Scientific research has shown that a decline in intracellular Nicotinamide Adenine Dinucleotide (NAD+) levels is associated with aging and age-related diseases. In animal models, therapeutic strategies aimed at increasing NAD+ levels have been effective in delaying or preventing such conditions. Numerous studies also suggest that supplementation with NAD+ precursors such as Nicotinamide Mononucleotide (NMN) can elevate NAD+ levels in the body, thereby improving cellular energy metabolism and alleviating age-associated functional decline.

The First Human Clinical Trial on NMN Safety

To evaluate the safety of NMN supplementation in humans, the first human clinical trial was conducted by Keio University School of Medicine in Japan. The study began in 2016, and its findings were published in 2019. This trial aimed to assess the clinical safety of a single dose of NMN by monitoring clinical and metabolic parameters in healthy Japanese men.

Study Overview

Title: Oral Administration of Nicotinamide Mononucleotide (NMN) Increases Nicotinamide Metabolism in Healthy Men: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial

Institution: Keio University, Japan

Study Start Date: 2016

Publication Date: 2019

Participants: 10 healthy Japanese men aged 40–60

Intervention: Single-arm, non-randomized intervention with a one-week washout period between doses. Each participant received a single oral dose of 100 mg, 250 mg, and 500 mg NMN. Clinical and pharmacokinetic parameters were assessed over a 5-hour period after each administration.

Conclusion: A single oral dose of up to 500 mg NMN was well-tolerated in healthy adult men, without causing significant adverse effects. NMN was efficiently metabolized.

Clinical Parameters

The study showed no significant clinical symptoms or changes in key vital signs such as heart rate, blood pressure, oxygen saturation, or body temperature following NMN administration.

Serum Biomarkers

Laboratory results indicated that serum bilirubin slightly increased, while creatinine, chloride, and glucose levels slightly decreased. However, all values remained within normal physiological ranges and were not dose-dependent.

Plasma Metabolite Profile

Post-administration plasma levels of NMN metabolites— namely, N-methyl-2-pyridone-5-carboxamide (2Py) and N-methyl-4-pyridone-5-carboxamide (4Py)—increased in a dose-dependent manner, indicating effective absorption and metabolism of NMN.

Ophthalmic Evaluation

Ophthalmological examinations conducted before and after NMN intake showed no significant differences across all doses. No adverse effects on visual function, optic nerve, or retinal health were observed.

Summary

This pioneering human clinical study confirms that oral NMN supplementation at doses up to 500 mg is safe and well-tolerated in healthy adult males. It also provides pharmacokinetic data supporting efficient metabolism of NMN in humans.

About Leadsynbio

At Leadsynbio, we believe that product efficacy begins with safe and consistent raw materials. As a synthetic biology-based manufacturer, we have innovated a fully enzymatic NMN production process that is green, efficient, and industrially scalable. Our platform enables us to supply NMN ingredients with high purity and batch-to-batch consistency, ensuring a solid foundation for clinical and commercial applications.