FoundMyFitness - #028 Sulforaphane and Its Effects on Cancer, Mortality, Aging, Brain and Behavior, Heart Disease & More

Episode Date: December 12, 2016

This podcast is about one of the most important biological pathways you could possibly take the time to learn about: the NRF2 pathway. The most potent naturally-occurring inducer of this pathway, a plant compound known as sulforaphane, may be one of the most potent health-enhancing compounds at our disposal and yet... no one is keeping it out of your hands! No $1,000 per pill markup is keeping it out of your hands -- it's available to anyone willing to take the little bit of time it takes each week to produce broccoli sprouts. Here are a few of the more salient points surrounding sulforaphane that are discussed in this podcast... (00:00) Introduction (03:36) Cruciferous vegetables reduce risk of death from all causes (07:15) Mechanisms of sulforaphane's anti-cancer effects  (12:02) Sulforaphane activates NRF2, detoxifying the body (18:53) Curciferous vegetables and cardiovascular disease (21:57) Does sulforaphane slow aging? (29:39) Sulforaphane improves symptoms of autism, schizophrenia, and depression (36:18) Neurodegernative diseases and taumatic brain injury can be treated with sulphoraphane (41:36) Concluding thoughts If you're interested in learning more, you can read the full show notes here. Join over 300,000 people and get the latest distilled information straight to your inbox weekly: https://www.foundmyfitness.com/newsletter Become a FoundMyFitness premium member to get access to exclusive episodes, emails, live Q+A's with Rhonda and more: https://www.foundmyfitness.com/crowdsponsor

Hello again, boys, girls, distinguished members of the electron transport chain and extraterrestrials, I'm back, bringing you a fresh edition of the Found My Fitness podcast. This podcast is so fresh your mama, if she heard it, would be telling it not to get fresh with her. I know it feels like it's been a while, but that's just because things move so fast here on the internet. But sometimes you've got to slow down or risk drowning in emojis and flat earth YouTube videos. You've been wondering where I've been, but I've been here all along, preparing. Just me in the dojo with PubMed, putting a stranglehold on the material. and methods, having discussions with the discussion, talking back to those abstracts and telling

them they need to be a little bit more concrete. I'm not going to lie to you. Going this deep on a podcast does things to the mind. Leaves you asking questions like, how my microbiome is feeling about the surrealness of this election cycle, or whether Bugs Bunny was really a wasa lastly rabbit or maybe he just had something to say. But don't worry, friends. We are in bat country no longer.

Today, I have some great stuff for you. We're going to talk about cruciferous vegetables as a group. In other words, we're going to be talking about broccoli, brussels, cabbage, cauliflower, collard greens, turnips, horseradish, radish, radish, mustard, rootabega, watercrest, landchrist, garden crest, bocchoy, packchoi, diacon, Mizuna, maca, tatoi, and wasabi. Yes, wasabi, who knew? We'll also be talking about broccoli sprouts so much about broccoli sprouts, and more importantly,

sulfurophane. We're going to talk about how sulfurophane is the most potent, naturally occurring dietary activator of a genetic pathway called NRF2 that controls over 200,000. hundred genes, many of which are antioxidant, anti-inflammatory, and inactivate potentially harmful compounds we are exposed to on a daily basis. We're going to be talking about the cancer preventative properties of sulfurane. We're going to be talking about the positive effects of sulfurine on behavior in humans and the potential, based on animal research, that it may later be shown to have for depression and neurodegenerative diseases like Alzheimer's and Parkinson's

disease. How sulfurine has a positive effect on biomarkers of cardiovascular disease and lowers inflammatory markers in people. We're going to talk about the role of sulfurophane in the aging process in general, how sulfurophane causes people to increase the excretion of carcinogens like fenzine and acrylene. We're going to talk about the bioavailability and dose and how I'm able to sustain my 40 to 60 milligram per day sulfurane have it cheaply through bulk sprouting and so much more. But before we get going, stop what you're doing, hit pause, go to my website at foundmyfitness.com, enter your email in the newsletter subscription box and click submit. This podcast has been baking in the oven for nearly four months. We're not done here. I need to be

able to communicate with you supplementary information that you don't want to miss. And if you're not on my list, I can't get it to you. That address is Found My Fitness, F-O-U-N-D-M-Y-F-F-I-T-N-E-S-S dot com. It's free and it's awesome. And hey, over 50,000 people can't be wrong. When you're done doing that, go to YouTube.com forward slash found my fitness or just Google found my fitness YouTube. Most of podcast come out as highly annotated videos that give extra definitions and facilitate better understanding as well as citations. And by subscribing, you're helping me achieve a personal milestone I'm working towards this year for subscribership over there. Finally, if you love this podcast and you just can't get enough, it's able to happen because of the amazing support of over a thousand people pledging to support

it for as little as a few bucks a month. You can learn more about that by going to foundmyfitness.com forward slash crowd sponsor. Once again, that's foundmyfitness.com forward slash C-R-O-W-D-S-P-O-N-S-O-R, crowd sponsor. All right, on to the podcast. 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 divided 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 cosmortar. 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%. 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 a 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 consume less than two and a half servings per month. Multiple studies have shown that women who consume cruciferous vegetables at least once a week had been. between a 17% to 50% decrease in breast cancer risk.

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 bioavillability 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% reduction in bladder cancer mortality and a 43% reduction. in all-cause mortality compared to those that just had one serving per month. Something is obviously going on here that's important.

These are some pretty powerful associations. But before we begin to establish causality, we have to establish a plausible mechanism. Our most likely candidate, isothiocinates. Isothiocinates are produced from compounds known as glucosinolates by an enzyme called myrosinase, which becomes activated when the cruciferous plant is chopped, crush, or chewed. but deactivated when subjected to prolonged high temperatures such as sustained boiling. One isothiocyanate sulfurophane stands out from all the rest because of its potency and the sheer amount of scientific scrutiny has been subjected to.

Remember how we said isocytocyanids? Sulfuriphanate is no exception. The glucosinolate sulfurophane is made from is known as glucoraphonin, but it's often simply referred to as sulfurophane glucosinolate. The single best source of glucoraphanin and thus sulfurphane are most likely broccoli sprouts, which contain up to 100 times more glucoraphon than their mature counterpart, broccoli. Moreover, broccoli sprouts are something that anyone can very, very cheaply produce at home in bulk. All it takes is around six glass jars, sprouting seeds, and continuous rotation to yield about

eight ounces every single day. This is something truly accessible to absolutely everyone since around 20 bucks. will buy you a couple pounds of seeds, which is enough to sustain production for months. There are several different mechanisms by which isothiocyanates, particularly sulfurophane, reduced cancer risk and kill cancer cells. And this involves many different molecular pathways, including inactivating a family of enzymes called phase one biotransformation enzymes, which are responsible for converting potential pro-carcinogens into carcinogens.

This is one way that sulfurophane prevents the formation of DNA attics, which is a type of DNA damage that forms after exposure to her carcinogen and has been shown to lead to cancer. Tobacco smoke has many carcinogens that form DNA addicts once they're inside the cell, which is why it's really nasty stuff that significantly increases the risk for several types of cancer, including lung cancer and bladder cancer, which may help explain the really strong association between just a few extra servings of cruciferous vegetables and a 55% reduction in lung cancer risk in smokers mentioned just a little while. while ago. But what about the study on bladder cancer? Here too, 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% 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 reduce cancer incidence when challenged with a tumor initiator. And what about the study on prostate cancer? Yet probably the isothiocinates too.

There have been a couple of clinical trials both involving prostate cancer investigating the effects of the active compound sulfurophan from broccoli sprouts on cancer treatment. Men with prostate cancer that were given 60 milligrams of sulfurophrane per day, an amount 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 rate at which a tumor marker is increased in a clinical trial by 86% that's pretty gigantic. It appears as though this robust effect of sulfurane on slowing the growth of prostate cancer

may be dose-dependent. In another study, when 35 milligrams of sulfurophrane 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 sulfurophane. In this case, bioaccumulation of the isothiocyanate. In 2007, a pilot study found that after receiving broccoli sprout extract containing about 37 milligrams of sulfurophan or the amount you might get from consuming about 85 grams of fresh broccoli sprouts, the accumulation of sulfurophan was detected in actual human breast tissue,

around 1.45 picomol per milligram for the right breast and two picomol 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 the breasts. Additionally, breast tissue also displayed increased levels of a gene called NQ01. 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 broccoli 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 sulfurine 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 isothiocyanides. But this stuff isn't cutting edge. I'm not the first person to rant and rave about this stuff. In fact, if we rewind a couple thousand years, an ancient Roman statesman, Cato the

elder, had this to say about a prominent member of the cruciferous family of vegetables. That cabbage, eaten crude with vinegar or cooked with oil or fat, banishes and cures all, from crampulence after exceeding too much wine or all the way up to serious diseases like cancer. Crapulence. Now that's a fun and totally legitimate word to throw around at parties. Okay, we already talked a little bit about how isothiocyanates can play a role at preventing the formation of carcinogens by inactivating phase one biotransformation enzymes. But what if, in addition to inactivating carcinogens, we got better at just getting rid of them. I'm talking

about excretion, removing them from the body. This relies on a whole different set of enzymes for which isothiocyanates are known to activate the phase two detoxification enzymes. This effect happens via the NRF2 pathway, for which sulfurophane is the most potent, naturally occurring, inducer of. NRF2 is a very important pathway because it controls literally hundreds of genes by a short sequence of DNA within these genes known as the antioxidant response element, which NRF2 is able to bind to and thereby initiate or suppress the transcription, of the gene. Phase 2 detoxification enzymes, like glutathione S-transferase, are important because they are

able to inactivate pro-carcinogenic agents by transforming them into water-soluble compounds known as conjugate that are usually less reactive and are able to be excreted in urine or bile. Additionally, these enzymes are able to decrease DNA damage by reducing inflammation and reactive oxygen species. So it's a good thing that an increase in glutathione S-transferralia. Transference 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 isothionic precursors, increased glutathione S-transferase circulating in their blood plasma by about 1.4 fold, while overall oxidative DNA damage went down by about 28%. Drops in DNA damage are a very good thing, since these are ultimately what? initiate cancer and are fundamental to the process of aging itself. But when it comes to showing off the ability of sulfurophane to help trigger systems that boost the excretion of carcinogens, there's really one study that stands out. This study demonstrated that sulfurophane and its precursor of glucoracinin can actually significantly increase the excretion of benzene.

Participants that were given a daily broccoli sprout beverage containing around 262.5 milligrams of glucoraphane and about 7.1 milligrams of sulfurophan, 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. For those of you that don't know, benzene is a nasty carcinogen that is known to cause cancer in humans and animals, particularly leukemia. Some of the major sources of bending that people are exposed to are from automobile exhaust

fumes and air pollution in general and cigarette smoke, even secondhand. Air pollution is the major bending source for non-smokers, and cigarette smoke really is the big culprit for smokers. In the U.S., cigarette smoke accounts for about half of the population's high exposure to bending, with the typical cigarette smoker inhaling around 10 times as much benzene per day as a non-smoker, or around 2 milligrams of benzene compared to 200 micrograms for a non-smoker. This starts to make a pretty interesting case for tobacco smokers, right? Here's the facts we've got so far.

Tobacco smokers that eat more cruciferous vegetables have a lower risk of lung cancer than smokers who don't. Smoking loads us up with the carcinogen called benzene, and interestingly, a supercharged broccoli sprout drink increases our excretion of bending. But even if you're not a smoker, which I really hope you're not, we still have plenty of other places we can get bending 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 bending. High dose bending 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 change 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 homogenate, 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 to individuals ranged from 25 grams of broccoli sprout homogenite 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 S-transferases, heem-oxygenase 1, and NQO-1, which is an enzyme we talked about earlier when we discussed breast cancer. Benzine isn't the only airborne carcinogen the anti-benzine broccoli sprout drink worked some magic on. Over the 12-week trial excretion of the carcinogen acrylene rapidly increased by 23%. Acraline is found in most of the major sources is 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 sulfurophofen led to a 50% increase in excretion of acrylene, crotonaldehyde, 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 isotheliorated. is found in watercress. In other words, different isothiocyanate in different

chrysivorous vegetable, but again, an effect on carcinogen excretion. In this study, 57 grams of watercress was given to smokers to eat with each meal for three days while they continue 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 sulfurophane, is a powerful way to deactivate and excrete harmful compounds that we are exposed to on a daily basis, but even more so if you're a smoker. While 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 incidents. 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 in 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 spout powder per day, which comes out to about 40 milligrams

of sulfurophan and is probably comparable to around 100 grams fresh weight for four weeks, lowered their serum triglyceride by 18.7 percent and lowered oxidized LDL ratio by 13.5 percent. Overall, this reduced trial participant's atherogenic index by just over 50 percent, 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 sulfurophane, have also demonstrated antithrogenic effects.

There are likely multiple mechanisms by which sulfurase vegetables in general positively affect cardiovascular health. One of the most important ones goes back to the genetic path, what we mentioned earlier. the same one responsible for activating those phase two detoxification enzymes, which is NRF2. And that is because NRF2 activates antioxidant genes. It activates anti-inflammatory genes. It deactivates inflammatory genes, which all affect cardiovascular health. Sulfurifane has been shown in rat studies to increase antioxidant activity and glutathione expression in endothelial cells that line the blood vessels. It also relaxes smooth muscle cells.

Additionally, sulfurphane appears to be able to reduce adhesive molecules. that are part of the atherogenic state that drives heart disease, such as E-Selectin, 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 in heart disease risk and consumption of cruciferates vegetables. So far, we have talked about how sulfurane has been shown to prevent cancer, cardiovascular disease, and soon we'll be talking about neurodegenerative diseases, all of which are

diseases of age. We've also talked about how associative studies, like the one mentioned at the beginning of the video, show reductions in all-cause mortality for the top 20% of cruciferous vegetable consumers. The question remains, however, does sulfurophane slow the aging process itself? One way to answer this question would be to see if sulfurophane 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, increased their mean lifespan by 30%. The lifespan extension from the broccoli extract depended on the activation of anoref2 and the FOXO pathway that is homologous to humans, FOXO3 longevity pathway. Finding out the benefits in these little critters are derived from the same genetic pathway that is conserved in humans is promising if we're to have any hope that the results might replicate

in a species a bit closer to us. Discovering that the FOXO genetic pathway is also involved, which is so closely linked with human longevity and I've talked about in numerous other videos and podcasts is just the cherry on top. In humans, for example, certain polymorphisms, which are genetic variations associated with increased activity of FOXO3A are associated with a 2.7fold increased likelihood that a given person will live to be a centenarian. The chances of actually becoming a centenarian, however, seem to depend a lot on keeping inflammation at bay. And it is now believed that suppression of inflammation is the single most important driver of successful longevity,

and that this actually increases importance with advancing age. And we're not just talking about survival either, but also a strong association with capability in terms of being able to more adequately perform activities of daily living, as well as cognition in all major age groups, including elderly, centenarians, semi-supercentenarians, which are 105 to 109 years old, and super centenarians, which are 110 years old and older. In fact, inflammation has been shown to be the single most important predictor of cognitive ability surpassed in its predictive ability

only by a person's chronological age itself. And this relationship isn't surprising. We know that if we take mice, for example, and induce chronic low-level activation of a master regulator of the pro-inflammatory response known as NFN, Kappa B, it can actually accelerate aging by 30% in mice. Again, suggesting that chronic enhancement of pro-inflammatory mediators really is not just a bystander, but an actual driver of aging.

Sulfurphane has been shown in mice to inhibit NF-CAPA-B through the activation of NRF-2. NF-CAPA-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-CAPA-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 decreased their circulating levels of IL-6 by 20%. Another study showed that a broccoli sprout powder containing a approximately 40 milligrams of sulfurophan, an amount you might get from around 100 grams of

fresh broccoli sprouts, reduce TNF alpha, a marker of inflammation by 11%, 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 IL6 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 sulfurophane from cruciferous vegetables is driving some of these reductions in inflammation by way of NRF2, we have to ask ourselves, what is happening to NRF2 and what does this mean for

other processes in the body? Under normal conditions, NRF2 is briefly activated every year. hundred and twenty-nine minutes or so. But when stimulated by sulfurophane, NRF-2's pattern of activation changes. It becomes activated every 80 minutes, which is a 61% increase. This increase in NRF2's activity is important because NRF2 regulates over 200 genes, many of which affect cellular aging. It protects from cancer, which is an age-related disease by inactivating carcinogens and increasing their excretion. It deactivates inflammatory genes. and activates antioxidant genes, which also protect DNA from damage that can lead to cancer, but also slow cellular aging in general. It does this by lowering the amount of damage that

accumulates within cells. This damage accelerates telomere shortening, and it causes cells, including stem cells, to become senescent and non-functional. Our immune cells, such as the adaptive immune cells, are susceptible to senescence with age, known as immunosinensens, and this, This can make us more susceptible to infection in older age. The adaptive immune response is the second immune strategies our body employs, which in contrast to the innate immune response is more specific. It functions by using and creating immunological memory after an initial response to a specific pathogen and leads to a more targeted response in subsequent encounters.

The adaptive immune system functionally declines with age, but mouse studies show us something interesting. Sulfururphane at a conservative dose of 1.6 milligrams per day was able to foster a regaining of much of that lost function. If we extrapolate this to a human equivalent dose, it turns out that it's actually a pretty conservative amount of around 20 milligrams per day of sulfurophane, which is what you would probably get from a little over 43 grams

of fresh broccoli sprouts. Okay, since we're talking about aging and I've dipped somewhat shamelessly into mouse studies already many times leading up into this point. I'll share one final thing, mostly just for fun, before we move on to another topic. For many folks, aging feels more like something that happens in the mirror rather than on a cellular level. You can't look in the mirror and see your telomeres getting shorter or DNA damage,

but you can see whether your hair is falling out. People might be more happy with keeping the hairs on their head 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 increased production of dihydro testosterone, which shortens the growth phase of hair follicles and results in decreased new hair growth. Interestingly, one study shows a pretty strong effect on hair regrowth from sulfurophane supplementation in mice subjected to experimentally induced hair loss. The effect from the injected sulfurophane was pretty,

strong. Somewhere on the order of around a 50% increase in hair regrowth, accompanied by a pretty robust decrease in dihydro testosterone levels. Okay, you guys know I love to talk about the brain. If I can find a way to tie in the brain into something I'm talking about, I will. Here too, sulfurophan, our favorite and most notable isothiocyanate, does not let us down. Sulfuripate can indeed cross the blood brain barrier, at least in mice. This is the first criteria that a substance must meet in order for there to be a compelling argument that it somehow exerts effects on the brain, though immunological effects can also qualify since we know the immune system and inflammatory mediators interact directly with the brain. The NRF2 pathway, the same pathway that

keeps coming up again and again in our discussion, is the body's strongest defense against oxidative stress. In fact, oxidative stress itself activates this pathway. For this reason, perhaps we shouldn't be too surprised to find that sulfurophane seems to also affect conditions of the brain for which we know oxidative challenge is a part of the ideology of. In a randomized, double-blinded placebo-controlled study, treatment with sulfurophane 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 glucoraphne. In other words, just the precursor to sulforophrane 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 disorders in the world.

The World Health Organization estimates that more than 350 million individuals of all ages have depression. According to the NIH, 10% of American adults are taking some form of a selective serotonin reuptake inhibitor, a broad category that includes drugs like fluoxetine, also known as Prozac. Mouting evidence suggests that nutrition plays a huge role in depression, more directly by impacting neurotransmitter production, which can be modulated by micronutrients, but also by affecting levels of systemic inflammation, which is now known to play a major role in depression. We know this because healthy people that are injected with either the pro-inflammatory cytokine interfere on gamma or lipopolysaccharide, which is a component of bacterial cell membranes that elicits an immunological response, immediately begin to experience depressive symptoms, which can then actually be alleviated with the polyunsaturated fatty acid known as Ecosapentinoic acid, or EPA, which is an omega-3 fatty acid, renounce of. noun for its anti-inflammatory properties. The reason these inflammatory molecules and

cytokines are 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, sulfurophane can lower important 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 same mice and giving them a whopping one milligram per kilogram of body weight a day of sulfurophene 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 and the 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 10 different models of stress-induced depression, sulfurphane alleviated depressive symptoms and anxiety

as well as the antidepressant Prozac in mice. Sulfurphane also decreased stress hormones and the inflammatory response in response to various social stressors, indicating that the neuroprotective effects on depression and anxiety may be associated with lower inflammation and lower stress hormones in this case as well. Mice that are repeatedly subjected to social defeat causes depression-like symptoms, including avoiding social situations. Sulfuriphan prevented this avoidance behavior when animals were given sulfurane. And even more interestingly, administration of the precursor to sulfur of glucoraphene during early development and adolescents prevented the social defeat during adulthood.

While the positive effects of sulfurophen and depression have only been shown in animal studies, this is enticing. We already have some evidence that sulfurophane has positive effects in other conditions of the brain in humans, such as autism. And we also have some evidence in humans that sulfurophan lowers many different biomarkers of inflammation, which also have a link to depression. For all of the aforementioned reasons, it seems very plausible that sulfurophane may have a similar effect on depression and anxiety in people. But the best we can hope for for now is that future studies will come out that can further illuminate this for us. Any discussion of inflammation in the brain would not be complete if we didn't briefly talk about neurodegenerative diseases,

often considered themselves to be diseases of aging, and also traumatic brain injury, for which chronic inflammation plays a central 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, sulfurophan, 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 normalized 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 surprise, however, to find that sulfurophane activates many heat shock proteins by increasing the levels of heat shock factor 1, known as HSF1, 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, sulfurophane's activation of NRF2 may, in addition to protecting against neurodegenerative diseases and potentially delaying brain aging, also have a special relevance for traumatic brain injury as well, which also has a very important inflammatory and oxidative stress component because of the post-injury production of reactive oxygen and reactive nitrogen species, the latter of which comes about as a consequence of activation of the immune system. There have been several studies showing that sulfur,

Sulfurifane can protect against traumatic brain injury or TBI in animals. For example, when administered by injection following TBI, sulfurophane has been demonstrated to attenuate blood-brain barrier 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 sulfurophane was given. Additionally, enhanced learning and working memory, was improved, but only if sulfurophane was administered within one hour post-injury.

It has also been shown that administration of sulfurophane 15 minutes after the onset of is a schemia, 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 by about 50% three days later. Sulfurifene increases neurite outgrowth, at least in cultured neurons, through the activation of NRF2. Neurite outgrowth is one of the most important mechanisms by which damage 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 neurotrophic factors. Rats with diabetes have reduced levels of the neurotrophic factors, brain-derived neurotrophic factor, or BDNF, and nerve growth factor or NGF. But this has been experimentally reversed by administration of sulfurophane. High levels of inflammation and oxidative stress, which are countered by NRF2, are known to negatively affect the production of neurotrophic factors.

To illustrate the importance of NRF2 in brain health, Mice that have had anoref2 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% reduction in neuroplasticity in the hippocampus. Neurotigener of diseases are not the only degenerative disease that sulfurophane shows some very early promise for. Duchen 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, sulfurophan was shown to increase skeletal muscle mass, muscle force by 30% and running distance by 20%.

Interestingly, in a separate cell culture study, sulfurophane was shown to inhibit myostatin in muscle satellite steles, 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 have a quick recap of the things we talked about. We started by talking about some of the epidemiological data showing associations between eating cruciferous vegetables and reduced all-cause mortality in general, but also mortality from many different types of cancer, including prostate, bladder, breast, and lung.

We talked about how there's a good chance that isothiocyanates, a group of compounds that notably include sulfurophan, are likely what is driving these associations and how we know this because of human studies where people that have already had different types of cancer and were given sulfurophan have a significant reduction in cancer death. We also know this from a variety of animal studies that cause cancer in animals and then go on to prevent it with sulfurophrane or combinations of isothiocyanates and sulfurophrane, or broccoli sprouts. We talked about how broccoli sprouts are the very best source of sulfurophan

having as much as 100 times more of the precursor to sulfurophan, glucoraphanin, than mature broccoli. We talked about the evidence that sulfurophan may be able to help us reduce DNA damage caused by oxidative stress and inflammation, how it lowers biomarkers of inflammation, which are central to cancer, aging, neurodegenerative diseases, and so much more. We talked about how broccoli sprout beverage was, shown to help people substantially increase their excretion rate of benzene by up to 61%,

which is a cancer-causing chemical that we can take in from our environment from a variety of different sources and how it also causes humans to excrete many more harmful compounds. We talked about how cardiovascular health and how cruciferates vegetable consumption has been shown to lower risk of cardiovascular disease, heart attack, and stroke, and some of the interesting human studies showing how supplementation with broccoli extract that contains sulfurophan cause substantial reductions in oxidized LDL, triglycerides, and even reduced atherogenic index of plasma by 50%, all of which are risk factors for cardiovascular disease.

We talked about how a beverage derived of broccoli sprouts improved behavioral scores for people with autism spectrum disorder and cognitive discores in a small trial of schizophrenic patients and how it shows promise ultimately for a variety of other neurological diseases and disorders, degenerative and otherwise, based on early animal research. Finally, we talked about how and what the role of NRF2 pathway is, which is potently activated by sulfurophan, and its relevance for virtually everything else we talked about, whether we're talking about mitigating inflammation, excreting carcinogens, ways in which it might help us prevent cancer, cardiovascular disease, or even the aging process in general.

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 sulfurophan 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 micromole of sulfurophan or about 0.25 milligrams of sulfurophane. Using this number, it might suggest that if a person wanted to get 60 milligrams of sulfur refrain 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 18.7%, and a reduction of oxidized LDL by around 13.5% with a daily dose of an extract that was equivalent to around 40 milligrams of sulfurophan, 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 sulfurophan showed promise in yet another study when it reduced TNF alpha, our marker of inflammation by 11%, and it lowered C-reactive protein, another marker of inflammation by 16%. The point is, your guess is as good as mine. 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 milligram sulfurophrane range, or 60 milligrams each for two people. Add in six jars in 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 sulfurophan and some factors influencing its formation. We've talked a lot about broccoli sprouts, but of course, sulfurane and other isothiocyanates can be derived from other cruciferous vegetables as well. There are many other cruciferous vegetables that contain the precursor to sulfurophane, glucoraphene. The levels of glucoraphene vary greatly between these different cruciferous plants,

but as a general rule of thumb, broccoli sprouts top the list as a source of glucoraphon, which is why we talk today a lot about the young sprouts of these plants. Only about 20% of glucoraphon, however, is bioavailable and converted into sulfururfane in the body. So, as you might imagine, it's important that your sulfurophrane source has a lot of this precursor to begin with. It's not just glucoraphidin that matters when it comes to maximizing sulfurophane, however. The work of actually converting this precursor into sulfurophane 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 my rosenase and thus can still manage to create some sulfurane from raw glucoraphon. 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 sulfurophene supplements on the market, which contain what is known as sulfurophane glucosanolate. In other words, they contain glucoraphenein, not synchloraphane, not.

sulforaphane, all the while lacking the requisite myrosinase needed to get the job done. There may be other ways to still accomplish things with supplementation. For example, simply eating cruciferous vegetables that do contain myrosinase along with your supplemental glucoraphon. One study showed that there was almost a twofold increase in sulfurophane 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 myrosanase as well. Finally, aside from supplementation, we have the question of how can we go about maximizing sulfurine production in the vegetables themselves? Some sources seem to indicate that three to four 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 epithiospecifer protein, which actually prevents the formation of sulfurophanes while still leaving myrosanase activated. If you're better able to control the conditions for what 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 increased the production of sulfurophane by around 3.5fold. However, if you increase the temperature much more substantially, you end up inactivating the myrosinase enzyme. That said, most of my estimates of the amount of broccoli sprouts needed to achieve a certain dose of sulfurophane 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 goyrogenic activity of isothiocyanates. The facts are that some studies have indicated that isothiocinids 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 isothiocinates that's roughly equivalent to the amount you might get in about 70 grams of broccoli sprouts, did not experience any negative effects on their thyroid hormones or demonstrate liver toxicity. If they are antinutrients, they are my favorite antinutrients. All right, that's it for this podcast. Thank you so much for listening.

If you're pumped up and you can't wait for the next podcast, you can be a part of my posse giving me the resources to bring it all together and to make it happen by pledging a few bucks a month. Learn more about that at foundmyfitness.com forward slash crowd sponsor. that's C-R-O-W-D-S-P-O-N-S-O-R. Don't forget to go get on my newsletter so that I can send you extra information when I release podcast including summaries, other relevant links, and much more. Get that on my website that's once again found at foundmyfitness.com.

You can also go check out the corresponding sulfurophane video where I cite everything, add helpful definitions, et cetera. You can find that at YouTube.com forward slash found my fitness, or by searching Found My Fitness YouTube on Google. Finally, last but not least, hit me up on Twitter, Instagram, Facebook, all of which I post on several times a week under the username Found My Fitness. I don't respond to absolutely everything, but I try my best and I do read a whole heck of a lot of it. Until next time, Dr. Rhonda Patrick over and out.