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Impact of wheat aleurone on biomarkers of cardiovascular disease, gut microbiota and metabolites in adults with high body mass index: a double-blind, placebo-controlled, randomized clinical trial.
Fava, F, Ulaszewska, MM, Scholz, M, Stanstrup, J, Nissen, L, Mattivi, F, Vermeiren, J, Bosscher, D, Pedrolli, C, Tuohy, KM
European journal of nutrition. 2022;61(5):2651-2671
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Cross-sectional studies have shown that whole grain cereal consumption can reduce the risk of cardiovascular disease (CVD, as well as reduce systemic inflammation, which is linked to many chronic diet associated diseases. Aleurone is a wheat grain fraction composed of a single cell layer that constitutes the outermost portion of the endosperm and contains many of the beneficial substances. The primary aim of this study was to investigate the effect of aleurone consumption on plasma homocysteine concentrations in overweight/ obese subjects. Secondary aim was to measure the impact of chronic aleurone supplementation on markers of CVD risk and on the human gut microbiota and its metabolic output. This study is a placebo-controlled, randomised, double-blind parallel trial with 2 test foods, wheat aleurone-rich foods or placebo foods (cellulose). Participants (n=74) were randomised to receive the active supplementation (aleurone 27 g per day) or placebo for 4 consecutive weeks. Results show that although average plasma homocysteine levels decreased upon wheat aleurone supplementation treatment, this change was not statistically significant, and homocysteine levels did not differ between groups after intervention. Furthermore, there was a significant increase in bifidobacteria both over time and compared to the placebo. Several significant and useful biomarkers of wheat aleurone intake, all related to wheat polyphenol metabolism by the gut microbiota, were identified. Authors conclude that wheat aleurone supplementation has the potential to modulate the gut microbial metabolic output and increase faecal bifidobacterial abundance, but it does not impact plasma homocysteine or other CVD biomarkers.
Abstract
PURPOSE Aleurone is a cereal bran fraction containing a variety of beneficial nutrients including polyphenols, fibers, minerals and vitamins. Animal and human studies support the beneficial role of aleurone consumption in reducing cardiovascular disease (CVD) risk. Gut microbiota fiber fermentation, polyphenol metabolism and betaine/choline metabolism may in part contribute to the physiological effects of aleurone. As primary objective, this study evaluated whether wheat aleurone supplemented foods could modify plasma homocysteine. Secondary objectives included changes in CVD biomarkers, fecal microbiota composition and plasma/urine metabolite profiles. METHODS A parallel double-blind, placebo-controlled and randomized trial was carried out in two groups of obese/overweight subjects, matched for age, BMI and gender, consuming foods supplemented with either aleurone (27 g/day) (AL, n = 34) or cellulose (placebo treatment, PL, n = 33) for 4 weeks. RESULTS No significant changes in plasma homocysteine or other clinical markers were observed with either treatment. Dietary fiber intake increased after AL and PL, animal protein intake increased after PL treatment. We observed a significant increase in fecal Bifidobacterium spp with AL and Lactobacillus spp with both AL and PL, but overall fecal microbiota community structure changed little according to 16S rRNA metataxonomics. Metabolomics implicated microbial metabolism of aleurone polyphenols and revealed distinctive biomarkers of AL treatment, including alkylresorcinol, cinnamic, benzoic and ferulic acids, folic acid, fatty acids, benzoxazinoid and roasted aroma related metabolites. Correlation analysis highlighted bacterial genera potentially linked to urinary compounds derived from aleurone metabolism and clinical parameters. CONCLUSIONS Aleurone has potential to modulate the gut microbial metabolic output and increase fecal bifidobacterial abundance. However, in this study, aleurone did not impact on plasma homocysteine or other CVD biomarkers. TRIAL REGISTRATION The study was registered at ClinicalTrials.gov (NCT02067026) on the 17th February 2014.
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Two apples a day lower serum cholesterol and improve cardiometabolic biomarkers in mildly hypercholesterolemic adults: a randomized, controlled, crossover trial.
Koutsos, A, Riccadonna, S, Ulaszewska, MM, Franceschi, P, Trošt, K, Galvin, A, Braune, T, Fava, F, Perenzoni, D, Mattivi, F, et al
The American journal of clinical nutrition. 2020;111(2):307-318
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Apples contain naturally occurring substances, called polyphenols, which in combination with fibre may be beneficial in preventing heart disease in a number of different ways. However, high quality research on this is lacking. This randomised control crossover trial of 40 individuals with slightly elevated cholesterol, aimed to assess the effects of consuming two apples a day for 20 weeks, on indicators for heart disease and in particular cholesterol levels. The results showed that consuming two apples per day resulted in decreased cholesterol and improved indicators for heart disease. It was concluded that the consumption of 2 apples per day decreased heart disease risk, attributed to the polyphenols and fibre they contain. Health professionals could use this study to recommend 2 apples per day in patients with slightly raised cholesterol in order to decrease their risk of heart disease.
Abstract
BACKGROUND Apples are rich in bioactive polyphenols and fiber. Evidence suggests that consumption of apples or their bioactive components is associated with beneficial effects on lipid metabolism and other markers of cardiovascular disease (CVD). However, adequately powered randomized controlled trials are necessary to confirm these data and explore the mechanisms. OBJECTIVE We aimed to determine the effects of apple consumption on circulating lipids, vascular function, and other CVD risk markers. METHODS The trial was a randomized, controlled, crossover, intervention study. Healthy mildly hypercholesterolemic volunteers (23 women, 17 men), with a mean ± SD BMI 25.3 ± 3.7 kg/m2 and age 51 ± 11 y, consumed 2 apples/d [Renetta Canada, rich in proanthocyanidins (PAs)] or a sugar- and energy-matched apple control beverage (CB) for 8 wk each, separated by a 4-wk washout period. Fasted blood was collected before and after each treatment. Serum lipids, glucose, insulin, bile acids, and endothelial and inflammation biomarkers were measured, in addition to microvascular reactivity, using laser Doppler imaging with iontophoresis, and arterial stiffness, using pulse wave analysis. RESULTS Whole apple (WA) consumption decreased serum total (WA: 5.89 mmol/L; CB: 6.11 mmol/L; P = 0.006) and LDL cholesterol (WA: 3.72 mmol/L; CB: 3.86 mmol/L; P = 0.031), triacylglycerol (WA: 1.17 mmol/L; CB: 1.30 mmol/L; P = 0.021), and intercellular cell adhesion molecule-1 (WA: 153.9 ng/mL; CB: 159.4 ng/mL; P = 0.028), and increased serum uric acid (WA: 341.4 μmol/L; CB: 330 μmol/L; P = 0.020) compared with the CB. The response to endothelium-dependent microvascular vasodilation was greater after the apples [WA: 853 perfusion units (PU), CB: 760 PU; P = 0.037] than after the CB. Apples had no effect on blood pressure or other CVD markers. CONCLUSIONS These data support beneficial hypocholesterolemic and vascular effects of the daily consumption of PA-rich apples by mildly hypercholesterolemic individuals.This trial was registered at clinicaltrials.gov as NCT01988389.
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Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake.
Meslier, V, Laiola, M, Roager, HM, De Filippis, F, Roume, H, Quinquis, B, Giacco, R, Mennella, I, Ferracane, R, Pons, N, et al
Gut. 2020;69(7):1258-1268
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Evidence suggests that the Mediterranean diet (MD) may help prevent cardiovascular disease (CVD). However, this could be influenced by an individual’s gut microbiome, highlighting a need for personalised nutrition practices. This randomised crossover control trial aimed to evaluate an 8-week personalised MD intervention in 82 overweight and obese subjects, who were at high risk of cardiovascular disease. The results showed that a personalised MD lowered cholesterol, regardless of the amount of energy consumed and the amount of exercise performed and relied upon adherence to the MD. Gut microbiome composition was altered by a MD and although markers for diabetes were not improved overall, there was an improvement in prediabetes in individuals with higher levels of Bacteroides species and lower levels of Prevotella species. It was concluded that a MD may reduce cholesterol and alter the gut microbiome to benefit cardiovascular health. Health professionals could use this study to switch patients to a MD whilst maintaining their energy intake to reduce cardiovascular risk. In order to see maximum benefit, it would be recommended to take a personalised approach and analyse an individual’s gut microbiome in order to tailor recommendations.
Abstract
OBJECTIVES This study aimed to explore the effects of an isocaloric Mediterranean diet (MD) intervention on metabolic health, gut microbiome and systemic metabolome in subjects with lifestyle risk factors for metabolic disease. DESIGN Eighty-two healthy overweight and obese subjects with a habitually low intake of fruit and vegetables and a sedentary lifestyle participated in a parallel 8-week randomised controlled trial. Forty-three participants consumed an MD tailored to their habitual energy intakes (MedD), and 39 maintained their regular diets (ConD). Dietary adherence, metabolic parameters, gut microbiome and systemic metabolome were monitored over the study period. RESULTS Increased MD adherence in the MedD group successfully reprogrammed subjects' intake of fibre and animal proteins. Compliance was confirmed by lowered levels of carnitine in plasma and urine. Significant reductions in plasma cholesterol (primary outcome) and faecal bile acids occurred in the MedD compared with the ConD group. Shotgun metagenomics showed gut microbiome changes that reflected individual MD adherence and increase in gene richness in participants who reduced systemic inflammation over the intervention. The MD intervention led to increased levels of the fibre-degrading Faecalibacterium prausnitzii and of genes for microbial carbohydrate degradation linked to butyrate metabolism. The dietary changes in the MedD group led to increased urinary urolithins, faecal bile acid degradation and insulin sensitivity that co-varied with specific microbial taxa. CONCLUSION Switching subjects to an MD while maintaining their energy intake reduced their blood cholesterol and caused multiple changes in their microbiome and metabolome that are relevant in future strategies for the improvement of metabolic health.
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Vitamin B12 Status Upon Short-Term Intervention with a Vegan Diet-A Randomized Controlled Trial in Healthy Participants.
Lederer, AK, Hannibal, L, Hettich, M, Behringer, S, Spiekerkoetter, U, Steinborn, C, Gründemann, C, Zimmermann-Klemd, AM, Müller, A, Simmet, T, et al
Nutrients. 2019;11(11)
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Veganism is growing in western societies and with it comes an increased risk of vitamin B12 deficiency which is principally found in animal products. Vitamin B12 is essential for multiple biological functions including DNA synthesis, digestive function and detoxification processes. It can take 2-5 years to exhaust natural stores of B12 within the body so deficiency risk is considered safe. This 2017 randomised control trial compared vitamin B12 status in 53 healthy omnivore subjects with 26 participants following an unsupplemented vegan diet for 4 weeks and the remaining 27 participants a meat-rich diet. The aim of the study was to answer two questions; (a) Do vitamin B12 markers respond to short-term dietary intervention with a meat-rich or a plant-based diet? and (b) Do meat-rich and vegan diets have an impact on plasma markers of inflammation and cardiovascular disease? Blood and urine samples were taken before and after the 4-week dietary protocol to also measure vitamin D status, Folate and Homocysteine levels as a marker for inflammation. The serum vitamin B12 levels (indicative of dietary B12) dropped significantly from 362.9 +/- 110.9 ng/mL to 296.1 +/- 94.1 ng/mL in the Vegan Diet group (p < 0.001) and remained stable in the Meat Diet group. Other markers measuring cellular B12 metabolism did not significantly vary. The short-term nature of the trial demonstrated rapid decrease in holo-TC, the bioactive form of vitamin B12 in plasma. The other blood and urinary markers demonstrated benefits to plant-based eating including reduced cholesterol intake and adequate profiles of nutrient and micronutrient status.
Abstract
Vegans are at an increased risk for certain micronutrient deficiencies, foremost of vitamin B12. Little is known about the short-term effects of dietary change to plant-based nutrition on vitamin B12 metabolism. Systemic biomarkers of vitamin B12 status, namely, serum vitamin B12 and holotranscobalamin, may respond quickly to a reduced intake of vitamin B12. To test this hypothesis, 53 healthy omnivore subjects were randomized to a controlled unsupplemented vegan diet (VD, n = 26) or meat-rich diet (MD, n = 27) for 4 weeks. Vitamin B12 status was examined by measurement of serum vitamin B12, holotranscobalamin (holo-TC), methylmalonic acid (MMA) and total plasma homocysteine (tHcy). Holo-TC decreased significantly in the VD compared to the MD group after four weeks of intervention, whereas metabolites MMA and tHcy were unaffected. Body weight remained stable in both groups. VD intervention led to a significant reduction of cholesterol intake, and adequate profiles of nutrient and micronutrient status. Lower intake of vitamin B12 was observed in VD, which was mirrored by a lower concentration of serum vitamin B12 and reduced holo-TC after 4 weeks. Plasma holo-TC may be a fast-responding biomarker to monitor adequate supply of vitamin B12 in plant-based individuals.
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Mixed Spices at Culinary Doses Have Prebiotic Effects in Healthy Adults: A Pilot Study.
Lu, QY, Rasmussen, AM, Yang, J, Lee, RP, Huang, J, Shao, P, Carpenter, CL, Gilbuena, I, Thames, G, Henning, SM, et al
Nutrients. 2019;11(6)
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An increasing body of evidence suggests that the gut microbiota has a profound impact on human health. While the microbiome of a healthy individual is relatively stable, gut microbial dynamics can be influenced by host lifestyle and dietary choices. The aim of this study was to investigate the effects of mixed spices (cinnamon, oregano, ginger, black pepper, and cayenne pepper) at culinary doses consumed over 2 weeks in a standardized 5g capsule on the production of gut microbiota and short-chain fatty acids The study is a randomised, placebo-controlled, double-blind pilot study carried out with a total of 31 healthy women and men aged between 18 and 65. The subjects were randomly allocated to one of the two intervention groups. Results indicate that daily intake of 5g of mixed spices for 2 weeks in healthy subjects resulted in a significant reduction in the relative abundance of the phylum Firmicutes (bacteria), and a trend of increasing in phylum Bacteroidetes (bacteria) as compared with a matched control group. Authors conclude that a mixture of spices at culinary doses affects the composition of gut microbiota.
Abstract
Spices were used as food preservatives prior to the advent of refrigeration, suggesting the possibility of effects on microbiota. Previous studies have shown prebiotic activities in animals and in vitro, but there has not been a demonstration of prebiotic or postbiotic effects at culinary doses in humans. In this randomized placebo-controlled study, we determined in twenty-nine healthy adults the effects on the gut microbiota of the consumption daily of capsules containing 5 g of mixed spices at culinary doses by comparison to a matched control group consuming a maltodextrin placebo capsule. The 16S ribosomal RNA sequencing data were used for microbial characterization. Spice consumption resulted in a significant reduction in Firmicutes abundance (p < 0.033) and a trend of enrichment in Bacteroidetes (p < 0.097) compared to placebo group. Twenty-six operational taxonomic units (OTUs) were different between the spice and placebo groups after intervention. Furthermore, there was a significant negative correlation between fecal short-chain fatty acid propionate concentration and Firmicutes abundance in spice intervention group (p < 0.04). The production of individual fecal short-chain fatty acid was not significantly changed by spice consumption in this study. Mixed spices consumption significantly modified gut microbiota, suggesting a prebiotic effect of spice consumption at culinary doses.
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Effects of Dietary Protein and Fat Content on Intrahepatocellular and Intramyocellular Lipids during a 6-Day Hypercaloric, High Sucrose Diet: A Randomized Controlled Trial in Normal Weight Healthy Subjects.
Surowska, A, Jegatheesan, P, Campos, V, Marques, AS, Egli, L, Cros, J, Rosset, R, Lecoultre, V, Kreis, R, Boesch, C, et al
Nutrients. 2019;11(1)
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High sugar diets can lead to increased fat accumulation in the liver and skeletal muscles, as intrahepatocellular lipid (IHCL) and intramyocellular lipid (IMCL) respectively. Elevation in these lipid concentrations is associated with an increased risk of various chronic diseases. The aim of this randomised crossover trial was to assess whether the consequences of a high sugar diet differed according to the protein and fat composition in 12 healthy adults. At the beginning of each trial period, participants consumed a 3-day weight maintenance diet followed by a 6-day high calorie, high sugar diet consisting of either low protein-high fat or high protein-low fat with a 4-8 week washout period. IHCL and IMCL concentrations, energy expenditure and blood metabolites were monitored after each weight maintenance diet and after each 6-day intervention diet period. This study found that both diets led to increased lipid concentrations, most notably the in liver cells. Lipid increases induced by the high protein-low fat diet were significantly lower than those induced by the low protein-high fat diet. Based on these results, the authors conclude that when overfed on a high sugar diet, high protein-low fat markedly reduces the amount of fat accumulation in liver and muscle cells and suggest that either dietary protein may have a protective effect of sugar and fat may have an additive adverse effect.
Abstract
Sucrose overfeeding increases intrahepatocellular (IHCL) and intramyocellular (IMCL) lipid concentrations in healthy subjects. We hypothesized that these effects would be modulated by diet protein/fat content. Twelve healthy men and women were studied on two occasions in a randomized, cross-over trial. On each occasion, they received a 3-day 12% protein weight maintenance diet (WM) followed by a 6-day hypercaloric high sucrose diet (150% energy requirements). On one occasion the hypercaloric diet contained 5% protein and 25% fat (low protein-high fat, LP-HF), on the other occasion it contained 20% protein and 10% fat (high protein-low fat, HP-LF). IHCL and IMCL concentrations (magnetic resonance spectroscopy) and energy expenditure (indirect calorimetry) were measured after WM, and again after HP-LF/LP-HF. IHCL increased from 25.0 ± 3.6 after WM to 147.1 ± 26.9 mmol/kg wet weight (ww) after LP-HF and from 30.3 ± 7.7 to 57.8 ± 14.8 after HP-LF (two-way ANOVA with interaction: p < 0.001 overfeeding x protein/fat content). IMCL increased from 7.1 ± 0.6 to 8.8 ± 0.7 mmol/kg ww after LP-HF and from 6.2 ± 0.6 to 6.9 ± 0.6 after HP-LF, (p < 0.002). These results indicate that liver and muscle fat deposition is enhanced when sucrose overfeeding is associated with a low protein, high fat diet compared to a high protein, low fat diet.