The Fever Effect on Autism Triggers New Views on Treatment

A change that comes over autistic children when they have a fever has profound implications for the nature of disorder—and how to treat it
April 12, 2021 Updated: April 12, 2021

Autism currently affects about one in 68 kids in the United States. There are no drugs to treat the core symptoms, never mind the underlying disorder itself—and the disorder appears to be on the rise. But what can we do about it?

Decades ago, a clue was published. A study called Fever in Autistics was published in Nature and it offered a ray of hope: “When autistics have a moderate fever, they invariably display dramatically more normal behavioral patterns, including a greater desire or ability to communicate,” wrote researcher Rodney Cotterill in 1985.

They can become less withdrawn, more alert, more talkative, and more communicative. Ruth Sullivan, one of the early leading researchers, had noticed the same effect.

What makes this idea so groundbreaking—so earth-shattering—is that it challenges the whole presumption that autism is some kind of static, irreversible brain disorder, where the brain is inexorably damaged in some way with no hope of recovery. The fever glimpses suggest it may be more of a dynamic brain disorder, where the normal healthy circuits are in there somewhere but are actively being suppressed, and the fever somehow lifts that suppression and relieves the active disorder process. In this way, it suggests that if we could figure out what’s going on, we could theoretically relieve it for not just days, but for forever.

But the discovery did not have the effect one might have expected, though nearly everyone who is knowledgeable about the disorder—parents and professionals alike who deal with autism day-to-day—evidently knows about it.

Part of the problem with researching the phenomena is the risk it poses to children with autism. Inducing fever can be dangerous, which means there are limited opportunities to study it, though other researchers did just that in an earlier era.

In fact, the first (and only) Nobel Prize for Medicine ever given to a psychiatrist for brain ailments went to the “father of fever therapy,” Julius Wagner-Jauregg in 1927, for his work treating people with paralytic dementia, a severe neuropsychiatric disorder, by injecting them with malaria. Some got better—if they didn’t die first from the malaria, that is. What is it about fever that can improve brain function? And, can we figure that out without killing people?

A 2007 study published in Pediatrics tried to do something along those lines by asking parents to fill out an aberrant behavior checklist during and after an incident of fever.

“The rapid behavioral changes reported during fever” in autism suggest that those neural networks in autism may still be intact, just dysfunctional, “and understanding the reasons for improvement during fever might provide insight” into what’s going on, reported the researchers. The “fever effect” in autism had been based on case reports and anecdotes until researchers undertook this formal study of the reported phenomenon, “given the … potential implications for treatment opportunities.”

But how it works remains a mystery and difficult to safely induce. While some of the completely unrelated healing effects of fever have been researched and induced by sitting in a hot tub or sauna, the same isn’t true with those related to the brain. That’s because the brain has special cooling mechanisms so it stays about the same temperature inside no matter what temperature it is outside, which is a good thing. This is the reason we can bite into a snow cone without literally getting brain freeze. When you get a fever, though, your internal thermostat gets turned up to fight infection, and there is actually an increase in brain tissue temperature.

Your brain has to be careful not to cook itself to death, so it releases heat shock proteins. As your brain turns up the heat to give you a fever, these proteins prevent and repair protein damage. At higher temperatures, proteins can start unraveling, which is known as protein denaturing. That’s what happens when you cook egg whites—the proteins denature—but that’s not what you want happening in your head.

What does this have to do with autism?

One of the causes of autism may be the dysregulation of synaptic function, meaning a dysregulation of the nerve-to-nerve signaling pathways in the brain. This dysregulation may play a key role in the cause of autism spectrum disorders. Well, guess what those heat shock proteins do: They protect and sustain synaptic function. Given that, the next question is whether there is any way to activate the heat shock response without having to get a high fever infection. This prompted an article published in the Journal of Neuroscience Research in 2016 that looked at foods that trigger similar biochemical reactions.

Sulforaphane, the active ingredient in cruciferous vegetables such as broccoli, kale, and collard greens, activates the heat shock response. No malaria necessary! So, in theory, according to the review, giving sulforaphane in the form of broccoli or broccoli sprouts to those with autism might reap the same kind of fever-related benefits in function.

That is a fascinating and important line of research and one we will talk about in the next part of this three-part series.

Michael Greger, M.D., FACLM, is a physician, New York Times bestselling author, and internationally recognized professional speaker on a number of important public health issues. He has lectured at the Conference on World Affairs, the National Institutes of Health, and the International Bird Flu Summit, testified before Congress, appeared on “The Dr. Oz Show” and “The Colbert Report,” and was invited as an expert witness in defense of Oprah Winfrey at the infamous “meat defamation” trial. This article was originally published on NutritionFacts.org.