#029 Jed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Moringa & Sulforaphane Supplementation
Dr. Jed Fahey, Director of the Cullman Chemoprotection Center at Johns Hopkins, discusses sulforaphane, its precursor glucoraphanin, and NRF2 pathway activation. He covers its role in detoxification, inflammation, and potential for neurodevelopmental disorders like autism and Alzheimer's.
Deep Dive Analysis
15 Topic Outline
Introduction to Sulforaphane and Dr. Jed Fahey's Expertise
Discovery and Biochemistry of Glucoraphanin and Sulforaphane
The NRF2 Pathway: A Master Regulator of Protective Enzymes
Cruciferous Vegetables as Sources of Sulforaphane Precursors
Impact of Cooking and Processing on Sulforaphane Bioavailability
Variability and Quality of Sulforaphane Supplements
Role of Gut Microbiome in Glucoraphanin Conversion
Sulforaphane's Effect on Helicobacter pylori and Stomach Health
Sulforaphane, Inflammation, and the Aging Process
Therapeutic Potential of Sulforaphane in Neurodevelopmental and Neurodegenerative Disorders
Challenges and Progress in Clinical Trials for Sulforaphane
Moringa as a Tropical Alternative to Sulforaphane-Rich Plants
Maximizing Sulforaphane Conversion from Cooked Broccoli
Sulforaphane for Bladder Cancer Prevention and Air Pollution Detoxification
Importance of Diverse Phytochemicals and Dietary Approaches
8 Key Concepts
Sulforaphane
A small, highly reactive molecule discovered in broccoli that is a potent inducer of protective enzymes. It is not present in intact plants but is formed from its precursor, glucoraphanin, when plant cells are broken.
Glucoraphanin
A stable precursor molecule to sulforaphane found in intact broccoli and other cruciferous vegetables. It is converted to sulforaphane by the enzyme myrosinase when plant tissue is damaged.
Myrosinase
An enzyme present in cruciferous plant tissues that converts glucoraphanin into sulforaphane. This enzyme is heat-sensitive and can be inactivated by cooking, but gut bacteria can also perform this conversion.
NRF2 Pathway
A crucial cellular pathway that upregulates protective enzymes and proteins, helping cells defend against various insults. Sulforaphane is considered one of the most potent natural activators of this pathway, controlling 3-5% of cellular proteins.
Hormetic Effect
A biological phenomenon where a low dose of an otherwise harmful agent (like sulforaphane at high concentrations) can induce an adaptive beneficial response in the cell or organism, gearing up protective mechanisms.
Helicobacter pylori (H. pylori)
A bacterium that colonizes the stomach, capable of neutralizing stomach acid in its microenvironment. While often commensal, high levels can cause ulcers and increase stomach cancer risk, and sulforaphane has shown selective antibiotic effects against it.
Progeria (Hutchinson-Gilford Progeria Syndrome)
A rare genetic disease characterized by extremely accelerated aging due to the accumulation of a mutant protein called progerin. Research suggests NRF2 is intimately related to this process, as progerin can bind and inhibit NRF2 activity in the nucleus.
Moringin
An isothiocyanate found in the tropical Moringa tree, a relative of broccoli. It exhibits similar bioactivity to sulforaphane, activating NRF2 and other pathways, and is being explored for nutritional and disease prevention benefits in developing regions.
8 Questions Answered
Glucoraphanin is a stable precursor molecule found in intact cruciferous plants, while sulforaphane is the highly reactive, biologically active compound formed from glucoraphanin by the enzyme myrosinase when the plant tissue is broken or chewed.
Broccoli sprouts contain much higher levels of glucoraphanin (the precursor to sulforaphane) compared to mature broccoli plants, making them a more potent source of the beneficial compound.
Cooking broccoli inactivates the plant's native myrosinase enzyme, which is necessary for converting glucoraphanin to sulforaphane. This means less sulforaphane is formed, but gut bacteria can still perform some conversion.
If glucoraphanin is ingested without active myrosinase (e.g., from cooked broccoli or certain supplements), bacteria in the gut can convert it to sulforaphane. However, the efficiency of this conversion varies widely among individuals and can be eliminated by antibiotics.
Studies have shown that sulforaphane, particularly from fresh broccoli sprouts, can reduce levels of H. pylori colonization and markers of inflammation in infected individuals, and it can kill antibiotic-resistant strains in vitro.
Unlike drugs that are quickly flushed from the system, sulforaphane upregulates enzymes that have relatively long half-lives, meaning their increased activity can persist for a period of days, possibly even weeks, after ingestion.
Sulforaphane is being investigated for its potential to help with conditions like autism, Alzheimer's disease, and schizophrenia, largely due to its ability to reduce inflammation (neuroinflammation) and upregulate the heat shock response, both of which are implicated in these disorders.
The quality of sulforaphane and glucoraphanin supplements varies widely. Many products may not contain the advertised amounts or have active myrosinase. It's important to choose reputable brands that have been validated, and some may require refrigeration to maintain stability.
39 Actionable Insights
1. Prioritize Natural NRF2 Activators
Incorporate sulforaphane into your diet as it is considered the most potent natural activator of the NRF2 pathway, which upregulates protective enzymes and proteins.
2. Activate NRF2 for Cellular Protection
Activate the NRF2 pathway, for which sulforaphane is a potent activator, as it controls 3-5% of cellular proteins involved in protection against various insults and chronic diseases.
3. Eat Raw Cruciferous for Sulforaphane
Consume cruciferous vegetables raw to preserve the heat-sensitive myrosinase enzyme, which is crucial for converting glucoraphanin into sulforaphane for maximum benefit, as cooking inactivates this enzyme.
4. Consume Broccoli Sprouts
Prioritize eating broccoli sprouts over mature broccoli heads, as sprouts contain much higher levels of glucoraphanin, the precursor to the protective compound sulforaphane.
5. Blend Raw Broccoli Seeds
Blend raw broccoli seeds with water to activate the myrosinase enzyme by crushing the seeds, potentially yielding a higher and more potent amount of sulforaphane than sprouts or cooked broccoli, though they may be bitter.
6. Chew Raw Cruciferous Vegetables
Chew raw cruciferous vegetables like radishes thoroughly to break plant cells, allowing the myrosinase enzyme to convert glucoraphanin into sulforaphane and other beneficial isothiocyanates quickly.
7. Allow Time for Sulforaphane Conversion
After blending broccoli sprouts, allow the smoothie to sit for several minutes (e.g., 10-30 minutes) to ensure sufficient time for the myrosinase enzyme to convert glucosinolates into sulforaphane, which can alter the taste.
8. Add Daikon to Cooked Broccoli
To maximize sulforaphane conversion from cooked broccoli, add a small amount of grated daikon or ground daikon seeds, as they contain active myrosinase without diverting enzymes.
9. Use Mustard Powder for Myrosinase
Sprinkle fresh mustard powder (which contains myrosinase) onto cooked cruciferous vegetables to aid in the conversion of glucosinolates to isothiocyanates, ensuring it still has a ‘bite’ to indicate active enzyme.
10. Blend Frozen Sprouts Immediately
When using frozen broccoli sprouts, blend them immediately after removing from the freezer to ensure the myrosinase enzyme acts on the glucosinolates in the liquid, maximizing sulforaphane formation before it degrades or binds.
11. Detoxify Air Pollutants with Sulforaphane
Consume sulforaphane (e.g., from broccoli sprout extract) to significantly enhance the detoxification and excretion of air pollutants like benzene (up to 60% increase in excretion within 24 hours) and acrolein.
12. Reduce Inflammation with Sulforaphane
Consume sulforaphane (e.g., from broccoli sprout extract) to significantly reduce systemic inflammation, as evidenced by lowered C-reactive protein (up to 20%) and IL-6 levels in human studies.
13. Inhibit NF-kappa B with Sulforaphane
Utilize sulforaphane to inhibit the NF-kappa B pathway, a primary inflammatory pathway in the body, contributing to its anti-inflammatory effects.
14. Upregulate Heat Shock Response
Consume sulforaphane to upregulate the heat shock response, which may play a role in neuroprotection against diseases involving protein aggregation like Alzheimer’s, Parkinson’s, and Huntington’s.
15. Consider Sulforaphane for Bladder Health
Consider sulforaphane for bladder cancer prevention or recurrence, as it and its active metabolites accumulate in high concentrations in the bladder, bathing the epithelium and potentially offering protection.
16. Sulforaphane for Prostate Health
Explore sulforaphane for prostate health, as studies suggest it can lower prostate inflammation and significantly slow the PSA doubling rate (by 86%) in men with prostate cancer.
17. Use Broccoli Sprouts for H. pylori
Consume fresh broccoli sprouts to potentially reduce Helicobacter pylori colonization levels and lower inflammation markers in the stomach, offering a dietary approach to managing this bacteria.
18. Sulforaphane Kills Antibiotic-Resistant H. pylori
Sulforaphane has demonstrated efficacy in killing Helicobacter pylori, including strains resistant to single or double antibiotics, suggesting its potential as an alternative or complementary treatment.
19. Sulforaphane Inhibits H. pylori Urease
Sulforaphane effectively inhibits urease, an enzyme used by H. pylori to neutralize stomach acid, which may be important for disease prevention, though it’s not the primary mechanism by which it kills the bacteria.
20. Explore Sulforaphane for Depression
Consider sulforaphane as a potential aid for depression, given its anti-inflammatory properties and animal studies showing efficacy comparable to fluoxetine in alleviating stress-induced depressive behaviors.
21. Consider Sulforaphane for Autism Symptoms
Explore sulforaphane’s potential to improve autism symptoms, particularly those that temporarily lessen during a fever, possibly by upregulating the heat shock response and reducing inflammation, based on a trial showing dramatic symptom reduction.
22. Smokers: Consume Broccoli Sprouts
If you smoke, consume broccoli sprouts regularly to help detoxify accumulated carcinogens like benzene and reduce the risk of associated cancers, such as bladder cancer, though quitting smoking remains the primary recommendation.
23. Sulforaphane Effects Last Days
Understand that the beneficial effects of sulforaphane, such as enzyme upregulation, last for several days (possibly weeks) due to the long half-life of the activated enzymes, so daily consumption may not be strictly necessary.
24. Prioritize Whole Foods Over Supplements
While supplements can be an option, prioritize adopting a healthier lifestyle with a diet rich in fruits and vegetables, as supplements alone are not a substitute for overall healthy eating and exercise habits.
25. Choose Validated Sulforaphane Supplements
Select sulforaphane or glucoraphanin supplements from reputable companies that have been tested and validated for content and bioavailability, such as Prostaphane (sulforaphane, currently not in US), Avmacol (glucoraphanin + myrosinase), or Thorne’s Crucerra SGS (glucoraphanin only).
26. Verify Supplement Quality
Prioritize supplements that have undergone rigorous quality assurance and microbial testing, ideally from companies that openly share their validation processes or have been vetted by independent research.
27. Refrigerate Myrosinase Supplements
If purchasing glucoraphanin supplements that claim to contain active myrosinase, refrigerate them like probiotics to help maintain the enzyme’s stability and increase sulforaphane bioavailability.
28. Check Supplement Expiration Dates
Always check expiration dates on supplements containing live active enzymes like myrosinase, as their stability and efficacy can degrade over time, unlike many shelf-stable multivitamins.
29. Consider Myrosinase with Glucoraphanin
If taking a glucoraphanin-only supplement, understand that its conversion to sulforaphane relies on gut bacteria with myrosinase activity, which varies significantly among individuals.
30. Maintain Gut Health for Sulforaphane
Support general gut health, as all living individuals appear to have myrosinase-producing bacteria, though at varying levels, which are crucial for converting glucoraphanin to sulforaphane.
31. Seek Myrosinase Probiotic
Look for future probiotic formulations containing myrosinase-producing bacterial strains, which could enhance the conversion of glucoraphanin from cruciferous vegetables into sulforaphane.
32. Diversify Plant-Rich Diet
Consume a wide variety of fruits and vegetables beyond cruciferous ones, as many other plants contain phytochemicals that target diverse biochemical mechanisms beyond NRF2, offering broad health benefits.
33. Consider Moringa as Sulforaphane Alternative
In tropical regions or for those seeking alternatives, consider Moringa, a tropical tree whose leaves contain an isothiocyanate with comparable or even greater activity than sulforaphane in some contexts.
34. Utilize Moringa for Nutrition
Incorporate Moringa leaves into the diet, especially in drought-prone tropical regions, as they are exceptionally high in protein and other micronutrients, and remain on trees longer than other leafy greens.
35. Store Dried Moringa Leaves
Dry and powder Moringa leaves for easy storage, as they maintain their high protein content for extended periods, making them a valuable and stable nutritional resource.
36. Choose Reputable Moringa Sources
When sourcing Moringa products, be cautious of outlandish claims and choose reputable companies like Kuli Kuli, which prioritize responsible production and product quality.
37. Add Ice to Sprout Smoothies
Add ice to broccoli sprout smoothies to help negate the bitterness, making them more palatable.
38. Support Chemoprotection Research
Consider donating to the Coleman Chemoprotection Center at Johns Hopkins (chemoprotectioncenter.org) to support research in areas like autism, schizophrenia, progeria, breast cancer prevention, and air pollution injury.
39. Support Podcast Research
Support the podcast through its subscriber crowdfunding model at foundmyfitness.com/crowdsponsor to enable more research visits and contributions to centers like Johns Hopkins.
5 Key Quotes
Sulforaphane is still probably the most potent activator of NRF2 to be found naturally, you know, from the natural world.
Dr. Jed Fahey
If you eat raw cruciferous vegetables, you're a bit better protected, again, based on the epidemiology.
Dr. Jed Fahey
Everybody that's living and breathing appears to have myrosinase producing bacteria in their gut.
Dr. Jed Fahey
Inflammation is a huge component of a number of those conditions. Schizophrenia, autism, Alzheimer's are among them.
Dr. Jed Fahey
If there was a gimme, that's a gimme. I mean, it's got to work there if it's going to work anywhere.
Dr. Jed Fahey
1 Protocols
Maximizing Sulforaphane from Cooked Broccoli
Dr. Jed Fahey- Cook broccoli (e.g., by steaming or boiling) to inactivate its native myrosinase enzyme.
- After cooking, add a small amount of a myrosinase-rich source, such as grated daikon radish or mustard powder, to the cooked broccoli.
- Allow the mixture to sit for several minutes (e.g., 10 minutes to half an hour) to allow the added myrosinase to convert glucoraphanin to sulforaphane.