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The Forgotten Man: Male Infertility and Its Causes

The Forgotten Man: Male Infertility and Its Causes

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Can antioxidants improve male fertility?

Infertility affects one in six couples, and it can be a devastating experience for those who wish to conceive.[1]

Half of all infertility cases are due to male factors,[2],[3],[4] yet men have been largely forgotten when it comes to the treatment of infertility.[1],[5] With the development of assisted reproductive technologies, the treatment burden for male and unexplained infertility has fallen mainly on women.[5]

Male infertility can be a result of genetic, hormonal, or anatomical abnormalities, such as varicocele (an enlargement of veins in the scrotum, which can be surgically corrected).

However, the majority of male infertility cases are caused by poor semen quality: inadequate sperm numbers, too many dead sperm, and/or sperm with low motility (that can’t swim).[6]

Sperm quality has declined over the past 40 years, by some accounts as much as 50%.

Some rather alarming statistics reveal that sperm quality has declined over the past 40 years, by some accounts as much as 50%.[3],[7],[8] Unhealthy lifestyles and increased pollution are considered to be the main causes of this decline.[9],[10],[11]

Environmental toxins such as bisphenol A (BPA) are implicated in declining sperm quality,[12],[13] as are smoking, alcohol consumption, psychological stress, obesity, unhealthy diets, and aging.[14],[15],[16]

What do these factors have in common? They all are associated with oxidative stress, a hidden condition that accounts for a high percentage of male infertility cases.[17],[18],[19]

Oxidative stress causes male infertility

In couples planning a pregnancy without knowing whether they are fertile, oxidative stress could cause them to take longer to conceive, and it may reduce the chance of a successful pregnancy.

Oxidative stress is caused by an excess of reactive oxygen species (ROS), a byproduct of normal metabolism. Low levels of ROS are needed for everyday functions, but if the levels of ROS get too high, they can damage sperm.[20]

Cells have developed antioxidant pathways to scavenge any excess ROS, in order to prevent harmful effects. In men who are fertile, ROS production and total antioxidant capacity are generally more in balance.

If ROS levels in sperm exceed antioxidant capacity, however, debilitating oxidative stress ensues.[21],[22] When this happens, the sperm DNA actually breaks into pieces (this is called DNA fragmentation), either inactivating sperm or causing them to die.[3],[17],[22],[23],[24] It’s not surprising that this damage contributes to infertility.[20],[24],[25],[26],[27],[28]

Additionally, DNA fragmentation is a major contributor to miscarriage – spouses of men who had more sperm DNA fragmentation were shown to have a higher chance of spontaneous miscarriage, compared to a control group.[29]

Importantly, 15% of men with normal-appearing semen may have oxidative stress without knowing it.[30],[31],[32] In couples planning a pregnancy without knowing whether they are fertile, oxidative stress could cause them to take longer to conceive, and it may reduce the chance of a successful pregnancy.[32],[33]

The good news is that lifestyle modifications (such as stopping smoking), a better diet, and antioxidant supplementation may help to correct this condition.[19],[34] Let’s look at the evidence.

Effects of dietary antioxidants on male fertility

In addition to a healthy diet, antioxidant supplementation may improve a couple’s chances of conception.

Balanced diets that focus on vegetables, fruits, nuts, legumes and whole grains, along with fish and low-fat dairy products, are associated with greater antioxidant intakes and better semen quality.[9],[10],[34],[35],[36],[37],[38],[39] For example, men who follow the Mediterranean diet, which emphasizes these healthy food groups, tend to have better semen quality than those consuming a typical Western diet.[40]

Healthy diets provide a variety of nutrients, including vitamins and minerals and countless phytonutrients that support the body’s total antioxidant capacity. These include vitamins C, E, and B complex, and trace elements such as zinc and selenium.[9],[35],[41] A deficiency of any one of these vitamins or minerals can impair fertility.[34],[42],[43]

When diets are inadequate (as they commonly are), supplementation with these vitamins and minerals may help reduce DNA fragmentation in sperm.[44] A study of healthy men, for example, found that those with the highest intakes of vitamin C had approximately 16% less sperm DNA damage than men with the lowest intake, with similar findings for vitamin E, folate, and zinc.[45]

Many specialists believe that, in addition to a healthy diet, antioxidant supplementation may improve a couple’s chances of conception.[24],[28],[46],[47],[48] Nearly every food-derived antioxidant that has been tested has some beneficial effect on sperm quality, at least in laboratory studies – including grape polyphenols,[49] alpha-lipoic acid,[50] resveratrol,[51] quercetin,[52] and naringin.[53],[54]

When it comes to supporting fertility, however, two antioxidants really stand out: melatonin and coenzyme Q10 (CoQ10). Current studies indicate that these natural products may be helpful for both male and female fertility.

Melatonin and male fertility

In couples undergoing IVF, melatonin supplementation of the male partners improved sperm quality and the quality of the embryos that were retrieved from the couples.

Melatonin is synthesized from tryptophan within the pineal gland, and it regulates the sleep-wake cycle.[55] It also is found in some foods, such as tomatoes, olives, walnuts, and sweet cherry.[56],[57],[58]

Most people are familiar with melatonin as a sleep aid, but it is also an antioxidant that plays an important role in reproduction.[59],[60],[61],[62] It has been used commercially, for example, to improve fertility in livestock.[63],[64]

In humans, sleep is triggered by a rise in melatonin production, which begins in the evening, reaching a peak around 2 to 4 a.m. Exposure to light from media devices disrupts sleep, decreases melatonin levels, and decreases sperm quality.[65],[66],[67],[68] So, to improve fertility, men should start by getting a good night’s sleep and avoid using media devices at night!

Men who are fertile tend to have higher blood and semen melatonin levels, on average, than those who are infertile.[66],[69] Higher levels of sperm melatonin are associated with greater sperm motility and fertilization success, which is relevant both for natural conception and for in vitro fertilization (IVF).[70],[71]

Importantly, melatonin has been shown to protect sperm from oxidative stress and DNA fragmentation, at least in laboratory studies.[72],[73],[74] The addition of melatonin to semen improves sperm viability, motility, and subsequent embryo development.[75],[76]

Melatonin and fertility

Melatonin also protects sperm against the damage caused by environmental pollutants, including bisphenol A (BPA),[77] heavy metals (cadmium, mercury, and lead),[78],[79],[80] and pesticides (diazinon and others).[81],[82]

Oral melatonin supplementation has been shown to increase melatonin levels in human testes, and to decrease oxidative stress-related markers.[83] In a study of couples undergoing IVF, melatonin supplementation of the male partners (6 mg melatonin daily for 45 days or more) improved sperm quality and the quality of the embryos that were retrieved from the couples.[74]

Although further studies are needed, the evidence points to melatonin as a supplement that can ameliorate oxidative stress and perhaps improve fertility, both for natural pregnancy and for IVF.

CoQ10 and male fertility

In a study of infertile men, CoQ10 supplementation improved sperm quantity and motility by 114% and 79%, respectively.

Coenzyme Q10 (CoQ10) is an antioxidant that is synthesized in the body from the amino acid tyrosine. CoQ10 is also present at low levels in meat, fish, nuts, and some oils.[84],[85]

You may be familiar with the use of CoQ10 (ubiquinol) for heart health,[86] but it also plays an important role in reproduction. CoQ10 is lipid-soluble, which means that it helps protect sperm membrane lipids against oxidative stress, thereby keeping sperm viable.[87]

Also important is the fact that CoQ10 supports energy production in mitochondria, the powerhouses within cells.[88] Fertilization requires a lot of energy, because sperm must swim long distances through the thick, sticky fluid of the female reproductive tract to reach the egg.[89] When lackluster human sperm were bathed in a CoQ10-enriched medium, their swimming ability improved.[90],[91],[92]

Semen CoQ10 concentrations are significantly correlated with sperm numbers and motility.[93] Several clinical trials have shown that supplemental CoQ10 (200 to 600 mg daily for three to six months) can raise CoQ10 levels in semen and improve sperm quality.[94],[95],[96],[97]

In men with unexplained infertility, CoQ10 supplementation (200 or 400 mg per day) was shown to improve sperm concentration and motility, with a slightly greater improvement at the higher dose.[98] The 400 mg daily dose was associated with a 50% increase in sperm concentration and total motility. In another study of infertile men, CoQ10 supplementation (300 mg twice daily for 12 months) improved sperm quantity and motility by 114% and 79%, respectively.[96]

If you choose to supplement with antioxidants, keep in mind that the goal is to restore physiological balance and not to eliminate ROS totally. In other words, more is not necessarily better. Scientists agree that massive antioxidant doses are not needed, and they may even be counterproductive.[99]

Summing up

If infertility is a concern, hope may be on the horizon. Consult a qualified health professional to rule out any underlying conditions in either partner, including varicocele in men. Consider lifestyle modifications, such as cessation of cigarette smoking, improving one’s diet, reducing stress, and getting a good night’s sleep, all of which are important for healthy sperm (and many other facets of life!). For antioxidant supplementation, the evidence to date favors melatonin and CoQ10, which can be combined with multivitamin and mineral supplementation to alleviate any nutrient deficiencies.

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