Kensler has pursued this work, funded primarily through the National Cancer Institute at John Hopkins, then at the University of Pittsburgh and now, for the three years he’s been at the Hutch, in part through Washington state’s Andy Hill CARE Fund for distinguished researchers.
His goal is to create a nimble, low-cost approach he calls “green chemoprevention” which can be used to “enhance the detoxication mechanism for those of us living in dirty air and dirty water environments,” he said..
Kensler hopes the agent can eventually be used in cities like Seattle where wildfires, brought on by climate change-driven drought, have created a health hazard every summer, a hazard scientists predict will continue to grow worse.
“With forest fire smoke episodes, Seattle can have double the pollution that Beijing faces on a typical day,” Kensler said. “We’re seeking to power the individual to be able to facilitate some degree of risk reduction on their own.”
So how does it work? You first have to understand what happens when toxins — like aflatoxin or, say, the airborne carcinogen benzene — enter the body.
“Toxins are fat-soluble, so they go into the body and become trapped,” Kensler said. “A toxin needs to become water-soluble so you can pee it out.”
To detoxify harmful agents, the body attaches what Kensler calls a “hitch,” a molecular chain, that can also make the chemical more reactive. But this process can go awry.
“Depending on the chemistry, it can be a bad actor and cause mutations,” he said. “The idea is to make the hitch, then couple it up quickly with sugars or amino acids using additional enzymes — think of it as a trailer on the hitch — that make it no longer reactive. They detoxify it and make it water-soluble.”
The liver struggles to do all of this on its own but Kensler’s research shows it’s possible to give the body an assist by using the phytochemicals found within cruciferous vegetables to boost our natural detoxication mechanisms.
“We’re using foods to enhance the activity of the enzyme that puts the ‘trailer onto the hitch,’” Kensler said.
Cruciferous veggies contain sulfurous phytochemicals called glucosinolates. Eating broccoli sets off a chain reaction between one of these glucosinolates — glucoraphanin — and the enzyme myrosinase. These two compounds are found in separate cellular chambers of the plant; when it’s chewed or chopped or otherwise damaged, active myrosinase is released and the two compounds mix.
The upshot? They form the chemoprotective agent sulforaphane, the plant’s natural “mustard oil bomb” defense mechanism (no relation to mustard gas, which is not a natural substance). That’s what gives these plants their bitterness and smell and how they fend off predators like fungi or insects. Our gut microbiota, which also produces myrosinase, has a similar effect.
In essence, “we humans have co-opted the plants' system for our defense,” Kensler said.
Kensler’s broccoli bombs — packed with soon-to-be-sulforaphane — target our body’s multifaceted cellular defense mechanism, the Keap1-Nrf2 pathway and the enzymes it regulates. These enzymes can transform fat- or lipid-soluble toxins to a stable molecule that’s water soluble. So all those nasty carcinogens can just be flushed away. Literally.
These phytochemicals also provide a broad-based mechanism, Kensler said, one that can “work for airborne, food-borne and waterborne pollutants.”
And nothing delivers quite like broccoli. Or rather, its three-day old sprouts grown from glucoraphanin-rich seeds. Over the years, Kensler and colleagues painstakingly researched plant varieties, seed germination, peak harvesting times and much more to achieve the maximum amount of sulforaphane precursor to boost detoxication. They investigated delivery systems and dosing in numerous clinical trials.
Turns out the correct dosing really matters; so does taste.
“Broccoli tea doesn’t taste all that good,” Kensler said of the beverage they brewed for some of their trials. “Most people find it obnoxiously bitter so we worked with a sensory company to mask the taste and it worked. Compliance was phenomenal.”
According to their analysis, Kensler and colleagues were able to increase the elimination of carcinogens from test subjects’ bodies by 67%, which he said, “should make a difference.”
For their last clinical trial, which ended in December 2019, they worked with a vendor to manufacture tablets from milled and powdered broccoli seeds mixed with freeze-dried broccoli sprouts.
“They’re coated so they’ll get into your GI tract,” he said. “We’re finding that this works really well. Much better than our teas.”
Not surprisingly, the supplement industry — which is unregulated and does not conduct studies with rigor, if at all — has already jumped on the broccoli bandwagon. Go online and you’ll find an assortment of products with glucoraphanin, myrosinase and sulforaphane. Kensler said an entrepreneur in China is already marketing a drink called SFN, which is supposed to contain sulforaphane, but doesn’t.
“We’re going to have to deal with the noise of bad products following good science,” the researcher warned.
Kensler’s most recent trial, the first evaluation of the supplement approach, ended just as the coronavirus pandemic closed borders. He came back to Seattle but had to leave most of his biospecimens behind. He said the vendor who created the broccoli sprout tablet for the trial used rigorous quality control through sourcing and manufacturing and distribution.
“That’s not what supplement companies do, but this group did,” Kensler said. “I’m encouraged about the supplement as the delivery tool to provide a quality and defined dose.”