The Effects of Resistant Starch Consumption in Adult Patients With Chronic Kidney Disease: A Systematic Review.

Background: Resistant starches (RSs) are not digested by human digestive enzymes and pass through the upper digestive tract to become substrates for colonic bacteria. Resistant starch supplementation has shown promising results in altering the microbiota of animal models of chronic kidney disease (CKD). Resistant starch consumption may influence the production of uremic toxins in CKD. Objective: To conduct a systematic review to determine whether the consumption of RS reduces the progression of kidney disease in adult patients with CKD. Design: We included randomized controlled trials comparing RS supplementation to placebo, no treatment, or standard care. Cochrane Central, Embase, MEDLINE, Web of Science, and CINAHL databases were searched. There was no limitation on publication date, but only English manuscripts were included. The search was conducted in July 2020. Patients: Adult outpatient populations with CKD, using any recognized diagnostic criteria. Measurements: The primary outcome was change in glomerular filtration rate (GFR) from baseline through the end of the trial in patients not on dialysis; secondary outcomes included change in uremic toxin concentrations (p-cresol/p-cresyl sulfate [p-CS], indoxyl sulfate [IS]) and inflammatory markers (tumor necrosis factor alpha [TNF-α], C-reactive protein [CRP], interleukin 6 [IL-6]) from baseline through the end of the trial, and changes in self-reported symptom scores. Methods: The Cochrane Collaboration Risk of Bias tool was used to assess risk of bias in included studies. The systematic review results are reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Results: We identified 4 unique studies, reported in 9 publications that met our inclusion criteria, including a total of 215 enrolled participants. Results were calculated using data from the longest reported follow-up time. The primary outcome of changes in kidney function markers was only studied in 1 trial; this trial reported an increase in creatinine and a decrease in blood urea nitrogen; no changes in GFR were reported. A review of the secondary outcomes showed an overall decline in IS, TNF-α, and IL-6, in RS groups, but with mixed results in p-CS and CRP/high-sensitivity CRP. Safety data showed that RS was well tolerated with no reports of excessive side effects. Limitations: We determined a meta-analysis was not feasible due to clinical heterogeneity between study populations and differences in reported outcomes in the included studies. Conclusion: There is limited and inconsistent evidence on the impact of RS in adult patients with CKD. Further research is needed to determine the safety and efficacy of RS supplementation in this population.

Contexte: Les amidons résistants ne sont pas dégradés par les enzymes digestives humaines; ils traversent le tube digestif supérieur et deviennent des substrats pour les bactéries du côlon. La supplémentation en amidons résistants a montré des résultats prometteurs dans la modification du microbiote chez les modèles animaux d'insuffisance rénale chronique (IRC). Dans ce contexte, la consommation d'amidons résistants pourrait avoir une incidence sur la production de toxines urémiques. Objectif: Procéder à une revue systématique afin de déterminer si la consommation d'amidons résistants limite la progression de la maladie chez les adultes atteints d'IRC. Conception de l'étude: Ont été inclus les essais contrôlés randomisés qui comparaient la supplémentation en amidons résistants à un placebo, à l'absence de traitement ou aux soins courants. La recherche a été effectuée en juillet 2020 dans les bases de données Cochrane Central, Embase, Medline, Web of Science et CINAHL. La date de publication n'était pas limitée, mais seuls les articles rédigés en anglais ont été inclus. Sujets: Des adultes atteints d'IRC et suivis en ambulatoire, selon tout critère de diagnostic reconnu. Mesures: Le principal critère d'évaluation était un changement dans le taux de filtration glomérulaire entre le début et la fin de l'essai chez les patients non dialysés. Les résultats secondaires comprenaient un changement, entre le début et la fin de l'essai, dans les concentrations de toxines urémiques (sulfate de p-crésol/crésyle, sulfate d'indoxyle) et de marqueurs d'inflammation (TNFα, CRP, IL-6), ainsi que dans les scores de symptômes auto-déclarés. Méthodologie: L'outil de Risque de Biais de la Collaboration Cochrane a été utilisé pour évaluer le risque de biais dans les études incluses. Les résultats de la revue systématique sont présentés conformément aux directives PRISMA. Résultats: Quatre études uniques, présentées dans neuf publications et portant sur un total de 215 patients, répondaient à nos critères d'inclusion. Les résultats ont été calculés à partir des données de la plus longue période de suivi rapportée. Un seul de ces essais avait examiné le critère principal d'évaluation, soit un changement dans les marqueurs de la fonction rénale. On y rapportait une augmentation du taux de créatinine et une diminution du taux de l'urée dans le sang. Aucun changement dans le débit de filtration glomérulaire n'avait été signalé. Un examen des résultats secondaires a révélé une diminution globale du sulfate d'indoxyle, du TNF alpha et d'IL-6 dans les groupes de patients qui prenaient des suppléments d'amidon résistants, mais des résultats mitigés en ce qui concerne les taux de p-CS et de CRP/hsCRP. Les données de sécurité montraient que les amidons résistants étaient bien tolérés, aucun effet secondaire important n'ayant été rapporté. Limites: Une méta-analyse n'était pas réalisable en raison de l'hétérogénéité clinique entre les populations étudiées et des différences dans les résultats rapportés dans les études incluses. Conclusion: Les données sur les effets d'une supplémentation en amidons résistants chez les adultes atteints d'IRC sont limitées et manquent d'uniformité. D'autres recherches examinant la sécurité et l'efficacité d'une supplémentation en amidons résistants dans cette population sont nécessaires.

A randomized double-blind cross-over trial to study the effects of resistant starch prebiotic in chronic kidney disease (ReSPECKD).

BACKGROUND: Chronic kidney disease (CKD) is associated with a reduced quality of life and an increased risk of kidney failure, cardiovascular events, and all-cause mortality. Accumulation of nitrogen-based uremic toxins leads to worsening of symptoms in individuals with CKD. Many uremic toxins, such as indoxyl and p-cresol sulphate, are produced exclusively by the gut microbiome through the proteolytic digestion of aromatic amino acids. Strategies to reduce the production of these toxins by the gut microbiome in individuals with CKD may lessen symptom burden and delay the onset of dialysis. One such strategy is to change the overall metabolism of the gut microbiome so that less uremic toxins are produced. This can be accomplished by manipulating the energy source available to the microbiome. Fermentable carbohydrates which reach the gut microbiome, like resistant starch (RS), have been shown to inhibit or reduce bacterial amino acid metabolism. This study aims to investigate the effects of resistant potato starch (RPS) as a prebiotic in individuals with CKD before the onset of dialysis. METHODS: This is a double-blind, randomized two-period crossover trial. Thirty-six eligible participants will consent to follow a 26-week study regimen. Participants will receive 2 sachets per day containing either 15 g of RPS (MSPrebiotic, resistant potato starch treatment) or 15 g cornstarch (Amioca TF, digestible starch control). Changes in blood uremic toxins will be investigated as the primary outcome. Secondary outcomes include the effect of RPS consumption on symptoms, quality of life and abundance, and diversity and functionality of the gut microbiome. DISCUSSION: This randomized trial will provide further insight into whether the consumption of RPS as a prebiotic will reduce uremic toxins and symptoms in individuals who have CKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04961164 . Registered on 14 July 2021.

Genosets for APOE and CYP7A1-rs3808607 variants do not predict LDL cholesterol lowering upon intervention with plant sterols in a randomized, double-blind, placebo-controlled trial.

BACKGROUND: The consumption of 2 g/d plant sterols (PSs) reduces circulating LDL cholesterol by ≤10%. The degree of LDL cholesterol lowering was associated with specific apolipoprotein E [APOE, Reference SNP (rs)429358] and cholesterol 7α-hydroxylase (CYP7A1, rs3808607) genosets in previous post hoc analyses of randomized controlled trials. However, because post hoc analyses do not conform to the randomization model, there is a greater potential that the findings could be due to type I error, thus warranting validation through an a priori-designed intervention trial. OBJECTIVES: The GenePredict Plant Sterol study (GPS) was designed to validate associations of LDL cholesterol lowering with specific APOE and CYP7A1 genosets through a priori recruitment of individuals carrying prespecified genosets. METHODS: A 2-center, double-blind, placebo-controlled, randomized 2-period crossover dietary intervention with 2 g/d PS for 28 d with a minimum 28-d washout was undertaken from July 2017 to December 2019. A priori recruitment of individuals with slightly elevated LDL cholesterol was based on genosets of APOE isoforms and CYP7A1 rs3808607. Randomization was performed with stratification by sex and genoset. RESULTS: The recruitment target of 64 participants with prespecified genosets could not be reached, despite the screening of 477 individuals; 42 participants completed the intervention trial. Reductions in LDL cholesterol were similar across all 3 genosets (-0.298 ± 0.164, -0.357 ± 0.115, -0.293 ± 0.109 mmol/L; P = 0.0002 overall; P = 0.9126 for treatment × genoset), providing evidence that the shortfall in recruitment might not have stopped the trial from meeting the objective. CONCLUSIONS: APOE and CYP7A1 genotypes did not influence the efficacy of LDL cholesterol reductions upon dietary intervention with PSs. Findings of previous post hoc analyses could not be validated in a trial using a priori genotype-based recruitment. Obtaining adequate numbers of participants is challenging in trials using genoset-based recruitment, even for common variants.

Genetic basis for prediction of non-responders to dietary plant sterol intervention (GenePredict-PS): a study protocol for a double-blind, placebo-controlled, randomized two-period crossover study.

BACKGROUND: Functional food ingredients and natural health products have been demonstrated to reduce disease risk and thereby help to lower health care costs across populations at risk for chronic or degenerative diseases. However, typically a wide range of interindividual variability exists in response across individuals to nutritional and natural health product bioactives, such as plant sterols (PS). This study aims to determine and utilize information on the associations between genosets and the degree of responsiveness to dietary PS intervention, with a long-term objective of developing genetic tests to predict responses to PS. METHODS: This clinical trial is designed as a double-blind, placebo controlled, randomized two-period crossover study. Sixty-four eligible participants with the specific a priori-determined single nucleotide polymorphisms (SNPs) associated with a responsiveness to PS will consume PS or a placebo treatment for two 4-week periods. The PS treatment consists of two daily single portions of margarine, each providing 1 g PS during the PS period (2.0 g/day of PS in total). The placebo will be an identical margarine containing no added PS. Low-density lipoprotein cholesterol (LDL-C) responsiveness to the controlled administration of PS will be investigated as the primary outcome, and the associations between interindividual genoset variabilities and response to PS consumption will be determined. DISCUSSION: This research will provide further insight into whether the associations between previously identified SNPs and the response of LDL-C to PS consumption can be used in a predictive manner. It will also provide insight into the complexities of undertaking a nutrigenetic trial with prospective recruitment based on genotype. TRIAL REGISTRATION: ClinicalTrials.gov: Identifier: NCT02765516. Registered on 6 May 2016.

Progress and perspectives in plant sterol and plant stanol research.

Current evidence indicates that foods with added plant sterols or stanols can lower serum levels of low-density lipoprotein cholesterol. This review summarizes the recent findings and deliberations of 31 experts in the field who participated in a scientific meeting in Winnipeg, Canada, on the health effects of plant sterols and stanols. Participants discussed issues including, but not limited to, the health benefits of plant sterols and stanols beyond cholesterol lowering, the role of plant sterols and stanols as adjuncts to diet and drugs, and the challenges involved in measuring plant sterols and stanols in biological samples. Variations in interindividual responses to plant sterols and stanols, as well as the personalization of lipid-lowering therapies, were addressed. Finally, the clinical aspects and treatment of sitosterolemia were reviewed. Although plant sterols and stanols continue to offer an efficacious and convenient dietary approach to cholesterol management, long-term clinical trials investigating the endpoints of cardiovascular disease are still lacking.

Inhibition of Intestinal Cellular Glucose Uptake by Phenolics Extracted from Whole Wheat Grown at Different Locations.

Whole grain consumption is associated with reduced risk of type 2 diabetes, and the underlying mechanism might be related to the actions of polyphenols. Dietary polyphenols contribute to low glycemic indices through inhibition of intestinal glucose transport proteins. This study has two objectives: (1) to evaluate how the contents of phenolic acids in wheat vary by genetic background and growth condition and (2) to evaluate how these changes translate into physiologic relevance by investigating cellular glucose transporter inhibitions. Phenolic acids were extracted from wheat varieties grown at different locations over two crop years. The degree of inhibition of glucose uptake into human Caco-2E cells was determined. Free and bound phenolic acid extracts of all wheat genotypes inhibited glucose uptake. Degree of glucose uptake inhibitions positively correlated with the contents of free and bound phenolic acids, and the correlation coefficients were R2=0.91 and R2=0.89, respectively. Genotype and environment influenced the content of free and bound phenolic acids which linearly translated to the degree of glucose uptake inhibition in a model of intestinal absorption (P < 0.05). Results of this work mechanistically support the hypothesis that dietary phenols positively influence the glycemic index and therefore the health properties of whole grain consumption.

Effects of genotype and temperature on accumulation of plant secondary metabolites in Canadian and Australian wheat grown under controlled environments.

Predictions of global increased temperature are for 1.8-4 °C by 2100. Increased temperature as an abiotic stress may exert a considerable influence on the levels of secondary metabolites in plants. These secondary metabolites may possibly exert biological activities beneficial in prevention or treatment of disorders linked to oxidative stress in human. Wheat secondary compounds in three Canadian and three Australian genotypes grown under controlled environments, in which the only changing parameter was temperature, were investigated. Kennedy and AC Navigator contained the highest amount of total phenolic acids among Australian and Canadian wheat genotypes, respectively. The total phenolic acids and total flavonoid contents of wheat genotypes increased following the increase of the growing temperature. In all the wheat genotypes, regardless of their growing temperatures, linoleic acid (C18:2n6) was measured as the main fatty acid. Significant increases in palmitic acid (C16:0) and oleic acid (C18:1n9) and significant decreases in linoleic acid (C18:2n6) and linolenic acid (C18:3n3) were observed at increased of growing temperature for all wheat genotypes. Growing temperature decreased campesterol content of wheat genotypes. Genotype and growing temperature significantly shifted the production of wheat secondary metabolites. This information might be used as a guide for breeding wheat varieties with higher antioxidant properties.