More isn’t always better: Texas A&M research links high-dose antioxidants to offspring birth defects

(Press-News.org) Antioxidants have been marketed as miracle supplements, touted for preventing chronic diseases and cancers; treating COPD and dementia; and slowing aging.

While antioxidant therapies are widely used to treat male infertility, a new study from the Texas A&M College of Veterinary Medicine and Biomedical Sciences (VMBS) found that regularly consuming high doses of antioxidants negatively influences sperm DNA and may lead to offspring born with differences in craniofacial development.

In a study, published in the journal Frontiers in Cell and Developmental Biology, a team of researchers led by Dr. Michael Golding examined the effects of N-acetyl-L-cysteine (NAC) and selenium (Se) — two widely used antioxidants — in mouse models.

They found that offspring of male mice exposed to antioxidants for six weeks exhibited skull and facial shape differences, even while the father’s health didn’t change.

These findings suggest that men should exercise caution when consuming high doses of antioxidants, especially if they’re planning to have children in the near future.   

When good goes too far Antioxidants like NAC — which is a key ingredient in many nutritional supplements, including multivitamins — are often used to treat oxidative stress, which can be caused by excessive alcohol consumption.

Because Golding’s lab has been studying the effects of parental alcohol consumption on offspring — and has successfully correlated this consumption to a whole host of issues in children born to males who consumed excessive amounts of alcohol, including craniofacial abnormalities — his team was interested in the impacts of adding NAC or Se to a male mouse’s diet.

“We know alcohol causes oxidative stress and we were looking to push back on it by adding a supplement known to lower oxidative stress,” said Golding, a professor in the VMBS’ Department of Veterinary Physiology and Pharmacology. “When we realized that offspring born to males that had only been given NAC were displaying skull and facial differences, it was a surprise because this molecule is universally thought to be good.

“When we sat down to think it through, we realized that it makes sense — you take a multivitamin to ensure that you’re in balance, but if the thing that you’re taking to ensure you’re in balance is unbalanced (the dose of antioxidants is too high), then you’re not doing a good thing.”

It is well established that high doses of antioxidants can have negative impacts; research has proven that antioxidants can diminish the effects of exercise in endurance athletes, for example, and, in the case of professional athletes, can lead to negative outcomes in performance metrics.

“Sperm health is another performance metric; it’s just not one that we think about in everyday life,” Golding said. “If you’re taking a high dose antioxidant, you could be diminishing your reproductive fitness and part of the journey toward the bad outcome is going to be the effects on the offspring.”

What the face reveals about the brain Among their unanticipated findings was that female offspring, in particular, exhibited significantly closer-set eyes and smaller skulls, which are also symptoms of fetal alcohol syndrome.

“There’s a very commonly accepted truism in pediatric medicine that the face mirrors the brain, because the brain and the face form at the same time,” Golding said. “When your face migrates (during gestation), it’s using cues from your brain to know where to go, and if the two things are not aligned, there’s either a delay or some kind of abnormality in brain development.

“So, if you see abnormalities in the midline of the face, you’re probably going to see midline abnormalities in the brain,” he said. “People with these abnormalities typically have problems with impulse control, neurological conditions like epilepsy, and other developmental issues.”

Whether the offspring in this project will exhibit central nervous system dysfunction will require further study.

The dose makes the difference While the lab continues to research this “unexplored frontier,” Golding says in the case of antioxidants, too much of a good thing can, in fact, be too much, especially in the absence of a medical reason to take an antioxidant supplement.

Because many men regularly take high doses of these supplements — including products that contain antioxidant-rich ingredients — it’s important to pay attention to how much of these compounds are listed on the label. This includes NAC, which is one of the key ingredients in many multivitamins and is often found in high doses in these pills.

“The larger message here is that there’s a balance,” Golding said. “Think of yourself as a plant — if you stick your plant out in the sun too long, it’s going to get dehydrated. If you overwater your plant, it gets root rot. But if you have the right balance of sunshine and water, that’s when growth occurs. Health is in that domain.

“If your vitamins are providing 1,000% of the recommended daily amount, you should be cautious,” he said. “If you stick to the 100% range, then you should be OK.”

By Jennifer Gauntt, Texas A&M University College of Veterinary Medicine and Biomedical Sciences

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