Dietary intake of dicarbonyl compounds and changes in body weight over time in a large cohort of European adults.

Dicarbonyl compounds are highly reactive precursors of advanced glycation end products (AGE), produced endogenously, present in certain foods and formed during food processing. AGE contribute to the development of adverse metabolic outcomes, but health effects of dietary dicarbonyls are largely unexplored. We investigated associations between three dietary dicarbonyl compounds, methylglyoxal (MGO), glyoxal (GO) and 3-deoxyglucosone (3-DG), and body weight changes in European adults. Dicarbonyl intakes were estimated using food composition database from 263 095 European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home in Relation to Anthropometry participants with two body weight assessments (median follow-up time = 5·4 years). Associations between dicarbonyls and 5-year body-weight changes were estimated using mixed linear regression models. Stratified analyses by sex, age and baseline BMI were performed. Risk of becoming overweight/obese was assessed using multivariable-adjusted logistic regression. MGO intake was associated with 5-year body-weight gain of 0·089 kg (per 1-sd increase, 95 % CI 0·072, 0·107). 3-DG was inversely associated with body-weight change (-0·076 kg, -0·094, -0·058). No significant association was observed for GO (0·018 kg, -0·002, 0·037). In stratified analyses, GO was associated with body-weight gain among women and older participants (above median of 52·4 years). MGO was associated with higher body-weight gain among older participants. 3-DG was inversely associated with body-weight gain among younger and normal-weight participants. MGO was associated with a higher risk of becoming overweight/obese, while inverse associations were observed for 3-DG. No associations were observed for GO with overweight/obesity. Dietary dicarbonyls are inconsistently associated with body weight change among European adults. Further research is needed to clarify the role of these food components in overweight and obesity, their underlying mechanisms and potential public health implications.

Associations of dietary choline and betaine with all-cause mortality: a prospective study in a large Swedish cohort.

PURPOSE: Investigate the association between choline and betaine intake and all-cause mortality in a large Swedish cohort. METHODS: Women (52,246) and men (50,485) attending the Västerbotten Intervention Programme 1990-2016 were included. Cox proportional hazard regression models adjusted for energy intake, age, BMI, smoking, education, and physical activity were used to estimate mortality risk according to betaine, total choline, phosphatidylcholine, glycerophosphocholine, phosphocholine, sphingomyelin, and free choline intakes [continuous (per 50 mg increase) and in quintiles]. RESULTS: During a median follow-up of 16 years, 3088 and 4214 deaths were registered in women and men, respectively. Total choline intake was not associated with all-cause mortality in women (HR 1.01; 95% CI 0.97, 1.06; P = 0.61) or men (HR 1.01; 95% CI 0.98, 1.04; P = 0.54). Betaine intake was associated with decreased risk of all-cause mortality in women (HR 0.95; 95% CI 0.91, 0.98; P < 0.01) but not in men. Intake of free choline was negatively associated with risk of all-cause mortality in women (HR 0.98; 95% CI 0.96, 1.00; P = 0.01). No other associations were found between intake of the different choline compounds and all-cause mortality. In women aged ≥ 55 years, phosphatidylcholine intake was positively associated with all-cause mortality. In men with higher folate intake, total choline intake was positively associated with all-cause mortality. CONCLUSION: Overall, our results do not support that intake of total choline is associated with all-cause mortality. However, some associations were modified by age and with higher folate intake dependent on sex. Higher intake of betaine was associated with lower risk of all-cause mortality in women.

Towards objective measurements of habitual dietary intake patterns: comparing NMR metabolomics and food frequency questionnaire data in a population-based cohort.

BACKGROUND: Low-quality, non-diverse diet is a main risk factor for premature death. Accurate measurement of habitual diet is challenging and there is a need for validated objective methods. Blood metabolite patterns reflect direct or enzymatically diet-induced metabolites. Here, we aimed to evaluate associations between blood metabolite patterns and a priori and data-driven food intake patterns. METHODS: 1, 895 participants in the Northern Sweden Health and Disease Study, a population-based prospective cohort study, were included. Fasting plasma samples were analyzed with 1H Nuclear Magnetic Resonance. Food intake data from a 64-item validated food frequency questionnaire were summarized into a priori Healthy Diet Score (HDS), relative Mediterranean Diet Score (rMDS) and a set of plant-based diet indices (PDI) as well as data driven clusters from latent class analyses (LCA). Orthogonal projections to latent structures (OPLS) were used to explore clustering patterns of metabolites and their relation to reported dietary intake patterns. RESULTS: Age, sex, body mass index, education and year of study participation had significant influence on OPLS metabolite models. OPLS models for healthful PDI and LCA-clusters were not significant, whereas for HDS, rMDS, PDI and unhealthful PDI significant models were obtained (CV-ANOVA p < 0.001). Still, model statistics were weak and the ability of the models to correctly classify participants into highest and lowest quartiles of rMDS, PDI and unhealthful PDI was poor (50%/78%, 42%/75% and 59%/70%, respectively). CONCLUSION: Associations between blood metabolite patterns and a priori as well as data-driven food intake patterns were poor. NMR metabolomics may not be sufficiently sensitive to small metabolites that distinguish between complex dietary intake patterns, like lipids.

Plasma Concentration of 36 (Poly)phenols and Prospective Body Weight Change in Participants from the EPIC Cohort.

INTRODUCTION: Dietary intake of (poly)phenols has been linked to reduced adiposity and body weight (BW) in several epidemiological studies. However, epidemiological evidence on (poly)phenol biomarkers, particularly plasma concentrations, is scarce. We aimed to investigate the associations between plasma (poly)phenols and prospective BW change in participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: This study included 761 participants with data on BW at baseline and after 5 years of follow-up. Plasma concentrations of 36 (poly)phenols were measured at baseline using liquid chromatography-tandem mass spectrometry. Associations were assessed through general linear mixed models and multinomial logistic regression models, using change in BW as a continuous or as a categorical variable (BW loss, maintenance, gain), respectively. Plasma (poly)phenols were assessed as log2-transformed continuous variables. The false discovery rate (FDR) was used to control for multiple comparisons. RESULTS: Doubling plasma (poly)phenol concentrations showed a borderline trend towards a positive association with BW loss. Plasma vanillic acid showed the strongest association (-0.53 kg/5 years; 95% confidence interval [CI]: -0.99, -0.07). Similar results were observed for plasma naringenin comparing BW loss versus BW maintenance (odds ratio: 1.1; 95% CI: 1.0, 1.2). These results did not remain significant after FDR correction. CONCLUSION: Higher concentrations of plasma (poly)phenols suggested a tendency towards 5-year BW maintenance or loss. While certain associations seemed promising, they did not withstand FDR correction, indicating the need for caution in interpreting these results. Further studies using (poly)phenol biomarkers are needed to confirm these suggestive protective trends.

Household, dietary, and clinical characteristics of childhood caries and overweight progression-A prospective cohort study.

BACKGROUND: Childhood caries and obesity are complex chronic diseases with negative health outcomes. AIM: This study sought a risk profile for childhood caries and overweight. DESIGN: Children were recruited into a longitudinal prospective cohort study. Caries and overweight characteristics were obtained at baseline, 6, 12, and 18 months. Sequential data modeling steps determined a disease risk profile. RESULTS: At baseline, 50% of the children (n = 194, 3.0 to 6.9 years) had caries; 24% were overweight, of whom 50% had caries. Correlation analysis separated child characteristics from household circumstances. Principal component modeling separated child snacking from meal-eating patterns, and household smoking from parent education variables. Baseline caries and overweight were not associated, but they grouped together in the modeling of composite features. Forty-five percent of children showed caries progression, 29% overweight progression, and 10% progression of both diseases. The strongest predictors of progression were disease presence, household-based characteristics, and sugary drinks. Children with caries and overweight progression shared multiple child- and household-based features. CONCLUSION: Individually, caries and overweight were not associated. Children with progression of both conditions shared a profile and multiple risk characteristics suggesting these findings could be useful in assessing the risk for the most extreme cases of caries and overweight.

Prediagnostic serum glyceraldehyde-derived advanced glycation end products and mortality among colorectal cancer patients.

Glyceraldehyde-derived advanced glycation end products (glycer-AGEs) could contribute to colorectal cancer development and progression due to their pro-oxidative and pro-inflammatory properties. However, the association of glycer-AGEs with mortality after colorectal cancer diagnosis has not been previously investigated. Circulating glycer-AGEs were measured by competitive ELISA. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for associations of circulating glycer-AGEs concentrations with CRC-specific and all-cause mortality among 1034 colorectal cancer (CRC) cases identified within the European Prospective Investigation into Cancer and Nutrition (EPIC) study between 1993 and 2013. During a mean of 48 months of follow-up, 529 participants died (409 from CRC). Glycer-AGEs were statistically significantly positively associated with CRC-specific (HRQ5 vs Q1  = 1.53, 95% CI: 1.04-2.25, Ptrend  = .002) and all-cause (HRQ5 vs Q1  = 1.62, 95% CI: 1.16-2.26, Ptrend  < .001) mortality among individuals with CRC. There was suggestion of a stronger association between glycer-AGEs and CRC-specific mortality among patients with distal colon cancer (per SD increment: HRproximal colon  = 1.02, 95% CI: 0.74-1.42; HRdistal colon  = 1.51, 95% CI: 1.20-1.91; Peffect modification  = .02). The highest HR was observed among CRC cases in the highest body mass index (BMI) and glycer-AGEs category relative to lowest BMI and glycer-AGEs category for both CRC-specific (HR = 1.78, 95% CI: 1.02-3.01) and all-cause mortality (HR = 2.15, 95% CI: 1.33-3.47), although no statistically significant effect modification was observed. Our study found that prediagnostic circulating glycer-AGEs are positively associated with CRC-specific and all-cause mortality among individuals with CRC. Further investigations in other populations and stratifying by tumor location and BMI are warranted.

Toward a More Climate-Sustainable Diet: Possible Deleterious Impacts on Health When Diet Quality Is Ignored.

BACKGROUND: Nutritional quality, and health and climate impacts are important considerations in the design of sustainable diets. OBJECTIVES: To investigate the association between diets varying in nutrient density and climate impact and MI and stroke HRs. METHODS: Dietary data of 41,194 women and 39,141 men (35-65 y) who participated in a Swedish population-based cohort study were employed. Nutrient density was calculated using the Sweden-adapted Nutrient Rich Foods 11.3 index. Dietary climate impact was calculated with data from life cycle assessments, including greenhouse gas emissions from primary production to industry gate. HRs and 95% CIs for MI and stroke were assessed with multivariable Cox proportional hazards regression, comparing a least-desirable diet scenario reference group (lower nutrient density, higher climate impact) with three diet groups that varied with respect to higher/lower nutrient density and higher/lower climate impact. RESULTS: Median follow-up time from the baseline study visit to MI or stroke diagnosis was 15.7 y for women and 12.8 y for men. The MI hazard was significantly higher for the men with diets of lower nutrient density and lower climate impact (HR: 1.19; 95% CI: 1.06, 1.33; P = 0.004), compared with the reference group. No significant association with MI was observed for any of the diet groups of women. No significant association with stroke was observed among any of the diet groups of women or men. CONCLUSIONS: The results among men suggest some adverse health effects for men when diet quality is not considered in the pursuit of more climate-sustainable diets. For women, no significant associations were detected. The mechanism underlying this association for men needs further investigation.

The breast milk and childhood gastrointestinal microbiotas and disease outcomes: a longitudinal study.

BACKGROUND: We aimed to characterize breast milk microbiota and define associations with saliva and fecal microbiota and selected diseases in preschool children. METHODS: In a longitudinal cohort study, the microbiotas from breast milk, mouth, and fecal samples were characterized by 16S rRNA gene sequencing. Questionnaires and medical records provided information on demographics, medical, and dental data. RESULTS: The phylogeny in breast milk, saliva swabs, and feces differed at all levels (p < 0.0003), though all harbored species in Streptococcus, Veillonella, and Haemophilus. Species richness was highest in breast milk with increasing resemblance with the oral swab microbiota by increasing age. Caries-affected children at age 5 had been fed breast milk with tenfold higher abundance of caries-associated bacteria, e.g., Streptococcus mutans, than caries-free children (p < 0.002). At that age, taxa, e.g., Neisseria sicca were overrepresented in saliva swabs of children with otitis media (LDA score >2, p < 0.05). Gut symbionts, e.g., Bacteroides, were underrepresented in 3-month fecal samples in children later diagnosed with allergic disease (LDA score >2, p < 0.05). CONCLUSIONS: Distinct microbiotas for the three sources were confirmed, though resemblance between milk and oral swab microbiota increased by age. Future studies should evaluate if the observed associations with disease outcomes are causal. IMPACT: Few studies have studied the association between breast milk microbiota and gastrointestinal microbiota beyond early infancy. The present study confirms distinct microbiota profiles in breast milk, saliva swabs, and feces in infancy and indicates increasing resemblance between breast milk and the oral microbiota by increasing age. The fecal microbiota at 3 months was associated with later allergic disease; the saliva microbiota by age 5 differed between children with and without otitis media at the same age; and children with caries by age 5 had been fed breast milk with a higher abundance of caries-associated bacteria.

Healthy Nordic diet and associations with plasma concentrations of metabolites in the choline oxidation pathway: a cross-sectional study from Northern Sweden.

BACKGROUND: The choline oxidation pathway and metabolites involved have been linked to diseases including cardiovascular disease, type 2 diabetes and cancer. A healthy Nordic diet is a recently defined dietary pattern associated with decreased risk for these diseases. Our aim was to explore associations between adherence to a healthy Nordic diet and plasma concentrations of metabolites of the choline oxidation pathway. METHODS: The Healthy Nordic Food Index (HNFI) and Baltic Sea Diet Score (BSDS) were applied to cross-sectional data (n = 969) from the Västerbotten Intervention Programme in Northern Sweden to score adherence to a healthy Nordic diet. Data included responses to a dietary questionnaire and blood sample analyses (1991-2008). Associations of diet scores with plasma concentrations of metabolites of the choline oxidation pathway and total homocysteine (tHcy), seven metabolites in total, were evaluated with linear regression, adjusting for age, BMI, education and physical activity. RESULTS: HNFI scores showed linear relationships with plasma choline (ß = 0.11), betaine (ß = 0.46), serine (ß = 0.98) and tHcy (ß = - 0.38), and BSDS scores with betaine (ß = 0.13) and tHcy (ß = - 0.13); unstandardized beta coefficients, all significant at P < 0.05. The regression models predicted changes in plasma metabolite concentrations (± 1 SD changes in diet score) in the range of 1-5% for choline, betaine, serine and tHcy. No other statistically significant associations were observed. CONCLUSIONS: A healthy Nordic diet was associated with plasma concentrations of several metabolites of the choline oxidation pathway. Although relationships were statistically significant, effect sizes were moderate. Further research is warranted to explore the underlying mechanisms and associations with health outcomes.

Adherence to the Swedish dietary guidelines and the impact on mortality and climate in a population-based cohort study.

OBJECTIVE: To assess the associations between adherence to the Swedish dietary guidelines and all-cause mortality (i.e. assessing the index' ability to predict health outcomes), as well as levels of dietary greenhouse gas emissions (GHGEs). DESIGN: A longitudinal study 1990-2016 within the population-based cohort Västerbotten Intervention Programme. Dietary data were based on FFQs. Diet quality was assessed by the Swedish Healthy Eating Index for Adults 2015 (SHEIA15), based on the 2015 Swedish dietary guidelines. Dietary GHGEs were estimated from life cycle assessment data including emissions from farm to industry gate. Hazard ratios (HR) and 95 % CI of all-cause mortality were evaluated with Cox proportional hazards regression, and differences in median GHGEs were tested between quintiles of SHEIA15 score using the Kruskal-Wallis one-way ANOVA test. SETTING: Northern Sweden. PARTICIPANTS: In total, 49 124 women and 47 651 men, aged 35-65 years. RESULTS: Median follow-up times were 16·0 years for women and 14·7 years for men, during which time 3074 women and 4212 men died. A consistent trend of lower all-cause mortality HR for both sexes with higher SHEIA15 scores was demonstrated. For women, the all-cause mortality HR was 0·81 ((95 % CI 0·71, 0·92); P = 0·001) and for men 0·90 ((95 % CI 0·81, 0·996); P = 0·041) between the quintile with the highest SHEIA15 score compared with the quintile with the lowest SHEIA15 score. A consistent trend of lower estimated dietary GHGEs among both sexes with higher SHEIA15 scores was also found. CONCLUSIONS: Adherence to Swedish dietary guidelines, estimated by SHEIA15, seems to promote longevity and reduce dietary climate impact.

Diet-wide association study of 92 foods and nutrients and lung cancer risk in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study.

It is unclear whether diet, and in particular certain foods or nutrients, are associated with lung cancer risk. We assessed associations of 92 dietary factors with lung cancer risk in 327 790 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) per SD higher intake/day of each food/nutrient. Correction for multiple comparisons was performed using the false discovery rate and identified associations were evaluated in the Netherlands Cohort Study (NLCS). In EPIC, 2420 incident lung cancer cases were identified during a median of 15 years of follow-up. Higher intakes of fibre (HR per 1 SD higher intake/day = 0.91, 95% CI 0.87-0.96), fruit (HR = 0.91, 95% CI 0.86-0.96) and vitamin C (HR = 0.91, 95% CI 0.86-0.96) were associated with a lower risk of lung cancer, whereas offal (HR = 1.08, 95% CI 1.03-1.14), retinol (HR = 1.06, 95% CI 1.03-1.10) and beer/cider (HR = 1.04, 95% CI 1.02-1.07) intakes were positively associated with lung cancer risk. Associations did not differ by sex and there was less evidence for associations among never smokers. None of the six associations with overall lung cancer risk identified in EPIC were replicated in the NLCS (2861 cases), however in analyses of histological subtypes, inverse associations of fruit and vitamin C with squamous cell carcinoma were replicated in the NLCS. Overall, there is little evidence that intakes of specific foods and nutrients play a major role in primary lung cancer risk, but fruit and vitamin C intakes seem to be inversely associated with squamous cell lung cancer.

A Prospective Diet-Wide Association Study for Risk of Colorectal Cancer in EPIC.

BACKGROUND & AIMS: Evidence regarding the association of dietary exposures with colorectal cancer (CRC) risk is not consistent with a few exceptions. Therefore, we conducted a diet-wide association study (DWAS) in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the associations between several dietary exposures with CRC risk. METHODS: The association of 92 food and nutrient intakes with CRC risk was assessed in 386,792 participants, 5069 of whom developed incident CRC. Correction for multiple comparisons was performed using the false discovery rate, and emerging associations were examined in the Netherlands Cohort Study (NLCS). Multiplicative gene-nutrient interactions were also tested in EPIC based on known CRC-associated loci. RESULTS: In EPIC, alcohol, liquor/spirits, wine, beer/cider, soft drinks, and pork were positively associated with CRC, whereas milk, cheese, calcium, phosphorus, magnesium, potassium, riboflavin, vitamin B6, beta carotene, fruit, fiber, nonwhite bread, banana, and total protein intakes were inversely associated. Of these 20 associations, 13 were replicated in the NLCS, for which a meta-analysis was performed, namely alcohol (summary hazard ratio [HR] per 1-SD increment in intake: 1.07; 95% confidence interval [CI], 1.04-1.09), liquor/spirits (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02-1.06), wine (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02-1.07), beer/cider (HR per 1-SD increment in intake, 1.06; 95% CI, 1.04-1.08), milk (HR per 1-SD increment in intake, 0.95; 95% CI, 0.93-0.98), cheese (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94-0.99), calcium (HR per 1-SD increment in intake, 0.93; 95% CI, 0.90-0.95), phosphorus (HR per 1-SD increment in intake, 0.92; 95% CI, 0.90-0.95), magnesium (HR per 1-SD increment in intake, 0.95; 95% CI, 0.92-0.98), potassium (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94-0.99), riboflavin (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92-0.97), beta carotene (HR per 1-SD increment in intake, 0.96; 95% CI, 0.93-0.98), and total protein (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92-0.97). None of the gene-nutrient interactions were significant after adjustment for multiple comparisons. CONCLUSIONS: Our findings confirm a positive association for alcohol and an inverse association for dairy products and calcium with CRC risk, and also suggest a lower risk at higher dietary intakes of phosphorus, magnesium, potassium, riboflavin, beta carotene, and total protein.

Food biodiversity and total and cause-specific mortality in 9 European countries: An analysis of a prospective cohort study.

BACKGROUND: Food biodiversity, encompassing the variety of plants, animals, and other organisms consumed as food and drink, has intrinsic potential to underpin diverse, nutritious diets and improve Earth system resilience. Dietary species richness (DSR), which is recommended as a crosscutting measure of food biodiversity, has been positively associated with the micronutrient adequacy of diets in women and young children in low- and middle-income countries (LMICs). However, the relationships between DSR and major health outcomes have yet to be assessed in any population. METHODS AND FINDINGS: We examined the associations between DSR and subsequent total and cause-specific mortality among 451,390 adults enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) study (1992 to 2014, median follow-up: 17 years), free of cancer, diabetes, heart attack, or stroke at baseline. Usual dietary intakes were assessed at recruitment with country-specific dietary questionnaires (DQs). DSR of an individual's yearly diet was calculated based on the absolute number of unique biological species in each (composite) food and drink. Associations were assessed by fitting multivariable-adjusted Cox proportional hazards regression models. In the EPIC cohort, 2 crops (common wheat and potato) and 2 animal species (cow and pig) accounted for approximately 45% of self-reported total dietary energy intake [median (P10-P90): 68 (40 to 83) species consumed per year]. Overall, higher DSR was inversely associated with all-cause mortality rate. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing total mortality in the second, third, fourth, and fifth (highest) quintiles (Qs) of DSR to the first (lowest) Q indicate significant inverse associations, after stratification by sex, age, and study center and adjustment for smoking status, educational level, marital status, physical activity, alcohol intake, and total energy intake, Mediterranean diet score, red and processed meat intake, and fiber intake [HR (95% CI): 0.91 (0.88 to 0.94), 0.80 (0.76 to 0.83), 0.69 (0.66 to 0.72), and 0.63 (0.59 to 0.66), respectively; PWald < 0.001 for trend]. Absolute death rates among participants in the highest and lowest fifth of DSR were 65.4 and 69.3 cases/10,000 person-years, respectively. Significant inverse associations were also observed between DSR and deaths due to cancer, heart disease, digestive disease, and respiratory disease. An important study limitation is that our findings were based on an observational cohort using self-reported dietary data obtained through single baseline food frequency questionnaires (FFQs); thus, exposure misclassification and residual confounding cannot be ruled out. CONCLUSIONS: In this large Pan-European cohort, higher DSR was inversely associated with total and cause-specific mortality, independent of sociodemographic, lifestyle, and other known dietary risk factors. Our findings support the potential of food (species) biodiversity as a guiding principle of sustainable dietary recommendations and food-based dietary guidelines.

Using national register data to estimate the heritability of periodontitis.

AIM: To identify whether periodontal traits derived from electronic dental records are biologically informative and heritable. MATERIALS AND METHODS: The study included 11,974 adult twins (aged 30-92 years) in the Swedish Twin Registry. Periodontal records from dental examinations were retrieved from a national register and used to derive continuous measures of periodontal health. A latent class approach was used to derive categorial measures of periodontal status. The correlation patterns in these traits were contrasted in monozygotic and dizygotic twin pairs using quantitative genetic models to estimate the heritability of the traits. RESULTS: For continuous traits, heritability estimates ranged between 41.5% and 48.3% with the highest estimates for number of missing tooth surfaces and rate of change in number of deep periodontal pockets (≥6 mm). For categorial traits, the latent class approach identified three classes (good periodontal health, mild periodontitis signs and severe signs of periodontitis) and there was a clear difference in the hazard for subsequent tooth loss between these three classes. Despite this, the class allocations were only slightly more heritable than a conventional dichotomous disease definition (45.2% vs. 42.6%). CONCLUSIONS: Periodontitis is a moderately heritable disease. Quantitative periodontal traits derived from electronic records are an attractive target for future genetic association studies.

Consumption of Meat, Fish, Dairy Products, and Eggs and Risk of Ischemic Heart Disease.

BACKGROUND: There is uncertainty about the relevance of animal foods to the pathogenesis of ischemic heart disease (IHD). We examined meat, fish, dairy products, and eggs and risk for IHD in the pan-European EPIC cohort (European Prospective Investigation Into Cancer and Nutrition). METHODS: In this prospective study of 409 885 men and women in 9 European countries, diet was assessed with validated questionnaires and calibrated with 24-hour recalls. Lipids and blood pressure were measured in a subsample. During a mean of 12.6 years of follow-up, 7198 participants had a myocardial infarction or died of IHD. The relationships of animal foods with risk were examined with Cox regression with adjustment for other animal foods and relevant covariates. RESULTS: The hazard ratio (HR) for IHD was 1.19 (95% CI, 1.06-1.33) for a 100-g/d increment in intake of red and processed meat, and this remained significant after exclusion of the first 4 years of follow-up (HR, 1.25 [95% CI, 1.09-1.42]). Risk was inversely associated with intakes of yogurt (HR, 0.93 [95% CI, 0.89-0.98] per 100-g/d increment), cheese (HR, 0.92 [95% CI, 0.86-0.98] per 30-g/d increment), and eggs (HR, 0.93 [95% CI, 0.88-0.99] per 20-g/d increment); the associations with yogurt and eggs were attenuated and nonsignificant after exclusion of the first 4 years of follow-up. Risk was not significantly associated with intakes of poultry, fish, or milk. In analyses modeling dietary substitutions, replacement of 100 kcal/d from red and processed meat with 100 kcal/d from fatty fish, yogurt, cheese, or eggs was associated with ≈20% lower risk of IHD. Consumption of red and processed meat was positively associated with serum non-high-density lipoprotein cholesterol concentration and systolic blood pressure, and consumption of cheese was inversely associated with serum non-high-density lipoprotein cholesterol. CONCLUSIONS: Risk for IHD was positively associated with consumption of red and processed meat and inversely associated with consumption of yogurt, cheese, and eggs, although the associations with yogurt and eggs may be influenced by reverse causation bias. It is not clear whether the associations with red and processed meat and cheese reflect causality, but they were consistent with the associations of these foods with plasma non-high-density lipoprotein cholesterol and for red and processed meat with systolic blood pressure, which could mediate such effects.

Nutrient-wide association study of 92 foods and nutrients and breast cancer risk.

BACKGROUND: Several dietary factors have been reported to be associated with risk of breast cancer, but to date, unequivocal evidence only exists for alcohol consumption. We sought to systematically assess the association between intake of 92 foods and nutrients and breast cancer risk using a nutrient-wide association study. METHODS: Using data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression was used to quantify the association between each food/nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to be replicated in the independent Netherlands Cohort Study (NLCS). RESULTS: Six foods and nutrients were identified as associated with risk of breast cancer in the EPIC study (10,979 cases). Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake = 1.05, 95% CI 1.03-1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment = 1.05, 95% CI 1.03-1.06 and 1.04, 95% CI 1.02-1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment = 0.96, 95% CI 0.94-0.98; 0.96, 95% CI 0.94-0.99; and 0.96, 95% CI 0.95-0.98, respectively). When evaluated in the NLCS (2368 cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk in the NLCS. CONCLUSIONS: Our findings confirm a positive association of alcohol consumption and suggest an inverse association of dietary fibre and possibly fruit intake with breast cancer risk.

Consortium-based genome-wide meta-analysis for childhood dental caries traits.

Prior studies suggest dental caries traits in children and adolescents are partially heritable, but there has been no large-scale consortium genome-wide association study (GWAS) to date. We therefore performed GWAS for caries in participants aged 2.5-18.0 years from nine contributing centres. Phenotype definitions were created for the presence or absence of treated or untreated caries, stratified by primary and permanent dentition. All studies tested for association between caries and genotype dosage and the results were combined using fixed-effects meta-analysis. Analysis included up to 19 003 individuals (7530 affected) for primary teeth and 13 353 individuals (5875 affected) for permanent teeth. Evidence for association with caries status was observed at rs1594318-C for primary teeth [intronic within ALLC, odds ratio (OR) 0.85, effect allele frequency (EAF) 0.60, P 4.13e-8] and rs7738851-A (intronic within NEDD9, OR 1.28, EAF 0.85, P 1.63e-8) for permanent teeth. Consortium-wide estimated heritability of caries was low [h2 of 1% (95% CI: 0%: 7%) and 6% (95% CI 0%: 13%) for primary and permanent dentitions, respectively] compared with corresponding within-study estimates [h2 of 28% (95% CI: 9%: 48%) and 17% (95% CI: 2%: 31%)] or previously published estimates. This study was designed to identify common genetic variants with modest effects which are consistent across different populations. We found few single variants associated with caries status under these assumptions. Phenotypic heterogeneity between cohorts and limited statistical power will have contributed; these findings could also reflect complexity not captured by our study design, such as genetic effects which are conditional on environmental exposure.

Dairy Products and Cancer Risk in a Northern Sweden Population.

The role of dairy products in cancer is unclear. We assessed consumption of fermented milk, non-fermented milk, cheese, and butter, estimated from semi-quantitative food frequency questionnaires, in relation to prospective risk of breast, prostate, colorectal, smoking-, and obesity-related cancers in 101,235 subjects, including 12,552 cancer cases, in the population-based Northern Sweden Health and Disease Study. Most analyses (n = 20) rendered null results. In men, we observed an increased prostate cancer risk among high-consumers of cheese (hazard ratio (HR) for highest vs. lowest quintile (Q5-Q1), 1.11; 95% CI, 0.97-1.27; Ptrend = 0.013). In women, high-consumers of cheese had a decreased risk of overall cancer (HR Q5-Q1, 0.95; 95% CI, 0.88-1.04; Ptrend = 0.039), smoking-related (HR Q5-Q1, 0.84; 95% CI, 0.72-0.97; Ptrend ≤ 0.001), and colorectal cancers (HR Q5-Q1, 0.82; 95% CI, 0.63-1.07; Ptrend = 0.048). Butter yielded a weak decreased obesity-related cancer risk in women (HR Q5-Q1, 0.91; 95% CI, 0.81-1.02; Ptrend = 0.049). Fermented milk yielded HRs below zero in women, but with no clear linear associations. In conclusion, this study does not support any major adverse or beneficial effects of fermented milk, non-fermented milk, cheese, and butter in the diet from a cancer risk perspective.

A nutrient-wide association study for risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition and the Netherlands Cohort Study.

PURPOSE: The evidence from the literature regarding the association of dietary factors and risk of prostate cancer is inconclusive. METHODS: A nutrient-wide association study was conducted to systematically and comprehensively evaluate the associations between 92 foods or nutrients and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cox proportional hazard regression models adjusted for total energy intake, smoking status, body mass index, physical activity, diabetes and education were used to estimate hazard ratios and 95% confidence intervals for standardized dietary intakes. As in genome-wide association studies, correction for multiple comparisons was applied using the false discovery rate (FDR < 5%) method and suggested results were replicated in an independent cohort, the Netherlands Cohort Study (NLCS). RESULTS: A total of 5916 and 3842 incident cases of prostate cancer were diagnosed during a mean follow-up of 14 and 20 years in EPIC and NLCS, respectively. None of the dietary factors was associated with the risk of total prostate cancer in EPIC (minimum FDR-corrected P, 0.37). Null associations were also observed by disease stage, grade and fatality, except for positive associations observed for intake of dry cakes/biscuits with low-grade and butter with aggressive prostate cancer, respectively, out of which the intake of dry cakes/biscuits was replicated in the NLCS. CONCLUSIONS: Our findings provide little support for an association for the majority of the 92 examined dietary factors and risk of prostate cancer. The association of dry cakes/biscuits with low-grade prostate cancer warrants further replication given the scarcity in the literature.

Diet and nutrient status of legume consumers in Sweden: a descriptive cross-sectional study.

BACKGROUND: Legumes are nutrient-dense foods and can be an environmentally sustainable alternative to meat consumption. Data on legume intake are scarce and data on legume consumption in Sweden are lacking. This study investigated dietary intake and dietary patterns, together with iron, vitamin D, and folate status, in relation to legume consumption in Sweden. METHODS: Cross-sectional dietary and biomarker data (n 1760) from the 2011 Riksmaten national survey were analyzed. All legume foods (including soy) were identified from 4-day dietary records and ferritin, folate, and vitamin D status in a subgroup (n 280). Participants were classified into non-consumers and quartiles of legume intake. Principal Component Analysis (PCA) was performed to uncover dietary patterns associated with legume intake. Partial Least Square (PLS) regression was used to identify variables associated with variations in legume consumption. RESULTS: Legumes were consumed by 44% of the population, with mean (SD) intake of 138 (84) g/d in the highest and 11 (5) g/d in the lowest quartiles. Among consumers, 6% reported being vegetarian, compared with 0.9% among non-consumers. Legume consumers drank less alcohol, but had higher intakes of energy, dietary fiber, folate, thiamin, and several minerals, and more often met recommended intake levels for folate and fiber, critical nutrients in Sweden. Biomarker status did not differ with legume intake. PCA revealed multiple loadings on legumes that generally reflected healthier eating habits for legume-consuming women. PLS revealed that vegetarianism was most influential for high legume intake. Other influential variables were high fruit, tea, nut, and seed intakes. High intake of meat, sodas, fast foods, and sweet foods, together with omnivorism, were influential for low legume intake. The associations were similar for men and women. CONCLUSIONS: This study supports dietary recommendations on inclusion of legumes in a healthy diet. Greater focus on assessment of legume intake is necessary to explore the population-wide health effects of legumes as sustainable meat alternatives, and to reinforce national nutritional guidelines.