MIB-626, an Oral Formulation of a Microcrystalline Unique Polymorph of β-Nicotinamide Mononucleotide, Increases Circulating Nicotinamide Adenine Dinucleotide and its Metabolome in Middle-Aged and Older Adults

This trial tested whether a pharmaceutical-grade formulation of NMN — MIB-626, a microcrystalline polymorph milled to a specific particle size — could reliably raise blood NAD+ levels in middle-aged and older adults. Thirty-two overweight or obese adults aged 55 to 80 were randomised to receive either 1,000 mg MIB-626 once daily, 1,000 mg twice daily, or placebo for fourteen days. Blood samples were collected in a way designed to preserve NMN and NAD from the rapid degradation that has complicated earlier trials.

Both dosing regimens were safe and well tolerated, with adverse-event frequencies matching placebo. The key finding was pharmacodynamic: NAD+ rose substantially above placebo in both treatment groups, and the increase was dose-related. By day 8 the treated groups had reached the NAD+ levels they would maintain through day 14, suggesting steady-state was achieved within a week.

Circulating levels of the major downstream metabolites — 2-PY, nicotinamide, 1-methyl nicotinamide, and nicotinamide riboside — all rose alongside NAD+. Very little unchanged NMN appeared in urine, meaning almost all of the administered dose was absorbed and metabolised. The authors position 1,000 mg daily as the minimum regimen worth carrying forward into efficacy trials, based on earlier dose-finding work showing that doses below 1,000 mg did not consistently raise NAD+.

• Blood NAD+ rose substantially above placebo at day 14 in both MIB-626 groups (p < .001 for Cmax and AUClast).
• Blood NMN concentrations on day 14 were 2.7-times and 4.5-times higher than placebo at Cmax in the once-daily and twice-daily groups, respectively.
• NAD+ levels on day 8 were already near day-14 levels, suggesting steady-state within about a week of dosing.
• All four measured NAD metabolites (2-PY, NAM, 1-methyl NAM, NR) rose from baseline; 2-PY was the most abundant.
• Very little unchanged NMN appeared in the urine, indicating near-complete absorption and metabolism of the oral dose.
• Adverse event frequency was similar to placebo. One participant on twice-daily dosing discontinued due to diarrhoea; two participants (one on 1,000 mg once daily, one on placebo) had mild AST/ALT elevations that resolved after discontinuation.
• No significant changes in fasting glucose, insulin, HOMA-IR, lipids, or uric acid over 14 days.

• Short duration (14 days) and small sample (n = 32) — not designed or powered to detect changes in metabolic outcomes such as insulin sensitivity or lipids.
• Narrow BMI (28–40 kg/m²) and age (55–80 years) range; participants were overweight or obese and medically stable. Generalisability to leaner, younger, or medically complex populations is limited.
• Findings are specific to the MIB-626 microcrystalline polymorph formulation. Pharmacokinetics of over-the-counter NMN products may differ, since manufacturing quality varies and NMN is prone to degradation.
• NAD+ was measured in whole blood as a surrogate for tissue NAD+; direct tissue measurement was not performed.
• Tier-2 evidence: establishes pharmacokinetics and short-term safety of a specific pharmaceutical-grade formulation. Efficacy in disease conditions requires dedicated trials.