Infertility is a major disease globally, with almost 30% of women being infertile in parts of Africa and 6% of married American women aged 15–45 reporting infertility. There can be numerous reasons for female infertility.
Female infertility is increasing due to women's choices of conceiving later in life.
Decreases of NAD+ levels have been implicated in age-related declines in bodily function, including fertility.
NMN is beneficial for conditions related to female fertility, such as obesity, diabetes; it has also shown improvements in the quality of oocytes and fertility in mice studies.
Further studies regarding NMN are required to make any general recommendations for women trying to conceive or those that are pregnant.
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However, age-related decreases in fertility are becoming more important as an increasing number of women of childbearing age choose to delay conception. In this context, NMN has been touted as a supplement that may benefit fertility.
What is NMN?
Nicotinamide mononucleotide (NMN) is an intermediate to nicotinamide adenine dinucleotide (NAD+). NMN helps with the production of NAD+, particularly in the bottleneck, and increases its levels that naturally fall with age.
NAD+ is one of the key chemicals necessary for all life. It aids in over 400 bodily functions, including DNA repair and energy metabolism. NAD+ has been implicated in numerous conditions, and NMN supplementation is beneficial in several contexts, such as diabetes, obesity, and alcohol-related liver damage.
NAD+ levels and fertility
In the same sense, age-related decline in female fertility has been demonstrated to be irreversible due to the declining quality of egg cells. Recently, studies have looked into explaining the mechanisms of such a decline but established that decreasing levels of NAD+ were partly to blame for most aging-related concerns.
In the same study, researchers supplemented aging mice with NMN. The results showed fertility restoration, increased egg cell quality, and beneficial effects on the embryo. These findings indicate that restoration of NAD+ levels by NMN supplementation may help reverse and/or delay age-related declines in fertility in females.
Other factors that have an impact on fertility
Obesity and being overweight are also tied to female infertility. Body fat produces numerous hormones and chemicals, such as estrone and adipokines, that affect female reproductive function. These ultimately lead to worse fetal outcomes in the context of chronic ovarian inflammation and decreased egg-cell quality. Furthermore, obesity is also associated with polycystic ovary syndrome (PCOS), another common cause of female infertility.
Nicotinamide mononucleotide supplementation has been shown to benefit obesity and insulin resistance, a hallmark of PCOS, and reduce age-associated weight gain. In a mice study, researchers have shown that NMN supplementation restored ovarian weight and reduced ovarian inflammation in obese mice. NMN supplementation also improved egg-cell quality and normalized fetal weight-related outcomes of obese mice.
From a fetal outcomes perspective, NAD+ deficiency has been shown to result in birth defects as well as various malformations. Although such extreme outcomes would be expected in mothers with underlying genetic mutations leading to issues with their NAD+ metabolisms, it is also likely that NMN supplementation may decrease the risk of numerous malformations associated with the so-called congenital NAD+ deficiency disorder (CNDD).
What does the science say?
As of yet, no direct human studies have been conducted to test the benefits of NMN on fertility and fetal outcomes. However, research findings in mice studies have shown the beneficial effects of NMN supplementation on conditions associated with infertility, such as obesity and diabetes, as well as positive effects on fetal outcomes and egg-cell quality. Therefore, it is most likely that NMN supplementation would be valuable for common types of female infertility, such as age-related loss of fecundity or PCOS-associated infertility.
NMN and fertility: is it safe?
The final question then revolves around the safety issues surrounding NMN. This is particularly relevant if supplementing pregnant women or those trying to become pregnant. This is also always a cost-benefit calculation. For example, folic acid supplementation is typically suggested in this context as it lowers the risks of neural tube defects. However, excessive maternal folic acid intake may be associated with adverse neurological effects in the offspring and increased asthma risks.
NMN is generally considered safe, with no acute or chronic adverse effects in most studies. However, it has been shown to be possibly “toxic” to neural tissue in higher doses. Furthermore, there’s also the hypothetical concern that NMN supplementation may accelerate cancer growth, as tumor growth has been shown to depend on speedy NAD metabolism. Given the lack of studies and the critical and rapid division of cells in early pregnancy, it would be most prudent to discuss possible NMN supplementation with an OB/GYN or a fertility specialist. This holds especially true if struggling with female infertility due to age, obesity, or PCOS.