Effects of NR Supplementation on Metabolic Flexibility in Zone 2 Training

March 16, 2026 updated by: ZHANG Jiaqi

Temporal and Dose-response Effects of Nicotinamide Riboside Supplementation on Metabolic Flexibility During Zone 2 Training in Adults: a Double-blinded, Randomized, Controlled, Crossover Trial

Zone 2 training, a low-intensity endurance exercise performed at approximately 66-80% of VO₂max or near the first ventilatory threshold, has gained popularity for improving aerobic capacity, fat metabolism, and mitochondrial efficiency. It preserves glycogen stores and delays fatigue, making it an essential training method for both athletes and recreational exercisers. Nicotinamide adenine dinucleotide (NAD) is a vital metabolite that regulates cellular energy metabolism and redox homeostasis. It participates in oxidative reactions within the tricarboxylic acid cycle and electron transport chain, sustaining ATP synthesis and mitochondrial efficiency. Exercise influences multiple pathways of NAD metabolism, altering the NAD⁺/NADH ratio and thereby affecting energy production and fatigue resistance. Studies have shown that both aerobic exercise and NAD precursor supplementation (e.g., nicotinamide riboside [NR]) can elevate body NAD levels and enhance mitochondrial function, though findings remain inconsistent due to variations in dosage and participants' characteristics. This study aims to investigate how acute NR supplementation interacts with Zone 2 cycling training in adults. Specifically, it examines the temporal and dose-dependent effects of NR supplementation on metabolic flexibility and exercise performance. The results may clarify the potential synergistic benefits of combining NAD supplementation with low-intensity endurance training to improve aerobic adaptability.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
16

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Please Select
      • Hong Kong, Please Select, China, 999077
        • Recruiting
        • G02, Kwok Sports Building, The Chinese University of Hong Kong
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Over 18 years old
  • BMI <30 kg/m2

Exclusion Criteria:

  • Present of health conditions that contraindicate participation in exercise training, such as a history of cardiovascular disease, cancer, or musculoskeletal disorders
  • Currently taking vitamin B supplements and/or NAD precursors
  • Taking medication that may affect the test results

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 300 mg
Dietary supplement: Nicotinamide Riboside (NR)
600 mg NR
Dietary supplement: Nicotinamide Riboside (NR)
300 mg NR
Experimental: 600 mg
Dietary supplement: Nicotinamide Riboside (NR)
600 mg NR
Dietary supplement: Nicotinamide Riboside (NR)
300 mg NR
No Intervention: 0 mg

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Substrate utilization (CHO and fat oxidation rate)
Time Frame: From enrollment to the end of treatment at 4 weeks
From enrollment to the end of treatment at 4 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Oxygen consumption
Time Frame: From enrollment to the end of treatment at 4 weeks
From enrollment to the end of treatment at 4 weeks
Heart rate
Time Frame: From enrollment to the end of treatment at 4 weeks
From enrollment to the end of treatment at 4 weeks
Blood glucose concentration
Time Frame: From enrollment to the end of treatment at 4 weeks
From enrollment to the end of treatment at 4 weeks
Blood lactate concentration
Time Frame: From enrollment to the end of treatment at 4 weeks
From enrollment to the end of treatment at 4 weeks
Peak power output
Time Frame: From enrollment to the end of treatment at 4 weeks
From enrollment to the end of treatment at 4 weeks
Mean power output
Time Frame: From enrollment to the end of treatment at 4 weeks
From enrollment to the end of treatment at 4 weeks
Rating of perceived exertion
Time Frame: From enrollment to the end of treatment at 4 weeks
From enrollment to the end of treatment at 4 weeks
Muscle pain scale
Time Frame: From enrollment to the end of treatment at 4 weeks
Muscle pain scale is a 5-point likert scale ranging from "1- Not at all" to "5- Extreme", with higher value indicating muscle pain.
From enrollment to the end of treatment at 4 weeks
Muscle fatigue scale
Time Frame: From enrollment to the end of treatment at 4 weeks
Muscle fatigue scale is a 5-point likert scale ranging from "1- Not at all" to "5- Extreme", with higher value indicating muscle fatigue.
From enrollment to the end of treatment at 4 weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Height
Time Frame: From enrollment to the end of treatment at 4 weeks
From enrollment to the end of treatment at 4 weeks
Weight
Time Frame: From enrollment to the end of treatment at 4 weeks
From enrollment to the end of treatment at 4 weeks
Power output at VT1
Time Frame: From enrollment to the end of treatment at 4 weeks
From enrollment to the end of treatment at 4 weeks
Health history questionnaire
Time Frame: From enrollment to the end of treatment at 4 weeks
This questionnaire includes questions regarding participant's present/past history of diseases and his/her family history of diseases.
From enrollment to the end of treatment at 4 weeks
International Physical Activity Questionnaire (IPAQ)
Time Frame: From enrollment to the end of treatment at 4 weeks
IPAQ is a validated questionnaire to measure the physical activity of participants during the past 7 days. The score will be transformed to metabolic equivalents of tasks per week (METs/week), with higher value indicating greater participation in physical activity.
From enrollment to the end of treatment at 4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
ZHANG Jiaqi

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 6, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 5, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 13, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 15, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 18, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 16, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SBRE-25-0349

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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