - 3.12, - 2.05) and 1.38 mmHg lower diastolic BP (95%CI - 1.66, - 1.10), compared with participants in the lowest quintile. Vegetable nitrate intake was inversely associated with CVD plateauing at moderate intakes (~ 60 mg/day); this appeared to be mediated by systolic BP (21.9%). Compared to participants in the lowest intake quintile (median, 23 mg/day), a moderate vegetable nitrate intake (median, 59 mg/day) was associated with 15% lower risk of CVD [HR (95% CI) 0.85 (0.82, 0.89)]. Moderate vegetable nitrate intake was associated with 12%, 15%, 17% and 26% lower risk of ischemic heart disease, heart failure, ischemic stroke and peripheral artery disease hospitalizations respectively. Consumption of at least ~ 60 mg/day of vegetable nitrate (~ 1 cup of green leafy vegetables) may mitigate risk of CVD.
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http://dx.doi.org/10.1007/s10654-021-00747-3DOI Listing
August 2021

Soft Drink and Juice Consumption and Renal Cell Carcinoma Incidence and Mortality in the European Prospective Investigation into Cancer and Nutrition.

Cancer Epidemiol Biomarkers Prev 2021 06 13;30(6):1270-1274. Epub 2021 Apr 13.

International Agency for Research on Cancer (IARC-WHO), Lyon, France.

Background: Renal cell carcinoma (RCC) accounts for more than 80% of kidney cancers in adults, and obesity is a known risk factor. Regular consumption of sweetened beverages has been linked to obesity and several chronic diseases, including some types of cancer. It is uncertain whether soft drink and juice consumption is associated with risk of RCC. We investigated the associations of soft drink and juice consumption with RCC incidence and mortality in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Methods: A total of 389,220 EPIC participants with median age of 52 years at recruitment (1991-2000) were included. Cox regression yielded adjusted HRs and 95% confidence intervals (CI) for RCC incidence and mortality in relation to intakes of juices and total, sugar-sweetened, and artificially sweetened soft drinks.

Results: A total of 888 incident RCCs and 356 RCC deaths were identified. In models including adjustment for body mass index and energy intake, there was no higher risk of incident RCC associated with consumption of juices (HR per 100 g/day increment = 1.03; 95% CI, 0.97-1.09), total soft drinks (HR = 1.01; 95% CI, 0.98-1.05), sugar-sweetened soft drinks (HR = 0.99; 95% CI, 0.94-1.05), or artificially sweetened soft drinks (HR = 1.02; 95% CI, 0.96-1.08). In these fully adjusted models, none of the beverages was associated with RCC mortality (HR, 95% CI per 100 g/day increment 1.06, 0.97-1.16; 1.03, 0.98-1.09; 0.97, 0.89-1.07; and 1.06, 0.99-1.14, respectively).

Conclusions: Consumption of juices or soft drinks was not associated with RCC incidence or mortality after adjusting for obesity.

Impact: Soft drink and juice intakes are unlikely to play an independent role in RCC development or mortality.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611361PMC
June 2021

Substitution of unprocessed and processed red meat with poultry or fish and total and cause-specific mortality.

Br J Nutr 2021 Apr 8:1-7. Epub 2021 Apr 8.

Danish Cancer Society Research Center, DK-2100 Copenhagen Ø, Copenhagen, Denmark.

Recent studies found positive associations between intake of red meat and processed meat and total mortality; however, substitution of red meat with poultry and fish has been poorly investigated. We aimed to investigate associations for substitutions of red meat (unprocessed/processed) and total mortality and deaths due to cancer or CVD. We used data from the Danish Diet, Cancer and Health cohort, including 57 053 participants aged 50-64 years at baseline. Information on diet was collected through a validated 192-item FFQ. Information regarding total mortality, deaths due to cancer and deaths due to CVD was obtained by record linkage. Cox proportional hazards models were used to estimate the hazard ratio (HR) of 150 g/week substitutions of red meat with poultry or fish. During a follow-up (mean 16·1 years), 8840 deaths occurred (4567 were due to cancer; 1816 due to CVD). The adjusted HR for total death when substituting 150 g/week total red meat with poultry was 0·96 (95 % CI 0·95, 1·00) and with fish 0·99 (95 % CI 0·97, 1·01). Corresponding HR for cancer death or CVD death were similar. Substitution of processed red meat with fish or poultry was more consistently associated with a lower mortality than substitution of unprocessed red meat. For example, the adjusted HR for total death when substituting 150 g/week processed red meat with poultry was 0·95 (95 % CI 0·92, 0·98). We found that replacing processed red meat with poultry or fish was associated with a lower risk of total mortality and deaths due to cancer, but not deaths due to CVD.
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http://dx.doi.org/10.1017/S0007114521001252DOI Listing
April 2021

Modifiable Lifestyle Recommendations and Mortality in Denmark: A Cohort Study.

Am J Prev Med 2021 06 26;60(6):792-801. Epub 2021 Mar 26.

Department of Public Health, Aarhus University, Aarhus, Denmark. Electronic address:

Introduction: Modifiable lifestyle behaviors represent a central target for public health interventions. This study investigates the association between adherence to 4 modifiable lifestyle recommendations and all-cause, cancer, or cardiovascular disease mortality.

Methods: Investigators used data from the Danish Diet, Cancer and Health cohort (1993-2013; N=54,276). Lifestyle recommendations included smoking (never smoking), diet (adherence to 6 national food-based dietary guidelines), alcohol consumption (≤7 units per week for women and ≤14 units per week for men), and physical activity (≥30 minutes per day of moderate-to-vigorous leisure-time physical activity). Pseudo-values were used to estimate the adjusted risk differences and 95% CIs for all-cause, cancer, or cardiovascular disease mortality. Data were analyzed in 2019-2020.

Results: A total of 8,860 participants died during a median follow-up of 17.0 years. Adherence to all modifiable lifestyle recommendations was associated with an 18.46% (95% CI= -20.52%, -16.41%) lower absolute risk of all-cause mortality than no adherence. Never smokers had a 13.19% (95% CI= -13.95%, -12.44%) lower risk, those adhering to dietary guidelines (diet score ≥5) had a 7.52% (95% CI= -8.89%, -6.14%) lower risk, and those adhering to recommended levels of alcohol (2.11%, 95% CI= -2.75%, -1.48%) and physical activity (1.58%, 95% CI= -2.20%, -1.00%) had a lower risk than those who did not adhere. Stronger associations were observed in men than in women and in older than in middle-aged participants.

Conclusions: Findings suggest that adherence to modifiable lifestyle recommendations is associated with a lower risk of mortality from all causes, cancer, and cardiovascular disease, underlining the importance of supporting adherence to national guidelines for lifestyle recommendations.
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http://dx.doi.org/10.1016/j.amepre.2021.01.003DOI Listing
June 2021

Replacing Red Meat with Other Nonmeat Food Sources of Protein is Associated with a Reduced Risk of Type 2 Diabetes in a Danish Cohort of Middle-Aged Adults.

J Nutr 2021 05;151(5):1241-1248

Department of Public Health, Aarhus University, Aarhus, Denmark.

Background: Few cohort studies have modelled replacements of red meat with other sources of protein on subsequent risk of type 2 diabetes using dietary changes.

Objectives: To determine whether replacing red meat with other food sources of protein is associated with a lower risk of type 2 diabetes.

Methods: We used data from the Danish Diet, Cancer, and Health cohort (n = 39,437) of middle-aged (55-72 years old) men and women who underwent 2 dietary assessments roughly 5 years apart to investigate dietary changes. The pseudo-observation method was used to model the average exposure effect of decreasing the intake of red meat while increasing the intake of either poultry, fish, eggs, milk, yogurt, cheese, whole grains, or refined grains on the subsequent 10-year risk of developing type 2 diabetes, compared with no changes in the intakes of these foods.

Results: Replacing 1 serving/day (100 g/day) of red meat with 1 serving/day of eggs [risk difference (RD), -2.7%; 95% CI: -4.0 to -1.1%; serving size: 50 g/day], milk (RD, -1.2%; 95% CI: -2.1 to -0.4%; 200 g/day), yogurt (RD, -1.5%; 95% CI: -2.4 to -0.7%; 70 g/day), whole grains (RD, -1.7%; 95% CI: -2.5 to -0.9%; 30 g/day), or refined grains (RD, -1.2%; 95% CI: -2.0 to -0.3%; 30 g/day) was associated with a reduced risk of type 2 diabetes. Analyses of replacements with poultry or cheese, but not fish, also suggested a lower risk, but with wide CIs. After further adjustment for potential mediators (BMI, waist circumference, and history of hypertension or hypercholesterolemia), only the replacement with eggs was associated with a reduced risk (RD, -1.7%; 95% CI: -3.0 to -0.5%; 50 g/day).

Conclusions: Replacing red meat with eggs in middle-aged adults may reduce the risk of type 2 diabetes. In models not adjusted for potential mediators, replacing red meat with milk, yogurt, whole grains, or refined grains was also associated with a reduced risk of type 2 diabetes.
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http://dx.doi.org/10.1093/jn/nxaa448DOI Listing
May 2021

Linoleic acid in adipose tissue and the risk of myocardial infarction: a case-cohort study.

Eur J Nutr 2021 Oct 9;60(7):3639-3646. Epub 2021 Mar 9.

Department of Public Health, Aarhus University, Aarhus, Denmark.

Purpose: We investigated risk of myocardial infarction (MI) associated with the content of linoleic acid (LA) in adipose tissue, a biomarker of long-term dietary intake of LA and a marker of endogenous LA exposure.

Methods: Between 1993 and 1997, 57,053 middle-aged subjects were included in the Danish Diet, Cancer and Health cohort. We performed a case-cohort study that included a random sample of the full cohort (n = 3167) and all incident MI cases appearing during 16 years of follow-up (n = 2819). Information on incident MI cases was obtained by linkage with Danish nationwide registries. Adipose tissue biopsies were taken from the buttocks of the participants, and their fatty acid composition was determined using gas chromatography. HRs (hazard ratios) with 95% confidence intervals (CIs) were used to describe the associations between content of LA in adipose tissue and the risk of MI. HRs were calculated using weighted Cox proportional hazards regression with robust variance.

Results: After adjustment for established risk factors of MI, adipose tissue content of LA was not associated with the risk of MI in men and women combined (quintiles 5 versus 1, HR, 1.03 (95% CI, 0.85-1.25), P-trend = 0.970) or in men and women separately (quintiles 5 versus 1, HR, 1.05 (95% CI, 0.83-1.33), P-trend = 0.871 and quintiles 5 versus 1, HR, 0.99 (95% CI 0.72-1.37), P-trend = 0.928, respectively). Investigating the association between LA and MI with a shorter, 5- or 10-year duration of follow-up provided similar results.

Conclusion: Content of LA in adipose tissue was not associated with the risk of MI.
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http://dx.doi.org/10.1007/s00394-021-02526-yDOI Listing
October 2021

Changes in intake of dairy product subgroups and risk of type 2 diabetes: modelling specified food substitutions in the Danish Diet, Cancer and Health cohort.

Eur J Nutr 2021 Sep 4;60(6):3449-3459. Epub 2021 Mar 4.

Division for Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark.

Purpose: We investigated the association between an increased intake of one dairy product subgroup at the expense of another within a 5-year period and the subsequent 10-year risk of type 2 diabetes.

Methods: The cohort included 39,393 adults with two measurements of diet assessed using food frequency questionnaires (FFQ) administered in 1993-1997 and 1999-2003. Dairy products were milk (skimmed, semi-skimmed, whole fat), buttermilk, low-fat yogurt, whole-fat yogurt, cheese and butter. Type 2 diabetes cases were ascertained from the Danish National Diabetes Register. The pseudo-observation method was used to calculate risk differences (RD) with 95% confidence intervals (CI). The data were analysed in age strata to fulfil the assumption of independent entry.

Results: Among participants aged 56-59 years at completion of the follow-up FFQ, increased intake of whole-fat yogurt in place of skimmed, semi-skimmed or whole-fat milk was associated with a reduced risk (RD% [95% CI]: - 0.8% [- 1.3, - 0.2]; - 0.6% [- 1,1, - 0.1]; - 0.7 [- 1.2, - 0.1]; per 50 g/d, respectively). Among participants aged 60-64 and 65-72, substitution of skimmed milk for semi-skimmed milk was associated with an increased risk of type 2 diabetes (0.5% [0.2, 0.7]; 0.4% [0.1, 0.7]; per 50 g/d, respectively). Similar patterns of associations were found after adjustment for potential mediators.

Conclusion: Our results suggest that substitution of whole-fat yogurt for milk among those aged 56-59 decreases risk of type 2 diabetes and substitution of skimmed milk for semi-skimmed milk may increase the risk among those aged 60-64 and 65-72.
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http://dx.doi.org/10.1007/s00394-021-02524-0DOI Listing
September 2021

Red Blood Cell Fatty Acids and Risk of Colorectal Cancer in The European Prospective Investigation into Cancer and Nutrition (EPIC).

Cancer Epidemiol Biomarkers Prev 2021 05 22;30(5):874-885. Epub 2021 Feb 22.

Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

Background: A growing body of evidence suggests that alterations of dietary fatty acid (FA) profiles are associated with colorectal cancer risk. However, data from large-scale epidemiologic studies using circulating FA measurements to objectively assess individual FA and FA categories are scarce.

Methods: We investigate the association between red blood cell (RBC) membrane FAs and risk of colorectal cancer in a case-control study nested within a large prospective cohort. After a median follow-up of 6.4 years, 1,069 incident colorectal cancer cases were identified and matched to 1,069 controls among participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). The FA composition of RBC phospholipids (in mol%) was analyzed by gas chromatography, and their association with risk of colorectal cancer was estimated by multivariable adjusted conditional logistic regression models.

Results: After correction for multiple testing, subjects with higher concentrations of RBC stearic acid were at higher risk for colorectal cancer (OR = 1.23; 95% CI = 1.07-1.42, per 1 mol%). Conversely, colorectal cancer incidence decreased with increasing proportions of RBC n-3 PUFA, particularly eicosapentaenoic acid (0.75; 0.62-0.92, per 1 mol%). The findings for the n-6 PUFA arachidonic acid were inconsistent.

Conclusions: The positive association between prediagnostic RBC stearic acid and colorectal cancer reflects putative differences in FA intake and metabolism between cancer cases and matched controls, which deserve further investigation. The inverse relationship between EPA and colorectal cancer is in line with the repeatedly reported protective effect of fish consumption on colorectal cancer risk.

Impact: These findings add to the evidence on colorectal cancer prevention.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1426DOI Listing
May 2021

Urine cadmium and acute myocardial infarction among never smokers in the Danish Diet, Cancer and Health cohort.

Environ Int 2021 05 8;150:106428. Epub 2021 Feb 8.

Program in Public Health, Department of Family, Population, & Preventive Medicine, Stony Brook University, Stony Brook, NY, USA.

Cadmium exposure has been associated with cardiovascular disease. Cigarette smoking is a key source of cadmium exposure and thus a potential confounder in observational studies of environmental cadmium and cardiovascular disease that include tobacco smokers. We leveraged up to 20 years of follow-up in the Danish Diet, Cancer and Health cohort to test the hypothesis that cadmium exposure is associated with acute myocardial infarction (AMI) among people who never smoked. Between 1993 and 1997, 19,394 never-smoking participants (ages 50-64 years) were enrolled and provided a urine sample. From this sample, we randomly selected a subcohort of 600 males and 600 females. We identified 809 AMI cases occurring between baseline and the end of 2015 using the Danish National Patient Registry. We quantified cadmium, creatinine, and osmolality in baseline urine samples. Using an unweighted case-cohort approach, we estimated adjusted hazard ratios (aHR) for AMI in Cox proportional hazards models with age as the time axis. Participants had relatively low concentrations of urinary cadmium, as expected for never smokers (median = 0.20; 25th, 75th = 0.13, 0.32 μg cadmium/g creatinine). We did not find strong evidence to support an association between higher urinary cadmium and AMI when comparing the highest versus lowest quartile (aHR = 1.16; 95% CI: 0.86 - 1.56) and per IQR increment in cadmium concentration (aHR = 1.02; 95% CI: 0.93 - 1.12). Results were not materially different across strata defined by sex. Results were generally similar using creatinine or osmolality to account for differences in urine dilution. While cadmium exposure has been identified as a risk factor for cardiovascular disease, we did not find strong evidence that urinary cadmium at relatively low-levels is associated with AMI among people who have never smoked.
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http://dx.doi.org/10.1016/j.envint.2021.106428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940585PMC
May 2021

Whole-Grain Intake and Pancreatic Cancer Risk-The Danish, Diet, Cancer and Health Cohort.

J Nutr 2021 03;151(3):666-674

Danish Cancer Society Research Center, Copenhagen, Denmark.

Background: Pancreatic cancer is a highly deadly disease with a poor prognosis. There is limited knowledge about prevention of the disease; thus, identification of risk factors is important to reduce the disease incidence.

Objective: The aim of the present study was to prospectively investigate associations between incidence of pancreatic cancer and whole-grain intake measured in 2 ways: as whole-grain product intake (g whole-grain products/d) and as whole-grain intake (grams of whole grains/d). Moreover, the intake of subgroups of these was also investigated: whole-grain products (rye bread, whole-grain bread, and oatmeal/muesli) and cereals (rye, wheat, and oats).

Methods: In total, 55,995 Danish adults aged 50-64 y, of whom 446 developed pancreatic cancer (17.5 y mean follow-up), were included in the study. Detailed information on daily intake of whole-grain products was available from a validated self-administered FFQ, and intake of whole-grain cereals (wheat, rye, and oats) was estimated using information from a 24-h dietary recall. The association between the whole-grain exposures and incidence of pancreatic cancer was investigated by Cox regression analyses adjusted for potential confounders.

Results: Total whole-grain product intake was associated with a 7% lower incidence of pancreatic cancer per serving (50 g/d) (HR: 0.93; 95% CI: 0.86, 1.00), and in the sex-specific analyses, an inverse association was found only in men. No association was found for total whole-grain intake (per 16-g serving size; HR: 0.96; 95% CI: 0.89, 1.03). When investigating specific whole-grain products and cereals individually, none were alone associated with lower incidence of pancreatic cancer.

Conclusion: Our findings indicate that intake of whole grains is associated with lower risk of pancreatic cancer in middle-aged men. Consuming ample amounts of whole grains may prove beneficial in terms of lowering pancreatic cancer risk.
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http://dx.doi.org/10.1093/jn/nxaa385DOI Listing
March 2021

Intake of marine n-3 polyunsaturated fatty acids and the risk of incident peripheral artery disease.

Eur J Clin Nutr 2021 Jan 29. Epub 2021 Jan 29.

Department of Cardiology, Aalborg University Hospital, 9000, Aalborg, Denmark.

Background: A high intake of marine n-3 polyunsaturated fatty acids (PUFAs) may lower the risk of coronary heart disease and ischemic stroke. The association between intake of marine n-3 PUFAs and development of peripheral artery disease (PAD), however, remains unexplored. We hypothesised that intake of marine n-3 PUFAs, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and the sum of EPA + DHA was associated with a lower risk of incident PAD.

Methods: We used data from the Danish Diet, Cancer and Health cohort and investigated the associations between intake of EPA, DHA and EPA + DHA and development of PAD. Information on intake of n-3 PUFAs was obtained through a validated food frequency questionnaire. Potential PAD cases were identified through linkage to the Danish National Patient Register and subsequently, all cases were validated.

Results: Data were available from 55,248 participants and during a median of 13.6 years of follow-up, 950 cases of PAD were identified. Multivariate Cox regression analyses with adjustments for established risk factors showed no statistically significant associations between intake of EPA (p = 0.255), DHA (p = 0.071) or EPA + DHA (p = 0.168) and the rate of incident PAD.

Conclusions: We did not confirm our hypothesis that intake of EPA, DHA or EPA + DHA was associated with a lower risk of incident PAD.
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http://dx.doi.org/10.1038/s41430-021-00858-wDOI Listing
January 2021

Replacement of potatoes with other vegetables and risk of myocardial infarction in the Danish Diet, Cancer and Health cohort.

Br J Nutr 2021 Jan 29:1-8. Epub 2021 Jan 29.

Department of Public Health, Aarhus University, AarhusDK-8000, Denmark.

Intake of vegetables is recommended for the prevention of myocardial infarction (MI). However, vegetables make up a heterogeneous group, and subgroups of vegetables may be differentially associated with MI. The aim of this study was to examine replacement of potatoes with other vegetables or subgroups of other vegetables and the risk of MI. Substitutions between subgroups of other vegetables and risk of MI were also investigated. We followed 29 142 women and 26 029 men aged 50-64 years in the Danish Diet, Cancer and Health cohort. Diet was assessed at baseline by using a detailed validated FFQ. Hazard ratios (HR) with 95 % CI for the incidence of MI were calculated using Cox proportional hazards regression. During 13·6 years of follow-up, 656 female and 1694 male cases were identified. Among women, the adjusted HR for MI was 1·02 (95 % CI 0·93, 1·13) per 500 g/week replacement of potatoes with other vegetables. For vegetable subgroups, the HR was 0·93 (95 % CI 0·77, 1·13) for replacement of potatoes with fruiting vegetables and 0·91 (95 % CI 0·77, 1·07) for replacement of potatoes with other root vegetables. A higher intake of cabbage replacing other vegetable subgroups was associated with a statistically non-significant higher risk of MI. A similar pattern of associations was found when intake was expressed in kcal/week. Among men, the pattern of associations was overall found to be similar to that for women. This study supports food-based dietary guidelines recommending to consume a variety of vegetables from all subgroups.
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http://dx.doi.org/10.1017/S0007114521000349DOI Listing
January 2021

Effects of substitution dietary guidelines targeted at prevention of IHD on dietary intake and risk factors in middle-aged Danish adults: the Diet and Prevention of Ischemic Heart Disease: a Translational Approach (DIPI) randomised controlled trial.

Br J Nutr 2021 Oct 28;126(8):1179-1193. Epub 2020 Dec 28.

Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, 2800Kgs. Lyngby, Denmark.

The objective was to investigate the effects of substitution (SUB) dietary guidelines (DG) targeted at the prevention of IHD on dietary intake and IHD risk factors in Danish adults with minimum one self-assessed IHD risk factor. A 6-month single-blinded parallel randomised controlled trial with a follow-up at month 12 included 219 subjects (median age 51 years, 59 % female, 73 % overweight or obese) randomised into an SUB DG, an official (OFF) DG or a control group following their habitual diet (HAB). Participants in the DG intervention groups received bi-weekly reminders of their DG and recipes for dishes and the HAB group received a greeting. Dietary intake and fasting blood, anthropometric and blood pressure measurements were obtained at baseline, month 6 and month 12. Linear regression analyses were applied. At month 6, when compared with the HAB, the SUB had a greater impact on the extent of dietary changes with increased intake of whole grains, dietary fibre and low fibre vegetables compared with the OFF DG, and both DG groups had similar decreased percentage of energy (E%) intake from SFA. The extent of dietary changes was similar at month 12. No overall significant changes from baseline were found in blood pressure, anthropometrics and IHD risk markers. In conclusion, both SUB and OFF DG resulted in cardioprotective dietary changes. However, neither the SUB nor the OFF DG resulted in any overall effects on the selected intermediate risk factors for IHD.
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http://dx.doi.org/10.1017/S0007114520005164DOI Listing
October 2021

Interaction Between GAD65 Antibodies and Dietary Fish Intake or Plasma Phospholipid n-3 Polyunsaturated Fatty Acids on Incident Adult-Onset Diabetes: The EPIC-InterAct Study.

Diabetes Care 2021 02 10;44(2):416-424. Epub 2020 Dec 10.

Medical Research Council Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, U.K.

Objective: Islet autoimmunity is associated with diabetes incidence. We investigated whether there was an interaction between dietary fish intake or plasma phospholipid n-3 polyunsaturated fatty acid (PUFA) concentration with the 65-kDa isoform of GAD (GAD65) antibody positivity on the risk of developing adult-onset diabetes.

Research Design And Methods: We used prospective data on 11,247 incident cases of adult-onset diabetes and 14,288 noncases from the EPIC-InterAct case-cohort study conducted in eight European countries. Baseline plasma samples were analyzed for GAD65 antibodies and phospholipid n-3 PUFAs. Adjusted hazard ratios (HRs) for incident diabetes in relation to GAD65 antibody status and tertiles of plasma phospholipid n-3 PUFA or fish intake were estimated using Prentice-weighted Cox regression. Additive (proportion attributable to interaction [AP]) and multiplicative interactions between GAD65 antibody positivity (≥65 units/mL) and low fish/n-3 PUFA were assessed.

Results: The hazard of diabetes in antibody-positive individuals with low intake of total and fatty fish, respectively, was significantly elevated (HR 2.52 [95% CI 1.76-3.63] and 2.48 [1.79-3.45]) compared with people who were GAD65 antibody negative and had high fish intake, with evidence of additive (AP 0.44 [95% CI 0.16-0.72] and 0.48 [0.24-0.72]) and multiplicative ( = 0.0465 and 0.0103) interactions. Individuals with high GAD65 antibody levels (≥167.5 units/mL) and low total plasma phospholipid n-3 PUFAs had a more than fourfold higher hazard of diabetes (HR 4.26 [2.70-6.72]) and an AP of 0.46 (0.12-0.80) compared with antibody-negative individuals with high n-3 PUFAs.

Conclusions: High fish intake or relative plasma phospholipid n-3 PUFA concentrations may partially counteract the increased diabetes risk conferred by GAD65 antibody positivity.
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http://dx.doi.org/10.2337/dc20-1463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818317PMC
February 2021

Food substitution models for nutritional epidemiology.

Am J Clin Nutr 2021 02;113(2):294-303

Division for Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark.

The advantage of using specified substitution analysis in nutritional epidemiology has been clearly demonstrated in studies of macronutrient intake and disease risk. However, the method has not been widely applied in studies of food intake. The aim of this article is to describe and compare the interpretation and application of different food substitution models in epidemiologic studies on diet and disease development. Both theoretically and in the context of a specific example, we discuss methodologic issues to be considered, including modeling of food substitutions using diet at a single time point or at multiple time points (focusing on dietary changes), choice of substitution unit, adjustment for total energy intake, and adjustment for confounding. We argue that specified food substitution analyses can be used to identify optimal food composition of the diet and that these analyses are thus highly relevant to inform public health policy decision makers.
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http://dx.doi.org/10.1093/ajcn/nqaa315DOI Listing
February 2021

Metabolic Signatures of Healthy Lifestyle Patterns and Colorectal Cancer Risk in a European Cohort.

Clin Gastroenterol Hepatol 2020 Dec 29. Epub 2020 Dec 29.

CIBER Epidemiología y Salud Pública, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain.

Background & Aims: Colorectal cancer risk can be lowered by adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines. We derived metabolic signatures of adherence to these guidelines and tested their associations with colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.

Methods: Scores reflecting adherence to the WCRF/AICR recommendations (scale, 1-5) were calculated from participant data on weight maintenance, physical activity, diet, and alcohol among a discovery set of 5738 cancer-free European Prospective Investigation into Cancer and Nutrition participants with metabolomics data. Partial least-squares regression was used to derive fatty acid and endogenous metabolite signatures of the WCRF/AICR score in this group. In an independent set of 1608 colorectal cancer cases and matched controls, odds ratios (ORs) and 95% CIs were calculated for colorectal cancer risk per unit increase in WCRF/AICR score and per the corresponding change in metabolic signatures using multivariable conditional logistic regression.

Results: Higher WCRF/AICR scores were characterized by metabolic signatures of increased odd-chain fatty acids, serine, glycine, and specific phosphatidylcholines. Signatures were inversely associated more strongly with colorectal cancer risk (fatty acids: OR, 0.51 per unit increase; 95% CI, 0.29-0.90; endogenous metabolites: OR, 0.62 per unit change; 95% CI, 0.50-0.78) than the WCRF/AICR score (OR, 0.93 per unit change; 95% CI, 0.86-1.00) overall. Signature associations were stronger in male compared with female participants.

Conclusions: Metabolite profiles reflecting adherence to WCRF/AICR guidelines and additional lifestyle or biological risk factors were associated with colorectal cancer. Measuring a specific panel of metabolites representative of a healthy or unhealthy lifestyle may identify strata of the population at higher risk of colorectal cancer.
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http://dx.doi.org/10.1016/j.cgh.2020.11.045DOI Listing
December 2020

Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations.

Diabetes Care 2021 01 17;44(1):98-106. Epub 2020 Nov 17.

Unit of Nutrition and Cancer, Cancer Epidemiology Research Program and Translational Research Laboratory; Catalan Institute of Oncology - ICO, Group of Research on Nutrition and Cancer, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet of Llobregat, Barcelona, Spain.

Objective: Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes.

Research Design And Methods: We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants.

Results: We identified 11 genomic regions associated with plasma vitamin C ( < 5 × 10), with the strongest signal at , and 10 novel genetic loci including , , , , , , , , , and . Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10).

Conclusions: These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.
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http://dx.doi.org/10.2337/dc20-1328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783939PMC
January 2021

Adherence to the Danish food-based dietary guidelines and risk of type 2 diabetes: the Danish diet, cancer, and health cohort.

Eur J Clin Nutr 2021 05 15;75(5):836-844. Epub 2020 Nov 15.

Department of Public Health, Aarhus University, DK-8000, Aarhus C, Denmark.

Background/objectives: We evaluated the association between adherence to the 2013 Danish dietary guidelines and the risk of type 2 diabetes (T2D) in a Danish cohort.

Subjects/methods: We used data from the Danish Diet, Cancer, and Health cohort. Participants aged 50-64 years were included from 1993-1997. Information on diet and covariates was collected at baseline using questionnaires and physical assessments. A diet index was developed to assess adherence to the Danish dietary guidelines. T2D cases were identified using the Danish National Diabetes Register. Cox proportional hazards regression was used to estimate hazard ratios (HR), and the pseudo-observation method was used to estimate risk differences, and 95% confidence intervals (CI).

Results: A total of 54,305 subject were included. During a median follow-up of 15 years, 7136 participants were diagnosed with T2D. After multivariable adjustment, the HR for high versus low adherence to the index was 0.57 (95 % CI: 0.48, 0.69) in men, and 0.71 (95% CI: 0.60, 0.83) in women. Compared with the lowest adherence to the index, high adherence was associated with a 6.58% (95% CI: -8.69; -4.47%) or 3.17% (95% CI: -4.90, -1.44%) lower risk of T2D in men and women, respectively.

Conclusions: High adherence to the Danish food-based dietary guidelines was associated with lower risk of T2D in a Danish cohort, both on a relative and an absolute scale. Shifting from low to high adherence to the dietary guidelines may provide public health benefit.
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http://dx.doi.org/10.1038/s41430-020-00805-1DOI Listing
May 2021

Genome-wide association analysis of type 2 diabetes in the EPIC-InterAct study.

Sci Data 2020 11 13;7(1):393. Epub 2020 Nov 13.

Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.

Type 2 diabetes (T2D) is a global public health challenge. Whilst the advent of genome-wide association studies has identified >400 genetic variants associated with T2D, our understanding of its biological mechanisms and translational insights is still limited. The EPIC-InterAct project, centred in 8 countries in the European Prospective Investigations into Cancer and Nutrition study, is one of the largest prospective studies of T2D. Established as a nested case-cohort study to investigate the interplay between genetic and lifestyle behavioural factors on the risk of T2D, a total of 12,403 individuals were identified as incident T2D cases, and a representative sub-cohort of 16,154 individuals was selected from a larger cohort of 340,234 participants with a follow-up time of 3.99 million person-years. We describe the results from a genome-wide association analysis between more than 8.9 million SNPs and T2D risk among 22,326 individuals (9,978 cases and 12,348 non-cases) from the EPIC-InterAct study. The summary statistics to be shared provide a valuable resource to facilitate further investigations into the genetics of T2D.
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http://dx.doi.org/10.1038/s41597-020-00716-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666191PMC
November 2020

Replacing the consumption of red meat with other major dietary protein sources and risk of type 2 diabetes mellitus: a prospective cohort study.

Am J Clin Nutr 2021 03;113(3):612-621

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: Greater consumption of red meat has been associated with a higher risk of type 2 diabetes mellitus (T2DM). A decreased intake of red meat and simultaneous increased intake of other high-protein foods may be associated with a lower risk of T2DM. These analyses of specific food replacements for red meat may provide more accurate dietary advice.

Objective: We examined the association between a decrease in intake of red meat accompanied by an increase in other major dietary protein sources and risk of T2DM.

Methods: We prospectively followed 27,634 males in the Health Professionals Follow-up Study, 46,023 females in the Nurses' Health Study, and 75,196 females in the Nurses' Health Study II. Diet was assessed by a validated FFQ and updated every 4 y. Cox proportional hazards models adjusted for T2DM risk factors were used to model the food replacements. We calculated HRs and 95% CIs for the T2DM risk associated with replacements of 1 daily serving of red meat with another protein source.

Results: During 2,113,245 person-years of follow-up, we identified 8763 incident T2DM cases from 1990 to 2013. In the pooled analyses, a decrease in total red meat intake during a 4-y period replaced with another common protein food was associated with a lower risk of T2DM in the subsequent 4-y period. The HR (95% CI) per 1 serving/d was 0.82 (0.75, 0.90) for poultry, 0.87 (0.77, 0.98) for seafood, 0.82 (0.78, 0.86) for low-fat dairy, 0.82 (0.77, 0.86) for high-fat dairy, 0.90 (0.81, 0.99) for eggs, 0.89 (0.82, 0.98) for legumes, and 0.83 (0.78, 0.89) for nuts. The associations were present for both unprocessed and processed red meat, although stronger for the replacement of processed red meat.

Conclusions: Replacing red meat consumption with other protein sources was associated with a lower risk of T2DM.
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http://dx.doi.org/10.1093/ajcn/nqaa284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948828PMC
March 2021
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