Isn’t it crazy to think of all the different kinds of foods so many of us eat every day? Chips, cookies, burgers, fries. Our bodies dutifully process whatever it is we choose to swallow – regardless of whether or not what we eat could actually harm us or shorten our lives. Our bodies are amazing as they try and pull out nutrients while trying to protect us from all the garbage. So – maybe – just maybe – we should try and give our bodies a break.
I’m Dr. Michael Greger and you’re listening to the Nutrition Facts podcast. I’m here to tell you that nutrition matters. We could choose a diet proven to not only prevent and treat but reverse our #1 killer, heart disease, along with other deadly diseases such as type 2 diabetes and high blood pressure. But many of us – don’t make that choice.
Our goal today is to help you make that choice – and present you with the results of the latest in peer-reviewed nutrition and health research, presented in a way that’s easy to understand.
Today, we’re going to look at Autism – the neurodevelopmental disorder characterized by impaired social interaction, impaired verbal and nonverbal communication, and restricted and repetitive behavior.
Research has shown dramatic improvements in autistic children when they get a fever. This suggests that the condition may be reversible if one could replicate the phenomenon in other ways.
Autism currently affects about 1 of 68 kids in the United States, yet we don’t even have drugs to treat the core symptoms—forget the underlying disease itself. I mean, we can treat some symptoms, just not the core symptoms of the disorder. Sure, if you’re aggressive, we can give you antipsychotic drugs—stimulants like Ritalin for ADHD—or, we can knock you out to help you sleep. But, for “social and communication” improvements—”the main signs and symptoms” of autism—we have little to offer, and the disease appears to be on the rise. What can we do about it?
Well, decades ago, a clue was published that offered a ray of hope. When autistic kids get a fever, “they invariably display dramatically more normal [behavior], including a greater desire or ability to communicate.” They can become less withdrawn, more alert, more talkative, more communicative. All hospital staff members working with autistic children “noted [the] marked behavioral [improvements].” But, as soon as the fever stopped, they went back to their baseline. So, you think, wow, if we could figure out what’s going on, maybe we could develop some sort of treatment. Yeah, but wait a second. Let’s take a step back, and realize what this could mean.
What makes this so groundbreaking, so earth-shattering, is that this challenges the whole presumption that autism is some kind of static, irreversible brain disease, where the brain is just inexorably damaged in some way, with no hope of recovery. But, the fever glimpses suggest no, it may be more of a dynamic brain disease, where the normal healthy circuits are in there somewhere, but being actively suppressed, and the fever somehow lifts that suppression, relieves the active disease process—suggesting if we could figure out what’s going on, we could theoretically relieve it not just for days, but for forever.
So, you’d think that would be what’s on every autism researcher’s mind. But unbelievably, “there is practically no mention of the high fever/improved behavior phenomenon in the entire autism [medical] literature,” even though nearly everybody “knowledgeable” about the disease—”both parent and professional” alike, who deals with it day to day—evidently knows about it. In fact, the first—and only—Nobel prize in medicine ever given to a psychiatrist for brain ailments was the so-called “father of fever therapy,” where he would inject malaria into people, and some got better, if they didn’t die first from the malaria, that is. What is it about fever that can improve brain function? If we could figure that out, maybe there’s a way we could do it without killing people.
Okay, but first, let’s confirm the phenomenon is real. Yes, 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.
But, this whole fever effect in autism was “based on case reports and anecdotes,”. “Given the potential implications…for treatment opportunities, [they] undertook a formal study of [the reported phenomenon].” And indeed, autistic children got better when they got a fever, officially documenting the phenomenon as real. Okay, so, full-steam ahead; let’s figure it out.
Who cares how it works, though? I mean, I know you can’t give kids malaria, but why not just take them to a sauna or hot tub, or something? Because it doesn’t work. When you sit in a sauna or hot tub, your skin gets hotter, but your brain pretty much stays the same temperature. It’s got special cooling mechanisms. So, no matter what temperature it is outside, your brain stays pretty much the same temperature inside. That’s a good thing; that way, you can bite into a snow cone without literally getting brain freeze. But, when you get a fever, your internal thermostat gets turned up to fight infection, and there is actually an increase in brain tissue temperature.
Now, 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, it releases heat shock proteins to prevent and repair protein damage. At higher temperatures, proteins can start unraveling—what’s called protein denaturing. That’s what happens when you cook egg whites; the proteins denature. That’s not what you want happening in your head. Okay, but what does this have to do with autism?
Well, 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 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. Okay. So now, the question becomes: is there any way to activate the heat shock response without having to get some high-fever infection?
Well, as you can imagine, “[t]here is now strong interest [among drug companies in] discovering and developing pharmacological agents capable of inducing the heat shock response.” But, broccoli beat them to it. Sulforaphane, the active ingredient in cruciferous vegetables—cabbage family vegetables like broccoli, kale, and collard greens—activates the heat shock response; no malaria necessary. So, in theory, giving those with autism sulforaphane in the form of broccoli, or broccoli sprouts, might reap the same kind of fever-related benefits in function.
At this point, you’d expect me to make some crack about Big Broccoli, and how such a study would never get funded, and you’d be right…until now. See, there are family foundations out there, non-profit foundations that just want to see people with autism get better, whether or not corporate stock prices get better, too. We’ll find out what happened, next.
One food may be able to combat all four purported causal factors of autism: synaptic dysfunction, oxidative stress, mitochondrial dysfunction, and neuroinflammation. Here’s the story.
Harvard neurologist, Martha Herbert, in a keynote address at an autism conference, said “we need to conduct research as if we know this is an emergency.” Already, up to one and a half percent of American children have autism, and it appears to be on the rise. Well, what about fever’s dramatic effect? This “dramatic relief of autistic behavior [during a fever] continues to tantalize parents and practitioners.” From a research standpoint, “what could be more revealing than a common event that virtually ‘normalizes’ autistic behavior for a time?” “There’s so much going on during fever,” though; where do you even begin?
Well, once it became understood that one cause of autism may reside in the synapses—the so-called “soul of the brain,” the nerve-to-nerve junctions where information is transmitted—attention turned to HSPs, heat shock proteins, released by the brain when you have a fever, that can improve synaptic transmission, and thus, may be “capable of improving long-range [brain] connectivity which is depressed in [autism].” ASD stands for autism spectrum disorder. And, there’s this compound, sulforaphane, that “upregulates” those heat shock proteins. So, you could potentially get the benefits without the fever. What drug company makes it? What do I ask for at the pharmacy? Nope, wrong aisle.
Sulforaphane is not made in chemical plant; it’s made by a plant. Sulforaphane is made by broccoli, kale, cabbage, collards, and cauliflower—in other words, cruciferous vegetables. So, maybe if we give some broccoli to those with autism, it will make things better by boosting the heat shock proteins.
But, synaptic dysfunction is not the only contributing cause of autism. There’s also oxidative stress. “The brain is particularly vulnerable to oxidative stress” because lots of free radicals are forged in the brain, which has few “antioxidant defense capacities.” And, indeed, “[t]here is a long history of studies showing that [autism] is associated with oxidative stress and diminished antioxidant capacity.” Nrf2 levels cut nearly in half, which is what triggers our body’s “antioxidant response.” If only there was a way we could boost Nrf2 with foods—boom! Sulforaphane just so happens to be perhaps “the most potent natural…inducer…of Nrf2” on the planet.
What’s this Nrf2 thing again? It’s “considered to be a master regulator of” our body’s response to environmental stressors. Under any kind of stress—oxidative stress, inflammatory stress—Nrf2 triggers our “antioxidant response elements,” activating all sorts of cell-protective genes that balance out and detoxify the free radicals, and facilitate protein and DNA repair.
So, maybe if we give some broccoli to those with autism, it will also make things better by triggering Nrf2, which activates those antioxidant response elements.
And then, there’s the mitochondrial dysfunction. “[C]hildren with autism [are] more likely to” suffer from dysfunctional mitochondria, the little power plants within our cells where metabolism takes place. If only there was some food that could improve mitochondrial function. And, there is. “A diet rich in cruciferous vegetables effectively retunes our metabolism by…restoring metabolic [balance].” Power plants for our cellular power plants.
Not only can sulforaphane boost the gene expression of heat shock proteins as much as six-fold within six hours, it can double the mass of mitochondria in human cells growing in a Petri dish. So, maybe if we give some broccoli to those with autism, it will also make things better by relieving some of that mitochondrial dysfunction that is creating even more free radicals. Okay. So, can we try giving some kids some broccoli already?
First, one final factor: neuroinflammation—brain inflammation, another causal factor in autism. If, at autopsy, you look at brain tissue of those with autism, you can see inflammation throughout the white matter. And, if you do a spinal tap, up to 200 times the levels of inflammatory mediators, like interferon, bathing their brains. What’s causing all that inflammation? Well, the master regulator of the inflammatory cascade is a protein called NF-kappa-beta, which induces inflammation and, if overexpressed, like in autism, can lead to “chronic or excessive inflammation.” If only there was a food. Wait—broccoli does that, too? In fact, it’s the major anti-inflammatory mechanism for sulforaphane, inhibiting NF-kappa-beta.
Well, then; that completes the picture. Give someone with autism broccoli, heat shock proteins are released to boost synaptic transmission, Nrf2 is activated to wipe out the free radicals, mitochondrial function is restored, and we suppress the inflammation triggered by NF-kappa-beta. One food to rule them all! One food to counter all four purported causal factors. That’s one of the differences between foods and drugs. Drugs tend to have single effects. But, autism spectrum disorder, ASD, “is multi-factorial”—no wonder there’s no drugs that work. But, “strategies using multi-functional phytochemicals [like sulforaphane] or even [better] the [whole] plants [themselves],…are highly attractive”—in theory. But, you don’t know, until you put it to the test, which I promise we’ll cover, next.
In a randomized, double-blind, placebo-controlled trial, the sulforaphane found in five cents’ worth of broccoli sprouts was found to benefit autism in a way no drug ever has.
You may remember my series of videos about the engine-of-aging enzyme, TOR. Well, kids with autism tend to have higher TOR activity in their bodies, and this “hyperactive…TOR…signaling” may actually play a role in causing autism, making TOR a potential target to treat autism—or even theoretically reverse it, if we could target downstream TOR signaling, like between TOR and S6K1. Well, that’s actually one of the ways broccoli compounds kill off prostate cancer cells—by inhibiting the “signal transduction between…TOR and S6K1.” Breast cancer too; sulforaphane is “a potent inhibitor” of breast cancer cells, because “it targets downstream elements of the [TOR] pathway.”
So, if we gave broccoli to those with autism, if it blocks TOR, maybe it would block some of the synaptic dysfunction that contributes to the features of autism. And, that’s in addition to blocking autism pathways four other ways: “oxidative stress and lower antioxidant capacity, [the] mitochondrial dysfunction,” the brain inflammation. And, not just in a Petri dish: “sulforaphane can cross the blood-brain-barrier.” You eat broccoli, and sulforaphane “quickly reach[es your brain] to exert its protective effects”—in theory, but you don’t know, until you put it to the test.
But now, you can understand why such a study could attract researchers from leading institutions: Harvard, Hopkins, get published in one of our most prestigious journals: PNAS (the Proceedings of the National Academy of Sciences). But what did they find? Well, first, what did they do? A “placebo-controlled, double-blind, randomized trial, young men (ages 13–27) with moderate to severe [autism] received…sulforaphane…from broccoli sprout[s], or [an] indistinguishable [sugar pill].” They “were dosed according to body weight.” Those under 100 pounds got about a tablespoon of broccoli sprouts worth of sulforaphane a day, which is about a cup’s worth of broccoli, between 100 and 200 pounds got about two cups of broccoli’s worth, or two tablespoons of fresh broccoli sprouts, and the big boys got three cups’ worth a day, or a little under a quarter-cup of broccoli sprouts. Why didn’t they just use actual broccoli, or actual sprouts? Because then you couldn’t have a blinded study; the patients, doctors, and parents would know who’s getting the special treatment and who’s not, and that could introduce bias just through the placebo effect. So, instead, no one knew, until the end, who got the sulforaphane, and who just got nothing in a pill.
They chose dietary sulforaphane because of its “capacity to reverse” oxidation, dysfunction, and inflammation. Yeah, but, when put to the test, did it actually work? Well, the placebo didn’t. Give people with autism nothing, and nothing much happens. But, effectively, secretly sneak them some broccoli, and “substantial…improvement…in [behavior], social interaction,…and verbal communication.” But, it all disappeared once the broccoli stopped. But, the study ended on week 18, and a month later, things were heading back to where they started.
Similar findings for a “Social Responsiveness Scale”—significant improvements until the treatment was stopped, and then caught right back up to how poorly those in the placebo group continued to function. And, these weren’t just scores on a page. “The substantial improvements…were conspicuous;” the doctors could see it; their parents and caregivers could see the improvements. No drug has ever been shown to have these kinds of effects. And, look, these were young men, starting at age 13. One could imagine it working as well, or even better, for younger children, because their brains are still developing.
What’s the downside? “Broccoli sprouts are widely consumed…all over the world…without any reports of adverse effects.” Now, remember, we’re talking about whole foods, not broccoli or sulforaphane supplements. Remember, I did videos about them. Broccoli sprouts work; commercial broccoli sprout supplements hardly at all. Broccoli has sulforaphane—florets more than the stems. Broccoli sprouts have like ten times more, but broccoli pills, powders, and supplements have little or none. So, broccoli and cruciferous vegetables for all kids—autism or not—and hey, maybe pregnant women as well, for potential “prenatal prevention” of autism in the first place.
To see any graphs, charts, graphics, images, or studies mentioned here, please go to the Nutrition Facts podcast landing page. There, you’ll find all the detailed information you need plus links to all the sources we cite for each of these topics.
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Thanks for listening to Nutrition Facts. I’m Dr. Michael Greger.
This is just an approximation of the audio content, contributed by Allyson Burnett.