NR and Exercise for Blood Pressure

Effects of Ten-Week Oral Nicotinamide Riboside Supplementation With Aerobic Exercises on Blood Pressure in Post- Menopausal Women With Elevated/Stage I Hypertension

Hypertension continues to pose a significant global health challenge, with rates of optimal blood pressure control remaining low - particularly in China, where fewer than 5% of individuals with hypertension achieve guideline-recommended targets.

Age-associated endothelial dysfunction and arterial stiffness are recognized as the key contributors to the development of hypertension and the unique role of nicotinamide adenine dinucleotide (NAD) depletion in the pathogenesis of vascular dysfunction has been recently discovered. Treatment with nicotinamide riboside (NR), an NAD precursor, has shown promise in preliminary clinical trials for improving blood pressure and vascular health in at-risk populations.

In parallel, aerobic exercise is a well-established non-pharmacologic intervention known to improve cardiovascular outcomes. Emerging studies suggest that exercise may modulate NAD biosynthesis pathways, pointing toward a synergistic potential when combined with NAD-boosting strategies. However, clinical data evaluating the combined effects of NR supplementation and aerobic exercise remain scarce.

Our randomized, placebo-controlled, four-arm, parallel-group design seeks to address this gap. The investigators will investigate the independent and combined effects of 10-week NR supplementation and brisk walking on blood pressure and vascular health in post-menopausal women with elevated/stage I hypertension. This population is specifically targeted due to their heightened risk for vascular dysfunction post-menopause and the observed responsiveness to NR-based interventions in prior studies.

The investigators believe the findings from this trial will provide insight into the feasibility, safety, and efficacy of combining NAD-boosting supplementation with structured exercise in a uniquely vulnerable and previously understudied population. The potential to identify a low-risk, non-pharmaceutical therapeutic approach holds strong implications for public health, particularly in aging women with early-stage hypertension.

Study Overview

• Status: Not yet recruiting
• Conditions: Hypertension (HTN)
• Intervention / Treatment: Other: Placebo; Behavioral: Brisk walking; Dietary supplement: Nicotinamide Riboside 1000 mg

• Study Type: Interventional
• Enrollment (Estimated): 112
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• women absent of menstruation for over one year,
• Chinese, and
• fulfill the criteria of elevated/stage I hypertension according to 2025 American College of Cardiology/American Heart Association Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults (i.e., blood pressure ≥120/80 mmHg based on an average of ≥2 readings obtained on ≥2 occasions)

Exclusion Criteria:

• presence of health conditions that contraindicate participation in exercise training, such as a history of cardiovascular disease, cancer, or musculoskeletal disorders,
• a history of hysterectomy,
• current use of vitamin B supplements and/or NAD precursors,
• ongoing hormone replacement therapy within the past six months,
• any changes in antihypertensive medication type or dosage within the last three months, or
• engagement in regular physical activity, defined as at least 150 minutes of moderate-intensity exercise or 75 minutes of vigorous-intensity exercise per week, during the three months prior to enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NR + BW; NR supplementation plus brisk walking	Behavioral: Brisk walking; Brisk walking twice per week; Dietary supplement: Nicotinamide Riboside 1000 mg; Nicotinamide Riboside supplementation 1000 mg per day
Placebo Comparator: PL + BW; Placebo plus brisk walking	Other: Placebo; Placebo; Behavioral: Brisk walking; Brisk walking twice per week
Active Comparator: NR; NR supplementation only	Dietary supplement: Nicotinamide Riboside 1000 mg; Nicotinamide Riboside supplementation 1000 mg per day
Placebo Comparator: PL; Placebo only	Other: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure	Blood pressure will be measured using an automated sphygmomanometer that meets the standards from the Association for the Advancement of Medical Instrumentation and the European Society for Hypertension and following standardized procedures. Two measurements will be taken after 5 min sitting rest in a quiet room with comfortable temperature. During assessments, participants will be seated with their back supported, feet flat on the floor, legs uncrossed, and their arm resting on a table with the midpoint of the upper arm aligned at heart level. Two readings of systolic and diastolic blood pressures will be obtained, spaced 2 minutes apart, and the average of the two measurements will be recorded as the final blood pressure reading. If the difference between the two measurements exceeds 5 mmHg, an additional reading will be taken, and the average of all three readings will be used as the final measurement.	From enrollment to the end of follow-up at 20 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Whole Blood NAD concentration	Whole blood NAD concentration will be analyzed with commercially available colorimetric assay kit according to manufacturer's instructions using thawed whole blood samples.	From enrollment to the end of follow-up at 20 weeks
Endothelin 1	ET-1 will be analyzed with commercially available ELISA kit according to manufacturer's instructions using thawed serum samples and will serve as indicators of vascular function.	From enrollment to the end of follow-up at 20 weeks
Angiotensin	Angiotensin will be analyzed with commercially available ELISA kit according to manufacturer's instructions using thawed serum samples and will serve as indicators of vascular function.	From enrollment to the end of follow-up at 20 weeks
Body mass	Measured with bioelectrical impedance analysis (BIA) (MC-780 MA, Tanita, Japan) with participants in minimum clothing and normal hydration status.	From enrollment to the end of follow-up at 20 weeks
Fat mass	Measured with bioelectrical impedance analysis (BIA) (MC-780 MA, Tanita, Japan) with participants in minimum clothing and normal hydration status	From enrollment to the end of follow-up at 20 weeks
Fat-free mass	Measured with bioelectrical impedance analysis (BIA) (MC-780 MA, Tanita, Japan) with participants in minimum clothing and normal hydration status.	From enrollment to the end of follow-up at 20 weeks
Fat percentage	Measured with bioelectrical impedance analysis (BIA) (MC-780 MA, Tanita, Japan) with participants in minimum clothing and normal hydration status.	From enrollment to the end of follow-up at 20 weeks
Height	Measured using a stadiometer (Seca, Leicester, UK).	From enrollment to the end of follow-up at 20 weeks
BMI	Calculated as body mass (kg) divided by height squared (m2).	From enrollment to the end of follow-up at 20 weeks
Waist Circumference	Measured using anthropometric tape.	From enrollment to the end of follow-up at 20 weeks
Seven-day accelerometry	Participants will be instructed to wear a wrist accelerometer device on their non-dominant wrists 24 hours for 7 days to measure habitual physical activity pattern. Data will be downloaded and saved in raw format, then processed and analyzed with R-package GGIR.	From enrollment to the end of follow-up at 20 weeks
30-second chair stand test	Muscle strength of the lower extremities will be assessed using the 30-second chair stand test. During the test, participants will be instructed to stand up to a full standing position and then sit back down as many times as possible within 30 seconds. The number of times participants achieve a full standing position will be recorded as their score.	From enrollment to the end of follow-up at 20 weeks
Handgrip strength	Measured using a hand-held dynamometer.	From enrollment to the end of follow-up at 20 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Food diary	A 24-hour diet log will be used to capture detailed information about the foods and beverages consumed by participants in the past 24 hours from midnight to midnight. Participants will be asked to retain their normal eating habits and will be required to report as detailed information as possible such as the preparation method, ingredients, portion, and size of food, etc. Macronutrients, sodium, and potassium intakes will be estimated using the online dietary assessment software FoodWorks.	From enrollment to the end of follow-up at 20 weeks
Medication usage	Participants will be instructed to record the dose and frequency associated with the use of any prescribed medications during baseline screening. Data on medication dose and frequency will be presented as the sum of the multiples of lowest recommended dose (LRD). Our project personnel will contact the participants monthly to record any changes in the use of medications.	From enrollment to the end of follow-up at 20 weeks
International Physical Activity Questionnaire (IPAQ)	IPAQ is a validated questionnaire to measure the physical activity of participants during the past 7 days.	From enrollment to the end of follow-up at 20 weeks
36-item short-form health survey	The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures.	From enrollment to the end of follow-up at 20 weeks
Menopause Rating Scale	The Menopause Rating Scale (MRS) is a validated, 11-item self-assessment tool used globally to measure the severity of menopausal symptoms (somatic, psychological, and urogenital).	From enrollment to the end of follow-up at 20 weeks
Pittsburgh Sleep Quality Index	The Pittsburgh Sleep Quality Index (PSQI) is a widely used self-report questionnaire that assesses sleep quality over a one-month time interval.	From enrollment to the end of follow-up at 20 weeks

Collaborators and Investigators

• Sponsor: ZHANG Jiaqi

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: March 12, 2026
• First Submitted That Met QC Criteria: March 12, 2026
• First Posted (Actual): March 16, 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: Vascular Diseases; Cardiovascular Diseases; Hypertension; nicotinamide-beta-riboside
• Other Study ID Numbers: NTEC-2025-596

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