Impaired sperm quality if one of the major reasons for involuntary infertility. Studies show that oxidative stress, an imbalance between harmful free radicals and protective antioxidants, causes damage to sperm cells. In a review article that is published in Reproductive Sciences, a group of researchers look closer at different molecular mechanisms and how vitamins C, E, selenium, zinc, and coenzyme Q10 plus other antioxidants protect the vulnerable sperm cells.
More and more evidence suggests that free radicals and oxidative stress cause metabolic and functional disturbances in sperm cells and this may the main reason why involuntary infertility is so common.
Free radicals, also known as ROS (Reactive Oxygen Species), are metabolic waste products of cellular oxygen turnover and have key roles in several physiological functions. In fact, sperm cells generate minor quantities of free radicals to support maturation, cell signaling, DNA structure, apoptosis (programmed self-destruction of cells), and a number of other functions.
Free radicals are essential for the health of all living cells, sperms cells included. However, it is vital to keep the free radicals on a tight leash. These extremely reactive molecules with one or several unpaired electrons are a potential threat. In an attempt to replace the missing electrons, free radicals steal electrons from other molecules, thereby setting off a chain reaction that oxidixes the unsaturated fatty acids in cell membranes. Once a cell membrane has sustained oxidative damage, the free radicals can continue wreaking havoc inside the cell. Free radicals are also produced in the wake of other factors such as intensive physical training, aging, smoking, poisoning, inflammation, and various stress types of stress. In other words, free radicals are caused by both internal and external factors, and elevated levels of these harmful compounds can damage sperm cells by way of lipid peroxidation and biochemical chain reactions that destroy the integrity of the cell membrane, block different enzyme activities, and trigger apoptosis, all of which are factors that contribute to infertility. Free radicals are even able to damage the DNA of the sperm cell, a process known as DNA fragmentation. If this happens, the egg will fail to develop normally and will be rejected by the body, even though it has been successfully fertilized by a seemingly normal and motile sperm cell.
Types of free radicals – ROS (Reactive Oxygen Species)
Antioxidants from the internal environment
The different antioxidants have a vital role by preventing oxidative stress and maintaining the so-called redox balance. Antioxidants work by donating an electron to free radicals and neutralizing them in the process. The antioxidants, however, do not lose their antioxidant power. The primary antioxidants that the body produces endogenously work as enzymes and include:
- Glutathione peroxidase (GPX) – contains selenium
- Superoxide dismutase (SOD) – contains zinc, cobber, and manganese.
- Catalase (CAT) – consists of polypeptide chains
These three antioxidants are found in relatively large quantities in sperm cell and seminal fluid and are thought to originate from the prostate gland primarily. Using different mechanisms, these three antioxidants protect sperm cells’ membranes, DNA, and energy-producing mitochondria.
There are also antioxidants that work extremely fast but have no enzyme activity. Q10 is a good example. This compound is also of vital importance to the energy turnover in sperm cells.
Antioxidants from the external environment
Antioxidants from our external environment are also called exogenous antioxidants and we get them from our diet. Among the essential nutrients are vitamins A, C, and E, plus selenium, zinc, and manganese. Also, various plant compounds work as exogenous antioxidants.
Dietary antioxidants affect both the synthesis and the activity of the endogenous antioxidants and work synergistically to maintain the redox balance. In their review article, the authors primarily look at vitamin E, vitamin C, zinc, selenium, and Q10. They also write about special compounds such as L-acetyl cysteine, L-carnitine, and lycopene and address the fact that the different antioxidants complement one another. That is why it is important to eat a balanced diet and take supplements of the nutrients that are especially important for sperm quality.
Vitamin E (α-Tocopherol) is a lipid-soluble antioxidant that we primarily have in our cell membranes. It neutralizes hydroxyl radicals and superoxide, thereby counteracting lipid peroxidation in cell membranes. Scientists have observed a link between levels of vitamin E in seminal fluid and the percentage of motile sperm cells in ejaculate. Most studies have been conducted using 400 mg of vitamin E (α-Tocopherol) daily.
Levels of vitamin C (ascorbic acid) in seminal fluid are 10 times higher than in blood serum. Vitamin C neutralizes hydrogen peroxide, hydroxyl radials, and super oxide, offering protection against oxidative stress in sperm cells. Studies have shown that the addition of vitamins C and E to seminal fluid reduces DNA fragmentation caused by oxidative stress. Vitamin C studies typically look at the effect of using 500 – 1,000 mg daily.
The greatest concentration of zinc in men is found in the prostate gland that produces seminal fluid. There is relatively much zinc in seminal fluid and the nutrient plays a key role in sperm cell health with regard to RNA and DNA metabolism, signal transduction (the transfer of one type of signal to another), gene activation and apoptosis. There is also zinc in the SOD antioxidant (superoxide dismutase) that protects the structure and DNA of sperm cells. Studies have shown that zinc helps protect bull sperm against exogen oxidative stress, thereby improving the chances of successful fertilization and development of the calf embryo. Human studies of zinc have typically looked at daily doses in the range of 25-400 mg. The safe upper intake level according to health authorities is 25 mg daily. High-dosed supplementation over extended periods of time should normally be supervised by a doctor because zinc in greater quantities works as a copper antagonist.
Selenium supports well over 25 selenium-dependent proteins (selenoproteins), several of which are important for normal sperm cell health, including the health and function of the tale (flagellum) that is responsible for the forward propulsion of the sperm cells. Selenium supports the GPX antioxidant (glutathione peroxidase) that is primarily found inside the energy-producing mitochondria of sperm cells. GPX protects the mitochondria, DNA, and other cellular components against oxidative stress. There is quite a lot of selenium in seminal fluid, and it is thought to come from the prostate gland. Studies link low selenium status with abnormal sperm cells, impaired sperm cell motility, and DNA fragmentation.
Selenium deficiency is rather common in Europe and other parts of the world due to nutrient-depletion of the farmland. Since the 1970’s, Danish farmers have routinely fed extra selenium to their livestock to prevent fertility problems and other deficiency problems.
Human studies of selenium have typically looked at doses of around 200 micrograms daily. Selenium yeast is best for supplementation because it contains a variety of different selenium species, just like you get by eating a balanced diet with selenium from many different sources.
Q10 is a unique molecule that occurs in two forms in nature. One is ubiquinone that is important for cellular energy turnover. The other is ubiquinol and primarily serves as an antioxidant. The body is able to shift one form of Q10 to the other and vice versa, depending on what it is needed for different body functions. This conversion process requires the presence of a selenium-containing enzyme. Sperm cell mitochondria contain a lot of Q10 to help them produce the vast amounts of energy that sperm cells consume when swimming the relatively great distance to reach the egg and fertilize it.
Q10 counteracts the production of hydrogen peroxide and super oxide, thereby protecting against oxidative stress. Studies have shown an inverse relation between Q10 levels on one side and the number of sperm cells and sperm cell motility on the other. Most studies use daily doses of 100-300 mg.
N-acetyl cysteine contains cysteine, the amino acid that is a precursor of the powerful glutathione antioxidant. Several studies have shown that N-acetyl cysteine can lower levels of free radicals at the same time as increasing the number of sperm cells and improve their motility. It also lowers the number of abnormal sperm cells and sperm cells with DNA fragmentation. Cysteine is also found in selenocysteine, an amino acid that is incorporated in 25 different selenoproteins (including glutathione peroxidase). Because of these mechanisms, N-acetyl cysteine exerts a positive effect on sperm quality and pregnancy rate. The effect is even better if your selenium status is good. Studies typically look at daily doses around 600 mg.
L-carnitine is a water-soluble, vitamin-like compound that is involved in cellular energy turnover. The body is able to synthesize L-carnitine from the amino acid lysine. The best sources of dietary L-carnitine are meat and dairy products. One of L-carnitine’s functions is to support sperm cell maturation in the epididymis. The concentration of free L-carnitine in the epididymis is 2,000 times greater than in blood plasma. Lack of L-carnitine may impair sperm cell motility. L-carnitine’s antioxidant function has been demonstrated in human and animal studies. In infertile men, daily supplementation with 1,500 mg of L-carnitine has been seen to increase the number of sperm cells and improve sperm cell motility. Studies of L-carnitine typically look at daily doses of 500-1,000 mg.
Lycopene belongs to a group of antioxidants known as carotenoids. Lycopene is found in red fruits and vegetables such as tomatoes, red bell pepper, red carrots, and water melon. Lycopene is a powerful antioxidant that can prevent oxidative stress from damaging sperm cells. Studies normally look at daily supplementation with 6-8 mg of lycopene.
Sperm cells are extremely vulnerable to oxidative stress. Even though they have their own antioxidant defense, sperm cells lose some of their protection if the body’s endogenous antioxidant production or the dietary supply of antioxidants are compromised. Studies from recent years have shown that oxidative stress caused by free radicals can destroy sperm cells in different ways and cause problems such as low fertility and involuntary childlessness.
Science has looked at different ways of treating male infertility with antioxidants, especially by using vitamin E, vitamin C, selenium, zinc, Q10, L-acetylcysteine, L-carnitine, and lycopene. There is a variety of different combination supplements on the market. Always make sure to buy preparations with documented quality and bioavailability.
Alicja Kowalczyk. The Role of the Natural Antioxidant Mechanism in Sperm cells. Reproductive Sciences. 2021
Aparna Shreenath. Selenium Deficiency. StatPearls. May 6, 2019
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