The Role of Glucosinolates and Isothiocyanates in Promoting Good Health

: Uma entrevista especial com Jed Fahey Pelo Dr. Joseph Mercola JM: Dr. Joseph Mercola JF: Jed Fahey JM: Bem-vindos a todos. Este é o Dr. Mercola, ajudando você a controlar sua saúde. Hoje, temos um verdadeiro prazer e vamos aprender mais sobre uma das razões pelas quais vegetais crucíferos e brócolis são tão saudáveis ​​para você e todos os benefícios que isso poderia proporcionar. Nós vamos aprender sobre isso com provavelmente o pesquisador líder em todo o mundo, que passou as últimas quatro décadas de sua vida descobrindo esses detalhes. Esse é realmente um dos focos do que tento fazer com essas entrevistas. É encontrar as melhores pessoas do mundo para compartilhar essencialmente os destaques de suas carreiras profissionais, para que você não precise e possa basicamente receber todos os resultados. Dr. Jed Fahey está na faculdade de medicina Johns Hopkins, onde é bioquímico nutricional com amplo treinamento, ampla experiência em fisiologia vegetal, nutrição humana, fitoquímica e bioquímica nutricional. Atualmente, ele é professor assistente lá. Bem-vindo e obrigado por se juntar a nós hoje, Dr. Fahey.

JF: Obrigado por me receber.

JM: Alright. I guess it’s been a long career for you. I’m just curious if you maybe can lay the foundation of how you started becoming interested in these plant compounds that could have so many benefits that we’ll discuss in a few minutes.

JF: I sure can. It’s quite a long story, so you may want to cut some of it out after you hear it. I suppose it starts in my high school days when I was going to become a marine biologist. I’m old enough that I was around the time Jacques Cousteau was coming on the scene. I wanted to be a marine biologist, so I went to get a master’s degree in algal physiology, or the physiology of algae, microalgae. There were no jobs available in algal physiology, of course, when I got my master’s degree in the late ‘70s. I wound up going into agriculture biotechnology for about 15 years and worked for some big and some small companies. There were a lot of promises made. There was a lot of hand waving. There were all sorts of wonderful ways that these companies are going to feed the world with plants. It didn’t happen. Of course, long-term projects were cancelled in these companies. I wound up going to Johns Hopkins in 1993 during the group of Paul Talalay, the very famous prevention scientist. He was a cancer biologist who worked in prevention. Prevention was a fairly radical theory back then, only 25 years ago, the idea that with food, with nutrition, plant foods primarily – It sounded a little bit like Michael Pollan perhaps, but, “Eat food. Mostly plants.” That was a radical idea, but I was delighted to join forces with Professor Talalay. Over the last 25 years, that’s pretty much what we’ve done. We’ve studied. We’ve tried to, as we’d like to say, to put teeth in the recommendations that you should eat more plants, that your diet that – stressed – was primarily plant-based, can be healthy for you. We’ve tried to understand and bring to the public ideas about how and why eating plants and the phytochemicals in plants, phytochemicals just being compounds or chemicals that are present in plants, can enhance one’s health span and allow one to live a longer life in full vigor and health. Perhaps then, one day, when we’re 100 or 110, take your pick, maybe 120, we just don’t wake up. But it’s been a fun ride until then. JM: Yes, indeed. One of those phytochemicals, the one that seems to be one of the primary focus is sulforaphane. That, of course, is not in broccoli, but it’s produced from the glucosinolate, glucoraphanin, that’s available in there. Maybe you can enlighten us and elaborate on the details of that and how the glucoraphanins convert into sulforaphane through myrosinase. JF: Sure. Glucoraphanin and all glucosinolates, in fact, are phytochemicals that are essentially inert. They’re not very active. They’re present in vacuoles. They’re little bags within plant cells. In a number of species, including all of the cruciferous vegetables and notably the plant called moringa oleifera. I’ve done a lot of work on moringa over the years. I’d love to circle back and talk about that because it also has these compounds. But glucosinolates are water-soluble. They don’t do much for the human body or the plant probably for that matter, except storing sulfur. When we as a predator or a bug, a worm, a caterpillar, a beetle or even a bacterial or fungal infection, when we break plant cells, when we lyse them, these bags of glucosinolates open up and spill their guts into the rest of the plant tissue. And then there are enzymes called myrosinase, which are present in the same plant cells and certainly the same plant tissues. Those enzymes go to work on the glucosinolates and form compounds called isothiocyanates. Those isothiocyanates are biologically active and they act as feeding deterrents. They act as toxins to insects. Many of them are bactericidal to varying degrees. As you might imagine, they repel the nasty bug, the bacterial infection or the fungal invasion of that plant. Evolutionarily, that’s what they were designed to do. We – And I give Paul Talalay great credit for realizing this 25 years ago – We as human beings, repurpose those compounds. What they do is that, these isothiocyanates, when we ingest them, they trigger or they induce various protective enzymes in our body cells. We can actually unconsciously utilize these plant compounds, these plant defensive compounds to ratchet up or gear up our endogenous defense mechanisms.

JM: I’m assuming that you’re referring to the nuclear factor erythroid 2-related factor 2 (Nrf2) pathways, which became popularized when you started studying this. Is that the one that you’re referring to?

JF: Esse é certamente um deles. Essa é a principal descoberta por pessoas aqui na Johns Hopkins. No Japão, Masakazu Yamamoto e seu grupo agora em Sendai, na Universidade Tohoku – Tom Kensler, Shyam Biswal, Paul Talalay, John Hayes em Dundee, Escócia, Albena Dinkova Kostova – realmente um grupo bastante pequeno de cientistas estava procurando, entre outras coisas, o que diabos esses isotiocianatos ou sulforafano desencadeiam no corpo humano. Eles mapearam essas vias Nrf2, que são altamente responsivas aos isotiocianatos e que regula positivamente todo um host de antioxidantes e outras enzimas protetoras. Curiosamente – podemos voltar a isso – mas, curiosamente, sulforafano e moringina, da planta moringa que mencionei, e outros isotiocianatos, também diminui a resposta do fator nuclear pró-inflamatório kappa-cadeia leve de células B ativadas (NF-κB) em humanos. Eles podem realmente ter um efeito na resposta ao choque térmico, que tem a ver com dobramento de proteínas e resgate de proteínas contra danos. Existe uma lista bastante assustadora de atividades biológicas benéficas que esses isotiocianatos têm. Mas Dr. Mercola, você está correto. O caminho do Nrf2 é certamente o caminho principal que começamos a observar e esse é certamente um mecanismo defensivo primário que é super-regulado. JM: Estou curioso. Parece que na sua história o caminho Nrf2 foi – A descoberta desse caminho foi catalisada pela onda de como o sulforafano funcionava. Isso é verdade? que tem a ver com dobragem de proteínas e resgate de proteínas contra danos. Existe uma lista bastante assustadora de atividades biológicas benéficas que esses isotiocianatos têm. Mas Dr. Mercola, você está correto. O caminho do Nrf2 é certamente o caminho principal que começamos a observar e esse é certamente um mecanismo defensivo primário que é super-regulado. JM: Estou curioso. Parece que na sua história o caminho Nrf2 foi – A descoberta desse caminho foi catalisada pela onda de como o sulforafano funcionava. Isso é verdade? que tem a ver com dobragem de proteínas e resgate de proteínas contra danos. Existe uma lista bastante assustadora de atividades biológicas benéficas que esses isotiocianatos têm. Mas Dr. Mercola, você está correto. O caminho do Nrf2 é certamente o caminho principal que começamos a observar e esse é certamente um mecanismo defensivo primário que é super-regulado. JM: Estou curioso. Parece que na sua história o caminho Nrf2 foi – A descoberta desse caminho foi catalisada pela onda de como o sulforafano funcionava. Isso é verdade? Parece que na sua história o caminho Nrf2 foi – A descoberta desse caminho foi catalisada pela onda de como o sulforafano funcionava. Isso é verdade? Parece que na sua história o caminho Nrf2 foi – A descoberta desse caminho foi catalisada pela onda de como o sulforafano funcionava. Isso é verdade?

JF: I think that it’s fair to say that it was catalyzed by some of the early work at the Talalay lab and others were doing on chemoprotection or chemoprevention. Take your pick of those two words. I think chemoprevention has become more popular, although we at our center go by the acronym, chemoprotection. [—–10:00—–]

JM: I did not know that. But it is a massively important pathway, one that most physicians and clinicians and primary care people are not really very familiar with. It’s recently been popularized. I’m wondering if you could expand on what it does because it’s so profoundly important for optimizing our physiology.

JF: Yeah. I mean it’s important because what happens is this is a nuclear transcription factor, which is found in the cytoplasm of the cell. And when molecules like sulforaphane and their whole host – There’s actually a large number of families of chemicals that upregulate this system. But the Nrf2 molecules in the cytoplasm, it’s actually tethered there by a chaperone protein. It goes by the acronym “KIP1.” There is a conformational change in KIP1. It’s a dimer. I’m simplifying. I’m not the molecular biologist who discovered this pathway, of course. But there’s a conformational change, and Nrf2 is released from that molecular tether, if you will, and it migrates to the nucleus, goes to the nucleus and binds to what’s known as an antioxidant response element. That then allows the transcription of a whole suite of antioxidant and chemoprotective genes, which go on to allow proteins to be formed, many of them are protective enzymes. We have an assay that was, again, developed close to 30 years ago now here, which we routinely use, which is sort of a signal that this pathway has been upregulated. But there’s a whole host of enzymes that’s coordinately upregulated that are protective. In our scientific ratings, we frequently talk about compounds, like sulforaphane being an indirect antioxidant. You didn’t ask about that, but before I forget to explain – It’s an important concept, because what happens is when you upregulate these antioxidant enzymes, you allow for protection against oxidative stress in those cells in which these enzymes are upregulated. These enzymes are rather long-lasting. In other words, they hang around in the cell and the tissue for a matter of certainly hours, in most cases, days, a few days, maybe longer than that. We refer, for example, to sulforaphane and isothiocyanates as indirect and as long-lasting antioxidants because they crank up the activities of these antioxidant enzymes. In and of themselves though, these molecules, like sulforaphane, are not direct antioxidants. Like for example, vitamin C. Many of the other antioxidants that folks are probably familiar with, which do their thing, protect against reactive oxygen species, reactive nitrogen species, and then they’re gone. They have to be replaced or replenished.

JM: Thank you for that explanation.

JF: Before you ask another question, I’m sorry. I’m rambling on here. I should stop and catch a breath more often.

JM: Tudo bem. Tudo bem. Eu só queria expandir isso e o esclarecimento de que a ativação do NRF2 geralmente é acreditada como sendo hormonalmente controlada. Isso é um pouco de algo que pode ser – Um pouco grande de dose que pode ser prejudicial. Uma dose menor pode ser benéfica, como o sulforafano. Mas acho que o mais importante é que, diferentemente de um antioxidante, que suprime indiscriminadamente os radicais livres, e alguns deles podem ser radicais livres muito benéficos, é por isso que a maioria dos estudos que analisaram a suplementação de antioxidantes parece não trazer benefícios para os radicais livres. longevidade ou tempo de saúde. Mas coisas como o sulforafano fazem isso de uma maneira que libera ou estimula a ativação dos elementos de resposta antioxidante quando é apenas necessário. Isso é verdade? Se sim, você pode expandir isso? JF: Bem, quero dizer, é verdade, mas acho que é preciso ver coisas como o sulforafano e esses isotiocianatos como compostos que – Sim. Eles são horméticos. Muito pouco não terá efeito ou poderá ter um efeito alternativo. Demasiado certamente poderia ter um efeito deletério. Ainda não sabemos o suficiente sobre a dose. Estamos trabalhando nisso. Podemos voltar a isso. Sugerimos na medida em que alguém pede nossa opinião, embora, é claro, não prescrevamos, mas podemos sugerir que uma dose razoável, que sabemos pelos estudos clínicos agora possa ter um efeito farmacodinâmico, o que significa que pode causar indução de essas enzimas. Pode até afetar vários sintomas. Mas podemos aproximar uma dose com base no que as pessoas que comem muito brócolis, por exemplo, comeriam. Ou, no caso da moringa, isso não é algo com o qual muitos americanos estejam familiarizados, mas as pessoas que comem moringa regularmente – este é um vegetal tropical – com base em nosso conhecimento da química, podemos medir a quantidade de glucosinolatos nessas plantas. Podemos estimar e usar o teste da literatura epidemiológica para saber quanto as pessoas receberiam se comessem essas plantas regularmente. Desculpe. Temos buzinas e sirenes ao fundo aqui. Eu estou falando de um hospital.

JM: Yeah.

JF: I’m afraid we’re not quite smart enough as a group of scientists who study this stuff yet to really be able to prescribe a dose really well. But yes, one can have too much and one can have too little. Not sure I fully answered the question that you had but –

JM: No. That’s fine for the hormesis, but I’m wondering about the activation of IRE transcription as a transcription factor. Is it modulated by the need for antioxidant or reduction of oxidative stress or is it just indiscriminate, like swallowing vitamin C and vitamin E?

JF: I think to a degree, the proteins that are transcribed from that upgenetic – from that chemical, rather upregulation of genes, there’s feedback on that to a degree. For example, if you upregulate a glutathione transferase or one of the various so-called antioxidant enzymes and there’s a large oxidant stress present in that tissue, then you’re going to use a very unscientific term. You’re going to wear out that enzyme. It’s going to crank through its useful lifetime and be used up. But again, this is a sort of indirect opposition or contrast to a direct antioxidant. You give vitamin C. It’s taken up. It spikes in the blood very quickly. It’s used upwards, but it’s flushed from the body in the urine within a matter of minutes to hours. If you give too much, you’re creating expensive urine. It’s active for a short period of time. When you upregulate the antioxidant enzymes, they’re active for a fairly lengthy period of time, as I said, hours or days, and then those enzymes go away. Dosing with sulforaphane would be – and we think it is, we can’t prove this to you chapter and verse yet – but dosing with something like sulforaphane can be done every day, perhaps every other day, perhaps every three days even. Because what you’re doing is cranking up activity and production of enzymes that are going to hang around the body for a little while before they go away.

JM: Okay. We’ll get back to that. I just want to clear up some of the other benefits that sulforaphane has and you mentioned. I really wasn’t aware until I listened to a presentation by one of your post-docs, Dr. Brian Cornblatt, who both were attending the same event. He mentioned the upregulation of – Actually, he mentioned two. He was going to med school, but you were responsible for getting him to go and do this type of work. You were a major influence in his life. But one of the things he mentioned with respect to sulforaphane was the upregulation you mentioned earlier, the upregulation of heat-shock proteins.

JF: Yes. JM: You mentioned that it’s responsible for enfolding. But I just want you to expand on that because it’s a one quick sentence that you mentioned. But most people are completely unaware of the need for refolding your proteins. I looked in on it and did a little more reading in some of the studies. I was just astounded to find that one-third of the proteins that we make, one-third are misfolded. They’re misfolded. They don’t work. You definitely need things like heat-shock proteins to refold them. [—–20:00—–] The heat-shock protein also, of course, has sort of a – is a cousin to autophagy and that it can target severely misfolded proteins to be destroyed and recycled if they’re beyond repair. It’s an important thing. Is there anything else you’d like to add to that to help us fully appreciate the benefit? This is one of the major benefits that the glucosinolates like sulforaphane provide – or actually, the isothiocyanates provide.

JF: Well, if you’ll allow me to go off on a slight tangent, I will answer your question indirectly. Yeah. You’re right. The heat-shock pathway or the heat-shock response is extremely important and these protein chaperones are certainly biologically very important. Again, I use the caveat. I can say this about everything. I’m not the expert on heat-shock.

JM: Você é bom o suficiente.

JF: Uma milha de largura e uma polegada de profundidade, certo? A história interessante que quero lhe contar é que sim, o sulforafano, a moringina da moringa e outros isotiocianatos parecem regular positivamente a resposta ao choque térmico. Cerca de dez anos atrás, um pouco menos, o Dr. Andrew Zimmerman, que na época estava em Harvard e Mass General, veio a Paul Talalay, meu mentor aqui em Hopkins, e disse algo para o efeito de – ele disse isso com mais eloquência – mas algo com o efeito de “Ei, Paul. Estamos analisando o autismo. ”Ele é especialista em autismo. Ele disse: “Curiosamente, algumas crianças com autismo e febre, seus sintomas desaparecem. Eles ficam muito melhores. Quando a febre desaparece, quando a febre desaparece, os sintomas voltam. ”Ele disse:“ Ei, Paul. Seu grupo e outros demonstraram que o sulforafano regula positivamente a resposta ao choque térmico. Não seria legal se essas duas coisas estivessem conectadas e se o sulforafano pudesse afetar o autismo? ”Esse é um alcance. Mas, em 2007, o Dr. Zimmerman e outros publicaram um pequeno estudo, um estudo clínico, no qual mostraram que, de fato, eles codificaram, até onde sei pela primeira vez, o que muitos psiquiatras e muitos médicos que tratam crianças com autismo sabiam. É esse o fato de que esse efeito da febre não foi chamado de efeito de choque térmico. Foi chamado efeito de febre. De fato, levantamos alguns fundos privados, algum dinheiro filantrópico. Isso não era algo que os Institutos Nacionais de Saúde (NIH) estavam prestes a financiar. Fizemos o estudo com o Dr. Zimmerman. Foi publicado em 2014 nos Anais da Academia Nacional de Ciências (PNAS). Nós tínhamos – acredito que com 44. Todos eram homens, 44 homens. Dois terços deles receberam sulforafano e um terço recebeu placebo. Isso durou 18 semanas por via oral, diariamente. Fizemos o sulforafano aqui no meu laboratório. Na verdade, tivemos que ir ao Oregon Freeze Dry (OFD) para congelar grandes quantidades secas para este teste. E depois de 18 semanas de tratamento, todos voltaram ao placebo. Eles pararam de tomar sulforafano. Os sintomas foram monitorados no início, três vezes durante o estudo, depois no final de 18 semanas e depois nas 22 semanas após o período do placebo. Surpreendentemente, para alguns – não é uma surpresa, eu acho, para aqueles que estavam ansiosos para ver se isso funcionava – mas houve uma redução dramática, significativa e substancial nos sintomas de autismo, muitos dos sintomas medidos por escalas que médicos ou cuidadores usam e as escalas que os pais usam para avaliar a gravidade do autismo em algumas, mais da metade das crianças. Esses sintomas voltaram, portanto, em outras palavras, as pontuações médias do grupo sulforafano voltaram mais ou menos à linha de base após o uso do placebo. Esse estudo foi publicado. Na verdade, tivemos um estudo de acompanhamento. Devo dizer que seguimos esses indivíduos por mais três anos. Acontece que quase todos eles, seus cuidadores ou pais os colocaram em algum tipo de suplemento comercial de sulforafano. Acontece que muitos deles relataram redução contínua e contínua dos sintomas após esse período. Devo dizer que agora temos – não devo dizer “Temos agora. Não sou o investigador principal em nenhum deles porque não sou psiquiatra – mas temos cinco estudos de acompanhamento realizados. Um com cerca de 120 crianças, homens e mulheres na China, outro com o mesmo grupo, o grupo do Dr. Zimmerman, que agora se mudou para o Centro Médico da Universidade de Massachusetts. Espero encontrá-lo no próximo mês. Vamos examinar alguns dos dados, que são – O julgamento terminou. A intervenção terminou. Veremos isso. Um já foi publicado. Foi um pequeno estudo sem controle de placebo na Universidade da Califórnia em São Francisco. E há outras duas que estão terminando ou em andamento. Estamos muito animados para ver o acompanhamento clínico desse primeiro estudo. Tudo isso resultou em voltar à sua pergunta original. Eu disse – eu divergi. Tudo deriva da ideia de que talvez essa seja uma resposta de choque térmico envolvida. Estamos procurando marcadores moleculares bioquímicos da resposta ao choque térmico em pelo menos alguns dos estudos, os estudos de acompanhamento. Eles não foram seguidos no primeiro estudo publicado.

JM: It’s great to do the studies. But when you have a severely impacted group like those parents who have autistic children, they’re likely not going to be continuing to use an intervention unless it works. Most likely, it does provide benefit. I’m curious because near-infrared saunas specifically are really noted to increase the production of heat-shock proteins. Is it similar to what sulforaphane does? Is it the same protein response? We know there’s a wide variety of different heat-shock proteins. Do you actually get a fever or an elevated temperature that you alluded to when you’re taking sulforaphane?

JF: Não. Você não fica com febre ou temperatura elevada quando toma sulforafano. A idéia é que você possa ser independente de uma resposta de temperatura. Você pode estar induzindo – ou é – você induz algumas dessas proteínas no corpo. Suponho que a melhor maneira de ver isso seja como um mecanismo alternativo de gatilho. Não sou suficientemente versado na literatura da sauna. Eu tenho amigos que – eu realmente sei que esse é um assunto quente. Eu sinto Muito. JM: Chalaça pretendida.

JF: Yeah. Pun intended. Right.

JM: Okay. That’s okay. That’s fine. But I was just curious and thought you might have some insights on that. Because it really is such an important explanation as to why this molecule provides such a good benefit. Now let’s get back to the timing as you mentioned, because I think it’s an important topic. First of all, one of the other benefits, before we get to the timing, is that it also facilitates detoxification, upregulates some of the enzymes in the cytochromes and the liver to help your body remove toxic molecules from your body. Typically, the detox phase is best activated if you divide normal human physiology in two phases. One is autophagy or the repair and the breakdown of tissue, and then catabolism, where you’re rebuilding tissue, so that it would seem that activation of those detox enzymes would be best done in autophagy periods, where you’re not eating, especially even better in longer fasts. I’m wondering if you looked at it with respect to the timing and the cycling. Because like everything, there’s probably an optimal time to give this molecule.

JF: I couldn’t agree with you more. The short answer to your question – I’ll see if I can give you a short answer this time – We haven’t done it, buddy. It hasn’t been done as far as I’m aware. It’s interesting when you do these sorts of clinical trials with a molecule like sulforaphane. Certainly, early on, it was hard to get funded because it was viewed as it is, a plant compound. It’s not supported by a drug company because it’s not patented. It’s a natural compound. [—–30:00—–] When you do a trial and you have a successful outcome of some sort, even if it’s just successful following it in the blood and urine, the next person or the next group that does the study with the same compound tends to use the same dose, the same amount, the same dosing regimen, because god forbid if they did something radically different, like delivered it during a fasting period when you didn’t, they might not replicate the results. That would be the end of clinical trials for those compounds. We started the trials, the very simple pharmacokinetics or bioavailability trials that we started doing. We almost always did on an empty stomach, first thing in the morning, 8 o’clock in the morning, delivered with a bottle of water. Then people were allowed to go out and have breakfast after they left the clinic. A lot of the trials that have followed up have gone that way. I started doing some trials in China with Tom Kensler. And Tom is the colleague who was here at Hopkins for many years and now is at the Fred Hutchinson Cancer Research Center in Seattle. The first trials that we did there, again, we made the broccoli sprout extracts and then delivered every day at the local village doctor’s house, actually. We gave a bottle of water so they could chase the dose. In the case of most of those studies were done in the evening when people would normally have dinner. That was last on the fasting state. But certainly, we haven’t looked at intermittent fasting or long-term fasting.

JM: Yeah. That is interesting. Thank you for your honesty in that and sharing the truth, which is that the studies haven’t been done. But there’s probably no one in the entire world who is more knowledgeable in the topic than you are. From your depth of understanding of the biochemistry and the pharmacokinetics, it doesn’t seem to make sense. Rather than to give it in the morning when you’re just starting to eat and activating catabolic phase, to give it at night or right after the last meal of the day and hopefully you’re not going to eat for another 16 or 18 hours or even on a longer fast, and to not take it when you’re trying to be in a catabolic phase and building muscle tissue.

JF: Sinceramente, não sei a melhor maneira de responder a essa pergunta, porque acho que alguém poderia argumentar que, se alguém a der de manhã com o estômago vazio, estará começando a cuidar dos negócios diários e a ser exposto, por exemplo, à poluição do ar. Se alguém trabalha fora ou ao sol, se trabalha fora, a luz UV é um agente cancerígeno, como todos sabemos, além de uma bênção para a vitamina D. Pode-se argumentar que, se o trabalho que o sulforafano faz no corpo, o a regulação positiva ou enzimas protetoras acontece rapidamente, e acontece que talvez seja melhor dar a primeira coisa pela manhã para se proteger contra os insultos do dia. Porque certamente, quando você está confortável como um inseto em um tapete na sua cama, não está sendo bombardeado com radiação ultravioleta. Você certamente não está mudando seu perfil de inalação de oxigênio reativo, como faria durante um dia de trabalho na cidade. JM: Bem, o contra-argumento pode ser que esses produtos químicos, pelo menos a partir da exposição a produtos químicos, que eles vão permanecer por ali e potencialmente sejam armazenados em suas células adiposas. Nesse caso, você gostaria de se livrar deles. Você faz isso durante a fase de desintoxicação. Pode parecer melhor. Não conheço a farmacocinética, pois você aludiu ao fato de que foi regulada positivamente por até três dias. Nesse caso, é um tanto irrelevante quanto ao tempo. Parece-me contra-intuitivo, a menos que você esteja tentando tratar de forma sintomática um problema sério, como o autismo, para apresentá-lo todos os dias, pois pode ser desenvolvida uma resistência parcial a ele. Não é necessariamente o que você encontraria na natureza, comer esses glucosinolatos todos os dias. JF: Você está correto. Eu acho que seu ponto de vista é bem aceito. Eu certamente concordaria que não é preciso, novamente, de uma perspectiva evolutiva, as pessoas provavelmente vão comer a mesma comida o tempo todo, todos os dias. De fato, Tom Kensler, meu colega que mencionei antes, foi um grande defensor da dosagem intermitente ou não diária. Felizmente, veremos isso na China em um desses estudos lá. Penso que, novamente, você nos lembrou algo que eu disse anteriormente. Isso significa que você regulamenta essas enzimas protetoras e elas ficam no corpo por um período de dias. Isso é absolutamente verdade. Eles são capazes de trabalhar em qualquer uma das etapas: a fase anabólica ou anabólica, a fase autofagia. Eu acho que a outra coisa que eu deveria mencionar – e isso é tranquilizador – é isso, novamente com o trabalho de Kensler na China, mostramos que prolongou – acredito que foram três meses, 84 dias. Isto é publicado. A administração diária prolongada de sulforafano não levou a uma fadiga dessa resposta ao Nrf2. Não fatigou nem reduziu a capacidade de resposta dessas enzimas de desintoxicação. Acho que essa é uma distinção importante. Você não desgasta o sistema. JM: Ok. JF: Mas eu entendo o seu ponto.

JM: No. That’s good to know. I wasn’t aware of that. I would assume that that was a potential risk. But thanks for confirming that it doesn’t appear to be.

JF: Yup. JM: I’m really curious. Because when you opened the discussion about this, you had mentioned quite rightfully so that these glucosinolates in the plants are essentially poisons that the plant uses to protect itself from predation. I’m quite certain that the answer’s going to be that the studies haven’t been done. But with your breadth of knowledge on this topic, I’m wondering if you have any guesses as to how in the heck these poisons evolved to provide such a beneficial response in humans. I mean it doesn’t seem to be a direct correlation to why that would happen.

JF: Well, look. I mean I think – That’s a question I suppose I should stop and think about and not give you a snap answer to. I mean you can, on one hand, live a pretty bland life with probably a normal life span by existing totally on soylent. I’m not putting in a commercial plug for this recent product.

JM: Sure.

JF: But it doesn’t have any fiber or it didn’t anyway when I first saw it appear. It didn’t have any phytochemicals. It’s just protein, carbohydrate, fat and all the vitamins that theoretically you need. Or you can eat a diet rich in plants. What are plants – I mean I would turn the question around on you a little bit I guess and say, “What are these plants offering?” And then I would turn to Michael Pollan and I wish I could remember. I’ve got to memorize the quote from his book. He says that during the millennia of evolution, while humans were busy mastering locomotion, plants were nefariously producing all of these phytochemicals to protect themselves since they’re rooted in one place. Pollan said it much more eloquently than I certainly did. But I mean all plants that you put in your mouth are going to be providing phytochemicals that in most cases – They may have direct detoxification antioxidant functions.

JM: Like sulforaphane or glucoraphanin.

JF: Well, all flavonoids and anthocyanins and so on. Or there may be compounds like sulforaphane. There are a ton of them that you need if you’re eating a plant-rich diet. Evolutionarily, I suppose I can’t give you a good answer. But we do now from work that my colleague, Yuesheng Zhang, did 20 years ago – more than that – is that when one of your body’s cells sees sulforaphane, it takes it up. It’s rapidly taken up. It’s concentrated in the cell to a couple of hundred times concentration it sees in the blood and the interstitial tissue. And then it’s conjugated with glutathione rapidly and then it’s dumped back out of the cell unceremoniously and quickly. In the process, we know that the cell, that the Nrf2 pathway and all these other pathways are upregulated. But it is viewed as a toxin. It is detoxified. And perhaps it’s that detoxification mechanism, that cranking up of glutathione, which is the body’s most prevalent antioxidant, that’s doing the good things. That’s the direct antioxidant, which it’s upregulating. And then those molecules have a chance to stay around long after sulforaphane is gone. [—–40:00—–]

JM: Yeah. I couldn’t agree more. There are so many people, clinicians who recommend supplemental glutathione, and I think that’s a mistake. Not only is it poorly absorbed and expensive, but it’s far better to have your body make it than to take it exogenously. I think molecules like sulforaphane make a lot of sense if you want to upregulate glutathione. If you could just comment on the point, because I’ve heard you mention in other interviews that, which is surprising, that sulforaphane is the most potent natural activator of the Nrf2 pathway compared to any other glucosinolate, or isothiocyanate rather, and any other natural compound. I mean there are synthetics that may be more potent, but nothing beats sulforaphane.

JF: Yeah. I’m happy to comment on that. I have to walk that back a little bit. We said that and I said that many years ago when we were first working on sulforaphane. It turns out when we just published this – I guess it was last year. Within the last year, there was another compound called moringin from moringa.

JM: Okay. Moringa.

JF: You can have a contest between isothiocyanates. How do you do that? Well, you could do it in clinical trials, but that’s expensive. I suppose you can make the case that it’s ethically perhaps taboo. You wouldn’t want to have a contest in a clinical trial. But you can use cultured cells and you can have all sorts of contests, a head-to-head contest of sulforaphane and a whole slew of other isothiocyanates. Moringin, the compound, it’s called 4-O-(α-L-rhamnopyranosyloxy)-benzyl glucosinolate.

JM: Pretty good, or otherwise known as moringin.

JF: Otherwise known as moringin. It’s more potent than sulforaphane in some assays, in some cell lines. For example, we first saw this when we had a head-to-head contest with helicobacter, trying to kill helicobacter, which caused these ulcers in the stomach and can cause stomach cancer. We saw that moringin, from Moringa oleifera, the tropical tree, was every bit as potent in killing helicobacter as sulforaphane was. Those two were better than the others. When you look at different cell cultures, in-vitro assays, moringin and sulforaphane go back and forth.

JM: Interesting.

JF: I love that because sulforaphane comes primarily from broccoli sprouts or market-stage broccoli. They’re a temperate-zone crop. People in rich – Americans, compared to the rest of the world, and Europeans and Australians can buy broccoli sprouts and can buy supplements. As everybody knows, there’s a large swath of the world, mostly in the tropics who can’t afford these things. Certainly, you wouldn’t recommend growing broccoli sprouts too because of the climate and the water quality. Moringa is a tree and it’s grown all throughout the tropics, where many people can’t even afford, you know, a course of antibiotics when they need them. This “food” as a drug I think is very powerful and is something we really shouldn’t ignore. Moringa is being viewed as a superfood in the U.S. Certainly, I think it’s great to add to your diet, and people do. But in the tropics, where it’s grown, its phytochemical punch, moringin, is really something that I think shouldn’t be ignored. We’re trying to get funding to look at moringin or moringa in autism, much in the same way we looked at –

JM: Interesting. That is an aspect of research that many people may not realize. There are a lot of information about sulforaphane out there, primarily because of your lab and many others who have really done the hard work over the last decades or so. But there are 500 cruciferous vegetables, moringa being one of them. Not as much work has been done in any of the others, so there may be benefits that have yet to be discovered just because the research isn’t there. That’s understandable because there’s really not much financial benefit in the long run because these are natural chemicals and they can’t be patented.

JF: Mais uma vez, você está cantando minha música. Eu acho que cai – eu não acho. Eu sei que cabe a pessoas como você divulgar o público consumidor que não vai ler a ciência altamente técnica. Eu acho que é parcialmente responsabilidade dos epidemiologistas tentar fazer melhor. Quero dizer, eles estão fazendo um bom trabalho, mas para melhorar ainda mais algumas das conexões entre – Desculpe.

JM: Tudo bem.

JF: That’s a siren in the background again. To uncover some of the connections between the plants we eat, the vegetables we eat in particular, fruits and vegetables, and the diseases we don’t get, or the syndromes we don’t come down with. You mentioned the cruciferous vegetables and the isothiocyanates. I think it’s worth stressing here. There’s moringa, which is actually technically not a cruciferous vegetable, but it’s related and has these compounds. There’s broccoli. Arugula is another good one that has an isothiocyanate that’s quite potent. Horse radish –

JM: It’s also the highest plant source of nitrates.

JF: Yes. Even higher than spinach, right? JM: Higher than beets. I wouldn’t touch spinach with a 10-foot pole because of its oxalates.

JF: Yeah, yeah. Arugula, there’s watercress. They all have different isothiocyanates. Mustard seed and mustard certainly and those we know, for example, my colleague, Yuesheng Zhang, looked at the bladder cancer and the compound in mustard seed. There’s a fairly short list, if you want to go to the cruciferous vegetables and find those that are good sources of isothiocyanates. I’ve mentioned some other cresses. Then you start looking at things like Brussels sprouts and cabbage. They have compounds called indoles in them. These are indole glucosinolates also. Those indole glucosinolates are actually converted to different compounds, not isothiocyanates. The jury’s still out. It’s sort of mixed, but the jury’s still out on the benefit of those indole compounds and what they’re turned into. We can talk about that another time or later. Whatever.

JF: Yeah.

JM: I’m curious about moringa. I started to grow it in my backyard. It’s a real scraggly tree. I mean it’s very thin and tall and not very significant. But I’m wondering from a pragmatic perspective how you harvest this thing, because I just tore it up because I couldn’t figure out how to harvest it. The leaves are so small. They’re smaller than your fingertip. I mean it would take you like an hour to get any significant amount of leaves. Is there any strategy to harvest this in useful quantities?

JF: Yeah. I assume you grew it in Florida or California?

JM: Yes. Florida.

JF: I mean, remember, it’s a tropical tree. The subtropics or whatever you call Southern Florida counts. But then it dies off in the winter. It’s not its optimal range.

JM: Right, right. JF: Probably the fact that it’s scraggly and not really an appealing looking tree is one of its blessings because it hasn’t been harvested to death. But it’s also extremely fast growing. It grows 10 to 20 feet in its first year. Short answer is in areas where it’s grown as a tree, you grow it, you strip off the leaves and let it grow back. They sort of do that in the Philippines, Africa, India and other places. Another way that people grow it –

JM: But it seems to be hard to strip off the leaves without getting some of the stem in, and no one wants to eat the stem. Or do you just put it in the blender?

JF: You just put it in the blender or you strip the leaves from the stems. Yeah it’s a little difficult. JM: It’s tedious. Because the leaves are so small. It’s like you’ve been there for hours to get enough leaves to be of any significance.

JF: It’s true. Of course I live in the temperate zone. I tried to grow it one year and when it died off in Baltimore in the winter, I stopped trying. Although we’ve grown one in our lab, in the window in our lab that’s been growing for about 20 years. The way you do it is you buy it from someone that responsibly and sustainably has it harvested.

JM: Okay. That’s the way to do it. [—–50:00—–]

JF: Okay. I mean I think in this country that’s the way. You probably are aware I’m on the scientific advisory board for Kuli Kuli, which is a company that does sustainably harvest it. I’ve never asked Lisa, my friend there, to take me to Africa and show me how it’s harvested. But I presume that they do harvest from growing trees. I wanted to tell you that the cooler way to do it, the interesting way to do it, which we’re trying to bring to the temperate zone, is to grow it very densely. I have colleagues in the Congo who are doing this. You plant the seeds very close to each other. They grow up and within a few weeks, you’ve got plants. Within six to eight weeks, you’ve got maybe knee-high to waist-high plants. It looks for all the world like a crop – to use the analogy of your favorite vegetable – of spinach. I mean they do have the small penny-sized leaves. But then they go through and you get a huge harvest from an acre or from a square footage of land.

JM: Interesting.

JF: They can actually chop them down and let them regrow. It’s called compassing, I think. They keep on letting them regrow. It’s a highly efficient way of harvesting. JM: I’m going to give it a try and let you know if it works. Because I’ve got about an acre of land that I’m experimenting with that I can definitely dedicate some more to moringa.

JF: I have to tell you, since you’re in Florida, go to ECHO Global Farm in North Fort Myers, Florida. ECHO is an acronym for the Educational Concern for Hunger Organization. They have a demonstration tropical farm. They have a lot of Peace Corps volunteers and missionaries, I think, who come and learn how to do tropical agriculture there. They are one of the groups that I first talked to about growing moringa. You’d enjoy going there. It’s probably close to you.

JM: Well, yeah. Actually, I live on the East Coast, but my office is on the West Coast. It’s very close to Fort Myers, actually. I’ll actually be there next week or in two weeks.

JF: It’s worth the visit. Yeah.

JM: Yeah. Well, thanks. That has been – You’ve gotten most of the questions I have. You’re such a wealth of knowledge. Is there something that we left out or something that you’d like to emphasize because there’s so much valuable insights that you have. I just want to make sure that we’re getting the benefit of your decades of research.

JF: Well, I can’t say that there’s something that I’ve been just dying to talk about. You’ve touched on a lot of, I think, the points that need to be touched on. I mean it’s so important to try to translate this highly technical science and give it in a palatable format that the average consumer will resonate with it. Because some way or another, those of us who work in the biomedical sciences and in the health care sciences, we have to get the message across: that healthier diets and healthier lifestyles are critical. Because we’re killing ourselves with this processed food. JM: Yeah. There is one area that I think we should go into some details before we sign off. We touched on it, but I think it would really be of benefit if you could expand on this. Because the glucosinolates need to be converted to isothiocyanates through that enzyme myrosinase, which is available in our gut but is widely variable. It’s also available in the plant itself. You’ve got to be really careful about that, especially if you’re going to be cooking the plant or preparing it or taking the supplement. Those are all variables that need to be addressed. You’ve looked at these very carefully. I’m wondering if you can enlighten us on that.

JF: Sure. We certainly did sort of forget to talk about that. It’s a great point. As you said, when you eat the plant or maybe we didn’t say this, when you eat the plant, you crunch it up, you become a predator. You release myrosinase. You allow that myrosinase to act on the food, the tissue as it goes down from mouth to the other end. There’s some release of isothiocyanates, some production of isothiocynates in a time-dependent and person-dependent manner. When we study bioavailability, it’s all over the map. It’s hard to predict who’s going to do what. Your gut is full of microbes, as most people know nowadays, I think. And those microbes have myrosinase activity. They will do the conversion. If you are someone who doesn’t like eating vegetables or doesn’t like broccoli, for example, or broccoli sprouts – many people don’t – then taking a supplement is a reasonable thing to do. Years ago, I thought supplements were the kiss of Satan because I thought it was beholden on all of us to just eat more fruits and vegetables. But, look, there are various reasons that people don’t. As we get older and many of us exercise less and eat less, supplements, I think, are smart. If you take a supplement of glucoraphanin or moringin, for that matter, although I don’t think there are any in the market, you’re not supplying myrosinase. But that’s not necessarily bad. You just may need to take a relatively larger dose because you’re still going to have the bacteria in your gut, the microbiome in your gut do the conversion. It is hard to tell how much conversion there will be, unless you do a urine test and a chemical test. There are some supplements on the market now, some of them good, some of them useless, I think. But there are some supplements that have myrosinase, active myrosinase in them. Those supplements certainly give a higher delivery or a higher rate of conversion of sulforaphane to the person who’s taking them. They also tend to cost more. It’s a bit of a balancing act. I don’t think one’s necessarily better than the other for the consumer. From a clinical trialist’s point of view, someone who wants to do clinical trials, you might argue that the supplements with myrosinase would work better. Although I would argue it from a clinical trialist’s point of view. We might as well just deliver sulforaphane and know exactly what we’re putting in that person or getting that person to ingest. JM: Yeah. If you’re going to purchase the supplement with myrosinase, it would probably, because it’s an enzyme that can degrade, it would be best to refrigerate it, it would seem.

JF: Yeah. The other thing we didn’t mention – Maybe this is good for another talk with you some other time – But we should talk about the fact that these compounds also protect against ultraviolet light. They’re not sunscreens in the sort of traditional sense, but they actually – This is sort of the proof that they’re whole body effective. If you ingest them, it actually may protect against ultraviolet erythema or reddening of the skin. This is really a whole other discussion as it were.

JM: Yeah. There’s a carotenoid, the most potent carotenoid, astaxanthin, which has a similar effect.

JF: Exactly, exactly. But if you get me started talking on that, we’ll go on for another hour. We’ll save that for another time.

JM: Okay. Let’s just tie this up for myrosinase. If you’re preparing a plant like broccoli – and many people do enjoy it – there’s a sweet spot it for it. You don’t want to undercook it. If you undercook it, you’re not going to activate myrosinase. If you overcook it, you’ll denature the myrosinase. Do you agree that that three- to four-minute window of steaming is where the justright texture is the optimum to convert the myrosinase?

JF: Actually, three to four minutes of microwaving or steaming may wipe out the myrosinase.

JM: Interesting.

JF: Yeah. I mean you may spare some, you may not. It’s sort of touching. What you will do, sort of the advantage to that is that you won’t leach out, you won’t just blast the hell out of the broccoli, for example, and leach out the glucosinolates. Remember, glucosinolates are water-soluble. When you start blasting, if you boil the heck out of broccoli and you start lysing cells with dead – not dead – with inactive myrosinase, then the pot liquor, or the liquor that accumulates in the bottom of the pot, is going to have glucosinolates. But no one ever drinks the juice out of the bottom of a Corning Ware dish full of broccoli after they microwaved it. So eating raw, you could argue that eating raw cruciferous vegetables or moringa gives you – that’s not an argument – it gives you active myrosinase. The degree in which you cook it will, to some extent, kill them, knock out the myrosinase. I would say that moderate or very light cooking or steaming is fine, but I wouldn’t argue that it spares all the myrosinase necessarily.

JM: Alright. That’s a great answer. I want to thank you so much for your time and all your years of dedicated research and provide us with this valuable information, and personally, for inspiring me to start my moringa patch. [—–1:00:00—–] I’m quite confident that I bet a large number of people, at least in the summer, if they start them early and sprout them inside or something, and then grow them outside, can harvest a crop of this moringa, at least during the summer. It will die in the winter, but that’s okay. A lot of annuals do. But I had no idea it was comparable to the benefits of broccoli sprouts. If you just harvest the tops and don’t worry about the small leaves, you can put it in a smoothie and get the benefits. Because you’re not heating it, but you’re mechanically disrupting it, which would release the myrosinase. Drink it within 15 to 20 minutes and you’re golden.

JF: Exactly. You have to allow me a little commercial plug here.

JM: Sure.

JF: It’s not a commercial plug, actually. It’s a scientific commercial plug. We’re coming out, hopefully, we’ll be accepted for publication with a paper in the next few weeks, I hope, in which we’re using moringa leaf powder and we’re making teas out of it. The idea is to deliver this moringa leaf powder in a palatable format. I mean I have two to three cups of moringa leaf tea every day as I’m working. I’d rather drink that than – Well, I drink green tea also and black tea, but certainly, I’d rather drink that than coffee if I don’t feel like I have to have caffeine. There are various ways to deliver it. Those of your listeners who read scientific papers, keep your eyes peeled for a paper on moringa tea. Hopefully it’s coming out soon. JM: Alright. I’ll put it on my list, for sure. I would definitely go over that over the black tea, because the black tea is also high in oxalates. As far as I know, at least the last time I looked, moringa was relatively low in oxalates.

JF: I believe so. JM: Another major benefit, because oxalates are a pernicious plant toxin that you’d want to stay away from. JF: Yeah. Well, moringa is also extremely high in protein, compared

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