Nicotinamide Mononucleotide and Nicotinamide Riboside Improve Dyslipidemia and Fatty Liver but Promote Atherosclerosis in Apolipoprotein E Knockout Mice
DesignMulti-cohort preclinical intervention study in diet-challenged C57BL/6J and ApoE-knockout mice, including long-term, established-plaque, route, supplier, and dose experiments.
PopulationC57BL/6J mice and apolipoprotein E knockout (ApoE−/−) mice; no human participants.
SampleMultiple mouse cohorts with sample size varying by experiment.
InterventionNMN or NR administered by intragastric gavage or drinking water across several protocols; key long-term experiments used NMN 300 mg/kg or NR 230 mg/kg, with additional NMN dose-ranging including approximately 100 mg/kg.
EndpointsBody weight and food intake; Serum lipids and glucose; Fatty-liver measures; Atherosclerotic plaque burden and lesion characteristics; Dose-, route-, supplier-, and duration-dependent vascular effects
What the publication reported
This mouse study tested NMN and nicotinamide riboside (NR) across several experimental protocols, including high-fat-diet conditions and ApoE-knockout mice that are prone to atherosclerosis.
The authors reported that NMN and NR lowered body weight, improved serum lipid measures, and reduced fatty-liver changes under several conditions. In ApoE-knockout mice, however, higher-dose supplementation also increased atherosclerotic plaque burden, including when treatment began after plaques were already present.
The vascular effect was dose-dependent in the authors' experiments, with doses around 100 mg/kg producing little observed harmful effect on atherosclerosis. These findings are mechanistic animal evidence and do not establish cardiovascular harm or a safe dose in humans.
Key findings
NMN (300 mg/kg) and NR (230 mg/kg) reduced body weight, serum lipid abnormalities, and fatty-liver changes in the reported mouse experiments.
In ApoE-knockout mice, NMN and NR aggravated atherosclerotic lesion burden after prolonged treatment.
Atherosclerosis also worsened in ApoE-knockout mice with pre-existing plaques under different NMN administration protocols.
The atherosclerosis findings were dose-dependent; doses around 100 mg/kg had little observed harmful effect in the reported model.
The same intervention could therefore show favorable metabolic effects and unfavorable vascular effects within the same disease-prone animal model.
What it cannot establish
The atherosclerosis experiments used ApoE-knockout mice, a specialized model with genetically accelerated plaque formation.
Mouse doses, pharmacokinetics, dietary context, and plaque biology cannot be directly translated into human supplementation risk.
The study evaluated surrogate and pathological endpoints in animals rather than cardiovascular events in people.
The work tested multiple suppliers, routes, durations, and doses, which improves mechanistic coverage but makes any single regimen an incomplete representation of the entire study.
These findings require human cardiovascular safety data before any inference about consumer risk.
HealthspanX claim boundary: This study does not establish that NMN causes atherosclerosis in humans, define a human safe dose, or determine the cardiovascular safety of any HealthspanX product.
