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

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

01/06/17 • 152 min

Dr. Jed Fahey is a multi-decade veteran of isothiocyanate research and is the director of the Cullman Chemoprotection Center at Johns Hopkins University.

Much of this conversation, as you might expect given Dr. Fahey's pedigree as a research scientist, is focused on isothiocyanates and, indeed, sulforaphane!

While we covered quite a lot on this very topic (isothiocyanates) via my solo podcast a few weeks ago, this covers everything that may have been overlooked.... and, indeed, so much more! Skip to the timeline below for a sampling.

Dr. Fahey and his colleagues have been, in a big way, at the absolute center of what is a staggering amount of research on these very powerful compounds.

There is hardly a topic which we can discuss in which he 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.

In this 2-hour and 30-minute interview, we discuss...

00:00:00 - the early history of sulforaphane research, including key initial discoveries.
00:00:37 - the serendipitous unfolding of events that lead to the converging of the research on the NRF2 stress response pathway with the sulforaphane-related research going on at the same institute Johns Hopkins.
00:05:06 - why cruciferous vegetables bother to create isothiocyanates in the first place.
00:07:26 - the involvement of the heat shock proteins, in addition to the increased activity of Nrf2, as an additional cellular response mechanism that's been observed in association with sulforaphane.
00:08:11 - how sulforaphane affects a diverse array of biochemical processes from glutathione synthesis to elimination of reactive oxygen species and detoxification of harmful compounds, including carcinogens.
00:15:01 - whether or not to cook your cruciferous vegetables.
00:15:34 - the epidemiological (associative) evidence that cruciferous vegetable consumption may help reduce the risk of cancer.
00:18:30 - the extremely unpredictable nature of endogenous conversion of glucorapahanin (the precursor) into sulforaphane between person to person.
00:22:14 - practical information surrounding supplementation of sulforaphane.
00:27:05 - the effect one particular french sulforaphane supplement had on the doubling rate of PSA, which is a marker for prostate cancer recurrence in prostate cancer patients.
00:28:17 - the role that the Cullman Chemoprotection Center at Johns Hopkins has played, in addition to fundamental research, in providing early, vital infrastructure enabling some of the efforts of the international research community in elucidating the effects of sulforaphane and related compounds and the underlying biological pathways.
00:28:26 - the incredible, almost geometric growth in new studies that has occurred since the advent of a few of the key discoveries about sulforaphane and its method of action.
00:32:48 - the practicality of probiotics as a way to improve endogenous myrosinase activity needed to convert the precursor to sulforaphane into the bioactive sulforaphane.
00:33:26 - the involvement of our gut bacteria in our ability to convert the precursor of sulforaphane into its active form.
00:37:13 - whether or not endogenous myrosinase activity improves as a function of repeated challenge with glucoraphanin (the precursor to sulforaphane).
00:39:30 - why probiotics may vary in their degree of efficacy.
00:43:00 - why consuming isothiocyanates to reduce the number of bacterial colonies of h. pylori, a risk factor for peptic ulcers and stomach cancer, may turn out to be a better intervention than complete eradication of the species with antibiotics.
00:47:21 - the bizarre relationship h. pylori has with childhood asthma, where it has been shown that having some h. pylori seems to reduce asthma incidence in childhood.
00:52:28 - the effect sulforaphane has on inflammation and why inflammation is often a great therapeutic target for many different diseases, including diseases of aging.
00:54:05 - the life extension properties broccoli has been shown to have in an insect model of aging.
00:59:27 - the underlying causes of Hutchinson-Gilford progeria and the promise sulforaphane may hold for this disease of rapi...

Dr. Jed Fahey is a multi-decade veteran of isothiocyanate research and is the director of the Cullman Chemoprotection Center at Johns Hopkins University.

Much of this conversation, as you might expect given Dr. Fahey's pedigree as a research scientist, is focused on isothiocyanates and, indeed, sulforaphane!

Dr. Fahey and his colleagues have been, in a big way, at the absolute center of what is a staggering amount of research on these very powerful compounds.

In this 2-hour and 30-minute interview, we discuss...

00:00:00 - the early history of sulforaphane research, including key initial discoveries.
00:00:37 - the serendipitous unfolding of events that lead to the converging of the research on the NRF2 stress response pathway with the sulforaphane-related research going on at the same institute Johns Hopkins.
00:05:06 - why cruciferous vegetables bother to create isothiocyanates in the first place.
00:07:26 - the involvement of the heat shock proteins, in addition to the increased activity of Nrf2, as an additional cellular response mechanism that's been observed in association with sulforaphane.
00:08:11 - how sulforaphane affects a diverse array of biochemical processes from glutathione synthesis to elimination of reactive oxygen species and detoxification of harmful compounds, including carcinogens.
00:15:01 - whether or not to cook your cruciferous vegetables.
00:15:34 - the epidemiological (associative) evidence that cruciferous vegetable consumption may help reduce the risk of cancer.
00:18:30 - the extremely unpredictable nature of endogenous conversion of glucorapahanin (the precursor) into sulforaphane between person to person.
00:22:14 - practical information surrounding supplementation of sulforaphane.
00:27:05 - the effect one particular french sulforaphane supplement had on the doubling rate of PSA, which is a marker for prostate cancer recurrence in prostate cancer patients.
00:28:17 - the role that the Cullman Chemoprotection Center at Johns Hopkins has played, in addition to fundamental research, in providing early, vital infrastructure enabling some of the efforts of the international research community in elucidating the effects of sulforaphane and related compounds and the underlying biological pathways.
00:28:26 - the incredible, almost geometric growth in new studies that has occurred since the advent of a few of the key discoveries about sulforaphane and its method of action.
00:32:48 - the practicality of probiotics as a way to improve endogenous myrosinase activity needed to convert the precursor to sulforaphane into the bioactive sulforaphane.
00:33:26 - the involvement of our gut bacteria in our ability to convert the precursor of sulforaphane into its active form.
00:37:13 - whether or not endogenous myrosinase activity improves as a function of repeated challenge with glucoraphanin (the precursor to sulforaphane).
00:39:30 - why probiotics may vary in their degree of efficacy.
00:43:00 - why consuming isothiocyanates to reduce the number of bacterial colonies of h. pylori, a risk factor for peptic ulcers and stomach cancer, may turn out to be a better intervention than complete eradication of the species with antibiotics.
00:47:21 - the bizarre relationship h. pylori has with childhood asthma, where it has been shown that having some h. pylori seems to reduce asthma incidence in childhood.
00:52:28 - the effect sulforaphane has on inflammation and why inflammation is often a great therapeutic target for many different diseases, including diseases of aging.
00:54:05 - the life extension properties broccoli has been shown to have in an insect model of aging.
00:59:27 - the underlying causes of Hutchinson-Gilford progeria and the promise sulforaphane may hold for this disease of rapi...

Previous Episode

Sulforaphane and Its Effects on Cancer, Mortality, Aging, Brain and Behavior, Heart Disease & More

This podcast is about one of the most important biological pathways you could possibly take the time to learn about: the NRF2 pathway.

The most potent naturally-occurring inducer of this pathway, a plant compound known as sulforaphane, may be one of the most potent health-enhancing compounds at our disposal and yet... no one is keeping it out of your hands! No $1,000 per pill markup is keeping it out of your hands -- it’s available to anyone willing to take the little bit of time it takes each week to produce broccoli sprouts.

In some respects, broccoli sprouts may even be a great equalizer in a way... while it’s true that healthy food can often be expensive, it’s even reasonably possible for a person to take $20 worth of seeds and feed their whole family some of the most healthful greens you could get your hands on. This video will tell you why.

Here are a few of the more salient points surrounding sulforaphane that are discussed in this podcast...

Profound changes in lipid biomarkers, reducing heart disease risk by as much as 50% in humans.
Massive reductions in cancer risk in humans and also highly effective as a cancer intervention, particularly prostate and breast but also many others.
Steep reductions in inflammation in humans.
Shown in mice to be as effective as prozac as an anti-depressant.
Steep behavioral changes in humans with respect to certain neurological disorders, such as autism.
Causes dramatic boosts in the excretion of air pollutants (up to 60%) in humans.

Key sections you may want to skip to:
00:03:35 - Cancer and mortality
00:21:56 - Aging
00:29:37 - Brain and behavior
00:41:33 - Final recap
00:44:18 - Dose

NOTE: If you enjoy this podcast, you'll enjoy the YouTube video more since it shows all of the figures and citations.

Next Episode

Roland Griffiths, Ph.D. on Psilocybin, Psychedelic Therapies & Mystical Experiences

Dr. Roland R. Griffiths is a clinical pharmacologist at Johns Hopkins and has been researching mood-altering compounds for over 40 years. As an unusually prolific scientist, having published over 360-times, he's also responsible for having started the psilocybin research program at Johns Hopkins nearly 2 decades ago.

In this 1-hour and 15-minute podcast, we discuss…

00:01:03 - the broader story of Dr. Griffiths 40 years of mood-altering drug research, including what got him started and how taking up a meditation practice ultimately influenced the eventual focuses of his research.
00:02:22 - the effect psilocybin has had in clinical trials in eliciting so-called mystical experiences that can act as a long-term catalyst for meaningful spiritual change and is amenable to being reproduced and clinically studied in a prospective manner.
00:03:45 - what distinguishes psilocybin from other drugs, particularly when reflecting backward on the experience months afterward.
00:05:11 - the process by which Dr. Griffiths and his team create an appropriate “setting” and facilitate feelings of safety for those participating in his trials.
00:06:42 - the elusive fundamental nature of a classical psychedelic experience whereby people often simultaneously describe the experience as ineffable (indescribable) but yet also often assign it a truth value that may even exceed that of everyday consensus reality.
00:07:36 - a description of the core features of a classical mystical experience that overlap with those found in a mystical experience induced by psilocybin.
00:08:58 - the qualities of the experience that Dr. Griffiths believes to most underlie the “reorganizational” potential it can have.
00:10:55 - the interesting potential areas for scientific exploration that the reproducibility of the psilocybin experience makes the substance amenable to.
00:11:25 - the promise psilocybin has shown as an effective therapeutic for anxiety and depression in patients with life-threatening cancer and also treatment-resistant depression in otherwise healthy patients (00:18:46).
00:13:04 - the lack of rigor in the very early trials on these compounds and the way in which cultural stigma surrounding psychedelic drugs ultimately played a role in impeding real, substantive clinical research for decades afterward.
00:16:31 - the long-term resilience of the antidepressant and anxiolytic effect, lasting six months and possibly even longer.
00:21:01 - the effect psilocybin has demonstrated in animal studies to increase hippocampal neurogenesis and enhance extinction of trace fear conditioning.
00:23:07 - the somewhat unintuitive neurobiological mechanism that may tie together some of the antidepressant properties of both psilocybin and ketamine, an anesthetic currently being studied as a rapid-onset antidepressant.
00:25:16 - whether or not the mystical subjective experiences are necessary for drugs like psilocybin to exert their antidepressant or anxiolytic effects.
00:26:43 - what the default mode network is and what its pattern of activity is in depression, long-term meditators, and after the acute use of psilocybin.
00:32:16 - the hard problem of consciousness.
00:37:26 - the challenge of finding the neurological correlates to match the phenomenology of individual’s subjective experiences.
00:38:16 - the promise psilocybin has shown in a small trial on smoking cessation where 60% of the treatment group were still abstinent a year afterward and plans Dr. Griffiths has to expand this area of research
00:41:10 - the possibility that the “reorganizational nature” of these experiences may open up new avenues as trials continue to try to embed the experience within different therapeutic contexts.
00:44:02 - the roadmap to FDA approval for use of psilocybin as a medication, particularly in the context of cancer-associated depression and anxiety.
00:45:05 - the risks inherent in taking psilocybin and the frequency of self-reported negative experiences in the general population.
00:47:22 - the criteria Dr. Griffiths and his colleagues use when screening for volunteers to participate in his studies involving psilocybin.
00:49:21 - the inability for clinicians to predict who is at risk of having challenging experiences defined by fear and anxiety (“bad trip”) and whether or not it is desirable, in terms of achieving a therapeutic outcome, to prevent these types of experiences altogether or not.
00:51:43 - the sort of dosages used in the trials.
00:54:45 - the clever ways devised by Dr. Griffiths to placebo control trials where expectation itself can affect outcome.
00:57:45 - some of the interesting anecdotes gleaned from Dr. Griffiths’ working with long-term meditators participating in the psilocybin tria...