This Rhonda Patrick article highlights Jed Fahey's expertise on sulforaphane and its potential health benefits. The information provided serves as a valuable resource for individuals interested in understanding the role of nutrition in optimizing health and preventing chronic diseases. By summarizing the latest research findings, discussing the importance of dietary choices, and offering practical tips for maximizing the benefits of sulforaphane, it empowers one to make informed decisions about their overall well-being. In short, they key to this all is, as with anything, remember this, too much of a good thing can end up being a bad thing. It's about balance and eating wholefoods (or taking wholefood supplements) is hard to "overdose" and the best way to go optimize, protect, and enhance in your diet.
Sulforaphane, an isothiocyanate compound derived from cruciferous plants such as broccoli and kale, was first discovered in the late 1950s and noted for its antimicrobial qualities. The molecule was largely forgotten until 1992, when it was re-discovered by the late Dr. Paul Talalay and his then student, Dr. Yuesheng Zhang. Talalay and Zhang noted that sulforaphane demonstrated the remarkable capability to switch on intrinsic protective mechanisms that defend cells against cancer and other environmental insults in a hormetic-type response.
Dr. Jed Fahey joined the research in 1994. His findings revealed that sulforaphane is an artifact of isolation: The molecule isn't present in the plants from which it is derived. Rather, it is an end-product of a simple chemical reaction that occurs when the plants sustain damage – whether by insect attack, food preparation techniques, or human consumption. The reaction involves an enzyme (myrosinase) and a precursor molecule (glucoraphanin). Glucoraphanin is a type of glucosinolate. Although many glucosinolates exist in nature – primarily in cruciferous plants – Fahey discovered that young broccoli plants (the sprouts) contain 10 to 100 times more glucoraphanin than any other plant.
Nearly three decades of cell, rodent, and human studies have since yielded a robust library of evidence demonstrating sulforaphane's beneficial effects, thrusting the molecule into the lexicons of the lay public, who seek strategies to optimize well-being and prolong healthspan.
Determining the optimal source and dose of sulforaphane poses challenges
Many questions have arisen regarding the optimal source (food versus supplements), formulation, and dosage of sulforaphane. A critical aspect of this discussion centers on glucoraphanin content in broccoli sprouts versus mature broccoli, which varies across species and cultivar and is influenced by factors such as soil and growing conditions, harvest time, and post-harvest storage.
Although clinical studies have assessed the merits of sulforaphane in a wide range of chronic and infectious diseases, including autism, aflatoxin toxicity, air pollution detoxication, cancer, cardiovascular disease, diabetes, neurodegenerative disease, Helicobacter pylori infection, and many others, doses in these studies have varied markedly in terms of quantity and whether supplied as glucoraphanin (the precursor) or sulforaphane (the end product). In general, however, data suggest that a dose range of 5 to 60 milligrams of sulforaphane daily will likely yield the greatest health effects.
Myrosinase factors into this discussion, as well. The enzyme is heat-sensitive and rapidly denatures during normal cooking processes. Adding ground mustard seed (which is rich in myrosinase) to cooked vegetables provides a culinary workaround to myrosinase losses incurred during cooking. Food preparation techniques that employ shorter cooking times and less water favor myrosinase stability and retention
But myrosinases are also found in the human gut, where they are produced by commensal bacteria that reside there. These bacterial myrosinases providing a fail-safe mechanism for sulforaphane production by converting unhydrolyzed glucoraphanin to sulforaphane. However, the conversion process is highly variable and subject to differences in commensal microbiota composition, the use of antimicrobial agents, or other factors that alter or reduce the gut microbial population.
Optimal glucoraphanin content in broccoli sprouts starts at the source
Key players in the glucoraphanin variability in broccoli sprouts are the seeds from which the tiny plants germinate. Seeds are inherently rich sources of phytochemicals. They house all the nutrients and protective compounds (such as glucoraphanin) the future plant will require as it sprouts and begins to grow. Although many seed vendors provide quality seeds that are free of pesticides and have high germination rates, determining the glucoraphanin content in broccoli seeds requires laboratory analysis that may be cost-prohibitive for most home growers.
The putative glucoraphanin abundance in broccoli seeds implies that consuming the seeds (rather than sprouting them) provides a better means of obtaining the end product. However, broccoli seeds are rich in erucic acid, an omega-9 fatty acid that exerts detrimental effects on heart tissue in rodents and is classified as a natural toxicant. Although prudence is warranted when consuming broccoli seeds directly, their bitter taste may provide a natural deterrent to copious consumption.
Sulforaphane optimizes glutathione, serving as a nutritional "seatbelt"
But consumption of this non-nutrient appears to be important – even essential – for optimal health. Sulforaphane promotes the production of glutathione, a powerful antioxidant that facilitates the body's excretion of a wide range of toxic substances, including pesticides, aflatoxin, and air pollutants. Glutathione binds with many of these toxins and forms mercapturic acids, which can be excreted and measured in urine.
Robust clinical evidence has demonstrated that sulforaphane is beneficial for people who live in areas where air quality is poor due to pollution levels. An intervention study in Qidong, China, an area known for its high levels of air pollution, found that sulforaphane markedly increased the production of mercapturic acid metabolites of benzene and acrolein, known carcinogens present in air pollution. These effects manifested within 24 hours of sulforaphane administration in a dose-dependent manner.
More importantly, however, these effects were sustained – even after several months – demonstrating that sulforaphane did not exhaust the body's capacity to protect itself from environmental threats and suggesting that regular consumption of sulforaphane in foods or dietary supplements provides a kind of nutritional "seatbelt" that protects against future toxic exposures. These findings have relevance for people living in the western part of the United States, where forest fires, which are sources of many airborne pollutants, are common.
Sulforaphane's protective effects extend to the brain.
A growing body evidence suggests that sulforaphane's protective effects extend to the brain. Glutathione is a likely mediator of these effects, as evidenced by data from preclinical models of glutathione deficiency and supported by magnetic resonance spectroscopy studies showing increased glutathione levels in the brains of people who receive sulforaphane.
But other mechanisms might be at play in the brain. Sulforaphane appears to enhance brain derived neurotrophic factor (a protein that controls and promotes the growth of new neurons) and inhibits histone deacetylation (an epigenetic modification that influences gene expression). Other evidence demonstrates that sulforaphane provides protection from methylglyoxal, a critical player in the pathogenesis of advanced glycation end products, commonly referred to as AGEs. AGE formation is a prominent feature of diabetes and a major contributor to amyloid-beta aggregation in the brain.
Sulforaphane may exert opposing effects on cancer.
Sulforaphane appears to preferentially target certain tissues, especially those of the prostate, breast, and bladder, where it exerts pharmacological effects that provide protection against cancer. The bladder, in particular, serves as a reservoir for byproducts of sulforaphane metabolism, including a variety of glutathione-derived conjugates.
These antioxidant compounds eventually end up in the urine, which is temporarily stored in the bladder prior to elimination, providing a unique environment in which to study the effects of sulforaphane and its metabolic byproducts on bladder tissue. Although human trials are lacking, some animal research suggests that sulforaphane and its byproducts protect against bladder cancer.
But the mechanisms by which sulforaphane exerts its cancer-preventive effects may backfire in existing cancers. The current state of the science regarding sulforaphane as a chemotherapeutic measure is meager and points to its role in prevention rather than treatment.
Sprouting offers a natural, cost-effective means of obtaining sulforaphane.
Sprouting is the natural process by which seeds germinate. It is inexpensive, easy to do, and requires very few supplies or even a green thumb. The process often yields far more edible product than most people can consume before quality and safety are compromised. Freezing is a practical strategy for storing sprouts for future use. An added bonus is that freezing and thawing sprouts activates myrosinase, further enhancing their value.
Not everyone can grow (or loves) broccoli sprouts.
We might be a little bit sad about that, but the truth is...
Growing sprouts may prove logistically challenging for some people! Not everyone cares for broccoli sprouts' flavor, which is largely due to their glucosinolate content. In general, the glucosinolates in cruciferous vegetables are described alternately as sharp, pungent, acrid, astringent, or lachrymatory (tear-inducing), but they are most widely regarded – in some cases inaccurately – as bitter. Whereas the glucosinolates in some vegetables are notably bitter, those found in broccoli and broccoli sprouts are much milder.
Nevertheless, for many people, the taste of broccoli sprouts is off-putting – a problem first noted during clinical trials in China in which compliance was crucial. Attempts to disguise the flavor of the broccoli sprout teas used in the trials eventually led them to enlist flavor analysis expertise. The end result was a palatable – and culturally acceptable – beverage, spiked with pineapple and lime. American palates may find a sweeter concoction more tolerable.
An easier, but less cost-effective solution that requires no masking is found in supplementation. Dietary supplements carry inherent risks, however, so choosing a supplement that contains the desired product – glucoraphanin or stabilized sulforaphane – will likely yield the desired results. Choosing a supplement manufacturer with a proven track record of safety is important, too. Some dietary supplements have been used in clinical studies of autism and prostate cancer, lending credence to their efficacy and safety.
Sulforaphane does not meaningfully interfere with thyroid function.
Some anti-nutritional effects of isothiocyanates have been reported. One example is seen in progoitrin, a glucosinolate found in cabbage, rapeseed, and kale. Progoitrin is hydrolyzed to goitrin, which is named for its antithyroid effects. Goitrin blocks tyrosine iodination and inhibits thyroxine (thyroid hormone) formation. Long-term ingestion of goitrin is associated with goiter formation in mammals, a phenomenon first observed in rabbits and described as “cabbage” goiter.
But broccoli sprouts carry little risk of goitrogenic effects. A 12-week study in China assessed the effects of daily sulforaphane consumption on thyroid status, hormone status, and autoimmune status and found that the compound elicited no adverse effects on thyroid function. Normal consumption of isothiocyanate-rich foods and supplements poses little risks to humans.
This episode provides answers to many of the questions submitted by the FMF family regarding sulforaphane, particularly those surrounding dosing, duration of effects, and its hormetic effects. It also addresses a wide range of concerns about sprouting broccoli seeds at home, including harvesting, storing, and consuming home-grown sprouts.
GLOSSERY
Acrolein
The simplest unsaturated aldehyde, created by the burning of glycerol in animal fat. Acrolein, a toxic, colorless liquid, is a strong irritant for the skin, eyes, and nasal passages of humans. It has a disagreeable, acrid smell, easily recognizable as the odor associated with burning fat.
Aflatoxin
A family of carcinogenic toxins produced by certain fungi endemic to areas with hot and humid climates. Aflatoxins are commonly found in agricultural crops such as maize (corn), peanuts, cottonseed, and tree nuts. In people who are infected with hepatitis B, aflatoxin markedly increases the risk for liver cancer.[1]
Alzheimer's disease
A neurodegenerative disorder characterized by progressive memory loss, spatial disorientation, cognitive dysfunction, and behavioral changes. The pathological hallmarks of Alzheimer's disease include amyloid-beta plaques, tau tangles, and reduced brain glucose uptake. Most cases of Alzheimer's disease do not run in families and are described as "sporadic." The primary risk factor for sporadic Alzheimer's disease is aging, with prevalence roughly doubling every five years after age 65. Roughly one-third of people aged 85 and older have Alzheimer's. The major genetic risk factor for Alzheimer's is a variant in the apolipoprotein E (APOE) gene called APOE4.
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Antioxidant
A molecule that inhibits oxidative damage to DNA, proteins, and lipids in cells. Oxidative damage plays a role in the aging process, cancer, and neurodegeneration. Many vitamins and plant-based compounds are antioxidants.
Apoptosis
Programmed cell death. Apoptosis is a type of cellular self-destruct mechanism that rids the body of damaged or aged cells. Unlike necrosis, a process in which cells that die as a result of acute injury swell and burst, spilling their contents over their neighbors and causing a potentially damaging inflammatory response, a cell that undergoes apoptosis dies in a neat and orderly fashion – shrinking and condensing, without damaging its neighbors. The process of apoptosis is often blocked or impaired in cancer cells. (May be pronounced “AY-pop-TOE-sis” OR “AP-oh-TOE-sis”.)
Arsenic
A naturally-occurring element found in soil, water, food, and air. Chronic arsenic exposure is associated with the development of several diseases, including cancer, cardiovascular disease, and diabetes. In utero and early childhood exposure to arsenic is associated with poor cognitive development and increased deaths in young adults.
Autism
A developmental disorder characterized by impaired social interaction, behavioral problems, and poor communication. Autism typically manifests in early childhood and is slightly more common among boys than girls. In clinical trials, sulforaphane, a compound derived from broccoli and broccoli sprouts, reduces the characteristic behaviors associated with autism.
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Benzene
An aromatic hydrocarbon compound produced during the distillation and burning of fossil fuels, such as gasoline. It is also present in the smoke from forest fires, volcanoes, and cigarettes. Benzene is a carcinogen that targets the liver, kidney, lung, heart, and brain and can cause DNA strand breaks, chromosomal damage, and genetic instability.
Bioavailability
The extent and rate at which drugs or other substances, such as plant-based dietary compounds, enter the body’s circulation. Bioavailability is influenced by a variety of factors, including dose, the presence of other foods or substances, and interindividual differences in metabolism due to gut absorptive surface and commensal microbial populations.
COVID-19
An infectious disease caused by the novel coronavirus SARS-CoV-2. COVID-19, or coronavirus disease 2019, was first identified in Wuhan, China, in late 2019. The disease manifests primarily as a lower respiratory illness, but it can affect multiple organ systems, including the cardiovascular, neurological, gastrointestinal, and renal systems. Symptoms include fever, cough, fatigue, shortness of breath, and loss of smell and taste. Some infected persons, especially children, are asymptomatic. Severe complications of COVID-19 include pneumonia, sepsis, acute respiratory distress syndrome, kidney failure, multiple organ dysfunction syndrome, and cytokine storm. Treatments currently involve symptom management and supportive care. Mortality varies by country and region, but approximately 6 percent of people living in the United States who are diagnosed with COVID-19 expire.[1] 1
Glucoraphanin
A glucosinolate (see definition) found in certain cruciferous vegetables, including broccoli, Brussels sprouts, and mustard. Glucoraphanin is hydrolyzed by the enzyme myrosinase to produce sulforaphane, an isothiocyanate compound that has many beneficial health effects in humans.
Glucosinolate
Plant secondary metabolites found primarily in cruciferous vegetables. Glucosinolates give rise to a variety of compounds that have been identified as potent chemoprotective agents in humans against the pathogenesis of many chronic diseases such as cancer, cardiovascular disease, and neurodegenerative disease, among others. These products are responsible for the pungent aroma, sharp flavor, and the “heat” commonly associated with some cruciferous vegetables such as wasabi and horseradish.
Glutathione
An antioxidant compound produced by the body’s cells. Glutathione helps prevent damage from oxidative stress caused by the production of reactive oxygen species.
Glycation
A chemical process in which a sugar molecule binds to a protein or lipid molecule. Glycation differs from glycosylation, which is an enzymatic reaction. It occurs in the bloodstream, primarily to the dietary sugars glucose, fructose, and galactose. Fructose is nearly 10 times more likely to be glycated than glucose.[1]
Heat shock protein
A family of proteins produced by cells in response to exposure to stressful conditions. Heat shock proteins are expressed in response to heat as well as exposure to cold and UV light, and during wound healing and tissue remodeling. Many heat shock proteins function as chaperones by stabilizing new proteins to ensure correct folding or by helping to refold proteins that were damaged by cell stress. A 30-minute 73ºC sauna session in healthy young adults has been shown to cause a robust and sustained increase in the production of heat shock proteins for up to 48 hours afterward.[1]
Histone
The chief protein components of chromatin found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes acting as spools around which DNA winds, and playing a role in gene regulation.
Homeostasis
An organism’s ability to maintain its internal environment within defined limits that allow it to survive. Homeostasis involves self-regulating processes that return critical bodily systems to a particular “set point” within a narrow range of operation, consistent with the organism’s survival.
Isothiocyanate
Byproduct of a reaction between two compounds (glucosinolates and myrosinase) that are found in cruciferous vegetables. Isothiocyanates inhibit phase I biotransformation enzymes, a class of enzymes that transform procarcinogens into their active carcinogenic state. Isothiocyanates activate phase II detoxification enzymes, a class of enzymes that play a protective role against DNA damage caused by reactive oxygen species and carcinogens. Examples of phase II enzymes include UDP-glucuronosyltransferases, sulfotransferases, N-acetyltransferases, glutathione S-transferases, and methyltransferases.
Mechanistic target of rapamycin (mTOR)
An enzyme that participates in genetic pathways that sense amino acid concentrations and regulate cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription. mTOR integrates other pathways including insulin, growth factors (such as IGF-1), and amino acids. It plays key roles in mammalian metabolism and physiology, with important roles in the function of tissues including liver, muscle, white and brown adipose tissue, and the brain. It is dysregulated in many human diseases, such as diabetes, obesity, depression, and certain cancers. mTOR has two subunits, mTORC1 and mTORC2. Also referred to as “mammalian” target of rapamycin.
Rapamycin, the drug for which this pathway is named (and the anti-aging properties of which are the subject of many studies), was discovered in the 1970s and is used as an immunosuppressant in organ donor recipients.
Mitochondria
Tiny organelles inside cells that produce energy in the presence of oxygen. Mitochondria are referred to as the "powerhouses of the cell" because of their role in the production of ATP (adenosine triphosphate). Mitochondria are continuously undergoing a process of self-renewal known as mitophagy in order to repair damage that occurs during their energy-generating activities.
Myrosinase
A family of enzymes whose sole known substrates are glucosinolates. Myrosinase is located in specialized cells within the leaves, stems, and flowers of cruciferous plants. When the plant is damaged by insects or eaten by humans, the myrosinase is released and subsequently hydrolyzes nearby glucosinolate compounds to form isothiocyanates (see definition), which demonstrate many beneficial health effects in humans. Microbes in the human gut also produce myrosinase and can convert non-hydrolyzed glucosinolates to isothiocyanates.
Nrf2
A protein typically present in the cytoplasm of mammalian cells. Nrf2 can relocate to the nucleus where it regulates the expression of hundreds of antioxidant and stress response proteins that protect against oxidative damage triggered by injury and inflammation. One of the most well-known naturally-occurring inducers of Nrf2 is sulforaphane, a compound derived from cruciferous vegetables such as broccoli.
Oxidative stress
A result of oxidative metabolism, which causes damage to DNA, lipids, proteins, mitochondria, and the cell. Oxidative stress occurs through the process of oxidative phosphorylation (the generation of energy) in mitochondria. It can also result from the generation of hypochlorite during immune activation.
Paraquat
A toxic chemical widely used to kill weeds on land and in aquatic settings. Paraquat is a type of dipyridylium herbicide. It is highly toxic to humans and other mammals due to its capacity to form free radicals, promoting oxidative stress and mitochondrial dysfunction. Exposure to paraquat can cause lung scarring and induce kidney, heart, and liver failure. Evidence indicates that paraquat exposure increases a person's risk of developing Parkinson's disease.[1]
Rotenone
A naturally occurring pesticide and insecticide derived from a variety of plant species, including those of the Fabaceae family. Rotenone interrupts complex I of the electron transport chain, eliciting mitochondrial dysfunction and nigrostriatal pathway cell loss. Acute exposure to rotenone in humans induces nausea, vomiting, tremors, lethargy, convulsions, and depression. Chronic exposure elicits dopaminergic neuron degeneration and subsequent symptoms of Parkinson's disease.
Scurvy
A disease caused by vitamin C deficiency. Scurvy is characterized by bleeding, swollen gums, poor wound healing, joint pain, and bruising. Clinical features of scurvy appear in a person in as little as 84 to 97 days of vitamin C depletion. As scurvy progresses, a person might experience shortness of breath, dry eyes, joint swelling, weakness, fatigue, and depression.
Secretory IgA
An antibody that plays key roles in immunity. Secretory IgA is the most abundant antibody in the mucosal immune system, accounting for nearly 20 percent of serum immunoglobulin. It is crucial in protecting the intestinal epithelium from toxins and pathogenic microorganisms.
Sulforaphane
An isothiocyanate compound derived from cruciferous vegetables such as broccoli, cauliflower, and mustard. Sulforaphane is produced when the plant is damaged when attacked by insects or eaten by humans. It activates cytoprotective mechanisms within cells in a hormetic-type response. Sulforaphane has demonstrated beneficial effects against several chronic health conditions, including autism, cancer, cardiovascular disease, diabetes, and others.