Nicotinamide Riboside Impact on Extracellular Nicotinamide Adenine Dinucleotide (NAD+)

NAD Clinical Trial

— NICE  

Official title:

Validation of an Enzymatic Assay for Quantification of Nicotinamide Adenine Dinucleotide in Blood Plasma After Ingestion of the Vitamin B3 Variant Nicotinamide Riboside: a Randomized Controlled Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06005350
• Other study ID #: EA4/210/19
• Status: Active, not recruiting
• Phase: N/A
• Start date: November 1, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: June 2024
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigation is a clinical study in which the impact of taking the dietary supplement nicotinamide riboside (NR) on the concentration of extracellular nicotinamide adenine dinucleotide (eNAD+) in human plasma over time will be determined. The study will be conducted in a randomized, double-blinded, and placebo-controlled manner.

Description:

The significance of nicotinamide adenine dinucleotide (NAD+) in promoting a healthy life is currently under intense research. Despite an increasing number of research groups focusing on NAD+, there is no validated measurement method for extracellular NAD+. With this research project, the investigators aim to address this research gap.

The coenzyme NAD+ is one of the central regulators of metabolism, existing mostly in its oxidized form, NAD+, and its reduced form, NADH, in a dynamic equilibrium. NAD+ is indispensable for various metabolic processes, and is especially key in ATP generation. It also enables gluconeogenesis, ketogenesis, pentose phosphate production, heme and lipid synthesis, and the elimination of oxygen radicals.

To validate the NAD+ assay as a robust and reliable quantification method of extracellular NAD+, a controlled increase of the measured metabolite in blood plasma is required through NAD+ precursor administration.

Multiple studies have already demonstrated that oral NR intake can increase NAD+ levels in mammalian cells, rodent tissues, and peripheral blood mononuclear cells (PBMCs) in humans. However, this relationship has not been explored in the extracellular space due to the lack of reliable quantification of eNAD+ levels. Now, using the NAD+ assay, the investigators aim to examine the increase of eNAD+ after oral NR intake and provide initial data on the effects of a 1000 mg/day dosage.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 54
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Good general health

• Normal nutritional status and

• Age >18 years.

Exclusion Criteria:

• Pregnancy and/or lactation, or

• Severe psychiatric disorders, or

• Conditions that involve attention deficits, or

• Severe medical conditions, or

• Withdrawal of consent by the participant.

Related Conditions & MeSH terms

• NAD

Intervention

Dietary Supplement:
• Niagen
Nicotinamide-Riboside-Chloride Preparation 1000mg/day

Other:
• Placebo
Placebo Preperation

Locations

Country	Name	City	State
Germany	Surgical Clinic, Campus Virchow-Klinikum / Campus Charité Mitte, Charité - Universitätsmedizin Berlin	Berlin

Sponsors (2)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	ChromaDex, Inc.

Country where clinical trial is conducted

Germany, 

References & Publications (8)

Bogan KL, Brenner C. Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition. Annu Rev Nutr. 2008;28:115-30. doi: 10.1146/annurev.nutr.28.061807.155443. — View Citation

Brunnbauer P, Leder A, Kamali C, Kamali K, Keshi E, Splith K, Wabitsch S, Haber P, Atanasov G, Feldbrugge L, Sauer IM, Pratschke J, Schmelzle M, Krenzien F. The nanomolar sensing of nicotinamide adenine dinucleotide in human plasma using a cycling assay in albumin modified simulated body fluids. Sci Rep. 2018 Oct 31;8(1):16110. doi: 10.1038/s41598-018-34350-6. — View Citation

Canto C, Houtkooper RH, Pirinen E, Youn DY, Oosterveer MH, Cen Y, Fernandez-Marcos PJ, Yamamoto H, Andreux PA, Cettour-Rose P, Gademann K, Rinsch C, Schoonjans K, Sauve AA, Auwerx J. The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab. 2012 Jun 6;15(6):838-47. doi: 10.1016/j.cmet.2012.04.022. — View Citation

Chi Y, Sauve AA. Nicotinamide riboside, a trace nutrient in foods, is a vitamin B3 with effects on energy metabolism and neuroprotection. Curr Opin Clin Nutr Metab Care. 2013 Nov;16(6):657-61. doi: 10.1097/MCO.0b013e32836510c0. — View Citation

Dolopikou CF, Kourtzidis IA, Margaritelis NV, Vrabas IS, Koidou I, Kyparos A, Theodorou AA, Paschalis V, Nikolaidis MG. Acute nicotinamide riboside supplementation improves redox homeostasis and exercise performance in old individuals: a double-blind cross-over study. Eur J Nutr. 2020 Mar;59(2):505-515. doi: 10.1007/s00394-019-01919-4. Epub 2019 Feb 6. — View Citation

Imai SI, Guarente L. It takes two to tango: NAD+ and sirtuins in aging/longevity control. NPJ Aging Mech Dis. 2016 Aug 18;2:16017. doi: 10.1038/npjamd.2016.17. eCollection 2016. — View Citation

Trammell SA, Schmidt MS, Weidemann BJ, Redpath P, Jaksch F, Dellinger RW, Li Z, Abel ED, Migaud ME, Brenner C. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun. 2016 Oct 10;7:12948. doi: 10.1038/ncomms12948. — View Citation

Yoshino J, Baur JA, Imai SI. NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR. Cell Metab. 2018 Mar 6;27(3):513-528. doi: 10.1016/j.cmet.2017.11.002. Epub 2017 Dec 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	NR increases plasma concentrations of eNAD+	The daily intake of 1,000 mg of NR changes the concentration of eNAD+ over the course of 10 days. The NAD+ assay measures the changes in concentrations of eNAD+ in plasma.	10 days