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

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

16

Phase

  • 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

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
Intervention / Treatment
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

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

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

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

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)

January 6, 2026

Primary Completion (Estimated)

July 1, 2027

Study Completion (Estimated)

July 1, 2027

Study Registration Dates

First Submitted

January 5, 2026

First Submitted That Met QC Criteria

January 13, 2026

First Posted (Actual)

January 15, 2026

Study Record Updates

Last Update Posted (Actual)

March 18, 2026

Last Update Submitted That Met QC Criteria

March 16, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID 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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