Oxidative stress is a biological mechanism that plays a big role in male fertility. A 2019 review in the Journal of Human Reproductive Sciences found that oxidative stress is linked to reduced sperm motility, increased sperm DNA damage, and an increased risk of miscarriage and genetic disease. This article will explore oxidative stress, how it can affect male fertility, and what you can do to reduce oxidative stress.

Key takeaways

• Oxidative stress is caused by too-high levels of free radicals, compared to antioxidants. Free radicals are produced as a natural byproduct of metabolism, and can be increased by poor lifestyle, illness, or toxin exposure.
• Oxidative stress can damage the membrane of sperm, affecting sperm motility, morphology, and DNA fragmentation. Some tests can directly measure oxidative stress in semen, but they’re not commonly use.
• Oxidative stress can be reduced by increasing antioxidant intake, treating infections and medical issues, and avoiding exogenous sources of stress (like smoking and poor diet).

Oxidative stress terms to understand

Before we delve into what oxidative stress is and how oxidative stress can affect male fertility, there are a few terms that are helpful to understand: Free radicals, reactive oxygen species (ROS), and antioxidants.

Free radicals

Free radicals are unstable molecules with unpaired electrons. Free radicals are produced by a number of natural body processes, including metabolism, and can be increased by exposure to radiation or pollution, smoking, or illness.

Free radicals can cause damage by “stealing” electrons from other cells. This damage can contribute to many diseases.

Reactive oxygen species (ROS)

ROS are a type of free radical that contains oxygen. Like other free radicals, they can cause cell injury.

Antioxidants

Antioxidants are nutrients that prevent or slow cellular damage caused by free radicals. Antioxidants lend an electron to free radicals, thereby neutralizing and stabilizing them. Examples of antioxidant nutrients include vitamin C, vitamin E, and CoQ10.

What is oxidative stress?

Free radicals are inevitable, since they’re a natural byproduct of human life. Ideally, free radicals can be neutralized by antioxidants before they can cause real damage to your cells.

When there are too many free radicals in your body and not enough antioxidants, the free radicals can begin to damage your DNA, proteins, and lipids (fatty tissue). This is oxidative stress.

Scientists define oxidative stress as “an excess production of reactive oxygen species (ROS) relative to antioxidant defense.” Essentially, this means your body has an imbalance between free radicals and antioxidants. In other words, the ratio of free radicals is too high, and the antioxidants can’t keep up.

Reactive oxygen species aren’t all bad. Free radicals can actually help fight off pathogens that may lead to infection. However, the issue comes when there is long-term exposure to oxidative stress. This can lead to problems such as:

• diabetes
• cardiovascular problems like heart disease, hardening of the blood vessels, and high blood pressure
• inflammatory conditions
• Parkinson’s disease
• Alzheimer’s disease
• various types of cancer
• fertility issues

Oxidative stress also contributes to signs of aging.

How does oxidative stress affect male fertility?

One of the cells that oxidative stress can damage: Sperm cells.

Research tells us that oxidative stress significantly impacts male fertility and has harmful effects on sperm, including DNA damage.

Reactive oxygen species can negatively impact sperm cell membranes, which contain a high concentration of unsaturated fatty acids. ROS can cause a process called “peroxidation of lipids,” in which free radicals steal electrons from the lipids in cell membranes, leading to cell damage.

Signs of oxidative stress in semen

Common indicators of oxidative stress on a semen analysis include:

• Poor sperm motility (asthenozoospermia)
• Poor sperm morphology (teratozoospermia)
• High number of round cells, including leukocytes (white blood cells), which could be a sign of infection
• Increased sperm DNA damage on a DNA fragmentation analysis

However, a number of other issues could also be contributing to these results. What are the specific signs of oxidative stress we can test in the semen?

• ROS levels in the semen. Specialized lab tests can identify the quantity of reactive oxygen species in the semen. However, further research is still necessary to understand what “normal” ROS levels look like.
• Total antioxidant capacity (TAC) in the semen. Measuring the levels of certain antioxidants in the semen can give an idea of how well the body is protected against oxidative stress, especially when weighed alongside ROS levels.
• MDA levels in the semen. MDA, or malondialdehyde, is an organic compound that’s considered a biological marker for oxidative stress. Specialized tests can detect MDA levels in the semen, which are typically elevated in infertile people with excess ROS production.

Lower measures of TAC and higher levels of ROS and MDA in the semen have consistently been correlated with poorer semen parameters and fertility outcomes.

For example, one study of 42 semen samples found that, on average, samples with low sperm motility, count, and morphology had 40% lower measures of total antioxidant capacity, compared to healthy samples. The MDA levels in the unhealthy samples, on the other hand, were about 56% higher than the levels in healthy samples. Several other small studies have made similar observations.

Oxidative stress plays an independent role in the cause of male infertility, with 30% to 80% of infertile men showing elevated ROS levels in their semen. However, we’re not yet at the point where ROS, TAC, or MDA are common tests for male fertility. While many experts are pushing for these tests to become more mainstream, there is still work to be done to establish a reference range for normal measures.

For now, many doctors may use semen analysis and DNA fragmentation results along with lifestyle, exposure, and medical history to assess whether oxidative stress may be affecting male fertility. Reducing oxidative stress can be a useful treatment strategy for male infertility.

What causes oxidative stress?

Oxidative stress is caused by the imbalance between the reactive oxygen species (ROS) and antioxidants in the semen. “Oxidative stress can result from either exogenous or endogenous factors that will eventually put pressure on the sperm quality and quantity,” explains Dr. Ramy Abou Ghayda, fellowship-trained urologist and chief medical officer at Legacy. 

“Endogenous” means internal factors, like a medical condition, such as varicocele, or hormonal abnormality. “Exogenous” means external factors, such as lifestyle or environmental exposure like smoking or pollution.

According to Dr. Ghayda, both of these factors can cause an increase in oxidative stress. “This will eventually and subsequently lead to lower semen parameters and might be associated with an abnormal success rate for fertility, whether through natural or assisted reproductive techniques,” he discusses.

Exogenous causes are a little more within our control, and include:

• poor diet and obesity
• smoking
• drinking alcohol
• taking certain medicines
• exposure to environmental factors such as radiation, toxins, air pollution, and pesticides

How to reduce oxidative stress

Dr. Ghayda discusses there are three ways to help reduce oxidative stress:

1. Try to avoid exposure to exogenous factors.
   • If you’re smoking, engage in a smoking cessation program and try to quit.
   • Consider wearing a mask in areas with high levels of air pollution.
   • Improve your diet. Include a lot of greens, avoid added sugars and trans fat, and reduce the number of processed foods you eat. Try the Mediterranean diet.
   • Wear sunscreen.
   • Make sure to speak with your healthcare provider to understand if any medications you’re taking might negatively impact fertility.
   • Getting a good night’s sleep is also essential, as chronic sleep loss can lead to oxidative stress. 

2. Seek medical help to try to treat any underlying endogenous causes. For example, if you have a varicocele causing oxidative stress and affecting fertility, a varicocelectomy (varicocele repair surgery) can correct the problem.

3. Consider consumption of antioxidants. Look for reputable, high-quality vitamins like coenzyme Q10 (which has the strongest evidence and research studies behind it), vitamin C, or vitamin E. You can also increase antioxidants in your diet by eating foods such as blueberries, strawberries, raspberries, kale, spinach, beets, and beans.

Other ways to improve fertility

Many general ways to help improve male fertility will also help reduce oxidative stress. Here are our top ten ways to boost fertility:

1. Quit smoking.
2. Avoid recreational drug use.
3. Try a healthy Mediterranean diet.
4. Aim for 7–9 hours of good quality sleep.
5. Keep your alcohol consumption to fewer than five drinks a week.
6. Try a male fertility supplement.
7. Avoid overheating your scrotum — reduce wearing tight underwear, sitting in hot tubs, putting your laptop directly on your lap, or cycling for long periods.
8. Get regular, moderate, exercise.
9. Minimize stress levels.

Learn more about improving sperm health.

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