A Summary of a NAD⁺ (Nicotinamide Adenine Dinucleotide) Clinical Study by Henderson et al. (2024)

Reviewed by Tamberlyn Blinsink, ND, MPH | Research & Development

Overview

The following summary reviews a clinical study examining a multi-ingredient dietary supplement designed to target multiple pathways in the NAD⁺ salvage pathway. The study evaluated its effects on whole blood NAD⁺ concentration and a range of aging-related biomarkers in healthy human adults across a broad age spectrum. The study authors describe NAD⁺ as a central mediator of multiple hallmarks of aging and note that age-related changes to NAD⁺-metabolizing enzymes—including a decline in nicotinamide phosphoribosyltransferase (NAMPT) and overexpression of CD38—limit the efficacy of single-precursor supplementation approaches. The study was designed to test whether a systems-based supplement addressing these root causes could more effectively restore NAD⁺ levels compared to conventional precursor-only strategies.

Summary

The use of a systems approach to increase NAD⁺ in human participants

Published in: npj Aging

Study Design: Double-blind, randomized, placebo-controlled crossover trial

Participants: 26 completers (18 female, 8 male) from an original recruitment of 33; ages 20–80 years; healthy adults with no significant chronic conditions or current use of NAD⁺ precursor supplements

Dose: 6 capsules per day (3 with breakfast, 3 with lunch) for 28 days per arm, separated by a 28-day washout period; the active supplement (Nuchido TIME+®) contained nicotinamide (500 mg), alpha lipoic acid (600 mg), zinc (10 mg), vitamin C (20 mg), and a 2,110 mg botanical blend comprising green tea extract (providing EGCG), rutin (providing quercetin and troxerutin), parsley leaf extract (providing apigenin), and black pepper fruit extract

Outcome Measures: Primary: whole blood NAD⁺ concentration measured by fluorometric enzymatic assay (NAD⁺/NADH-Glo, Promega) and LC–MS. Secondary: NAM and NMN concentrations by LC–MS; SIRT1, NAMPT, PGC1α, and CD38 protein expression in peripheral blood mononuclear cells (PBMCs) by western blotting; plasma cytokine panel (IL-2, IL-4, IL-5, IL-23, and 10 additional cytokines) by multiplex assay; serum protein glycation; IgG glycosylation profiling as a measure of biological age (GlycanAge commercial service); markers of hepatic function (alanine aminotransferase, alkaline phosphatase, albumin)

What Was Studied: Henderson et al. (2024) investigated whether a multi-target dietary supplement (Nuchido TIME+®) formulated using a systems biology approach could effectively increase NAD⁺ levels in whole blood compared to placebo. The researchers designed the supplement to address age-associated impairments in the NAD⁺ salvage pathway—including reduced NAMPT activity, elevated CD38 expression, and increased NNMT-mediated NAM excretion—by combining an NAD⁺ precursor with botanical agents targeting each of these enzymatic steps. Using a double-blind, crossover design, participants consumed either the active supplement or a placebo for 28 days, with blood collected at baseline and weekly throughout each intervention arm. In addition to the primary NAD⁺ endpoint, the study examined changes in protein expression of key NAD⁺-metabolizing and aging-related enzymes in PBMCs, as well as plasma inflammatory cytokines, serum protein glycation, and IgG glycosylation patterns as indicators of aging trajectory.

About the Reviewer

Name & Title: Tamberlyn Blinsink, Scientific Researcher at Solaray
Credentials: Naturopathic Doctor, Master of Public Health

Bio: Tamberlyn Blinsink, ND, MPH, a licensed naturopath who earned her Doctorate of Naturopathic Medicine from Bastyr University and her Master of Public Health from Purdue University. In addition to her experience in private practice, Dr. Blinsink, ND, MPH is a researcher in the natural products industry. She believes in giving back and has served as a lecturer at continuing education conferences and as a board member at Naturopaths Without Borders and NC Association of Naturopathic Physicians.

Reference

Henderson JD, Quigley SNZ, Chachra SS, Conlon N, Ford D. The use of a systems approach to increase NAD⁺ in human participants. npj Aging. 2024;10:7. https://pubmed.ncbi.nlm.nih.gov/38302501/

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