Nicotinamide mononucleotide ameliorates adriamycin-induced renal damag

DesignRandomized preclinical adriamycin-nephropathy mouse experiment with renal histology, biochemical and epigenetic assays, cultured podocyte experiments, and observational human-biopsy staining.

PopulationEight-week-old male BALB/c mice with adriamycin-induced focal segmental glomerulosclerosis-like injury; cultured renal cells and human biopsy specimens were used for supporting mechanistic observations.

SampleMain mouse groups: 12 per group; individual analyses generally used 6–20 observations per group

InterventionIntraperitoneal NMN at 100, 300, or 500 mg/kg/day after adriamycin; the main regimen used 500 mg/kg/day for 14 days versus saline, with follow-up to day 28.

EndpointsUrinary albumin-to-creatinine ratio, serum creatinine, creatinine clearance, and cholesterol; Glomerulosclerosis, basement-membrane and podocyte measures; Renal NAD+, NMN, and nicotinamide; SIRT1, SIRT6, Claudin-1, Synaptopodin, Dnmt1, Nmnat1, PARP1, Twist2, and histone methylation

What the publication reported

Male mice with adriamycin-induced kidney injury received NMN by daily injection. Higher NMN doses reduced albuminuria, and the main high-dose regimen improved several kidney-function and tissue measures. The investigators linked these effects to changes in NAD-related enzymes and epigenetic regulation. Because this was a high-dose injection study in one mouse model, it cannot show that oral NMN benefits people with kidney disease.

Key findings

NMN at 300 and 500 mg/kg reduced urinary albumin-to-creatinine ratio, while 100 mg/kg did not. The 500 mg/kg regimen improved creatinine clearance, serum creatinine, cholesterol, glomerulosclerosis, and podocyte measures and preserved renal NAD+. It restored SIRT1, SIRT6, Dnmt1, and histone methylation and suppressed Claudin-1, Nmnat1, and PARP1. Some effects persisted to day 28, while basement-membrane thickness and several lower-dose comparisons were not significantly changed.

What it cannot establish

The intervention was studied in male mice with adriamycin-induced renal injury, not in humans. NMN was given intraperitoneally at doses up to 500 mg/kg/day and around the time of induced injury, which differs from oral consumer use. Whole-kidney NAD+ measurements limit cellular precision, glomerular elasticity was not measured, and the human tissue component was observational rather than an NMN trial. Translation, dosing, efficacy, and safety in patients remain unknown.

HealthspanX claim boundary: This preclinical study does not establish that oral NMN prevents or treats human kidney disease, improves renal function in consumers, or predicts outcomes for HealthspanX Ultra Pure NMN.

Source identifiers

DOI: 10.1038/s41598-022-18147-2
PubMed: PMID 35962139
PubMed Central: PMC9374671
Trial registration: Not reported (animal study)
Publication type: Animal intervention study
Publication: Scientific Reports, 2022. 12(1):13712

Transparency

Funding: Scientific Research Fund of Japan MEXT (Grant 22K0835400).
Declared interests: The authors declared no competing interests.

HealthspanX observation: The main regimen was a high intraperitoneal dose in male mice and began around experimentally induced adriamycin injury; the human biopsy observations were not an NMN intervention.

Interpretive status: Mechanistic contextThe controlled mouse and cell experiments support a renal mechanism, but high-dose intraperitoneal treatment in one injury model cannot establish human efficacy or oral-product effects.

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