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The Effect of Selenium Supplementation on Clinical Outcomes, Metabolic Profiles, and Pulsatility Index of the Uterine Artery in High-Risk Mothers in Terms of Preeclampsia Screening with Quadruple Test: a Randomized, Double-Blind, Placebo-Controlled Clinical Trial : Selenium and preeclampsia.
Mesdaghinia, E, Shahin, F, Ghaderi, A, Shahin, D, Shariat, M, Banafshe, H
Biological trace element research. 2023;201(2):567-576
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Preeclampsia (PE) is a disease related to high blood pressure during pregnancy, which can result in birth complications and even death of the mother and/or infant. Selenium, which is a nutrient derived from the diet is involved in several processes within the body and levels have shown controversial relationships with PE. This randomised control trial of 60 individuals aimed to determine the effects of selenium supplementation for 12 weeks in women at high risk of PE. The results showed that selenium supplementation helped to alleviate inflammation, which is associated with PE. It also helped to improve blood flow to the uterus, sleep quality, depression, and feelings of anxiety. It was concluded that selenium supplementation for 12 weeks in pregnant women at an increased risk of PE had beneficial effects on factors which may contribute to PE. This study could be used by healthcare professionals to understand that nutrient deficiencies may be involved in poorer outcomes during pregnancy and the importance of recommending a nutrient dense diet and pregnancy vitamins which contain adequate amounts of selenium.
Abstract
Data on the effects of selenium (Se) supplementation on clinical outcomes, metabolic profiles, and pulsatility index (PI) in high-risk mothers in terms of preeclampsia (PE) screening with quadruple tests are scarce. This study evaluated the effects of Se supplementation on clinical outcomes, metabolic profiles, and uterine artery PI on Doppler ultrasound in high-risk mothers in terms of PE screening with quad marker. The current randomized, double-blind, placebo-controlled trial was conducted among 60 high-risk pregnant women screening for PE with quad tests. Participants were randomly allocated into two groups (30 participants each group), received either 200 µg/day Se supplements (as Se amino acid chelate) or placebo from 16 to 18 weeks of pregnancy for 12 weeks. Clinical outcomes, metabolic profiles, and uterine artery PI were assessed at baseline and at the end of trial. Se supplementation resulted in a significant elevation in serum Se levels (β 22.25 µg/dl; 95% CI, 18.3, 26.1; P < 0.001) compared with the placebo. Also, Se supplementation resulted in a significant elevation in total antioxidant capacity (β 82.88 mmol/L; 95% CI, 3.03, 162.73; P = 0.04), and total glutathione (β 71.35 µmol/L; 95% CI, 5.76, 136.94; P = 0.03), and a significant reduction in high-sensitivity C-reactive protein levels (β - 1.52; 95% CI, - 2.91, - 0.14; P = 0.03) compared with the placebo. Additionally, Se supplementation significantly decreased PI of the uterine artery in Doppler ultrasound (β - 0.09; 95% CI, - 0.14, - 0.04; P = 0.04), and a significant improvement in depression (β - 5.63; 95% CI, - 6.97, - 4.28; P < 0.001), anxiety (β - 1.99; 95% CI, - 2.56, - 1.42; P < 0.001), and sleep quality (β - 1.97; 95% CI, - 2.47, - 1.46; P < 0.001). Se supplementation for 12 weeks in high-risk pregnant women in terms of PE screening with quad marker had beneficial effects on serum Se level, some metabolic profiles, uterine artery PI, and mental health. IRCT Registration: htpp:// www.irct.ir ; identifier IRCT20200608047701N1.
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Plasma anthocyanins and their metabolites reduce in vitro migration of pancreatic cancer cells, PANC-1, in a FAK- and NF-kB dependent manner: Results from the ATTACH-study a randomized, controlled, crossover trial in healthy subjects.
Mostafa, H, Behrendt, I, Meroño, T, González-Domínguez, R, Fasshauer, M, Rudloff, S, Andres-Lacueva, C, Kuntz, S
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2023;158:114076
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Pancreatic cancer is commonly associated with poor prognosis and low overall five-year survival rate (5–7%) due to the early metastatic potential of pancreatic cancer cells. Strategies to improve the health outcomes in pancreatic cancer are challenging. The aims of this study where to investigate: - whether plasma metabolites, isolated after a 28-day intervention, would reduce migration of two pancreatic cancer cell lines (PANC-1 and AsPC-1); - whether expression of adhesion molecules on cancer and endothelial cells were influenced by plasma anthocyanins (ACN) metabolites; - which molecular mechanisms were involved; and - which metabolites in plasma and urine were altered during a long-term ACN intake and how they associate with the inhibitory effects on migration. This study is a randomised, double-blind, placebo-controlled, cross-over, 28-days intervention - ATTACH study (Anthocyanins Target Tumor cell Adhesion—Cancer vs. Endothelial Cell (HUVEC)). Thirty-five (female n = 27 and male n = 8) young, healthy volunteers participated in the intervention. Results show that ACN and metabolites isolated from plasma after a long-term ACN-rich juice intervention reduced the migration and expression of cell adhesion molecules in PANC-1 cancer cells in vitro through activation of two pathways [focal adhesion kinase- and nuclear factor kappa light chain enhancer of activated B cells (NF-kB)-pathways] as well as the reduction of reactive oxygen species. Authors conclude that their findings can lead to the investigation of interactions of ACNs with classical cancer prevention strategies.
Abstract
Pancreatic cancer is primarily considered to be a metastatic disease with a low 5-year survival rate. We aimed to detect if plasma-isolated anthocyanins and their metabolites (PAMs) modulate pancreatic cancer cells migration and to describe molecular targets of PAMs in this process. Plasma metabolites were isolated by solid-phase extraction before and after a 28-days intervention trial involving 35 healthy subjects comparing effects of a daily anthocyanin-rich juice intake vs. placebo. Plasma extracts were used for migration and mechanistic in vitro studies as well as for metabolomic analysis. Pancreatic PANC-1 and AsPC-1 were used for migration studies in a Boyden chamber co-cultured with endothelial cells. Expression of adhesion molecules on cancer and endothelial cells were determined by flow cytometry and NF-kB (nuclear factor-kappa B) p65 and focal adhesion kinase activation were measured by immunoassays. UHPLC-MS/MS metabolomics was done in plasma and urine samples. Plasma extracts isolated after the intake of the anthocyanin-rich juice significantly reduced PANC-1 migration, but not AsPC-1 migration. In PANC-1, and to a lower extent in endothelial cells, plasma extracts after juice intake decreased the expression of ß1- and ß4-integrins and intercellular adhesion molecule-1. Pooled plasma from volunteers with the highest inhibition of PANC-1 migration (n = 10) induced a reduction of NF-kB-p65 and FAK-phosphorylation in cancer and in endothelial cells. Concerning metabolites, 14 were significantly altered by juice intervention and PANC-1 migration was inversely associated with the increase of o-coumaric acid and peonidin-3-galactoside. PAMs were associated with lower PANC-1 cell migration opening new strategies for metastatic pancreatic cancer treatment.
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Effects of a Mediterranean Diet Intervention on Maternal Stress, Well-Being, and Sleep Quality throughout Gestation-The IMPACT-BCN Trial.
Casas, I, Nakaki, A, Pascal, R, Castro-Barquero, S, Youssef, L, Genero, M, Benitez, L, Larroya, M, Boutet, ML, Casu, G, et al
Nutrients. 2023;15(10)
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Stress and anxiety are frequent occurrences among pregnant women. Mental disorders can appear before pregnancy, with a changing course during pregnancy and postpartum. During pregnancy, evidence has been provided regarding the potential beneficial effects that structured dietary interventions based on a Mediterranean diet (MedDiet) can have, not only on pregnant women, but also their offspring and the pregnancy itself. The aim of this study was to evaluate the influence of a structured intervention during pregnancy based on a MedDiet on maternal stress and anxiety, mindful state, quality of life and sleep. This study is a parallel, unblinded randomised clinical trial. Participants - pregnant women at high risk for small-for-gestational-age newborns - were randomly assigned (1:1:1) to one of the three study groups: a MedDiet supplemented with extra-virgin olive oil and walnuts; a stress reduction intervention based on the Mindfulness-Based Stress Reduction (MBSR) programme; or usual care without any intervention (control group). Results show that an intervention based on MedDiet during pregnancy: - significantly improved well-being and sleep quality. - is associated with a reduction in maternal anxiety/stress, together with an increase in the cortisol-deactivating enzyme. Authors conclude that a MedDiet intervention significantly reduces maternal anxiety and stress, as well as improving well-being and sleep quality during gestation.
Abstract
Stress and anxiety are frequent occurrences among pregnant women. We aimed to evaluate the effects of a Mediterranean diet intervention during pregnancy on maternal stress, well-being, and sleep quality throughout gestation. In a randomized clinical trial, 1221 high-risk pregnant women were randomly allocated into three groups at 19-23 weeks' gestation: a Mediterranean diet intervention, a Mindfulness-Based Stress Reduction program, or usual care. All women who provided self-reported life-style questionnaires to measure their anxiety (State Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS)), well-being (WHO Five Well Being Index (WHO-5)), and sleep quality (Pittsburgh sleep quality index (PSQI)) at enrollment and at the end of the intervention (34-36 weeks) were included. In a random subgroup of 106 women, the levels of cortisol and related metabolites were also measured. At the end of the intervention (34-36 weeks), participants in the Mediterranean diet group had significantly lower perceived stress and anxiety scores (PSS mean (SE) 15.9 (0.4) vs. 17.0 (0.4), p = 0.035; STAI-anxiety mean (SE) 13.6 (0.4) vs. 15.8 (0.5), p = 0.004) and better sleep quality (PSQI mean 7.0 ± 0.2 SE vs. 7.9 ± 0.2 SE, p = 0.001) compared to usual care. As compared to usual care, women in the Mediterranean diet group also had a more significant increase in their 24 h urinary cortisone/cortisol ratio during gestation (mean 1.7 ± SE 0.1 vs. 1.3 ± SE 0.1, p < 0.001). A Mediterranean diet intervention during pregnancy is associated with a significant reduction in maternal anxiety and stress, and improvements in sleep quality throughout gestation.
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Mixed Tree Nuts, Cognition, and Gut Microbiota: A 4-Week, Placebo-Controlled, Randomized Crossover Trial in Healthy Nonelderly Adults.
Haskell-Ramsay, CF, Dodd, FL, Smith, D, Cuthbertson, L, Nelson, A, Lodge, JK, Jackson, PA
The Journal of nutrition. 2023;152(12):2778-2788
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Cognitive impairment is a growing worldwide health concern as our population ages. In the absence of effective pharmaceutical treatments, modifiable lifestyle factors such as nutrition represent crucial targets in preventing cognitive decline. The aim of this study was to investigate the cognitive and mood effects of mixed tree nut supplementation in healthy non-elderly adults aged 18 to 49 years. This study is a randomised, placebo-controlled, double-blind, counterbalanced crossover design. Participants (n = 81) were randomly assigned to one of the two groups; the treatment or placebo group. Results showed that nut consumption led to improved picture recognition in terms of increased accuracy and faster reaction time. Furthermore, there was an enrichment of an unclassified type of bacterial community (Lachnospiraceae) but limited changes to the urinary metabolome. On the other hand, supplementation with mixed nuts failed to evince effects on mood. Authors conclude by pointing out that their findings are attributed to a sample of healthy and nonelderly participants. Thus, more profound effects may be shown with higher quantities of nuts or in those at risk, such as those experiencing cognitive decline or in those suffering gut dysbiosis.
Abstract
BACKGROUND Beneficial effects of nut supplementation on cognitive function have previously been demonstrated in young and older adults. Alterations to gut microbiota have also been shown following tree nut consumption. However, no data exists on the effects of nuts on cognition and intestinal microbial communities assessed within the same study. OBJECTIVES The study aimed to examine the effects of daily consumption of tree nuts for 4 wk on cognitive function (primary outcome), mood, metabolomics, and gut microbial species (secondary outcomes) in healthy, nonelderly adults. METHODS This randomized, placebo-controlled, double-blind, counterbalanced crossover study assessed the effects of 4 wk of supplementation with 30 g/d mixed tree nuts versus placebo on cognition and mood in 79 healthy adults aged 18-49 y. Metabolic responses, gut bacterial community structure, and the potential for these to impact cognition were explored using a multi-omic approach. Bacterial community analysis was conducted in Quantitative Insights Into Microbial Ecology 2 (QIIME2). RESULTS Mixed model analysis indicated that nut consumption led to significant improvements to accuracy (placebo M = 92.2% compared with NUTS M = 94.5%; P = 0.019) and speed of response (placebo M = 788 ms compared with NUTS M = 757 ms; P = 0.004) on a picture recognition task. No significant changes to bacterial community α or β diversity were observed when comparing nut consumption to the placebo arm. However, an unclassified Lachnospiraceae amplicon sequence variant (ASV) was significantly enriched in participants when supplemented with nuts (P = 0.015). No correlations were observed between the changes to picture recognition and the changes to the unclassified Lachnospiraceae ASV. There were no significant changes to the urinary metabolome. CONCLUSIONS These findings indicate a positive effect of nut on cognition following only 4 wk of consumption in a healthy nonelderly sample, as well as upregulation of a microbial taxa associated with gut health. The effects appear to be independent of one another, but further exploration is required in those experiencing cognitive decline and/or gut dysbiosis.
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Metabolomic Profiles Associated With Blood Pressure Reduction in Response to the DASH and DASH-Sodium Dietary Interventions.
Kim, H, Appel, LJ, Lichtenstein, AH, Wong, KE, Chatterjee, N, Rhee, EP, Rebholz, CM
Hypertension (Dallas, Tex. : 1979). 2023;80(7):1494-1506
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DASH (Dietary Approaches to Stop Hypertension) diet is recommended for reducing blood pressure (BP) and the risk of cardiovascular disease (CVD). The DASH diet emphasises the intake of fruits, vegetables, and low-fat dairy, includes a variety of protein sources and it is low in red and processed meats and sugar-sweetened beverages. The aim of this study was to identify metabolites associated with differences in systolic blood pressure (SBP) or diastolic blood pressure (DBP) in response to the diet interventions. This study used data from 2 randomised controlled feeding trials (DASH trial and DASH-Sodium trial). Results show the identification of 42 unique metabolites (9 serum and 33 urine) which were significantly associated with changes in SBP or DBP DASH diet versus control diet interventions. Furthermore, pathway overrepresentation analysis revealed metabolite pathways that were relevant for the association between DASH diet and BP. Authors conclude that their findings provide insights on formulating intervention strategies to reduce BP.
Abstract
BACKGROUND The DASH (Dietary Approaches to Stop Hypertension) diets reduced blood pressure (BP) in the DASH and DASH-Sodium trials, but the underlying mechanisms are unclear. We identified metabolites associated with systolic BP or diastolic BP (DBP) changes induced by dietary interventions (DASH versus control arms) in 2 randomized controlled feeding studies-the DASH and DASH-Sodium trials. METHODS Metabolomic profiling was conducted in serum and urine samples collected at the end of diet interventions: DASH (n=219) and DASH-Sodium (n=395). Using multivariable linear regression models, associations were examined between metabolites and change in systolic BP and DBP. Tested for interactions between diet interventions and metabolites were the following comparisons: (1) DASH versus control diets in the DASH trial (serum), (2) DASH high-sodium versus control high-sodium diets in the DASH-Sodium trial (urine), and (3) DASH low-sodium versus control high-sodium diets in the DASH-Sodium trial (urine). RESULTS Sixty-five significant interactions were identified (DASH trial [serum], 12; DASH high sodium [urine], 35; DASH low sodium [urine], 18) between metabolites and systolic BP or DBP. In the DASH trial, serum tryptophan betaine was associated with reductions in DBP in participants consuming the DASH diets but not control diets (P interaction, 0.023). In the DASH-Sodium trial, urine levels of N-methylglutamate and proline derivatives (eg, stachydrine, 3-hydroxystachydrine, N-methylproline, and N-methylhydroxyproline) were associated with reductions in systolic BP or DBP in participants consuming the DASH diets but not control diets (P interaction, <0.05 for all tests). CONCLUSIONS We identified metabolites that were associated with BP lowering in response to dietary interventions. REGISTRATION URL: https://www. CLINICALTRIALS gov/ct2/show/NCT03403166; Unique identifier: NCT03403166 (DASH trial). URL: https://www. CLINICALTRIALS gov/ct2/show/NCT00000608; Unique identifier: NCT00000608 (DASH-Sodium trial).
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A 2-yr Randomized Controlled Trial on Creatine Supplementation during Exercise for Postmenopausal Bone Health.
Chilibeck, PD, Candow, DG, Gordon, JJ, Duff, WRD, Mason, R, Shaw, K, Taylor-Gjevre, R, Nair, B, Zello, GA
Medicine and science in sports and exercise. 2023;55(10):1750-1760
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Osteoporosis is a bone disease that gradually develops when bone mineral density (BMD) or bone mass decreases and the quality of bone is impaired. This randomised controlled trial conducted over 2 years wanted to test the effects of creatine monohydrate supplementation on BMD at several bone sites during a supervised resistance training and walking program in post menopausal women. 120 were randomly allocated to creatine and 117 to placebo. All participants received a daily supplement of 500 mg of calcium and 10 μg -400 IU of vitamin D. The researchers were particularly interested in finding out whether the creatine group showed improved (BMD) at the femoral neck, lower spine and upper thigh bone also known as the proximal femur which connects the hip joint. Bone density scans, dual-energy X-ray’s and ultrasounds were used to measure BMD and assess areas of bone. Falls and fractures were recorded for a total of 3 years. Dietary intake and physical activity outside of study requirements was assessed using food frequency and exercise questionnaires. Fasting blood and urine analyses along with 24-h urine analysis were taken. The authors conclude that creatine supplementation during a resistance training and walking program had no effect on BMD at the femoral neck, total hip, or lower spine. They further acknowledge relatively low compliance with the creatine supplements, and exercise protocols, along with a high drop out rate. Further studies of larger sample sizes are needed.
Abstract
PURPOSE Our purpose was to examine the effects of 2 yr of creatine monohydrate supplementation and exercise on bone health in postmenopausal women. METHODS Two hundred and thirty-seven postmenopausal women (mean age, 59 yr) were randomized to receive creatine (0.14 g·kg -1 ·d -1 ) or placebo during a resistance training (3 d·wk -1 ) and walking (6 d·wk -1 ) program for 2 yr. Our primary outcome was the femoral neck bone mineral density (BMD), with lumbar spine BMD and proximal femur geometric properties as the secondary outcomes. RESULTS Compared with placebo, creatine supplementation had no effect on BMD of the femoral neck (creatine: 0.725 ± 0.110 to 0.712 ± 0.100 g·cm -2 ; placebo: 0.721 ± 0.102 to 0.706 ± 0.097 g·cm -2 ), total hip (creatine: 0.879 ± 0.118 to 0.872 ± 0.114 g·cm -2 ; placebo: 0.881 ± 0.111 to 0.873 ± 0.109 g·cm -2 ), or lumbar spine (creatine: 0.932 ± 0.133 to 0.925 ± 0.131 g·cm -2 ; placebo: 0.923 ± 0.145 to 0.915 ± 0.143 g·cm -2 ). Creatine significantly maintained section modulus (1.35 ± 0.29 to 1.34 ± 0.26 vs 1.34 ± 0.25 to 1.28 ± 0.23 cm 3 (placebo), P = 0.0011), predictive of bone bending strength, and buckling ratio (10.8 ± 2.6 to 11.1 ± 2.2 vs 11.0 ± 2.6 to 11.6 ± 2.7 (placebo), P = 0.011), predictive of reduced cortical bending under compressive loads, at the narrow part of the femoral neck. Creatine reduced walking time over 80 m (48.6 ± 5.6 to 47.1 ± 5.4 vs 48.3 ± 4.5 to 48.2 ± 4.9 s (placebo), P = 0.0008) but had no effect on muscular strength (i.e., one-repetition maximum) during bench press (32.1 ± 12.7 to 42.6 ± 14.1 vs 30.6 ± 10.9 to 41.4 ± 14 kg (placebo)) and hack squat (57.6 ± 21.6 to 84.4 ± 28.1 vs 56.6 ± 24.0 to 82.7 ± 25.0 kg (placebo)). In the subanalysis of valid completers, creatine increased lean tissue mass compared with placebo (40.8 ± 5.7 to 43.1 ± 5.9 vs 40.4 ± 5.3 to 42.0 ± 5.2 kg (placebo), P = 0.046). CONCLUSIONS Two years of creatine supplementation and exercise in postmenopausal women had no effect on BMD; yet, it improved some bone geometric properties at the proximal femur.
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The effect of polyphenols on DNA methylation-assessed biological age attenuation: the DIRECT PLUS randomized controlled trial.
Yaskolka Meir, A, Keller, M, Hoffmann, A, Rinott, E, Tsaban, G, Kaplan, A, Zelicha, H, Hagemann, T, Ceglarek, U, Isermann, B, et al
BMC medicine. 2023;21(1):364
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Biological age differs from chronological age and is determined by assessing our DNA, this is known as mAge. A healthy lifestyle and weight loss have been shown to be of benefit to mAge. The Mediterranean (MED) diet includes ingredients such as vitamins and naturally occurring chemicals, known as polyphenols, which may alter biological age. This randomised control trial of 256 aimed to determine the effects of a MED diet richer in green vegetables and lower in meat (Green-MED) compared to the MED diet and recommendations for healthy eating. The results showed that after 18 months of healthy eating and weight loss, none of the diets was able to lower the biological age, however the Green-MED diet and in particular the intake of green tea and the vegetable Mankai were associated with slower biological ageing compared to the other two diets. The polyphenol tyrosol was also associated with slower biological ageing. It was concluded that the diets were unable to reverse biological ageing, but a GreenMed diet rich in polyphenols, may be able to slow it. This study could be used by healthcare professionals to understand that as higher biological age is associated with poorer health outcomes, a diet rich in polyphenols may have additional benefits beyond just weight loss.
Abstract
BACKGROUND Epigenetic age is an estimator of biological age based on DNA methylation; its discrepancy from chronologic age warrants further investigation. We recently reported that greater polyphenol intake benefitted ectopic fats, brain function, and gut microbiota profile, corresponding with elevated urine polyphenols. The effect of polyphenol-rich dietary interventions on biological aging is yet to be determined. METHODS We calculated different biological aging epigenetic clocks of different generations (Horvath2013, Hannum2013, Li2018, Horvath skin and blood2018, PhenoAge2018, PCGrimAge2022), their corresponding age and intrinsic age accelerations, and DunedinPACE, all based on DNA methylation (Illumina EPIC array; pre-specified secondary outcome) for 256 participants with abdominal obesity or dyslipidemia, before and after the 18-month DIRECT PLUS randomized controlled trial. Three interventions were assigned: healthy dietary guidelines, a Mediterranean (MED) diet, and a polyphenol-rich, low-red/processed meat Green-MED diet. Both MED groups consumed 28 g walnuts/day (+ 440 mg/day polyphenols). The Green-MED group consumed green tea (3-4 cups/day) and Mankai (Wolffia globosa strain) 500-ml green shake (+ 800 mg/day polyphenols). Adherence to the Green-MED diet was assessed by questionnaire and urine polyphenols metabolomics (high-performance liquid chromatography quadrupole time of flight). RESULTS Baseline chronological age (51.3 ± 10.6 years) was significantly correlated with all methylation age (mAge) clocks with correlations ranging from 0.83 to 0.95; p < 2.2e - 16 for all. While all interventions did not differ in terms of changes between mAge clocks, greater Green-Med diet adherence was associated with a lower 18-month relative change (i.e., greater mAge attenuation) in Li and Hannum mAge (beta = - 0.41, p = 0.004 and beta = - 0.38, p = 0.03, respectively; multivariate models). Greater Li mAge attenuation (multivariate models adjusted for age, sex, baseline mAge, and weight loss) was mostly affected by higher intake of Mankai (beta = - 1.8; p = 0.061) and green tea (beta = - 1.57; p = 0.0016) and corresponded with elevated urine polyphenols: hydroxytyrosol, tyrosol, and urolithin C (p < 0.05 for all) and urolithin A (p = 0.08), highly common in green plants. Overall, participants undergoing either MED-style diet had ~ 8.9 months favorable difference between the observed and expected Li mAge at the end of the intervention (p = 0.02). CONCLUSIONS This study showed that MED and green-MED diets with increased polyphenols intake, such as green tea and Mankai, are inversely associated with biological aging. To the best of our knowledge, this is the first clinical trial to indicate a potential link between polyphenol intake, urine polyphenols, and biological aging. TRIAL REGISTRATION ClinicalTrials.gov, NCT03020186.
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Wild blueberry (poly)phenols can improve vascular function and cognitive performance in healthy older individuals: a double-blind randomized controlled trial.
Wood, E, Hein, S, Mesnage, R, Fernandes, F, Abhayaratne, N, Xu, Y, Zhang, Z, Bell, L, Williams, C, Rodriguez-Mateos, A
The American journal of clinical nutrition. 2023;117(6):1306-1319
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The risk of developing both cardiovascular and neurodegenerative diseases increases with aging. Growing evidence from epidemiological and human intervention trials indicates that (poly)phenols may have cardioprotective properties as well as the ability to improve cognitive function. The aim of this study was to investigate the effects of daily wild blueberry (WBB) (poly)phenol consumption on vascular function and cognitive performance in healthy older individuals. This study was a randomised, double-blinded, placebo-controlled parallel design study. A total of 61 healthy older individuals were recruited and randomly assigned to one of the two arms; placebo intervention or blueberry intervention group. Results showed that long-term consumption of a dietary achievable amount of WBB enhanced vascular and cognitive function in older adults. Authors conclude that gut microbiota and vascular blood flow may play important roles in mediating the cognitive benefits shown by the consumption of (poly)phenol-rich foods.
Abstract
BACKGROUND Evidence suggests that the intake of blueberry (poly)phenols is associated with improvements in vascular function and cognitive performance. Whether these cognitive effects are linked to increases in cerebral and vascular blood flow or changes in the gut microbiota is currently unknown. METHODS A double-blind, parallel randomized controlled trial was conducted in 61 healthy older individuals aged 65-80 y. Participants received either 26 g of freeze-dried wild blueberry (WBB) powder (302 mg anthocyanins) or a matched placebo (0 mg anthocyanins). Endothelial function measured by flow-mediated dilation (FMD), cognitive function, arterial stiffness, blood pressure (BP), cerebral blood flow (CBF), gut microbiome, and blood parameters were measured at baseline and 12 wk following daily consumption. Plasma and urinary (poly)phenol metabolites were analyzed using microelution solid-phase extraction coupled with liquid chromatography-mass spectrometry. RESULTS A significant increase in FMD and reduction in 24 h ambulatory systolic BP were found in the WBB group compared with the placebo group (0.86%; 95% CI: 0.56, 1.17, P < 0.001; -3.59 mmHg; 95% CI: -6.95, -0.23, P = 0.037; respectively). Enhanced immediate recall on the auditory verbal learning task, alongside better accuracy on a task-switch task was also found following WBB treatment compared with placebo (P < 0.05). Total 24 h urinary (poly)phenol excretion increased significantly in the WBB group compared with placebo. No changes in the CBF or gut microbiota composition were found. CONCLUSIONS Daily intake of WBB powder, equivalent to 178 g fresh weight, improves vascular and cognitive function and decreases 24 h ambulatory systolic BP in healthy older individuals. This suggests that WBB (poly)phenols may reduce future CVD risk in an older population and may improve episodic memory processes and executive functioning in older adults at risk for cognitive decline. Clinical Trial Registration number in clinicaltrials.gov: NCT04084457.
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Serum, Urine, and Fecal Metabolome Alterations in the Gut Microbiota in Response to Lifestyle Interventions in Pediatric Obesity: A Non-Randomized Clinical Trial.
Lee, Y, Cho, JY, Cho, KY
Nutrients. 2023;15(9)
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Paediatric obesity is linked to an increased risk of type 2 diabetes, hypertension, dyslipidaemia, and metabolic syndrome. Diverse evidence suggests that obesity is associated with alterations in the gut microbiota and its metabolites. The aim of this study was to understand the metabolic pathways underlying paediatric obesity and the effect of intervention, which could provide guidance for the treatment of obesity. This study was a non-randomised clinical trial which enrolled 50 children with obesity and 22 normal-weight children aged 7–18 years. Results showed that imbalances in microbiota and metabolites were associated with both obesity and response to the intervention. The most distinct metabolic alterations in the obese group were branched-chain amino acid and purine changes. Authors conclude that the findings of their study could be valuable for identifying novel targets and biomarkers for the treatment of obesity.
Abstract
Pediatric obesity is associated with alterations in the gut microbiota and its metabolites. However, how they influence obesity and the effect of lifestyle interventions remains unknown.. In this non-randomized clinical trial, we analyzed metabolomes and microbial features to understand the associated metabolic pathways and the effect of lifestyle interventions on pediatric obesity. Anthropometric/biochemical data and fasting serum, urine, and fecal samples were collected at baseline and after an eight-week, weight-reduction lifestyle modification program. Post-intervention, children with obesity were classified into responder and non-responder groups based on changes in total body fat. At baseline, serum L-isoleucine and uric acid levels were significantly higher in children with obesity compared with those in normal-weight children and were positively correlated with obesogenic genera. Taurodeoxycholic and tauromuricholic α + β acid levels decreased significantly with obesity and were negatively correlated with obesogenic genera. Branched-chain amino acid and purine metabolisms were distinguished metabolic pathways in the obese group. Post-intervention, urinary myristic acid levels decreased significantly in the responder group, showing a significant positive correlation with Bacteroides. Fatty acid biosynthesis decreased significantly in the responder group. Thus, lifestyle intervention with weight loss is associated with changes in fatty acid biosynthesis, and myristic acid is a possible therapeutic target for pediatric obesity.
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Host-diet-gut microbiome interactions influence human energy balance: a randomized clinical trial.
Corbin, KD, Carnero, EA, Dirks, B, Igudesman, D, Yi, F, Marcus, A, Davis, TL, Pratley, RE, Rittmann, BE, Krajmalnik-Brown, R, et al
Nature communications. 2023;14(1):3161
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Composition of the human gut microbiome has been shown to be associated with chronic diseases such as obesity, however whether they have a causal effect in disease development or whether microbiota composition is a direct result of the disease is unclear. This randomised control trial of 17 individuals aimed to determine the effects of a diet designed to modulate the gut microbiome (MBD) on human energy balance compared to a typical Western style diet (WD). The MBD diet maximised fibre, resistant starch, and limited processed foods and resulted in a significant decrease in the amount of energy produced by individuals compared to the WD. It was also shown that the MBD increased the microbial composition and decreased nutrient breakdown. It was concluded that the MBD increased the amount of gut bacteria and altered the amount of energy produced by individuals on this diet. This study could be used by healthcare practitioners to understand that composition of the gut microbiome can affect the amount of energy gained from food. Diets high in fibre, starch and low in processed foods, which promote microbial diversity may help individuals to lose weight.
Abstract
The gut microbiome is emerging as a key modulator of human energy balance. Prior studies in humans lacked the environmental and dietary controls and precision required to quantitatively evaluate the contributions of the gut microbiome. Using a Microbiome Enhancer Diet (MBD) designed to deliver more dietary substrates to the colon and therefore modulate the gut microbiome, we quantified microbial and host contributions to human energy balance in a controlled feeding study with a randomized crossover design in young, healthy, weight stable males and females (NCT02939703). In a metabolic ward where the environment was strictly controlled, we measured energy intake, energy expenditure, and energy output (fecal and urinary). The primary endpoint was the within-participant difference in host metabolizable energy between experimental conditions [Control, Western Diet (WD) vs. MBD]. The secondary endpoints were enteroendocrine hormones, hunger/satiety, and food intake. Here we show that, compared to the WD, the MBD leads to an additional 116 ± 56 kcals (P < 0.0001) lost in feces daily and thus, lower metabolizable energy for the host (89.5 ± 0.73%; range 84.2-96.1% on the MBD vs. 95.4 ± 0.21%; range 94.1-97.0% on the WD; P < 0.0001) without changes in energy expenditure, hunger/satiety or food intake (P > 0.05). Microbial 16S rRNA gene copy number (a surrogate of biomass) increases (P < 0.0001), beta-diversity changes (whole genome shotgun sequencing; P = 0.02), and fermentation products increase (P < 0.01) on an MBD as compared to a WD along with significant changes in the host enteroendocrine system (P < 0.0001). The substantial interindividual variability in metabolizable energy on the MBD is explained in part by fecal SCFAs and biomass. Our results reveal the complex host-diet-microbiome interplay that modulates energy balance.