Publications by authors named "Johanna M Geleijnse"

217 Publications

Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies.

Nat Commun 2021 04 22;12(1):2329. Epub 2021 Apr 22.

MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.

The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. We found that, after multivariable adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. No associations were seen with the 18-carbon omega-3, alpha-linolenic acid. These findings suggest that higher circulating levels of marine n-3 PUFA are associated with a lower risk of premature death.
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http://dx.doi.org/10.1038/s41467-021-22370-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062567PMC
April 2021

Dairy consumption and mortality after myocardial infarction: a prospective analysis in the Alpha Omega Cohort.

Am J Clin Nutr 2021 07;114(1):59-69

Division of Human Nutrition and Health, Wageningen University, Wageningen, Netherlands.

Background: Population-based studies generally show neutral associations between dairy consumption and ischemic heart disease (IHD) mortality, whereas weak inverse associations were found for cardiovascular disease (CVD) and stroke mortality. Whether dairy consumption affects long-term survival after myocardial infarction (MI) is unknown.

Objectives: We studied types of dairy and long-term mortality risk in drug-treated post-MI patients.

Methods: We included 4365 Dutch patients from the Alpha Omega Cohort aged 60-80 y (21% women) with an MI ≤10 y before enrollment. Dietary data were collected at baseline (2002-2006) using a 203-item FFQ and patients were followed for cause-specific mortality through December 2018. HRs of CVD, IHD, stroke, and all-cause mortality for types of dairy were obtained from Cox models, adjusting for age, sex, energy intake, physical activity, smoking, alcohol intake, diabetes, obesity, and dietary factors.

Results: Most patients were Dutch, 24% were obese, 20% had diabetes, and 97% used cardiovascular medication. Median intakes were 39 g/d for plain yogurt, 88 g/d for total nonfermented milk, and 17 g/d for hard cheeses. Of the cohort, 10% consumed high-fat milk. During ∼12 y of follow-up (48,473 person-years) 2035 deaths occurred, including 903 from CVD, 558 from IHD, and 170 from stroke. Yogurt was linearly inversely associated with CVD mortality (HR: 0.96; 95% CI: 0.93, 0.99; per 25 g/d) and nonlinearly inversely associated with all-cause mortality. Milk was not associated with any of the outcomes (HRs: ∼1.0 per 100 g/d), except for a higher mortality risk in high-fat milk consumers (HR: 1.30; 95% CI: 1.13, 1.49). Other dairy groups were not associated with mortality risk.

Conclusions: In Dutch post-MI patients, yogurt consumption was inversely associated with CVD mortality and all-cause mortality. Associations for milk and other dairy products were neutral or inconsistent.This trial was registered at clinicaltrials.gov as NCT03192410.
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http://dx.doi.org/10.1093/ajcn/nqab026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246616PMC
July 2021

Plasma fatty acids and kidney function decline in post-myocardial infarction patients of the Alpha Omega Cohort.

Nutr Metab Cardiovasc Dis 2021 05 29;31(5):1467-1476. Epub 2021 Jan 29.

Division of Human Nutrition and Health, Wageningen University, Wageningen, the Netherlands.

Background And Aims: Age-related kidney function decline is accelerated in patients with coronary heart disease (CHD). CHD and chronic kidney disease may share common etiologies. We examined plasma fatty acids (FAs) as novel biomarkers of kidney function decline after myocardial infarction (MI).

Methods And Results: The analysis included 2329 Dutch post-MI patients aged 60-80y (Alpha Omega Cohort) most receiving state-of-the-art medications. Plasma FAs (% total FAs) in cholesteryl esters were assessed at baseline (2002-2006), and ∼40 months change in creatinine-cystatin C based glomerular filtration rate was estimated (eGFR, in ml/min per 1.73 m). Beta coefficients for annual eGFR change in relation to plasma linoleic acid (LA; 50.1% of total FAs in CE), omega-3 FAs (EPA + DHA; 1.7%), odd-chain FAs (C15:0 and C17:0; 0.2%), and C14:0 (0.7%) were obtained from linear regression analyses adjusted for age, sex, smoking, and alcohol intake. Mean baseline eGFR ±SD was 78.5 ± 18.7, which declined by 4.7 ± 13.1 during follow-up, or 1.4 ± 3.9 per year. The annual decline in eGFR was less in patients with higher plasma LA (adjusted beta: 0.40 for LA >47 vs ≤ 47%, 95% CI: 0.01; 0.78; p = 0.046). Associations of plasma LA with annual eGFR decline were stronger in 437 patients with diabetes (1.21, 0.24; 2.19) and in 402 patients with CKD (eGFR<60; 0.90, -0.09; 1.89). Weaker, non-significant associations with kidney function decline were observed for the other plasma FAs.

Conclusion: Higher plasma LA may be a good predictor of less kidney function decline after MI, particularly in patients with diabetes. The Alpha Omega Cohort is registered with clinicaltrials.gov, NCT03192410.
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http://dx.doi.org/10.1016/j.numecd.2021.01.012DOI Listing
May 2021

n-3 Fatty Acid Biomarkers and Incident Type 2 Diabetes: An Individual Participant-Level Pooling Project of 20 Prospective Cohort Studies.

Diabetes Care 2021 05 3;44(5):1133-1142. Epub 2021 Mar 3.

Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Objective: Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis.

Research Design And Methods: For our analysis we incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline. De novo harmonized analyses were performed in each cohort following a prespecified protocol, and cohort-specific associations were pooled using inverse variance-weighted meta-analysis.

Results: A total of 16,693 incident T2D cases were identified during follow-up (median follow-up ranging from 2.5 to 21.2 years). In pooled multivariable analysis, per interquintile range (difference between the 90th and 10th percentiles for each fatty acid), EPA, DPA, DHA, and their sum were associated with lower T2D incidence, with hazard ratios (HRs) and 95% CIs of 0.92 (0.87, 0.96), 0.79 (0.73, 0.85), 0.82 (0.76, 0.89), and 0.81 (0.75, 0.88), respectively (all < 0.001). ALA was not associated with T2D (HR 0.97 [95% CI 0.92, 1.02]) per interquintile range. Associations were robust across prespecified subgroups as well as in sensitivity analyses.

Conclusions: Higher circulating biomarkers of seafood-derived n-3 fatty acids, including EPA, DPA, DHA, and their sum, were associated with lower risk of T2D in a global consortium of prospective studies. The biomarker of plant-derived ALA was not significantly associated with T2D risk.
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http://dx.doi.org/10.2337/dc20-2426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132316PMC
May 2021

Metabolic syndrome-related dietary pattern and risk of mortality in kidney transplant recipients.

Nutr Metab Cardiovasc Dis 2021 04 19;31(4):1129-1136. Epub 2021 Jan 19.

Department of Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Background And Aims: Presence of the metabolic syndrome (MetS) importantly contributes to excess mortality in kidney transplant recipients (KTRs). However, it is unclear which dietary factors drive the adverse role of MetS in KTRs. We aimed to define a dietary pattern that maximally explained the variation in MetS components, and to investigate the association between this MetS-related dietary pattern (MetS-DP) and all-cause mortality in KTRs.

Methods And Results: We included 429 adult KTRs who had a functioning graft ⩾1 year. A MetS-DP was constructed using habitual dietary intake derived from a 177-item food frequency questionnaire. We used reduced rank regression (RRR), and defined the six components of MetS (waist circumference, systolic blood pressure, diastolic blood pressure, serum triglycerides, HbA1c, and HDL cholesterol) as response variables and 48 food groups as predictor variables. We evaluated the association between the MetS-DP and all-cause mortality using multivariable Cox regression analysis. The MetS-DP was characterized by high intakes of processed meat and desserts, and low intakes of vegetables, tea, rice, fruits, milk, and meat substitutes. During a mean follow-up of 5.3 ± 1.2 years, 63 KTRs (14.7%) died. Compared to the lowest tertile of the Mets-DP score, those with the greatest adherence had a more than 3-fold higher risk of all-cause mortality (hazard ratio [HR] = 3.63; 95% confidence interval [CI], 1.70-7.74, P < 0.001), independent of potential confounders.

Conclusions: We identified a MetS-related dietary pattern which was independently associated with all-cause mortality in KTRs. The association between this dietary pattern and all-cause mortality was mediated by MetS. Clinical trial reg. no. NCT02811835.
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http://dx.doi.org/10.1016/j.numecd.2021.01.005DOI Listing
April 2021

The Mediterranean diet from past to future: Key concepts from the second "Ancel Keys" International Seminar.

Nutr Metab Cardiovasc Dis 2021 03 2;31(3):717-732. Epub 2021 Jan 2.

Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.

The year 2020 celebrated the tenth anniversary of the recognition of the Mediterranean Diet as Intangible Cultural Heritage of Humanity by the UNESCO Intergovernmental Committee. This event represented a milestone in the history of nutrition, as the Mediterranean diet was the first traditional food practice to receive such award. Since then, a lot has been discussed not only on the beneficial aspects of the Mediterranean diet, but also on its complex role as a lifestyle model that includes a set of skills, knowledge and intercultural dialogue. This process ended up with the recognition in 2019 of Mediterranean diet as a possibly universal model of healthy diet from the EAT-Lancet Commission. These concepts were widely debated at the 2019 "Ancel Keys" International Seminar, held in Ascea (Italy) (for more information see: www.mediterraneandietseminar.org) with the aim to stimulate interest and awareness of a young group of participants on the current problems inherent to the effective implementation of the Mediterranean diet. The present article collects the contributions of several lecturers at the Seminar on key issues such as methodological and experimental approach, sustainability, molecular aspects in disease prevention, future exploitation, without neglecting a historical view of the Seven Countries Study. From the Seminar conclusions emerged a still vibrant and modern role of Mediterranean diet. The years to come will see national and international efforts to reduce the barriers that limit adherence to Mediterranean diet in order to plan for multi-factorial and targeted interventions that would guide our populations to a sustainable healthy living.
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http://dx.doi.org/10.1016/j.numecd.2020.12.020DOI Listing
March 2021

Improving health and carbon footprints of European diets using a benchmarking approach.

Public Health Nutr 2021 02 23;24(3):565-575. Epub 2020 Sep 23.

Division of Human Nutrition and Health, Wageningen University, P.O. Box 17, 6700 AAWageningen, the Netherlands.

Objective: This study aimed to identify diets with improved nutrient quality and environmental impact within the boundaries of dietary practices.

Design: We used Data Envelopment Analysis to benchmark diets for improved adherence to food-based dietary guidelines (FBDG). We then optimised these diets for dietary preferences, nutrient quality and environmental impact. Diets were evaluated using the Nutrient Rich Diet score (NRD15.3), diet-related greenhouse gas emission (GHGE) and a diet similarity index that quantified the proportion of food intake that remained similar as compared with the observed diet.

Setting: National dietary surveys of four European countries (Denmark, Czech Republic, Italy and France).

Subjects: Approximately 6500 adults, aged 18-64 years.

Results: When dietary preferences were prioritised, NRD15·3 was ~6 % higher, GHGE was ~4 % lower and ~85 % of food intake remained similar. This diet had higher amounts of fruit, vegetables and whole grains than the observed diet. When nutrient quality was prioritised, NRD15·3 was ~16 % higher, GHGE was ~3 % lower and ~72 % of food intake remained similar. This diet had higher amounts of legumes and fish and lower amounts of sweetened and alcoholic beverages. Finally, when environmental impact was prioritised, NRD15·3 was ~9 % higher, GHGE was ~21 % lower and ~73 % of food intake remained similar. In this diet, red and processed meat partly shifted to either eggs, poultry, fish or dairy.

Conclusions: Benchmark modelling can generate diets with improved adherence to FBDG within the boundaries of dietary practices, but fully maximising health and minimising GHGE cannot be achieved simultaneously.
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http://dx.doi.org/10.1017/S1368980020003341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844616PMC
February 2021

Urinary Excretion of -Methylnicotinamide and -Methyl-2-Pyridone-5-Carboxamide and Mortality in Kidney Transplant Recipients.

Nutrients 2020 Jul 10;12(7). Epub 2020 Jul 10.

Department of Internal Medicine, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.

It is unclear whether niacin nutritional status is a target for improvement of long-term outcome after renal transplantation. The 24-h urinary excretion of -methylnicotinamide (-MN), as a biomarker of niacin status, has previously been shown to be negatively associated with premature mortality in kidney transplant recipients (KTR). However, recent evidence implies higher enzymatic conversion of -MN to -methyl-2-pyridone-5-carboxamide (2Py) in KTR, therefore the need exists for interpretation of both -MN and 2Py excretion for niacin status assessment. We assessed niacin status by means of the 24-h urinary excretion of the sum of -MN and 2Py (-MN + 2Py), and its associations with risk of premature mortality in KTR. -MN + 2Py excretion was measured in a longitudinal cohort of 660 KTR with LS-MS/MS. Prospective associations of -MN + 2Py excretion were investigated with Cox regression analyses. Median -MN + 2Py excretion was 198.3 (155.9-269.4) µmol/day. During follow-up of 5.4 (4.7-6.1) years, 143 KTR died, of whom 40 due to an infectious disease. -MN + 2Py excretion was negatively associated with risk of all-cause mortality (HR 0.61; 95% CI 0.47-0.79; < 0.001), and infectious mortality specifically (HR 0.47; 95% CI 0.29-0.75; = 0.002), independent of potential confounders. Secondary analyses showed effect modification of hs-CRP on the negative prospective association of -MN + 2Py excretion, and sensitivity analyses showed negative and independent associations of -MN and 2Py excretion with risk of all-cause mortality separately. These findings add further evidence to niacin status as a target for nutritional strategies for improvement of long-term outcome in KTR.
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http://dx.doi.org/10.3390/nu12072059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400946PMC
July 2020

Associations of linoleic acid with markers of glucose metabolism and liver function in South African adults.

Lipids Health Dis 2020 Jun 16;19(1):138. Epub 2020 Jun 16.

Centre of Excellence for Nutrition, Faculty of Health Sciences, North-West University, Potchefstroom, South Africa.

Background: The relation between dietary and circulating linoleic acid (18:2 n-6, LA), glucose metabolism and liver function is not yet clear. Associations of dietary and circulating LA with glucose metabolism and liver function markers were investigated.

Methods: Cross-sectional analyses in 633 black South Africans (aged > 30 years, 62% female, 51% urban) without type 2 diabetes at baseline of the Prospective Urban Rural Epidemiology study. A cultural-sensitive 145-item food-frequency questionnaire was used to collect dietary data, including LA (percentage of energy; en%). Blood samples were collected to measure circulating LA (% total fatty acids (FA); plasma phospholipids), plasma glucose, glycosylated hemoglobin (HbA1c), serum gamma-glutamyl transferase (GGT), alanine (ALT) and aspartate aminotransferase (AST). Associations per 1 standard deviation (SD) and in tertiles were analyzed using multivariable regression.

Results: Mean (±SD) dietary and circulating LA was 6.8 (±3.1) en% and 16.0 (±3.5) % total FA, respectively. Dietary and circulating LA were not associated with plasma glucose or HbA1c (β per 1 SD: - 0.005 to 0.010, P > 0.20). Higher dietary LA was generally associated with lower serum liver enzymes levels. One SD higher circulating LA was associated with 22% lower serum GGT (β (95% confidence interval): - 0.25 (- 0.31, - 0.18), P < 0.001), but only ≤9% lower for ALT and AST. Circulating LA and serum GGT associations differed by alcohol use and locality.

Conclusion: Dietary and circulating LA were inversely associated with markers of impaired liver function, but not with glucose metabolism. Alcohol use may play a role in the association between LA and liver function.

Trial Registration: PURE North-West Province South Africa study described in this manuscript is part of the PURE study. The PURE study is registered in ClinicalTrials.gov (Identifier: NCT03225586; URL).
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http://dx.doi.org/10.1186/s12944-020-01318-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296762PMC
June 2020

Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies.

PLoS Med 2020 06 12;17(6):e1003102. Epub 2020 Jun 12.

MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.

Background: De novo lipogenesis (DNL) is the primary metabolic pathway synthesizing fatty acids from carbohydrates, protein, or alcohol. Our aim was to examine associations of in vivo levels of selected fatty acids (16:0, 16:1n7, 18:0, 18:1n9) in DNL with incidence of type 2 diabetes (T2D).

Methods And Findings: Seventeen cohorts from 12 countries (7 from Europe, 7 from the United States, 1 from Australia, 1 from Taiwan; baseline years = 1970-1973 to 2006-2010) conducted harmonized individual-level analyses of associations of DNL-related fatty acids with incident T2D. In total, we evaluated 65,225 participants (mean ages = 52.3-75.5 years; % women = 20.4%-62.3% in 12 cohorts recruiting both sexes) and 15,383 incident cases of T2D over the 9-year follow-up on average. Cohort-specific association of each of 16:0, 16:1n7, 18:0, and 18:1n9 with incident T2D was estimated, adjusted for demographic factors, socioeconomic characteristics, alcohol, smoking, physical activity, dyslipidemia, hypertension, menopausal status, and adiposity. Cohort-specific associations were meta-analyzed with an inverse-variance-weighted approach. Each of the 4 fatty acids positively related to incident T2D. Relative risks (RRs) per cohort-specific range between midpoints of the top and bottom quintiles of fatty acid concentrations were 1.53 (1.41-1.66; p < 0.001) for 16:0, 1.40 (1.33-1.48; p < 0.001) for 16:1n-7, 1.14 (1.05-1.22; p = 0.001) for 18:0, and 1.16 (1.07-1.25; p < 0.001) for 18:1n9. Heterogeneity was seen across cohorts (I2 = 51.1%-73.1% for each fatty acid) but not explained by lipid fractions and global geographical regions. Further adjusted for triglycerides (and 16:0 when appropriate) to evaluate associations independent of overall DNL, the associations remained significant for 16:0, 16:1n7, and 18:0 but were attenuated for 18:1n9 (RR = 1.03, 95% confidence interval (CI) = 0.94-1.13). These findings had limitations in potential reverse causation and residual confounding by imprecisely measured or unmeasured factors.

Conclusions: Concentrations of fatty acids in the DNL were positively associated with T2D incidence. Our findings support further work to investigate a possible role of DNL and individual fatty acids in the development of T2D.
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http://dx.doi.org/10.1371/journal.pmed.1003102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292352PMC
June 2020

Effects of Potassium or Sodium Supplementation on Mineral Homeostasis: A Controlled Dietary Intervention Study.

J Clin Endocrinol Metab 2020 09;105(9)

Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, RB Groningen, the Netherlands.

Context: Although dietary potassium and sodium intake may influence calcium-phosphate metabolism and bone health, the effects on bone mineral parameters, including fibroblast growth factor 23 (FGF23), are unclear.

Objective: Here, we investigated the effects of potassium or sodium supplementation on bone mineral parameters.

Design, Setting, Participants: We performed a post hoc analysis of a dietary controlled randomized, blinded, placebo-controlled crossover trial. Prehypertensive individuals not using antihypertensive medication (n = 36) received capsules containing potassium chloride (3 g/d), sodium chloride (3 g/d), or placebo. Linear mixed-effect models were used to estimate treatment effects.

Results: Potassium supplementation increased plasma phosphate (from 1.10 ± 0.19 to 1.15 ± 0.19 mmol/L, P = 0.004), in line with an increase in tubular maximum of phosphate reabsorption (from 0.93 ± 0.21 to 1.01 ± 0.20 mmol/L, P < 0.001). FGF23 decreased (114.3 [96.8-135.0] to 108.5 [93.5-125.9] RU/mL, P = 0.01), without change in parathyroid hormone and 25-hydroxy vitamin D3. Fractional calcium excretion decreased (from 1.25 ± 0.50 to 1.11 ± 0.46 %, P = 0.03) without change in plasma calcium. Sodium supplementation decreased both plasma phosphate (from 1.10 ± 0.19 to 1.06 ± 0.21 mmol/L, P = 0.03) and FGF23 (from 114.3 [96.8-135.0] to 108.7 [92.3-128.1] RU/mL, P = 0.02). Urinary and fractional calcium excretion increased (from 4.28 ± 1.91 to 5.45 ± 2.51 mmol/24 hours, P < 0.001, and from 1.25 ± 0.50 to 1.44 ± 0.54 %, P = 0.004, respectively).

Conclusions: Potassium supplementation led to a decrease in FGF23, which was accompanied by increase in plasma phosphate and decreased calcium excretion. Sodium supplementation reduced FGF23, but this was accompanied by decrease in phosphate and increase in fractional calcium excretion. Our results indicate distinct effects of potassium and sodium intake on bone mineral parameters, including FGF23.

Clinical Trial Registration Number: NCT01575041.
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http://dx.doi.org/10.1210/clinem/dgaa359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365698PMC
September 2020

Designing healthier and acceptable diets using data envelopment analysis.

Public Health Nutr 2020 09 17;23(13):2290-2302. Epub 2020 Apr 17.

Division of Human Nutrition and Health, Wageningen University, 6708 WEWageningen, The Netherlands.

Objective: The objective of this research is to propose methodology that can be used to benchmark current diets based on their nutrient intakes and to provide guidelines for improving less healthy diets in a way that is acceptable for the studied population.

Design: We discuss important limitations of current diet models that use optimisation techniques to design healthier and acceptable diets. We illustrate how data envelopment analysis could be used to overcome such limitations, and we describe mathematical models that can be used to calculate not only healthier but also acceptable diets.

Setting: We used data from the Nutrition Questionnaires plus dataset of habitual diets of a general population of adult men and women in The Netherlands (n 1735).

Participants: Adult population.

Results: We calculated healthier diets with substantial higher intakes of protein, fibre, Fe, Ca, K, Mg and vitamins, and substantially lower intakes of Na, saturated fats and added sugars. The calculated diets are combinations of current diets of individuals that belong to the same age/gender group and comprise of food item intakes in proportions observed in the sample.

Conclusions: The proposed methodology enables the benchmarking of existing diets and provides a framework for proposing healthier alternative diets that resemble the current diet in terms of foods intake as much as possible.
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http://dx.doi.org/10.1017/S1368980019004774DOI Listing
September 2020

Consumption of a diet high in dairy leads to higher 15:0 in cholesteryl esters of healthy people when compared to diets high in meat and grain.

Nutr Metab Cardiovasc Dis 2020 05 25;30(5):804-809. Epub 2020 Jan 25.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. Electronic address:

Background And Aims: A higher dairy product intake has been associated to higher blood concentrations of 15:0 (pentadecanoic acid), 17:0 (margaric acid), and 14:0 (myristic acid). This study investigates whether a diet high in dairy products influences cholesteryl ester fatty acid concentrations of these specific fatty acids (FA).

Methods And Results: In a randomized multiple cross-over study, 13 men and 17 women aged 22 ± 4 years with a BMI of 21.6 ± 2.2 kg/m received 3 isocaloric intervention diets (dairy, meat or grain) in random order. For this post-hoc analysis, FA in plasma cholesteryl esters were measured using gas chromatography. We performed a linear mixed model per centered log-ratio transformed FA, adjusting for period, and the interaction between diet and period. Consumed total fat intake per controlled intervention diet was 31.0 ± 0.9 en%/day (dairy), 31.5 ± 0.6 en%/day (meat), and 28.4 ± 1.2 en%/day (grain), respectively. The dairy diet led to higher relative concentrations of 15:0 when compared to diets high in meat and grain, (β; 0.27, 95%CI: 0.18,0.37; p = 1.2 × 10, and β: 0.15; 95%CI: 0.06,0.24; p = 1.2 × 10, respectively). The dairy diet also led to higher 14:0 when compared to the meat diet (β: 0.34; 95%CI: 0.21,0.46; p = 6.0 × 10), but not when compared to the grain diet. 17:0 did not differ between diets.

Conclusion: The plasma cholesteryl ester fraction after a diet high in dairy was characterized by higher 15:0 levels. Concentrations of 14:0 were only higher when comparing the FA profile after a diet high in dairy when compared to a diet high in meat.

Clinical Trial Registration: ClinicalTrials.gov, NCT01314040.
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http://dx.doi.org/10.1016/j.numecd.2020.01.006DOI Listing
May 2020

Inter-Individual Variation in Cancer and Cardiometabolic Health Outcomes in Response to Coffee Consumption: A Critical Review.

Mol Nutr Food Res 2020 04 4;64(7):e1900479. Epub 2020 Mar 4.

Rowett Institute of Nutrition and Health, University of Aberdeen, Foresterhill, AB25 2ZD, Aberdeen, UK.

Scope: Coffee is associated with a lower risk of cancer, cardiovascular disease, and type 2 diabetes at the population level. However, individual susceptibility to the effects of coffee consumption will cause heterogeneity in health responses between individuals. In this critical review determinants of inter-individual variability in cancer and cardiometabolic health outcomes in response to coffee and caffeine consumption are systematically evaluated.

Methods And Results: Embase and MEDLINE are searched for observational studies and clinical trials that examined variation in the response to coffee consumption. A total of 74 studies meet the inclusion criteria, which report variation in cancer (n = 24) and cardiometabolic health (n = 50) outcomes. The qualitative analysis shows that sex, BMI, smoking, alcohol intake, menopausal status, and genetic polymorphisms are probable or possible determinants of inter-individual variability in cancer and cardiometabolic health outcomes in response to coffee and caffeine consumption, albeit the majority of studies have insufficient statistical power to detect significant interaction between these factors and coffee consumption.

Conclusion: Several genetic and non-genetic determinants of inter-individual variability in the responses to coffee and caffeine consumption are identified, indicating that some of the health benefits of coffee may only occur in a subgroup of subjects.
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http://dx.doi.org/10.1002/mnfr.201900479DOI Listing
April 2020

Urinary Excretion of -methyl-2-pyridone-5-carboxamide and -methylnicotinamide in Renal Transplant Recipients and Donors.

J Clin Med 2020 Feb 6;9(2). Epub 2020 Feb 6.

Department of Internal Medicine, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.

-methylnicotinamide (-MN) and -methyl-2-pyridone-5-carboxamide (2Py) are successive end products of NAD catabolism. -MN excretion in 24-h urine is the established biomarker of niacin nutritional status, and recently shown to be reduced in renal transplant recipients (RTR). However, it is unclear whether 2Py excretion is increased in this population, and, if so, whether a shift in excretion of -MN to 2Py can be attributed to kidney function. Hence, we assessed the 24-h urinary excretion of 2Py and -MN in RTR and kidney donors before and after kidney donation, and investigated associations of the urinary ratio of 2Py to -MN (2Py/-MN) with kidney function, and independent determinants of urinary 2Py/-MN in RTR. The urinary excretion of 2Py and -MN was measured in a cross-sectional cohort of 660 RTR and 275 healthy kidney donors with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Linear regression analyses were used to investigate associations and determinants of urinary 2Py/-MN. Median 2Py excretion was 178.1 (130.3-242.8) μmol/day in RTR, compared to 155.6 (119.6-217.6) μmol/day in kidney donors ( < 0.001). In kidney donors, urinary 2Py/-MN increased significantly after kidney donation (4.0 ± 1.4 to 5.2 ± 1.5, respectively; < 0.001). Smoking, alcohol consumption, diabetes, high-density lipoprotein (HDL), high-sensitivity C-reactive protein (hs-CRP) and estimated glomerular filtration rate (eGFR) were identified as independent determinants of urinary 2Py/-MN in RTR. In conclusion, the 24-h urinary excretion of 2Py is higher in RTR than in kidney donors, and urinary 2Py/-MN increases after kidney donation. As our data furthermore reveal strong associations of urinary 2Py/-MN with kidney function, interpretation of both -MN and 2Py excretion may be recommended for assessment of niacin nutritional status in conditions of impaired kidney function.
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http://dx.doi.org/10.3390/jcm9020437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074074PMC
February 2020

Potato consumption, by preparation method and meal quality, with blood pressure and body mass index: The INTERMAP study.

Clin Nutr 2020 10 22;39(10):3042-3048. Epub 2020 Jan 22.

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, UK; NIHR Biomedical Research Centre, Diet, Anthropometry and Physical Activity (DAPA) Group, MRC Epidemiology Unit, University of Cambridge, Cambridge, UK. Electronic address:

Background And Aims: Previous studies have reported associations between higher potato intake and higher blood pressure (BP) and/or risk of hypertension and obesity. These studies rarely considered preparation methods of potatoes, overall dietary pattern or the nutrient quality of the meals. These factors may affect the association of potato intake with BP and body mass index (BMI). This study investigated potato consumption by amount, type of processing, overall dietary pattern, and nutrient quality of the meals in relation to BP and BMI.

Methods: Cross-sectional analyses were conducted among 2696 participants aged 40-59 y in the US and UK samples of the International Study of Macro- and Micro-Nutrients and Blood Pressure (INTERMAP). Nutrient quality of individual food items and the overall diet was assessed with the Nutrient-Rich Foods (NRF) index.

Results: No associations with BP or BMI were found for total potato intake nor for boiled, mashed, or baked potatoes or potato-based mixed dishes. In US women, higher intake of fried potato was associated with 2.29 mmHg (95% CI: 0.55, 3.83) higher systolic BP and with 1.14 mmHg (95% CI: 0.10, 2.17) higher diastolic BP, independent of BMI. Higher fried potato consumption was directly associated with a +0.86 kg/m difference in BMI (95% CI: 0.24, 1.58) in US women. These associations were not found in men. Higher intakes of fried potato meals with a lower nutritional quality (NRF index≤ 2) were positively associated with systolic (3.88 mmHg; 95% CI: 2.63, 5.53) and diastolic BP (1.62 mmHg; 95% CI: 0.48, 2.95) in US women. No associations with BP were observed for fried potato meals with a higher nutritional quality (NRF index> 2).

Conclusions: Fried potato was directly related to BP and BMI in women, but non-fried potato was not. Poor-nutrient quality meals were associated with intake of fried potatoes and higher BP, suggesting that accompanied dietary choices are key mediators of these associations.
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http://dx.doi.org/10.1016/j.clnu.2020.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219046PMC
October 2020

Integration of epidemiologic, pharmacologic, genetic and gut microbiome data in a drug-metabolite atlas.

Nat Med 2020 01 13;26(1):110-117. Epub 2020 Jan 13.

Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.

Progress in high-throughput metabolic profiling provides unprecedented opportunities to obtain insights into the effects of drugs on human metabolism. The Biobanking BioMolecular Research Infrastructure of the Netherlands has constructed an atlas of drug-metabolite associations for 87 commonly prescribed drugs and 150 clinically relevant plasma-based metabolites assessed by proton nuclear magnetic resonance. The atlas includes a meta-analysis of ten cohorts (18,873 persons) and uncovers 1,071 drug-metabolite associations after evaluation of confounders including co-treatment. We show that the effect estimates of statins on metabolites from the cross-sectional study are comparable to those from intervention and genetic observational studies. Further data integration links proton pump inhibitors to circulating metabolites, liver function, hepatic steatosis and the gut microbiome. Our atlas provides a tool for targeted experimental pharmaceutical research and clinical trials to improve drug efficacy, safety and repurposing. We provide a web-based resource for visualization of the atlas (http://bbmri.researchlumc.nl/atlas/).
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http://dx.doi.org/10.1038/s41591-019-0722-xDOI Listing
January 2020

Adherence to the Dutch dietary guidelines and 15-year incidence of heart failure in the EPIC-NL cohort.

Eur J Nutr 2020 Dec 7;59(8):3405-3413. Epub 2020 Jan 7.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Purpose: A healthy diet may contribute to the primary prevention of heart failure (HF), but evidence is still inconclusive. We aimed to study the association between adherence to the Dutch dietary guidelines and incidence of HF.

Methods: We studied 37,468 participants aged 20-70 years and free of HF at baseline from the EPIC-NL cohort. At baseline (1993-1997), data were collected on demographics, lifestyle, and presence of chronic diseases. Dietary intake was assessed using a 178-item validated food frequency questionnaire. Dietary intake data were used to calculate scores on the Dutch Healthy Diet 2015 Index (DHD15-index) measuring adherence to the Dutch dietary guidelines. The DHD15-index is based on the average daily intake of 14 food groups resulting in a total score ranging between 0 and 140, with higher scores indicating better adherence. HF morbidity and mortality during follow-up were ascertained through linkage with national registries. Cox proportional hazards analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between DHD15 adherence and HF risk, adjusting for sociodemographic and lifestyle characteristics.

Results: The average score on the DHD15-index was 71 (SD = 15). During a median follow-up of 15.2 years (IQR 14.1-16.5), 674 HF events occurred. After adjustment for demographic and lifestyle characteristics, higher scores on the DHD15-index were associated with lower risk of HF (HR 0.73; 95% CI 0.58-0.93; P 0.001).

Conclusion: In a large Dutch population of middle-aged adults, higher adherence to the Dutch dietary guidelines was associated with lower risk of HF.
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http://dx.doi.org/10.1007/s00394-019-02170-7DOI Listing
December 2020

Tryptophan Intake and Tryptophan Losses in Hemodialysis Patients: A Balance Study.

Nutrients 2019 Nov 21;11(12). Epub 2019 Nov 21.

Department of Nephrology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.

Tryptophan depletion is common in hemodialysis patients. The cause of this depletion remains largely unknown, but reduced nutritional tryptophan intake, losses during dialysis or an increased catabolism due to an inflammatory state are likely contributors. Currently, little is known about tryptophan homeostasis in hemodialysis patients. We assessed dietary tryptophan intake, measured plasma tryptophan during dialysis, and measured the combined urinary and dialysate excretion of tryptophan in 40 hemodialysis patients (66 ± 15 years and 68% male). Patients had low tryptophan concentrations (27 ± 9 µmol/L) before dialysis. Mean dietary tryptophan intake was 4454 ± 1149 µmol/24 h. Mean urinary tryptophan excretion was 15.0 ± 12.3 μmol/24 h, dialysate excretion was 209 ± 67 μmol/24 h and combined excretion was 219 ± 66 µmol/24 h, indicating only 5% of dietary tryptophan intake was excreted. No associations were found between plasma tryptophan concentration and tryptophan intake, plasma kynurenine/tryptophan ratio or inflammatory markers. During dialysis, mean plasma tryptophan concentration increased 16% to 31 ± 8 µmol/L. Intradialytic increase in plasma tryptophan was associated with a lower risk of mortality, independent of age, sex and dialysis vintage (HR: 0.87 [0.76-0.99]; = 0.04). Tryptophan intake was well above the dietary recommendations and, although tryptophan was removed during dialysis, mean plasma tryptophan increased during dialysis. The cause of this phenomenon is unknown, but it appears to be protective.
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http://dx.doi.org/10.3390/nu11122851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950375PMC
November 2019

Associations of dairy and fiber intake with circulating odd-chain fatty acids in post-myocardial infarction patients.

Nutr Metab (Lond) 2019 13;16:78. Epub 2019 Nov 13.

1Division of Human Nutrition and Health, Wageningen University, PO Box 17, 6700 AA Wageningen, The Netherlands.

Background: Circulating odd-chain fatty acids pentadecanoic (15:0) and heptadecanoic acid (17:0) are considered to reflect dairy intake. In cohort studies, higher circulating 15:0 and 17:0 were associated with lower type 2 diabetes risk. A recent randomized controlled trial in humans suggested that fiber intake also increased circulating 15:0 and 17:0, potentially resulting from fermentation by gut microbes. We examined the associations of dairy and fiber intake with circulating 15:0 and 17:0 in patients with a history of myocardial infarction (MI).

Methods: We performed cross-sectional analyses in a subsample of 869 Dutch post-MI patients of the Alpha Omega Cohort who had data on dietary intake and circulating fatty acids. Dietary intakes (g/d) were assessed using a 203-item food frequency questionnaire. Circulating 15:0 and 17:0 (as % of total fatty acids) were measured in plasma phospholipids (PL) and cholesteryl esters (CE). Spearman correlations ( ) were computed between intakes of total dairy, dairy fat, fiber, and circulating 15:0 and 17:0.

Results: Patients were on average 69 years old, 78% was male and 21% had diabetes. Total dairy intake comprised predominantly milk and yogurt (69%). Dairy fat was mainly derived from cheese (47%) and milk (15%), and fiber was mainly from grains (43%). Circulating 15:0 in PL was significantly correlated with total dairy and dairy fat intake (both  = 0.19,  < 0.001), but not with dietary fiber intake (  = 0.05,  = 0.11). Circulating 17:0 in PL was correlated both with dairy intake (  = 0.14 for total dairy and 0.11 for dairy fat,  < 0.001), and fiber intake (  = 0.19,  < 0.001). Results in CE were roughly similar, except for a weaker correlation of CE 17:0 with fiber (  = 0.11,  = 0.001). Circulating 15:0 was highest in those with high dairy intake irrespective of fiber intake, while circulating 17:0 was highest in those with high dairy and fiber intake.

Conclusions: In our cohort of post-MI patients, circulating 15:0 was associated with dairy intake but not fiber intake, whereas circulating 17:0 was associated with both dairy and fiber intake. These data suggest that cardiometabolic health benefits previously attributed to 17:0 as a biomarker of dairy intake may partly be explained by fiber intake.
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http://dx.doi.org/10.1186/s12986-019-0407-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854617PMC
November 2019

Plasma and Dietary Linoleic Acid and 3-Year Risk of Type 2 Diabetes After Myocardial Infarction: A Prospective Analysis in the Alpha Omega Cohort.

Diabetes Care 2020 02 14;43(2):358-365. Epub 2019 Nov 14.

Division of Human Nutrition and Health, Wageningen University, Wageningen, the Netherlands.

Objective: To study plasma and dietary linoleic acid (LA) in relation to type 2 diabetes risk in post-myocardial infarction (MI) patients.

Research Design And Methods: We included 3,257 patients aged 60-80 years (80% male) with a median time since MI of 3.5 years from the Alpha Omega Cohort and who were initially free of type 2 diabetes. At baseline (2002-2006), plasma LA was measured in cholesteryl esters, and dietary LA was estimated with a 203-item food-frequency questionnaire. Incident type 2 diabetes was ascertained through self-reported physician diagnosis and medication use. Hazard ratios (with 95% CIs) were calculated by Cox regressions, in which dietary LA isocalorically replaced the sum of saturated (SFA) and fatty acids (TFA).

Results: Mean ± SD circulating and dietary LA was 50.1 ± 4.9% and 5.9 ± 2.1% energy, respectively. Plasma and dietary LA were weakly correlated (Spearman = 0.13, < 0.001). During a median follow-up of 41 months, 171 patients developed type 2 diabetes. Plasma LA was inversely associated with type 2 diabetes risk (quintile [Q]5 vs. Q1: 0.44 [0.26, 0.75]; per 5%: 0.73 [0.62, 0.86]). Substitution of dietary LA for SFA+TFA showed no association with type 2 diabetes risk (Q5 vs. Q1: 0.78 [0.36, 1.72]; per 5% energy: 1.18 [0.59, 2.35]). Adjustment for markers of de novo lipogenesis attenuated plasma LA associations.

Conclusions: In our cohort of post-MI patients, plasma LA was inversely related to type 2 diabetes risk, whereas dietary LA was not related. Further research is needed to assess whether plasma LA indicates metabolic state rather than dietary LA in these patients.
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http://dx.doi.org/10.2337/dc19-1483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971780PMC
February 2020

Urinary Excretion of -Methylnicotinamide, as a Biomarker of Niacin Status, and Mortality in Renal Transplant Recipients.

J Clin Med 2019 Nov 12;8(11). Epub 2019 Nov 12.

Department of Internal Medicine, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.

Renal transplant recipients (RTR) commonly suffer from vitamin B deficiency and its functional consequences add to an association with poor long-term outcome. It is unknown whether niacin status is affected in RTR and, if so, whether this affects clinical outcomes, as vitamin B is a cofactor in nicotinamide biosynthesis. We compared 24-h urinary excretion of -methylnicotinamide (-MN) as a biomarker of niacin status in RTR with that in healthy controls, in relation to dietary intake of tryptophan and niacin as well as vitamin B status, and investigated whether niacin status is associated with the risk of premature all-cause mortality in RTR. In a prospective cohort of 660 stable RTR with a median follow-up of 5.4 (4.7-6.1) years and 275 healthy kidney donors, 24-h urinary excretion of -MN was measured with liquid chromatography-tandem mass spectrometry LC-MS/MS. Dietary intake was assessed by food frequency questionnaires. Prospective associations of -MN excretion with mortality were investigated by Cox regression analyses. Median -MN excretion was 22.0 (15.8-31.8) μmol/day in RTR, compared to 41.1 (31.6-57.2) μmol/day in healthy kidney donors ( < 0.001). This difference was independent of dietary intake of tryptophan (1059 ± 271 and 1089 ± 308 mg/day; = 0.19), niacin (17.9 ± 5.2 and 19.2 ± 6.2 mg/day; < 0.001), plasma vitamin B (29.0 (17.5-49.5), and 42.0 (29.8-60.3) nmol/L; < 0.001), respectively. -MN excretion was inversely associated with the risk of all-cause mortality in RTR (HR 0.57; 95% CI 0.45-0.71; < 0.001), independent of potential confounders. RTR excrete less -MN in 24-h urine than healthy controls, and our data suggest that this difference cannot be attributed to lower dietary intake of tryptophan and niacin, nor vitamin B status. Importantly, lower 24-h urinary excretion of -MN is independently associated with a higher risk of premature all-cause mortality in RTR.
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http://dx.doi.org/10.3390/jcm8111948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912198PMC
November 2019

SHARP-Indicators Database towards a public database for environmental sustainability.

Data Brief 2019 Dec 7;27:104617. Epub 2019 Oct 7.

Division of Human Nutrition and Health, Wageningen University, PO Box 17, 6700 AA Wageningen, the Netherlands.

To initiate the achievement of an European-wide applicable public database for indicators of environmental sustainability of the diet, we developed the SHARP Indicators Database (SHARP-ID). A comprehensive description of the development of the SHARP-ID is provided in this article. In the SHARP-ID, environmental impact assessment was based on attributional life cycle analyses using environmental indicators greenhouse gas emission (GHGE) and land use (LU). Life cycle inventory data of 182 primary products were combined with data on production, trade and transport, and adjusted for consumption amount using conversions factors for production, edible portion, cooking losses and gains, and for food losses and waste in order to derive estimates of GHGE and LU for the foods as eaten. Extrapolations based on similarities in type of food, production system and ingredient composition were made to obtain estimates of GHGE and LU per kg of food as eaten for 944 food items coded with a unique FoodEx2-code of EFSA and consumed in four European countries, i.e. Denmark, Czech Republic, Italy and France. This LCA-food-item database can be linked to food intake data collected at the individual level in order to calculate the environmental impact of individual's diets. The application of this database to European survey data is described in an original research article entitled "Dietary choices and environmental impact in four European countries" (Mertens et al., 2019).
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http://dx.doi.org/10.1016/j.dib.2019.104617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6806457PMC
December 2019

Urinary Taurine Excretion and Risk of Late Graft Failure in Renal Transplant Recipients.

Nutrients 2019 Sep 13;11(9). Epub 2019 Sep 13.

Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.

Taurine is a sulfur containing nutrient that has been shown to protect against oxidative stress, which has been implicated in the pathophysiology leading to late graft failure after renal transplantation. We prospectively investigated whether high urinary taurine excretion, reflecting high taurine intake, is associated with low risk for development of late graft failure in renal transplant recipients (RTR). Urinary taurine excretion was measured in a longitudinal cohort of 678 stable RTR. Prospective associations were assessed using Cox regression analyses. Graft failure was defined as the start of dialysis or re-transplantation. In RTR (58% male, 53 ± 13 years old, estimated glomerular filtration rate (eGFR) 45 ± 19 mL/min/1.73 m), urinary taurine excretion (533 (210-946) µmol/24 h) was significantly associated with serum free sulfhydryl groups (β = 0.126; = 0.001). During median follow-up for 5.3 (4.5-6.0) years, 83 (12%) patients developed graft failure. In Cox regression analyses, urinary taurine excretion was inversely associated with graft failure (hazard ratio: 0.74 (0.67-0.82); < 0.001). This association remained significant independent of potential confounders. High urinary taurine excretion is associated with low risk of late graft failure in RTR. Therefore, increasing taurine intake may potentially support graft survival in RTR. Further studies are warranted to determine the underlying mechanisms and the potential of taurine supplementation.
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http://dx.doi.org/10.3390/nu11092212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770760PMC
September 2019

A metabolic profile of all-cause mortality risk identified in an observational study of 44,168 individuals.

Nat Commun 2019 08 20;10(1):3346. Epub 2019 Aug 20.

Division of Human Nutrition, Wageningen University, PO Box 17, 6700 AA, Wageningen, The Netherlands.

Predicting longer-term mortality risk requires collection of clinical data, which is often cumbersome. Therefore, we use a well-standardized metabolomics platform to identify metabolic predictors of long-term mortality in the circulation of 44,168 individuals (age at baseline 18-109), of whom 5512 died during follow-up. We apply a stepwise (forward-backward) procedure based on meta-analysis results and identify 14 circulating biomarkers independently associating with all-cause mortality. Overall, these associations are similar in men and women and across different age strata. We subsequently show that the prediction accuracy of 5- and 10-year mortality based on a model containing the identified biomarkers and sex (C-statistic = 0.837 and 0.830, respectively) is better than that of a model containing conventional risk factors for mortality (C-statistic = 0.772 and 0.790, respectively). The use of the identified metabolic profile as a predictor of mortality or surrogate endpoint in clinical studies needs further investigation.
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http://dx.doi.org/10.1038/s41467-019-11311-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702196PMC
August 2019

Fruit and Vegetable Intake and Risk of Posttransplantation Diabetes in Renal Transplant Recipients.

Diabetes Care 2019 09 11;42(9):1645-1652. Epub 2019 Jul 11.

Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Objective: Posttransplantation diabetes mellitus (PTDM) contributes to risk for cardiovascular morbidity and mortality in renal transplant recipients (RTRs). In the general population, consumption of a diet containing few fruits and vegetables predisposes to type 2 diabetes. The role of diet as a potential modifiable risk factor for PTDM has not been explored. Our focus was to investigate the prospective associations of fruit and vegetable intake with risk of PTDM in stable RTRs.

Research Design And Methods: We included 472 adult RTRs who had a functioning graft ≥1 year. Fruit and vegetable intake was assessed by using a 177-item food frequency questionnaire. PTDM was defined according the American Diabetes Association's diagnostic criteria for diabetes.

Results: During 5.2 years of follow-up, 52 RTRs (11%) developed PTDM. Fruit intake was not associated with PTDM (hazard ratio [HR] 0.90 [95% CI 0.79-1.03] per log g/day; = 0.13), whereas vegetable intake was inversely associated with PTDM (HR 0.77 [95% CI 0.63-0.94] per log g/day; = 0.009). Mediation analyses revealed that ±50% of the association between vegetable intake and PTDM was mediated by variations in key components of the metabolic syndrome (i.e., HDL cholesterol, triglycerides, and waist circumference) as determined by the National Cholesterol Education Program's Adult Treatment Panel III Expert Panel.

Conclusions: In this study vegetable intake, but not fruit intake, was associated with lower risk of PTDM in RTRs, likely largely through beneficial effects on key components of the metabolic syndrome. These findings further support accumulating evidence that supports a recommendation of higher vegetable intake by RTRs.
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http://dx.doi.org/10.2337/dc19-0224DOI Listing
September 2019

Total Fermented Dairy Food Intake Is Inversely Associated with Cardiovascular Disease Risk in Women.

J Nutr 2019 10;149(10):1797-1804

School of Public Health, University of Queensland, Brisbane, Queensland, Australia.

Background: The relation between fermented dairy consumption and type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in an Australian population remains to be established.

Objectives: The aim of this study was to investigate the association between fermented dairy consumption and T2DM and CVD risk.

Methods: The Australian Longitudinal Study on Women's Health included Australian women (aged 45-50 y) at baseline in 2001, who were followed up through 5 surveys until 2016. Dietary intake was assessed through the use of a validated 101-item FFQ at baseline. Main study outcomes were self-reported physician-diagnosed T2DM and CVD. Logistic regression models adjusted for sociodemographic and lifestyle factors were used to estimate the association between dairy intake and T2DM and CVD risk.

Results: Of 7633 women free of diabetes at baseline, 701 (9.2%) developed T2DM during a maximum 15-y follow-up period. Women in the highest tertile of yogurt intake had lower adjusted odds of T2DM than those in the lowest tertile (OR: 0.81; 95% CI: 0.67, 0.99; P = 0.041). This relation became nonsignificant after adjustment for dietary variables and total energy intake (OR: 0.88; 95% CI: 0.71, 1.08; P = 0.21). Of 7679 women free of CVD at baseline, 835 (10.9%) cases of CVD were reported during follow-up. High intake of yogurt and total fermented dairy was associated with lower CVD risk (OR: 0.84; 95% CI: 0.70, 1.00; P = 0.05, 0.80; 0.67, 0.96; 0.017, respectively) than observed in the lowest tertile of dairy product intake. Additional adjustment attenuated the relation (OR: 0.87; 95% CI: 0.72, 1.04; P = 0.13, 0.83; 0.69, 1.00; 0.048, for yogurt and total fermented dairy, respectively). No associations were found with other dairy groups.

Conclusion: The findings from this population-based study of Australian women suggest an inverse association between total fermented dairy intake and CVD risk, which may partly be accounted for by other dietary components.
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http://dx.doi.org/10.1093/jn/nxz128DOI Listing
October 2019

High Dietary Intake of Vegetable Protein Is Associated With Lower Prevalence of Renal Function Impairment: Results of the Dutch DIALECT-1 Cohort.

Kidney Int Rep 2019 May 21;4(5):710-719. Epub 2019 Feb 21.

Department of Internal Medicine/Nephrology, Ziekenhuis Groep Twente, Almelo, the Netherlands.

Introduction: Dietary protein intake may influence development of renal function impairment in diabetes mellitus type 2 (T2DM). We assessed the association between sources of protein and prevalence of renal function impairment.

Methods: Cross-sectional analyses were performed in baseline data of 420 patients of the DIAbetes and LifEstyle Cohort Twente-1 (DIALECT-1) study. Protein intake was assessed using a Food Frequency Questionnaire, modified for accurate assessment of protein intake, including types and sources of protein. Renal function impairment was defined as estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m (Chronic Kidney Disease Epidemiology Collaboration formula).

Results: Among 420 patients with T2DM, 99 renal function impairment cases were identified. Multivariate Cox proportional hazard models were used and adjusted for the main lifestyle and dietary factors. The prevalence ratios in the fully adjusted model were 1 (reference), 0.74 (95% confidence interval [CI]: 0.44-1.27;  = 0.28) and 0.47 (95% CI: 0.23-0.98;  = 0.04) according to increasing tertiles of vegetable protein intake. For animal protein intake the prevalence ratios were 1 (reference), 1.10 (95% CI: 0.64-1.88;  = 0.74) and 1.06 (95% CI: 0.56-1.99;  = 0.87) according to increasing tertiles of intake. Theoretical replacement models showed that replacing 3 energy percent from animal protein by vegetable protein lowered the prevalence ratio for the association with renal function impairment to 0.20 (95% CI: 0.06-0.63;  = 0.01).

Conclusion: In conclusion, we found that higher intake of vegetable protein was associated with a lower prevalence of renal function impairment, and theoretical replacement of animal protein with vegetable protein was inversely associated with renal function impairment among patients with T2DM.
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http://dx.doi.org/10.1016/j.ekir.2019.02.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506707PMC
May 2019

Plasma Malondialdehyde and Risk of New-Onset Diabetes after Transplantation in Renal Transplant Recipients: A Prospective Cohort Study.

J Clin Med 2019 Apr 4;8(4). Epub 2019 Apr 4.

Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.

New-onset diabetes after transplantation (NODAT) is a frequent complication in renal transplant recipients (RTR). Although oxidative stress has been associated with diabetes mellitus, data regarding NODAT are limited. We aimed to prospectively investigate the long-term association between the oxidative stress biomarker malondialdehyde (measured by high-performance liquid chromatography) and NODAT in an extensively phenotyped cohort of non-diabetic RTR with a functioning graft ≥1 year. We included 516 RTR (51 ± 13 years-old, 57% male). Median plasma malondialdehyde (MDA) was 2.55 (IQR, 1.92-3.66) µmol/L. During a median follow-up of 5.3 (IQR, 4.6-6.0) years, 56 (11%) RTR developed NODAT. In Cox proportional-hazards regression analyses, MDA was inversely associated with NODAT, independent of immunosuppressive therapy, transplant-specific covariates, lifestyle, inflammation, and metabolism parameters (HR, 0.55; 95% CI, 0.36-0.83 per 1-SD increase; < 0.01). Dietary antioxidants intake (e.g., vitamin E, α-lipoic acid, and linoleic acid) were effect-modifiers of the association between MDA and NODAT, with particularly strong inverse associations within the subgroup of RTR with relatively higher dietary antioxidants intake. In conclusion, plasma MDA concentration is inversely and independently associated with long-term risk of NODAT in RTR. Our findings support a potential underrecognized role of oxidative stress in post-transplantation glucose homeostasis.
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http://dx.doi.org/10.3390/jcm8040453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518172PMC
April 2019

Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality.

Circulation 2019 05;139(21):2422-2436

Benjamin Leon for Geriatrics Research and Education, Herbert Wertheim College of Medicine, Florida International University, Miami (P.H.M.C.).

Background: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.

Methods: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available).

Results: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships.

Conclusions: In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.038908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582360PMC
May 2019
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