As we get older, challenges to fertility can occur. These include age-related changes to ovarian integrity and decreases in the quality and amount of reproductive cells. Optimal cellular functioning and mitochondrial integrity are key components of ovarian health. 

The production of cellular energy occurs in the mitochondria and is dependent on NAD+ (nicotinamide adenine dinucleotide). NAD+ is found in every living cell and plays a role in more than 500 reactions in the body. It helps support DNA repair, gene expression, and the body’s stress response. NAD+ deficiencies have been associated with certain age-related changes. 

While the pathophysiology of ovarian senescence (deterioration due to aging) is not fully understood, research suggests that mitochondrial dysfunction and decreases in ovarian NAD+ levels over time may play a role. Increases in oxidative stress and higher levels of DNA damage have been observed in the process of ovarian senescence. This may result in reductions in oocyte quality and quantity. Evidence indicates that nicotinamide riboside (NR) may help support the body’s response to age-related changes to mitochondrial function and ovarian senescence. NR is a building block for NAD+ and has been shown in clinical studies to help promote healthy cellular NAD+ levels to support mitochondrial function and promote the body’s response to inflammation, senescent cells, and certain age-related illnesses. 

An animal study involving aging mouse models assessed the potential relationship between NR administration and ovarian health. This 12-month study found that NR helped increase ovarian NAD+ levels. It also helped promote an increased number of ovarian follicles and ovulatory potential. Reductions in spindle anomalies in aging oocytes and reactive oxygen species were also observed in the presence of NR alongside improvements in mitochondrial energy metabolism. 

A recent study investigated ovarian cell integrity in polycystic ovary syndrome (PCOS), an endocrine disorder characterized by ovarian dysfunction. It involved the collection of granulosa cells (GCs) from individuals with PCOS (n=31) and healthy controls (n=32). GCs are linked to ovulation and oocyte development. The study found that significant decreases in NAD+ levels occurred in individuals with PCOS when compared with controls. Changes to cellular energy production, mitochondrial membrane potential, and oxidative stress were also observed in those with PCOS. The authors conclude that supplementation with NR may help promote ovarian health and NAD+ levels in those with PCOS; however, no clinical evidence exists currently to support this claim. Despite this, research suggests that clinical studies involving NR supplementation in those with PCOS are warranted. 

While future studies are still needed, evidence indicates that NR may help support certain aspects of cellular health. It may help promote antioxidative stress, DNA repair, and mitochondrial function. 

By Dr. C. Ambrose, ND, MAT