| 221. |
- Eussen, Simone J. P. M., et al.
(författare)
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North-south gradients in plasma concentrations of B-vitamins and other components of one-carbon metabolism in Western Europe: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) Study
- 2013
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Ingår i: British Journal of Nutrition. - 1475-2662 .- 0007-1145. ; 110:2, s. 363-374
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Tidskriftsartikel (refereegranskat)abstract
- Different lifestyle patterns across Europe may influence plasma concentrations of B-vitamins and one-carbon metabolites and their relation to chronic disease. Comparison of published data on one-carbon metabolites in Western European regions is difficult due to differences in sampling procedures and analytical methods between studies. The present study aimed, to compare plasma concentrations of one-carbon metabolites in Western European regions with one laboratory performing all biochemical analyses. We performed the present study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort among 5446 presumptively healthy individuals. Quantile regression was used to compare sex-specific median concentrations between Northern (Denmark and Sweden), Central (France, Germany, The Netherlands and United Kingdom) and Southern (Greece, Spain and Italy) European regions. The lowest folate concentrations were observed in Northern Europe (men, 10.4 nmol/l; women, 10.7 nmol/l) and highest concentrations in Central Europe. Cobalamin concentrations were slightly higher in Northern Europe (men, 330 pmol/l; women, 352 pmol/l) compared with Central and Southern Europe, but did not show a clear north-south gradient. Vitamin B-2 concentrations were highest in Northern Europe (men, 22.2 nmol/l; women, 26.0 nmol/l) and decreased towards Southern Europe (P-trend < 0.001). Vitamin B-6 concentrations were highest in Central Europe in men (77.3 nmol/l) and highest in the North among women (70.4 nmol/l), with decreasing concentrations towards Southern Europe in women (P-trend < 0.001). In men, concentrations of serine, glycine and sarcosine increased from the north to south. In women, sarcosine increased from Northern to Southern Europe. These findings may provide relevant information for the study of regional differences of chronic disease incidence in association with lifestyle.
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| 222. |
- Gaziano, Liam, et al.
(författare)
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Mild-to-moderate kidney dysfunction and cardiovascular disease : Observational and mendelian randomization analyses
- 2022
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 146:20, s. 1507-1517
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke.METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank.RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD.CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.
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| 223. |
- Grenville, Z. S., et al.
(författare)
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Diet and BMI Correlate with Metabolite Patterns Associated with Aggressive Prostate Cancer
- 2022
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 14:16
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 224. |
- Hernández-Maldonado, Luz M, et al.
(författare)
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In Vitro Gastrointestinal Digestion and Colonic Fermentation of High Dietary Fiber and Antioxidant-Rich Mango (Mangifera indica L.) "Ataulfo"-Based Fruit Bars
- 2019
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Mango (Mangifera indica L.) is a tropical fruit which is considered to be a source of dietary fiber (DF) and phenolic compounds (PCs). In this study, high DF mango-based fruit bars were developed from whole mango (peel and pulp). The bars were evaluated for their nutritional composition, the bioaccesibility of PCs during gastrointestinal digestion, and the PCs metabolites profile after in vitro colonic fermentation. The amount of DF in a 30 g portion of mango bars was 9.5 g, i.e., 35% of the recommended daily intake. Phenolic acids such as gallic acid; cinnamic acids, such as ferulic, coumaric, and caffeic acids; flavonoids such as quercertin; and xanthones such as mangiferin and mangiferin gallate, were identified as the main PCs in the bars. The antioxidant capacity associated with the PCs profile, together with the high DF content are indicative of the potential functional features of these natural fruit bars. The bioaccesibility of PCs in the mango bar was 53.78%. During fermentation, the PCs were bioconverted mainly to hydroxyphenolic acids and the main short-chain fatty acid produced was acetic acid. The xanthone norathyriol was identified after 12 h of fermentation. This study on the digestion and colonic fermentation of mango-based bars using in vitro models provides hints of the potential physiological behavior of PCs associated with DF, which constitutes relevant information for further development of natural and health-promoting fruit-based bars.
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| 225. |
- Kotelnikova, E, et al.
(författare)
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Signaling networks in MS: a systems-based approach to developing new pharmacological therapies
- 2015
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 21:2, s. 138-146
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Tidskriftsartikel (refereegranskat)abstract
- The pathogenesis of multiple sclerosis (MS) involves alterations to multiple pathways and processes, which represent a significant challenge for developing more-effective therapies. Systems biology approaches that study pathway dysregulation should offer benefits by integrating molecular networks and dynamic models with current biological knowledge for understanding disease heterogeneity and response to therapy. In MS, abnormalities have been identified in several cytokine-signaling pathways, as well as those of other immune receptors. Among the downstream molecules implicated are Jak/Stat, NF-Kb, ERK1/3, p38 or Jun/Fos. Together, these data suggest that MS is likely to be associated with abnormalities in apoptosis/cell death, microglia activation, blood-brain barrier functioning, immune responses, cytokine production, and/or oxidative stress, although which pathways contribute to the cascade of damage and can be modulated remains an open question. While current MS drugs target some of these pathways, others remain untouched. Here, we propose a pragmatic systems analysis approach that involves the large-scale extraction of processes and pathways relevant to MS. These data serve as a scaffold on which computational modeling can be performed to identify disease subgroups based on the contribution of different processes. Such an analysis, targeting these relevant MS-signaling pathways, offers the opportunity to accelerate the development of novel individual or combination therapies.
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| 226. |
- Lanuza, Fabian, et al.
(författare)
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Comparison of Flavonoid Intake Assessment Methods Using USDA and Phenol Explorer Databases: Subcohort Diet, Cancer and Health-Next Generations—MAX Study
- 2022
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Ingår i: Frontiers in Nutrition. - : Frontiers Media SA. - 2296-861X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Flavonoids are bioactive plant compounds that are widely present in the human diet. Estimating flavonoid intake with a high degree of certainty is challenging due to the inherent limitations of dietary questionnaires and food composition databases. This study aimed to evaluate the degree of reliability among flavonoid intakes estimated using four different approaches based on the two most comprehensive flavonoid databases, namely, United States Department of Agriculture (USDA) and Phenol Explorer (PE). In 678 individuals from the MAX study, a subcohort of the Diet, Cancer and Health-Next Generations cohort, dietary data were collected using three 24-h diet recalls over 1 year. Estimates of flavonoid intake were compared using flavonoid food content from PE as (1) aglycones (chromatography with hydrolysis), (2) aglycones transformed (converted from glycosides by chromatography without hydrolysis), (3) as they are in nature (glycosides, aglycones, and esters), and 4) using flavonoid content from USDA as aglycones (converted). Spearman's intra-class correlation (ICC) coefficient and weighted kappa (K) coefficient were calculated for the reliability analysis. When comparing PE total aglycones to USDA total aglycones, there was a moderate reliability when a continuous variable was used [ICC: 0.73, 95% confidence interval (CI): 0.70–0.76] and an excellent reliability when flavonoid intake was modeled as a categorical variable (K: 0.89, 95% CI: 0.88–0.90). The degree of reliability among all methods of estimated flavonoid intakes was very similar, especially between database pairs, for the flavanol subclass, while larger differences were observed for flavone, flavonol, and isoflavone subclasses. Our findings indicate that caution should be taken when comparing the results of the associations between flavonoid intakes and health outcomes from studies, when flavonoid intakes were estimated using different methods, particularly for some subclasses.
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| 227. |
- Lanuza, Fabian, et al.
(författare)
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Dietary polyphenols, metabolic syndrome and cardiometabolic risk factors: An observational study based on the DCH-NG subcohort
- 2023
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Ingår i: Nutrition, Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753 .- 1590-3729. ; 33:6, s. 1167-1178
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Polyphenol-rich foods have beneficial properties that may lower cardiometabolic risk. We aimed to prospectively investigate the relationship between intakes of dietary polyphenols, and metabolic syndrome (MetS) and its components, in 676 Danish residents from the MAX study, a subcohort of the Danish Diet, Cancer and Health–Next Generations (DCH-NG) cohort. Methods and results: Dietary data were collected using web-based 24-h dietary recalls over one year (at baseline, and at 6 and 12 months). The Phenol-Explorer database was used to estimate dietary polyphenol intake. Clinical variables were also collected at the same time point. Generalized linear mixed models were used to investigate relationships between polyphenol intake and MetS. Participants had a mean age of 43.9y, a mean total polyphenol intake of 1368 mg/day, and 75 (11.6%) had MetS at baseline. Compared to individuals with MetS in Q1 and after adjusting for age, sex, lifestyle and dietary confounders, those in Q4 – for total polyphenols, flavonoids and phenolic acids–had a 50% [OR (95% CI): 0.50 (0.27, 0.91)], 51% [0.49 (0.26, 0.91)] and 45% [0.55 (0.30, 1.00)] lower odds of MetS, respectively. Higher total polyphenols, flavonoids and phenolic acids intakes as continuous variable were associated with lower risk for elevated systolic blood pressure (SBP) and low high-density lipoprotein cholesterol (HDL-c) (p < 0.05). Conclusions: Total polyphenol, flavonoid and phenolic acid intakes were associated with lower odds of MetS. These intakes were also consistently and significantly associated with a lower risk for higher SBP and lower HDL-c concentrations.
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| 228. |
- Lanuza, Fabian, et al.
(författare)
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Plasma metabolomic profiles of plant-based dietary indices reveal potential pathways for metabolic syndrome associations
- 2023
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Ingår i: Atherosclerosis. - 1879-1484 .- 0021-9150. ; 382
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Plant-based dietary patterns have been associated with improved health outcomes. This study aims to describe the metabolomic fingerprints of plant-based diet indices (PDI) and examine their association with metabolic syndrome (MetS) and its components in a Danish population. Methods: The MAX study comprised 676 participants (55% women, aged 18-67 y) from Copenhagen. Sociodemographic and dietary data were collected using questionnaires and three 24-h dietary recalls over one year (at baseline, and at 6 and 12 months). Mean dietary intakes were computed, as well as overall PDI, healthful (hPDI) and unhealthful (uPDI) scores, according to food groups for each plant-based index. Clinical variables were also collected at the same time points in a health examination that included complete blood tests. MetS was defined according to the International Diabetes Federation criteria. Plasma metabolites were measured using a targeted metabolomics approach. Metabolites associated with PDI were selected using random forest models and their relationships with PDIs and MetS were analyzed using generalized linear mixed models. Results: The mean prevalence of MetS was 10.8%. High, compared to low, hPDI and uPDI scores were associated with a lower and higher odd of MetS, respectively [odds ratio (95%CI); hPDI: 0.56 (0.43–0.74); uPDI: 1.61 (1.26–2.05)]. Out of 411 quantified plasma metabolites, machine-learning metabolomics fingerprinting revealed 13 metabolites, including food and food-related microbial metabolites, like hypaphorine, indolepropionic acid and lignan-derived enterolactones. These metabolites were associated with all PDIs and were inversely correlated with MetS components (p < 0.05). Furthermore, they had an explainable contribution of 12% and 14% for the association between hPDI or uPDI, respectively, and MetS only among participants with overweight/obesity. Conclusions: Metabolites associated with PDIs were inversely associated with MetS and its components, and may partially explain the effects of plant-based diets on cardiometabolic risk factors.
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| 229. |
- Mavaddat, Nasim, et al.
(författare)
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Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 107:5, s. 036-036
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.
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