Have you heard of the Cell Danger Response as a theory to explain all comorbid symptoms associated with Autism?

There are a number of triggering factors associated with a higher incidence of Autism and comorbid conditions. These include genetics, mitochondrial disorders, alterations to the microbiome etc.

But in what is like the String Theory of Disease, Dr. Bob Naviaux proposed the Cell Danger Response (made famous by the excellent Suramin study) as a thread tying the different triggers into one integrating factor.

Dr. John Green makes the Cell Danger Response easy to understand and helps us look at practical methods to work with our children with Autism to reduce this alarm signaling in their bodies.



Audio Transcription:

Hey fellow travelers. Thanks for coming back to say hi to functional nutrition and learning for kids. Episode Number 30. I cannot believe that we’ve done 30 episodes so far. And in honor of this big number. My guest today is the very inspiring Dr. Greene, one of my favorite pediatricians. Today before we start, I want to express my gratitude to you for sticking with me through 30 episodes. If you have any questions you would like me to answer on this podcast please write to me at Weisz. That’s V for Victor AI sh. So that’s advice at functional nutrition for kids.com.

I am super happy today because my guest is Dr. JOHN green, who is one of the most well known doctors working on the pathophysiology of comorbid conditions associated with autism. Dr. Green is a medical doctor and after medical school, he trained in holistic and Environmental Medicine and is board certified in the latter. Since the beginning of his practice in 1975, Dr. Green has worked with both children and adults with chronic health problems, which have not responded to conventional therapies. His patients frequently experienced significant improvements by exploring toxic load factors, allergy sensitivities, hormones and psychological influences, and also modifying diet and nutrition.

Now here the past two decades he has worked with and supported over 3000 children with autism from around the world. Dr. Greens also mentored doctors around the world and is presented at various specialized medical and biomed conferences such as maps, Taka, and many others. I consider Dr. Green and esteemed mentor and he’s one of the most compassionate people that I’ve had the fortune of knowing. So welcome Dr. Greene. I’m super excited that you’re here with us today. And thanks for coming. Thank you, my dear, what a generous introduction.

I know that you’re very passionate about the topic of alarm signaling, and I’ve heard you talk about this myself. So would you please explain to the audience what that means to look, look back into the way that this series of problems has unraveled or unfolded over the years, and the work about nevio. Looking at his cell danger response. One of the important observations of his was that has been that there are a number of risk factors that contribute or lead to autism or Autism Spectrum Disorder, including genetics, mitochondrial disorders,encephalitis, pesticides, proximity to freeways, vinyl floors,oil refineries, return on stress, alterations and microbiome,SSRI drugs, old dad’s c section, etc, etc. So all of these different risk factors, when present, especially if several are present lead to more or less the same syndrome of those three disturbances in communication, socialization, regulation, repetitious behaviors, so how is it that the syndrome is.

Perpetuated or produced and perpetuated? what’s what’s going on? Deep inside and we identify many biochemical disturbances and methylation pathways around production, oxidative stress,microbiome, food reactivity that are expressive of alarm signaling. I’ll give you a chance to break in before I go too far. No, no, this is good. So it’s kind of like I’m in my mind and thinking of thinking of it like the string theory in physics, where you’re tying different things into one theory. Would that be accurate? Yes, yes. So this syndrome, when they look into the biochemistry of kids that have become autistic for a variety of reasons, we find many of the same alterations and biochemistry, alterations and adrenal function, autoimmune food, sensitivity and things I was just talking about. alteration microbiome is a big one. And so the question that he’s asked and began to explore is what’s what’s causing it and what’s perpetuating it?

It’s a lead into mitochondrial so danger response.

Which is a an organized, choreographed,you could say choice. Oh, that anthropomorphic, but at active activation of the mitochondria to alter their function to protect the host? And did you use the word choice, Dr. Greene. So it’s like they’re taking, they’re making that active choice in order to alter their function. I use the word choice, which is sort of implies consciousness, but there’s an intelligence in the mitochondria, that’s extraordinary. their capacity to commit suicide to defend the greater being that they’re part of is is pretty extraordinary. Wow, they, you know, they self destructive, if it’s necessary, which is part of the defensive response. So his work and it’s supported by good studies and animals and by small study, that’s foreign people and boys with autism.

Research shows that intervention to change the, the signaling that purinergic signaling, which sets up the cell danger response mitigates the vast majority of the biochemical abnormalities and the symptoms in in children with autism. It’s there’s a large study that he’s has approved, and he’s organizing and expecting to be initiating in the floor with Sherman,a big fan of Dr. navios work as well. So I’m just be probably being a little repetitive here. But I want to, I want to reiterate, the idea that you’re saying, and Dr. navio is saying is that the fact that mitochondria are changing from one form to another, is is now considered the root the root cause, if you will, of all the symptoms associated with autism, no matter what the triggering cause may be.

I think that’s a little daring to say it’s the root cause. What it would say is that intervening to alter expressions of the soul danger activation to alter the damage biochemistry that is a byproduct of that help kids to recover how kids to heal, okay. Healing is a way that kids recover. It’s not curing, it’s and we’re not treating a disease, we’re treating a state of the system, which is a dynamic state.

It manifests through all the alterations in biochemistry, that we when we look into the deep biochemistry of find all sorts of disturbances, which I was referring to describing a few of them.

So when we find an abnormality and corrected, we really reduce the demands on the system, we lessen the alarm activation, which is I think, the most important thing from a parent point of view, that recognizing the alarm signaling is contributing deeply. To the symptomatology of the child.

We look for ways to weaken correct abnormalities. Not everything is correctable, but we look for those things which can be corrected, that aggravate the situation by basically producing biochemical stress.

And those include adrenal dysfunction, unstable blood sugar, food allergies, pollen, allergies, sinusitis, any disturbance in the system whatsoever, feeds into the load, the load on the immune system, the load on metabolism. So Neff, navios work resonated with what I’ve found over the many years, what I’ve called self perpetuating cycles of injury, or self reinforcing cycles of injury, where one problem leads to another problem lead to a third problem leads back to the first problem reinforces the whole thing.

For example, being allergic to milk, or sensitive to milk may cause sinusitis issues that lead to antibiotics, antibiotics cause microbiome disturbances in the gut, which increases the sensitivity to foods, you include other foods, more antibiotics and so on. So, any any time we can identify a negative cycle and cake out of an aspect of it correct an aspect of my take on milk or find a better way to treat sinusitis and with amoxicillin, let’s say we You hand back to the organism to the child, the capacity to correct his own imbalances to restore microbiome, to improve immune regulation, let’s say and break break a cycle, and has more than Herbert said so well, the brain is downstream, the peripheral physiology, the heart, liver, kidneys got all of that, or upstream so to speak, and whatever comes through those organs, passes also through the brain. So the brain is a recipient and a participant in what’s happening outside the brain. Therefore, it’s it’s interesting and critically important to think about the microbiome in particular, which have been called the third brain. gym, secondary. Jim Adams work with fecal transplant, having demonstrated multiple benefits, way beyond diarrhea, constipation, bloating, etc.

His resonates with this finding, that there’s a conversation going on between what’s happening in the gut, and what’s happening in the nervous system. And just to take a quick pause here, Dr. Green, so you’re talking about Jim Adams work on fecal microbial transplant, I don’t actually know the full details of the study, but where he worked with many autistic kids, and many of them showed signs of improvement after the transplant and lasting improvement. Basically, he’s the the approaches to provide new microbial new bacterial organisms to complement what may be missing and children with autism.And in the lasting benefit that he’s shown in quite a large number of children is really support the importance of whatever we’re doing whatever we can to correct the microbiome. And I had mentioned that one of the effects of so alarm, so dangerous signaling or the alarm signaling is that the microbiome is also impacted.

The digestive function is impacted the parasympathetic sympathetic balance, the balance between fight or flight, and vegetation digest and repair, restore, is shifted on. One of the analogies Dr. navios given is, of a body being like a castle with all sorts of activities going on inside the safety of the walls, that the agriculture and animal husbandry goes on outside the walls where there’s more space. Because the barbarians come, everything comes inside and the crops may be burned, the which the repair, restore nourish, functions of the, of the organism are threatened by outside influences like barbarians, let’s say are infections or mercury or vaccines or pesticides or whatever in in in that state of alarm.

People are frightened, the adrenals are activated, sleep may be disturbed, immune function is activated, in a sense, a different sort of immune dysfunction than someone who has chemotherapy and suppress the immune system.

It’s more of an over activated hypervigilant immune response which we see in these kids. Which, parenthetic parenthetically they tend to be better defended their parents or their siblings, in many cases, you can’t generalize too much, but in Corona, COVID threats. But we don’t know yet about a kid with autism that from the flu experience, it’s quite common that kids with autism have less severe flu than their siblings, their parents.

related to what I’m saying about having an activated immune response. Weapons are already out, so to speak. So many of the factors that you mentioned Dr. Lindsay, you were talking about an over activation of the immune system of like fight or flight response, impaired digestion, disturbed microbiome, and probably a few other things that I’ve missed. So do these go both ways is that a bi directional access with the alarm signaling by when you’re an alarm, these things get disturbed, but when these things are disturbed, then you’re more an alarm. That’s a really important observation that goes back to what II was describing as the self perpetuating cycles. Alarm creates imbalances, imbalances create alarm, the mitochondria have exquisite sensing.

org tools to identify changes in the concentration of metabolites, good and bad metabolites, the concentration of amino acids glucose, fatty acids, ATP, the energy and transmitting pure purine purinergic substance that is a, an activator of the cell danger response. If they’re increasing levels of entered of byproducts of ATP. In the extracellular environment, it’s an indication of cell damage. And many things can cause cell damage. So if the ATP leaks out of the cell, then it activates alarm intensively.

Okay. So it’s a little complicated analogy that I give is, the blood vessels are like the freeway, and exits and streets go along,you know, to deliver whatever’s on the freeway to the homes. If you see cars driving in your lawn, it’s activating, it’s upsetting that there’s certain locations and pathways that nutrients should flow and toxins should return. And if you see them in your yard, or in your extracellular environment, right around yourselves, which are like homes, it activates defense, the defense system, something’s wrong. Another part of the analogy is the leaky Bell, where the intestinal tract has been damaged by one of many different causes infections, or toxins or imbalances in the good and bad, feel digestion.

comes into the blood in completely broken down food has an identity. That’s a threat. And the way that God protects us from food that would be a problem if we injected it into the blood is to break it down so that it loses its identity. This is another example of activator of alarm. And we see this in great, great many of the kids that are making antibodies against food against a harmless substance. Because they they’re perceiving it as a threat. Do we have labs that can detect if the mitochondria are an alarm?

We do and we’ve been sort of fragmenting these looking into different conceptual bases to explain autism, like methylation pathway is for example is very sensitive to negative feedback from cell danger response which which is involved by the production of glutathione production of energy, the production of antioxidant defenses, production of sulfate and taurine, which are involved in digestion and detox.

So that pathway alone is a pivotal area where purinergic signaling from danger alarm activation changes the output of that pathway. It’s been called oxidative stress, because oxygen production oxygen utilization by mitochondria doesn’t shut down entirely, but diminishes significantly put with cell danger activation and becomes toxic. And we produce peroxides and superoxide and very active reactive molecules that actually kill microbes. Right. So danger response evolved and as President, lower organisms to defend us against infections.

So these are indirect markers of the alarm signaling being on Yes, widespread recognition, lots of work showing elevated byproducts of oxidative stress in kids with autism. these are these are markers that can be used as biomarkers to be tracked. They’re most useful if you can change those things which you can change are most useful to study. And those those markers which we can track to identify whether we’re succeeding, our most most valuable to study.

I haven’t found it is helpful to look at headaches which are predisposing factors that to look at output, which actually happening. You can have bad genetics and be healthy and good genetics can be sick. There’s more than that. So we’re looking interested in looking at the expression of mitochondrial output carnitine production, creatine production, the parasympathetic vagal activation, which which depends, much of this depends on methylation.

The parasympathetic nervous system uses assay to Coleen is a neurotransmitter, which is requires methylation to produce Coleen the mitochondria need methylation to produce carnitine for the carnitine activation and for creating which are both energy involved in energy pathways. In my mind, the metaphor for for the cell danger response is, is is fight or flight. So when you see a constant presence of fight or flight in an autistic child, which is often the case, and you can see physic physical signs of it, often, dilated pupils, and so on is that an indirect or even a direct indicator of the alarm signaling being on.

it’s an aspect of it, sweaty palms, rapid heartbeat, and other things like tunnel vision and muscle tension, hyper focus. But there, it’s bigger than that, in a mitochondrial level, energy pathways shift to only the first, primarily only the first step in glucose metabolism, which is very inefficient, the production of repair molecules goes down the production of long chain fatty acids, and proteins goes down. So they’re there. There’s microscopic metabolic changes beyond adrenaline related. So for example, in heart rate variability studies, which are associated with typical fight or flight stress,

the unexpected, unpredictable variations in heart rate, variability and kids on the spectrum, they don’t always show fight or flight in a way in a typical way that we expected, they may be an exhaustion, so that they can This is my own hypothesis, hypothesis, I don’t know. But there may be an exhaustion, so that they can activate the way that we do, who are able to go in and out of cell danger response.

And I know you have something else to say I wouldn’t say one more thing, the cell danger response is not a theory, it’s very well established. The part that is theoretical, is that a persistently activated cell danger response causes the symptoms of autism. Now, viewers work strongly supports that. But there hasn’t been enough work yet to prove it.

Understood. And I thank you, I think that’s an important statement for everybody to know. I was going to as we come to the end of the podcast, I was going to ask you, either for action items or for things that you do in your practice work that has helped you in attenuating. This response, the biggest single agent for a change in in children with autism is diet, right? Working on identifying and eliminating toxins in foods, foods that act like toxins for this child, and the work you’re doing is so extremely important in that way.

The same also, beyond that, is to detoxify the environment. And I’m not just talking about environmental toxins, I’m talking about emotional toxins, toxins, bullying, people with negative expectations, people who have a bad attitude toward a child or use negative reinforcement, or who think they’re stupid with the toxicity that we need to avoid. Those are the non negotiables before we get into any deeper work.

Absolutely. Thank you for being here Dr. Rena, with a very enlightening discussion. I learned a lot. Thank you. I enjoy talking with you so much. Wow, what a discussion. I love and Dr. Green said that the biggest single agent of change in children with autism is diet, followed by environmental factors. This is what we’re focusing on in this podcast. My next podcast is going to be on the five major dietary changes that you can’t afford not to make. Unfortunately, there is no doubt dancing around that topic. So this is going to be a straight, honest episode. I can’t wait to share it with you. Until then. I’m your host, Dr. Weisz, Sarathy,  and Dr. Like PhD, and today’s music was composed and played by my nine year old daughter, my three. See you next week. Bye.