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

dr. Matta Patrick here today is a big day we're going to be talking about some pretty important stuff I'm very excited we're going to be talking about cruciferous vegetables as a group in other words we're going to be talking about broccoli brussel sprouts cauliflower cabbage collard greens bok choy packed oi watercress land cress radish daikon wasabi yes wasabi it's a cruciferous vegetable who knew we're also going to be talking about broccoli sprouts so much about broccoli sprouts and more importantly sulfur vein we're going to talk about household fur fan is the most potent naturally occurring dietary activator of the genetic pathway and rf2 which regulates over 200 different genes many genes which are antioxidant anti-inflammatory and genes that are involved in activating and potentially harmful compounds that we may be exposed to on a daily basis we're going to be talking about the cancer preventive effects of so far or fame its effects on cardiovascular disease and on the brain we're going to be talking about its effects on excreting carcinogens bioavailability and dose and we're going to talk about how I'm able to sustain my forty to sixty milligram of sulforaphane a day by sprouting and so much more let's start with the basics and by basics I mean staying alive in 2011 a study was published in the American Journal of Clinical Nutrition that showed if we took the population and divide them up by their vegetable consumption those in the top 20% of the population eating the most vegetables had a 16% reduction in what is known as all cause mortality what this means is that for that period of time study they were 16% less likely to die from all non accidental deaths compared to others in their age group regardless of many other health factors like exercise hey that's pretty good right but if instead of just looking at vegetable consumption we look at the top 20% of cruciferous vegetable consumers the effect on all cause mortality is even more substantial the top 20% of consumers of cruciferous vegetables reduce their all-cause mortality by 22 percent well that alone is actually almost enough to make me start a broccoli farm there's been a lot of research on the profound associations between cruciferous vegetable consumption and risk of cancer for example one study found that men that ate between three to five servings of cruciferous vegetables a week had 40% decrease in prostate cancer risk compared to men that ate less than one serving per week another study found that men who ate two or more half cup servings of broccoli per week had a 44% lower incidence of bladder cancer compared to men who ate less than one serving each week smokers who consumed at least four and a half servings of raw cruciferous vegetables a month had a 55% reduction in lung cancer risk compared with those who consumed less than two and a half servings per month multiple studies have shown that women who have consumed Pacific vegetables at least once a week had between a 17% or as much as a 50% decrease in breast cancer risk for those consuming it every day the variation between these studies likely has to do with the preparation of the cruciferous vegetables and whether they were fresh or frozen all of which actually affect the bioavailability of the active compounds which we'll talk about in a minute but what if you already had cancer people with bladder cancer that had just four servings of raw broccoli per month had a 57 percent reduction in bladder cancer mortality and a 43 percent reduction in all cause mortality compared to those that just had one serving per month something is obviously going on here these are some pretty powerful associations but before we can begin to establish causality we must establish a plausible mechanism our most likely candidate isothiocyanates isothiocyanates are formed from compounds known as clue constantly it's by an enzyme called Myra sanae's which is activated when the cruciferous plant tissue is crushed or chopped or chewed but is inactivated under conditions of prolong heat such as sustained boiling one particular isothiocyanate sulfur fain stands out from all the rest because of its potency and because of the sheer volume of scientific scrutiny it's been subjected to remember a minute ago when I said isothiocyanates are formed from glucosinolates while surfer faint is no exception the glucosinolate that sulfur Fein is formed from is known as gluco raffinate or it's more often simply referred to as sulfur if an glucosinolate the single best source of glucoraphanin and the sulfur refrain are likely broccoli sprouts which contain up to a hundred times more glucose then they're mature counterpart broccoli moreover sprouting is something that is extremely inexpensive and can be done at home there are several different mechanisms by which isothiocyanates particularly sulfur ofing reduce cancer risk and kill cancer cells and these occur through multiple different pathways including deactivation of a family of enzymes known as phase one biotransformation enzymes which are responsible for converting Pro carcinogens into active carcinogens this is one way in which sulforaphane can prevent the formation of DNA addicts which is a type of DNA damage that has been shown to lead to cancer which occurs after exposure to particular types of carcinogens tobacco smoke is loaded with carcinogens that form DNA addicts which is why it's really nasty stuff that increases the risk of several different types of cancer including lung and bladder cancer it also may explain why just a few extra servings of cruciferous vegetables a month may lower the risk of lung cancer by 55% like we just discussed a while ago but what about the study on bladder cancer here - we've got pretty good cause to believe that it's the isothiocyanates in a study where rats were given a chemical compound that causes bladder cancer almost 96 percent of those animals went on to develop large tumors by comparison only 38% of the animals that were given a very high dose of isothiocyanates at the same time went on to develop cancer and those that did develop cancer the tumors were much smaller in size many other animal studies have also mechanistically shown that isothiocyanates reduced cancer incidence when challenged with a tumour initiator and what about the study on prostate cancer yet probably the isothiocyanates - there have been a couple of clinical trials both involving prostate cancer investigating the effects of the active compound toll for fame from broccoli sprouts on cancer treatment men with prostate cancer that were given 60 milligrams of sulforaphane per day in a mount in about 140 grams of fresh broccoli sprouts resulted in the slowing of the doubling rate of a cancer biomarker known as prostate specific antigen or PSA by 86% compared to placebo first of all think about that for a second slowing the doubling rate by which a tumor markers increased by 86 percent that's pretty gigantic the robust effects of sulforaphane appeared to be dose dependent in another study 35 milligrams of sulfur refrain was used instead of 60 milligrams and while it theoretically still slowed the growth of prostate cancer it only increased the average PSA doubling time by 57% which while impressive isn't quite as jaw-dropping as the 86% from the previous study and breast cancer again interesting things going back to the sulfur refrain in this case bioaccumulation of the isothiocyanate in 2007 a pilot study found that after receiving broccoli sprout extract containing about 37 milligrams of sulfur a vein or the amount you might get from consuming about 85 grams of fresh broccoli sprouts the accumulation of sulfur refrain was detected in actual human breast tissue around 1. 45 pica mole per milligram for the right breast and 2 Pico mole per milligram for the left don't bother looking up what a Pico is it's extremely small this is however interesting in the sense that we're seeing the molecule itself actually making its way to breast additionally breast tissue also displayed the increased levels of a gene called NQ o1 this gene makes an enzyme that has many protective functions including detoxification of certain compounds preventing them from damaging cells and even more interestingly protecting a very important tumor suppressor gene called p53 from being degraded all of this is happening within one hour after consuming brothy sprout extract p53 is itself so important to cancer biology that over 50% of all adult cancers have a mutated or broken p53 gene keeping our p53 working well is very important we've also seen a bit more directly that in my sulfur freeing is able to inhibit the growth of breast cancer stem cells look I know I'm trying to blow your freaking mind here I'm trying to suck you into my world and get you interested in isothiocyanates but this stuff isn't cutting-edge I'm not the first person to rant and rave about the cruciferous vegetable family in fact if we rewind a couple of thousand years the ancient Roman statesman Cato the Elder had this to say about a prominent member of the cruciferous family that cabbage can banish and cure all from crapulous from excess wine consumption to serious diseases like cancer crappyland now there's a totally fun and legitimate word to throw around at parties okay we talked about how isothiocyanates can prevent cancer by deactivating a family of enzymes known as phase one biotransformation enzymes but what if in addition to deactivating carcinogens we just got better at getting rid of them I'm talking excretion removing them from the body this relies on a whole other family of enzymes for which isothiocyanates are known to activate called Phase two detoxification enzymes this effect is mediated via the nrf2 pathway for which sulforaphane is the most potent naturally occurring inducer of enter of two is a very important pathway because it literally controls hundreds of genes by a short sequence of DNA that's present within a gene known as an antioxidant response element nrf2 will bind to this short sequence of DNA and it will either activate or repress transcription of the gene phase two detoxification enzymes like glutathione as transferase are important because they're able to deactivate Pro carcinogenic agents and transform them into water-soluble conjugates which are usually less reactive and are able to be excreted in urine and bile additionally they lower DNA damage because they also lower that the inflammation and reactive oxygen species burden so it's a good thing that an increase in glutathione s transfer is is exactly what we see when people start bumping up their cruciferous vegetable consumption in one study where participants were asked to eat 300 grams of Brussels sprouts per day which is one of the cruciferous vegetables higher in isothiocyanate precursors increased glutathione as transferase circulating in their blood plasma by about 1.

4 fold while overall oxidative DNA damage went down by about 28% drops and DNA damage are a very good thing since these are ultimately what initiate cancer and are mental to the process of aging itself but when it comes to showing off the ability of sulfur refrain to help trigger systems that boost the excretion of carcinogens there's really one study that stands out this study demonstrated that sulfur refrain and it's precursor glucoraphanin can actually significantly increase the excretion of benzene participants that were given a daily broccoli sprout beverage containing around two hundred and sixty two point five milligrams of glucagon and about seven point one milligrams of sulfur ofing which is about probably an effective dose of something like 135 grams of fresh broccoli sprouts per day increase the rate of excretion of benzene by 61% beginning on the first day of consuming the drink and continuing throughout the entire 12 week period of the trial just so you know benzene is a carcinogen that's been shown to cause cancer in humans and in animals particularly leukemia the major source of benzene is from automobile exhaust and air pollution but also from cigarette smoke even secondhand the major source of source of benzene for non-smokers is from air pollution whereas smokers are mostly exposed to benzene from cigarette smoke in fact in the u. s. cigarette smokers are exposed to around 10 times more benzene than non-smokers or around two milligrams a day compared to only two hundred micrograms a day in non-smokers this starts to make a pretty interesting case for smokers right so here's what we've got so far smokers that he a lot of cruciferous vegetables have a decreased risk of lung cancer smoking loads us up with a carcinogen called benzene and drinking a supercharged broccoli sprout drink increases our excretion of benzene but even if you're not a smoker which I really hope you're not there are plenty of other sources that we can be exposed to benzene from air pollution is another place we get it that's because air pollution in the United States primarily comes from automobile exhaust which is a source of benzine high-dose benzene exposure from air pollution has been shown to increase oxidative DNA damage in a dose-dependent manner in people while even low-dose exposure to benzene from air exposure and gasoline exposure has been shown to epigenetically chain genes that are involved in suppressing leukemia if we wish to concern ourselves with air pollution however we should look to a study published in 2008 on the use of a broccoli sprout homogenate this study found that broccoli sprouts when administered as a Majin ate had a direct effect on increasing the expression of Phase two detoxification enzymes in the upper airway in other words right where it counts the doses they gave two individuals ranged from 25 grams of broccoli sprout homogenate all the way up to 200 grams with a clear dose response relationship where the largest dose had the most potent effect strongly increasing the production of various glutathione related enzymes such as glutathione as transferases heme oxygenase 1 and NQ o 1 which is an enzyme we talked about earlier when we discussed breast cancer benzene isn't the only airborne carcinogen the anti benzene brothy sprout drink worked some magic on over the 12-week trial excretion of the carcinogen acrolein rapidly increased by 23% acrolein is found in most of the major sources already mentioned for benzene including air pollution but it differs in that it can also be formed when carbohydrates proteins and fats are heated another study found that consumption of a broccoli sprout beverage containing 27 milligrams of sulfur refrain led to a 50% increase in excretion of acrolein croton aldehyde ethylene oxide and benzene finally yet another study showed that a tobacco specific lung carcinogen called nnk can be detoxified through the action of an ISO thiocyanate that is found in watercress in other words different isothiocyanate in different cruciferous vegetable but again an effect on carcinogen excretion in this study fifty seven grams of watercress was given to smokers to eat with each meal for three days while they continued to smoke those dirty Rascals this led to a 35% increase in excretion for biomarkers indicating the inactivation of the carcinogen and NK the bottom line is that consumption of cruciferous vegetables including watercress but perhaps especially broccoli sprouts since they are so rich in sulfur Fame is a powerful way to do to bait and excrete harmful compounds that we are exposed to on a daily basis but even more so if you're a smoker well some of this carcinogen excretion stuff is somewhat new the general anti-cancer properties of glucosinolates and their metabolites isothiocyanates are pretty well established which is one reason why many studies looking into the effects of cruciferous vegetables specifically look at cancer incidence what's interesting however is the effect cruciferous vegetables have on cardiovascular risk factors remember that study I mentioned earlier that showed a 22% reduction in all cause mortality for the highest quintile of cruciferous vegetable consumption it turns out the reduced risk of death was mostly associated with reduction and death from cardiovascular disease which is still the number one killer in the United States which may be surprising since we spent so much time talking about the number of cancer studies floating around out there in fact multiple studies have found that people that eat a higher quantity of cruciferous vegetables have a lower risk of cardiovascular disease heart attack and stroke compared to those with a lower intake but better still is actually measuring the strength of this effect one study in people with type 2 diabetes showed that it's possible to actually drive real changes in biomarkers that are predictive of future heart disease supplementing with 10 grams of broccoli sprout powder per day which comes out to about 40 milligrams of sulfur refrain and is probably comparable to around 100 grams fresh weight for four weeks lower their serum triglyceride by eighteen point seven percent and lowered oxidized LDL ratio by 13.

5 percent overall this reduced trial participants atherogenic index by just over 50% which is a measure of cardiovascular disease that incorporates a wide variety of factors not to mention they also had a nearly 20% drop in fasting blood sugar which is a pretty darn good thing if you're a type 2 diabetic other studies using fresh sprouts but with a similar effective dose of sulfur refrain have also demonstrated anti atherogenic effects there are likely multiple mechanisms by which sulfur refrain and cruciferous vegetables in general positively affect cardiovascular health one of the most important ones goes back to the genetic pathway we mentioned earlier this name one responsible for activating those phase 2 detoxification enzymes which is nrf2 and that is because enter up to activates antioxidant genes it activates anti inflammatory genes deactivates inflammatory genes which all affect cardiovascular health Sofer frame has been shown in rat studies to increase antioxidant activity include a thigh own expression and endothelial cells that line the blood vessels it also relaxes smooth muscle cells additionally sulfur refrain appears to be able to reduce adhesive molecules that are part of the atherogenic state that drives heart disease such as issa lectin which is a cell adhesion molecule expressed only in endothelial cells and activated by inflammatory cytokines studies like these ultimately help give us some insights into what might be happening at a mechanistic level to drive these larger associations at a population level that are being seen between reductions and heart disease risk and consumption of cruciferous vegetables we've talked about how sulforaphane can reduce cancer can reduce cardiovascular disease and soon we'll be talking about neurodegenerative diseases all of which are diseases of age we've talked about associative studies that have shown reductions in all cause mortality for the top 20% of cruciferous vegetable consumers but the question still remains does sulforaphane effect or slow the aging process itself one way to answer this question would be to see if sulfur rain has a direct effect on lifespan unfortunately this hasn't to my knowledge been done in animals I'd love to see that happen I did however run across a bit of a tease a study looking at the effect of broccoli extract on a type of beetle known as red flower beetles that were given a diet supplemented with 1% broccoli extract it increased their mean lifespan by 15% under normal physiological conditions and under conditions of higher oxidative stress increase their mean lifespan by 30 percent the lifespan extension from the broccoli extract depended on the activation of an or of two and the FOXO pathway that is homologous to humans Fox o3 longevity pathway finding out that the aging benefits in these little critters are derived from the same nrf2 genetic pathway that is conserved in humans is really good news if we're ever to have any hope in replicating this data in a species a little more closer to us finding out that the Fox of genetic pathway is also involved is really just a cherry on top the Fox o3 genetic pathway which I've talked about in multiple podcasts and videos is very closely related to human longevity for example humans that have a gene polymorphism in the Fox oh three gene that make it more active are 2. 7 times more likely to live to be a centenarian the chances of living to be a centenarian however seem to depend a lot on keeping inflammation at bay in fact it is now believed that suppression of inflammation is the single most important predictor of successful aging and we're not just talking about lifespan either we're talking about capability in terms of performing functions of daily life and also cognition yes inflammation was an important predictor of cognition itself and this was shown in populations including elderly people all the way up through super centenarians which live to be a hundred and ten years old and this relationship isn't surprising we know that if we take mice for example an induced chronic low level activation of a master regulator of the pro-inflammatory response known as NF kappa-b it can actually accelerate aging by 30 percent in mice again suggesting that chronic enhancement of pro-inflammatory mediators really is not just a bystander but an actual driver of Aging so fur Fane has been shown in mice to inhibit NF kappa-b through the activation of nrf2 NF kappa-b activates a multitude of inflammatory pathways and induces cytokines that regulate the immune response one such example is il-6 which is often activated downstream of NF kappa-b higher circulating levels of il-6 are associated with increased risk for cancers and other age-related diseases here we see a benefit in humans healthy individuals given 14 grams of cruciferous vegetables per kilogram body weight daily decrease their circular levels of il-6 by 20% another study showed that a broccoli sprout powder containing approximately 40 milligrams of sulfur Fein an amount you might get from around hundred grams of fresh broccoli sprouts reduced tnf-alpha a marker of inflammation by eleven percent and lowered c-reactive protein another marker of inflammation by 16% in people with type 2 diabetes associative studies in humans show a similar effect on inflammation when comparing the top 20% consumers of cruciferous vegetables with the bottom 20% they had on average a reduction of circulating il-6 by 25% and a similar decrease for other important inflammatory cytokines like TNF alpha which was lowered by 12. 6% if we accept the premise that sulfur fane derived from cruciferous vegetables is driving reductions in inflammation and this is happening via the nrf2 pathway then we have to ask ourselves what is actually happening to enter up to itself and what does this mean for other processes inside the body under normal conditions nrf2 is briefly activated every hundred and twenty nine minutes however when stimulated by sulfur fain its activity pattern changes it becomes activated every eighty minutes which is about a 61% increase this increase in nrf2 activity is hugely important because it regulates over 200 genes many of these genes affect cellular aging enter up to protects against cancer which is an age-related disease by deactivating carcinogens and increasing their excretion it also deactivates genes involved in inflammation and activates antioxidant genes both which lower DNA damage which can lead to cancer but also slows the aging process in general it does this by lowering the total amount of damage that accumulates within cells damage that accumulates within cells can accelerate telomere shortening and also causes cells including stem cells to become senescent and non-functional our immune cells including our adaptive immune cells are more prone to cellular senescence with age called immuno senescence and this makes us more susceptible to infections as we get older the adaptive immune response is the second immune strategy that our bodies employ and in contrast to the innate immune response which is less specific it functions by using and creating immunological memory after initial exposure to a pathogen which then makes its more its response more targeted and specific in subsequent encounters the adaptive immune system functionally declines with age but mouse studies show us something interesting a conservative dose of about 1.

6 milligrams per day in old mice was able to render a regaining of some of that lost function in the adaptive immune system if we extrapolate that to a human equivalent dose it comes out to around 20 grams of so farofa in a day which is an amount you might expect to find in around 43 grams of fresh broccoli sprouts since we're talking about aging and I've already somewhat shamelessly dipped into animal studies many times leading up until this point I'll share one more thing with you mostly just for fun before we move on to another topic for most people aging is something that occurs in the mirror rather than a cellular phenomenon you can't look in the mirror and see that your telomeres are getting shorter or see that you're accumulating more and more DNA damage with each passing day what you can see however is the formation of wrinkles or whether or not your hair is starting to fall out most people are probably more happy with just keeping the hairs on their head rather than concerning themselves with DNA damage the most common type of hair loss that occurs with age is androgenetic alopecia and it's mediated through the production of dihydrotestosterone which slows the growth phase of a new hair follicle and result in decreased production of new hair interestingly one study shows a pretty strong effect on hair regrowth from sulfur refrain supplementation in my subjected to experimentally induced hair loss the effect from the injected sulfur refrain was pretty strong somewhere on the order of around a 50% increase in hair regrowth accompanied by a pretty robust decrease in dihydrotestosterone levels you guys know I love to talk about the brain if I can find a way to tie the brain into something I'm talking about I'll do it here to our favorite and mo notable isothiocyanates Ophir fame does not let us down so fervent crosses the blood-brain barrier at least in mice and we also know it has very potent effects on lowering inflammation inflammation itself also has a direct effect on the brain the nrf2 pathway is the body's strongest defense against oxidative stress in fact oxidative stress itself activates this pathway perhaps then we should not be too surprised to find out that sulphur Fane also plays a role in conditions of the brain for which oxidative stress is known to be part of the etiology of in a randomized double-blinded placebo-controlled study treatment with sulphur faint extracted from broccoli sprouts at doses ranging from around 9 milligrams to 25 milligrams which is an amount found in probably around 65 grams of fresh broccoli sprouts on the high end was able to improve autistic behavior checklist scores by 34% and significantly improved social interaction abnormal behavior and verbal communication in young men with autism spectrum disorder another trial found supplementation with 30 milligrams per day of glucose often in other words just the precursor to sulfur refrain by itself for eight weeks was effective in improving certain scores of cognitive impairment in a very small group of medicated patients with schizophrenia it's worth noting that schizophrenia like autism does seem to have an oxidative stress component the degree of which may even be an indicator for the acute severity of symptoms let's talk depression depression is one of the most common psychiatric illnesses in the world the World Health Organization estimates around 350 million individuals have depression according to the NIH around 10 percent of American adults are on some form of a selective serotonin reuptake inhibitor a broad category which includes drugs like flu exiting or also known as prozac mounting evidence suggests that nutrition plays a huge role in depression more directly by impacting neurotransmitter production and function which can be modulated by micronutrients but also by affecting systemic inflammation which is now known to play a major role in depression how do we know whether inflammation can play a causal role in depression we know this because healthy individuals that are injected with either a pro-inflammatory cytokine interferon gamma or lipopolysaccharide which is a component of bacterial cell membranes that elicits an immune response begin to experience depressive symptoms that can actually be alleviated with a polyunsaturated fatty acid i cosas pentanoic acid also known as EPA which is an omega-3 fatty acid that is well known for its anti-inflammatory properties the reason these inflammatory molecules and cytokines were able to have these sorts of effects is because they are able to cross over the blood-brain barrier and disrupt neurotransmitter production and release the significance of this inflammation linked to depression is reinforced by observations that the risk for major depression is increased by 44% for each standard deviation increase in log c-reactive protein which is a common measure of systemic inflammation that is also used as a measure of cardiovascular disease risk elevated levels of the pro-inflammatory cytokine il-6 have also been linked to depression if you've been paying attention up until now then you know where I'm going with this already a little while ago we talked about inflammation in the context of aging but it's similarly valid here if for example sulfur frame can lower import inflammatory cytokines such as il-6 upwards of 20% in humans on top of it being able to cross the blood-brain barrier maybe we have a chance of it being helpful in depression as well as a plausible mechanism for being helpful for depression we see promise in animal studies mice given lipopolysaccharide to induce an inflammatory response experience depressive symptoms just like humans do however taking these say mice in giving them a whopping 1 milligram per kilogram of body weight a day of sulfur ofing reverses these depressive symptoms this paper I'm referring to is interesting in part for reasons of what it states right in the abstract and that is that nrf2 may be a good target for novel antidepressant drugs but also because they're inducing depression through inflammation tricking the immune system into thinking it's under attack however isn't the only way to induce a depression phenotype a variety of stressors can do that social stress messing with the circadian rhythm water deprivation in ten different models of stress induced depression sulfur Fame alleviated depressive symptoms and anxiety as well as the antidepressant Prozac in mice sulfur free and also decreased stress hormones and the inflammatory response in response to various social stressors indicating that the neuro protective effects on depression and anxiety may be associated with lower inflammation and lower stress hormones in this case as well my set of repeatedly subjected to social defeat causes depression like symptoms including avoiding social situations so further if rain prevented this avoidance behavior when animals were given sulfur rain and even more interestingly administration of the precursor to sulfur fin glucoraphanin during early development and adolescence prevented the social defeat during adulthood while the positive effects of sulfur and on depression have only been shown in animals this is enticing we already have some evidence that sulfur rain can have a positive effect on other conditions of the brain in humans such as autism we also have evidence that sulfur Irrfan can lower biomarkers of inflammation also in humans and we know that inflammation is directly linked to depression for the f-4 mentioned reasons it seems very plausible that sulforaphane may have a similar effect on depression and anxiety in humans but the best we can hope for is for future studies to be done in people to help illuminate this for us any discussion of the brain and inflammation would not be complete without mention of neurodegenerative diseases which are often considered to be diseases of ageing themselves and also traumatic brain injury for which chronic inflammation plays a major role in later outcome brain inflammation and reactive oxygen species are hallmarks of neurodegenerative diseases such as Alzheimer's Parkinson's and Huntington's disease the inflammation and high oxidative stress play a role in causing abnormal protein aggregates in the brain a common denominator between these neurodegenerative diseases injection of our favorite nrf2 activator sulforaphane has been shown to improve spatial working memory and short-term memory in mice injected with amyloid beta aggregates in order to cause a disease similar to Alzheimer's disease it's been shown to decrease tremors and normalize dopamine levels in mice given a chemical that induces parkinson's disease and it's been shown to clear aggregates from the brains of mice that were genetically engineered to have Huntington's disease as one of the most potent inducers of the cellular antioxidant and anti-inflammatory network through its robust activation of nrf2 it probably shouldn't surprise us that it has been shown to prevent the death of neurons and improve pathologies associated with neurodegenerative diseases in the brains of animals I was a little surprised however to find that sulfur vein activates many heat shock proteins by increasing the levels of heat shock factor one known as H s f1 which is a major regulator of many different heat shock proteins the induction of heat shock proteins may be an additional mechanism the body has against the aggregation of proteins which have been shown to confer some protection against Alzheimer's disease Parkinson's disease and Huntington's disease putting aside heat shock proteins for a moment so for reference activation of enter up to in addition to protecting against neurodegenerative diseases and delaying brain aging in general also has special relevance for traumatic brain injury because traumatic brain injury also has a very important inflammatory and oxidative stress components to it there have been several studies showing that sulforaphane can protect against traumatic brain injury or TBI in animals for example when administered by injection following TBI Sulphur Irvine has been demonstrated to attenuate blood brain barrier Pullman permeability which means the body is better able to control what is and is not allowed to enter the brain as well as a reduction in cerebral edema regardless of how soon after the injury the sulphur refrain was given additionally enhanced learning and working memory with improved but only if Stiffler refrain was administered within one hour post-injury he has also been shown that administration of sulfur referring 15 minutes after the onset Asst of ischemia which is a dangerous lack of oxygen that can occur in the brain as a consequence of injuries caused a reduction in infarct volume in other words the amount of dead tissue three days later so fervent increases neuro outgrowth at least in cultured neurons through the activation of nrf2 neuro outgrowth is one of the most important mechanisms by which damaged neurons and synapses repair themselves after damage from TBI nrf2 is also key for growing new neurons which is largely regulated by growth factors that are able to promote the growth of new neurons and promote the survival of existing neurons certain lifestyle factors can increase or decrease these neurotrophic growth factors for example obesity and type 2 diabetes can decrease the production of neurotrophins rats with diabetes have reduced levels of the neurotropic factors brain derived neurotrophic factor or BDNF and nerve growth factor or ngf but this has been experimentally reversed by administration of sulphur fame high levels of inflammation oxidative stress which are countered by nrf2 are known to negatively affect the production of neurotropic factors to illustrate the importance of nrf2 in brain health - that I've had an Arab who deleted have a 30% reduction in brain derived neurotrophic factor in the hippocampus a 30% reduction in the growth of new synapses and a 38 percent reduction in neuroplasticity in the hippocampus neurodegenerative diseases are not the only degenerative disease that sulphur fame shows some very early promise for Duchenne muscular dystrophy leads to a progressive loss of muscle tissue and eventual premature death there is no cure and the only treatment that has been proven to delay symptoms are corticosteroids in a mouse model of muscular dystrophy Sofer frame was shown to increase skeletal muscle mass muscle force by 30% and running distance by 20% interestingly in a separate cell culture study sulphur Frane was shown to inhibit myostatin in muscle satellite cells which is a well-known inhibitor of muscle growth while the overall relevance of these animal studies to these disorders in actual humans is still tenuous at best here again we can at least be hopeful that future research will illuminate more for us wow this was a long one let's take a moment to recap and talk about some of the things that we talked about we started off by talking about some of the epidemiological evidence showing that increased consumption of cruciferous vegetables was associated with reductions in all cause mortality it was also associated with reductions in cancer specific mortality including cancer of the prostate bladder long and breast we talked about how there is a good chance that isothiocyanates a group of compounds that notably include sulfur fain are likely what's driving these associations we know this from human studies where humans that already have cancer and then are given sulfur fain it lowers biomarkers of cancer progression we also know this from animal studies in which animals were given a carcinogen that causes cancer along with sulfur of fame and the sulfur fen prevented the cancer from forming we talked about how broccoli sprouts are the best source of sulfur roofing containing up to a hundred times more of the precursor to sulfur Irrfan glucoraphanin than mature broccoli we also talked about evidence about how sulforaphane lowers DNA damage by lowering oxidative stress and inflammation which are central to cancer aging 'nor general diseases and more we talked about how I brought this about beverage was able to increase the excretion rate of benzene by up to 61% people and also how it was shown to increase the excretion rate of other harmful compounds that were exposed to on a daily basis we talked about cardiovascular health and how consumption of cruciferous vegetables lowers heart disease risk we also talked about how people that were given sulfur frame lowered biomarkers of cardiovascular disease risk including oxidized LDL and triglycerides and also reduced atherogenic index by up to 50% we talked about how a beverage derived with broccoli sprouts was able to improve behavioral scores in people with autism and how it can improve cognition in a small trial in people with schizophrenia we also talked about household fur frein holds promise in treating a variety of other brain disorders including depression and neurodegenerative diseases based on early animal research finally we talked about the role of the nrf2 pathway and how sulforaphane potently activates it and its relevance from everything from excreting carcinogens to mitigating inflammation and how this is important for slowing diseases of aging we talked about so much in fact it's mind-boggling but the one thing we didn't talk about is dose if a person wanted to get the benefits of sulphur refrain in their diet and they choose to get them in their more concentrated source namely broccoli sprouts how many sprouts would one have to eat for this I used a conservative estimate that each gram of fresh uncooked broccoli sprouts yields around 2. 4 micro moles of sulfur ofing or about 0. 4 to 5 milligrams of sulfur fain using this number it might suggest that if a person wanted to get 60 milligrams of sulfur a frame per day which was shown to reduce the doubling rate of a marker for prostate cancer by 86% then they would probably have to consume around 140 grams fresh weight of broccoli sprouts or they could try to mimic the study done in people with type 2 diabetes which showed a reduction in triglycerides of around eighteen point seven percent and a reduction of oxidized LDL by around thirteen point five percent with a daily dose of an extract that was equivalent to around 40 milligrams of sulfur frame or what you might get from about 100 grams of fresh broccoli sprouts or maybe our hypothetical individual is somewhat more concerned with general inflammation in which case 40 milligrams of support sulfur refrain should promise and yet another study when it reduced tnf-alpha our marker of inflammation by 11 percent and lowered c-reactive protein another marker of inflammation by 16 percent the point is your guess is as good as mine I only have the doses used in some of these human studies to go off of as it turns out when sprouting at home using the mason jar method i found i can yield up to around 280 grams fresh weight per jar in other words one jar seems to yield enough broccoli sprouts to get pretty close to the 120 milligrams sulforaphane range or 60 milligrams each for two people add in six jars and rotation like I'm currently doing and you've got enough to do that almost every day for two people if you want to let's take a quick second to talk about sources of sulfur rain and some factors influencing its formation we've talked a lot about broccoli sprouts but of course sulfur rain and other isothiocyanates can be derived from other cruciferous vegetables as well there are many other cruciferous vegetables that contain the precursor to sulfur refrain glucoraphanin the levels of glucose often vary greatly between these different cruciferous plants but as a general rule of thumb broccoli sprouts topped the list as a source of glucoraphanin which is why we talk today a lot about the young sprouts of these plants only about 20% of glucoraphanin however is bioavailable and converted into sulfur or fane in the body so as you might imagine it's important that your sulfur free source has a lot of this precursor to begin with it's not just glucoraphanin that matters when it comes to maximizing sulfur fine however the work of actually converting this precursor into sulfur refrain is done by an enzyme called myrosinase this enzyme which is released when the plant matter is crushed or chewed unfortunately is heat sensitive this is where a lot of people get into trouble prolonged heating and boiling of cruciferous vegetables is a great way to ensure that your myrosinase is thoroughly inactivated even if you lack dietary sources of myrosinase most of us have some gut bacteria that itself produces myrosinase and thus can still manage to create some sulfur refrain from raw glucoraphanin the ability to do this however is widely variable from person to person in some people it's very efficient whereas in others it's extremely inefficient this is one reason why i'm not a huge fan of the alleged sulfur in supplements on the market which contain what is known as so far if and glucosinolate in other words they contain glucoraphanin not so far refrain all the while lacking the requisite Meyerson is needed to get the job done there may be other ways to still things with supplementation for example simply eating cruciferous vegetables that do contain myrosinase along with your supplemental glucoraphanin one studies showed that there was almost a two-fold increase in sulfur fee and absorption when broccoli sprouts and broccoli sprout powder were consumed together plasma and urine metabolites were observed earlier and at a much higher level than when either was eaten alone additionally it's also been suggested that mustard seed may be an effective supplemental source of myrosinase as well finally aside from supplementation we have the question of how can we go about maximizing sulfur free and production in vegetables themselves some sources seem to indicate that 3 to 4 minutes of very light steaming is the best way to go the reason is because a light steam has the effect of deactivating a protein known as epipheo specifiy protein which actually prevents the formation of sulfur ofing while still leaving Meyerson a is activated if you're better able to control the conditions for which you're cooking a similar effect can be achieved by heating your mature broccoli to 60 degrees Celsius for just 10 minutes or your broccoli sprouts which are a little bit less heat sensitive to around 70 degrees Celsius for 10 minutes one study showed that doing this in broccoli sprouts increase the production of sulfur refrain by around 3.

5 fold however if you increase the temperature much more substantially you end up in activating the Meyerson ease enzyme that said most of my estimates of the amount of broccoli sprouts needed to achieve a certain dose of sulfur ofing have been based off of raw consumption of broccoli sprouts not this blanching treatment as a final point we should take a moment to talk about the alleged goitrogenic activity of isothiocyanates the facts are that some studies have indicated that isothiocyanates can compete with iodine for transport into the thyroid gland most evidence indicates that this may only be a problem under conditions of severe iodine deficiency which is not common reinforcing this healthy people given an amount of isothiocyanates that's roughly equivalent to the amount you might get in about 70 grams of broccoli sprouts did not experience and any negative effects on their thyroid hormones or demonstrate liver toxicity it is my opinion that the evidence of the usefulness of isothiocyanates is too strong to simply dismiss them as anti nutrients I'm dr.