NMN Update: Study Reveals Gender-Specific Effects on Lifespan and Health

For years, Nicotinamide Mononucleotide (NMN) has been one of the most discussed supplements in longevity science, primarily due to its potential role in boosting NAD+ levels. NAD+ (nicotinamide adenine dinucleotide) is a critical molecule involved in cellular metabolism, energy production, and DNA repair. The theory has long been that increasing NAD+ levels through NMN supplementation could slow aging and even extend lifespan. However, despite strong theoretical backing, definitive empirical evidence in mammals has been lacking—until now.

In June 2024, a groundbreaking study led by Dr. David Sinclair attempted to answer the question of whether NMN supplementation could genuinely extend lifespan in mammals. The study, although not yet peer-reviewed, is one of the most comprehensive longevity studies on NMN to date. It was funded by Metrobiotech, a company closely associated with Sinclair and one that has a vested interest in the efficacy of NMN. This raises potential concerns about conflicts of interest, but the study itself offers some compelling insights—both confirming and contradicting prior assumptions about NMN’s role in longevity.

This article breaks down the study's methodology, key findings, and what it means for those currently taking or considering NMN supplements. Importantly, we’ll also explore how NMN’s effects appear to differ between males and females, suggesting that its benefits may not be as universal as previously thought.

Study Design: A Closer Look at the Research
 
Dr. David Sinclair is one of the most prominent figures in the field of aging and longevity research. He is a professor of genetics at Harvard Medical School. Over the past two decades, Sinclair has focused on understanding the mechanism of aging and how they can be targeted to extend healthspan and lifespan.

Recently, Dr. Sinclair’s study was designed to maximize the potential benefits of NMN supplementation. The researchers administered NMN to mice at human-equivalent doses of 3 grams per day for women and 3.5 grams per day for men—significantly higher than the typical NMN dose taken by most users today.

Unlike Sinclair’s personal supplementation routine, where he takes NMN as a single bolus dose, the study delivered NMN gradually throughout the day via the mice’s drinking water. This distinction is crucial because it mirrors how NMN is naturally provided in human breast milk, where it is supplied continuously rather than in one large dose.

By tracking multiple biomarkers of aging, including lifespan, tumor development, physical performance, frailty, and gene expression changes, the study aimed to offer a comprehensive evaluation of NMN’s effects. 

Given the high-quality design and broad range of measured outcomes, this study provides one of the clearest looks at NMN’s true potential—or limitations.

Key Findings: NMN's Effects on Longevity and Health

1. No Lifespan Extension in Male Mice, Modest Benefits in Females

One of the study’s most striking findings was that NMN did not increase lifespan in male mice. However, female mice saw an 8.5% increase in median lifespan and a 7.9% increase in maximum lifespan.

This suggests that NMN’s longevity effects may be gender-dependent, possibly due to hormonal or metabolic differences.

2. NMN Improves Healthspan in Sex Dependent Manner

While NMN did not extend the lifespan of male mice, it did improve several health markers in both males and females, albeit in different ways:

Additionally, NMN treatment in middle-aged (18-24 months old) male mice prevented weight gain by reducing fat mass and increasing lean mass, as measured by DEXA imaging. However, NMN-treated female mice were found to have inflamed kidneys in some cases, indicating potential sex-specific adverse effects.

3. No Impact on Tumor Growth or Cancer Risks

There has been concern in the longevity community about whether NAD+ boosters like NMN could accelerate cancer growth. This fear stemmed from previous research showing that another NAD+ precursor, Nicotinamide Riboside (NR), increased cancer progression in mice. 

However, this study found no such effects—neither positive nor negative—on tumor formation. NMN did not protect against cancer, but it also did not increase cancer risk.

4. No Effect on Epigenetic Clocks

Dr. Sinclair has long theorized that NAD+ boosters help preserve epigenetic information and slow aging at the cellular level. However, this study found no effect on epigenetic clocks in either male or female mice. 

This directly challenges the idea that NMN influences aging by preserving epigenetic integrity.

5. NMN Enhances Gut Microbiome Health

The study found that NMN increased the abundance of Anaerotruncus colihominis, a beneficial bacterial species associated with lower inflammation and improved longevity. This bacterium is also enriched in human centenarians, suggesting that NMN may contribute to longevity by supporting a healthier gut microbiome.

6. NMN Reduced Frailty but Did Not Improve Overall Physical Performance

NMN supplementation reduced frailty markers, particularly in females. Male mice showed increased physical activity levels and improved fat oxidation (as indicated by a lower respiratory exchange ratio), suggesting enhanced mitochondrial function. 

However, NMN had no significant effect on grip strength, nesting behavior, or other common markers of physical performance.

Practical Implications for NMN Supplementation

Based on these findings, what should individuals consider before supplementing with NMN?

1. Consider Splitting NMN Doses Throughout the Day

The study suggests that NMN supplementation may be more effective when taken multiple times throughout the day rather than in a single large dose. Since NAD+ consumption varies across tissues, spacing out NMN intake every 6-8 hours may offer better results.

2. Expect Different Effects Based on Gender

Men: Should not expect NMN to extend lifespan but may experience benefits in muscle function, fat metabolism, and energy levels. If no noticeable improvements occur within 3-4 weeks, NMN supplementation may not be worthwhile.

Women: May experience longevity benefits due to gut microbiome alterations and reduced frailty risk. However, more human studies are needed to confirm these effects.

3. Combine NMN with NAD+ Recycling Strategies

Given NMN’s limited impact on lifespan, focusing on NAD+ recycling strategies may be more beneficial. These include:

The 2024 NMN study challenges many prior assumptions about NAD+ boosters. While NMN may not be the longevity miracle some had hoped for, it still offers notable benefits, particularly for women and for improving muscle function in aging men. 

However, those seeking anti-aging benefits should prioritize NAD+ recycling strategies like fasting and exercise over relying solely on supplementation.

As more research emerges, particularly in human trials, our understanding of NMN’s role in longevity will continue to evolve.

This study highlights the importance of gender-specific research in longevity science. As institutions like the NIH push for more inclusive studies, we may find that many anti-aging interventions need to be tailored based on sex, genetics, and individual physiology. Until more human research is available, NMN remains an intriguing yet nuanced supplement in the pursuit of longevity.