Effects of Vitamin B3 Derivative Nicotinamide Riboside (NR) in Bone, Skeletal Muscle and Metabolic Functions in Aging

A Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Effects of Vitamin B3 Derivative Nicotinamide Riboside (NR) in Bone, Skeletal Muscle and Metabolic Functions in Aging

Researchers are trying to determine if the vitamin B3 derivative Nicotinamide Riboside (NR) has any effects in bone, skeletal muscle, and metabolic functions and structure in aging.

Study Overview

• Status: Completed
• Conditions: Healthy Elderly Volunteers
• Intervention / Treatment: Dietary supplement: Nicotinamide Riboside; Dietary supplement: Placebo

Detailed Description

Primary Objective: To assess the effect of "NAD boosting" through NR intake in skeletal muscle and bone metabolism function, and biochemical evidence of improvement of DNA damage repair in healthy elderly female patients with and without exercise.

Secondary Objective: To assess the effect of NR in metabolic functions of glucose and lipid profile as well as to determine the safety of long term administration of NR in healthy elderly female patients with and without exercise.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 80 years (Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy elderly female subjects between 65 and 80 years of age

Exclusion Criteria:

• General Exclusion Criteria

  • Subjects who participate in regular structured exercise more than 2 hours and 30 min per week or 1hour and 15 min of vigorous exercise per week.
  • Unwilling to comply with the follow-up schedule
  • Inability or refusal to give informed consent by the patient
  • Subject who takes multivitamins containing vitamin B3 derivatives in a dose > 200 mg/day
  • Participation in another investigational drug study within 1 year of treatment

• Laboratory Exclusion Criteria

  • Serum 25-hydroxyvitamin D < 15 ng/ml
  • Serum phosphorus > 5 mg/dL
  • Serum alkaline phosphatase 50% above normal limit
  • Serum aspartate transaminase 50% above normal limit
  • Serum calcium > 10.5 mg/dL
  • Estimated Glomerular Filtration Rate (eGFR) < 30 mL/min Creatinine Clearance < 50%
  • Poorly controlled Diabetes Mellitus (HbA1c>8)

• Clinical History Exclusion Criteria

  • Confirmed diagnosis of Diabetes Mellitus in use of insulin
  • Subjects presenting systolic BP>180 mmHg or a diastolic BP>90 mmHg on initial evaluation
  • Previous diagnosis of liver disease
  • Previous chronic kidney disease stages III and IV
  • Malignancy
  • Malabsorption syndrome
  • Hypo- or Hyperparathyroidism
  • Acromegaly
  • Cushing's syndrome
  • Hypopituitarism
  • Severe chronic obstructive pulmonary disease
  • Congestive heart failure
  • Musculoskeletal disorder
  • History of rheumatoid arthritis
  • Previous gastric bypass surgery
  • Clinical history of osteoporotic fracture (spine, hip, or distal forearm) within past year
  • Extreme of BMI (≤ 18.5 kg/m2 or ≥ 40 kg/m2)

• Medication Exclusion Criteria

  • History of methotrexate therapy
  • History of denosumab therapy
  • History of oral or inhaled corticosteroid use > 3 months
  • Current use of anticoagulants in general
  • Anticonvulsant therapy (within previous year)
  • Sodium fluoride (any history)
  • Treatment within the past 3 years with bisphosphonates
  • Treatment within the past 3 years with parathyroid hormone
  • Treatment within the past 3 years with calcitonin
  • Treatment within the past 3 years with estrogen
  • Treatment within the past 3 years with selective estrogen receptor modulator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nicotinamide Riboside; NR is a single chemical moiety containing nicotinamide and ribose. The investigational product is a synthetic NR that is nature-identical to naturally-occurring NR, does not induce flushing or pruritus and has no effect on lipid levels.	Dietary supplement: Nicotinamide Riboside; It will be administered a total of 1000 mg/day of NR in a regimen of 500mg every 12 hours by mouth for 4.5 months. After 4.5 months, an advanced individual training (AIT) will be implemented in addition to administration of 1000mg/day (500mg every 12 hours) for 6 weeks more, completing total of 6 months.
Placebo Comparator: Placebo; Correspondent placebo, a pill not containing the active component.	Dietary supplement: Placebo; It will be administered a correspondent placebo with the same shape and color as the active pill 12 hours by mouth for 4.5 months. After 4.5 months, an advanced individual training (AIT) will be implemented in addition to administration of correspondent placebo every 12 hours for 6 weeks more, completing total of 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal oxygen uptake (VO2 max) test	Maximal oxygen uptake (VO2 max) test measures the maximum rate of oxygen consumption during incremental exercise (exercise of increasing intensity) and reflects the cardiorespiratory fitness of an individual and is an important determinant of their endurance capacity during prolonged exercise.	6 months
Skeletal muscle function	The 6-minute walk test (6MWT) quantifies the distance a person can walk in six minutes and will be used to document the mobility/functional status of a patient. Originally developed to evaluate the physical capacity of patients with cardiopulmonary diseases, the test has been used to assess treatment effects, physical function status, and to predict morbidity and mortality in several patient populations including frail older adults.	6 months
Short Physical Performance Battery (SPPB)	The SPPB captures domains of strength, endurance, and balance and is highly predictive of subsequent disability.	6 months
Respiration rate on muscle biopsy samples	The samples will be analyzed for respiration rate in isolated mitochondria and permeabilized fibers	6 months
PCR on muscle biopsy samples	RT-PCR for gene expression	6 months
Immunoblot on muscle biopsy samples	Immunoblot in skeletal lysates for protein expression	6 months
Bone metabolism	Serum Carboxy-terminal Telopeptide (CTX), tartrate-resistant acid phosphatase isoform type 5b (TRAP5b), Amino-terminal Pro-peptide (P1NP), and osteocalcin will all be measured to monitor bone turnover markers.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose profile	Serum glucose measure	6 months
Insulin	Serum insulin measure	6 months
Lipid profile	Blood cholesterol measure	6 months
Hemoglobin A1C	Hb A1C measure in blood sample	6 months
Oral glucose tolerance test	An 18-gauge cannula will be inserted in a retrograde fashion into a dorsal hand vein of the non-dominant arm. The hand will be placed in a heated box (55°C) to enable sampling of arterialized venous blood. Blood will be drawn at 0 (baseline), 10, 20, 30, 60, 90, and 120 minutes for the measurement of glucose, insulin, and C-peptide concentrations. After the baseline blood draw, subjects will ingest 75 g of glucose over a period of 5 minutes.	6 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Eduardo N Chini, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2019
• Primary Completion (Actual): November 8, 2024
• Study Completion (Actual): November 8, 2024

Study Registration Dates

• First Submitted: January 23, 2019
• First Submitted That Met QC Criteria: January 24, 2019
• First Posted (Actual): January 28, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 24, 2025
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Aging; Nicotinamide Riboside; NAD boosting therapy; NAD precursors
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Micronutrients; Vitamin B Complex; Vitamins; Vasodilator Agents; Hypolipidemic Agents; Lipid Regulating Agents; Niacin; Niacinamide; Nicotinic Acids
• Other Study ID Numbers: 18-000224

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
• product manufactured in and exported from the U.S.: No