Inulin and Nitrate's Effects on Vascular Health and Gut Microbiome
NCT Number: NCT06502535
Status: ACTIVE_NOT_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Endothelial Dysfunction|High Blood Pressure|Gut Microbiota Dysbiosis and Nutrition
Interventions: DIETARY_SUPPLEMENT: Inulin|DIETARY_SUPPLEMENT: Potassium nitrate and inulin
Sponsor: University of Exeter
Collaborators: University of East Anglia
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 22
Study Design: Allocation: RANDOMIZED|Intervention Model: CROSSOVER|Masking: DOUBLE (PARTICIPANT, INVESTIGATOR)|Primary Purpose: BASIC_SCIENCE
Start Date: 2023-05-09
Completion Date: 2024-07-31
Locations: University of Exeter, Exeter, Devon, EX2 4TH, United Kingdom

Summary:
Previous research has revealed that adults with pre-hypertensive and hypertensive blood pressure levels typically exhibit impaired vasodilation, which is a crucial aspect of blood vessel function, due to decreased nitric oxide production. Flow-mediated dilation (FMD) is a widely used technique for assessing vasodilation, which gauges the capacity of blood vessels to widen in response to increased blood flow. Nitrate supplements have been shown to enhance blood vessel function both in the short and long term by elevating nitric oxide (NO) production. Similarly, acetate, a by-product of fibre digestion, has demonstrated anti-inflammatory effects in the gut and may also increase NO production. However, further investigation is needed to determine whether these two supplements work synergistically to improve FMD responses by augmenting NO production in the human body. This study will involve administering inulin plus nitrate supplements to adults aged 45-74 with untreated high blood pressure (120-139/80-89 mmHg and 140/90 mmHg or higher) for a period of 4 weeks, followed by a subsequent 4-week period where only inulin supplements are consumed. The supplements will be provided in the form of powder, to be mixed with water, and will be given in a cross-over and counterbalanced order. Various measurements, including brachial artery function, faecal samples, blood pressure, plasma nitrate and nitrite levels, plasma short-chain fatty acid levels, red blood cell and whole blood S-Nitrosothiols, and salivary nitrate and nitrite levels, will be taken at the baseline and after each supplementation period. Additionally, acute supplementation measurements will be collected on two separate occasions before the start of the longer-term supplement regimen.

Primary Outcome Measures: Flow-mediated dilation (FMD) with ultrasound to detect a change in brachial artery FMD, Absolute percentage change in FMD response between the 'inulin plus nitrate' and 'inulin' supplementations, measured from baseline to the 4-week chronic supplementation., Day 0, Month 3|Plasma nitrite and nitrate levels, Differences in the concentrations of plasma nitrate and nitrite between the 'inulin plus nitrate' and 'inulin' supplementations as assessed by chemiluminescence, measured from baseline to the 4-week chronic supplementation., Day 0, Month 3|Plasma Short-Chain Fatty Acid (SCFA) levels, Differences in the concentrations of plasma acetate, butyrate, and propionate between the 'inulin plus nitrate' and 'inulin' supplementations as assessed by liquid chromatography coupled with tandem mass spectrometry, measured from baseline to the 4-week chronic supplementation., Day 0, Month 3|Gut microbial composition using 16S sequencing, Changes in microbial composition, including alpha and beta diversity indexes, will be evaluated using the 16S rRNA V3-V4 region. These changes will be observed from baseline to the 4-week intervention following both inulin plus nitrate and inulin-only supplementation., Day 0, Month 3|Gut microbial composition using 16S sequencing, Changes in microbial composition, including Least Discriminant Analysis (LDA) evaluated using the 16S rRNA V3-V4 region, will be observed from baseline to the end of the 4-week intervention following supplementation with inulin plus nitrate and inulin alone., Day 0, Month 3|Gut microbial composition using 16S sequencing, Changes in microbial composition, including the relative abundances of Operational Taxonomic Units (OTUs), will be evaluated using the 16S rRNA V3-V4 region. These changes will be observed from baseline to the end of the 4-week intervention following supplementation with inulin plus nitrate and inulin alone., Day 0, Month 3
Secondary Outcome Measures: Flow-mediated dilation (FMD) with ultrasound to detect a change in brachial artery FMD, Absolute percentage change in FMD response between the 'inulin plus nitrate' and 'inulin' supplementations, measured from baseline to 4 h post-consumption of the supplements., Baseline, 4 hour post supplement consumption|Plasma nitrite and nitrate levels, Differences in the concentrations of plasma nitrate and nitrite between the 'inulin plus nitrate' and 'inulin' supplementations as assessed by chemiluminescence, measured from baseline to 4 h post-consumption of the supplements., Baseline, 4 hour post supplement consumption|Plasma Short-Chain Fatty Acid (SCFA) levels, Differences in the concentrations of plasma acetate, butyrate, and propionate between the 'inulin plus nitrate' and 'inulin' supplementations as assessed by liquid chromatography coupled with tandem mass spectrometry, measured from baseline to 4 h post-consumption of the supplements., Baseline, 4 hour post supplement consumption|S-nitrosothiols (RSNO) in red blood cells and whole blood, Differences in the concentrations of RSNO in red blood cells and whole blood following the 'inulin plus nitrate' and 'inulin' supplementations as assessed from chemiluminescence, measured from baseline to 4 h post-consumption of the supplements., Baseline, 4 hour post supplement consumption|S-nitrosothiols (RSNO) in red blood cells and whole blood, Differences in the concentrations of RSNO in red blood cells and whole blood following the 'inulin plus nitrate' and 'inulin' supplementations as assessed from chemiluminescence, measured from baseline to the 4-week intervention., Day 0, Month 3|Resting blood pressure, Differences in resting blood pressure following the 'inulin plus nitrate' and the 'inulin' supplementations as assessed by an automatic sphygmomanometer, measured from baseline to 4 h post-consumption of the supplements., Baseline, 4 hour post supplement consumption|Resting blood pressure, Differences in resting blood pressure following the 'inulin plus nitrate' and the 'inulin' supplementations as assessed by an automatic sphygmomanometer, measured from baseline to the 4-week intervention., Day 0, Month 3|Tolerability of inulin defined by gastrointestinal wellbeing, Tolerability of a 4-week intervention with inulin with or without nitrate, assessed by completion of gastrointestinal wellbeing questionnaires, also known as the Gastrointestinal Symptom Rating Scale (GSRS). GSRS score will be calculated as per Revicki 1997:

Response scale

1. No discomfort at all
2. Slight discomfort
3. Mild discomfort
4. Moderate discomfort
5. Moderately severe discomfort
6. Severe discomfort
7. Very severe discomfort

The 14 items combine into five symptom clusters: Reflux, Abdominal pain, Indigestion, Diarrhoea and Constipation., Day 0, Month 3|Rate of habitual fibre intake before and during the intervention, Participants will be categorised based on their habitual dietary fibre intake to determine if the effects of the supplemented inulin are independent of their overall fibre consumption.

The questionnaire includes 5 questions addressing the intake from the five main food groups contributing to fibre intake: fruit, vegetables, bread and cereals, nuts and seeds, and legumes. The intake of these food groups will be evaluated using the following scale:

Never Less than 1 serving per month 1-3 servings per month

1 serving per week 2-4 servings per week 5-6 servings per week

1. serving per day
2. servings per day
3. servings per day
4. servings per day
5. servings per day
6. or more servings per day, Pre intervention, at baseline|Dietary intake, 4-day recall questionnaire filled out during 4 different occasions to evaluate dietary intake, including macronutrients and caloric intake., Day 0, Month 3|Body weight, Changes in body weight in Kg following supplementation with 'inulin plus nitrate' and 'inulin' will be measured with the use of electronic scales., Day 0, Month 3|Body fat percentage, Changes in body fat percentage following supplementation with 'inulin plus nitrate' and 'inulin' will be assessed using bioimpedance analysis., Day 0, Month 3|Hip circumference, The changes in hip circumference, measured at the largest circumference around the buttocks, following supplementation with 'inulin plus nitrate' and 'inulin,' will be used to calculate the waist-to-hip ratio in conjunction with waist measurement, from baseline to the 4-week intervention., Day 0, Month 3|Waist circumference, The changes in waist circumference, measured halfway between the lower ribs and the iliac crest, following supplementation with 'inulin plus nitrate' and 'inulin', will be used to calculate the waist-to-hip ratio in conjunction with hip measurement, from baseline to the 4-week intervention., Day 0, Month 3