NRF2
Episodes
Dr. Rhonda Patrick answers audience questions on various health, nutrition, and science topics in this Q&A session.
In this clip, Dr. Jed Fahey enumerates the vegetables in which sulforaphane is found.
In this clip, Dr. Jed Fahey discusses how sulforaphane promotes glutathione production in the brain, even with long-term consumption.
-
Rhonda Vitamin D Gut Ketosis Insulin Resistance Fasting Sulforaphane Intestinal Permeability NRF2 Urolithin ADr. Rhonda Patrick answers audience questions on various health, nutrition, and science topics in this Q&A session.
-
In this clip, Dr. Jed Fahey enumerates the vegetables in which sulforaphane is found.
-
In this clip, Dr. Jed Fahey discusses how sulforaphane promotes glutathione production in the brain, even with long-term consumption.
-
In this clip, Dr. Jed Fahey describes how sulforaphane facilitates the detoxication of heavy metals by increasing glutathione synthesis.
-
In this clip, Dr. Jed Fahey describes sulforaphane's opposing effects on cancer.
-
In this clip, Dr. Jed Fahey discusses the effects of urinary excretion of sulforaphane byproducts.
-
In this clip, Dr. Jed Fahey discusses the current state of the science regarding sulforaphane and brain health.
-
In this clip, Dr. Jed Fahey discusses the pros and cons of sprouting and whether broccoli seeds contain erucic acid.
-
In this clip, Dr. Jed Fahey describes how sulforaphane promotes the excretion of toxicants in air pollution.
-
In this clip, Dr. Jed Fahey names several reliable supplemental sources of sulforaphane.
-
In this clip, sulforaphane expert Dr. Jed Fahey describes some of the problems that complicate determining the optimal source and dose of sulforaphane.
-
In this clip, Dr. Jed Fahey disputes claims that sulforaphane causes goiters.
-
A special two-hour Q&A with Dr. Jed Fahey, an expert on sulforaphane, chemoprotection, and phytochemicals.
-
In this clip, Dr. Rhonda Patrick describes the potential interaction between sulforaphane and iodine and stresses that iodine-deficient individuals or those with hypothyroidism should work with their physician to monitor thyroid hormone levels.
-
In this clip, Dr. Rhonda Patrick discusses the current sulforaphane research as it pertains to DNA damage, and highlights the importance of considering the different forms of studies.
-
In this clip, Dr. Rhonda Patrick describes advances in sulforaphane research that are particularly relevant to the brain.
-
In this clip, Dr. Rhonda Patrick describes the advantages and disadvantages of the various dietary and supplemental sources of sulforaphane.
-
Dr. Jed Fahey describes a study that demonstrated sulforaphane's chemoprotective qualities against benzene exposure.
-
Dr. Jed Fahey discusses the potential therapeutic benefit of sulforaphane in treating depression.
-
Dr. Jed Fahey describes the health benefits associated with moringin and discusses the chemical structure differences between it and sulforaphane.
-
Dr. Fahey describes the metabolic fate of sulforaphane and the current state of research on its effects against bladder cancer.
-
Dr. Jed Fahey describes the chemical reaction that produces isothiocyanates and the time frame required for full conversion.
-
Dr. Jed Fahey describes factors that influence isothiocyanate production.
-
Dr. Jed Fahey describes the beneficial effects of sulforaphane in modulating the symptoms of autism and other brain disorders.
-
Dr. Jed Fahey describes the current state of the science of understanding how sulforaphane influences longevity.
-
Dr. Jed Fahey discusses the importance of having active myrosinase in dietary supplements for optimizing the conversion of glucoraphanin to sulforaphane.
-
Dr. Jed Fahey discusses concerns about the sulforaphane dietary supplement industry and offers advice about how to choose quality products.
-
Dr. Jed Fahey describes how sulforaphane was discovered, how it is produced in plants, and the mechanisms by which it produces health effects in humans.
-
Dr. Jed Fahey describes the early co-discoveries of sulforaphane and Nrf2, and describes the importance of the Nrf2 pathway.
-
Rhonda Nutrition Cancer Diet Aging Performance Omega-3 Fasting Magnesium Drug Sulforaphane Sauna NRF2Dr. Rhonda Patrick on Kevin Rose Show: metformin, magnesium L-threonate, fish oil, brain health, sulforaphane, goitrogenic activity, sauna, and more.
-
This is a video on how to plausibly increase the sulforaphane created from the glucoraphanin in your broccoli sprouts by up to 3.5-fold.
-
Sulforaphane Nutrition Brain Diet Nootropics Inflammation Heat Stress Autism Isothiocyanates NRF2 Moringa SupplementsDr. Jed W. Fahey discusses the health benefits of isothiocyanates, including sulforaphane and moringa.
-
Sulforaphane Brain Cancer Aging Heart Disease Insulin Resistance Inflammation Depression Behavior Mental Health Autism Mortality NRF2This podcast is about one of the most important biological pathways you could possibly take the time to learn about: the NRF2 pathway.
Topic Pages
News & Publications
-
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.
-
New research may explain unexpected effects of common painkillers. www.sciencedaily.com
Some NSAIDs dampen inflammation by switching on the activity of Nrf2.
Non-steroidal anti-inflammatory drugs, or NSAIDs, are among the most widely used drugs worldwide, available in both prescription and over-the-counter forms. NSAIDs generally work by inhibiting the activity of cyclooxygenase, a type of enzyme that drives inflammatory processes. But because the drugs often elicit off-target effects, questions remain regarding other mechanisms that might be involved in their activities. A recent study demonstrates that some NSAIDs switch on the activity of Nrf2, a type of transcription factor.
Nrf2, or nuclear factor erythroid 2-related factor 2, is a cellular protein that regulates the expression of antioxidant and stress response proteins. It is an element of the Keap1-Nrf2-ARE biological pathway. Nrf2 activates the transcription of cytoprotective proteins that protect against oxidative stress due to injury and inflammation. Sulforaphane, a compound derived from broccoli and broccoli sprouts, is the most potent naturally occurring inducer of Nrf2.
Using cells from humans and mice, the investigators determined that various NSAIDs could induce the activity of GDF15 (a type of growth factor). This induction was dependent upon the activation of Nrf2. Then, using animal models of gout (an inflammatory disorder of the joints) and endotoxemia (a systemic inflammatory condition), they observed that the NSAIDs mediated the inflammation associated with the conditions and promoted Nrf2 gene expression. Deleting the Nrf2 gene in the cells canceled out the beneficial effects of the NSAIDs on gout and endotoxemia.
This study demonstrates a novel mechanism by which NSAIDs ameliorate inflammation and answers questions regarding some of their off-target effects. It also opens the door to future research on these commonly prescribed drugs.
-
Curcumin may improve exercise tolerance through antioxidant-regulating protein Nrf2. journals.physiology.org
Curcumin is the principal bioactive compound present in the yellow spice turmeric. An abundance of scientific evidence indicates that curcumin has antioxidant, anti-inflammatory, anticancer, and neuroprotective properties in humans. Findings from a 2019 study suggest that curcumin improves exercise tolerance in mice with heart failure via its activation of Nrf2.
Heart failure, commonly referred to as the end stage of heart disease, affects more than 26 million people worldwide. Exercise intolerance is a common feature of heart failure and is typically attributed to low ejection fraction – a measure of ventricular efficiency. A critical driver of low ejection fraction is oxidative stress.
Nrf2 is a cellular protein that regulates the expression of antioxidant and stress response proteins via participation in the Keap1-Nrf2-ARE biological pathway. Nrf2 activates the transcription of cytoprotective proteins that protect against oxidative stress due to injury and inflammation.
The study investigators gauged the effects of curcumin in mice that had heart failure with reduced ejection fraction and in mice with healthy hearts. A subset of the mice received daily curcumin supplementation, while the others did not. The investigators measured the animals' heart function via echocardiogram, assessed their exercise performance on a treadmill, and measured the expression of Nrf2 and its target proteins in their muscles.
They found that both groups of mice that received curcumin (including those with healthy hearts) had improved exercise capacity compared to those that did not receive the compound. They also found that Nrf2 expression and antioxidant proteins increased in the mice with heart failure that received curcumin.
These findings suggest that impaired Nrf2 drives oxidative stress in skeletal muscle in those who have heart failure with low ejection fraction. Curcumin counters these effects by upregulating antioxidant defenses in skeletal muscle, likely mediated by Nrf2 activation. Many plant-based dietary compounds induce Nrf2 activity, including sulforaphane, a compound derived from broccoli and broccoli sprouts. Learn more about Nrf2 and sulforaphane in this episode featuring Dr. Jed Fahey.
-
Sulforaphane improves behavioral symptoms of autism. molecularautism.biomedcentral.com
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.
-
Sulforaphane inhibits activation of the NLRP3 inflammasome in mice microglia cells. www.sciencedirect.com
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.
-
Sulforaphane improves blood glucose control in obese people with type 2 diabetes. stm.sciencemag.org
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.
-
Sulforaphane reduces biochemical recurrence in men who have had prostate cancer. pubmed.ncbi.nlm.nih.gov
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.
-
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.
-
Sulforaphane reduces behavioral symptoms of autism in young men. www.ingentaconnect.com
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.
-
Nrf2 pathway is a major target for sulforaphane. www.sciencedirect.com
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.
-
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.
-
Seasonal variation in Nrf2 antioxidant pathway influence winter depression-like behavior in fish. neurosciencenews.com
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.