Exercise Fatiguability in Older Adults: The Protective Effects of Dietary Nitrate Supplementation

Vascular and skeletal muscle function decline with age and are associated with decreased nitric oxide (NO) bioavailability. Dietary nitrate supplementation in the form of beet root juice increases NO bioavailability and improves exercise tolerance in younger adults, yet its effects on fatigability in older adults are largely unknown. The proposed research will investigate the impact of increased NO bioavailability on vascular function, skeletal muscle bioenergetics, and fatigability in older (≥65 yrs) men and women.

Study Overview

• Status: Recruiting
• Conditions: Aging
• Intervention / Treatment: Dietary supplement: Beetroot Juice; Other: Placebo Beetroot Juice

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Timothy Fulton, PhD; Phone Number: 319-290-5529; Email: timothy.fulton@marquette.edu

Study Locations

• United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53233
      • Recruiting
      • Marquette University
      • Contact: Lauren J Opielinski, MS; Email: hunterlab@marquette.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy men and women ≥ 60 years old

Exclusion Criteria:

1. body mass index ≥40 kg/m2;
2. type 1 or type 2 diabetes or HbA1c >6.5%
3. uncontrolled hypertension;
4. active cancer, cancer in remission, or having received treatment for any form of cancer in the previous five years;
5. coronary artery disease;
6. cardiovascular disease (e.g., PAD, PVD);
7. abnormal and untreated thyroid function;
8. chronic and/or regular nonsteroidal anti-inflammatory drugs (NSAID) consumption,
9. tobacco use (includes smoking);
10. any condition that presents a limitation to exercise (e.g., severe arthritis, COPD, neuromuscular disorder, moderate or severe cognitive impairment, Alzheimer's Disease, severe untreated sleep apnea).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Beetroot Juice; The subject will ingest 140mL of a nitrate-rich beetroot juice each day for 7 consecutive days.	Dietary supplement: Beetroot Juice; 7 days of 140 mL per day of beetroot juice; Other Names: James White Drinks Beet It Sport 400
PLACEBO_COMPARATOR: Placebo Beetroot Juice; The subject will ingest 140mL of a placebo (nitrate-depleted) beetroot juice each day for 7 consecutive days.	Other: Placebo Beetroot Juice; 7 days of 140 mL per day of placebo beetroot juice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in fatigability of the knee extensor muscles with beetroot juice supplementation	Fatigability will be quantified as the reduction in limb muscle power output during a 4-minute dynamic fatiguing exercise task using a dynamometer. Fatigability after 7 days of beetroot juice supplementation will be compared with fatigability after 7 days of placebo supplementation, with the outcome measure being the change (or difference) between these two supplementation conditions.	Day 8 (after 7 days of placebo supplementation) and day 29 (after 14 days of a washout period with no supplementation plus 7 days of beetroot juice supplementation)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in femoral artery blood flow with beetroot juice supplementation	Femoral artery blood flow will be quantified as the change in femoral artery blood flow during a 4-minute dynamic fatiguing exercise task using a ultrasonography. Femoral artery blood flow after 7 days of beetroot juice supplementation will be compared with Femoral artery blood flow after 7 days of placebo supplementation, with the outcome measure being the change (or difference) between these two supplementation conditions.	Day 8 (after 7 days of placebo supplementation) and day 29 (after 14 days of a washout period with no supplementation plus 7 days of beetroot juice supplementation)
Change in muscle efficiency with beetroot juice supplementation	Muscle efficiency will be quantified as the ATP cost of contraction using phosphorus magnetic resonance spectroscopy (P-MRS). Muscle efficiency after 7 days of beetroot juice supplementation will be compared with muscle efficiency after 7 days of placebo supplementation, with the outcome measure being the change (or difference) between these two supplementation conditions.	Day 8 (after 7 days of placebo supplementation) and day 29 (after 14 days of a washout period with no supplementation plus 7 days of beetroot juice supplementation)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in plasma nitrate concentration with beetroot juice supplementation	Plasma nitrate concentration will be quantified using a nitrate colorimetric assay. Plasma nitrate concentration after 7 days of beetroot juice supplementation will be compared with plasma nitrate concentration after 7 days of placebo supplementation, with the outcome measure being the change (or difference) between these two supplementation conditions.	Day 8 (after 7 days of placebo supplementation) and day 29 (after 14 days of a washout period with no supplementation plus 7 days of beetroot juice supplementation)
Change in plasma nitrite concentration with beetroot juice supplementation	Plasma nitrite concentration will be quantified using a nitrite colorimetric assay. Plasma nitrite concentration after 7 days of beetroot juice supplementation will be compared with plasma nitrite concentration after 7 days of placebo supplementation, with the outcome measure being the change (or difference) between these two supplementation conditions.	Day 8 (after 7 days of placebo supplementation) and day 29 (after 14 days of a washout period with no supplementation plus 7 days of beetroot juice supplementation)

Collaborators and Investigators

• Sponsor: Marquette University

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2022
• Primary Completion (ANTICIPATED): December 31, 2023
• Study Completion (ANTICIPATED): December 31, 2023

Study Registration Dates

• First Submitted: February 14, 2022
• First Submitted That Met QC Criteria: March 28, 2022
• First Posted (ACTUAL): April 6, 2022

Study Record Updates

• Last Update Posted (ACTUAL): August 24, 2022
• Last Update Submitted That Met QC Criteria: August 22, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: HR-4040

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No