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Gut Microbiome and Its Cofactors Are Linked to Lipoprotein Distribution Profiles.
Castro-Mejía, JL, Khakimov, B, Aru, V, Lind, MV, Garne, E, Paulová, P, Tavakkoli, E, Hansen, LH, Smilde, AK, Holm, L, et al
Microorganisms. 2022;(11)
Abstract
Increasing evidence indicates that the gut microbiome (GM) plays an important role in dyslipidemia. To date, however, no in-depth characterization of the associations between GM with lipoproteins distributions (LPD) among adult individuals with diverse BMI has been conducted. To determine such associations, we studied blood-plasma LPD, fecal short-chain fatty acids (SCFA) and GM of 262 Danes aged 19-89 years. Stratification of LPD segregated subjects into three clusters displaying recommended levels of lipoproteins and explained by age and body-mass-index. Higher levels of HDL2a and HDL2b were associated with a higher abundance of Ruminococcaceae and Christensenellaceae. Increasing levels of total cholesterol and LDL-1 and LDL-2 were positively associated with Lachnospiraceae and Coriobacteriaceae, and negatively with Bacteroidaceae and Bifidobacteriaceae. Metagenome-sequencing showed a higher abundance of biosynthesis of multiple B-vitamins and SCFA metabolism genes among healthier LPD profiles. Metagenomic-assembled genomes (MAGs) affiliated to Eggerthellaceae and Clostridiales were contributors of these genes and their relative abundance correlated positively with larger HDL subfractions. The study demonstrates that differences in composition and metabolic traits of the GM are associated with variations in LPD among the recruited subjects. These findings provide evidence for GM considerations in future research aiming to shed light on mechanisms of the GM-dyslipidemia axis.
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The effect of daily protein supplementation, with or without resistance training for 1 year, on muscle size, strength, and function in healthy older adults: A randomized controlled trial.
Mertz, KH, Reitelseder, S, Bechshoeft, R, Bulow, J, Højfeldt, G, Jensen, M, Schacht, SR, Lind, MV, Rasmussen, MA, Mikkelsen, UR, et al
The American journal of clinical nutrition. 2021;(4):790-800
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Abstract
BACKGROUND Protein supplementation alone or combined with resistance training has been proposed to be effective in counteracting age-related losses of muscle mass and strength. OBJECTIVES To investigate the effect of protein supplementation alone or combined with light-intensity or heavy-load resistance exercise on muscle size, strength, and function in older adults. METHODS In a 1-y randomized controlled trial, 208 healthy older adults (>65 y) were randomly assigned to 1 of 5 interventions: 1) carbohydrate supplementation (CARB); 2) collagen protein supplementation (COLL); 3) whey protein supplementation (WHEY); 4) light-intensity resistance training 3-5 times/wk with whey protein supplementation (LITW); and 5) heavy resistance training 3 times weekly with whey protein supplementation (HRTW). Protein supplements contained 20 g protein + 10 g carbohydrate, whereas CARB contained 30 g of carbohydrates. All intervention groups received the supplement twice daily. The primary outcome was change in the quadriceps cross-sectional area (qCSA). Secondary outcomes included measures of lower extremity strength and power, functional capabilities, and body composition. RESULTS There were 184 participants who completed the study. COLL and WHEY did not affect any measured parameter compared to CARB. Compared to WHEY, HRTW improved the qCSA size (between-group difference, +1.68 cm2; 95% CI, +0.41 to +2.95 cm2; P = 0.03), as well as dynamic (+18.4 Nm; 95% CI, +10.1 to +26.6 Nm; P < 10-4) and isometric knee extensor strength (+23.9 Nm; 95% CI, +14.2 to +33.6 Nm; P < 10-5). LITW did not improve the qCSA size, but increased dynamic knee extensor strength compared to WHEY (+13.7 Nm; 95% CI, +5.3 and +22.1 Nm; P = 0.01). CONCLUSIONS Recommending protein supplementation as a stand-alone intervention for healthy older individuals seems ineffective in improving muscle mass and strength. Only HRTW was effective in both preserving muscle mass and increasing strength. Thus, we recommend that future studies investigate strategies to increase long-term compliance to heavy resistance exercise in healthy older adults. This trial was registered at clinicaltrials.gov as NCT02034760.
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Daily Protein and Energy Intake Are Not Associated with Muscle Mass and Physical Function in Healthy Older Individuals-A Cross-Sectional Study.
Højfeldt, G, Nishimura, Y, Mertz, K, Schacht, SR, Lindberg, J, Jensen, M, Hjulmand, M, Lind, MV, Jensen, T, Jespersen, AP, et al
Nutrients. 2020;(9)
Abstract
Dietary protein has a pivotal role in muscle mass maintenance with advancing age. However, an optimal dose and distribution of protein intake across the day as well as the interaction with energy intake for the maintenance of muscle mass and physical function in healthy older adults remain to be fully elucidated. The purpose of this study was to examine the association between muscle mass, strength, and physical function, and the total amount and distribution of protein and energy intake across the day in healthy older individuals. The research question was addressed in a cross-sectional study including 184 Danish men and woman (age: 70.2 ± 3.9 years, body mass: 74.9 ± 12.1 kg, Body Mass Index (BMI): 25.4 ± 3.7 kg/m2) where a 3-day dietary registration, muscle mass, strength, and functional measurements were collected. We found that neither daily total protein intake nor distribution throughout the day were associated with muscle mass, strength, or physical function. Consequently, we do not provide an incentive for healthy older Danish individuals who already adhere to the current internationally accepted recommended dietary protein intake (0.83 g/kg/day) to change dietary protein intake or its distribution pattern throughout the day.
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Effects of vitamin D supplementation on cardiometabolic outcomes in children and adolescents: a systematic review and meta-analysis of randomized controlled trials.
Hauger, H, Laursen, RP, Ritz, C, Mølgaard, C, Lind, MV, Damsgaard, CT
European journal of nutrition. 2020;(3):873-884
Abstract
PURPOSE In observational studies, higher S-25-hydroxyvitamin D [S-25(OH)D] has been associated with a more favorable cardiometabolic profile in childhood, but results may be confounded. We examined effects of vitamin D supplementation on cardiometabolic outcomes in children and adolescents. METHODS We systematically searched relevant databases for randomized controlled trials (RCTs) examining effects of vitamin D supplementation compared to placebo or a lower dose of vitamin D on blood glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), glycated hemoglobin, cholesterol [total, high-density, and low-density lipoprotein (LDL-C)], triglycerides, or blood pressure. We conducted random-effects meta-analyses of weighted mean differences in all participants and in subgroups of overweight/obese versus normal weight participants with or without baseline S-25(OH)D < 50 nmol/L. We also explored associations between responses in S-25(OH)D and outcomes by meta-regression. RESULTS Fourteen RCTs with a total of 1088 participants aged 4-19 years were included. In the meta-analysis, vitamin D supplementation increased S-25(OH)D by 27 nmol/L [95% CI 16; 37] (P < 0.0001) and increased LDL-C by 0.11 mmol/L [0.02; 0.20] (P = 0.02) without any subgroup differences and a generally low to moderate heterogeneity. Vitamin D supplementation had no other effects. However, in the meta-regression analysis, HOMA-IR decreased by 0.51 points [- 0.97; - 0.04] per 10 nmol/L increase in the endpoint S-25(OH)D among overweight/obese participants (P = 0.04). CONCLUSIONS These results do not support the use of vitamin D supplementation for improving cardiometabolic health in childhood. Indicated beneficial effects on insulin resistance in those with obesity could be investigated further, while unfavorable effects on LDL-C may be a concern.
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Breastmilk Lipids and Oligosaccharides Influence Branched Short-Chain Fatty Acid Concentrations in Infants with Excessive Weight Gain.
Pekmez, CT, Larsson, MW, Lind, MV, Vazquez Manjarrez, N, Yonemitsu, C, Larnkjaer, A, Bode, L, Mølgaard, C, Michaelsen, KF, Dragsted, LO
Molecular nutrition & food research. 2020;(3):e1900977
Abstract
SCOPE The aim is to identify breastmilk components associated with fecal concentration of SCFAs and to investigate whether they differ between infants with high weight gain (HW) and normal weight gain (NW). METHODS AND RESULTS Breastmilk and fecal samples are collected from mother-infant dyads with HW (n = 11) and NW (n = 15) at 5 and 9 months of age. Breastmilk is profiled on ultra-performance LC-quadrupole TOF-MS platform. Fecal SCFAs are quantified using an isotope-labeled chemical derivatization method. Human milk oligosaccharides (HMOs) are quantified using HPLC after fluorescent derivatization. Lower levels of α-linolenic acid, oleic acid, 3-oxohexadecanoic acid, LPE (P-16:0), LPC (16:0), LPC (18:0), PC (36:2) in breastmilk from mothers from the HW-group at 5 months of age is found. Fecal SCFA concentrations are increased during the transition period from breastfeeding to complementary feeding. Fecal butyrate concentration is higher in the NW-group at 9 months of age. Fecal branched SCFAs are positively associated with breastmilk phospholipid levels, free-fatty acid levels, HMO-diversity, sialylated-HMOs, 6'-sialyllactose, and disialyl-lacto-N-hexaose. CONCLUSION Fecal branched SCFA concentrations seem to be affected by breastmilk lipid and HMO composition. These differences in breastmilk metabolites may partially explain the excessive weight gain in early life.
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Early Nutrition and Its Effect on Growth, Body Composition and Later Obesity.
Grenov, B, Larnkjær, A, Lind, MV, Michaelsen, KF
World review of nutrition and dietetics. 2019;:119-137
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Genetic predisposition to higher body fat yet lower cardiometabolic risk in children and adolescents.
Viitasalo, A, Schnurr, TM, Pitkänen, N, Hollensted, M, Nielsen, TRH, Pahkala, K, Lintu, N, Lind, MV, Atalay, M, Frithioff-Bøjsøe, C, et al
International journal of obesity (2005). 2019;(10):2007-2016
Abstract
BACKGROUND Most obese children show cardiometabolic impairments, such as insulin resistance, dyslipidemia, and hypertension. Yet some obese children retain a normal cardiometabolic profile. The mechanisms underlying this variability remain largely unknown. We examined whether genetic loci associated with increased insulin sensitivity and relatively higher fat storage on the hip than on the waist in adults are associated with a normal cardiometabolic profile despite higher adiposity in children. METHODS We constructed a genetic score using variants previously linked to increased insulin sensitivity and/or decreased waist-hip ratio adjusted for body mass index (BMI), and examined the associations of this genetic score with adiposity and cardiometabolic impairments in a meta-analysis of six cohorts, including 7391 European children aged 3-18 years. RESULTS The genetic score was significantly associated with increased degree of obesity (higher BMI-SDS beta = 0.009 SD/allele, SE = 0.003, P = 0.003; higher body fat mass beta = 0.009, SE = 0.004, P = 0.031), yet improved body fat distribution (lower WHRadjBMI beta = -0.014 SD/allele, SE = 0.006, P = 0.016), and favorable concentrations of blood lipids (higher HDL cholesterol: beta = 0.010 SD/allele, SE = 0.003, P = 0.002; lower triglycerides: beta = -0.011 SD/allele, SE = 0.003, P = 0.001) adjusted for age, sex, and puberty. No differences were detected between prepubertal and pubertal/postpubertal children. The genetic score predicted a normal cardiometabolic profile, defined by the presence of normal glucose and lipid concentrations, among obese children (OR = 1.07 CI 95% 1.01-1.13, P = 0.012, n = 536). CONCLUSIONS Genetic predisposition to higher body fat yet lower cardiometabolic risk exerts its influence before puberty.
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Effect of folate supplementation on insulin sensitivity and type 2 diabetes: a meta-analysis of randomized controlled trials.
Lind, MV, Lauritzen, L, Kristensen, M, Ross, AB, Eriksen, JN
The American journal of clinical nutrition. 2019;(1):29-42
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Abstract
BACKGROUND Various mechanisms link higher total homocysteine to higher insulin resistance (IR) and risk of type 2 diabetes (T2D). Folate supplementation is recognized as a way to lower homocysteine. However, randomized controlled trials (RCTs) show inconsistent results on IR and T2D outcomes. OBJECTIVE The aim of this study was to examine the effect of folate supplementation on IR and T2D outcomes. DESIGN We conducted a systematic literature search in PubMed, Web of Science, and EMBASE and prior systematic reviews and meta-analyses and identified 29 RCTs (22,250 participants) that assessed the effect of placebo-controlled folate supplementation alone or in combination with other B vitamins on fasting glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), or risk of T2D. The meta-analysis was conducted using both random- and fixed-effects models to calculate weighted mean differences (WMDs) or risk ratios with 95% CIs. Subgroup analyses were conducted based on intervention type (folate alone or in combination with other B vitamins), as well as analysis based on population characteristics, duration, dose, and change in homocysteine. RESULTS When compared with placebo, folate supplementation lowered fasting insulin (WMD: -13.47 pmol/L; 95% CI: -21.41, -5.53 pmol/L; P < 0.001) and HOMA-IR (WMD: -0.57 units; 95% CI: -0.76, -0.37 units; P < 0.0001), but no overall effects were observed for fasting glucose or HbA1c. Heterogeneity was low in all meta-analyses, and subgroup analysis showed no signs of effect modification except for change in homocysteine, with the most pronounced effects in trials with a change of >2.5 µmol/L. Changes in homocysteine after folate supplementation correlated with changes in fasting glucose (β = 0.07; 95% CI: 0.01, 0.14; P = 0.025) and HbA1c (β = 0.46; 95% CI: 0.06, 0.85; P = 0.02). Only 2 studies examined folate supplementation on risk of T2D, and they found no change in RR (pooled RR: 0.91; 95% CI: 0.80, 1.04; P = 0.16). CONCLUSION Folate supplementation might be beneficial for glucose homeostasis and lowering IR, but at present there are insufficient data to conclusively determine the effect on development of T2D. This trial was registered on the Prospero database as CRD42016048254.
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Reply to RB Yarandi.
Lind, MV, Lauritzen, L, Kristensen, M, Ross, AB, Eriksen, JN
The American journal of clinical nutrition. 2019;(4):1233-1234
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Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial.
Roager, HM, Vogt, JK, Kristensen, M, Hansen, LBS, Ibrügger, S, Mærkedahl, RB, Bahl, MI, Lind, MV, Nielsen, RL, Frøkiær, H, et al
Gut. 2019;68(1):83-93
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Plain language summary
Whole grain consumption has been linked with decreased risk of lifestyle-related diseases. While animal studies have shown the gut microbiome to be a mediator of metabolic health, human studies examining the effect of whole grain intake of the gut remain inconclusive. The aim of this study was to investigate the effects of a whole grain diet on the gut microbiome, gut functionality and biomarkers of metabolic health. In this randomised, controlled, crossover study, 50 participants completed two 8-week dietary intervention periods comprising of a whole grain diet and a refined grain diet with a 6-week washout period. Examinations were done at the beginning and end of each intervention period to assess anthropometry and various plasma and gut markers. This study found that a whole grain diet as compared with a refined grain diet reduced energy intake and body weight as well as circulating markers of inflammation. Contrary to the hypothesis, these benefits were all observed independent of changes in the gut microbiome. Based on these results, the authors conclude higher intake of whole grains should be recommended to those at risk of inflammation-related disease.
Abstract
OBJECTIVE To investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. DESIGN 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of ≥6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. RESULTS 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye. CONCLUSION Compared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic low-grade inflammation. TRIAL REGISTRATION NUMBER NCT01731366; Results.