HoldsUp

FoundMyFitness · 2017-01-06 · Rhonda Patrick (host), Jed W. Fahey

Jed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Moringa & Sulforaphane Supplementation

83 claims checked against research: 3 overstated 5 needing context 69 supported 6 unverified

69

Supported by research

0:00:46Jed W. Faheysupportedhigh

Sulforaphane was identified in broccoli by Paul Talalay and Yanyan Zhang in 1992 as an inducer of Phase 2 cytoprotective enzymes in cell culture and animal models.

"So sulforaphane is a small molecule that was discovered in broccoli by Paul Talalay and Yanyan Zhang, his student at the time, in 1992 or so. They published on it, and it was of interest in particular because it was a huge inducer of protective enzymes in people. Of course, it wasn't known that this occurred in people at the time, but in cell cultures and in animals, they showed that it upregulated the protective enzyme cytoprotective enzyme system known by some as the Phase 2 enzyme system." (said at 0:00:46)

In a landmark 1992 paper published in the Proceedings of the National Academy of Sciences (PNAS), Yanyan Zhang, Paul Talalay, and colleagues isolated and identified sulforaphane from broccoli as a potent and selective inducer of Phase 2 detoxication enzymes (such as quinone reductase and glutathione S-transferases) in murine hepatoma cell culture and mouse tissues.

0:03:45Jed W. Faheysupportedhigh

Intact broccoli plants contain the stable precursor molecule glucoraphanin rather than sulforaphane, which is highly reactive.

"What's more is we realized that sulforaphane is not what's present in the intact plant. So what's present in the plant is something called glucoraphanin, and that is a thioglucose-conjugated molecule. Not to get too heavily into the biochemistry of it, but it's a bigger molecule, it's a precursor, and it's very stable. Sulforaphane is not at all stable; it's highly reactive." (said at 0:03:45)

Biochemical and plant physiology research confirms that sulforaphane is not present in intact broccoli tissues. Instead, intact plants store glucoraphanin, a stable glucosinolate precursor consisting of a thio-linked glucose and a sulfonated oxime group. When plant cells are damaged (e.g., through chopping, chewing, or crushing), glucoraphanin comes into contact with the enzyme myrosinase (a thioglucosidase), which hydrolyzes it to generate the reactive isothiocyanate sulforaphane.

0:05:25Jed W. Faheysupportedhigh

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.

0:08:20Jed W. Faheysupportedhigh

Plant myrosinase converts vacuole-stored glucoraphanin into sulforaphane when plant tissue cells are ruptured.

"there is an enzyme that the plant tissue contains called myrosinase, and that enzyme converts glucoraphanin, the precursor which is stored in vacuoles in the plant cells, to sulforaphane. And typically in nature, the plant does that as a protective mechanism. If an insect starts chewing on the leaf of a broccoli plant, for example, it breaks open cells, right? And so those cells then release their glucoraphanin, and the enzyme that's present at the same site hydrolyzes glucoraphanin and forms sulforaphane." (said at 0:08:20)

The speaker's statement accurately describes the classical plant defense mechanism known as the glucosinolate-myrosinase system (often referred to as the 'mustard oil bomb'). In Brassicales plants (such as broccoli and cabbage), glucoraphanin and the enzyme myrosinase are compartmentalized (stored in vacuoles and specialized myrosin cells). When plant tissues are physically ruptured or chewed by herbivores/insects, myrosinase comes into contact with glucoraphanin and hydrolyzes it into the bioactive isothiocyanate sulforaphane.

0:08:50Jed W. Faheysupportedvery low

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.

0:09:52Jed W. Faheysupportedmoderate

Sulforaphane is the most potent natural activator of Nrf2 discovered to date.

"And it turns out that sulforaphane is still probably the most potent activator of Nrf2 to be found naturally in, you know, from from the natural world." (said at 0:09:52)

Sulforaphane (an isothiocyanate derived from glucoraphanin found in cruciferous vegetables like broccoli sprouts) is widely recognized in pharmacological and biochemical literature as the most potent naturally occurring dietary activator of the Keap1-Nrf2 antioxidant/cytoprotective pathway. Comparative screenings of natural dietary electrophiles confirm its leading potency and efficacy among natural compounds, though synthetic derivatives (such as synthetic triterpenoids like CDDO-Im) have been engineered to be more potent.

0:11:00Jed W. Faheysupportedhigh

Chewing radishes causes myrosinase to convert a glucoraphanin-like glucosinolate into sulforaphene and other isothiocyanates.

"you're breaking the plant cells by crunching on the radish, you're releasing a compound that's very, very similar to glucoraphanin in radishes. It happens to be more of a lachrymator, it's got a more mucus-inducing effect in people, and you're letting myrosinase in those radish tissues act on glucoraphanin and form sulforaphene and some other related isothiocyanates" (said at 0:11:00)

Plant and food chemistry literature confirms that radishes (Raphanus sativus) contain glucosinolates such as glucoraphenin (and glucoraphasatin), which are structurally closely related to glucoraphanin. When plant tissues are disrupted (e.g., through mechanical crunching, chewing, or grinding), endogenous myrosinase enzymes hydrolyze these glucosinolates into isothiocyanates, predominantly sulforaphene and raphasatin.

0:13:00Jed W. Faheysupportedhigh

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).

  • supports: The Diversity of Chemoprotective Glucosinolates in Moringaceae (Moringa spp.). (Scientific reports 2018) · cited 88x in the literature
    "Glucosinolates (GS) are metabolized to isothiocyanates that may enhance human healthspan by protecting against a variety of chronic diseases. Moringa oleifera, the drumstick tree, produces unique GS but little is known about GS variation within M. oleifera, and even less in the 12 other Moringa species, some of which are very rare." (abstract, passage verified)
    pubmedfull study (doi)
  • supports: A Strategy to Deliver Precise Oral Doses of the Glucosinolates or Isothiocyanates from Mor… (Nutrients 2019) · cited 51x in the literature
    "The tropical tree Moringa oleifera produces high yields of protein-rich leaf biomass, is widely used as a food source, contains an abundance of phytochemicals, and thus has great potential for chronic disease prevention and perhaps, treatment. We have developed and characterized standardized ways of preparing aqueous "teas" from moringa leaves to deliver precisely calibrated levels of phytochemicals for use in clinical trials. These phytochemicals, especially the glucosinolate glucomoringin and the isothiocyanate moringin, produced from it following hydrolysis by the enzyme myrosinase, provide potent anti-inflammatory and cytoprotective indirect antioxidant activity." (abstract, passage verified)
    pubmedfull study (doi)
0:15:20Jed W. Faheysupportedhigh

Baking or heat treatment inactivates the myrosinase enzyme in cruciferous seeds and vegetables.

"The problem is if you bake them, you kill the enzyme, you kill myrosinase." (said at 0:15:20)

Thermal processing such as baking, boiling, or extensive cooking denatures and inactivates the plant enzyme myrosinase in cruciferous vegetables and seeds. Myrosinase is responsible for hydrolysing glucosinolates into bioactive isothiocyanates (such as sulforaphane). Inactivation by heat prevents this conversion in the plant tissue, leaving glucosinolate breakdown dependent on lower-efficiency conversion by colonic microflora.

0:15:36Jed W. Faheysupportedlow

Epidemiological studies indicate that higher intake of raw cruciferous vegetables is associated with a greater reduction in cancer risk (such as breast and lung cancer) than cooked cruciferous vegetables.

"there actually have been some epidemiologic studies... suggesting that people who eat certain amounts of cruciferous vegetables have reduced risks of various cancers. Breast cancer and lung cancer are high on the list of cancers that have been studied, excuse me. And it turns out that if you eat raw cruciferous vegetables, you're a bit better protected." (said at 0:15:36)

Epidemiological observational studies (primarily case-control studies) have reported that higher consumption of raw or lightly cooked cruciferous vegetables is associated with reduced risk of several cancers, including breast, bladder, stomach, and pancreatic cancers, whereas cooked or long-cooked cruciferous vegetables often show weaker or non-significant protective associations. This difference is biologically plausible because extensive cooking inactivates the heat-labile enzyme myrosinase, which is required to convert glucosinolates into bioactive isothiocyanates (such as sulforaphane). However, the evidence base is observational (case-control designs), which carries inherent risks of recall bias and residual confounding, resulting in a low GRADE certainty.

0:18:12Jed W. Faheysupportedhigh

Human gut bacteria can hydrolyze glucoraphanin and other glucosinolates into isothiocyanates in the absence of plant myrosinase.

"if you ingest glucoraphanin or glucosinolates without myrosinase at all, you then can count on the bacteria in your gut, in your intestines primarily, to do that to make that conversion." (said at 0:18:12)

Human gut bacteria possess myrosinase-like enzymatic activity capable of hydrolyzing glucoraphanin and other glucosinolates into bioactive isothiocyanates (such as sulforaphane and erucin) even when active plant myrosinase is absent, such as after thermal inactivation from cooking.

0:19:13Jed W. Faheysupportedhigh

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%).

0:19:58Jed W. Faheysupportedhigh

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%).

0:21:00Jed W. Faheysupportedmoderate

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.

0:27:01Jed W. Faheysupportedmoderate

A published clinical trial showed that the sulforaphane supplement Prostaphane altered PSA trajectory in men following treatment for prostate cancer.

"There's been at least one publication that looked at its ability to change the the PSA trajectory in in men who have had prostate cancer." (said at 0:27:01)

A double-blind, randomized, placebo-controlled clinical trial evaluated 60 mg/day of stabilized free sulforaphane (Prostaphane) for 6 months in 78 men experiencing biochemical recurrence (rising PSA) following radical prostatectomy. While the study did not achieve its primary endpoint (a predefined reduction in log PSA slope), secondary endpoints showed a significantly longer PSA doubling time in the sulforaphane group compared with placebo (28.9 months vs. 15.5 months, an 86% increase) and significantly lower net increases in PSA levels.

0:27:25Jed W. Faheysupportedmoderate

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%).

0:05:11Jed W. Faheysupportedhigh

Sulforaphane functions in cruciferous plants as a chemical defense mechanism, repelling or exerting toxicity against herbivorous insects when plant tissue is damaged.

"If an insect starts chewing on the leaf of a broccoli plant, for example, it breaks open cells, right? And so those cells then release their glucoraphanin, and the enzyme that's present at the same site hydrolyzes glucoraphanin and forms sulforaphane. And sulforaphane repels those bugs or is in some cases toxic to those bugs, so they go and they fly away or they crawl away." (said at 0:05:11)

The speaker's description accurately reflects the classical 'mustard oil bomb' chemical defense system in cruciferous plants (Brassicaceae). Glucosinolates such as glucoraphanin are physically compartmentalized separately from the enzyme myrosinase (thioglucoside glucohydrolase). When tissue is disrupted by insect chewing or mechanical damage, the enzyme hydrolyzes glucoraphanin into bioactive isothiocyanates, including sulforaphane, which exert repellent, deterrent, or toxic effects against herbivorous insects.

0:14:34Jed W. Faheysupportedhigh

The discovery that broccoli sprouts and seeds contain rich concentrations of glucoraphanin was published in 1997.

"when we discovered that, and this was this was published in 1997, so it's ancient history—it's probably before you were born, right? But when we discovered that broccoli sprouts and seeds were such a potent source of sulforaphane or its precursor" (said at 0:14:34)

The seminal discovery that young broccoli sprouts contain extraordinarily high concentrations of glucoraphanin (the glucosinolate precursor of sulforaphane)—roughly 10 to 100 times higher than mature broccoli—was published by Jed Fahey, Paul Talalay, and colleagues in the Proceedings of the National Academy of Sciences (PNAS) in 1997.

0:31:06Jed W. Faheysupportedhigh

Nutramax manufactures a supplement called Avmacol that contains glucoraphanin and myrosinase.

"One of them is called Nutramax, and they have a product called Avmacol, which they sort of took a page from our playbook and they make something with glucoraphanin and myrosinase." (said at 0:31:06)

Published clinical trials and biomedical literature verify that Avmacol is a dietary supplement manufactured by Nutramax Laboratories consisting of broccoli seed and sprout extract containing glucoraphanin and the active enzyme myrosinase to facilitate the enzymatic conversion to sulforaphane.

0:33:33Jed W. Faheysupportedmoderate

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.

0:34:17Jed W. Faheysupportedmoderate

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.

0:34:50Jed W. Faheysupportedmoderate

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%).

0:35:37Jed W. Faheysupportedmoderate

Strains of Enterococcus, Lactobacillus, and Bifidobacterium species possess myrosinase activity.

"Others have shown that there are—I believe one of them is an Enterococcus; there are Lactobacilli that have myrosinase activity; there are Bifidobacterium, I believe, that have it." (said at 0:35:37)

Multiple in vitro and microbiological studies confirm that specific strains belonging to the genera Enterococcus, Lactobacillus, and Bifidobacterium possess myrosinase-like (glucosinolate-hydrolyzing) enzymatic activity. For example, strains such as Enterococcus casseliflavus, Lactobacillus agilis, Lactobacillus plantarum, Bifidobacterium adolescentis, and Bifidobacterium longum have been shown to hydrolyze various glucosinolates (such as glucoraphanin, sinigrin, and gluconasturtiin) into bioactive isothiocyanates (e.g., sulforaphane, allyl isothiocyanate) and nitriles.

0:41:16Jed W. Faheysupportedmoderate

Probiotic strains have demonstrated therapeutic effects in clinical trials for childhood diarrhea and asthma.

"there are studies, as you say, with with a small number of specific strains showing showing effects. I think some of the more some of the more striking effects have to do with childhood diarrhea and and there even studies showing effects on on asthma" (said at 0:41:16)

Clinical trials and systematic reviews confirm that specific probiotic strains have demonstrated therapeutic effects in pediatric populations. For childhood acute diarrhea, meta-analyses of randomized controlled trials (RCTs) show that specific strains (such as Lactobacillus rhamnosus GG) significantly reduce diarrhea duration and stool frequency. For asthma, meta-analyses of RCTs in pediatric and adult cohorts indicate that probiotic supplementation can reduce acute asthma exacerbations, improve symptom control scores (such as the Childhood Asthma Control Test), and lower inflammatory markers (like fractional exhaled nitric oxide), although improvements in objective pulmonary function tests (e.g., FEV1) have not been consistently observed.

0:43:30Jed W. Faheysupportedhigh

Helicobacter pylori utilizes the urease enzyme to neutralize stomach acid and create a microenvironment of neutral pH in the gastric mucosa.

"It apparently has an enzyme that is called urease, but an enzyme that allows it to neutralize the pH in a in a little microenvironment around the bacterial cells in the in the stomach. I shouldn't use the term gut because we also use the term gut to refer to the intestines. So the stomach is very acid, extremely acid—that's part of the way it does its job—and Helicobacter tunnels into the mucus layer inside the stomach and creates, with enzymes, creates this little zone of neutral pH which allows it to thrive." (said at 0:43:30)

Extensive microbiological and physiological literature confirms that Helicobacter pylori utilizes the enzyme urease to survive in the acidic environment of the stomach. Urease catalyzes the hydrolysis of urea into ammonia and carbon dioxide. The generated ammonia neutralizes gastric acid, buffering the bacterium's periplasm and immediate microenvironment to maintain a near-neutral pH, enabling it to colonize the gastric mucosa.

0:46:00Jed W. Faheysupportedhigh

The World Health Organization estimates that Helicobacter pylori colonization confers a 3- to 6-fold increased risk of gastric cancer.

"I believe the the last estimate I saw was that the World Health Organization considers Helicobacter to confer a four—I think a three or four to sixfold increased risk of stomach cancer if you're colonized." (said at 0:46:00)

The World Health Organization's International Agency for Research on Cancer (IARC) classified Helicobacter pylori as a Group 1 (definite) human carcinogen in 1994 based on prospective epidemiological studies demonstrating an approximate 3- to 6-fold increase in gastric cancer risk. Subsequent collaborative pooled analyses of nested prospective cohorts found an overall odds ratio of 3.0 (95% CI: 2.3–3.8) for non-cardia gastric cancer, which increased to 5.9 (95% CI: 3.4–10.3) when blood samples were collected 10 or more years prior to cancer diagnosis.

0:47:35Jed W. Faheysupportedmoderate

There is an inverse correlation between Helicobacter pylori infection and the incidence of childhood asthma.

"it's been shown—I believe this was Martin Blaser who showed this a number of years ago—that there's an inverse correlation between Helicobacter infection and childhood asthma." (said at 0:47:35)

Martin Blaser and colleagues published landmark epidemiological studies using NHANES data demonstrating a significant inverse association between Helicobacter pylori colonization and childhood asthma (Chen & Blaser, J Infect Dis 2008). Subsequent systematic reviews and meta-analyses have consistently confirmed this relationship; a 2022 meta-analysis of 18 observational studies comprising 17,196 children found that H. pylori infection was associated with significantly reduced odds of childhood asthma (OR 0.68; 95% CI, 0.54–0.87), particularly for CagA-positive strains.

0:48:40Jed W. Faheysupportedmoderate

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.

0:49:30Jed W. Faheysupportedvery low

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.

0:51:15Jed W. Faheysupportedhigh

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.

0:52:48Rhonda Patrick (host)supportedmoderate

Broccoli sprout extract powder supplementation reduces human C-reactive protein (CRP) and IL-6 levels by up to 20%.

"And you've shown this and others have shown that, you know, even broccoli sprout extract powder given to people can lower C-reactive protein levels by as much as 20%. Other inflammatory cytokines, IL-6, can be lowered by something similar, you know?" (said at 0:52:48)

Human clinical trials evaluate the effect of broccoli sprout powder and fresh broccoli sprouts on systemic inflammatory markers, demonstrating significant reductions in both C-reactive protein (CRP) and interleukin-6 (IL-6). In a randomized clinical trial of patients with type 2 diabetes, supplementation with broccoli sprouts powder (6 g/day for 28 days) significantly lowered high-sensitivity CRP by approximately 23% (from 3.0 ± 2.5 mg/L to 2.3 ± 2.1 mg/L, p < 0.05). Similarly, a 10-week intervention trial in overweight individuals demonstrated significant reductions in both CRP and IL-6 (mean IL-6 decreased from 4.76 pg/mL to 2.11 pg/mL). Evidence is rated moderate certainty due to modest sample sizes in the published trials.

0:53:46Rhonda Patrick (host)supportedvery low

Feeding broccoli sprout extract to red flour beetles extended their lifespan by 15% at high doses and by 30% under chronic oxidative/heat stress in an Nrf2-dependent manner.

"So the scientists fed these red flour beetles different doses of broccoli sprout extract, and the doses were ranged from—it was low to high, I can't recall, but it was a dose response. And what they found is that at the—I think it was at the highest dose, these it extended the lifespan of these beetles by 15%. And when they exposed these beetles to high oxidative stress all the time by keeping them in a warmer environment constantly, it extended their lifespan by 30%. And it was totally dependent on Nrf2. So if they knocked down Nrf2, the lifespan extension went away." (said at 0:53:46)

A 2013 study in the red flour beetle (Tribolium castaneum) demonstrated that dietary supplementation with lyophilized broccoli (or its active isothiocyanate sulforaphane) significantly extended lifespan under both baseline conditions (32 °C) and chronic heat stress (42 °C). Furthermore, RNA interference knockdown of Nrf-2 (as well as Jnk-1 and Foxo-1 homologs) completely abrogated the lifespan-extending benefits of the broccoli-supplemented diet. Because this evidence is derived entirely from an invertebrate model organism, the GRADE certainty is very low.

  • supports: Longevity in the red flour beetle Tribolium castaneum is enhanced by broccoli and depends … (Genes & nutrition 2013) · cited 31x in the literature
    "Here, we show that 1 % lyophilized broccoli, added to flour as a dietary source, significantly increases the life span of the red flour beetle (Tribolium castaneum) under physiological conditions (32 °C) and under heat stress (42 °C). The beneficial effects of broccoli could also be reproduced by supplementing flour with the isothiocyanate sulforaphane at concentrations found in the broccoli-supplemented diet. We identified stress-resistant genes responsible for these effects on longevity by microinjecting pupae with double-stranded RNA to induce RNA interference (RNAi). The knockdown of transcripts encoding homologs of Nrf-2, Jnk-1 and Foxo-1 reduced the life span of beetles and abrogated the beneficial effects of broccoli" (abstract, results, passage verified)
    pubmedfull study (doi)
1:00:26Jed W. Faheysupportedhigh

Hutchinson-Gilford progeria syndrome is characterized by the accumulation of progerin, a mutant lamin protein carrying a persistent farnesyl tag.

"is characterized by accumulation of a protein called progerin, which is actually a mutant protein that has—again, I'm not sure if your audience is ready for this—a farnesylation, a farnesyl tag on it." (said at 1:00:26)

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic premature aging disorder primarily caused by a point mutation in the LMNA gene (c.1824C>T). This mutation activates an internal cryptic splice site that removes 50 amino acids near the C-terminus of prelamin A, deleting the cleavage recognition site for the ZMPSTE24 endoprotease. As a result, the protein cannot undergo the final cleavage step that normally removes the C-terminal farnesylated cysteine, resulting in the mutant protein progerin, which retains a permanent farnesyl lipid modification and accumulates abnormally in the nuclear lamina.

1:01:57Jed W. Faheysupportedmoderate

Children born with progeria typically do not live past their teens and suffer from accelerated aging, cardiomyopathy, and stroke.

"dramatically increased aging, so that kids who are born with it don't live past their teens. It's a uniformly fatal disease, and it's characterized by cardiac—especially by cardiac cardiomyopathy and stroke and the diseases that many older people die of." (said at 1:01:57)

Hutchinson-Gilford progeria syndrome (HGPS) is a rare, uniformly fatal genetic condition characterized by accelerated segmental aging. Natural history cohorts demonstrate that untreated individuals have an average life expectancy of approximately 14.6 years (typically dying in their early to mid-teens), with the primary causes of morbidity and mortality being cardiovascular disease (such as myocardial infarction, heart failure/cardiomyopathy, and severe atherosclerosis) and stroke.

1:02:59Jed W. Faheysupportedvery low

Karima Djabali's research group demonstrated that sulforaphane reverses the cellular phenotype in progeria models.

"Others have shown that sulforaphane has an effect in reversing the phenotype in sulforaphane—this is Karima Djabali in Germany showed this a couple of years ago." (said at 1:02:59)

Karima Djabali's research group published in vitro studies demonstrating that sulforaphane stimulates autophagy and proteasome activity, enhances progerin clearance, and reverses cellular phenotypic hallmarks in Hutchinson-Gilford progeria syndrome (HGPS) fibroblast cell cultures. Because the evidence is derived exclusively from in vitro cellular models, the certainty of evidence for clinical relevance is very low.

1:04:47Jed W. Faheysupportedmoderate

Healthy humans produce small amounts of progerin, and its levels increase during normal aging.

"It turns out that all of us have some small amount of progerin, this protein, in our systems. And I believe the evidence is that it increases somewhat as we age, not certainly to the acute levels that you find in kids with progeria." (said at 1:04:47)

Published literature confirms that healthy humans produce low levels of progerin due to sporadic utilization of the cryptic LMNA splice site that is constitutively active in Hutchinson-Gilford Progeria Syndrome (HGPS). Research in human cells and tissues demonstrates that progerin is present in small amounts in non-HGPS individuals and accumulates with physiological aging (particularly in dermal fibroblasts and vascular tissues), albeit at substantially lower concentrations than those observed in individuals with HGPS.

1:05:15Jed W. Faheysupportedvery low

Tom Misteli's group published findings showing that progerin binds and traps Nrf2 at the nuclear lamina as it enters the nucleus.

"there's a very interesting and, I think, quite important publication from Tom Misteli's group at the NIH showing that, in fact, Nrf2 is very intimately related to this process in progeria, and that what happens is that progerin, the sticky protein that I told you is on the inside of the nucleus, actually binds Nrf2 as it enters the nucleus to do its signaling thing, and it gloms it up against the inside of the nucleus, so to speak." (said at 1:05:15)

A 2016 study led by Tom Misteli's group at the NIH (published in Cell) demonstrated that progerin binds and sequesters NRF2, leading to its subnuclear mislocalization and trapping, which impairs NRF2-driven antioxidant gene transcription and accelerates oxidative stress and cellular aging phenotypes in Hutchinson-Gilford progeria syndrome models.

1:07:03Jed W. Faheysupportedvery low

Sulforaphane treatment upregulates RNA expression levels of Nrf2 and Keap1.

"It upregulates its production. So if you look at RNA levels for Nrf2 or for Keap1, its tether protein that's present in the cytoplasm, after treatment with sulforaphane, you see those levels going up." (said at 1:07:03)

Preclinical in vitro and animal studies demonstrate that sulforaphane treatment increases the mRNA transcription levels of Nrf2 (NFE2L2), largely via epigenetic promoter demethylation, as well as downstream antioxidant response pathway components. While sulforaphane's primary canonical mechanism of action is post-translational (modifying cysteine residues on Keap1 to inhibit Nrf2 ubiquitination and degradation), direct upregulation of Nrf2 mRNA and Keap1 protein levels has been observed in cell and rodent models. Evidence is limited to preclinical models.

1:09:44Jed W. Faheysupportedlow

Sulforaphane inhibits the NF-κB inflammatory pathway.

"What we haven't talked about yet is the fact that sulforaphane actually inhibits the NF-κB pathway, which is one of the main inflammatory pathways in the body." (said at 1:09:44)

Numerous preclinical, cell culture, and animal studies demonstrate that sulforaphane inhibits nuclear factor kappa B (NF-κB) signaling, downregulating pro-inflammatory cytokine expression and inflammatory cascades. Because available evidence supporting this molecular mechanism is largely derived from in vitro cellular models and animal experiments rather than direct clinical trials in humans, certainty is graded as low.

1:10:08Jed W. Faheysupportedlow

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.

1:10:47Jed W. Faheysupportedlow

A 2007 paper by Curran and colleagues documented that fever temporarily improves autistic symptoms in children.

"Andy Zimmerman had shown previously—this was published in 2007—that the fever, the so-called fever response of children with autism, was real. In other—he sort of codified it and got it in print." (said at 1:10:47)

A 2007 prospective study published in Pediatrics by Curran, Zimmerman, and colleagues investigated 30 children with autism spectrum disorders during and after an acute fever episode compared with 30 matched afebrile controls. The study found transient reductions in parent-reported aberrant behaviors (including irritability, hyperactivity, stereotypy, and inappropriate speech) during fever, documenting the clinical phenomenon of temporary behavioral changes associated with fever.

1:13:24Jed W. Faheysupportedhigh

Autism has an incidence ratio of approximately 4:1 male to female in the United States.

"As you probably know, autism is about 4:1 male to female in terms of its incidence in this country, anyway." (said at 1:13:24)

Epidemiological surveillance data and meta-analyses consistently report that autism spectrum disorder (ASD) is diagnosed approximately 4 times more often in males than in females. A comprehensive systematic review and meta-analysis of 54 prevalence studies found an overall pooled male-to-female odds ratio of 4.20 (95% CI 3.84–4.60), reflecting the widely cited ~4:1 ratio, though active screening studies suggest the true biological ratio may be closer to 3:1 due to underdiagnosis in females.

1:13:34Jed W. Faheysupportedhigh

More than 1 in 100 children in the United States are diagnosed with autism.

"And more than 1 in 100 kids now are born with autism, so it's a huge problem." (said at 1:13:34)

Surveillance data from the Centers for Disease Control and Prevention (CDC) Autism and Developmental Disabilities Monitoring (ADDM) Network consistently demonstrate that autism spectrum disorder (ASD) prevalence in the United States is well above 1 in 100 children (1%). Surveillance among 8-year-old children across multi-state sites estimated the prevalence to be 1 in 44 (23.0 per 1,000) in 2018, 1 in 36 (27.6 per 1,000) in 2020, and 1 in 31 (32.2 per 1,000) in 2022.

1:14:28Jed W. Faheysupportedmoderate

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.

  • supports: Sulforaphane treatment of autism spectrum disorder (ASD). (Proceedings of the National Academy of Sciences of the United States of America 2014) · cited 459x in the literature
    "In a placebo-controlled, double-blind, randomized trial, young men (aged 13-27) with moderate to severe ASD received the phytochemical sulforaphane (n = 29)--derived from broccoli sprout extracts--or indistinguishable placebo (n = 15)... After 18 wk, participants receiving placebo experienced minimal change (<3.3%), whereas those receiving sulforaphane showed substantial declines (improvement of behavior): 34% for ABC (P < 0.001, comparing treatments) and 17% for SRS scores (P = 0.017). On CGI-I, a significantly greater number of participants receiving sulforaphane had improvement in social interaction, abnormal behavior, and verbal communication (P = 0.015-0.007)." (abstract, results, passage verified)
    pubmedfull study (doi)
1:15:55Jed W. Faheysupportedvery low

Dr. Hashimoto's group published a 10-subject pilot trial evaluating sulforaphane in schizophrenia patients.

"So they only had 10 subjects in that trial, um and I've met uh This was Dr. Hashimoto's work. I think I think he was the the corresponding author on that." (said at 1:15:55)

The speaker accurately described an open-label pilot trial led by Dr. Kenji Hashimoto's group (Shiina et al., 2015), which evaluated sulforaphane-rich broccoli sprout extract (30 mg glucoraphanin per day for 8 weeks) in 10 outpatients with schizophrenia (7 of whom completed the study). As an uncontrolled, open-label pilot study with a small sample size, the clinical certainty of efficacy is very low.

1:17:07Rhonda Patrick (host)supportedvery low

Animal studies have shown that sulforaphane or broccoli sprout extract is as effective as fluoxetine (Prozac) in alleviating stress-induced depression models.

"there's been some animal studies that you may have may have seen where the the sulforaphane—broccoli sprout extract and sulforaphane have shown to be even as good as uh fluoxetine, in which is Prozac, and um alleviating like all these different, you know, methods of stress they have to make an animal depressed, and then they give it Prozac or broccoli sprout extract, and it worked just as well" (said at 1:17:07)

Preclinical animal research supports the claim that sulforaphane produces antidepressant- and anxiolytic-like effects in rodent models of stress-induced depression. In adult mice subjected to behavioral paradigms like the forced swimming test, tail suspension test, and chronic mild stress (CMS), repeated administration of sulforaphane significantly reversed depressive-like behaviors (reducing immobility time and restoring sucrose preference) and attenuated stress-induced increases in corticosterone, ACTH, IL-6, and TNF-α, matching effects typically seen with standard antidepressant positive controls like fluoxetine. However, evidence is strictly limited to animal models, and clinical efficacy in humans has not been established.

1:11:12Jed W. Faheysupportedmoderate

Sulforaphane targets and modulates the mTOR signaling pathway.

"The mTOR pathway is another. So with all of these biochemical pathways that sulforaphane targets, many of them seem to come together in a few of the neurodegenerative or neurodevelopmental diseases." (said at 1:11:12)

Preclinical in vitro and in vivo studies, along with network pharmacology analyses, demonstrate that sulforaphane modulates the mammalian target of rapamycin (mTOR) signaling pathway (typically downregulating mTOR/mTORC1/2 activity and inducing autophagy). Reviews and mechanistic analyses specifically evaluate this modulation in the context of neurodevelopmental conditions such as autism spectrum disorder as well as other disease models.

1:17:48Jed W. Faheysupportedmoderate

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.

1:08:27Jed W. Faheysupportedhigh

Francis Collins discovered the genetic mutation causing Hutchinson-Gilford progeria syndrome.

"And so in progeria, actually Francis Collins, the head of the NIH, made this discovery, I think back in the early '90s. There's a mutation which allows this sticky protein to persist, and so that accumulates on the inside of the nucleus" (said at 1:08:27)

Francis Collins led the research team that discovered the genetic basis of Hutchinson-Gilford progeria syndrome (HGPS), published in 2003 in Nature (PMID: 12714972). The team demonstrated that a recurrent de novo point mutation in the LMNA gene (c.1824C>T, p.Gly608Gly) activates a cryptic splice site, resulting in a mutant prelamin A protein (progerin) that lacks an endoproteolytic cleavage site. Consequently, progerin retains its lipid farnesyl moiety (the 'sticky' modification referred to by the speaker), permanently anchoring it to the inner nuclear membrane and disrupting nuclear envelope architecture.

1:34:01Jed W. Faheysupportedvery low

Moringa contains an isothiocyanate that has biological activity and efficacy comparable to or greater than sulforaphane in many situations.

"Moringa is happens to be a tropical tree that grows everywhere. It's a weed, um and it's also full of an isothiocyanate that is in in many cases more active than sul- It may be better than sulforaphane in many in many situations. Um, it better or worse, but, you know, it's sort of on the same level of efficacy as sulforaphane." (said at 1:34:01)

Preclinical studies evaluating moringa isothiocyanate (MIC-1, also known as moringin or 4-[(alpha-L-rhamnosyloxy)benzyl] isothiocyanate) demonstrate that it possesses biological activity comparable to sulforaphane, including similar potency in activating the Nrf2-ARE antioxidant pathway and upregulating downstream cytoprotective and anti-inflammatory genes. Because the comparative evidence is derived entirely from preclinical in vitro cell culture models rather than direct head-to-head human clinical trials, the certainty of the evidence is very low.

1:37:25Jed W. Faheysupportedhigh

Isothiocyanates bind to reactive cysteine sulfhydryl groups on Keap1, inducing a conformational change in the protein.

"all of the isothiocyanates from cruciferous plants and from Moringa all have that NCS group, um which is sort of what's responsible which is what's responsible for um uh binding to the Keap1 um molecule. Um, there are two sulfhydryl groups on reactive cysteines on that Keap1 molecule, and our colleague Dinkova-Kostova has shown that, um and the isothiocyanate binds there and causes a change in conformation of that protein." (said at 1:37:25)

The claim is supported by biochemical and cellular research, including key studies co-authored by Albena Dinkova-Kostova. Isothiocyanates (such as sulforaphane, which contains the reactive -N=C=S group) activate the Nrf2 cytoprotective pathway by reacting with sulfhydryl groups on specific reactive cysteine residues (notably C273 and C288) of the Keap1 sensor protein, inducing conformational changes in Keap1 that prevent it from targeting Nrf2 for degradation.

1:40:50Rhonda Patrick (host)supportedhigh

Clinical studies show taking broccoli sprout extract increases excretion of air pollutants like benzene by approximately 60% within 24 hours.

"sulforaphane is very powerful, and this has been shown in multiple clinical studies to immediately start to detoxify um air pollutants that we're exposed to, like benzene, um acrolein, but benzene's a big one, like I mean, you start to excrete benzene by like 60% after just 24 hours of taking broccoli sprout extract." (said at 1:40:50)

Multiple randomized clinical trials have evaluated the effects of glucoraphanin- and sulforaphane-rich broccoli sprout preparations on airborne pollutant detoxification in heavily exposed populations in Qidong, China. In a 12-week randomized placebo-controlled trial of 291 adults (Egner et al., 2014), consumption of a broccoli sprout beverage resulted in a rapid and sustained 61% increase in the urinary excretion of benzene glutathione conjugates (S-phenylmercapturic acid) and a 23% increase for acrolein compared to placebo. A subsequent dose-ranging randomized controlled trial (Chen et al., 2019) confirmed a statistically significant 63.2% increase in urinary benzene mercapturic acids in the high-dose group.

1:42:57Jed W. Faheysupportedmoderate

Moringa leaves have a higher protein content than kale, broccoli, or most other leafy green vegetables.

"The leaves are very high in protein—way higher than kale or broccoli or most other leafy green vegetables." (said at 1:42:57)

Nutritional analyses and food science reviews confirm that Moringa oleifera leaves contain an exceptionally high concentration of protein compared to conventional green leafy vegetables such as kale, broccoli, and spinach. Fresh moringa leaves typically provide around 6.7 to 9.4 g of crude protein per 100 g (and 20% to over 30% of dry matter), whereas fresh kale and broccoli typically provide roughly 2.5 to 4.3 g per 100 g.

1:48:03Jed W. Faheysupportedhigh

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.

1:48:31Jed W. Faheysupportedhigh

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.

1:52:25Jed W. Faheysupportedvery low

Animal studies of indole-3-carbinol (I3C) have shown that whether it prevents or promotes cancer depends on whether it is administered before or after exposure to a carcinogen.

"there were an equivalent number of animal studies showing a cancer-preventive effect of indole-3-carbinol, I3C, to those which showed that it actually promoted cancer. And some of these were even in the same animal model. And what it turned out was that the preventive effect depended on whether you gave I3C before or after you gave a carcinogen." (said at 1:52:25)

Animal literature confirms that the timing of indole-3-carbinol (I3C) administration relative to carcinogen exposure substantially alters its effect on tumorigenesis. In established animal models (such as the rainbow trout aflatoxin B1 model and various rodent models), I3C administered before or during carcinogen exposure inhibits tumor initiation by altering carcinogen metabolism and reducing DNA adduct formation, whereas post-initiation administration (given after the carcinogen) has been shown to act as a tumor promoter in liver and other tissues. Because this body of evidence consists entirely of animal and mechanistic data, the GRADE certainty is very low.

1:56:38Jed W. Faheysupportedhigh

Broccoli contains epithiospecifier protein (ESP), which diverts glucosinolate breakdown away from sulforaphane and prevents complete conversion.

"broccoli has this epithiospecifier protein means that you're not getting complete conversion to sulforaphane if you use the broccoli enzyme." (said at 1:56:38)

Broccoli contains epithiospecifier protein (ESP), a heat-sensitive non-catalytic protein cofactor that interacts with the plant enzyme myrosinase during tissue disruption. Instead of allowing myrosinase to convert glucoraphanin exclusively into the bioactive isothiocyanate sulforaphane, ESP diverts hydrolysis toward the formation of sulforaphane nitrile (and other epithionitriles/nitriles), which lacks sulforaphane's phase II enzyme-inducing activity. In vitro and plant tissue experiments demonstrate that ESP activity is inversely correlated with sulforaphane yield, preventing complete conversion of glucoraphanin to sulforaphane under natural conditions.

1:58:15Jed W. Faheysupportedlow

Daikon sprouts lack epithiospecifier protein (ESP), allowing more direct conversion of glucosinolates to isothiocyanates.

"Yanyan Zhang, who's now at the Roswell Park Cancer Institute, then pointed out to me that, "Hey, did you know that we found the epithiospecifier protein isn't in daikon sprouts?"" (said at 1:58:15)

Epithiospecifier protein (ESP) is a plant protein present in certain Brassica species (such as broccoli) that redirects the myrosinase-catalyzed hydrolysis of glucosinolates away from bioactive isothiocyanates and toward inactive nitriles or epithionitriles. Radish (daikon, Raphanus sativus) sprouts possess active myrosinase but lack functional ESP activity, resulting in direct conversion of glucosinolates into isothiocyanates and significantly reducing nitrile formation.

  • supports: Intensifying sulforaphane formation in broccoli sprouts by using other cruciferous sprouts… (Food science and biotechnology 2018) · cited 11x in the literature
    "Sulforaphane is a significant chemopreventive compound which is the predominant glucosinolate in broccoli sprouts. However, the existence of the epithiospecifier protein could direct the hydrolysis of glucosinolates toward sulforaphane nitrile formation instead of sulforaphane... According to the results, the addition of radish, rocket and rape sprouts to broccoli sprouts could promote the hydrolysis of the glucoraphanin to anticancer effective sulforaphane to 2.03, 2.32 and 1.95-fold, respectively, compared to single broccoli sprouts. Meanwhile, the formation of non-bioactive sulforaphane nitrile in these three groups decreased greatly." (abstract, results, passage verified)
    pubmedfull study (doi)
1:58:52Jed W. Faheysupportedhigh

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.

1:51:18Jed W. Faheysupportedmoderate

Broccoli sprouts contain essentially no indole glucosinolates, unlike mature broccoli heads, and therefore do not generate indole-3-carbinol (I3C) or diindolylmethane (DIM).

"Well, there are some other compounds called indoles that we can talk about in a minute, and they're present in the broccoli heads. They're not present to any large degree in broccoli sprouts... we were quite happy when we determined that in broccoli sprouts there were essentially no indole glucosinolates, therefore there was no indole-3-carbinol or diindolylmethane that we would have to worry about." (said at 1:51:18)

Phytochemical characterization of Brassica oleracea cultivars shows that young broccoli sprouts contain negligible quantities of indole glucosinolates (such as glucobrassicin) compared to mature broccoli heads. Consequently, broccoli sprouts do not generate significant amounts of indole-3-carbinol (I3C) or its acid-condensation product 3,3'-diindolylmethane (DIM) upon enzymatic hydrolysis.

1:51:41Jed W. Faheysupportedmoderate

Indole-3-carbinol (I3C) and diindolylmethane (DIM) can polymerize into dimers or tetramers that structurally resemble dioxin.

"So indoles from broccoli form something called indole-3-carbinol, or I3C, which is omnipresent in health food stores and on supplement sites, or DIM, diindolylmethane. These compounds have gotten a mixed sort of a mixed review from a health perspective, because it's been shown that they can polymerize or form dimers or tetramers that actually resemble dioxin, the potent toxin." (said at 1:51:41)

Under acidic conditions, such as in the stomach, indole-3-carbinol (I3C) undergoes non-enzymatic oligomerization/condensation into diindolylmethane (DIM, a dimer), trimers, tetramers, and indolo[3,2-b]carbazole (ICZ). ICZ and related planar condensation products structurally and functionally resemble 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD/dioxin), binding the aryl hydrocarbon receptor (AhR) with high affinity to modulate cytochrome P450 enzymes and estrogen receptor signaling.

1:43:48Jed W. Faheysupportedhigh

Moringa oleifera originated in Northern India near the border with Pakistan.

"Its origin was in Northern India near the Pakistan border, and it spread around the world since. It spread a long time ago, but it spread around the world from those points of origin." (said at 1:43:48)

Botanical and agricultural literature establishes that Moringa oleifera is native to the sub-Himalayan tracts of Northern India and the northwestern Indian subcontinent (adjoining Pakistan). It has since been introduced and widely cultivated throughout tropical and subtropical regions worldwide.

2:00:57Jed W. Faheysupportedmoderate

When plant tissue like broccoli sprouts is frozen and thawed, cells break down, releasing myrosinase to interact with its substrate and form sulforaphane, which then begins binding to proteins and macromolecules.

"Because what happens is when you freeze the plant tissue, when you thaw the plant tissue, I guess, you've broken down many of the cells. So the lignin, the structure on the outside of the plant cells, is still there, but the cells are trashed... ice crystals are forming, and it releases the enzyme, allows the enzyme and the substrate to come into contact, form sulforaphane." (said at 2:00:57)

The speaker accurately describes the biochemical process in cruciferous plant tissue. In intact plant cells, the enzyme myrosinase is compartmentalized separately from its glucosinolate substrate (glucoraphanin). Freezing causes ice crystal formation that disrupts cellular membrane integrity, and subsequent thawing allows the released enzyme and substrate to come into contact and hydrolyze glucoraphanin into sulforaphane (provided myrosinase has not been thermally inactivated by blanching).

2:03:20Jed W. Faheysupportedmoderate

Deep freezing or quick freezing broccoli sprouts and maintaining them in a frozen state during freeze-drying preserves both myrosinase and glucosinolates by preventing enzymatic contact.

"You can actually freeze-dry broccoli sprouts very nicely as long as you deep freeze them or quick freeze them and maintain them in the frozen state when you go to dry them, and that will retain the myrosinase. The myrosinase is not coming in contact with the glucosinolate then." (said at 2:03:20)

The speaker accurately describes the biochemical and processing principles of freeze-drying (lyophilization) Brassica materials such as broccoli sprouts. In intact plant cells, glucosinolates and the hydrolyzing enzyme myrosinase are compartmentalized separately. Quick-freezing and maintaining low temperatures during vacuum sublimation prevents liquid water formation and premature cellular mixing, preserving both active myrosinase and intact glucosinolates in the resulting powder.

2:10:38Jed W. Faheysupportedhigh

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.

2:11:35Jed W. Faheysupportedmoderate

The majority of sulforaphane is excreted in urine conjugated with glutathione, acetylcysteine, or other glutathione-derived conjugates, all of which retain some Nrf2-upregulating activity.

"it winds up being excreted in the urine as either sulforaphane free, being clear, or the majority of it comes out as its conjugates with glutathione, one of the main antioxidant peptides in the body, glutathione or acetylcysteine, sulforaphane, a variety of sort of antioxidant glutathione-derived conjugates. And all of them have some activity in upregulating Nrf2 also." (said at 2:11:35)

Sulforaphane is metabolized via the mercapturic acid pathway, where it is rapidly conjugated with glutathione and sequentially cleaved to form cysteinylglycine, cysteine, and N-acetylcysteine conjugates (dithiocarbamates). In humans, these glutathione-derived conjugates represent the major urinary excretion products of sulforaphane. Published mechanistic and metabolic studies confirm that sulforaphane and its dithiocarbamate conjugates retain biological activity in activating the Nrf2-antioxidant response element (ARE) pathway and inducing phase 2 detoxification enzymes.

2:12:15Jed W. Faheysupportedmoderate

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.

2:15:52Jed W. Faheysupportedvery low

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.

2:21:50Rhonda Patrick (host)supportedhigh

Broccoli sprouts contain higher concentrations of glucoraphanin than mature cruciferous vegetables.

"But broccoli sprouts are unique in that they actually have higher amounts of glucoraphanin." (said at 2:21:50)

Published analytical studies confirm that young broccoli sprouts contain substantially higher concentrations of glucoraphanin (the glucosinolate precursor to sulforaphane) than mature broccoli and other adult cruciferous vegetables, typically by a factor of 10- to 100-fold depending on the cultivar and developmental stage.

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