Inulin and Nitrate's Effects on Vascular Health and Gut Microbiome

NCT06502535 | Completed

• 1 other identifier: 550689
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Endothelial Dysfunction; High Blood Pressure; Gut Microbiota Dysbiosis and Nutrition

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (14)

• Flow-mediated dilation (FMD) with ultrasound to detect a change in brachial artery FMD

  Baseline, 4 hour post supplement consumption

• Plasma nitrite and nitrate levels

  Baseline, 4 hour post supplement consumption

• Plasma Short-Chain Fatty Acid (SCFA) levels

  Baseline, 4 hour post supplement consumption

• S-nitrosothiols (RSNO) in red blood cells and whole blood

  Baseline, 4 hour post supplement consumption

• S-nitrosothiols (RSNO) in red blood cells and whole blood

  Day 0, Month 3

Study Arms (2)

Inulin (15 g)

EXPERIMENTAL

Participants will receive 15 g inulin in powder form once daily for 4 weeks.

Dietary Supplement: Inulin

Inulin (15 g) and potassium nitrate (1300 mg)

EXPERIMENTAL

Participants will receive 15 g inulin in powder form once daily for 4 weeks and 1300 mg potassium nitrate in powder form once daily for 4 weeks.

Dietary Supplement: Potassium nitrate and inulin

Interventions

Inulin DIETARY_SUPPLEMENT

15 g inulin once daily for 4 weeks.

Inulin (15 g)

Potassium nitrate and inulin DIETARY_SUPPLEMENT

1300 mg potassium nitrate once daily for 4 weeks and 15 g inulin once daily for 4 weeks.

Inulin (15 g) and potassium nitrate (1300 mg)

Eligibility Criteria

• Age: 45 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide informed consent
• Adults aged 45-74
• Adults with untreated elevated blood pressure as SBP 120 to 129 mm Hg and DBP \< 80 mm Hg or untreated stage 1 hypertension (i.e., pre-hypertension) as SBP 130 to 139 mm Hg or DBP 80 to 89 mm Hg or untreated stage 2 hypertension as SBP equal to or higher than 140 mm Hg or DBP equal to or higher than 90 mm Hg (ACC/AHA and ESC/ESH guidelines and Blood Pressure UK)
• Weight-stable in the 3 months prior to enrolment (self-report)

You may not qualify if:

• Body mass index \> 40 kg/m\^2 at screening;
• History of symptomatic coronary artery disease, stroke, or other known atherosclerotic disease;
• History of gastrointestinal disease (e.g., irritable bowel syndrome, inflammatory bowel disease, coeliac disease, Chron's disease) or former abdominal surgery, weight loss surgery e.g., gastric by-pass (except for appendectomy);
• History of chronic viral hepatitis (including presence of hepatitis B surface antigen or hepatitis C antibody), or other chronic hepatic disorders;
• History of malignancy within the past 5 years, other than non-melanoma skin cancer;
• History of diabetes and/or any endocrine disorder;
• Current use of nitrate medications, including glyceryl trinitrate (GTN), isosorbide dinitrate and isosorbide mononitrate and blood pressure medications;
• Consumption of a low calorie or other special diet during the last month prior to the study, or if following a slimming or medically prescribed diet, or a vegan or macrobiotic lifestyle;
• Use of antibiotics during the three months prior to screening;
• Consumption of pre- or probiotics during the last month prior to screening and during the study, unless discontinued 3 weeks before the start of the trial. This is referred to the use of supplements only and NOT foods containing probiotics and/or prebiotics foods;
• Consumption of dietary supplements such as vitamins C and E during the last month prior to the screening and during the trial, unless discontinued 3 weeks before the start of the trial;
• Consumption of fish oil 6 weeks prior to the screening and during the trial, unless discontinued 6 weeks before the start of the trial;
• Allergies or intolerance against the substances used in the study and/or food intolerances associated with gastrointestinal upset;
• Any apparent dependence on or abuse of alcohol, tobacco, and cannabis products;
• Pregnancy, breast-feeding, or plans to become pregnant during the duration of the study;

Sponsors & Collaborators

• University of Exeter: lead
• University of East Anglia: collaborator

Study Sites (1)

University of Exeter

Exeter, Devon, EX2 4TH, United Kingdom

Location

Related Publications (16)

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• Jones T, Dunn EL, Macdonald JH, Kubis HP, McMahon N, Sandoo A. The Effects of Beetroot Juice on Blood Pressure, Microvascular Function and Large-Vessel Endothelial Function: A Randomized, Double-Blind, Placebo-Controlled Pilot Study in Healthy Older Adults. Nutrients. 2019 Aug 2;11(8):1792. doi: 10.3390/nu11081792.

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• Kleinbongard P, Dejam A, Lauer T, Jax T, Kerber S, Gharini P, Balzer J, Zotz RB, Scharf RE, Willers R, Schechter AN, Feelisch M, Kelm M. Plasma nitrite concentrations reflect the degree of endothelial dysfunction in humans. Free Radic Biol Med. 2006 Jan 15;40(2):295-302. doi: 10.1016/j.freeradbiomed.2005.08.025. Epub 2005 Nov 10.

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MeSH Terms

Conditions

Hypertension

Interventions

Inulin; potassium nitrate

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Starch; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Carbohydrates; Carbohydrates; Fructans; Polysaccharides

Study Officials

• Luciana Torquati, PhD

  University of Exeter

  PRINCIPAL INVESTIGATOR

• Jessica Virgili, MSc

  University of Exeter

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This study will be conducted under a double-blind setup, which implies that neither the participants nor the researcher will be aware of whether the participants are being given inulin or a combination of inulin and nitrate. The supplements will be labelled A and B by an independent party otherwise not involved in the study, and the investigator and participants will not know which supplement is which letter during the study period.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be assigned randomly to receive either A) a combination of inulin and nitrate, or B) inulin alone. This will be done following a crossover and counterbalanced design, ensuring that all participants will receive both treatments in a randomised order.

Study Record Dates

• First Submitted: May 14, 2024
• First Posted: July 16, 2024
• Study Start: May 9, 2023
• Primary Completion: July 31, 2024
• Study Completion: July 31, 2024
• Last Updated: January 9, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)