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.

Nutritional intake and determinants of nutritional quality changes from pregnancy to postpartum-a longitudinal study.

Nutrient requirements vary across the reproductive cycle, but research on changes in nutritional intake and quality from pregnancy to beyond the lactation period is limited. Thus, we aimed to study nutritional intake and quality changes, among Swedish pregnant participants from late pregnancy to 18 months postpartum and to study the determinants of nutritional quality changes. Participants (n = 72) were studied longitudinally from the third trimester of pregnancy and postpartum (2 weeks 4, 12, and 18 months postpartum). At each visit, participant characteristics and 4-day food diaries were collected. Nutritional quality was assessed by energy adjusted Nutrient Rich Food Index 11.3. Linear mixed models were used to analyze the determinants of change in nutritional quality. Intakes of carbohydrate energy percentage (E%), fiber, vitamin A, vitamin C, and potassium were higher in the third trimester compared to postpartum, whereas intakes of E% protein and monounsaturated fat were lower. Adherence to recommended intakes was low at all study visits for saturated fat (4%-11%), fiber (15%-39%), vitamin D (8%-14%), folate (0%-2%), and iron (6%-21%). Overall, nutritional quality did not differ significantly from third trimester to postpartum. Shorter duration (<4 months) of lactation was negatively related to nutritional quality changes, whereas higher age was positively related to changes. In conclusion, nutritional intake from pregnancy to postpartum changed, whereas quality remained relatively stable, with age and lactation duration as determinants. Identification of people at risk of adverse dietary changes from pregnancy to the postpartum period should be further addressed in future larger and more diverse study populations.

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.

Dietary patterns, untargeted metabolite profiles and their association with colorectal cancer risk.

We investigated data-driven and hypothesis-driven dietary patterns and their association to plasma metabolite profiles and subsequent colorectal cancer (CRC) risk in 680 CRC cases and individually matched controls. Dietary patterns were identified from combined exploratory/confirmatory factor analysis. We assessed association to LC-MS metabolic profiles by random forest regression and to CRC risk by multivariable conditional logistic regression. Principal component analysis was used on metabolite features selected to reflect dietary exposures. Component scores were associated to CRC risk and dietary exposures using partial Spearman correlation. We identified 12 data-driven dietary patterns, of which a breakfast food pattern showed an inverse association with CRC risk (OR per standard deviation increase 0.89, 95% CI 0.80-1.00, p = 0.04). This pattern was also inversely associated with risk of distal colon cancer (0.75, 0.61-0.96, p = 0.01) and was more pronounced in women (0.69, 0.49-0.96, p = 0.03). Associations between meat, fast-food, fruit soup/rice patterns and CRC risk were modified by tumor location in women. Alcohol as well as fruit and vegetables associated with metabolite profiles (Q2 0.22 and 0.26, respectively). One metabolite reflecting alcohol intake associated with increased CRC risk, whereas three metabolites reflecting fiber, wholegrain, and fruit and vegetables associated with decreased CRC risk.

Exploring the differences in serum metabolite profiles after intake of red meat in women with rheumatoid arthritis and a matched control group.

PURPOSE: Studies have suggested that women with RA tend to avoid red meat more often than women without RA, based on their perception that it exacerbates their symptoms. Therefore, the aim of this study is to investigate and compare the postprandial metabolic response following the consumption of a red meat meal in patients with RA and a matched control group. METHODS: Participants were challenged with a meal with red meat and blood samples were collected before and at 0.5, 1, 2, 3 and 5 h after the meal. Serum metabolites were quantified by Nuclear Magnetic Resonance (NMR) analysis. Orthogonal Projections to Latent Structures with Discriminant Analysis (OPLS-DA) was used to evaluate separation by metabolites due to diagnosis of RA or not and to identify changes in metabolites related to RA. Incremental area under the curve was calculated for univariate comparisons for 23 metabolites. RESULTS: The matched groups, including 22 women with RA and 22 women without RA, did not differ significantly in age, body mass index, diet quality or reported physical activity. OPLS-DA models had a limited quality indicating that there were no differences in metabolite patterns between the groups. However, phenylalanine was significantly higher in concentration in women with RA compared to controls in both fasting and postprandial samples. CONCLUSION: To conclude, this well-controlled postprandial intervention study found a significantly higher concentration of phenylalanine in both fasting and postprandial samples of women with RA compared to matched women without RA. These findings warrant further investigation in larger studies. TRIAL REGISTRATION: The PIRA (Postprandial Inflammation in Rheumatoid Arthritis) trial is Registered at Clinicaltrials.gov (NCT04247009).

Supplement use in relation to dietary intake in pregnancy: an analysis of the Swedish GraviD cohort.

We aimed to study supplement use in relation to dietary intake among pregnant women in Sweden, and adherence to the Nordic Nutrition Recommendations among supplement and non-supplement users. Pregnant women were recruited at registration to antenatal care in 2013­2014. In third trimester, supplement use was collected using a questionnaire, and dietary intake was collected using a FFQ. The majority (64 %) of the 1044 women reported use of one or more supplements. Among all, 0­23 % reported dietary intakes above recommended intake (RI) of vitamin D, folate, Fe and Se. Median dietary intakes of thiamine (1·4 v. 1·3 mg P = 0·013), phosphorus (1482 v. 1440 mg P = 0·007), folate (327 v. 316 µg P = 0·02), Fe (12 v. 11·5 mg P = 0·009), Mg (361 v. 346 mg P < 0·001) and Zn (10·7 v. 10·4 mg P = 0·01) were higher among supplement users compared with non-users. Larger proportions of supplement users than non-users adhered to RI of dietary intakes of thiamine (42 % v. 35 % P = 0·04) and Mg (75 % v. 69 % P = 0·05). Among non-users, a minority had dietary intakes above RI for vitamin D (6 %), folate (10 %) and Fe (21 %). The majority (75­100 %) of supplement users had total intakes above RI for most nutrients. In conclusion, supplement use contributed substantially to reaching RI for vitamin D, folate and Fe. Supplement users had a higher dietary intake of several nutrients than non-users. This highlights that non-supplement users are at risk of inadequate nutrient intakes during pregnancy, suggesting a need for heightened awareness of nutritional adequacy for pregnant women.

Dietary Greenhouse Gas Emissions and Diet Quality in a Cross-Sectional Study of Swedish Adolescents.

BACKGROUND: Interventions to improve dietary intake and reduce dietary greenhouse gas emissions (dGHGE) are urgently needed. Adolescence presents a unique time in life to promote sustainable diets. Detailed dietary data are needed to inform public health strategies aiming at improving adolescents' diet quality and reducing dGHGE. OBJECTIVE: This study aimed to describe dGHGE in Swedish adolescents' diets by socio-demographic characteristics, evaluate how food groups contribute to dGHGE, and examine dGHGE in relation to diet quality. METHODS: Data come from the national, school-based, cross-sectional dietary survey Riksmaten Adolescents 2016-17 of 3099 females and males attending school grades 5 (11-12 y old), 8 (14-15 y old) and 11 (17-18 y old). Participants completed 2 web-based 24-h recalls and questionnaires on lifestyle factors. dGHGE was estimated based on life cycle assessment data. Diet quality was estimated using NRF11.3 (Nutrient Rich Food Index) and SHEIA15 (Swedish Healthy Eating Index for Adolescents 2015). RESULTS: dGHGE were higher in males than females (medians 4.2 versus 3.8 kg CO2e/10 MJ, P < 0.001). In females, dGHGE were highest in grade 5 (4.0 kg CO2e/10MJ), whereas in males, emissions were highest in grade 11 (4.4 kg CO2e/10MJ), P < 0.001 for the sex/grade interaction. Overweight/obesity was positively associated with CO2e/10MJ, but parental education, birthplace, and degree of urbanization were not. In females, the proportion of dGHGE from animal-based foods was lowest in grade 11, whereas the proportions from plant-based foods and sweet foods/beverages were highest. In males, these proportions were similar across grades. NRF11.3 was not associated with CO2e/10MJ, whereas healthier eating, according to SHEIA15, was inversely associated with CO2e/10MJ. CONCLUSIONS: Food choices and dGHGE per calorie differ by sex in adolescents. Thus, intervention strategies to improve dietary sustainability need to be tailored differently to females and males. Diet quality should also be considered when promoting reduced GHGE diets.

Maternal vitamin D status and risk of childhood overweight at 5 years of age in two Nordic cohort studies.

Introduction: Maternal vitamin D status during pregnancy has been suggested to have a role in childhood adiposity development, but results are conflicting. Our aims were to investigate [1] the relationships between maternal 25-hydroxyvitamin D (25OHD) during pregnancy and the child's body mass index (BMI) and risk of overweight at 5 years of age, and [2] maternal pre-pregnancy BMI as effect modifier for these associations. Methods: Data sources included a subsample from the Norwegian Mother, Father and Child Cohort Study (MoBa sub-cohort; N = 2,744) and the Swedish GraviD cohort study (N = 891). Maternal 25OHD was analyzed in gestational week 18 in the MoBa sub-cohort and week 10 in the GraviD cohort. In the MoBa sub-cohort, parents reported their child's documented measures of weight and length or height from the health card at routine check-up. In the GraviD cohort, this information was collected directly from medical records. Childhood overweight (including obesity) was identified using the International Obesity Task Force cut-offs. Linear and logistic regression models were used to investigate the association between maternal 25OHD and child's BMI and risk of overweight at 5 years of age in each cohort separately, and in a pooled dataset. Results: In the pooled analysis, maternal 25OHD <30 nmol/L was associated with lower BMI in children at 5 years of age, but not with risk of overweight. Interaction analysis showed that the association was predominant among children of mothers with pre-pregnancy BMI ≥25 kg/m2. Conclusion: Low maternal vitamin D status, particularly in mothers with overweight or obesity, predicted lower BMI in their five-year-old children. However, there was no evidence of an effect on overweight in these children.

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.

Dietary biomarkers and food records indicate compliance to study diets in the ADIRA (Anti-inflammatory Diet In Rheumatoid Arthritis) trial.

Background: In the ADIRA (Anti-inflammatory Diet In Rheumatoid arthritis) trial, compliance to the study diets has previously been described primarily with a score based on reported intake of trial foods from telephone interviews. The aim of this study was to evaluate compliance using objective dietary biomarkers for whole grain, fruit and vegetables, margarine and oil, seafood and overall fat quality, as well as reported intake from food records of key components of the study diets. Methods: Fifty patients with rheumatoid arthritis were randomized to begin with the intervention diet (rich in whole grain, fruit and vegetables, margarine/oil and seafood) or the control diet (rich in meat and high-fat dairy) for 10 weeks, followed by a ~ 4 months wash-out period, and then switched diet. Compliance was evaluated using plasma alkylresorcinols (AR) as biomarkers for intake of whole grain wheat and rye, serum carotenoids for fruit and vegetables, plasma linoleic acid (LA, 18:2 n-6) and -α-linolenic acid (18:3, n-3) for margarine and cooking oil, plasma eicosapentaenoic acid (EPA, 20:5 n-3), -docosahexaenoic acid (DHA 22:6, n-3) and -docosapentaenoic acid (22:5 n-3) for seafood, and plasma fatty acid pattern for the overall dietary fat quality. Reported intake of whole grain, fruit, berries and vegetables, seafood, red meat, and fat quality was extracted from 3-d food records. Results: Plasma AR C21:0 and C23:0, LA, EPA, and DHA were higher while total serum carotenoids were lower after the intervention diet period compared to the control diet period (AR and carotenoids: p = <0.05, fatty acids: p = <0.001). Reported intake of whole grain, fruit, berries and vegetables, and seafood was higher and reported intake of red meat was lower during the intervention diet period compared to the control diet period (p = <0.001). Plasma- and reported fatty acid pattern differed as intended between the diet periods. Conclusion: This study indicates that the participants in the ADIRA trial were compliant to the study diets regarding intake of whole grain, cooking fat, seafood, and red meat, and the intended overall dietary fat quality. Compliance to instructions on fruit- and vegetable intake remains uncertain. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT02941055?term=NCT02941055&draw=2&rank=1, NCT02941055.

Vitamin D intake and determinants of vitamin D status during pregnancy in The Norwegian Mother, Father and Child Cohort Study.

Background: Norwegian data on vitamin D status among pregnant women indicate a moderate to high prevalence of insufficient vitamin D status (25-hydroxyvitamin D (25OHD) concentrations ≤50 nmol/L). There is a lack of population-based research on vitamin D intake and determinants of 25OHD in pregnant women from northern latitudes. The aims of this study were (1) to evaluate total vitamin D intake from both diet and supplements, (2) to investigate determinants of vitamin D status, and (3) to investigate the predicted response in vitamin D status by total vitamin D intake, in pregnant Norwegian women. Methods: In total, 2,960 pregnant women from The Norwegian Environmental Biobank, a sub-study within The Norwegian Mother, Father and Child Cohort Study (MoBa), were included. Total vitamin D intake was estimated from a food frequency questionnaire in gestational week 22. Concentrations of plasma 25OHD was analyzed by automated chemiluminescent microparticle immunoassay method in gestational week 18. Candidate determinant variables of 25OHD were chosen using stepwise backward selection and investigated using multivariable linear regression. Predicted 25OHD by total vitamin D intake, overall and stratified by season and pre-pregnancy BMI, was explored using restricted cubic splines in an adjusted linear regression. Results: Overall, about 61% of the women had a total vitamin D intake below the recommended intake. The main contributors to total vitamin D intake were vitamin D supplements, fish, and fortified margarine. Higher 25OHD concentrations were associated with (in descending order of the beta estimates) summer season, use of solarium, higher vitamin D intake from supplements, origin from high income country, lower pre-pregnancy BMI, higher age, higher vitamin D intake from foods, no smoking during pregnancy, higher education and energy intake. During October-May, a vitamin D intake according to the recommended intake was predicted to reach sufficient 25OHD concentrations >50 nmoL/L. Conclusion: The findings from this study highlight the importance of the vitamin D intake, as one of few modifiable determinants, to reach sufficient 25OHD concentrations during months when dermal synthesis of vitamin D is absent.

Corrigendum: Characterization of the degree of food processing in the European Prospective Investigation into Cancer and Nutrition: application of the Nova classification and validation using selected biomarkers of food processing.

[This corrects the article DOI: 10.3389/fnut.2022.1035580.].

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.

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.

Influence of Dietary n-3 Long Chain Polyunsaturated Fatty Acid Intake on Oxylipins in Erythrocytes of Women with Rheumatoid Arthritis.

Oxylipins derived from n-3 fatty acids are suggested as the link between these fatty acids and reduced inflammation. The aim of the present study was to explore the effect of a randomized controlled cross-over intervention on oxylipin patterns in erythrocytes. Twenty-three women with rheumatoid arthritis completed 2 × 11-weeks exchanging one cooked meal per day, 5 days a week, for a meal including 75 g blue mussels (source for n-3 fatty acids) or 75 g meat. Erythrocyte oxylipins were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results were analyzed with multivariate data analysis. Orthogonal projections to latent structures (OPLS) with effect projections and with discriminant analysis were performed to compare the two diets' effects on oxylipins. Wilcoxon signed rank test was used to test pre and post values for each dietary period as well as post blue-mussel vs. post meat. The blue-mussel diet led to significant changes in a few oxylipins from the precursor fatty acids arachidonic acid and dihomo-É£-linolenic acid. Despite significant changes in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and free EPA in erythrocytes in the mussel group, no concurrent changes in their oxylipins were seen. Further research is needed to study the link between n-3 fatty-acid intake, blood oxylipins, and inflammation.

Maternal vitamin D status in relation to infant BMI growth trajectories up to 2 years of age in two prospective pregnancy cohorts.

Background: Early childhood growth can affect the child's health status later in life. Maternal vitamin D status has been suggested to affect early childhood growth. However, there is a lack of studies investigating the role of maternal vitamin D status on growth trajectories during infancy. By using growth mixture modeling (GMM), maternal vitamin D status during pregnancy can be investigated in relation to different classes of infant growth trajectories. Objectives: To examine the association between maternal 25-hydroxyvitamin D (25OHD) and classes of infant body mass index (BMI) growth trajectories. Methods: Mother-child pairs were included from the Norwegian Mother, Father, and Child Cohort Study (MoBa, n = 2522) and the Swedish GraviD cohort (n = 862). Maternal 25OHD in pregnancy was analyzed by liquid chromatography tandem mass spectrometry. Children's weights and heights were registry-based. GMM identified classes of infant BMI growth trajectories up to 2 years. The association between maternal 25OHD and infant BMI class by cohort was estimated using a log-link generalized linear model. Mixed model analysis estimated the pooled association including both cohorts. Results: Two infant BMI classes were identified, stable normal and stable high. In MoBa, maternal 25OHD <50 and 50-75 nmol/L were associated (RR 2.70, 95% CI 1.26-5.77 and RR 2.56, 95% CI 1.20-5.47) with a higher risk of the infant stable high BMI class, compared with 25OHD >75 nmol/L. In GraviD, no association was found. In pooled analysis, maternal 25OHD ≤75 nmol/L was non-significantly associated with a higher risk of the stable high BMI growth class. Conclusions: Maternal 25OHD ≤75 nmol/L may be associated with a higher class of BMI growth trajectory during infancy.

Identification of Single and Combined Serum Metabolites Associated with Food Intake.

Assessment of dietary intake is challenging. Traditional methods suffer from both random and systematic errors; thus objective measures are important complements in monitoring dietary exposure. The study presented here aims to identify serum metabolites associated with reported food intake and to explore whether combinations of metabolites may improve predictive models. Fasting blood samples and a 4-day weighed food diary were collected from healthy Swedish subjects (n = 119) self-defined as having habitual vegan, vegetarian, vegetarian + fish, or omnivore diets. Serum was analyzed for metabolites by 1H-nuclear magnetic resonance spectroscopy. Associations between single and combined metabolites and 39 foods and food groups were explored. Area under the curve (AUC) was calculated for prediction models. In total, 24 foods or food groups associated with serum metabolites using the criteria of rho > 0.2, p < 0.01 and AUC ≥ 0.7 were identified. For the consumption of soybeans, citrus fruits and marmalade, nuts and almonds, green tea, red meat, poultry, total fish and shellfish, dairy, fermented dairy, cheese, eggs, and beer the final models included two or more metabolites. Our results indicate that a combination of metabolites improve the possibilities to use metabolites to identify several foods included in the current diet. Combined metabolite models should be confirmed in dose−response intervention studies.

A longitudinal evaluation of alcohol intake throughout adulthood and colorectal cancer risk.

BACKGROUND: Alcohol intake is an established risk factor for colorectal cancer (CRC); however, there is limited knowledge on whether changing alcohol drinking habits during adulthood modifies CRC risk. OBJECTIVE: Leveraging longitudinal exposure assessments on alcohol intake at different ages, we examined the relationship between change in alcohol intake and subsequent CRC risk. METHODS: Within the European Prospective Investigation into Cancer and Nutrition, changes in alcohol intake comparing follow-up with baseline assessments were investigated in relation to CRC risk. The analysis included 191,180, participants and 1530 incident CRC cases, with exclusion of the first three years of follow-up to minimize reverse causation. Trajectory profiles of alcohol intake, assessed at ages 20, 30, 40, 50 years, at baseline and during follow-up, were estimated using latent class mixed models and related to CRC risk, including 407,605 participants and 5,008 incident CRC cases. RESULTS: Mean age at baseline was 50.2 years and the follow-up assessment occurred on average 7.1 years later. Compared to stable intake, a 12 g/day increase in alcohol intake during follow-up was positively associated with CRC risk (HR = 1.15, 95%CI 1.04, 1.25), while a 12 g/day reduction was inversely associated with CRC risk (HR = 0.86, 95%CI 0.78, 0.95). Trajectory analysis showed that compared to low alcohol intake, men who increased their alcohol intake from early- to mid- and late-adulthood by up to 30 g/day on average had significantly increased CRC risk (HR = 1.24; 95%CI 1.08, 1.42), while no associations were observed in women. Results were consistent by anatomical subsite. CONCLUSIONS: Increasing alcohol intake during mid-to-late adulthood raised CRC risk, while reduction lowered risk.

Diet and BMI Correlate with Metabolite Patterns Associated with Aggressive Prostate Cancer.

Three metabolite patterns have previously shown prospective inverse associations with the risk of aggressive prostate cancer within the European Prospective Investigation into Cancer and Nutrition (EPIC). Here, we investigated dietary and lifestyle correlates of these three prostate cancer-related metabolite patterns, which included: 64 phosphatidylcholines and three hydroxysphingomyelins (Pattern 1), acylcarnitines C18:1 and C18:2, glutamate, ornithine, and taurine (Pattern 2), and 8 lysophosphatidylcholines (Pattern 3). In a two-stage cross-sectional discovery (n = 2524) and validation (n = 518) design containing 3042 men free of cancer in EPIC, we estimated the associations of 24 dietary and lifestyle variables with each pattern and the contributing individual metabolites. Associations statistically significant after both correction for multiple testing (False Discovery Rate = 0.05) in the discovery set and at p < 0.05 in the validation set were considered robust. Intakes of alcohol, total fish products, and its subsets total fish and lean fish were positively associated with Pattern 1. Body mass index (BMI) was positively associated with Pattern 2, which appeared to be driven by a strong positive BMI-glutamate association. Finally, both BMI and fatty fish were inversely associated with Pattern 3. In conclusion, these results indicate associations of fish and its subtypes, alcohol, and BMI with metabolite patterns that are inversely associated with risk of aggressive prostate cancer.

Determinants of blood acylcarnitine concentrations in healthy individuals of the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND & AIMS: Circulating levels of acylcarnitines (ACs) have been associated with the risk of various diseases such as cancer and type 2 diabetes. Diet and lifestyle factors have been shown to influence AC concentrations but a better understanding of their biological, lifestyle and metabolic determinants is needed. METHODS: Circulating ACs were measured in blood by targeted (15 ACs) and untargeted metabolomics (50 ACs) in 7770 and 395 healthy participants of the European Prospective Investigation into Cancer and Nutrition (EPIC), respectively. Associations with biological and lifestyle characteristics, dietary patterns, self-reported intake of individual foods, estimated intake of carnitine and fatty acids, and fatty acids in plasma phospholipid fraction and amino acids in blood were assessed. RESULTS: Age, sex and fasting status were associated with the largest proportion of AC variability (partial-r up to 0.19, 0.18 and 0.16, respectively). Some AC species of medium or long-chain fatty acid moiety were associated with the corresponding fatty acids in plasma (partial-r = 0.24) or with intake of specific foods such as dairy foods containing the same fatty acid. ACs of short-chain fatty acid moiety (propionylcarnitine and valerylcarnitine) were moderately associated with concentrations of branched-chain amino acids (partial-r = 0.5). Intake of most other foods and of carnitine showed little association with AC levels. CONCLUSIONS: Our results show that determinants of ACs in blood vary according to their fatty acid moiety, and that their concentrations are related to age, sex, diet, and fasting status. Knowledge on their potential determinants may help interpret associations of ACs with disease risk and inform on potential dietary and lifestyle factors that might be modified for disease prevention.