Are there long-terms health risks to using Botox?

A safe and sure-fire way to smooth wrinkles and fine lines? Or a toxin that fixes your features into a permanent "frozen" expression? Either way, Botox is big business.

Botox (a brand name for the botulinum neurotoxin) is the most common cosmetic procedure performed worldwide, with nearly three million injections estimated to take place each year. Originally derived from a potent neurotoxin produced by bacteria, it works by blocking signals from the nerves that control the facial muscles. The muscles relax, and fine lines and wrinkles disappear. The result? A more youthful visage – for three to four months, at least.

It's "widely viewed as safe, effective and largely devoid of serious side effects". But is this reputation justified?

Most reported side effects are minor and fleeting. They include pain, swelling or mild bruising at the injection site, and a headache and flu-like symptoms for the first 24 hours. Temporary weakness and droopiness in the face can also sometimes occur.

However, more serious reactions have sometimes been observed. In April 2024, The US Center for Disease Control and Prevention (CDC) released an alert warning that 22 women between the ages of 25 and 59 had recently reported "harmful reactions" to counterfeit or mishandled Botox.

Eleven people were hospitalised, and six were treated with an antitoxin because of concerns of botulism – a condition where the toxin spreads beyond the local site and attacks the central nervous system causing muscle paralysis, difficulty breathing, and even death.

Reported symptoms included blurry and double vision, drooping eyelids, difficulty swallowing, slurred speech, difficulty breathing, fatigue, and weakness. All 22 cases took place after the women received Botox injections from unlicensed or untrained people in places that were not healthcare settings.

"The CDC, FDA [Federal Drug Administration], and jurisdictional partners are actively investigating these illnesses that happened after injection with mishandled or counterfeit botulinum toxin," says Michelle Waltenburg, an epidemiologist with CDC's Epidemic Diseases Epidemiology Branch.

The problem we've had is that there are dodgy counterfeit versions in circulation – Ash Mosahebi

In 2023, 67 Botulism cases in the UK were traced back to weight loss Botox injections given from a private hospital in Izmir, Turkey.

But how common are adverse effects like these?

"If the botulinum toxin is manufactured properly and comes from a good brand, the strength is such that even if it spreads a little bit, it doesn't cause a huge amount of side effects," says Ash Mosahebi, professor of plastic surgery at University College London.

"The dosage is extremely low. That amount of toxin cannot give botulism to people. However, the problem we've had is that there are dodgy counterfeit versions in circulation. They are poorly made and manufactured, and not well controlled."

What is Botox?

Botulinum neurotoxins are extremely lethal poisons produced by the bacteria Clostridium botulinum. They enter neurons and bind to the vesicles that carry the neurotransmitter acetylcholine (Ach), preventing its release.

As Ach causes muscles to contract, Botulinum toxins cause muscular paralysis. There are seven distinct forms of botulinum toxin, types A-G.

Botulinum toxin A, the most potent, is a million times more toxic than cobra toxin, and more poisonous than cyanide. Botox treatments use the purified and heavily diluted botulinum neurotoxin type A.

So counterfeit Botox is bad news. But what about the safety of regular botulinum toxin? A 2020 study reviewed the safety of cosmetic Botox injections, and concluded that reports of serious side effects such as those seen by the CDC were rare. For example, between 2002-03 only 36 serious adverse effects were reported to the FDA relating to cosmetic use, with the majority concerning difficulty swallowing. The risk of serious adverse effects was 33 times higher for therapeutic uses of Botox than for cosmetic cases (Botox is sometimes used to treat migraines, neck spasms, sweating, overactive bladder, lazy eye and other conditions).

However, it could be that adverse reactions are simply not being reported. A 2023 study by Mosahebi and colleagues at UCL found that 69% of respondents to a survey had experienced long-lasting adverse effects, such as pain, anxiety and headaches from Botox. There were also serious psychological and emotional consequences for patients when procedures went wrong.

"If administered incorrectly you can have a kind of drooping of your eyelids, and that can last for six months," says Mosahebi.

"It can lead to embarrassment at work and impact your confidence in a way that is potentially long lasting."

Long-term effects

Very little is known about the long-term health effects of taking Botox, as most clinical trials only follow up on patients for six months or so. However some studies have found that long-lasting cosmetic use of botulinum toxin can trigger permanent changes in facial expression, with persons no longer able to flex their facial muscles. A 2022 review study found that people who regularly received Botox injections showed changes in their muscle composition, function, and appearance up to four years after their last injection.

Some transported toxins escaped into other neurons via an unknown mechanism

"If you didn't use your abs [abdominal muscles] for 10 years, they would waste away," says Mosahebi.

"So in a similar way, if the muscle that causes the creasing of your face doesn't get used, or is paralysed with Botox, after a while it's not as strong as before, so you have less of an expression."

It's even possible that the Botox toxin could escape its location in the nerve terminal close to the muscle and travel into the wider central nervous system. In 2015, scientists led by Frederic Meunier at the University of Queensland in Australia used cutting-edge microscopes to view single molecules of botulinum toxin travelling at high speed along rat neurons (nerve cells). Previously, it was thought that the botulinum toxin would remain in the nerve terminal part of the neuron – where neurotransmitter release occurs – before being degraded. However, this wasn't the case.

"We watched a few of the toxin molecules enter the nerve terminal, and be transported along the axon all the way back to the cell body for degradation." says Meunier.

Some transported toxins escaped into other neurons via an unknown mechanism.

"The only other toxin that we know can do this is the tetanus toxin, which can travel all the way along motor neurons, up to the spinal cord and block transmission there," says Meunier.

It's important to note, however, that the concentrations of botulinum toxin that were used in the study were much higher than would ever be used in Botox injections, Meunier adds.

"In humans, I think the idea of this [the toxin] going all the way back to the central nervous system and having an effect there is unlikely."

Yet there is some evidence that long-term Botox use could have a psychological impact on patients. In a 2023 study, Mitchell Brin, a neurologist at the University of California, Irvine, and colleagues scanned the brains of 10 women before and after they received Botox injections. During the functional magnetic resonance imaging of their brains, the subjects were shown photos of angry and happy faces interspersed with neutral photos. On the post-Botox scan, the women showed altered activity in two regions of the brain known to play a role in processing emotion: the amygdala and fusiform gyrus.

Receiving Botox injections can make it harder to recognise and process the emotions of others

This fits the findings of other studies, which have shown that receiving Botox injections can make it harder to recognise and process the emotions of others.

According to Brin, the explanation could be down to how our brains recognise other people's emotions. For example, when we see expressions of happiness or sadness in others, we unconsciously copy them using our own facial muscles. This helps us understand and interpret how others are feeling.

But because Botox paralyses facial muscles, we can no longer mimic other people's faces, potentially making us less empathetic.

This effect can, in some instances, have a more positive effect; other research has found that an inability to frown may help patients suffering from depression.

So what can people do to minimise the risks of taking Botox? First, people should only get Botox injections from licensed providers who are trained in how to administer it, and ideally in a healthcare setting.

Allergan Aesthetics, the makers of Botox, said in a statement to BBC Future that users should ensure they only undergo procedures with a licensed medical professional.

A spokesperson for the company added: "Our priority is the health and safety of patients and all reports of counterfeit product are thoroughly investigated by our team and in conjunction with law enforcement and regulatory authorities.

"We have a rigorous and sophisticated manufacturing and distribution process to ensure product quality and authenticity, including stringent anti-counterfeit features."

Mosahebi recently conducted an analysis of the UK's cosmetic injectables industry, and found that 68% of cosmetic practitioners who administer injections such as Botox are not medical doctors.

IBut if administered correctly, there's every reason to think that Botox is largely safe.

"It's really widely used, and the safety profile is excellent," says Meunier.

"There have been some people who have had adverse effects, but you have to put that into the context of the millions of people who have taken this toxin since the 1980s and 90s."

-bbc