HoldsUp

Jed W. Fahey

Cullman Chemoprotection Center at Johns Hopkins

Jed W. Fahey, Sc.D., is a nutritional biochemist and director of the Cullman Chemoprotection Center at Johns Hopkins with a background in plant physiology, human nutrition, and phytochemistry. His research primarily focuses on the bioavailability and biological effects of isothiocyanates, particularly sulforaphane and glucoraphanin derived from broccoli seeds and sprouts. His published work includes clinical and laboratory studies evaluating these compounds in the contexts of metabolic health, skin disorders, autism spectrum disorder, schizophrenia, and cancer.

74 claims checked on air: 3 context 1 overstated 64 supported 6 unverified 1 flagged

What they said on air - citing their own research

23 citing their own research

0:05:25supportedhightheir own paperJed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Morin

Broccoli sprouts have much higher levels of glucoraphanin than mature broccoli heads, while broccoli seeds contain the highest amount on a per-gram basis.

"broccoli sprouts had much higher levels of the precursor of sulforaphane, glucoraphanin, than did the mature plants, the heads of broccoli that you buy in the market... because it turns out the seeds have the highest amount on a per-gram basis of glucoraphanin." (said at 0:05:25)

Published analytical studies directly confirm that glucoraphanin (the glucosinolate precursor to sulforaphane) is most concentrated in ungerminated broccoli seeds and declines throughout plant ontogeny. Three-day-old broccoli sprouts contain roughly 10 to 100 times the glucoraphanin concentration found in mature broccoli heads, while ungerminated seeds contain the highest levels on a per-weight basis.

0:08:50supportedvery lowtheir own paperJed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Morin

Sulforaphane activates the antioxidant response element by binding or interacting with Keap1 in the cytoplasm, triggering the release and nuclear translocation of Nrf2.

"Then there is actually a chaperone protein that's in the cytoplasm, it's called Keap1. That molecule, when it binds to sulforaphane or vice versa, changes in conformation, and it releases Nrf2, which then migrates to the nucleus and turns on or upregulates the antioxidant response element, which is responsible for the transcription, for initiating transcription of a whole series of protective genes, or genes encoding for a bunch of protective enzymes." (said at 0:08:50)

The statement accurately describes the established biochemical mechanism of sulforaphane action. Keap1 is a cysteine-rich cytoplasmic repressor protein that facilitates the degradation of Nrf2 under basal conditions. Interaction of sulforaphane with reactive sulfhydryl groups on Keap1 induces conformational changes that disrupt Keap1-mediated degradation, allowing Nrf2 to accumulate, translocate to the nucleus, and bind the antioxidant response element (ARE) to initiate transcription of cytoprotective and detoxification enzymes. Because this claim describes molecular intracellular signaling mechanisms demonstrated primarily in cellular and animal models, the certainty grade is very low.

0:13:00supportedhightheir own paperJed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Morin

The glucosinolate-myrosinase-isothiocyanate system is present in Moringa, a tropical tree related to Brassica.

"Moringa is the one which has gotten most attention recently and we've been interested in for about 20 years. It's a relative of broccoli, but it's a tropical plant, it's actually a tree, and it, too, has this system of glucosinolate, myrosinase, and isothiocyanate, the former being the storage form in the plant, the latter being the biologically active form." (said at 0:13:00)

Phytochemical and botanical evidence confirms that Moringa (specifically Moringa oleifera) is a tropical tree containing the glucosinolate-myrosinase-isothiocyanate system. Glucosinolates (predominantly glucomoringin) stored in the plant are enzymatically converted by myrosinase upon extraction or tissue disruption into bioactive isothiocyanates (such as moringin).

0:19:13supportedhightheir own paperJed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Morin

When glucoraphanin is ingested alone without myrosinase, the average bioavailability in 24-hour urine collections is approximately 10%.

"And it turns out that if we looked at 100 different people, and we did, after giving them one dose of glucoraphanin, their bioavailability, the amount they gave back to us in their urine, was all over the map. It ranged from very, very little, but always something, to 40 or 50 or even 60 or 70% of what we gave them, but the mean was pretty low, it was about 10%." (said at 0:19:13)

Human pharmacokinetic and clinical crossover trials show that when glucoraphanin is ingested without active myrosinase (relying solely on gut microflora for conversion to sulforaphane), average urinary metabolite excretion is roughly 5% to 10%, with substantial inter-individual variability. In contrast, when active myrosinase is present, urinary recovery increases substantially (averaging approximately 30% to 70%).

0:19:58supportedhightheir own paperJed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Morin

Direct administration of sulforaphane results in approximately 70% to 80% bioavailability in 24-hour urine.

"So when you give sulforaphane itself, the the end product, the active ingredient, if you will, we get more like 70, 75, 80% bioavailability." (said at 0:19:58)

Human clinical and crossover pharmacokinetic trials show that direct administration of free sulforaphane (such as via sulforaphane-rich broccoli sprout extracts) results in high bioavailability, with approximately 70% to 80% (typically reported around 70% to 90%) of the ingested dose recovered as dithiocarbamate metabolites in urine. In contrast, administration of the precursor glucoraphanin without active myrosinase yields substantially lower bioavailability (~5% to 20%).

0:21:00supportedmoderatetheir own paperJed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Morin

Co-delivering active myrosinase with glucoraphanin increases average bioavailability from approximately 10% to 35-40%.

"What it what did happen is that we moved the bar up, so that instead of 10% bioavailability, we had about 35 or 40%. So the average moved up substantially, it was about three times, three or four times more, but there was still quite large person-to-person variability." (said at 0:21:00)

Clinical pharmacokinetics studies confirm that co-delivering glucoraphanin with active plant myrosinase increases the bioavailability/conversion to sulforaphane (measured by urinary metabolite excretion) by approximately 3- to 4-fold compared to glucoraphanin delivered without active myrosinase (which relies entirely on variable gut microbial conversion, typically yielding around 10% conversion). Active myrosinase formulations yield average bioavailability of approximately 35% to 40%, alongside substantial inter-individual variability.

0:27:25supportedmoderatetheir own paperJed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Morin

The bioavailability of sulforaphane from Prostaphane tablets was found to be essentially identical to that from laboratory-prepared freeze-dried broccoli sprout powder extracts.

"The bioavailability of the sulforaphane from those tablets was essentially identical to that from powders that we made in the lab by extracting broccoli sprouts and treating them with myrosinase and freeze-drying them." (said at 0:27:25)

Clinical pharmacokinetic trials comparing various cruciferous formulations show that delivering preformed, free sulforaphane—whether via standardized commercial tablets (such as Prostaphane) or laboratory-prepared broccoli sprout extracts treated with myrosinase to convert glucoraphanin to sulforaphane prior to drying—achieves high and essentially equivalent bioavailability, yielding approximately 70% to 90% urinary metabolite excretion. In contrast, precursor glucoraphanin delivered without prior conversion yields much lower and variable bioavailability (roughly 5% to 35%).

0:33:33supportedmoderatetheir own paperJed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Morin

Administering a Fleet enema alongside preoperative antibiotics depletes intestinal bacteria by 5 to 6 orders of magnitude and reduces human conversion of glucoraphanin to sulforaphane to zero.

"we showed that if volunteers took a Fleet enema, self-administered enema, which reduces the number of bacteria in their, certainly in their large intestine, by, I don't know, five or six orders of magnitude, and took a preoperative antibiotic course—in other words, something that one would take prior to having intestinal surgery—they essentially wiped out most of the bacteria in their intestines. And those people went from whatever their level of conversion of glucoraphanin to sulforaphane, its metabolites, was, which was, as you heard earlier, 10 to 70%—to nothing." (said at 0:33:33)

Human pharmacokinetic studies investigating the role of the gut microbiome in glucosinolate metabolism demonstrate that mechanical bowel preparation and enteric antibiotics abolish the conversion of glucoraphanin (a glucosinolate) to sulforaphane and related isothiocyanates. In studies led by Fahey and colleagues, heat-inactivated broccoli sprout extracts (devoid of plant myrosinase) rely entirely on gastrointestinal microflora for conversion; when gut bacteria are depleted via bowel cleansing and antibiotics, urinary excretion of isothiocyanate metabolites drops to near-undetectable levels.

0:34:17supportedmoderatetheir own paperJed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Morin

Following antibiotic and enema-induced bowel clearance, human subjects gradually recover their capacity to convert glucoraphanin to sulforaphane within two to four weeks.

"And then over the course of a couple of weeks, I think, as I recall, we followed them with one or two subsequent challenges with glucoraphanin two weeks and four weeks later, I think. They gradually regained their ability to to do that reaction." (said at 0:34:17)

Human metabolic studies conducted by the Johns Hopkins research group demonstrated that gut microflora are required for the conversion of glucosinolates (such as glucoraphanin) into isothiocyanates (such as sulforaphane) in the absence of active plant myrosinase. Following mechanical bowel preparation and enteric antibiotics, conversion efficiency was almost completely abolished, and subsequent challenges demonstrated a gradual recovery of conversion capacity over several weeks as the intestinal microflora recolonized.

0:34:50supportedmoderatetheir own paperJed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Morin

All living human individuals tested harbor intestinal bacteria with myrosinase activity capable of converting glucoraphanin.

"So we have looked at hundreds and hundreds of people's ability to do this conversion, and nobody can't do it. So everybody that everybody that's living and breathing appears to have myrosinase-producing bacteria in their gut." (said at 0:34:50)

Human feeding studies evaluating glucoraphanin bioavailability demonstrate that intestinal microbiota in all evaluated subjects possess some capacity to convert glucoraphanin into sulforaphane or its metabolites, though the conversion efficiency exhibits substantial inter-individual variability (typically ranging from <1% to ~40%).

0:48:40supportedmoderatetheir own paperJed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Morin

In a 50-person clinical trial in Japan, fresh broccoli sprout consumption reduced Helicobacter pylori gastric colonization and lowered inflammation markers in colonized patients.

"What we ultimately found, and this was done with collaborators in Japan in a in a 50-person trial, we found that Helicobacter can reduce the levels—sorry, that sulforaphane or broccoli sprouts, actually fresh broccoli sprouts, were able to reduce levels of colonization in infected people or colonized people, and were able to reduce markers of inflammation in those same people." (said at 0:48:40)

A randomized controlled trial conducted in Japan by Yanaka et al. (2009) evaluated 48 Helicobacter pylori-infected patients assigned to consume either sulforaphane-rich fresh broccoli sprouts (70 g/day) or alfalfa sprouts as a control for 8 weeks. Daily intake of broccoli sprouts significantly reduced biomarkers of H. pylori colonization (urease measured by urea breath test and H. pylori stool antigen) and lowered serum pepsinogens I and II, which serve as biomarkers of gastric inflammation.

0:49:30supportedvery lowtheir own paperJed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Morin

In vitro studies published around 2002 demonstrated that sulforaphane kills natural and doubly antibiotic-resistant clinical strains of Helicobacter pylori.

"So he and I discovered and published in about 2002 that in vitro, in a test tube, sulforaphane was very capable of killing Helicobacter. Not only did it kill natural strains, but it killed strains that were that he had recultured from some of his patients—he's a gastroenterologist—and it killed singly and doubly antibiotic-resistant strains." (said at 0:49:30)

In a 2002 study published in PNAS (Fahey, Lozniewski, et al.), researchers demonstrated that sulforaphane exhibits bacteriostatic and bactericidal activity in vitro against reference strains and 45 clinical isolates of Helicobacter pylori, irrespective of their resistance to conventional antibiotics (including singly and doubly resistant strains), as well as eliminating intracellular bacteria in cell culture. Because this evidence is derived from in vitro laboratory experiments, certainty is very low regarding clinical therapeutic outcomes.

0:51:15supportedhightheir own paperJed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Morin

Sulforaphane acts as an effective inhibitor of the bacterial urease enzyme, but urease inhibition is not the mechanism by which sulforaphane kills Helicobacter pylori.

"Kitty Stephenson, who works here with us, and I started looking at the ability of sulforaphane to inhibit urease, which is that enzyme that I told you that creates—that neutralizes the pH in the mucus of the stomach. And we found that indeed, sulforaphane is quite an effective inhibitor of that enzyme. But so again, we thought we had a real Eureka! moment. But it turned out that wiping out that enzyme wasn't sufficient to kill Helicobacter, because strains—how do I put this?—strains of Helicobacter that had been engineered by others to not contain urease were still killed by sulforaphane." (said at 0:51:15)

In vitro microbiological and enzymatic investigations by Fahey, Stephenson, and colleagues demonstrated that sulforaphane inactivates Helicobacter pylori urease via dithiocarbamate formation with cysteine thiols. However, experiments showed that sulforaphane is equally bactericidal against both urease-positive and urease-negative H. pylori mutant strains, and other isothiocyanates that inactivate urease lack bactericidal activity, proving that urease inactivation is not the mechanism responsible for killing the bacterium.

1:10:08supportedlowtheir own paperJed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Morin

Sulforaphane upregulates the cellular heat shock response.

"Sulforaphane also upregulates the so-called heat shock response, and I'll try to tie these together in a second, but there are a number of other pathways in which it's active." (said at 1:10:08)

Preclinical and exploratory human biomarker studies demonstrate that sulforaphane activates the cellular heat shock response. In vitro studies show that sulforaphane induces heat shock transcription factor 1 (HSF1)-mediated transcription and upregulates heat shock proteins such as Hsp27 and Hsp70. In human peripheral blood mononuclear cells (PBMCs) from both healthy individuals and patients receiving oral sulforaphane, increases in HSP27 and HSP70 mRNA expression have also been observed. Because the evidence is derived primarily from in vitro mechanistic studies, animal models, and small exploratory biomarker analyses, the certainty is low.

1:14:28supportedmoderatetheir own paperJed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Morin

A 2014 clinical trial showed that sulforaphane-rich broccoli sprout extract led to substantial improvement in behavioral symptoms in young men with autism compared to placebo.

"So at any rate, we did this trial. It was published in 2014. We, for various reasons, biomarkers of inflammation of the Nrf2 pathway and a heat shock response were not evaluated in blood from those subjects. But what we showed was a rather dramatic reduction in many of the symptoms of autism in about half of the subjects compared to placebos" (said at 1:14:28)

A 2014 randomized, double-blind, placebo-controlled trial (Singh et al., published in PNAS) evaluated sulforaphane derived from broccoli sprout extract in 44 young men (aged 13–27) with moderate to severe autism spectrum disorder over 18 weeks. Participants receiving sulforaphane demonstrated substantial behavioral improvements compared to placebo, including a 34% reduction in Aberrant Behavior Checklist (ABC) scores (P < 0.001) and significant improvements on the Social Responsiveness Scale (SRS) and Clinical Global Impression Improvement Scale (CGI-I), which diminished upon treatment discontinuation.

1:17:48supportedmoderatetheir own paperJed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Morin

Sulforaphane from sulforaphane-rich broccoli sprout extract is approximately 70% bioavailable.

"The first trial delivered sulforaphane-rich broccoli sprout extract. Okay, remember that's 70% bioavailable." (said at 1:17:48)

A randomized crossover clinical trial evaluated the bioavailability of sulforaphane from two broccoli sprout formulations in 50 healthy adults. When participants consumed the sulforaphane-rich (SFR) beverage prepared by treating glucoraphanin with myrosinase, the mean bioavailability—determined by the urinary excretion of sulforaphane and its dithiocarbamate metabolites over approximately 12 hours—was 70%, compared to only 5% from a glucoraphanin-rich precursor beverage.

1:48:03supportedhightheir own paperJed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Morin

The glucosinolate in Moringa is glucomoringin, with the chemical name 4-(alpha-L-rhamnopyranosyloxy)benzyl glucosinolate.

"It's called glucomoringin. The lengthy scientific term is 4-(α-L-rhamnopyranosyloxy)benzyl glucosinolate." (said at 1:48:03)

Glucomoringin is the predominant glucosinolate identified in Moringa oleifera, with the systematic chemical name 4-(α-L-rhamnopyranosyloxy)benzyl glucosinolate. Analytical profiling of M. oleifera leaves, seeds, and bark confirms that this compound is the primary glucosinolate characteristic of the plant.

1:48:31supportedhightheir own paperJed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Morin

Myrosinase hydrolyzes glucomoringin in moringa leaves to produce moringin, or 4-(alpha-L-rhamnopyranosyloxy)benzyl isothiocyanate.

"And it's hydrolyzed by myrosinase that's present in moringa leaves to moringin, or 4-(α-L-rhamnopyranosyloxy)benzyl isothiocyanate." (said at 1:48:31)

The speaker accurately describes the enzymatic hydrolysis pathway found in Moringa oleifera. The precursor glucosinolate glucomoringin [4-(alpha-L-rhamnopyranosyloxy)benzyl glucosinolate] present in Moringa is cleaved by the plant enzyme myrosinase to yield the active isothiocyanate moringin, chemically identified as 4-(alpha-L-rhamnopyranosyloxy)benzyl isothiocyanate.

1:58:52supportedhightheir own paperJed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Morin

Mustard seed is rich in the glucosinolate sinigrin, which converts upon hydrolysis to allyl isothiocyanate.

"Mustard seed has isothiocyanates. It has glucosinolates, rather. Sinigrin is the name of the glucosinolate it's rich in; it produces a compound called allyl isothiocyanate." (said at 1:58:52)

Published biochemical and phytochemical research confirms that mustard seeds (particularly brown and Indian mustard, Brassica juncea and Brassica nigra) are rich in the glucosinolate sinigrin. Upon cell disruption or hydration, endogenous myrosinase enzymatically hydrolyzes sinigrin into allyl isothiocyanate (AITC), the volatile compound responsible for mustard's characteristic pungency.

2:10:38supportedhightheir own paperJed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Morin

A large clinical trial evaluating sulforaphane or broccoli sprout extract for chronic obstructive pulmonary disease (COPD) failed to show a therapeutic effect.

"all of them have had positive effects to one degree or another, with one exception. And that was unfortunately a large trial on COPD, chronic obstructive pulmonary disease, that we were involved with that just didn't show an effect." (said at 2:10:38)

A multicenter, randomized, double-blind, placebo-controlled phase 2 trial (Wise et al., 2016) evaluating oral sulforaphane (25 μmol or 150 μmol daily for 4 weeks) in 89 patients with chronic obstructive pulmonary disease (COPD) found no significant effect on Nrf2 target gene expression, markers of oxidative stress, airway inflammation, or pulmonary function tests compared to placebo.

2:12:15supportedmoderatetheir own paperJed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Morin

Topical application of sulforaphane protects human skin against ultraviolet radiation.

"or you can even put it on your skin—we've done a number of trials showing protection against ultraviolet radiation" (said at 2:12:15)

Clinical and experimental studies in humans demonstrate that topical application of sulforaphane-rich broccoli sprout extracts activates Nrf2-mediated cytoprotective phase 2 enzymes and significantly reduces ultraviolet radiation (UVR)-induced erythema, an established surrogate marker of acute skin damage.

2:15:52supportedvery lowtheir own paperJed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Morin

Animal studies conducted with Yuesheng Zhang and Rex Munday showed significant reductions in bladder cancer tumor number and size following administration of sulforaphane or broccoli sprout extracts.

"We actually were partnered on three or four animal studies with Yuesheng Zhang and Rex Munday in New Zealand, and it was extremely impressive to see the difference in in bladder cancer tumor number, size." (said at 2:15:52)

Preclinical animal research conducted by Yuesheng Zhang, Rex Munday, and colleagues demonstrated that dietary administration of an extract from broccoli sprouts (rich in sulforaphane and other isothiocyanates) significantly inhibited chemically induced bladder cancer in rats. The treatment dose-dependently reduced tumor incidence, multiplicity (number), size, and disease progression without causing histologic toxicity to the bladder epithelium. Because the supporting evidence comes exclusively from animal models, the certainty of evidence for clinical efficacy in humans is very low.

2:18:00overstatedmoderatetheir own paperJed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Morin

A 2014 clinical study in China found that broccoli sprout extract consumption increased the urinary excretion of benzene and acrolein conjugates by 60%.

"And so the most recent of those studies we published in 2014 showed really a dramatic enhancement of the clearance of benzene and acrolein and other pollutant conjugates in lockstep with broccoli sprout extract consumption. It was a 60% increase in excretion, which is just phenomenal." (said at 2:18:00)

A 2014 randomized clinical trial in Qidong, China (n=291) tested a broccoli sprout beverage providing glucoraphanin and sulforaphane against placebo for 12 weeks. The trial found a statistically significant 61% increase in urinary excretion of benzene-derived glutathione conjugates (mercapturic acids), but the increase for acrolein conjugates was 23%, and no significant increase was observed for crotonaldehyde. Claiming a 60% increase for both benzene and acrolein overstates the effect size observed for acrolein.

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