The results of a new autism study were so surprising even one of the authors called it “far- fetched,” at least on the surface. “If you tell someone you’re treating autism with broccoli, they would think you are off your rocker,” said Paul Talalay, who is head of the Laboratory for Molecular Pharmacology at Johns Hopkins University.
He and his collaborators announced today that when they gave a compound called sulforaphane, derived from broccoli, to a small group of severely to moderately autistic teenage boys and young men, there was a dramatic improvement in the subjects’ symptoms. They were calmer, more social and in some cases, more verbal.
This experiment was no long shot, however. It grew out of a long history involving the intersection of two well-developed courses of research.
Coming at it from one side was Talalay, who had been following his curiosity about cancer prevention and vegetables. From another angle came pediatric neurologist Andrew Zimmerman, who had been fascinated by anecdotal reports from parents that their autistic children improved during bouts of fever.
The study was small, involving just 29 patients who got the compound and 15 on a placebo. The results were rejected by the New England Journal of Medicine, but accepted into the Proceedings of the National Academy of Science. (Addendum: Talalay is a member of the National Academy of Sciences, and academy members can submit papers to this journal without standard peer review. Such papers are reviewed but the authors can choose their own reviewers.)
That suits the researchers fine, since they say the findings must be replicated before they would be of clinical use, and yet the paper reveals new insights into the physiological underpinnings of autism - or autism spectrum disorder - which affects about one in 68 people. “The result implies these symptoms can be changed,” said Zimmerman. “They are not set in stone.”
Talalay explained that his part of this line of inquiry started in the 1980s, when he was investigating cancer prevention – then a rather radical and unexplored topic. (Talalay is now in his mid-80s and has spent 51 years doing research at Johns Hopkins.)
Experimental work at the time was showing that certain food preservatives known as BHA and BHT appeared to prevent cancer in animals. “I asked the question, how does it work?” The answer to that question, he said, “is at the heart of this entire field of work.”
The answer, he found, was that cells have evolved an intrinsic mechanism to protect themselves from inevitable damage – carcinogenic chemicals, radiation, and damage that comes from the way animal cells use oxygen. We need oxygen for respiration but the process leaves byproducts called oxygen radicals, or free radicals, which damage our cells’ DNA. Talalay found that BHT and BHA amplified the production of enzymes that protect cells from this kind of degradation.
That led him to a very basic question – why are vegetables good for us? Could it be they contain substances that rev up those natural mechanism for protecting cells? To find out, he sent his graduate students to the grocery store.
They brought back a variety of vegetables, but those with the most dramatic effects were the so-called cruciferous vegetables, including broccoli, cauliflower and cabbage. From broccoli he and his students extracted a single compound called sulforaphane with a strong protective effect. His work on the substance led to a front page New York Times story in 1992. It also led to a whole body of research on sulforaphane, he said, with three or four papers published every week exploring its mechanism of action.
At the same time and unbeknownst to Talalay, pediatric neurologist Andrew Zimmermen of Massachusetts General Hospital was investigating anecdotal reports that fever temporarily makes some autistic people more relaxed, more communicative and in some cases better able to express their thoughts in words.
That line of inquiry led him to link the phenomenon to a physical mechanism – fever induces cells to produce substances called heat shock proteins, which can protect cells. He said a body of scientific work also showed that some autistic people have abnormalities in their cells – they show increased damage from oxygen radicals, high levels of inflammation and other signs that the normal protective mechanisms are not working.
About five years ago, Zimmerman came to Talalay and Johns Hopkins colleague Kirby Smith and they started looking at the cell biology of autism and substances that might have a positive effect. “That was a wonderful collaboration,” said Zimmerman. At the time, it wasn’t clear whether the heat shock proteins would have any relevance, or whether the cellular abnormalities were a cause or a symptom of autism.
Zimmerman said he’d never heard of sulforaphane, the broccoli compound, but the collaborators found it seemed to reverse the cellular abnormalities associated with autism. “That was a new realization for us,” said Talalay. It led them to recruit people for a small human study. They used young males, aged 13 to 27 with moderate to severe autism. 29 got a standardized dose of the sulforaphane – more than you could get from eating broccoli. 15 got a placebo.
The results were striking. “I was bowled over by it,” said Talalay. The improvements were almost too good to be true – a nagging sign that there might have been a mistake. He said they decided to have the results audited by an independent firm. But what they really need is independent confirmation.
Though there’s no harm in encouraging people eating broccoli, Talalay warns that when they tested the vegetable from various supermarkets, the levels of sulforaphane vary by a factor of 20. But in the meantime there’s a lot more to the study and its history, he said. “The insight it provides into what autism is all about may more important.”
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