Friendly Fire: How the Brain’s Tiniest Cells Hold Hope for Autoimmune Diseases & Mental Disorders with Donna Jackson Nakazawa

Victoria: Hi Andy.

Andy: Hi Victoria.

Victoria: Today we have the pleasure of speaking with Donna Jackson Nakazawa and you turned me on to her new book. 

Andy: It's called the Angel and the Assassin. I think it's the most interesting book I've read in the past year. It completely changed my views about the brain and the immune system and specialized cells in the brain called the microglia.

And it made me very optimistic about new therapies, non- invasive therapies that are becoming available for the treatment of depression, other mental disorders and possibly even Alzheimer's disease.

Victoria: Fantastic. Let's get Donna on the line. 

Andy: All right. 

Victoria: Hello, we are delighted to have Donna Jackson Nakazawa as our guest today.

Donna is an award-winning science journalist and author, and her interest in the immune system began after she was paralyzed temporarily, thank goodness. And later diagnosed with Guillain-Barré syndrome, which is an autoimmune disease, and this experience led her to study the world of neuro immunology, which is what we're going to be talking about today.

Her new book is just amazing. It's called the angel and the assassin, and it, teaches us essentially about something that. Maybe you have never heard of, and that's microglia, which are cells in the brain, sometimes called the housekeeper cells of the brain and how they could act as either friend or foe.

We're going to be talking a lot about inflammation. Andy, if you could help our listeners understand the role of inflammation in the body. 

Andy: We all know inflammation on the surface of the body. It's local redness, heat, swelling, and pain at an area that's injured or under attack.

And while it may be uncomfortable, inflammation is actually the cornerstone of the body's healing response. It's the way. The body gets more nourishment and more immune activity to an area that needs it, but inflammation is so powerful and it's so potentially destructive that it's very important that it stay where it's supposed to stay and end when it's supposed to end.

If inflammation serves no purpose, if it escapes its boundaries of time and space, it becomes productive of disease.It's important that you produce enough inflammation because if you can't, you're vulnerable to infection, uh, but not produce too much. Because if you do, you are likely to develop allergies or autoimmune conditions.

And more recently, we have begun to see that chronic low-level imperceptible inflammation is the common root of many of the most serious diseases of aging. 

Andy: I commonly hear people refer to the auto immune system at the body. There is no such thing. Auto immunity is a pathological condition in which the immune system attacks the body's own tissues. That is a malfunction of immunity and it can be set off by many triggers by infection.

There may be a genetic predisposition by psychological trauma, either in the past or present. Uh, and it can be very destructive and painful. And depending on which tissues the immune system target, we have different disease entities, you know, ranging from things like rheumatoid arthritis to lupus. Uh, two very rare ones.

And I understand, Donna, you had an episode of Guillain-Barré earlier in your life, which got you interested in some of this. 

Donna: Yes. Yes. In fact, I was in grand rounds at Hopkins many times because I had it not once, but twice. So a lot of attacking of the cells in my body. 

And that does spark your interest when you're raising your small children from bed, um, you do start to look around and look at the world differently and find work, like what you all are doing and start to rethink your approach. To how you want to live in this world. And again, I think when we think about the fact that we can be exposed to too many triggers, I think it kind of like a barrel you know, we have so many things that come into the barrel of our immune system and we're good. You know, we can handle a lot. Think of what we're handling. Just any seconds, right? We're taking different pathogens and our body's fighting them off. But we're not there. All gets too full and that lasts. A little hit comes in, you know, the waters spills over.

And that image to me is profoundly hopeful actually, because as you all have shown so much through your work over the years. There are many things we can take out so that we don't overwhelm the body and it doesn't begin to attack the cells. And we can apply a lot of that same thinking to the idea that micro CLIA also needs to be in a state of homeostasis so that they don't get overwhelmed and start attacking a brain.

So, um, I think like a really exciting is that this is actually leading the field of neuroscience. And how very exciting and promising race to find. I think you guys will like this more, less invasive technique to treating two sorters of the mind, which has been a black box of medicine. Any psychiatrist who's being honest will tell me that their field is lagging 60 years behind other fields.

So. These are exciting times. It's a little scary. And also as a reporter in science journalists, you know, when I first reported on this and thought about it, I thought, Oh great. You know, I get one more thing, right? You know, my body's attacking itself. God knows what's happening in my brain, but it's really not scary in that it's the driver for a complete paradigm shift.

For the future of psychiatry, and that's huge. We need it. 

Andy: We desperately need it. Our center sponsored a national conference on integrative mental health. This was actually the second one that we've done, and the hunger for a new model to deal with psychiatric. Disorders is just enormous. I think psychiatry of all specialties is most, uh, held back by the materialistic paradigm that says that all mental disorders are the results of disordered brain biochemistry, and that the only way of dealing with that is through medication.

And those medications are sadly ineffective.

Victoria: Donna in the Angel and The Assassin, you really focus on this common root to many different neurological problems. Do you want to say how you got to that. 

Donna: Well, I have been reporting on the brain and the bodies for a long time. And about seven years ago, I started to see a big shift in the research, but not in the fields of medicine and psychiatry. And that shift was a pivot from an idea that had been held by scientists and clinicians for the longest time, which was.

That's a brain is the only organ in the human body, not ruled by the immune system. So all the things that Andy talked about. We think of that inflammatory process getting going. It's really ruled by our immune function and all of medicine had held this idea that the brain was not ruled by the immune system.

But that really began to change around 2012 when researchers at Harvard discovered something that the rest of the field had missed, and that comes down to that little cell you mentioned microglia, the tiniest cell in the brain turn out to have the same property that immune cells have in the body. And as they began to research this, it turned out that much of the search that we've all been searching for that How can we prove the mind body connection? Much of that comes down to this tiny little cell microglia, which is not a boring housekeeper cell. It's one of the most powerful cells. In human body and just as the way we think of white blood cells. governing our body's health. Microglia are really the white blood cells of the brain, and they govern our brain for good or for ill, from cradle to grave. So I began to follow this research and really I just wanted to tell the story of the birth and exploration and really the promise of this science. I think it's one of the most promising and powerful stories in the history of medicine, and it also often offers up a lot of new ways to start to think about repairing the brain that we could not previously have dreamt up before we understood the true role of these cells in the brain.

Andy: Well, that's very exciting. And I must say that, first of all, it was astounding to me to read about all this because it was so different from what I was taught in my medical education. Uh, as you say that the brain was a privileged organ, exempt from the immune system function that the microglia where structural cells that really had no important role.

And it had always seemed to me working with patients with autoimmune conditions, there was such an obvious correlation between, psychological ups and downs and the exacerbations and remissions of disease. And I've always felt that autoimmune conditions are made to order for integrative medicine because the conventional management of them is not terrific. You know, it relies on medications that are toxic and may over long term use actually reduce the chance of a remission. And there are not only many, uh, less toxic ways of modulating the inflammatory response, but also the mind-body connection is just there waiting to be taken advantage of.

Donna: Absolutely. I think what's so promising and fascinating about this research is that, you know, when we think of our immune system, it's a fear. It gives us a lot of agency, right? Like we can think, okay, what could be triggering my body's immune system to rub into overdrive? And we have to consider chronic stressors, childhood trauma, our diet, how we're moving our body, our environment talks in past histories of different pathogens or infections. Well, guess what? Just as detecting that those things are off kilter in the body can cause our body's immune system to rev into overdrive and cause inflammation and disease these are the same stressors that can trigger microglia to become overexcited. When you talked about inflammation in the body being red, hot, painful, and swollen, it's a little different in the brain, which is another reason we missed it. The brain really can't get red hot, painful, and swollen, except in a big injury, right? Because we have this thing called the skull, and that prevents that swelling that we might get if we hit ours with a hammer. But when these microglia cells are over excited by a plethora of stressors in the environment, there's dancing all the time with our environment they’re morphed into these large pack men like fellows and [00:08:08] they begin eating synapses. Now we also know that loss of synapses and key areas of the brain where we need to see robust, narrow connectivity that those we can see on brain scans are also related to patterns that set the stage for common mental health disorders, depression, anxiety, mood disorders, bipolar, as well as neurological disorders like Alzheimer's.

Victoria: One of the things I thought was really exciting about your new book, Donna, is your focus on some of the new treatments, and I was thinking it would be interesting to talk about a few of them. So for example, you talk about QEEG or quantitative electroencephalogram biofeedback. And I'm wondering if you could let our listeners know what that is and what it's especially good for.

Donna: Sure. And I think it'll open up, a conversation about a lot of different what I call brain hacking methods that are noninvasive that are coming to light. So QEEG is just one way in which practitioners are able to now take really novel and advanced neuro engineering tools and see what's happening in the brain in real time.

So if they're looking at this moving film of the brain. Which you're able to take by connecting, someone up to 19 different electrodes, which are just tiny little metal, flat metal things that they taste to the scalp, to the brain. There's no, you know, no pain, no anything. They can then use the signals coming from the brain to take these lives, moving pictures to the brain.

And as soon as they are showing up red. It tends to mean that there is too much connectivity in that area of the brain. Other colors stand for a loss of connectivity. Green means you're good compared to tens of thousands of other healthy functioning brains. So using that is allowing researchers to do a couple of different things, more advanced forms of neuro feedback.

Which help a patient training to brains and selves by using computer models, games, um, feedback from the practitioner. Um, it also is opening up the door to transcranial magnetic stimulation in real time. And that refers to a noninvasive process in which practitioners apply a very low magnetic pulse to the brain, which really makes sense when you think about the fact that the brain is actually an electrical organ.

And guess what establishes that based direct current field from which all brainwaves merge - microglia. So when we affect the brainwave, in the brain, we are actually also affecting the behavior of microglia. And in transcranial magnetic stimulation, we are practitioners are able to send a reboot pulse to the brain which helps microglia to back off and we boot and return to their really good job. Which is today, the angels and the good governors, the brain, and run around and make sure that neurons are happy and that synapses are connecting. So it's possible to intervene. And one of the last most extent, most exciting areas of brain hacking, I think is coming out of the Picard lab at MIT, where I spent a lot of time with a researcher, Li-Huei Tsai.

She developed a little wand with led lights that deliver a 40 Hertz light pulse. And you see in animal models that is now moving through human clinical trials. And she was able to do this and get microglia to stop attacking synapses, and instead they start to clean up and clear the brain of beta amyloid protein, which we associate with Alzheimer's.

So it's an exciting time, of course. And I would love your point of view on this. No, we always want to caution patients to proceed with the help of a physician. We don't want people to run out and try everything. So I wonder how you would frame this coming, sea change and how you would bring it together with wanting patients to, um move forward with good medical advice.

Andy: Well, I think, first of all, letting people know that these therapies exist is most important. One question I have is that I see that there, there's some of these devices are offered online and patients are going out and just buying them and using them. And I wonder if you have any opinion on that.

Donna: Well, you know, I don't like that. And I'll tell you why I don't like it, but you may feel differently. And so, you know, I really want to hear your point of view. 30 years I've written six books, hundreds of magazine articles and columns and op ads, and I’ve seen that when we have a sea change, we come up with 20 things.

You know, we certainly tell this in pharmacology, right? And we think they're all great. And many of them turn out later to have groups, which possibly should be excluded. For instance, with TMS, one group will not 100% sure of are patients with severe depression who might convert to bipolar. So if somebody is also showing signs of severe mood changes, we want to think carefully if they're going to have TMS, who are they going to see? Who's going to have the oversight and the fund of knowledge to treat the brain in a way that it can be treated to help that patient without doing harm. And so I know that for me, my greatest gains as a patient from severe autoimmune issues have come working closely with an integrative physician.

And so I would like your perspective on that. I don't like the idea of people reading the book and running out and find something that they put on their brain that is stimulating it. What do you think?

Andy: I share your concern about that. And my, my preference would be that, uh, people find a reputable practitioner who's trained in these methods and the experience in that way.

Victoria: And the only problem and the part of me that sympathizes with people who just want access, as we know, it can take 18 years in medicine from an innovation to be studied and seen to be a value until it actually becomes part of common practice. And you can imagine people who have a diagnosis of mild cognitive impairment who want to do everything they can to not move into Alzheimer's. And you capture some of these folks in your book have treatment resistant depression and here's this other possible therapy that they really want to get access to. At the same time. It takes time sometimes to figure out, well, what's the right dose? I mean, we're doing this transcranial magnetic stimulation.

I'm guessing that there's really a wide range of potential doses, and have we fully figured that out? How much stimulation in what area for what person are the same for light? You know, what's the best wavelength? How much, how often, and until. The basic science is done to answer some of those questions. I think there's some risk as people experiment on themselves without guidance.

Donna: And the good news is that with TMS and neurofeedback, there are some really terrific, very well-educated practitioners out there who do know, Oh, okay when I see this, it relates over my 10 years of practice and 20,000 patients, you know, to knowing this, and I've watched them, you know, I was a fly on the wall.

I watched them work, and it was really an art and a science. But I also agree that we have to push, patients need to push their physicians and psychiatrists for these answers, for these options. Because, you know, Thomas Kuhn, the scientific philosopher said exactly what you said, Victoria, 20 years, two decades from the lab to the clinic and the clock is ticking. That is not okay. I know you all see patients who are suffering. I hear from patients who are suffering every day, so how to safely push this forward. And also help patients choose things that they can do right now. One area I reported on in the book that again, I caution you have to do with the practitioner, is different types of intermittent fasting and fasting mimicking diet.

They are rebooting microglia in the brain. There are things that we can choose to do. Again, a patient with autoimmune disease doesn't want to do intermittent fasting and experienced syncope, right? So there's this kind of chiaroscuro between what we want patients to have, what we want them to safely be able to do on their own.

And then dot, dot, dot, the big $64 million question. How in the world can they find practitioners like you guys? That is one of the questions I get over and over from patients. Who can I go to? How can I afford it? You know, practices are full for really good people. It's expensive and people are trained by the psychiatric community, you know, by medication bills and therapy pills and autoimmune bills.

So we're facing all these questions, which is good because it means we're in a moment of change, but it's also going to be something, a time through which patients will need skilled guidance. 

Victoria: I have to mention that our community of graduates is listed on our website, which is azcim.org and people can find one of our graduates. We've now trained people in all 50 States and in many countries around the world. But I also wanted to point to a therapy that's absolutely freethat we believe is quite safe and that Andy's been teaching for many years. This is a way to help tone your Vegas nerve, which is going to also have an effect on the immune system.

Victoria: At the end of this podcast you can find a clip of Andy teaching the 4-7-8 breath and learn it and practice it yourself. 

Donna: I love this practice, I used this practice right before you got on the phone. 

Andy: Oh good! But this is a practice. You've got to do this every day and the benefits appear over weeks and months. And it's, as you say, it's free. It takes no equipment. It is extremely effective. 

Victoria: Another therapy I will say that is also potentially free, is what Donna just mentioned. Intermittent fasting. And this can be done in many, many different ways. It's increasingly studied and one of the ways people do it is that they eat for an eight hour period each day and they don't eat there four for 16 hours each day.

Andy, I believe you experimented with this a little bit. What did you find? 

Andy: I found that very difficult for me. I got ravenously hungry, so I'm now experimenting with other schedules to see, find one that works for me. 

Victoria: Do you have one you like at this point? 

Andy: I'm experimenting with the five-two program, which is eating normally five days of the week and then on two non-consecutive days. Eating a greatly reduced calorie intake. 

Victoria: One of the exciting things about intermittent fasting is that it's not just, you know, fasting. I think sometimes people think about weight loss, they think about spiritual practice, but it also has a profound effect on the immune system and metabolic systems. 

Donna: One of the interesting things about intermittent fasting, and I delve into this in the book, is that researchers at USC center for Longevity, Valter Longo. They're also experimenting with fasting mimicking diet, where they've developed ways to deliver to the body the essential nutrients needed so that we don't have as many of the side effects of fasting, the hunger, the fatigue.

That's another really interesting way in which the field is going. People are also combining intermittent and fasting mimicking diet with cancer protocols. and it's just getting to be a very interesting field. And as you said, Victoria, if you are safely doing one of these tasking protocols.

We shrink everything down in our body. And when we do that, it sends the message to our immune cells, both, um, the white blood cells and macrophages in the body and white blood cells or microglia in the brain that they need to reboot. They've got to clean out the bad guys. Get rid of them and we see kind of this rebirth, this neurogenesis in the brain and this birth of healthier immune cells in the body.

So it's really promising and interesting research. One other thing is, Andy, you mentioned the Vegas nerve and your breathing techniques for that. Well, research is going on now, connecting messages between the gut, right? It's no surprise. And the micro bio and microglia, they chat. There's a two-way conversation.

There's a brain gut super high way where, immune dysfunction in the gut. Gut dysbiosis and hundreds of different permutations we can see of that and microglia in the brain are chit chatting and they chit chat through the vagus nerve so that when you help to increase your vagal tone, you're actually helping microglia to get [00:28:37] better, healthier messages as well as figuring out dietary protocols that work for you to help clean out the gut. So, it's just opening up all these different doors. 

Andy: Donna, I have a, a sort of offbeat question for you. 

Donna:  Oh I love those!

Andy:  Okay. There's some curiosities about the incidents of autoimmune diseases.

They are much more common in women. There are more common in left-handed people and there are geographical hotspots for them. One notably is Finland. Um, and I wonder if you have any thoughts about what might explain, explain those. 

Donna: I do. And, um, so to take Finland, off the list there. So of course, we see that exposure to sunlight, um, is related in some ways to help your immune function.

There's been a lot of work on that, that people who live in dark reclines. Tend to have more expression of autoimmunity and in depression, we see that as well, which you know, has brought out the advent of lightboxes and light therapies to help ameliorate that in terms of women having what I call the three one rate, and in many diseases it's higher, but three times as many likelihood of autoimmune disease and also depression and anxiety. And now we're starting to see a prevalence of female prevalence in Alzheimer's. So, we also see a correlation and it's actually something I'm working on in the next, next book. So it's really a great question. Is the fact that when estrogen comes on board for girls in puberty and adolescence, it stimulates the immune response in a way that makes environmental triggers, and there are many for girls and women more likely to cause the immune system to make changes that alter the genes that oversee the stress response. Right? So that estrogen is this really great thing.

It makes it possible for us to do everything that a guy can do on like little less machinery or her smaller lungs are smaller and we have to carry a baby to term. So different, you know, you guys know more about this than I do, but estrogen is one of the things that helps us be able to do more on less and also glucocorticoids.

But what happens when estrogen revs and there was a lot of stress or other environmental agitators in a person's life and body is that the immune response can be so robust and the immune oversight that should keep the body from hurting itself or white blood cells from attacking self or microglia from attacking synapses aren't as able to do their job as they need to be.

So we think that's why we're seeing what I call the three to one. Three times the rate of autoimmunity and women. Three times the rate of depression, anxiety, Alzheimer's, and I think it's an area that requires urgent research and attention. 

Victoria: Donna, I have a very different kind of question.

You've talked about so many of the things that we can do to be healthier in our lives. I'm wondering whether there's one guilty pleasure, one vice that you may have that you struggle with and that you might want to share with our listeners. 

Donna: I think it's going to be my favorite interview ever.

Um, so I will say that the one guilty vise that I have, and I do lots of things, if you know. Anyone who's had Guillain Barre or be paralyzed twice. I have a pacemaker and other autoimmune diseases. You learn pretty quick that you're the driver of your health and if you want to feel good any given day is going to have to involve a combination of exercise and walking and yoga and meditation and loving kindness and maybe neurofeedback and maybe acupuncture, all of that. I incorporate all of it. Not all of it in one day or I wouldn't have a job, right, but because work has to be done. But one guilty pleasure I have, and I always feel so bad about this, is that around two o'clock in the afternoon, I got to have chocolate.

I know it's good for us, but it keeps me up at night. And it always has a little sugar in it. My husband will have like that black chocolate with no sugar. Um, and he falls asleep very easily, but I like to cut that out and I probably overdo the Earl Gray tea in the morning, so they're just certain tastes that I love. And a, um, they're pretty much serving me and my cortisol system. Um, so anyways, there you go. 

Victoria: I have to say, Donna, as someone who loves chocolate, um, you just need to do, you just need to eat it earlier in the morning. We want you to sleep, but you know, chocolate in the morning. 

Donna: I know, like the French, I know.

Like, I get my little craving right at two o'clock as soon as we hang up I’m going to have some chocolate.

Victoria: Well, thank you so much for bringing your expertise to our listeners. Thank you for writing the Autoimmune Epidemic and the Angel and the Assassin and your other four books. We are excited to have had you as our guests. 

Andy: Yes. Thank you. 

Donna: I so appreciate this time and thank you for having me and thank you guys for, you know, you've really sparked the sea change in how we see our bodies and our physical health and an integrative health and mental health.

So none of my work would happen if people like you weren't paving the way. 

Victoria: Thank you.