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Background: Venous thromboembolism (VTE) has been associated with several modifiable factors (MFs) and cardiovascular comorbidities. However, the mechanisms are largely unknown., Objectives: We aimed to decipher proteomic pathways underlying the associations of VTE with MFs and cardiovascular comorbidities., Methods: A 2-stage network Mendelian randomization analysis was conducted to explore the associations between 15 MFs, 1151 blood proteins, and VTE using data from a genome-wide meta-analysis including 81 190 cases of VTE. We used protein data from 35 559 individuals as the discovery analysis, and from 2 independent studies including 10 708 and 54 219 participants as the replication analyses. Based on the identified proteins, we assessed the druggability and examined the cardiovascular pleiotropy., Results: The network Mendelian randomization analyses identified 10 MF-VTE, 86 MF-protein, and 34 protein-VTE associations. These associations were overall consistent in the replication analyses. Thirty-eight pathways with directionally consistent direct and indirect effects in the MF-protein-VTE pathway were identified. Low-density lipoprotein receptor-related protein 12 (LRP12: 34.3%-58.1%) and coagulation factor (F)XI (20.6%-39.6%) mediated most of the associations between 3 obesity indicators and VTE. Likewise, coagulation FXI mediated most of the smoking-VTE association (40%; 95% CI, 20%-60%) and insomnia-VTE association (27%; 95% CI, 5%-49%). Many VTE-associated proteins were highly druggable for thrombotic conditions. Five proteins (interleukin-6 receptor subunit alpha, LRP12, prothrombin, angiopoietin-1, and low-density lipoprotein receptor-related protein 4) were associated with VTE and its cardiovascular comorbidities., Conclusion: This study suggests that coagulation FXI, a druggable target, is an important mediator of the associations of obesity, smoking, and insomnia with VTE risk., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background & Aims: Ultra-processed food (UPF) intake has been associated with multiple health outcomes, but data on the association between UPF intake and venous thromboembolism (VTE) risk are lacking. We conducted this study to examine the association between UPF intake and the risk of incident VTE., Methods: This prospective cohort study was based on 186,323 participants free of baseline VTE from the UK Biobank. UPF intake was assessed by 24-h recall questionnaires. Data on incident VTE came from the nationwide inpatient and primary care datasets and the death registry. Cox proportional hazards regression was used to estimate the association between UPF intake and incident VTE risk. Multiplicative interactions and stratified analyses by age, sex, and body mass index were performed., Results: During a 10.5-year (median) follow-up, 4235 incident VTE cases were diagnosed. After adjusting for covariates, the hazard ratio of VTE among individuals with the highest quintile of UPF intake was 1.05 (95% confidence interval [CI] 0.94, 1.17) for UPF in servings, 1.12 (95% CI 1.01, 1.24) in grams, 1.10 (95% CI 1.00, 1.22) in grams %, 1.21 (95% CI 1.10, 1.33) in energy, and 1.15 (95% CI 1.05, 1.27) in energy % compared to those in the lowest quintile. Age, sex, and body mass index did not modify the associations (P interaction > 0.05)., Conclusions: Higher UPF intake was associated with a moderately increased risk of VTE., Competing Interests: Conflict of interest All authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background Colon cancer incidence is rising globally, and factors pertaining to urbanization have been proposed involved in this development. Traffic noise may increase colon cancer risk by causing sleep disturbance and stress, thereby inducing known colon cancer risk-factors, e.g. obesity, diabetes, physical inactivity, and alcohol consumption, but few studies have examined this. Objectives The objective of this study was to investigate the association between traffic noise and colon cancer (all, proximal, distal) in a pooled population of 11 Nordic cohorts, totaling 155,203 persons. Methods We identified residential address history and estimated road, railway, and aircraft noise, as well as air pollution, for all addresses, using similar exposure models across cohorts. Colon cancer cases were identified through national registries. We analyzed data using Cox Proportional Hazards Models, adjusting main models for harmonized sociodemographic and lifestyle data. Results During follow-up (median 18.8 years), 2757 colon cancer cases developed. We found a hazard ratio (HR) of 1.05 (95% confidence interval (CI): 0.99-1.10) per 10-dB higher 5-year mean time-weighted road traffic noise. In sub-type analyses, the association seemed confined to distal colon cancer: HR 1.06 (95% CI: 0.98-1.14). Railway and aircraft noise was not associated with colon cancer, albeit there was some indication in sub-type analyses that railway noise may also be associated with distal colon cancer. In interaction-analyses, the association between road traffic noise and colon cancer was strongest among obese persons and those with high NO 2 -exposure. Discussion A prominent study strength is the large population with harmonized data across eleven cohorts, and the complete address-history during follow-up. However, each cohort estimated noise independently, and only at the most exposed façade, which may introduce exposure misclassification. Despite this, the results of this pooled study suggest that traffic noise may be a risk factor for colon cancer, especially of distal origin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The implication of calcium and magnesium in drinking water for cardiovascular disease is unclear., Objectives: To assess the association of the concentration of calcium and magnesium in drinking water with incidence of myocardial infarction and stroke, accounting for dietary mineral intake., Methods: We linked drinking water monitoring data to residential information of 26,733 women from the population-based Swedish Mammography Cohort, who completed a 96-item FFQ at baseline. Drinking water was categorized into low (magnesium <10 mg/L and calcium <50 mg/L) or high (magnesium ≥10 mg/L or calcium ≥50 mg/L) mineral concentration. Incident cases of myocardial infarction and stroke types were ascertained 1998-2019 using the National Patient Register., Results: The mean ± SD concentration of calcium and magnesium in drinking water was 29 ± 7 mg/L and 5 ± 1 mg/L in the low-exposed area and 52 ± 20 mg/L and 10 ± 3 mg/L in the high-exposed area, respectively. During 16 years of follow-up, we ascertained 2023, 2279, and 452 cases of myocardial infarction, ischemic stroke, and hemorrhagic stroke, respectively. High drinking water calcium and magnesium was associated with lower risk of ischemic and hemorrhagic stroke HRs of 0.87 (95% CI: 0.80, 0.95) and 0.78 (95% CI: 0.65, 0.95), whereas the HR for myocardial infarction was 0.93 (95% CI: 0.85, 1.02). In separate analyses, only drinking water magnesium, not calcium, remained associated with ischemic stroke (HR: 0.69; 95% CI: 0.54, 0.88)., Conclusions: Drinking water with a high concentration of calcium and magnesium, particularly magnesium, may lower the risk of stroke in postmenopausal women., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Acrylamide is a food contaminant linked to developmental toxicity in animals and possibly in humans., Objectives: We performed a systematic review and dose-response meta-analysis of epidemiological studies evaluating the relationship between maternal acrylamide exposure during pregnancy and the risk of being small for gestational age (SGA) and birth weight, birth head circumference and birth length., Methods: We performed the literature search in PubMed, Scopus, and Web of Science, until June 6th, 2022. Studies carried out in mother-newborn pairs, assessing maternal acrylamide exposure during pregnancy, either via dietary assessments or biomarkers i.e., hemoglobin adducts of acrylamide (AA-Hb) and glycidamide (GA-Hb), and evaluating birth outcomes were included. We employed a random-effects model to assess the pooled effect estimates and their 95% confidence intervals (CI) for the association between acrylamide exposure and birth outcomes. Risk of Bias for Nutrition Observational Studies tool was used for bias assessment., Results: Out of 169 records identified, five original studies were eligible, including 53,870 mother-newborn pairs in total. Means were 21.9 μg/day for estimated dietary acrylamide exposure (3 studies), and 18.4 and 14.9 pmol/g for AA-Hb and GA-Hb, respectively (2 studies). Higher risk of SGA and lower birth weight and head circumference were observed in the highest quartile of AA-Hb [odds ratio (OR): 1.20 (95% CI: 1.08; 1.33); mean difference (MD): -131 g (95% CI: -204; -58) and -0.31 cm (95% CI: -0.58; -0.04), respectively], and GA-Hb [OR: 1.36 (95% CI: 1.13; 1.64), MD: -161 g (95% CI: -271; -52); and MD: -0.38 cm (95% CI: -0.66; -0.10), respectively], whereas a lower birth length was observed only in the highest quartile of GA-Hb (MD: -0.85 cm (95% CI: -1.38; -0.33). Results from the dose-response meta-analysis between increasing maternal acrylamide exposure during pregnancy and birth weight showed no clear evidence of a deviation from linearity., Conclusions: Overall, our findings strengthen the evidence of an adverse effect of maternal acrylamide exposure during pregnancy on fetal growth. These results encourage to increase preventive actions towards lowering acrylamide exposure in the population., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the joint associations of multiple modifiable lifestyle factors with the risk of symptomatic peripheral artery disease (PAD) referred to secondary care in the healthy, community based population., Methods: A prospective cohort study was conducted including 37 633 men from the Cohort of Swedish Men and 31 816 women from the Swedish Mammography Cohort who were free of clinically diagnosed PAD and 45 - 83 years of age at baseline. Healthy lifestyle factors were defined as avoidance of excessive alcohol consumption (≤ 2 drinks/day), high adherence to a healthy diet (modified Mediterranean diet score ≥ 4), moderate to high level of physical activity (≥ 30 minutes/day), and never smoking. PAD cases were ascertained by linkage with the Swedish National Patient Registry. Cox proportional hazards regression was used to analyse the data., Results: During a mean of 18.1 years of follow up (from 1 January 1998 to 31 December 2019), 2 795 incident symptomatic PAD cases were ascertained. All healthy lifestyle factors were associated with a reduced PAD risk. Individuals who adhered to all four healthy lifestyle factors had a 45% (95% confidence interval [CI] 38 - 51) lower risk of PAD compared with the remainder of the population (0 - 3 healthy lifestyle factors) and a 71% (95% CI 61 - 79) lower risk of PAD compared with the group without any healthy lifestyle factor. Adherence to the combination of four healthy lifestyle factors was estimated to prevent 40% (95% CI 34 - 47) of PAD cases., Conclusion: Healthy lifestyle factors were associated with a reduced risk of PAD., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The impact of the Nutri-Score labelling system on renal function is unknown., Objective: To assess the association between food consumption based on the nutrient profile system underlying the Nutri-Score and renal function decline in older adults., Methods: We used data from the Spain-based Seniors-ENRICA cohort, a study with 1312 community-dwelling adults aged ≥60 years recruited during 2008-2010 and followed up to December 2015. At baseline, a validated dietary history was obtained. Based on their nutritional quality, foods consumed were categorized into five labels (A/Green-best quality, B, C, D, E/Red-worst quality) using the established Nutri-Score algorithm. For each participant, a Nutri-Score dietary index (DI) was calculated in g/day/kg of weight. At baseline and at follow-up, measured serum creatinine (SCr) and estimated glomerular filtration rate (eGFR) levels were obtained, and time changes were calculated. A combined outcome for renal decline was defined as: any increase in SCr or any decrease in eGFR beyond expected-for-age. Statistical analyses were performed with logistic regression adjusting for socioeconomic, lifestyle, total energy intake, fresh foods, and comorbidity confounders., Results: A total of 183 cases of renal-function decline occurred over a mean 6-year follow-up. Participants with a higher (less favorable) Nutri-Score DI (interquartile range (IQR)13.2-17.7 (g/day/kg of weight); 46 cases) had higher probability of renal decline than those with a lower Nutri-Score DI (IQR 36.6-46.2; 44 cases); the corresponding odds ratios (95% confidence interval) across increasing quartiles of Nutri-Score DI were 1 (reference), 1.26 (0.78-2.04), 1.55 (0.92-2.62), and 1.82 (1.01-3.30), P-trend = 0.045. Per each 10-point increase in the Nutri-Score DI the odds of renal decline increased by 27% (6%-52%)., Conclusions: Higher Nutri-Score DI, reflecting the consumption of foods with less favourable Nutri-Score rating, was associated with higher kidney function decline in older adults. Consequently, Nutri-Score labeling might be a useful policy tool for preventing kidney function decline, adding to the potential health benefits of this front-of-pack labelling system., Competing Interests: Conflict of interest The authors have declared that no competing interests exist., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: Systemic inflammation plays a role in peripheral artery disease (PAD), and therefore, an anti-inflammatory diet may reduce PAD risk. We examined the association between the anti-inflammatory diet and PAD risk by smoking status, a trigger of systemic inflammation., Methods: The study was based on two cohorts of 82 295 Swedish adults aged 45-83 years (38 823 women from Swedish Mammography Cohort and 45 472 men from Cohort of Swedish Men). An anti-inflammatory diet index (AIDI; 0-17 scores) was used to estimate the anti-inflammatory potential of diet. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs)., Results: Over a median 22-year (interquartile range 7.5 years) follow-up period, 3413 PAD cases were ascertained. Compared with individuals in the lowest quartile of the AIDI (score ≤4), the HR of PAD for those in the highest quartile (score ≥8) was 0.84 (95% CI, 0.74-0.94). The inverse association was observed in current and past smokers but not in never smokers. The HR of PAD comparing extreme quartiles of the AIDI was 0.67 (95% CI, 0.53-0.86) in current smoker, 0.78 (95% CI, 0.63-0.97) in past smoker, and 1.00 (95% CI, 0.82-1.23) in never smokers. Among foods included in AIDI, high consumption of breakfast cereals, chocolate, red wine, and olive/canola oil, and low consumption of processed red meat and organ meats were associated with low PAD risk., Conclusions: The study suggests that adherence to a diet with high anti-inflammatory potential may lower PAD risk, especially in smokers., Competing Interests: Conflicts of interest All authors declare no conflict of interest with the exception for SMD who receives research support from RenalytixAI and personal consulting fees from Calico Labs, outside the scope of the current research., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: Inflammation has been revealed to facilitate thrombogenesis and to increase the risk of venous thromboembolism (VTE). However, limited data are available on the association between the anti-inflammatory diet and incident VTE. We conducted a cohort analysis to examine this association and to further examine whether this association is modified by smoking status, a trigger of systemic inflammation., Methods and Results: We used data from two cohorts including 81,507 middle-aged and older Swedish adults without previous VTE at baseline. An empirically validated anti-inflammatory diet index (AIDI), based on 12 foods with anti-inflammatory potential and 5 foods with pro-inflammatory potential, was employed to estimate the anti-inflammatory potential of diet. Hazard ratios (HRs), with corresponding 95% confidence intervals (CIs), of VTE were estimated by Cox proportional hazards regression models. During a mean follow-up of 17.8-years, 5241 VTE cases were diagnosed. Compared with individuals in the lowest quartile of the AIDI (score ≤4), those in the highest quartile (score ≥8) had a 9% (95% CI, 0-17%) lower risk of VTE. The inverse association was observed in current and past smokers (HR between the two extreme quartiles, 0.80, 95% CI, 0.70-0.91) but not in never smokers (HR, 1.03, 95% CI, 0.91-1.17). French fries (HR per serving, 1.33, 95% CI, 1.06, 1.67) but no other foods included in AIDI was associated with VTE., Conclusion: The study suggests that a consumption of foods with high anti-inflammatory potential may play a role in the prevention of VTE in smokers., Competing Interests: Declaration of competing interest All authors declare no conflict of interest with the exception for SMD who receives research support from RenalytixAI and personal consulting fees from Calico Labs, outside the scope of the current research., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Ultra-processed food (UPF) consumption has been associated with higher cardiovascular disease (CVD) and mortality risks., Objectives: The aim of this study was to assess the relationship between UPF consumption and incident dyslipidemia in older adults, where evidence is limited., Methods: We studied a prospective cohort of 1082 community-dwelling adults in Spain, older than 60 (mean age, 68 ± 6 years old). Participants (52% were women) were recruited between 2008-10 and followed up to 2015. At baseline, food intake data were collected using a validated computerized face-to-face dietary history. UPFs were identified according to the nature and extent of their industrial processing (NOVA classification). Triglycerides, HDL cholesterol, and LDL cholesterol were measured in fasting plasma samples collected at baseline and at follow-up. Statistical analyses were performed with logistic regression adjusted for the main potential confounders., Results: Among those free of corresponding dyslipidemia at baseline, and after a follow-up of between 5 to 7 years, 60 (out of 895) developed incident hypertriglyceridemia (≥150 mg/dL), 112 (out of 878) had low HDL cholesterol (<40 in men/<50 mg/dL in women), and 54 (out of 472) had high LDL cholesterol (>129 mg/dL). The mean percentage of UPF consumption was 19% ± 11% of total energy intake. Those in the highest versus the lowest tertile of energy intake from UPFs had more than twice the odds of incident hypertriglyceridemia (OR, 2.66; 95% CI: 1.20-5.90; P-trend, 0.011) or low HDL cholesterol (OR, 2.23; 95% CI: 1.22-4.05; P-trend, 0.012). UPF consumption was not associated with high LDL cholesterol plasma concentrations., Conclusions: Although UPF consumption in Spain was low among older adults, high consumption of UPFs was clearly associated with incident dyslipidemia. The increase in CVD risk recently found to be associated with UPF consumption might be mediated by these atherogenic lipid abnormalities., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Abdominal obesity has been shown to be a superior measure over overall obesity for detecting cardiovascular risk., Objective: We conducted this study to compare the effects of overall and abdominal obesity on venous thromboembolism (VTE) and to calculate population attributable fraction for obesity for VTE., Methods: Body mass index (BMI) and waist circumference (WC) were used to represent overall and abdominal obesity, respectively. In the cohort study, we included 74317 Swedish adults with anthropometric measures in 1997 and of whom 4332 were diagnosed with VTE until the end of 2017. A Mendelian randomization study was conducted to investigate causal associations of BMI, WC, and WC adjusted for BMI with VTE using data from FinnGen and UK Biobank study. Population attributable fraction was calculated for overall and abdominal obesity for VTE., Results: In the cohort study, there were dose-response associations of BMI and WC with VTE. The association between BMI and VTE was attenuated largely after adjusting for WC. Among individuals with normal BMI, participants with substantially increased WC had 53% higher (hazard ratio 1.53; 95% confidence interval, 1.28, 1.81) risk of VTE compared to those with normal WC. The causality of the association of WC adjusted for BMI with VTE was confirmed in Mendelian randomization analysis. The estimated population-attributable risk due to elevated BMI and WC were 12.4% (8.4%, 16.5%) and 23.7% (18.1%, 29.4%), respectively., Conclusions: WC might be a preferable indicator linking obesity to VTE. A large proportion of VTE cases can be prevented if the population maintained a healthy BMI and WC., (© 2020 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

Background: There is conflicting evidence regarding the association between fish intake and type 2 diabetes (T2D) incidence, possibly owing to measurement errors in self-reported intake and coexposure to persistent organic pollutants (POPs) present in fish., Objective: The aim of this study was to identify plasma metabolites associated with fish intake and to assess their association with T2D risk, independently of POPs, in Swedish adults., Methods: In a case-control study nested in the Swedish Västerbotten Intervention Programme, fasting plasma samples from 421 matched T2D case-control pairs of men and women aged 30-60 y at baseline and 10-y follow-up samples from a subset of 149 pairs were analyzed using untargeted metabolomics. Moreover, 16 plasma POPs were analyzed for the 149 pairs who had repeated samples available. Fish-related plasma metabolites were identified using multivariate modelling and partial correlation analysis. Reproducibility of metabolites and metabolite patterns, derived via principal component analysis (PCA), was assessed by intraclass correlation. A unique component of metabolites unrelated to POPs was dissected by integrating metabolites and POPs using 2-way orthogonal partial least squares regression. ORs of T2D were estimated using conditional logistic regression., Results: We identified 31 metabolites associated with fish intake that had poor to good reproducibility. A PCA-derived metabolite pattern strongly correlated with fish intake (ρ = 0.37, P < 0.001) but showed no association with T2D risk. Integrating fish-related metabolites and POPs led to a unique metabolite component independent of POPs, which tended to be inversely associated with T2D risk (OR: 0.75; 95% CI: 0.54, 1.02, P = 0.07). This component mainly consisted of metabolites reflecting fatty fish intake., Conclusions: Our results suggest that fatty fish intake may be beneficial for T2D prevention, after removing the counteractive effects of coexposure to POPs in Swedish adults. Integrating metabolite markers and POP exposures appears a promising approach to advance the understanding of associations between fish intake and T2D incidence., (Copyright © American Society for Nutrition 2019.)

Background: Persistent organic pollutants (POPs) have been associated with type 2 diabetes (T2D), but causality is uncertain., Objective: Within longitudinal population-based data from northern Sweden, we assessed how POPs associated with T2D prospectively and cross-sectionally, and further investigated factors related to individual changes in POP concentrations., Methods: For 129 case-controls pairs matched by age, sex and date of sampling, plasma concentrations of hexachlorobenzene (HCB), dichlorodiphenyl-dichloroethylene (p,p'-DDE), dioxin-like (DL) polychlorinated biphenyl congeners (PCB-118 and PCB-156), and non-dioxin like (NDL-PCB: PCB-74, -99, -138 -153, -170, -180, -183 and PCB-187) were analyzed twice (baseline and follow-up, 9-20 years apart). The cases received their T2D diagnose between baseline and follow-up. Prospective (using baseline data) and cross-sectional (using follow-up data) odds ratios (ORs) for T2D on lipid standardized POPs (HCB, p,p'-DDE, ∑DL-PCBs, ∑NDL-PCBs) were estimated using conditional logistic regression, adjusting for body mass index (BMI) and plasma lipids. The influence of BMI, weight-change, and plasma lipids on longitudinal changes in POP concentrations were evaluated among non-diabetic individuals (n = 306)., Results: POPs were associated with T2D in both the prospective and cross-sectional assessments. Of a standard deviation increase in POPs, prospective ORs ranged 1.42 (95% CI: 0.99, 2.06) for ∑NDL-PCBs to 1.55 (95% CI: 1.01, 2.38) for HCB (p < 0.05 only for HCB), and cross-sectional ORs ranged 1.62 (95% CI: 1.13; 2.32) for p,p'-DDE to 2.06 (95% CI: 1.29, 3.28) for ∑DL-PCBs (p < 0.05 for all POPs). In analyses of non-diabetic individuals, higher baseline BMI, decreased weight and decreased plasma lipid concentrations were associated with a slower decrease of POPs. Cases had, besides a higher BMI, reduced cholesterol and weight gain at follow-up compared to controls, which can explain the higher ORs in the cross-sectional assessments., Discussion: The association between POPs and T2D was confirmed, but an indication that individuals body fat history might influence POP-T2D associations weakens the epidemiological support for a causal association. It also warrants studies based on other exposure metrics than biomonitoring. In addition, we note that a cross-sectional design overestimates the ORs if T2D cases have successfully intervened on weight and/or blood lipids, as changes in these factors cause changes in POPs., (Copyright © 2019. Published by Elsevier Inc.)

Nutritional epidemiology is an inherently complex and multifaceted research area. Dietary intake is a complex exposure and is challenging to describe and assess, and links between diet, health, and disease are difficult to ascertain. Consequently, adequate reporting is necessary to facilitate comprehension, interpretation, and generalizability of results and conclusions. The STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement is an international and collaborative initiative aiming to enhance the quality of reporting of observational studies. We previously presented a checklist of 24 reporting recommendations for the field of nutritional epidemiology, called "the STROBE-nut." The STROBE-nut is an extension of the general STROBE statement, intended to complement the STROBE recommendations to improve and standardize the reporting in nutritional epidemiology. The aim of the present article is to explain the rationale for, and elaborate on, the STROBE-nut recommendations to enhance the clarity and to facilitate the understanding of the guidelines. Examples from the published literature are used as illustrations, and references are provided for further reading., Competing Interests: Author disclosures: AH, CB, EF, C Larsson, ES, AÅ, C Lachat, DH, PK, GB, WDK, JVC, JEC, DCG, NS, MC, ME, IH, and EW, no conflicts of interest. JEC is Principal Investigator and DCG is Co-Investigator on a grant from the Medical Research Council (MR/L02019X/1) that is looking at ways to improve the quality of dietary assessment. MC acted as coordinator of the STROBE collaboration.

Background: Conflicting evidence associates diet acidity with the incidence of chronic diseases such as hypertension, diabetes, kidney disease, and bone-mineral disorders. It is currently unknown whether dietary acidity is associated with death., Objective: We investigated the association of dietary acid load with the risk of all-cause and cardiovascular disease (CVD) mortality., Methods: We used data from 2 prospective cohorts, the Swedish Mammography Cohort and the Cohort of Swedish Men, which included 36,740 women and 44,957 men aged 45-84 y at the start of a 15-y follow-up period (1998-2012). Acid load was estimated from food-frequency questionnaires by use of the validated potential renal acid load (PRAL) algorithm. Deaths were ascertained via record linkage. Associations of PRAL with mortality were modeled by use of restricted cubic splines., Results: The median PRAL was 0.65 mEq/d (range: -109 to 81.5 mEq/d) in women and 12.3 mEq/d (-111 to 121 mEq/d) in men. During a mean of 13.5 ± 3.3 y of follow-up, there were 8576 and 13,332 deaths, of which 3203 and 5427 were attributed to cardiovascular causes in woman and men, respectively. In both sexes, a nonlinear U-shaped relation was observed, with higher mortality rates for both dietary acid and alkali excess. Compared with neutral PRAL (0 mEq/d), the HRs for all-cause mortality for the 10th and 90th percentiles of PRAL were 1.05 (95% CI: 1.01, 1.10) and 1.03 (95% CI: 0.98, 1.08), respectively, in women. The corresponding results for men were HRs 1.01 (95% CI: 1.00, 1.02) and 1.04 (95% CI: 1.00, 1.08) respectively. This relation was slightly stronger for CVD mortality., Conclusions: Excess diet alkalinity and acidity both showed weak associations with higher mortality in Swedish adults. An acid-base balanced diet was associated with the lowest mortality, but the magnitude of mortality reduction was modest. The Swedish Mammography Cohort was registered at clinicaltrials.gov as NCT01127698 The Cohort of Swedish Men was registered at clinicaltrials.gov as NCT01127711., (© 2016 American Society for Nutrition.)

There is increasing evidence of adverse health effects due to elevated lithium exposure through drinking water but the impact on calcium homeostasis is unknown. This study aimed at elucidating if lithium exposure through drinking water during pregnancy may impair the maternal calcium homeostasis. In a population-based mother-child cohort in the Argentinean Andes (n=178), with elevated lithium concentrations in the drinking water (5-1660μg/L), blood lithium concentrations (correlating significantly with lithium in water, urine and plasma) were measured repeatedly during pregnancy by inductively coupled plasma mass spectrometry and used as exposure biomarker. Markers of calcium homeostasis included: plasma 25-hydroxyvitamin D3, serum parathyroid hormone (PTH), and calcium, phosphorus and magnesium concentrations in serum and urine. The median maternal blood lithium concentration was 25μg/L (range 1.9-145). In multivariable-adjusted mixed-effects linear regression models, blood lithium was inversely associated with 25-hydroxyvitamin D3 (-6.1nmol/L [95%CI -9.5; -2.6] for a 25μg/L increment in blood lithium). The estimate increased markedly with increasing percentiles of 25-hydroxyvitamin D3. In multivariable-adjusted mixed-effects logistic regression models, the odds ratio of having 25-hydroxyvitamin D3<30nmol/L (19% of the women) was 4.6 (95%CI 1.1; 19.3) for a 25μg/L increment in blood lithium. Blood lithium was also positively associated with serum magnesium, but not with serum calcium and PTH, and inversely associated with urinary calcium and magnesium. In conclusion, our study suggests that lithium exposure through drinking water during pregnancy may impair the calcium homeostasis, particularly vitamin D. The results reinforce the need for better control of lithium in drinking water, including bottled water., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: The Mediterranean diet, which is palatable and easily achievable, has been associated with lower all-cause and cardiovascular disease (CVD) incidence and mortality. Data on heart failure (HF) and stroke types are lacking. The aim was to examine a Mediterranean diet in relation to incidence of myocardial infarction (MI), HF and stroke types in a Swedish prospective cohort., Methods: In a population-based cohort of 32,921 women, diet was assessed through a self-administered questionnaire. The modified Mediterranean diet (mMED) score was created based on high consumption of vegetables, fruits, legumes, nuts, whole grains, fermented dairy products, fish and monounsaturated fat, moderate intakes of alcohol and low consumption of red meat, on a 0-8 scale. Relative risks (RR) with 95% confidence intervals (CI), adjusted for potential confounders, were estimated by Cox proportional hazards regression models., Results: During 10 y of follow-up (1998-2008), 1109 MIs, 1648 HFs, 1270 ischemic strokes and 262 total hemorrhagic strokes were ascertained. A high adherence to the mMED score (6-8), compared to low, was associated with a lower risk of MI (RR: 0.74, 95% CI: 0.61-0.90, p = 0.003), HF (RR: 0.79, 95% CI: 0.68-0.93, p = 0.004) and ischemic stroke (RR: 0.78, 95% CI: 0.65-0.93, p = 0.007), but not hemorrhagic stroke (RR: 0.88, 95% CI: 0.61-1.29, p = 0.53)., Conclusions: Better adherence to a Mediterranean diet was associated with lower risk of MI, HF and ischemic stroke. The Mediterranean diet is most likely to be beneficial in primary prevention of all major types of atherosclerosis-related CVD., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Some studies have found that egg consumption is associated with a higher risk of ischemic heart disease in patients with diabetes. Epidemiologic studies of egg consumption in relation to risk of heart failure (HF) and stroke types are scarce., Objective: The aim of this study was to examine whether egg consumption is associated with incidence of HF, myocardial infarction (MI), or stroke types., Design: In prospective cohorts of 37,766 men (Cohort of Swedish Men) and 32,805 women (Swedish Mammography Cohort) who were free of cardiovascular disease (CVD), egg consumption was assessed at baseline with a food-frequency questionnaire. Incident CVD cases were identified through linkage with the Swedish National Patient and Cause of Death Registers. The data were analyzed with the use of a Cox proportional hazards regression model., Results: During 13 y of follow-up, we ascertained 1628 HFs, 3262 MIs, 2039 ischemic strokes, and 405 hemorrhagic strokes in men and 1207 HFs, 1504 MIs, 1561 ischemic strokes, and 294 hemorrhagic strokes in women. There was no statistically significant association between egg consumption and risk of MI or any stroke type in either men or women or HF in women. In men, consumption of ≤6 eggs/wk was not associated with HF risk; however, daily egg consumption (≥1/d) was associated with a 30% higher risk of HF (RR: 1.30; 95% CI: 1.01, 1.67). Egg consumption was not associated with any CVD outcome in individuals with diabetes., Conclusions: Daily egg consumption was not associated with risk of MI or any stroke type in either men or women or with HF in women. Consumption of eggs ≥1 time/d, but not less frequent consumption, was associated with an elevated risk of HF in men., (© 2015 American Society for Nutrition.)

Background: Epidemiologic studies of red meat consumption in relation to risk of heart failure (HF) are limited. We examined the associations between long-term unprocessed red meat and processed red meat consumption and incidence of HF in women., Methods: The population-based prospective Swedish Mammography Cohort included 34,057 women, aged 48-83 years, with no history of HF or ischemic heart disease at baseline (in 1997). Meat consumption was assessed using a self-administered food-frequency questionnaire (FFQ) in 1997 as well as FFQ administered in 1987-90. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs)., Results: During a mean follow-up of 13.2 years, 2806 women were diagnosed with HF. Consumption of processed meat (FFQ 1997) was statistically significant positively associated with HF incidence. Women who consumed ≥ 50 g/day processed red meat compared to those who consumed < 25 g/day had a 1.23 (95% CI: 1.09-1.39, P-trend=0.003) higher risk of HF. Long-term high consumption of processed red meat (average from 1987 to 1997) ≥ 50 g/day in comparison to < 25 g/day was associated with HR: 1.30 (95% CI: 1.05-1.60, P-trend=0.002). Women who consistently consumed (in both 1987 and 1997) ≥ 50 g/day vs. < 25 g/day had a 1.78 (95% CI: 1.00-3.16) higher risk of HF. Consumption of unprocessed meat was not associated with increased risk of HF incidence., Conclusions: Findings from this prospective study of women indicate that processed red meat, but not unprocessed red meat, consumption is associated with an increased risk of HF incidence., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Fish consumption may promote cardiovascular health. The role of major food contaminants, such as polychlorinated biphenyls (PCBs) common in fatty fish, is unclear. We assessed the association between dietary PCB exposure and risk of myocardial infarction taking into account the intake of long-chain omega-3 fish fatty acids., Methods: In the prospective population-based Swedish Mammography Cohort, 33,446 middle-aged and elderly women, free from cardiovascular disease, cancer and diabetes at baseline (1997) were followed-up for 12 years. Validated estimates of dietary PCB exposure and intake of fish fatty acids (eicosapentaenoic acid and docosahexaenoic acid; EPA-DHA) were obtained via a food frequency questionnaire at baseline., Results: During follow-up 1386 incident cases of myocardial infarction were ascertained through register-linkage. Women in the highest quartile of dietary PCB exposure (median 286 ng/day) had a multivariable-adjusted RR of myocardial infarction of 1.21 (95% confidence interval [CI], 1.01-1.45) compared to the lowest quartile (median 101 ng/day) before, and 1.58 (95% CI, 1.10-2.25) after adjusting for EPA-DHA. Stratification by low and high EPA-DHA intake, resulted in RRs 2.20 (95% CI, 1.18-4.12) and 1.73 (95% CI, 0.81-3.69), respectively comparing highest PCB tertile with lowest. The intake of dietary EPA-DHA was inversely associated with risk of myocardial infarction after but not before adjusting for dietary PCB., Conclusion: Exposure to PCBs was associated with increased risk of myocardial infarction, while some beneficial effect was associated with increasing EPA and DHA intake. To increase the net benefits of fish consumption, PCB contamination should be reduced to a minimum., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Recent epidemiological as well as in vivo and in vitro studies collectively suggest that the metalloestrogen cadmium (Cd) could be a potential risk factor for hormone-related cancers in particularly breast cancer. Assessment of the association between Cd exposure and levels of endogenous sex hormones is of pivotal importance, as increased levels of such have been associated with a higher risk of breast cancer in postmenopausal women. The present study investigated the perceived relationship (multivariable-adjusted linear regression analyses) between Cd exposure [blood Cd (B-Cd) and urinary Cd (U-Cd)], and serum levels of androstenedione, testosterone, estradiol, and sex-hormone binding globulin (SHBG), in 438 postmenopausal Swedish women without hormone replacement therapy (HRT). A significant positive association between B-Cd (median 3.4 nmol/L) and serum testosterone levels, as well as a significant inverse association between B-Cd and serum estradiol levels and with the estradiol/testosterone ratio were encountered. However, U-Cd (median 0.69 nmol/mmol creatinine) was inversely associated with serum estradiol levels only. Our data may suggest that Cd interferes with the levels of testosterone and estradiol in postmenopausal women, which might have implications for breast cancer risk., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Polychlorinated biphenyls (PCBs) induce a broad spectrum of biochemical and toxic effects in mammals including alterations of the vital retinoid (vitamin A) system. The aim of this study was to characterize alterations of tissue retinoid levels in rat offspring and their dams following gestational and lactational exposure to the PCB mixture Aroclor 1254 (A1254) and to assess the interrelationship of these changes with other established sensitive biochemical and toxicological endpoints. Sprague-Dawley rat dams were exposed orally to 0 or 15 mg/kg body weight/day of A1254 from gestational day 1 to postnatal day (PND) 23. Livers, kidneys and serum were collected from the offspring on PNDs 35, 77 and 350. Tissue and serum retinoid levels, hepatic cytochrome P450 (CYP) enzymes and serum thyroid hormones were analyzed. A multivariate regression between A1254 treatment, hepatic retinoid levels, hepatic CYP enzymes activities, thyroid hormone levels and body/liver weights was performed using an orthogonal partial least-squares (PLS) analysis. The contribution of dioxin-like (DL) components of A1254 to the observed effects was also estimated using the toxic equivalency (TEQ) concept. In both male and female offspring short-term alterations in tissue retinoid levels occurred at PND35, i.e. decreased levels of hepatic retinol and retinoic acid (RA) metabolite 9-cis-4-oxo-13,14-dihydro-RA with concurrent increases in hepatic and renal all-trans-RA levels. Long-term changes consisted of decreased hepatic retinyl palmitate and increased renal retinol levels that were apparent until PND350. Retinoid system alterations were associated with altered CYP enzyme activities and serum thyroid hormone levels as well as body and liver weights in both offspring and dams. The estimated DL activity was within an order of magnitude of the theoretical TEQ for different endpoints, indicating significant involvement of DL congeners in the observed effects. This study shows that tissue retinoid levels are affected both short- and long-term by developmental A1254 exposure and are associated with alterations of other established endpoints of toxicological concern., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The relation between dairy foods, particularly specific foods, and risk of cardiovascular disease (CVD) remains unclear. We examined the association between total, as well as specific, dairy food intakes and incidence of myocardial infarction (MI) in a prospective population-based cohort. We followed 33,636 women (aged 48-83 y), free from CVD, cancer, and diabetes at baseline (1997), in the Swedish Mammography Cohort. Consumption of milk, cultured milk/yogurt, cheese, cream, crème fraiche, and butter was obtained from a validated self-administered FFQ at baseline. We used Cox proportional hazards regression models to estimate HRs and 95% CIs, adjusted for relevant CVD risk factors. MI incidence was ascertained from national registries. Over 11.6 y of follow-up, we ascertained 1392 cases of MI. When the highest quintile was compared with the lowest quintile, total dairy food intake was inversely associated with MI risk [multivariable adjusted HR: 0.77 (95% CI: 0.63, 0.95)]. Among specific dairy food products, total cheese was inversely associated [HR: 0.74 (95% CI: 0.60, 0.91)] and butter used on bread but not on cooking was positively associated [HR: 1.34 (95% CI: 1.02, 1.75)] with MI risk. Other specific dairy food products were not significantly associated with MI risk. No differences were observed between consumption of specific low-fat and high-fat dairy foods, expressed as either absolute intakes or intakes relative to the total, and MI risk. Failure to consider dairy foods as a heterogeneous group in future studies could hamper important insights of relevance for the development of dietary guidelines.