United States Army Research Institute of Environmental Medicine
Natick, Massachusetts, 01760, United States
NCT Number: NCT06054607
Randomized, double-blind, placebo-controlled crossover study designed to determine the effects of increasing colonic short-chain fatty acid (SCFA) content on aerobic endurance in healthy adults, and to identify underpinning mechanisms. In random order, healthy physically active adults will consume provided diets low in fiber and supplemented with SCFA-enriched high amylose maize starch (a poorly digested resistant starch considered a fermentable fiber) or low amylose maize starch (a rapidly digestible starch) for 1-week separated by a ≥2-week washout. At the end of each intervention period, participants will complete an endurance exercise bout followed by a time trial. Biological samples will be collected to assess muscle and whole body metabolism, gut microbiota, inflammation, and gastrointestinal function.
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Notify Me17 year–39 year
All sexes
Interventional
Not applicable
Natick, Massachusetts, 01760, United States
Healthy volunteers accepted: Yes
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
Cardiac disease (including arrhythmia or fast or skipped heart beats) Hypertension Musculoskeletal injuries that compromise exercise capability Metabolic or cardiovascular abnormalities (e.g., kidney disease, diabetes, etc.) Disease of the GI tract including, but not limited to diverticulitis, inflammatory bowel disease, irritable bowel syndrome, peptic ulcer disease, Crohn's disease, and ulcerative colitis Allergy to skin adhesive or Lidocaine (or other local anesthetic being used in place of Lidocaine) Suspected or known strictures, fistulas, or physiological/mechanical GI obstruction History of gastric bezoar Swallowing disorders; severe dysphagia to food or pills Implanted or portable electro-mechanical medical devices (e.g., pacemaker)
High-amylose maize starch (HAMS), commercially available as Hylon VII (Ingredion, Inc.), to which the SCFA acetate or butyrate has been chemically added. Hylon VII is a HAMS containing ~70% amylose and used in a variety of food products. To produce SCFA-enriched HAMS, Hylon VII is chemically modified through esterification with the SCFA acetate or butyrate.
Rapidly digestible low-amylose maize starch (0% amylose, 100% amylopectin) sold commercially as AMIOCA (Ingredion, Inc).
Time frame: Phases 1 and 2, day 8
Time to complete a 5km treadmill run
Time frame: Phases 1 and 2, day 8
Muscle glycogen content
Time frame: Phases 1 and 2, day 8
Glucose production, utilization and metabolic clearance rate measured during endurance steady state exercise using 6,6-[2H2] glucose tracer
Time frame: Phase 1 and 2, day 8
Carbohydrate and fat oxidation rates measured during endurance steady state exercise using indirect calorimetry
Time frame: Phases 1 and 2, day 8. Measured fasted (-300 minutes) and before (0 minutes) and at the end (80 minutes) of steady state endurance exercise
Serum acetate, butyrate and propionate concentrations
Time frame: Phases 1 and 2, days 1 and 7
Fecal acetate, butyrate and propionate concentrations
Time frame: Phases 1 and 2, day 8
Small and large intestine permeability measured by saccharide excretion in urine
Time frame: Phases 1 and 2, daily on days 1 through 8
Gastrointestinal symptoms (bloating, pain, nausea, flatulence, discomfort, urge to defecate) measured by 10 cm (0 = low, 10 = high) visual analog scale
Time frame: Phases 1 and 2, day 8. Measured before (-300minutes, 0minutes) and during (20, 40, 60, 80minutes) steady state endurance exercise.
Serum/plasma glucose, insulin, free fatty acids, glycerol, lactate and beta-hydroxybutyrate
Time frame: Phases 1 and 2, day 8
Total protein content measured in muscle collected before and after steady state endurance exercise.
Time frame: Phases 1 and 2, day 8
Muscle protein signalling measured by Western blotting in muscle collected before and after steady state endurance exercise. Total protein expression of molecular markers associated with regulation of muscle metabolism will be measured to include (but not be limited to): Akt, p-AktSer473, AMPKα, p- AMPKαThr172, PGC-1α , SIRT1, ACC, p-ACCSer79, p53, p-p53Ser15, PDK4, IRS1, p-IRS1Ser302, GSK-3β, p-GSK-3βSer9, GSK-3α , p-GSK-3α Ser21, GS, p-GSSer641, and GLUT4.
Time frame: Phases 1 and 2, day 8
Muscle protein signalling measured by Western blotting in muscle collected before and after steady state endurance exercise. Phosphorylation status of molecular markers associated with regulation of muscle metabolism will be measured to include (but not be limited to): Akt, p-AktSer473, AMPKα, p- AMPKαThr172, PGC-1α , SIRT1, ACC, p-ACCSer79, p53, p-p53Ser15, PDK4, IRS1, p-IRS1Ser302, GSK-3β, p-GSK-3βSer9, GSK-3α , p-GSK-3α Ser21, GS, p-GSSer641, and GLUT4 .
Time frame: Phases 1 and 2, day 8
Pyruvate dehydrogenase activity in muscle before and after steady state endurance exercise measured colorimetric assay.
Time frame: Phases 1 and 2, day 8
Expression of genes regulating carbohydrate and fat oxidation in muscle collected before and after steady state endurance exercise. Individual primers will be used to determine the mRNA expression of known intracellular targets regulating substrate metabolism to include (but not limited to): FAT, PDK4, HADHA, PGC-1α, PPARδ, PPARγ, FABP, CPT1a, ACOX1, GS, GSK3α, GLUT4, and HK2.
Time frame: Phases 1 and 2, day 8
Expression of genes and microRNA regulating carbohydrate and fat oxidation in muscle collected before and after steady state endurance exercise. microRNA analysis will be conducted using microarray, assessing microRNA that may be associated with substrate metabolism.
Time frame: Phases 1 and 2, days 1 and 7
Relative abundance of bacterial taxa measured by 16S rRNA amplicon sequencing
Time frame: Phases 1 and 2, days 1 and 7
Relative abundances of microbial genes measured by shotgun metagenomics sequencing
Time frame: Phases 1 and 2, day 8. Measured before (-300minutes) and at the end (80minutes) of steady state endurance exercise.
Serum interleukin (IL)-6, IL-10, IL-17, IL-8, IL-1ralpha, IL-1beta, tumor necrosis factor-alpha, interferon gamma
Time frame: Phases 1 and 2, day 8. Measured fasted (-300minutes) and before (0minutes), during (40minutes) and at the end (80minutes) of steady state endurance exercise.
Serum claudin-3, intestinal fatty acid binding protein and zonulin
Time frame: Phases 1 and 2, day 8. Measured fasted (-15minutes) and at the end (80minutes) of steady state endurance exercise.
Serum C-microRNA
Time frame: Phases 1 and 2, daily on days 1 through 7
Appetite (hunger, fullness, desire to eat, prospective consumption) measured by 10 cm (0 = low, 10 = high) visual analog scale
Time frame: Phases 1 and 2, day 8. Measured fasting (-300minutes) and before (0minutes) and at the end (80minutes) of steady state endurance exercise
Breath hydrogen and methane concentrations
United States Army Research Institute of Environmental Medicine
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