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Exploring the Impact of NMN, Resveratrol, and Spermidine on Fertility: A Comprehensive Review of Recent Studies and Dosage Guidelines

Understanding the minute details of our body’s biochemistry and maintaining a healthy diet and lifestyle are crucial to achieving fertility. But with the passage of time, the fertility rate declines. According to the CDC, approximately 19% of reproductive-aged women in the US experience infertility or other pregnancy-related challenges.

Beyond advancing age, lifestyle choices, inadequate diets, compromised sperm quality, and complications in the ovaries, fallopian tubes, and uterus are contributing to the rise in infertility issues.

Given these discouraging numbers, it’s no wonder individuals are looking for methods to increase their chances of improving fertility. But recent research on mammals indicates the potential possibility of an approach that could mitigate certain consequences of female reproductive aging and increase fertility beyond 40.

Also, the scientific community has recently become very interested in the possible functions of resveratrol (RSV), nicotinamide mononucleotide (NMN), and spermidine (SPD) in promoting fertility. They have already brought attention due to their distinct biological functions and possible health advantages.

Nicotinamide mononucleotide (NMN) For Fertility

Nicotinamide mononucleotide (NMN) is a precursor to NAD+ (nicotinamide adenine dinucleotide), a key component in many biological processes.
It has recently been the subject of much interest. The anti-aging benefits of NMN have been at the forefront for the last 20 years. In addition, research has shown that taking NMN supplements can improve fertility and potentially turn back the clock on egg cell aging.

Mechanisms: Supplementing with NMN can increase NAD+ levels, which may reduce the severity of various age-related health issues, according to studies conducted in cell cultures, animal models, and a small number of human clinical trials. The idea is that if NAD+ levels are elevated, cells may repair DNA damage more efficiently, which might have repercussions on several processes associated with aging, as well as on energy levels, metabolism, fertility, and the lifetime of cells.

Research on NMN for Enhancing Fertility

Fertility

Image source: https://hello100.com/nmn-fertility/

Professor David Sinclair, one of the most renowned authorities on longevity, published case reports reporting that NMN supplementation increased different animal species’ metabolism, energy levels, and fertility.

To date, no human studies have directly examined the potential benefits of NMN on pregnancy outcomes and fertility. In contrast, investigations conducted on rodents have demonstrated the advantageous impacts of NMN supplementation on various conditions linked to infertility, including diabetes and obesity (1)(2). Furthermore, it has been found to affect fetal outcomes and the integrity of egg cells positively.
The study done in 2020 in mice has shown encouraging results that an NAD+ dosage of 200–500 mg can improve egg quality. This groundbreaking study suggests that it may be possible to reverse the detrimental effects of aging on oocyte development. Enhancing NAD+ concentrations via NMN, an NAD+ precursor, could potentially restore these cells’ quality.

Another 2020 research showed similar results, in which a dosage of (2 g/L, drinking water) of NMN was given, and a higher ovulation rate, more competent and fertilized oocytes, higher-quality blastocytes, and more live births were observed as a result.

However, the most recent study published in 2023 shows that supplementing with NMN at doses of 1 mol/L, 10 mol/L, and 100 mol/L may help swine eggs mature more slowly. This NMN supplementation showed that aging eggs could improve the health of mitochondria and decrease the accumulation of toxic compounds. It showed an increased likelihood that NMN-treated eggs would develop into early-stage embryos. This suggests that it may be used as a dietary supplement to enhance the health and developmental potential of elderly pig eggs.

All of the above data shows that NMN supplementation offers a natural, low-risk, and non-invasive alternative to costly and invasive treatments to improve fertility and the quality of egg cells with age.

Resveratrol (RSV) and Fertility

The potential of RSV to enhance fertility has been the subject of research, specifically concerning the age-related deterioration of reproductive function. It is well known that oxidative stress, which its antioxidant properties reduce, contributes to decreased fertility. The antioxidant resveratrol may help reproductive cells stay healthy and increase fertility by removing harmful free radicals. Trans-resveratrol is the active ingredient in resveratrol supplements, and it delivers all the antioxidant benefits without being poorly absorbed.

Mechanisms of Action: The antioxidant properties of resveratrol are its primary benefit for fertility.  RSV may increase fertility by balancing hormonal levels, improving ovarian function, and enhancing the integrity of oocytes (egg cells). Anti-inflammatory properties are also present, which may be advantageous for improving fertility.

It has also been found to balance the sex hormones, including estrogen and testosterone. Reproductive health depends on this control of hormones.

Research on Resveratrol (RSV) for Enhancing Fertility

In men: Research indicates that resveratrol can improve sperm quality and motility. It has been found that several sperm parameters, including concentration, count, and motility, can be improved by resveratrol dosages of 6 and 15 µM, respectively. In another study, a supplement containing resveratrol had a dosage of 150 mg and had better sperm motility and quality after 3 and 6 months of treatment.

In women: RSV is a phytoestrogen, which means it is a molecule derived from plants that can influence estrogen action in the body. It is comparable to other estrogen-related compounds. Scientific studies have shown that RSV can enhance the impact of estrogen hormones, which are crucial for the reproductive well-being of women.

source: https://academic.oup.com/jcem/article/101/11/4322/2765013?login=false

One prevalent cause of infertility in women, polycystic ovarian syndrome (PCOS), may find improvement with the use of resveratrol, according to research. The research used 1500 mg of resveratrol for 3 months, and the sample population saw a reduction in testosterone levels. Fasting insulin levels, total testosterone, and dehydroepiandrosterone sulfate were all markedly reduced after resveratrol treatment, and insulin sensitivity impairment was corrected.

However, this is not resveratrol’s sole effect on fertility. Because it reduces inflammation and oxidative stress in the reproductive system, which can harm egg quality, it is also very helpful for those with endometriosis.

In animals: Research on the effects of resveratrol on animal fertility has shown encouraging findings for treating reproductive issues. (1) (2) (3).

  • Increase in blood testosterone: A Korean study found that using resveratrol significantly increased blood testosterone levels by almost 50% after 28 days. This is particularly beneficial for men who need a boost, as natural testosterone decline is a natural part of aging.
  • Healthy ovary aging: It has also been found in another study that RSV consumption of 100 mg/kg can slow down aging, combat tumors in human tissues, and activate Sirt1 and telomerase. This all potentially affects the ovaries’ aging process, thus promoting fertility by reducing the ovaries’ aging.
  • Improves the mitochondrial health of eggs: Japanese scientists have discovered that a resveratrol dosage of 240 mg mixed in food can restore fertility in middle-aged mice by improving the mitochondrial health of their egg cells, thereby reversing age-related infertility. The mice’s live offspring rates increased significantly after the therapy, reaching levels typically seen in younger animals. The study also highlighted the role of sirtuins, enzymes linked to lifespan, activated by resveratrol.

Several mechanisms, including resveratrol’s antioxidant, anti-inflammatory, and hormone-regulating properties, suggest that it may improve fertility. However, further study is required to determine its safety and effectiveness in fertility augmenting, especially including human participants.

Spermidine (SPD) and Fertility

Spermidine, a metabolite first discovered in semen, has since been discovered in various tissues, including the ovaries. Inflammation, oxidative stress, genomic stability, mitochondrial repair, and proteostasis, as well as an important function in male and female fertility, are just a few of the many basic metabolic and aging-related processes that this polyamine has been discovered to regulate.

Mechanisms of Action: Spermidine may help with fertility because it lowers oxidative stress and maintains cellular homeostasis, two essential processes for making healthy gametes (sperm and eggs). Hormonal balance is important for reproduction in both sexes, and spermidine may affect this. Additionally, it is recognized for its involvement in DNA stability and control of gene expression, both of which are crucial for maintaining reproductive health.

Research on Spermidine (SPD) for Enhanced Fertility

According to previous studies, spermidine induces autophagy, increasing cell survival in both model species and humans. Other research that has been proven to work in favour of spermidine enhancing fertility are,

Female Fertility: Evidence suggests that oxidative stress, which worsens with age, might impair oocytes, and the reproductive cells of a woman and ultimately lower her fertility.

However, studies have shown that spermidine can improve ovarian function, potentially enhancing female fertility. A recent 2023 study on mice showed that supplementing the spermidine-depleted ovaries of old mice with 5mg/kg of spermidine for 10 days increases their fertility by promoting follicle formation, oocyte maturation, early embryonic development, and spermidine level. Spermidine promotes healthy oocytes by triggering mitophagy, a cellular mechanism that removes and recycles damaged mitochondria.

Male Fertility: Spermidine has also demonstrated promise for enhancing male fertility. Spermidine concentrations are comparatively higher in fertile males than in those unable to reproduce. It is essential for sperm production and sexual reproduction; it was first found in semen.

In males, spermidine has been linked to improved sperm quality, as per a 2022 research. It has been found that the dosage of 5mg/kg of spermidine may influence sperm motility and vitality, which are critical factors in male fertility.

It also has the potential to increase testosterone and DHEAS levels, which are signs of better sexual performance, and decrease cortisol levels, a stress hormone. It proves that spermidine may help men maintain or increase their fertility in later life.

More human clinical trials are required to completely understand the effect of spermidine on human fertility, despite encouraging findings in animal research.

Before attempting to supplement on your own, it is advisable to consult with an OB/GYN or fertility specialist regarding the possibility of using all the supplements mentioned above.   This will help us understand its effects thoroughly.

Substances such as NMN, resveratrol, and spermidine are promising in the ever-changing field of reproductive research. These substances are strong contenders in the fight against aging-related infertility because of their distinctive biological roles. The research, mostly done on animals, suggests that these supplements might improve the quality of eggs and sperm, control hormones, and decrease oxidative stress, which could increase fertility in both sexes.

New hope for those struggling with infertility may lie in a mix of healthy lifestyle choices and, maybe, specialized nutritional supplements as scientists explore deeper into the secrets of human fertility. We may not be able to stop time, but we can take charge of our reproductive health by arming ourselves with information and taking advantage of new scientific discoveries.

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