Nicotinamide adenine dinucleotide (NAD+) is a coenzyme found in every cell of the body, functioning as a helper molecule fundamental to cellular metabolism and energy production. It is central to converting nutrients into adenosine triphosphate (ATP), the primary energy currency for all cellular processes. Testosterone is the primary male sex hormone, influencing physical characteristics, energy levels, and vitality. Because both NAD+ and testosterone levels decline naturally with age, interest has grown in whether boosting the coenzyme can positively affect hormone production. This article explores the biological relationship between these two molecules and reviews the current scientific findings regarding supplementation.
Defining NAD+ and Testosterone’s Roles
NAD+ participates in hundreds of metabolic reactions, acting primarily as a carrier for electrons in energy generation. This molecule is necessary for the continuous operation of metabolic pathways that extract energy from food, such as the citric acid cycle. Beyond energy production, NAD+ serves as a cofactor for enzymes involved in maintaining cellular integrity, including those that detect and repair damage to the cell’s genetic material. The concentration of this coenzyme naturally decreases with advancing age, which can lead to a decline in cellular function.
Testosterone is a steroid hormone produced mainly in the testes. Its primary functions relate to the development of male secondary sexual characteristics and the maintenance of physical health throughout life. The hormone plays a significant role in promoting muscle protein synthesis, leading to increased lean muscle mass and strength. It also supports bone density, fat distribution, and regulates libido. Like NAD+, testosterone levels begin a steady decline in men, typically starting around the age of 30.
The Theoretical Pathway Linking NAD+ and Hormone Production
The potential connection between NAD+ availability and testosterone production lies in specialized enzymes that rely on the coenzyme to function. A group of proteins called sirtuins, particularly Sirtuin 1 (SIRT1), are NAD+-dependent deacetylases that require NAD+ to perform their regulatory actions. These sirtuins are known to be involved in regulating the hypothalamic-pituitary-gonadal (HPG) axis, the system that controls testosterone synthesis.
When NAD+ levels are high, SIRT1 activity is enhanced, which can stabilize and activate specific transcription factors within the Leydig cells of the testes. These cells are the primary sites of testosterone manufacturing, converting cholesterol into the hormone through a complex series of steps. Research suggests that SIRT1’s presence is necessary for the optimal function of these Leydig cells. NAD+ is also a cofactor for steroidogenic enzymes, such as 17-beta hydroxysteroid dehydrogenase, directly involved in converting precursor hormones into active testosterone. Therefore, a decline in NAD+ with age may impair the cellular environment in the testes and regulatory signaling from the brain, potentially leading to suboptimal hormone output.
Clinical Findings: Does Supplementation Increase Testosterone?
While the mechanistic evidence from cellular and animal studies suggests a link, the results from human clinical trials are less conclusive. Some animal studies, including those on boars and mice, have shown that increasing NAD+ levels through precursor supplementation significantly raises serum testosterone levels and improves testicular health, particularly in models of aging. These findings highlight the coenzyme’s restorative potential in a compromised hormonal system.
In human research, a small-scale study involving older men indicated that supplementation with Nicotinamide Mononucleotide (NMN) appeared to influence testosterone levels. This study also noted an improvement in muscle strength and physical performance in the participants receiving the NMN. However, this finding is not universally supported across the limited human trials conducted to date.
There is no broad, direct evidence confirming that NAD+ precursor supplementation reliably increases testosterone in healthy men. The primary focus of most human trials has been on the coenzyme’s effects on metabolic health, energy, and physical function, with testosterone often not being the main outcome measured. The results that are seen may be an indirect consequence of improved metabolic health, reduced inflammation, or enhanced cellular energy, which in turn creates a better environment for the body’s natural hormone production processes to function efficiently. Larger, long-term human trials specifically designed to monitor serum testosterone as a primary endpoint are still needed to draw a definitive conclusion.
Considerations for NAD+ Supplementation
Individuals interested in boosting their NAD+ levels typically use precursor supplements that the body can readily convert into the coenzyme. The two most common precursors are Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN). These molecules bypass certain enzymatic bottlenecks in the body’s natural production pathway, making them efficient ways to elevate NAD+ concentrations.
Dosage ranges used in human research vary, but NMN has been studied at daily doses between 250 milligrams and 1,200 milligrams. Nicotinamide Riboside is often studied at doses ranging from 250 milligrams to 500 milligrams per day. In short-term studies, both NMN and NR have been generally well-tolerated by participants, with minimal to no serious adverse effects reported.
While NAD+ boosting is a strategy for supporting overall cellular health, it should be approached with realistic expectations regarding hormonal changes. Any potential effect on testosterone is considered a secondary benefit resulting from an overall improvement in cellular function and metabolic environment. It is advisable to consult a health professional before beginning any new supplement regimen, especially considering the long-term safety data for these precursors is still being gathered.