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Sulforaphane

Sulforaphane featured article

Sulforaphane is a bioactive compound derived from certain cruciferous vegetables, particularly broccoli (and its sprouts) and red kale. Robust evidence from epidemiological, clinical, rodent, and in vitro studies has demonstrated that sulforaphane exhibits antioxidant and anti-inflammatory properties and may be beneficial against a wide range of chronic and acute diseases, including autism, cancer, metabolic dysfunction, and many others and may ameliorate some of the harmful effects associated with exposure to air pollution.

Sulforaphane exerts its therapeutic effects through various mechanisms, such as inhibition of phase 1 drug-metabolizing enzymes, induction of phase 2 protective enzymes, and inhibition of cell proliferation. When used in conjunction with various anticancer treatments, sulforaphane appears to work in a synergistic fashion to potentiate the drugs' effects.

This overview describes sulforaphane's chemistry and synthesis, factors that...

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  • Sulforaphane

    Sulforaphane is an isothiocyanate that activates NRF2-mediated antioxidant response by covalently modifying KEAP1 cysteine residues.

News & Publications

  • Sulforaphane-rich broccoli sprout extract modestly lowers fasting blood sugar in some people with prediabetes, perhaps due to variations in gut microbiota and individual metabolic traits. www.nature.com
    Diet Diabetes Sulforaphane

    Many people with prediabetes never receive structured treatment, even though early intervention offers the best chance of reversing high blood sugar. While lifestyle changes are the primary recommendation, they are challenging to implement and often ineffective. A recent study found that a broccoli sprout extract rich in sulforaphane modestly lowered fasting blood sugar in some people with prediabetes.

    Researchers conducted a 12-week, randomized, double-blind, placebo-controlled trial involving 74 participants with prediabetes who had not previously taken medication for the condition. Participants took a daily dose of broccoli sprout extract or a placebo, and researchers measured changes in their fasting blood sugar. They also analyzed gut microbial composition and genetic markers to explore potential differences in response.

    Overall, the extract slightly reduced fasting blood sugar levels (3.6 milligrams per deciliter, mg/dL) compared to the placebo but did not meet the predefined target for effectiveness. However, a subgroup of participants with mild obesity, lower insulin resistance, and reduced insulin secretion saw a greater reduction in blood sugar—about 7.2 mg/dL. These participants also had a distinct gut microbiota composition, including a higher abundance of bacterial genes linked to sulforaphane activation.

    Sulforaphane forms when glucoraphanin, found in broccoli sprouts, interacts with the enzyme myrosinase. Myrosinase activates when the plant cells are damaged, such as during chewing or processing. In the absence of myrosinase, some people’s gut microbes produce similar enzymes, helping convert more glucoraphanin into sulforaphane. This variation in gut bacteria may explain why some people respond more strongly to sulforaphane-rich foods or supplements.

    These findings suggest that gut microbes and individual metabolic traits may influence the effectiveness of nutritional interventions for prediabetes. One in three people in the U.S. has prediabetes. Learn more in this clip featuring Dr. Michael Snyder.

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  • Sulforaphane, derived from broccoli, activates Nrf2, mitigating age-related skin changes and boosting the antioxidant defense system in mice. t.co
    Aging Skin Sulforaphane NRF2 Oxidative Stress

    The skin is the body’s first line of defense against environmental exposures. However, the skin changes considerably as we age, reducing its defense capacity. A 2021 study in mice found that sulforaphane, a bioactive compound derived from broccoli, mitigates age-related skin changes by activating Nrf2, a protein that participates in the body’s antioxidant defense system.

    Researchers fed young and old mice regular mouse chow or chow supplemented with sulforaphane for three months. They assessed the antioxidant capacity and protein expression levels in the animals' skin. They also measured levels of reactive oxygen species and matrix metalloproteinase-9 (MMP9, a protein involved in tissue remodeling, inflammation, and wound healing), assessed epidermal and dermal thickness changes, and analyzed collagen content.

    They found that sulforaphane reduced reactive oxygen species and MMP9 levels in older mice. It also increased the skin’s antioxidant capacity, as evidenced by enhanced Nrf2 production. They observed no difference in epidermal thickness between young and old SFN-treated mice, but dermal layers were thinner in older mice. Collagen content improved in young and old mice, with more substantial structural improvements observed in the older group.

    These findings suggest that dietary supplementation with sulforaphane ameliorates age-related skin changes in mice by activating the Nrf2 pathway, enhancing antioxidant defenses and reducing oxidative stress.

    Notably, the dose provided in this mouse study was very high, translating to about 2,500 milligrams of sulforaphane in humans – roughly the amount supplied in 63 cups of broccoli sprouts. Nevertheless, sulforaphane’s antioxidant-inducing capacity is well established, and consumption of sulforaphane-rich foods is associated with increased healthspan and lifespan. Broccoli sprouts are excellent sources of sulforaphane and are easy to grow at home. For tips on how to grow broccoli sprouts, check out our comprehensive Sprouting Guide, a members-only perk.

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  • Sulforaphane from broccoli sprouts shows promise in preventing Alzheimer's disease – boosting memory and enhancing mitochondrial function in mice. www.mdpi.com
    Brain Alzheimer's Mitochondria Dementia Sulforaphane Oxidative Stress

    Alzheimer’s disease affects more than 24 million people worldwide, with numbers expected to grow as the population ages. A growing body of evidence links mitochondrial dysfunction and oxidative stress to the development of Alzheimer’s disease. A recent study in mice found that sulforaphane, a bioactive compound derived from broccoli and broccoli sprouts, boosts memory, improves mitochondrial function, and reduces oxidative stress.

    Researchers studied normal mice and mice prone to developing a condition similar to Alzheimer’s. They fed half of each type of mice standard mouse chow. They fed the other half normal chow supplemented with a broccoli sprout powder rich in glucoraphanin and myrosinase – the precursors to sulforaphane. They subjected the mice to various memory tests and assessed their mitochondrial function.

    They found that Alzheimer’s disease-prone mice that ate the broccoli sprout powder-supplemented chow performed better on memory tests than those that didn’t. These mice demonstrated higher levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1α) and mitochondrial transcription factor A – proteins that regulate mitochondrial biogenesis (the production of new mitochondria). They also showed upregulated expression of cellular antioxidant defense system components that protect against oxidative stress.

    These findings suggest that sulforaphane from broccoli sprouts prevents age-related cognitive decline by maintaining mitochondrial function, thereby reducing oxidative stress in mice.

    Sulforaphane is an isothiocyanate compound with robust antioxidant, anti-inflammatory, and anti-cancer effects. It reduces oxidative stress by switching on the activity of Nrf2, a cellular protein that activates the transcription of cytoprotective proteins that protect against oxidative stress due to injury and inflammation. Sulforaphane is the most potent naturally occurring inducer of Nrf2. Learn how to grow your own broccoli sprouts – a terrific source of sulforaphane – in this short video.

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  • Breathwork enhances endogenous antioxidant enzyme activity to counter oxidative stress. www.frontiersin.org
    Vitamin C Mortality Sulforaphane Glutathione Nitric Oxide Antioxidant Oxidative Stress Breathing Technique

    Breathwork has shown promise in ameliorating oxidative stress – a driver of many chronic diseases – in healthy people and those with chronic conditions. However, scientists don’t fully understand the underlying mechanisms that drive these effects. A recent review found that breathwork promotes the activity of endogenous antioxidant enzymes.

    Researchers analyzed the findings of 10 randomized controlled trials (519 participants) investigating the effects of breathwork. The studies encompassed a range of breathwork styles and measured various biomarkers, including malondialdehyde, superoxide dismutase, glutathione, nitric oxide, vitamin C, and total antioxidant capacity levels.

    They found that participants who engaged in breathwork exhibited greater changes in the biomarkers than those who did not. In particular, breathwork increased the activity of the endogenous antioxidant enzymes superoxide dismutase and glutathione activities and decreased levels of malondialdehyde, a marker of oxidative stress.

    Breathwork is an umbrella term that refers to various breathing exercises and techniques. Evidence suggests that breathwork improves heart rate variability and promotes resilience to stress. People often engage in breathwork as part of general relaxation practices, yoga, or meditation.

    These findings suggest that breathwork reduces oxidative stress by promoting the activity of endogenous antioxidant enzymes. Only 10 studies were included in the analysis, however, so more research is needed to support the findings. Sulforaphane, a bioactive compound derived from broccoli, reduces oxidative stress, too. Learn more in this clip featuring sulforaphane expert Dr. Jed Fahey.

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  • Every 1 percent drop in body weight slows brain aging by nearly nine months, highlighting the substantial, and often overlooked, neuroprotective benef elifesciences.org
    Brain Obesity Aging Dementia Sulforaphane Weight Loss Neurodegeneration

    Excess body fat harms multiple organ systems, including the central nervous system, potentially accelerating brain aging. A new study shows that a 1 percent weight loss delays brain aging by nearly nine months.

    Researchers conducted a study involving 102 participants enrolled in the DIRECT-PLUS study who underwent an 18-month lifestyle intervention to promote weight loss. Using magnetic resonance imaging, the researchers assessed the resting-state functional connectivity in the participants' brains and predicted their brain ages. They also evaluated how various health factors, such as body measurements, blood markers, and fat deposits, affect brain aging.

    They found that the brain age prediction model accurately predicted the participants' chronological ages. They also found that brain aging slowed by 8.9 months for every 1 percent of body weight loss, an effect linked with improved liver health and reduced liver, visceral, and subcutaneous fat. Their analysis revealed that lower consumption of processed foods, sweets, and beverages delayed brain aging.

    These findings suggest that weight loss may benefit the brain’s aging process, potentially slowing its aging trajectory. They also underscore the importance of maintaining a healthy weight throughout the lifespan to support overall brain health. Sulforaphane, a bioactive compound derived from broccoli, benefits brain health and may influence its aging, too. Learn more in this episode featuring Dr. Rhonda Patrick.

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  • Eating broccoli may safeguard the gut by increasing the number of goblet and Paneth cells. www.sciencedaily.com
    Gut Diet Inflammation Immune System Sulforaphane

    The list of health attributes of broccoli includes anticancer, antioxidant, and anti-diabetes effects, as well as many others. Now a new study in mice shows that eating broccoli protects the gut. Molecules in broccoli interact with proteins present in the small intestine, increasing the number of cells involved in safeguarding the gut.

    Researchers fed one group of mice a diet containing 15 percent freeze-dried broccoli – roughly equivalent to 3.5 cups of fresh broccoli in the human diet. They fed another group their typical food, which included no broccoli. Then they examined the animals' small intestines to assess the effects of broccoli consumption on the gut.

    They found that molecules in the broccoli – likely phytochemicals, microbiota, or byproducts of metabolism – bound with specific proteins in the gut called aryl hydrocarbon receptors. Subsequently, the number of goblet and Paneth cells in the animals' guts increased. Goblet cells produce mucus, which protects and lubricates the gut to facilitate the passage of food. Paneth cells produce antimicrobial peptides and immune factors that regulate the gut microbial composition.

    These findings suggest that broccoli consumption protects the gut via interaction with the aryl hydrocarbon receptor. Broccoli is a rich source of phytochemicals, including sulforaphane, an isothiocyanate compound with potent antioxidant, anticancer, and anti-inflammatory properties. Learn more about sulforaphane in this episode featuring Dr. Jed Fahey.

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  • Harmful effects of concussion are still present six months post-injury. medicalxpress.com
    Brain Memory Concussion Sulforaphane

    Press release:

    The harmful effects of concussion on the brain can linger long after the initial injury, a new study shows. Nearly half of all people who experienced even a mild concussion exhibited altered brain connectivity and impaired emotional and cognitive function six months post-injury.

    Researchers compared brain scans of 108 people who had experienced a mild concussion to those of 76 healthy people. They also assessed those who had had a concussion for persistent symptoms.

    They found that 47 percent of the people with mild concussion were not fully recovered six months post-injury, demonstrated by hyperconnectivity in the thalamus – a region of the brain that relays sensory impulses from receptors in various parts of the body to the cerebral cortex. This hyperconnectivity was associated with impaired emotional and cognitive function.

    A concussion is a disruption in normal brain function caused by an external mechanical force. Even mild concussions have been shown to elicit acute and chronic damage to the brain. Symptoms of concussion include depression, cognitive impairment, headaches, and fatigue, many of which are still present as late as six months post-injury. People who experience three or more concussions tend to exhibit cognitive deficits that worsen with each subsequent concussion.

    These findings indicate that even mild concussions can have long-term deleterious effects on the brain. Evidence suggests that sulforaphane, a bioactive compound derived from broccoli, promotes recovery from concussion. Learn more in this clip featuring Dr. Rhonda Patrick.

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  • Intake of sulforaphane precursor may improve sleep quality. www.sciencedirect.com
    Diet Sleep Sulforaphane Glucoraphanin

    A compound present in broccoli sprouts may help you sleep better at night, a new study shows. People who consumed glucoraphanin – a bioactive compound found in broccoli sprouts that is a precursor to sulforaphane – slept better and had lower inflammatory markers than those who didn’t take the compound.

    Researchers conducted a small, randomized, placebo-controlled trial involving 18 healthy adults. Twelve of the participants took 30 milligrams of glucoraphanin daily for four weeks while the remaining six took a placebo. The participants wore sleep monitors and reported their sleep quality. The researchers measured the participants' melatonin and inflammatory markers.

    They found that the participants who took the glucoraphanin experienced better sleep quality than those who took the placebo. They also had higher blood concentrations of melatonin and lower levels of prostaglandin D2, a pro-inflammatory mediator.

    Melatonin is a hormone produced deep within the brain, in the pineal gland. It is a key player in the body’s circadian metabolic processes and serves as the body’s natural sleep inducer. Melatonin production may be impaired in a pro-inflammatory state, and increased oxidative stress and inflammation may reduce sleep quality.

    Glucoraphanin is found in certain cruciferous vegetables, including broccoli (especially broccoli sprouts) and red kale. Glucoraphanin is hydrolyzed by the enzyme myrosinase to produce sulforaphane, which demonstrates many beneficial effects in humans. Learn more about the health effects of sulforaphane in this live Q&A featuring Dr. Jed Fahey.

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  • Broccoli sprout extract may promote tumor-infiltration of immune cells and drive cell death in breast cancer. onlinelibrary.wiley.com
    Breast Cancer Immune System Apoptosis Sulforaphane

    Nearly four million women living in the United States have a history of breast cancer. Evidence suggests that dietary interventions improve breast cancer outcomes and enhance survival. Findings from a recent study indicate that consumption of an isothiocyanate-rich broccoli sprout extract may improve outcomes in women with breast cancer.

    Isothiocyanates are byproducts of a reaction between compounds present in cruciferous vegetables. Isothiocyanates inhibit the activity of enzymes that transform procarcinogens into carcinogens. One of the most studied isothiocyanates is sulforaphane, which is derived from broccoli and is particularly abundant in broccoli sprouts.

    The study involved 30 women (average age, 61 years) who were about to undergo surgery to remove breast cancer tumors. The investigators randomly assigned half of the women to receive 200 micromoles of isothiocyanates from a broccoli sprout extract every day for two weeks prior to their surgery. (This daily dose of broccoli sprout extract is roughly equivalent to that provided in 500 grams – a little more than one pound – of fresh broccoli.) The remaining half of the women received a placebo. The investigators measured isothiocyanate metabolites and cytoprotective proteins in the women’s urine and biomarkers of anticancer activity in the excised tumor tissue.

    They identified multiple proteins in the participants' urine that indicated increased activity of cytoprotective pathways, including the Nrf2-mediated oxidative response pathway. They also observed changes in biomarkers of anticancer activity, including a trend toward increased levels of proteins that regulate programmed cell death and immune cells that recognize and kill cancer cells, as well as a trend toward decreased levels of proteins involved in proliferation. These changes were not statistically significant, however.

    These findings indicate that consumption of an isothiocyanate-rich broccoli sprout extract may improve outcomes in women with breast cancer. The authors posited that the absence of statistically significant findings was likely due to their small sample size and suggested further study with a larger sample.

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  • Sulforaphane exhibits antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses in vitro and in mice www.nature.com
    Sulforaphane COVID-19

    Sulforaphane may be beneficial for the prevention and treatment of coronavirus infections.

    Sulforaphane is a bioactive compound derived from certain cruciferous vegetables, including broccoli (especially broccoli sprouts) and red kale. Robust evidence from epidemiological, clinical, rodent, and in vitro studies indicates that sulforaphane exhibits antioxidant, anti-inflammatory, and antiviral properties. Findings from a recent study suggest that sulforaphane is beneficial for the prevention and treatment of coronavirus infections.

    Coronaviruses are a group of related viruses that cause illness in birds and mammals, including humans. Members of this group include SARS-CoV-1 (which causes severe acute respiratory syndrome, or SARS), MERS-CoV (which causes Middle East respiratory syndrome, or MERS), SARS-CoV-2 (which causes COVID-19), and HCoV-OC43 (which causes the common cold), as well as others.

    The investigators conducted a two-part study involving cultured cells and mice. First, they exposed the cells to sulforaphane for one to two hours and then infected them with SARS-CoV-2 and HCoV-OC43. They also assessed the effects of sulforaphane on previously infected cells. They found that sulforaphane roughly halved the replication of the two viruses in both scenarios. Then they repeated the experiment, but they added remdesivir, an antiviral medication commonly used to treat COVID-19, to the sulforaphane and found that the compounds worked in a synergistic fashion to potently reduce viral replication.

    Next, they gave mice sulforaphane prior to infecting them with SARS-CoV-2 and gauged the compound’s effects. They found that sulforaphane decreased viral replication in the animals' lungs by 1.5 orders of magnitude – a 30-fold reduction – compared to infected mice that didn’t receive sulforaphane. The mice that received sulforaphane also exhibited less lung inflammation, one of the hallmarks of COVID-19 and a driver of poor disease outcomes.

    These findings demonstrate that sulforaphane may be beneficial for preventing or treating COVID-19 while modulating inflammation that typically accompanies the illness. Learn about other strategies that reduce the risk of COVID-19 infection in this episode featuring Dr. Roger Seheult.

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  • Sulforaphane improves behavioral symptoms of autism. molecularautism.biomedcentral.com
    Autism Sulforaphane NRF2 Myrosinase Glucoraphanin

    Autism – often referred to as autism spectrum disorder, or ASD – is a neurodevelopmental disorder characterized by impaired social interaction and communication, as well as restrictive, repetitive patterns of behavior. The disorder typically manifests in early childhood and is slightly more common among boys than girls. Roughly one in 54 people living in the United States has ASD. Findings from a recent clinical trial suggest that sulforaphane improves behavioral symptoms associated with autism.

    Sulforaphane is a bioactive compound derived from precursors (glucoraphanin and myrosinase) in broccoli and broccoli sprouts. It exhibits antioxidant and anti-inflammatory properties and may be beneficial against a wide range of chronic and acute diseases, including cardiovascular disease, neurological disease, cancer, and others. Previous research has demonstrated that sulforaphane reduces behavioral symptoms of autism in young men. Sulforaphane exerts its therapeutic effects through a variety of mechanisms, the most notable of which is the activation of Nrf2, a cellular protein that regulates the expression of antioxidant and stress response proteins that provide protection against oxidative stress due to injury and inflammation. Sulforaphane is the most potent naturally occurring inducer of Nrf2.

    The randomized, placebo-controlled trial, which involved 45 children (ages 3 to 12 years) with autism, occurred in three distinct phases. During the first phase, half of the children received a commercially available dietary supplement containing glucoraphanin and myrosinase (yielding approximately 15 micromoles of sulforaphane) every day for 15 weeks, while the other half received a placebo. During the second phase, which also lasted 15 weeks, all the children received the supplement. During the third phase, which lasted six weeks, none of the children received the supplement. Before and after the intervention, caregivers and investigators evaluated the participants' symptoms using standardized behavioral assessments. Investigators collected blood and urine samples from the participants to assess metabolic and biochemical changes.

    They found that behavioral symptoms among the children who received the sulforaphane supplement improved during the first phase (compared to those on the placebo), but the differences between the two groups were not statistically significant. However, both groups' behavioral symptoms improved during the second phase, as did markers of oxidative stress, mitochondrial respiration, inflammation, and heat shock proteins. The supplement elicited no adverse effects and was well tolerated.

    These findings suggest that sulforaphane improves behavioral symptoms associated with autism. However, the study investigators caution that further study is needed to fully elucidate the clinical effects and mechanisms of action associated with the compound’s effects on autism.

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  • Sulforaphane inhibits activation of the NLRP3 inflammasome in mice microglia cells. www.sciencedirect.com
    Inflammation Sulforaphane NRF2 NLRP3

    Sulforaphane is a bioactive compound derived from certain cruciferous vegetables, such as broccoli and broccoli sprouts. It exerts potent anti-inflammatory properties and switches on the activity of a vast array of cellular protective proteins. A new study in mice demonstrates that sulforaphane inhibits activation of the NLRP3 inflammasome in mice microglia cells via inhibition of the NF-kB pathway and altered gene expression.

    Inflammasomes are large, intracellular complexes that detect and respond to internal and external threats. Activation of inflammasomes has been implicated in a host of inflammatory disorders. The NLRP3 inflammasome in particular triggers the release of proinflammatory cytokines interleukin-1 beta (IL-1β) and IL-18 and drives pyroptosis, a form of cell death that is triggered by proinflammatory signals and closely linked with inflammation.

    Microglia are the brain’s resident immune cells. They serve an essential role in maintaining brain microenvironment homeostasis. Acute activation of microglia modulates inflammation and neurotoxicity, but chronic activation promotes brain inflammation and damage.

    NF-kB is a family of proteins present in mammalian cells. NF-kB influences several aspects of the body’s stress response via its participation in signaling pathways that drive pro-inflammatory processes, ultimately regulating DNA transcription, cytokine production, cell survival, and immune function.

    The authors of the study triggered the activity of the NLRP3 inflammasome in mice microglia cells that had been treated with or without sulforaphane. Then they assessed the level of pyroptosis in the cells, measured expression of IL-1β and IL-18, and tracked the activity of NF-kB. They also measured the cells' mitochondrial production of reactive oxygen species and mitochondrial membrane integrity. The cells treated with sulforaphane showed less pyroptosis, reduced expression of IL-1β and IL-18, and impaired NF-kB activity than the untreated cells. Sulforaphane also reduced reactive oxygen species production and helped maintain mitochondrial membrane integrity.

    These findings suggest that sulforaphane protects the brain via inhibition of the NF-kB pathway and subsequent inhibition of the NLRP3 inflammasome.

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  • Sulforaphane extends lifespan and healthspan in worms via insulin and insulin-like growth factor-1 signaling. www.aging-us.com
    Sulforaphane NRF2

    Sulforaphane is a bioactive compound derived from certain cruciferous vegetables, including broccoli (especially broccoli sprouts) and kale. Robust evidence from epidemiological, clinical, rodent, and in vitro studies indicates that sulforaphane exhibits antioxidant and anti-inflammatory properties and may be beneficial against a wide range of chronic and acute diseases. Evidence from a recent study demonstrates that sulforaphane extends lifespan and healthspan in worms via insulin and insulin-like growth factor-1 (IGF-1) signaling.

    The insulin and IGF-1 pathways play key roles in mammalian metabolism, physiology, and aging and ultimately influence the expression of a variety of antioxidant genes. IGF-1 inhibits the activity of FOXO3, a master regulator of many mammalian genes involved in oxidative stress tolerance and aging. Mice that lack the insulin receptor or the IGF-1 receptor live longer and are more resistant to oxidative stress than normal mice.

    The authors of the study used C. elegans, a type of nematode worm that is commonly used in aging studies. They fed the worms a concentration of sulforaphane that roughly corresponded to 10 milligrams per kilogram of body weight – an amount commonly used in other animal models – and assessed several markers of the worms' health.

    They found that sulforaphane consumption promoted the worms' health and extended their lifespan. The mechanisms that mediated these effects involved inhibition of insulin and IGF-1 signaling and the activation of a FOXO analog called DAF-16. The downstream effect of this inhibition was increased expression of antioxidant genes similar to those involved in oxidative stress tolerance and aging in mammals.

    These findings demonstrate that sulforaphane shows promise as an anti-aging compound via its capacity to reduce oxidative stress. Learn more about sulforaphane in this Q&A featuring Dr. Jed Fahey.

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  • Sulforaphane protects the brain during stroke via hormetic preconditioning. www.sciencedirect.com
    Brain Sulforaphane Stroke NRF2

    Stroke is one of the leading causes of death and disability worldwide, claiming the lives of roughly 5 million people and leaving another 5 million permanently disabled every year. A 2013 study demonstrated that sulforaphane protects the brain during ischemic stroke via hormetic preconditioning.

    Ischemic stroke occurs when blood flow to the brain is reduced or interrupted, starving neurons of oxygen and nutrients. Neuronal death occurs in the immediate area of a stroke within the first few hours of the incident, but nearby cells can be rescued with appropriate therapies. Heme oxygenase-1 (HO-1), an antioxidant enzyme, attenuates neuronal injury. Nrf2, a protein that regulates the expression of antioxidant and stress response proteins, induces HO-1 expression.

    The authors of the study gave mice sulforaphane (5 milligrams per kilogram of body weight) or corn oil with saline via injection. After the mice experienced a stroke, the authors measured the animals' Nrf2 and HO-1 gene expression and assessed behavioral changes, blood-brain barrier integrity, and neurological deficits.

    The mice that received sulforaphane treatment showed increased HO-1 expression, reduced blood-brain barrier damage, and fewer neurological deficits than mice that received the corn oil/saline. Levels of peroxynitrite, a short-lived reactive oxygen species associated with cell death, increased in the mice, suggesting that hormetic preconditioning mediated the protection sulforaphane provided against stroke.

    These findings suggest that dietary or supplemental interventions (such as sulforaphane) that precondition the brain against injury offer promise as strategies to reduce complications associated with stroke.

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  • Gut microbial conversion of glucosinolates to isothiocyanates is highly variable in humans. cancerpreventionresearch.aacrjournals.org
    Gut Microbiome Sulforaphane Isothiocyanates Myrosinase Glucoraphanin

    Glucoraphanin, a precursor to sulforaphane, is a type of glucosinolate found primarily in broccoli and kale. Its conversion to sulforaphane requires myrosinase, an enzyme co-located within the leaves, stems, and other components of the plants in which it is found. Cooking temperatures inactivate myrosinase, effectively preventing isothiocyanate conversion and allowing unhydrolyzed glucosinolates to pass into the gut. In humans, myrosinase-producing gut bacteria can convert these glucosinolates to their cognate isothiocyanates. Findings from a 2012 study indicate that microbial conversion of glucosinolates to isothiocyanates is highly variable.

    Previous research has demonstrated that sulforaphane administration promotes uniformly high urinary excretion of dithiocarbamate metabolites, accounting for as much as 90 percent of the administered sulforaphane over a 24-hour period. Dithiocarbamate levels in urine serve as a biomarker of glucosinolate intake.

    The study involved two dissimilar groups of people: rural Han Chinese and racially mixed Baltimoreans. The participants abstained from cruciferous vegetable consumption for three days prior to the beginning of the study. They had not taken antibiotics for two weeks prior. Each of the participants kept a food diary, provided their medical history, and kept track of their bowel activity. The participants took a glucoraphanin-rich broccoli sprout extract that provided 200 micromoles of glucoraphanin in water. The authors of the study collected urine samples from 8 a.m. to 4 p.m. and from 4 p.m. until 8 a.m. on the following morning.

    They found that microbial-induced conversion of glucoraphanin to sulforaphane is highly variable (ranging from 1 to 40 percent of dose) and subject to interindividual differences in gut bacteria populations. As such, conversion is distinguished by “high converters” – people with high elimination profiles, and “low converters”– those with low elimination profiles. The authors of the study identified no demographic factors that affected conversion efficiency, but they did note that conversion of glucoraphanin to dithiocarbamate was greater during the day.

    Watch this clip in which Dr. Jed Fahey describes some of the factors that influence the conversion of myrosinase-driven conversion of glucoraphanin to sulforaphane.

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  • Sulforaphane improves blood glucose control in obese people with type 2 diabetes. stm.sciencemag.org
    Nutrition Diabetes Sulforaphane NRF2 Metformin Glucoraphanin

    Type 2 diabetes is a progressive metabolic disorder characterized by high blood glucose levels and insulin resistance. Long-term complications from poorly controlled type 2 diabetes include heart disease, stroke, and kidney failure, among others. Findings from a 2017 study demonstrated that sulforaphane reduces glucose production in the liver and improves blood glucose control. Glucose is the body’s primary metabolic fuel. In the fasted state, the body can produce glucose via gluconeogenesis, a highly conserved pathway that occurs primarily in the liver. Increased liver gluconeogenesis among people with type 2 diabetes is a major contributor to high blood glucose and subsequent disease complications.

    The authors of the study investigated the effects of sulforaphane in several rodent models of type 2 diabetes and found that sulforaphane ameliorated many of the hallmark characteristics of the disease. Then they assessed sulforaphane’s effects in 97 people with type 2 diabetes. Sixty of the participants had well-regulated disease, but 37 had poorly regulated disease. Of those with poorly regulated disease, 17 had obesity. Nearly all of the participants took metformin, a common blood glucose-lowering drug.

    Participants received either an oral placebo or glucoraphanin-rich broccoli sprout extract every day for 12 weeks. The authors of the study measured the participants' fasting blood glucose and HbA1c (a measure of long-term blood glucose control) levels and assessed their glucose tolerance prior to and after the intervention.

    Sulforaphane administration improved fasting blood glucose and HbA1c levels in the obese participants who had poorly regulated type 2 diabetes. Sulforaphane mediated these effects via Nrf2 activity and subsequent reduced expression of enzymes that promote glucose production in the liver.

    These findings suggest that sulforaphane ameliorates some of the hallmark characteristics of diabetes in humans. The mechanisms by which sulforaphane mediates these effects differ from those of metformin, suggesting that the two could work in a complementary manner to improve blood glucose control in obese people with type 2 diabetes.

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  • Sulforaphane reduces biochemical recurrence in men who have had prostate cancer. pubmed.ncbi.nlm.nih.gov
    Cancer Prostate Sulforaphane NRF2

    Prostate cancer is the second most common cancer among men, affecting more than 1.3 million men worldwide. Many men undergo radical prostatectomy to treat their cancer. Findings from a 2015 study demonstrated that sulforaphane reduces biochemical recurrence in men who have had prostate cancer.

    Biochemical recurrence is a phenomenon in which serum levels of prostate specific antigen (PSA) levels increase. It is an indicator of localized or metastatic disease. As many as 40 percent of men treated with radical prostatectomy experience biochemical recurrence; 34 percent of these will develop metastatic disease.

    The double-blind, randomized, placebo-controlled study involved 75 men (average age, 69 years) who had undergone radical prostatectomy and were experiencing increased PSA levels. Roughly half of the men took a supplement providing 60 milligrams of sulforaphane for six months; the other half took a placebo. The authors of the study measured the men’s PSA levels before and two months after the treatment ended.

    Increases in the average PSA levels were much lower among the men who took the sulforaphane. The PSA doubling time among men who took sulforaphane was ~29 months; doubling time among the men who took the placebo was ~16 months – an 86 percent difference. The effects of sulforaphane remained up to three months after the intervention.

    These findings suggest that sulforaphane shows promise as a strategy to prevent biochemical recurrence among men who have had radical prostatectomy for prostate cancer. Additional studies are needed to confirm these findings.

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  • Sulforaphane promotes urinary excretion of benzene, a common air pollutant. academic.oup.com
    Pollution Sulforaphane NRF2

    Sulforaphane promotes the production of glutathione, a powerful antioxidant that facilitates the body’s excretion of toxic substances. When glutathione binds with benzene, a known carcinogen present in air pollution, the two form mercapturic acids, which can be excreted and measured in urine. Findings from a 2019 study demonstrated that sulforaphane provided in a broccoli sprout beverage promoted excretion of benzene, as reflected in urinary mercapturic acid levels.

    The intervention study involved 170 healthy adult participants between the ages of 21 and 65 years living in Qidong, China, an area known for its high levels of air pollution. The participants drank a placebo or a broccoli-sprout beverage containing one of three doses of sulforaphane – “high,” “medium,” or “low" – twice a day for a period of 10 days. After drinking the beverage, the participants provided a urine sample, which was assessed for benzene metabolites.

    The authors of the study found that the high dose of sulforaphane markedly increased the production of several urinary metabolites. In particular, excretion of mercapturic acids increased by more than 63 percent in those taking the high dose. Mercapturic acid excretion in those who received the medium and low dose, however, was not significantly different from those who took the placebo.

    These findings demonstrated that a broccoli sprout beverage containing sulforaphane enhanced the detoxication of benzene, an important airborne pollutant, and suggest that population-based strategies that employ a dietary approach are viable options for improving healthspan in humans.

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  • Sulforaphane reduces behavioral symptoms of autism in young men. www.ingentaconnect.com
    Autism Sulforaphane NRF2

    Autism spectrum disorder, or ASD, is a neurodevelopment disorder characterized by impaired social interaction and communication, as well as restrictive, repetitive patterns of behavior. ASD affects roughly one in 68 people and is more common among males than females. A 2014 study showed that sulforaphane reduces communication impairments and behavioral symptoms in young men with autism.

    Sulforaphane demonstrates low toxicity. It has been shown to reverse physiological anomalies commonly associated with ASD, including increased oxidative stress, mitochondrial dysfunction, and neuroinflammation.

    The placebo-controlled, double-blind, randomized trial involved 44 young men between the ages of 13 and 27 years who had been diagnosed with moderate to severe ASD. The authors of the study gave 29 of the participants sulforaphane derived from broccoli sprout extracts and gave the remaining 15 participants a placebo. They received their respective treatments for 18 weeks, followed by four weeks without treatment. Sulforaphane doses ranged between 50 and 150 micromoles (~9 milligrams and 26 milligrams, respectively). The participants' parents, caregivers, and physicians provided assessments of the young men’s behavior using the Aberrant Behavior Checklist, Social Responsiveness Scale, and Clinical Global Impression Improvement Scale (CGI-I).

    After 18 weeks on the treatment, the participants who took the placebo experienced little change, but those who took the sulforaphane showed marked improvements in their behaviors. In particular, the CGI-I scores reflected improvements in social interaction, behavior, and verbal communication. After the sulforaphane treatment ended, the participants' scores rose toward pretreatment levels on all assessments.

    These findings suggest that sulforaphane ameliorates many of the behavioral symptoms associated with ASD. A follow-up study reflected similar effects.

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  • A pilot trial finds sulforaphane treatment increases glutathione levels in the brain. www.karger.com
    Brain Sulforaphane Glutathione NRF2 Moringa

    Cellular damage incurred by oxidative stress underlies the pathophysiology of many chronic health disorders, including neuropsychiatric conditions such as schizophrenia. Glutathione, an antioxidant compound produced by the body’s cells, helps prevent damage from oxidative stress. Evidence from a 2018 study suggests that sulforaphane increases glutathione in the brain.

    Scientists typically rely on magnetic resonance spectrometry (MRS) for measuring glutathione levels in brain tissue. Evidence suggests MRS is inadequate, however, and often yields inconsistent results across studies. These inconsistencies have prompted some investigators to explore the reliability of glutathione level measurements in blood as an indicator of oxidative stress-associated brain changes.

    The pilot clinical study involved nine healthy adults. Eight of the participants were between the ages of 21 and 26 years; one was 56 years old. Each of the participants took 100 micromoles of sulforaphane (from a standardized broccoli sprout extract) by mouth every morning for one week. The authors of the study collected urine and blood specimens from the participants and performed MRS scans on their brains prior to the first dose of sulforaphane and within four hours of the final dose.

    At the end of the week-long study, the participants' blood cell glutathione levels increased 32 percent. The MRS scans revealed similar increases in the thalamus, a region of the brain involved in information processing and a key player in schizophrenia. These observations were consistent regardless of age, sex, or race of the participants.

    These findings suggest that sulforaphane shows promise as a therapeutic strategy for modulating oxidative stress in the brain, an underlying feature of schizophrenia. Some evidence that moringin, an isothiocyanate compound derived from moringa, may be useful in treating some of the symptoms of schizophrenia. Watch this clip in which Dr. Jed Fahey describes the health benefits associated with moringin and discusses the chemical structure differences between it and sulforaphane.

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  • Nrf2 pathway is a major target for sulforaphane. www.sciencedirect.com
    Nutrition Sulforaphane Glutathione NRF2

    Nrf2 (nuclear factor erythroid 2-related factor 2) is a cellular protein that regulates the expression of antioxidant and stress response proteins. It participates in the Keap1/Nrf2/ARE biological pathway – the primary mechanism by which sulforaphane exerts its beneficial effects. A 2017 review describes the role of sulforaphane in the Keap1/Nrf2/ARE pathway and summarizes the beneficial health effects associated with the compound.

    The Keap1/Nrf2/ARE pathway is a key mediator of cytoprotective responses to oxidative and electrophilic stressors. Under normal cellular conditions, Keap1 tethers Nrf2 in the cytoplasm (the region of the cell outside the nucleus), where it can be tagged and delivered for degradation. However, following exposure to stressors, Keap1 undergoes modifications that impair its ability to bind to and target Nrf2 for degradation. As a result, Nrf2 is free to travel to the nucleus, where it binds to antioxidant response elements (AREs) of DNA. AREs are sequences in the regulatory regions of genes that activate transcription of a diverse group of cytoprotective enzymes.

    Isothiocyanates react with certain regions on Keap1, eliminating Keap1’s ability to target Nrf2 for degradation – effectively serving the role of stressor. Sulforaphane, an isothiocyanate derived from broccoli and broccoli sprouts, is the most potent naturally occurring inducer of Nrf2.

    The authors of the review presented evidence that sulforaphane protects against carcinogenesis in models of skin, oral, stomach, colon, lung, prostate, and bladder cancer. They also reported that feeding studies involving humans and consumption of isothiocyanate-rich cruciferous vegetables have demonstrated measurable Nrf2 activity, reflected in increased levels antioxidant proteins and enzymes, including glutathione S-transferase and NQO1. Future research will inform optimal dosages and formulations for clinical trials.

    Watch this clip in which Dr. Jed Fahey describes the early co-discoveries of sulforaphane and Nrf2 and describes the importance of the Nrf2 pathway.

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  • Gut myrosinases convert glucosinolates to sulforaphane. cancerpreventionresearch.aacrjournals.org
    Nutrition Sulforaphane NRF2 Glucoraphanin

    The conversion of glucoraphanin to sulforaphane requires myrosinase, an enzyme co-located within the leaves, stems, and other components of the plants in which it is found. Cooking temperatures inactivate myrosinase, effectively preventing isothiocyanate conversion and allowing unhydrolyzed glucosinolates to pass into the gut. In humans, myrosinase-producing gut bacteria can convert these glucosinolates to their cognate isothiocyanates. Findings from a 2012 study indicate that microbial conversion of glucosinolates to isothiocyanates is highly variable.

    Previous research has demonstrated that sulforaphane administration promotes uniformly high urinary excretion of dithiocarbamate metabolites, accounting for as much as 90 percent of the administered sulforaphane over a 24-hour period. Dithiocarbamate levels in urine serve as a biomarker of glucosinolate intake.

    The study involved two dissimilar groups of people: rural Han Chinese and racially mixed Baltimoreans. The participants abstained from cruciferous vegetable consumption for three days prior to the beginning of the study. They had not taken antibiotics for two weeks prior. Each of the participants kept a food diary, provided their medical history, and kept track of their bowel activity. The participants took a glucoraphanin-rich broccoli sprout extract that provided 200 micromoles of glucoraphanin in water. The authors of the study collected urine samples from 8 a.m. to 4 p.m. and from 4 p.m. until 8 a.m. on the following morning.

    They found that microbial-induced conversion of glucoraphanin to sulforaphane is highly variable (ranging from 1 to 40 percent of dose) and subject to interindividual differences in gut bacteria populations. As such, conversion is distinguished by “high converters” – people with high elimination profiles, and “low converters”– those with low elimination profiles. The authors of the study identified no demographic factors that affected conversion efficiency, but they did note that conversion of glucoraphanin to dithiocarbamate was greater during the day.

    Watch this clip in which Dr. Jed Fahey describes some of the factors that influence the conversion of myrosinase-driven conversion of glucoraphanin to sulforaphane.

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  • Determining the optimal dose and source of sulforaphane poses challenges. www.mdpi.com
    Nutrition Sulforaphane NRF2 Myrosinase Glucoraphanin

    A substantial body of evidence from experimental, epidemiological, and clinical studies demonstrates the beneficial effects of sulforaphane consumption on human health. Many questions remain, however, regarding optimal formulation, bioavailability, and dosage of sulforaphane. A 2019 review discusses these and other aspects of the current state of evidence surrounding sulforaphane.

    Sulforaphane is the end-product of a chemical reaction between two naturally occurring plant compounds – glucoraphanin and myrosinase. These compounds, often referred to as secondary metabolites, are not required for the plant’s growth or reproduction. Rather, they confer an advantage to the plant, particularly in terms of defense, participating in a dual-component chemical defense system – commonly referred to as the “mustard oil bomb” – that protects plants from environmental stressors. Glucoraphanin content in broccoli sprouts and mature broccoli vary across species and cultivar and is influenced by factors such as soil and growing conditions, harvest time, and post-harvest storage.

    Most rodent studies of sulforaphane’s effects administer the end product via oral, intraperitoneal, or topical means. The median effective dose is 175 micromoles (~30 milligrams) per kilogram of the animal’s body weight when given orally; the median effective dose when given intraperitoneally is 113 micromoles (~20 milligrams) per kilogram. Most studies report beneficial outcomes, but this might be due to publication bias – the tendency for researchers to publish favorable results only. High doses (greater than 150 milligrams) elicited negative effects, including sleepiness, hypothermia, impaired motor coordination, and even death. When given with other drugs, sulforaphane potentiated some of the drugs' effects.

    In humans, sulforaphane undergoes extensive biotransformation in the gut to yield mercapturic acid, which can be measured in urine and serves as a biomarker of intake. In general, sulforaphane is rapidly absorbed and eliminated, with most people excreting between 70 and 90 percent of the dose taken.

    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 varied markedly and in terms of whether supplied as glucoraphanin (the precursor) or sulforaphane (the end product). The median dose of glucoraphanin was 190 micromoles (~76 milligrams) and of sulforaphane was 100 micromoles (~18 milligrams).

    The authors of the review enumerate several issues that must be overcome in designing and conducting clinical studies with sulforaphane, but they stress the importance of plant-based diets as delivery modes for not only sulforaphane but other bioactive compounds that promote health. They also noted concerns that determining dose is inherently difficult in light of the differences in bioavailability of glucoraphanin and sulforaphane; translating animal data to humans poses many challenges.

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  • Sulforaphane inhibits enzyme involved in amyloid-beta production. www.mdpi.com
    Nutrition Alzheimer's Sulforaphane NRF2

    Amyloid-beta is a toxic 42-amino acid peptide that clumps and forms plaques in the brain with age. Amyloid-beta is associated with Alzheimer’s disease, a progressive neurodegenerative disease and the most common cause of dementia. Findings from a new study demonstrate that sulforaphane impairs BACE1, an enzyme involved in the production of amyloid-beta.

    BACE1, or beta site amyloid precursor protein cleaving enzyme 1, is produced primarily in the central nervous system. People with Alzheimer’s disease often have high levels of BACE1 in their brains.

    The authors of the study set out to evaluate sulforaphane’s capacity to inhibit BACE1. They used fluorescence resonance energy transfer analysis to determine the enzyme’s activity and then calculated its kinetics. They assessed sulforaphane’s enzyme selectivity in the presence of several other enzymes and compared its effects to those of resveratrol and quercetin, bioactive compounds that exert beneficial effects on human health.

    They found that sulforaphane was six times more effective against BACE1 compared to resveratrol and quercetin. Sulforaphane demonstrated high affinity for BACE1 and had few off-target effects, suggesting that sulforaphane shows promise as a candidate to reduce the activity of BACE1, potentially playing a role in preventing Alzheimer’s disease.

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  • Sulforaphane mitigates age-related skeletal and heart muscle dysfunction via activation of Nrf2. onlinelibrary.wiley.com
    Sulforaphane NRF2

    Sulforaphane is a plant-based dietary compound derived from cruciferous vegetables such as broccoli (especially broccoli sprouts), kale, and others. It exerts a wide range of beneficial health effects on the human body. A new study suggests that sulforaphane mitigates sarcopenia and cardiac dysfunction via activation of Nrf2.

    Sarcopenia, the loss of muscle tissue that occurs during the aging process, and cardiac dysfunction are common features of aging. Key players in the pathophysiology of these conditions are mitochondrial dysfunction and oxidative damage.

    Nrf2 is a cellular protein that regulates the expression of antioxidant and stress response proteins. Nrf2 is an element of the Keap1-Nrf2-ARE biological pathway. It activates the transcription of cytoprotective proteins that protect against oxidative damage due to injury and inflammation. Sulforaphane is the most potent naturally occurring inducer of Nrf2.

    The authors of the study fed young and old mice either regular mouse chow or a sulforaphane-supplemented chow for 12 weeks. At the end of the study period, they assessed the animals' Nrf2 activity, mitochondrial function, and skeletal and cardiac muscle function.

    They found that the older mice that ate the regular chow showed marked reductions in Nrf2 activity, mitochondrial function, and skeletal and cardiac function, compared to young mice. But the older mice that ate sulforaphane-supplemented chow showed improvements in Nrf2 activity, mitochondrial function, cardiac function, exercise capacity, and measures of metabolic function.

    These findings suggest that the declines in Nrf2 activity and mitochondrial function that commonly occur with aging drive the development of age‐related disease processes. Consequently, sulforaphane supplementation might be a safe and effective strategy to protect against these processes.

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  • Maternal immune activation during pregnancy increases the severity of autism symptoms in children. www.eurekalert.org
    Pregnancy Autism Sulforaphane Autoimmunity

    Autism spectrum disorder (ASD) is a developmental condition characterized by impaired social interaction, behavioral problems, and poor communication. The disorder typically manifests in early childhood and is slightly more common among boys than girls. Roughly one in 54 people living in the United States has ASD. Findings from a new study suggest that maternal immune activation during pregnancy increases the severity of ASD in offspring.

    Maternal immune activation due to autoimmune disorders, asthma, or allergies switches on the activity of inflammatory pathways and proinflammatory molecules. Many of these molecules can cross the blood–brain barrier and the placenta, potentially disrupting fetal development. Elevated levels of these proinflammatory molecules have been found at birth or during development in some people with ASD – a finding that has been linked with increased severity of symptoms.

    The study involved 363 children who were enrolled in the Autism Phenome Project or the Girls with Autism Imaging of Neurodevelopment studies, along with their mothers. The authors of the study assessed children’s behavioral and emotional problems and reviewed the mothers' pregnancy histories.

    They found that asthma was the most common immune condition among the mothers, but other conditions, including Hashimoto’s thyroiditis, rheumatoid arthritis, and psoriasis were reported as well. Roughly 20 percent of the mothers of male children with ASD had asthma. Maternal immune conditions were associated with increased behavioral and emotional problems but not cognitive function in both sexes.

    These findings indicate that maternal immune conditions may influence the severity of ASD symptoms in offspring and the severity of these symptoms may vary between males and females. Although there is no cure for ASD, robust data demonstrate that sulforaphane, a bioactive compound derived from cruciferous vegetables, especially broccoli sprouts, may be beneficial in reducing many of the behavioral and emotions symptoms associated with the condition.

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  • Seasonal variation in Nrf2 antioxidant pathway influence winter depression-like behavior in fish. neurosciencenews.com
    Depression Sulforaphane NRF2 Traditional Medicine

    Seasonal affective disorder (SAD) is a form of depression that is influenced by seasonal changes in weather and daylight. It commonly occurs in the dark, cool days of winter but can occur during other times of the year, as well. Approximately 10 percent of people worldwide experience SAD. A new study suggests that seasonal variation in the Nrf2 antioxidant pathway regulates winter depression-like behavior in fish.

    Nrf2 (short for nuclear factor erythroid 2-related factor 2) is a cellular protein that regulates the expression of antioxidant and stress response proteins. Nrf2 functions within a biological pathway called Keap1-Nrf2-ARE, where it switches on the transcription of various cytoprotective proteins that protect against oxidative damage triggered by injury and inflammation.

    The authors of the study exposed medaka, a type of fish that exhibits seasonal SAD-like differences in its behavior to either summer- or winter-like conditions. Then they examined the metabolites produced in their brains. They found evidence that winter-like conditions altered levels of 68 metabolites, some of which are associated with depression. In particular, winter-like conditions reduced levels of glutathione, a powerful antioxidant compound produced by the body’s cells. Glutathione helps prevent inflammation, a key driver in depression.

    Then the study authors analyzed gene expression in the fish and found that winter-like conditions altered signaling pathways that are implicated in depression, including Nrf2. Results of a chemical screen indicated that celastrol, a plant-based compound commonly used in traditional Chinese medicine, activated Nrf2 signaling, which in turn induced the activity of Nrf2 target genes, including glutathione.

    These findings demonstrate that celastrol could be beneficial in treating some of the symptoms associated with seasonal depression by switching on the activity of antioxidant pathways such as Nrf2. Interestingly, sulforaphane, an isothiocyanate compound derived from broccoli, is the most potent naturally occurring inducer of Nrf2 activity. Watch this clip featuring sulforaphane expert Dr. Jed Fahey in which he describes the importance of the Nrf2 pathway.

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  • Sulforaphane from broccoli sprout extract improves fasting glucose and HbA1c in obese patients with dysregulated type 2 diabetes. www.sciencedaily.com
    Diabetes Sulforaphane Insulin Isothiocyanates Blood Sugar NRF2

    Type 2 diabetes is a metabolic disorder characterized by high blood sugar and insulin resistance. Long-term complications from poorly controlled type 2 diabetes include heart disease, stroke, diabetic retinopathy (and subsequent blindness), kidney failure, and diminished peripheral blood flow, which may lead to amputations. An estimated 500 million people worldwide are living with type 2 diabetes. A 2017 study suggests that sulforaphane may be beneficial in treating the symptoms of type 2 diabetes.

    Sulforaphane is an isothiocyanate compound derived from cruciferous vegetables such as broccoli, Brussels sprouts, and mustard. Sulforaphane is produced when the cruciferous plant is damaged by insects or eaten by humans. The compound activates cytoprotective mechanisms within cells in a hormetic-type response and has demonstrated beneficial effects against several chronic health conditions, including autism, cancer, cardiovascular disease, and others.

    The authors of the study identified sulforaphane out of more than 3,800 drugs and natural products as a potential therapeutic for type 2 diabetes based on statistical analysis that showed that sulforaphane’s protective effects (called a drug signature) had the potential to counteract diabetes’ harmful effects (called a disease signature).

    They then conducted a randomized double-blind placebo-controlled study involving 97 adults with type 2 diabetes. All the participants were of Scandinavian ethnicity and had diabetes for less than 10 years. Sixty of the participants had well-controlled diabetes; the remaining 37 had poorly controlled diabetes. Of those with poorly controlled diabetes, 17 were obese, and 20 were not obese.

    After undergoing blood tests to check their fasting blood sugar and HbA1c (a measure of long-term blood sugar control) and taking an oral glucose challenge, the participants took either a placebo or powdered broccoli sprout extract (containing 150 µmol sulforaphane per dose) every day for 12 weeks.

    At the end of the study period, the blood tests and the oral glucose challenge were repeated. The participants who took broccoli sprout extract and whose diabetes was well-controlled experienced no changes in their fasting blood sugar or HbA1c levels. The participants who were heaviest and had poorly controlled diabetes saw the greatest benefits from the broccoli sprout extract. After 12 weeks of treatment, obese participants’ fasting blood sugar levels and HbA1c levels decreased, but the participants who received a placebo experienced slightly increased blood sugar and HbA1c levels.

    The researchers also measured the amount of sulforaphane in the participants’ blood and noted that the levels varied from person to person. The higher the blood concentration, however, the greater the change in the participants’ fasting blood sugar.

    Although very few of the participants experienced any negative effects after taking the broccoli sprout extracts, the authors of the study cautioned against prescribing it to patients because more testing needs to be done to understand how sulforaphane works and who would benefit most from it.

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  • New placebo-controlled trial finds that healthy adults given a broccoli sprout beverage high in sulforaphane had a 63% increase in benzene excretion. academic.oup.com
    Cancer Pollution Sulforaphane NRF2 Glucoraphanin

    A new placebo-controlled trial finds that healthy adults given a broccoli sprout beverage high in sulforaphane had a 63% increase in excretion in the carcinogen benzene which is a compound found in air pollution and tobacco smoke.

    The study also showed that the sulforaphane’s role in benzene excretion was dose-dependant. The high sulforaphane dose increased benzene excretion by 63% and half the sulforaphane dose caused an 11% increase in benzene excretion.

    The high dose broccoli sprout beverage contained 600 μmol of glucoraphanin (sulforaphane precursor) and 40 μmol sulforaphane, whereas the half dose contained 300 μmol of glucoraphanin and 20 μmol of sulforaphane.

    I have referred to other studies showing similar effects of broccoli sprouts on benzene excretion. To learn more about how sulforaphane increases the excretion of carcinogens like benzene check out the in-depth episode we did on sulforaphane. https://www.foundmyfitness.com/episodes/sulforaphane

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  • A small trial finds that when people eat cooked broccoli with 1 gram of powdered mustard seed the bioavailability of sulforaphane increased 4x. www.ncbi.nlm.nih.gov
    Sulforaphane NRF2 Myrosinase Glucoraphanin

    A small trial finds that when people eat cooked broccoli with 1 gram of powdered mustard seed the bioavailability of sulforaphane increased more than 4-fold compared to eating cooked broccoli alone.

    This is very applicable data because cooking broccoli inactivates the enzyme (called myrosinase) that converts glucoraphanin into sulforaphane. The mustard seed powder provides a viable source of the enzyme myrosinase that can be sprinkled on top of the broccoli after it is cooked. Other studies have shown similar data. I usually try to sprinkle mustard seed on my cooked broccoli and other cooked cruciferous vegetables like sauteed kale.

    Check out our very comprehensive video on sulforaphane and our interview with Dr. Jed Fahey for more information on the benefits of sulforaphane. The comprehensive sulforaphane video: https://www.foundmyfitness.com/episodes/sulforaphane The podcast episode with Dr. Jed Fahey: https://www.foundmyfitness.com/episodes/jed-w-fahey

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  • Another pilot clinical study finds sulforaphane increased blood glutathione levels and increased levels in brain. www.ncbi.nlm.nih.gov
    Sulforaphane Glutathione NRF2

    Another pilot clinical study finds sulforaphane (abundant in broccoli sprouts and other cruciferous vegetables) increased blood glutathione levels and this correlated with increased glutathione in certain brain regions in healthy people.

    Sulforaphane is one of the strongest inducers of the Nrf2 genetic pathway which activates genes involved in glutathione production. Other studies have found that sulforaphane increased blood glutathione levels in people but this study is the first to show that glutathione was also increased in certain brain regions and this correlated with increased plasma glutathione.

    The increased glutathione in the brain may be one mechanism by which sulforaphane helps improves symptoms of autism which it has been shown to do in multiple clinical studies. Schizophrenia is also linked to increased oxidative stress in the brain and sulforaphane has been shown to improve symptoms of schizophrenia in a small open-label study. A larger randomized placebo-controlled study investigating the effects of sulforaphane on schizophrenia is ongoing and is expected to end in July of 2019.

    The dose of sulforaphane used in this study was approximately 17.7 mg for 7 days.

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  • A new study found sulforaphane (found in broccoli sprouts) improved behavior & social responsiveness in children with autism. www.ncbi.nlm.nih.gov
    Autism Sulforaphane NRF2

    A new study found sulforaphane (found in broccoli sprouts) improved behavior and social responsiveness in children with autism spectrum disorder. It also found that clinical improvements were correlated with two urinary metabolites known to be involved in redox metabolism, which sulforaphane is known to affect.

    This study builds upon findings from a prior randomized, placebo-controlled trial which showed sulforaphane improved symptoms of autism in young adults.

    I did a podcast with one of the scientists involved in both of these clinical studies, Dr. Jed Fahey. We discuss the effects of sulforaphane on the brain and specifically how it helps treat autism spectrum disorder.

    You can find the episode on sulforaphane with Dr. Fahey along with show notes and a transcript on the foundmyfitness episodes page: https://www.foundmyfitness.com/episodes/jed-w-fahey Link to the previous RCT: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4217462/

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  • Sulforaphane, which is high in broccoli sprouts, clears away brain amyloid plaques and tau tangles and ameliorated memory defects in mice. www.ncbi.nlm.nih.gov
    Alzheimer's Sulforaphane Protein NRF2

    Sulforaphane, which is high in broccoli sprouts, clears away brain amyloid plaques and tau tangles and ameliorated memory defects in mice engineered to get Alzheimer’s disease.

    The sulforaphane also increased heat shock proteins in the brain. Heat shock proteins play a role in disaggregating protein aggregates.

    The precursor to sulforaphane is found in cruciferous vegetables but is highest in broccoli sprouts which can contain up to 100 times more than mature broccoli.

    To learn more about the role sulforaphane plays in human health, check out my comprehensive video and the podcast I did with sulforaphane expert Dr. Jed Fahey.

    Sulforaphane video: https://www.foundmyfitness.com/episodes/sulforaphane

    Dr. Jed Fahey podcast: https://www.foundmyfitness.com/episodes/jed-w-fahey

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  • UDP-glucuronosyltransferases (UGTs) of the blood-brain barrier: their role in drug metabolism and detoxication www.frontiersin.org
    Brain Sulforaphane Dopamine

    [Abstract]

    UDP-glucuronosyltransferases (UGTs) form a multigenic family of membrane-bound enzymes expressed in various tissues, including brain. They catalyze the formation of β-D-glucuronides from structurally unrelated substances (drugs, other xenobiotics, as well as endogenous compounds) by the linkage of glucuronic acid from the high energy donor, UDP-α-D-glucuronic acid.

    In brain, UGTs actively participate to the overall protection of the tissue against the intrusion of potentially harmful lipophilic substances that are metabolized as hydrophilic glucuronides. These metabolites are generally inactive, except for important pharmacologically glucuronides such as morphine-6-glucuronide. UGTs are mainly expressed in endothelial cells and astrocytes of the blood brain barrier (BBB). They are also associated to brain interfaces devoid of BBB, such as circumventricular organ, pineal gland, pituitary gland and neuro-olfactory tissues.

    Beside their key-role as a detoxication barrier, UGTs play a role in the steady-state of endogenous compounds, like steroids or dopamine (DA) that participate to the function of the brain. UGT isoforms of family 1A, 2A, 2B and 3A are expressed in brain tissues to various levels and are known to present distinct but overlapping substrate specificity. The importance of these enzyme species with regard to the formation of toxic, pharmacologically or physiologically relevant glucuronides in the brain will be discussed.

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  • Probiotic was engineered to make an enzyme able to produce sulforaphane from the precursor in broccoli extract. It reduced tumor size by over 75%. www.nature.com
    Cancer Sulforaphane NRF2

    Scientists use a probiotic and broccoli extract to target colorectal cancer cells.

    Probiotic was engineered to make an enzyme able to produce sulforaphane from the precursor in broccoli extract. It reduced tumor size by over 75% (in mice).

    This is pretty clever because they modified the e.coli to bind to cancer cells. One issue w/ broccoli extract is that the conversion to sulforaphane in vivo depends on gut bacteria, usually resulting in different bioavailability from person to person.

    For a great discussion on sulforaphane, watch these two podcasts.

    Sulforaphane and Its Effects on Cancer, Mortality, Aging, Brain and Behavior, Heart Disease & More: https://www.foundmyfitness.com/episodes/sulforaphane

    Interview with expert Dr. Jed Fahey: https://www.foundmyfitness.com/episodes/jed-w-fahey

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  • Consumption of broccoli sprouts during late gestation & lactation confers protection against developmental delay induced by maternal inflammation. www.sciencedirect.com
    Nutrition Brain Diet Development Sulforaphane Protein Lipopolysaccharide

    This is an interesting rodent study. The problem is, however, broccoli sprouts are not usually advisable for women that are pregnant because they can be a source of foodborne illness. If proven safe, however, it seems (at the surface) plausible that there could be ways to reduce the risk of in the future. Perhaps through supplementation?

    FTA:

    Methods: Pregnant Long-Evans rats were administered i.p. Injections of saline (100 μl) or lipopolysaccharide (LPS, 200 μg/kg), every 12 h on embryonic day (E) 19 and 20. In the treatment groups, dams were supplemented with 200 mg/day of dried BrSp from E14 until postnatal day 21. Pups underwent a series of neurodevelopmental reflex tests from postnatal day 3–21 followed by neuropathological analyses.

    Note: LPS elicits a strong immune response.

    Results: Pups born from the LPS group were significantly growth restricted (p < 0.001) and delayed in hindlimb placing (p < 0.05), cliff avoidance (p < 0.05), and gait (p < 0.001) compared to controls. […] Dietary supplementation with [broccoli sprouts] to offspring exposed to LPS had increased birth weights (p < 0.001), were no longer delayed in acquiring hindlimb placing, cliff avoidance, gait, and posture, and groomed less compared to LPS alone pups (p < 0.01). Histological analyses revealed that LPS pups had reduced myelin basic protein compared to controls.

    The discussion had some interesting things to say about why mitigating the fetal inflammatory response is a big deal:

    An important recognized antepartum risk factor is the systemic fetal inflammatory response (FIR) [3], which is associated with a four-fold increase in the risk of developing [cerebral palsy]. Both clinical and experimental studies have provided strong evidence supporting the association between FIR and brain injury leading to [cerebral palsy].

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  • Sulforaphane reduces circulating lead by almost 2/3rds and improve memory-related water maze task in lead-exposed mice. www.sciencedirect.com
    Fulltext Brain Alzheimer's Memory Environment Sulforaphane Vitamin A NRF2

    This study shows some pretty interesting things in terms of a dramatic ability to (apparently) decrease lead status in the blood and seems to also really improve memory performance and reduce oxidative stress (from the lead) in the brain. It’s really pretty impressive, especially in light of the fact that, according to this paper, the neurotoxic effects are associated with amyloid beta production. This makes it plausibly relevant in the context of Alzheimer’s.

    FTA:

    “Compared with the normal saline and [corn oil-treated] groups, the lead level in the blood of sulforaphane and SFN + Vitamin E group had a significant decrease. In water maze test, the mice treated with sulforaphane or/and Vitamin E performed better than mice of the normal saline and corn oil groups. In addition, a remarkable decrease in MDA (malondialdehyde) level was found in mice treated with sulforaphane or/and vitamin E than those in normal saline and corn oil groups.”

    Not stated explicitly so far as I could tell in the article, but the figure 2 makes it look like lead content in the blood is reduced by almost 2/3rds. According to figure 6, MDA in the hippocampus, a marker for oxidative status, rises by approximately half of what the lead-exposed non-SFN group did (normal saline). In other words: more oxidative stress than control in the hippocampus, but not as much as lead without sulforaphane. It’s almost like they got half the lead exposure, if the dose-response was linear. Similarly, actual memory function was dramatically improved (measured by maze task) relative to non-sulforaphane group… but still lagged control by a little bit.

    Altogether interesting study!

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  • Type 2 diabetics given broccoli sprout extract containing 150 μmol sulforaphane for 12 weeks lowered blood glucose levels by 10% compared to placebo. www.newscientist.com
    Diet Diabetes Insulin Resistance Sulforaphane Insulin NRF2 Metformin

    Broccoli sprout extract reduced HbA1c by 7.04% in obese patients with dysregulated type 2 diabetes. It has been demonstrated that a 1% decrease of HbA1c corresponds to 37% reduced risk of microvascular complications.

    Sulforaphane reduces glucose by suppressing liver enzymes that otherwise stimulate the production of glucose.

    In animals, sulforaphane also attenuated exaggerated glucose production and glucose intolerance by a magnitude similar to that of metformin.

    Further investigations showed that while both metformin and sulphoraphane cut blood glucose, they do it in different ways. Metformin makes cells more sensitive to insulin, so they sponge more surplus glucose out of the bloodstream. Sulphoraphane reduces glucose by suppressing liver enzymes that otherwise stimulate the production of glucose. For this reason, Rosengren thinks the broccoli extract is complementary to metformin, not competitive."

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  • Sulforaphane Ameliorates Bladder Dysfunction through Activation of the Nrf2-ARE Pathway in a Rat Model of Partial Bladder Outlet Obstruction www.hindawi.com
    Abstract Prostate Sulforaphane NRF2

    Study used a silk thread to create an animal model of “bladder outlet obstruction (BOO),” which is a condition affecting nearly 30% of men over the age of 60 and usually caused by benign prostatic hyperplasia (BPH).

    FTA:

    The bladder pressure was significantly increased in obstructed rats relative to sham rats. However, the peak voiding pressure of bladders in obstructed rats treated by SFN is lower than obstructed rats at the 4-week time point. Bladder capacity was significantly higher in BOO rats compared to sham rats. Rats of the BOO+SFN group showed the highest bladder capacity among all groups. Bladder compliance decreased significantly at the 4-week time point after BOO. However, SFN treatment rescued the compliance increase in bladder capacity. Moreover, we found that the interval of micturition was shorter in BOO rats than in sham rats. The micturition interval in BOO+SFN rats was significantly increased compared to BOO rats (Table 2).

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  • Sulforaphane (found in broccoli sprouts) causes 20% fat loss by changing gut bacteria & increasing mitochondria in fat in mice. www.sciencedaily.com
    Gut Obesity Microbiome Metabolism Inflammation Sulforaphane Fatty Liver NRF2 Endotoxemia Lipopolysaccharide Visceral Fat

    Sulforaphane from broccoli sprouts causes 20% visceral fat loss by changing gut bacteria and increasing mitochondria in fat in mice. The mice fed sulforaphane also lowered fatty liver and reduced blood glucose levels. Sulforaphane reduced inflammation by decreasing a species of bacteria in the gut that is responsible for producing endotoxin, which is a major source of inflammation. Also, sulforaphane increased the levels of UCP1, which is responsible for increasing mitochondrial biogenesis (the generation of new mitochondria) in fat (called browning of fat). The browning of fat increases fat metabolism and can lead to fat loss. There have been human studies showing that sulforaphane decreases inflammatory biomarkers and improves blood glucose levels. It will be interesting to see future studies looking at these two new functions of sulforaphane in humans. For more information check out my video on sulforaphane or my podcast with Dr. Jed Fahey, who discovered broccoli sprouts are the best source of sulforaphane. Sulforaphane video: https://youtu.be/zz4YVJ4aRfg Sulforaphane podcast: https://youtu.be/Q0lBVCpq8jc

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  • Epithiospecifier protein activity in broccoli: The link between terminal alkenyl glucosinolates and sulphoraphane nitrile www.sciencedirect.com
    Sulforaphane Isothiocyanates Protein Myrosinase

    Please take note of the graphs and timeline, these can provide valuable information on how to optimize your processing of broccoli sprouts for sulforaphane content.

    Abstract The chemical nature of the hydrolysis products from the glucosinolate-myrosinase system depends on the presence or absence of supplementary proteins, such as epithiospecifier proteins (ESPs). ESPs (non-catalytic cofactors of myrosinase) promote the formation of epithionitriles from terminal alkenyl glucosinolates and as recent evidence suggests, simple nitriles at the expense of isothiocyanates. The ratio of ESP activity to myrosinase activity is crucial in determining the proportion of these nitriles produced on hydrolysis. Sulphoraphane, a major isothiocyanate produced in broccoli seedlings, has been found to be a potent inducer of phase 2 detoxification enzymes. However, ESP may also support the formation of the non-inductive sulphoraphane nitrile. Our objective was to monitor changes in ESP activity during the development of broccoli seedlings and link these activity changes with myrosinase activity, the level of terminal alkenyl glucosinolates and sulphoraphane nitrile formed. Here, for the first time, we show ESP activity increases up to day 2 after germination before decreasing again to seed activity levels at day 5. These activity changes paralleled changes in myrosinase activity and terminal alkenyl glucosinolate content. There is a significant relationship between ESP activity and the formation of sulforaphane nitrile in broccoli seedlings. The significance of these findings for the health benefits conferred by eating broccoli seedlings is briefly discussed.

    Graphical abstract We measured ESP activity over 15 days of broccoli seedling development and correlated these with myrosinase activity and the levels of terminal alkenyl glucosinolates and sulphoraphane nitrile. We show ESP activity increases to day 2 before decreasing to imbibed seed activity at day 5. Terminal alkenyl glucosinolate and sulforaphane nitrile content and ESP activity correlated closely.

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  • "Broccolio-sprout beverage" makes people excrete benzene in their urine, mitigating effects of breathing polluted air www.theatlantic.com
    Cancer Diet Sulforaphane

    A few take-home points from the article:

    Rapid and Sustainable Detoxication of Airborne Pollutants by Broccoli Sprout Beverage: Results of a Randomized Clinical Trial in China. (PubMed Abstract)

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