Jed Fahey, ScD, on Isothiocyanates, the Nrf2 Pathway, Moringa, & Sulforaphane Supplementation

Posted on January 19th 2017 (almost 2 years)

Jed W. Fahey, ScD, MS, is a nutritional biochemist with a broad, extensive background in plant physiology, human nutrition, phytochemistry, and nutritional biochemistry. He is an assistant professor of medicine at the Johns Hopkins School of Medicine and serves as the director of the Lewis B. and Dorothy Cullman Chemoprotection Center. Dr. Fahey earned his master’s degree in plant physiology from the University of Maryland and his doctoral degree in human nutrition from the Johns Hopkins University.

Dr. Fahey’s work focuses on understanding the mechanisms that plants use to protect themselves against stress – specifically the production of compounds that may influence disease prevention and even improve healthspan in humans. He draws on his knowledge of a wide range of scientific disciplines to develop nutritional strategies for cancer chemoprotection in humans.

The bulk of Fahey’s work has focused on glucosinolates and their byproducts, isothiocyanates. Of particular interest is sulforaphane, an isothiocyanate derived from cruciferous vegetables such as broccoli. Sulforaphane is a potent inducer of key enzymes that promote detoxification of carcinogens in humans. Fahey discovered that broccoli sprouts are an exceptionally rich and consistent source of what is now one of the most well-characterized insect antifeedants that seem to be largely beneficial for human health, sulforaphane.

The 1992 discovery that sulforaphane, a compound produced when the leaves and stems of certain edible plants are damaged, induces innate cytoprotective enzymes put broccoli and other cruciferous vegetables on the nutritional map. It also provided the impetus for a diverse range of scientific research dedicated to understanding the mechanisms – and the possibilities – associated with the compound.

A potent inducer of cytoprotective enzymes

"So we started growing them in incubators in the labs starting from seeds. And lo and behold, it turns out that broccoli sprouts had much higher levels of the precursor of sulforaphane, glucoraphanin, than did the mature plants." - Jed. W Fahey Click To Tweet

Researchers at the Johns Hopkins University – and later Dr. Fahey – were at the forefront of this research. They quickly realized that sulforaphane is the single most potent naturally occurring inducer of cytoprotective enzymes. But they also discovered that sulforaphane is an artifact of isolation – the byproduct of a chemical reaction between an enzyme called myrosinase and a precursor molecule called glucoraphanin, a type of glucosinolate. Although many glucosinolates exist in nature – primarily in cruciferous plants – Dr. Fahey discovered that young broccoli sprouts contain 10 to 100 times more glucoraphanin than any other plant.

In parallel to these discoveries, groups in Japan and England were investigating biological pathways that upregulate key enzymes and proteins that cells use to protect themselves against various stressors and insults. One of these pathways, the Keap1-Nrf2-ARE pathway (see glossary definition of Nrf2), is a key mediator of cytoprotective responses to oxidative and electrophilic stress, and sulforaphane is a key player in its activation.

Since sulforaphane’s discovery, countless studies have investigated its effects on many human diseases, including air pollution toxicity, asthma, autism[1][2], radiation dermatitis, schizophrenia, cancers of the bladder, breast, colon, lung, and prostate, and many others. A unifying element in nearly all of these effects is sulforaphane’s participation in the Keap1-Nrf2-ARE pathway.

Click here for a broad video overview on the diverse array of effects of sulforaphane.

A surprising benefit for the gut microbiome

"Something like 55% of the world's population at the moment has Helicobacter in their systems. [...] It's a commensal symbiotic organism, it would appear. It may actually confer benefit on its host." - Jed. W Fahey Click To Tweet

Fahey’s work has revealed that sulforaphane is an effective treatment against Helicobacter pylori, a bacterium implicated in the cause of peptic ulcer disease and stomach cancer. The goal of traditional antibiotics in treating H. Pylori is to completely eradicate the microorganism. Unfortunately, eradication rates in many studies are as low as 70%. Interesting, however, is the fact that it may not be necessary to completely eradicate H. Pylori. Some evidence even suggests that H. Pylori at subpathogenic levels may have benefits, such as the reduction of GERD symptoms. Sulforaphane, rather than strictly eliminating H. Pylori, may reduce the levels of this commensal and widespread organism while also preventing some of the more deleterious effects of excessive antibiotic use.

Sulforaphane's effectiveness in treating or preventing disease may be modulated by its bioavailability, which is influenced by a variety of factors, including the type and age of the food consumed, food preparation techniques (heat during cooking can reduce the formation of sulforaphane), and interindividual differences in gut microbial population.

A cost-effective public health measure

While broccoli sprouts and other cruciferous vegetables are gaining popularity in the US and other developed countries, other countries – and Dr. Fahey – are turning their attention to moringa, a plant common to the tropics and many underdeveloped regions. Moringa produces the isothiocyanate moringin – another potentially beneficial Nrf2-inducing insect antifeedant – which may provide a means to improve the lives and health of people living in underdeveloped countries, at far less cost than many other public health measures.

In this episode, Dr. Fahey and Rhonda discuss sulforaphane supplements, the factors that influence sulforaphane’s bioavailability, its role as an antibiotic against Helicobacter pylori, and its possible benefits against aging.

Few topics come up in their discussion where Dr. Fahey doesn't have an anecdote about a study he was involved in, or, in some cases, "tribal knowledge" that may not even be published but is nonetheless interesting and an important part of the story that is unique to his particular vantage point.

Learn more about Dr. Jed W. Fahey

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