NAD Supplementation Study (NADS)

The Effects of NAD+-Precursor Supplementation on Energy Metabolism in Physically Compromised Elderly

This research project aims to determine whether supplementing with a mixture of the NAD+-precursors NA, NAM, and tryptophan can stimulate skeletal muscle mitochondrial function in physically compromised, elderly humans. Outcomes are related to mitochondrial function, energy metabolism, and physical function will be investigated.

Study Overview

• Status: Terminated
• Conditions: Aging; Mitochondrial Function
• Intervention / Treatment: Dietary supplement: NAD-precursors; Dietary supplement: Control

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229ER
      • Maastricht University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 75 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females
• Age ≥ 65 ≤ 75 years;
• BMI ≥ 20 kg/m2 ≤ 30 kg/m2;
• Normal physical activity levels: maximum of 1 hour per week engagement in a structured exercise session;
• SPPB score 4-9 and (pre-)frail;
• Subject should be in sufficient health to participate in the experiments, to be judged by the responsible physician based on the subject's medical history.

Exclusion Criteria:

• Not meeting all inclusion criteria;
• Smoking;
• Excessive alcohol use and/or drug abuse;
• Subjects with diabetes mellitus type 2;
• Significant food allergies or intolerances concerning the study products;
• Participation in another biomedical study within 1 month before the first study visit, possibly interfering with the study results;
• Medication use known to hamper subject's safety during the study procedures;
• Subjects who use selective serotonin re-uptake inhibitors (SSRI), or selective norepinephrin re-uptake inhibitors (SNRI), or monoamino oxidase inhibitors (MAO-inhibitors), or clomipramine, or St. John's wort (Hypericum perforatum);
• Subjects with contra-indications for MRI;
• Subjects who do not want to be informed about unexpected medical findings;
• Subjects who do not want that their treating physician to be informed;
• Co-morbidities to which the intervention or program the may pose as a complicating factor;
• Inability to participate and/or complete the required measurements.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control	Dietary supplement: Control; Control product containing amino-acid mixture resembling whey-protein not containing the NAD+-precursors nicotinic acid, nicotinamide, and tryptophan. To be taken for 31 days.
Active Comparator: Intervention	Dietary supplement: NAD-precursors; Intervention product containing the NAD+-precursors nicotinic acid, nicotinamide, and tryptophan (total of 204 NE per serving) in a whey protein source for 31 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ex vivo mitochondrial respiration	Ex vivo mitochondrial function in skeletal muscle measured by oxygen consumption in muscle fibres (muscle biopsy vastus lateralis) on lipid-derived and carbohydrate-derived substrates.	After 4 weeks of supplementation.
Basal metabolic rate	Basal metabolic rate expressed as kcal/kg/min	After 4 weeks of supplementation.
In vivo mitochondrial capacity	In vivo mitochondrial capacity measured with 31P-MRS.	After 4 weeks of supplementation.
Submaximal exercise energy expenditure	Submaximal exercise energy expenditure expressed as kcal/kg/min	After 4 weeks of supplementation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose tolerance	Glucose tolerance measured by oral glucose tolerance test.	After 4 weeks of supplementation.
Ectopic lipid accumulation	Liver and skeletal muscle lipid accumulation measured with H-MRS in vivo.	After 4 weeks of supplementation.
Acetylcarnitine levels	Skeletal muscle acetylcarnitine levels measured with H-MRS in vivo, before and after exercise stimulation (cycling).	After 4 weeks of supplementation.
Physical function	Measured by Short Physical Performance Battery and Frailty criteria.	After 4 weeks of supplementation.

Collaborators and Investigators

• Sponsor: Maastricht University

Publications and helpful links

General Publications

• Connell NJ, Grevendonk L, Fealy CE, Moonen-Kornips E, Bruls YMH, Schrauwen-Hinderling VB, de Vogel J, Hageman R, Geurts J, Zapata-Perez R, Houtkooper RH, Havekes B, Hoeks J, Schrauwen P. NAD+-Precursor Supplementation With L-Tryptophan, Nicotinic Acid, and Nicotinamide Does Not Affect Mitochondrial Function or Skeletal Muscle Function in Physically Compromised Older Adults. J Nutr. 2021 Oct 1;151(10):2917-2931. doi: 10.1093/jn/nxab193.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2017
• Primary Completion (Actual): March 6, 2020
• Study Completion (Actual): March 6, 2020

Study Registration Dates

• First Submitted: October 10, 2017
• First Submitted That Met QC Criteria: October 10, 2017
• First Posted (Actual): October 16, 2017

Study Record Updates

• Last Update Posted (Actual): August 20, 2020
• Last Update Submitted That Met QC Criteria: August 18, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: NL61204.068.17

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