NAD+ Precursor Dosing: Single vs. Divided Dose
For a 300 mg dose of nicotinamide riboside (NR) or similar NAD+ precursors in healthy adults, the medication can be taken as a single daily dose—there is no requirement to divide it. 1
FDA-Approved Dosing Regimen
- The FDA labeling for nicotinamide riboside explicitly states that the usual adult dose is "one or two tablets taken once or twice a day with or without food," indicating flexibility for single daily dosing at the 300 mg level. 1
- This dosing can be taken with or without food, providing additional convenience. 1
Pharmacokinetic Evidence Supporting Single-Dose Administration
- Clinical pharmacokinetic studies demonstrate that single oral doses of 100,300, and 1,000 mg of NR produce dose-dependent increases in blood NAD+ metabolites, with the 300 mg dose increasing whole blood NAD+ by approximately 51% within 2 weeks. 2, 3
- The bioavailability and NAD+ elevation from a single 300 mg dose is sustained and clinically meaningful, eliminating the need for dose division. 2
- Blood NAD+ levels can rise as much as 2.7-fold with single oral doses in humans, demonstrating robust absorption without requiring divided dosing. 2
Safety Profile at 300 mg Single Dose
- The no observed adverse effect level (NOAEL) for NR in animal studies was 300 mg/kg/day, which translates to approximately 21,000 mg for a 70 kg human—far exceeding the 300 mg clinical dose. 4
- In an 8-week randomized controlled trial, 300 mg daily NR showed no significant adverse events compared to placebo, no flushing, and no dysregulation of lipid or metabolic parameters. 3
- Unlike nicotinic acid (which causes flushing at doses as low as 30 mg), nicotinamide-based compounds like NR do not cause flushing and have a much more favorable tolerability profile. 5, 6
Comparison to Related Niacin Compounds
- Standard dietary niacin recommendations are 14-16 mg/day for adults, but therapeutic doses of nicotinamide up to 900 mg/day are considered safe by nutrition guidelines. 5, 6
- The upper intake level for nicotinamide is approximately 900 mg/day for adults (12.5 mg/kg body weight/day), meaning 300 mg is well within safe limits even as a single dose. 5, 7
- For context, pellagra treatment uses 300 mg/day of nicotinamide as a single dose, establishing precedent for this dosing strategy. 5
Clinical Considerations
- There is no pharmacokinetic advantage to dividing a 300 mg dose—the compound is well-absorbed and maintains elevated NAD+ levels throughout the day with once-daily dosing. 2, 3
- Dividing the dose would only add complexity without improving efficacy or tolerability at this dose level. 1
- The only scenario where divided dosing might be considered is if gastrointestinal symptoms occur, though this is uncommon at 300 mg. 5