Impact of NAD+ on Female Fertility

Impact of NAD+ on Female Fertility

Introduction to NAD+:

NAD+ is a co-enzyme that exists in every cell of the human body. It is essential for the production of ATP (adenosine triphosphate) which is consumed for energy. Numerous cellular processes and functions are regulated by NAD+, which is utilized as a cofactor or substrate by hundreds of enzymes. These functions and processes are still being studied.(1) Roughly a century ago, it was discovered that NAD+ levels and health are related. NAD+ decreases with increasing age throughout our lifetime as it reduces by nearly 80% in people aged 40 or above. A person's sirtuin and PARP activity are lost when their NAD+ levels drop to half of what they were when they were younger by the time they reach middle age. Recent research has demonstrated that administering PARP inhibitors or precursors of NAD+ to elderly mice can significantly enhance their quality of life.(2) Increased insulin sensitivity, reversal of mitochondrial dysfunction, decreased senescence of stem cells, and longevity are among the observed outcomes.

A brief look at the fertility:

In almost every nation on the planet, fertility rates have sharply decreased over the last 50 years. Growing prosperity is primarily responsible for this global reduction in fertility through the mediation of social factors, the most potent of which are women's education and a concomitant shift in life purpose away from childbearing. Long-term alterations are taking place as a result of a confluence of genetic, lifestyle, and environmental variables. These changes have the potential to permanently harm our species' ability to reproduce.(3) Oocyte quality, which drastically decreases starting in the latter part of the third decade of life in humans, is the rate-limiting factor for a healthy pregnancy. A therapeutically feasible strategy to maintain or renew oocyte quality with aging—defined as the oocyte's ability to support meiotic maturation, fertilization, and subsequent embryonic development does not exist, despite the overwhelming demand. The demand for assisted reproductive technologies (ARTs) like in vitro fertilization (IVF) has been fueled by a rate-limiting barrier to pregnancy with aging that may be removed by a non-invasive, pharmaceutical treatment to maintain or restore oocyte quality during aging.(4)

NAD+ role in female fertility:

In humans and animals, low levels of nicotinamide adenine dinucleotide (NAD+) have been linked to a higher risk of miscarriage and congenital abnormalities; in older people, increasing levels of NAD+ by dietary supplements resulted in enhanced oocyte quality and embryo development. Studies performed on female mice by moderating NAD+ levels show that ovarian aging significantly improves resulting in fertility enhancement. (5) An increasing amount of research indicated a need to learn more about how NAD+ preserves female fertility as women age. The connection between NAD and sirtuins provides one explanation that could be of interest. The seven members of the NAD-dependent deacetylase family including sirtuins (SIRT1–7) have been shown to play regulatory roles in the female reproductive system. It has been demonstrated that slowing down the aging of sirtuins protects female fertility in several ways, including better controlling oocyte development and preserving spindle integrity.(4)


1.              Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021 Feb;22(2):119–41.

2.              Pollard CL, Gibb Z, Swegen A, Grupen CG. NAD+, Sirtuins and PARPs: enhancing oocyte developmental competence. J Reprod Dev. 2022 Dec 19;68(6):345–54.

3.              Aitken RJ. The changing tide of human fertility. Human Reproduction. 2022 Apr 1;37(4):629–38.

4.              Kordowitzki P, Ho WHJ, Listijono DR. Nicotinamide Adenine Nucleotide—The Fountain of Youth to Prevent Oocyte Aging? Cells. 2021 Sep;10(9):2441.

5.              Liang J, Huang F, Song Z, Tang R, Zhang P, Chen R. Impact of NAD+ metabolism on ovarian aging. Immunity & Ageing. 2023 Dec 2;20(1):70.