September 16, 2024 • 61 mins
For this episode, we discuss the roles and sensitivity of mitochondria with Dr. Richard Frye, MD, PhD. Dr. Frye received an MD and a PhD in Physiology and Biophysics from Georgetown University. He is board certified in Pediatrics, Neurology with special competence in Child Neurology, and as a Certified Principal Investigator. In addition, he has a Masters in Biomedical Sciences and Biostatistics from Drexel University. Dr. Frye has over 300 publications in leading journals and book chapters.
He currently sees patients as a Neurologists and Director of Research at Rossingnol Medical Center and at Neurodevelopmental Precision Medicine. In 2022, Dr. Frye co-founded the Autism Discovery and Treatment Foundation where they are dedicated to discover biomarkers, metabolic endophenotypes, and treatments for neurodevelopemental disorders.
Dr. Frye shares many figures during the conversation so the listener can follow along.
Dr, Richard Frye https://drfryemdphd.com
CV https://wparticles.seek2understand.org/wp-content/uploads/2023/02/DrFryeCVJan2023.pdf
Rossingnol Medical Center Facebook https://www.facebook.com/RossignolMedicalCenter
Neurobiology of Disease 2024 paper https://www.sciencedirect.com/science/article/pii/S0969996124001190?via%3Dihub
Autism and GI, and exploring how changes in Light have major implications (Apple) https://podcasts.apple.com/us/podcast/from-the-spectrum-finding-superpowers-with-autism/id1737499562?i=1000664349495
0:00 Dr. Richard Frye
6:13 Intro into mitochondria & energy production, various disease & dysfunction
11:16 Mitochondrial DNA, sensitivity, and the roles with epigenetics
16:16 Biomarkers of mitochondrial dysfunction, delicate delivery (space and time) into the electron transport chain
20:58 Cytochrome C Oxidase (complex IV); Carnitine, Fat, and Creatine
26:57 Molecules connected to aging & cellular respiration, environemental signals implicating mitochondria
30:26 Terrible Trio: oxidative stress, mitochondria dysfunction, immune/inflammation, DAMPS & inflammation
34:29 Environmental risks for the Embryo, overreactivity of mitochondria (200%) and physiological insults and regression
42:50 Tryptophan (aromatic amino acid), NAD, and Gastrointestinal biosynthesis
45:52 Light as an environmental change factoring into the Autistic Phenotype, Infant Tree and Adult Tree examples; Vitamin D (skin & brain are connected through Neuroectoderm)
54:54 Future Research
59:58 Wrap up, Reviews/Ratings
X: https://twitter.com/rps47586
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:00):
My guest today is Dr. Richard Fry.
(00:05):
Dr. Fry received an MD and a PhD in physiology and biophysics
from Georgetown University and a master's in biomedical sciences
and biostatistics from Drexel University.
Dr. Fry holds board certifications in pediatrics and neurology
(00:28):
with special competence in child neurology.
Dr. Fry is a leader in autism research with over 300 publications
in leading journals, book chapters, and he serves on several editorial boards.
He has held numerous academic appointments and most recently of Professor of Neurology
(00:53):
at Phoenix Children's Hospital and Creighton School of Medicine,
Professor of Pediatric Neurology at Mayo Clinic Alex School of Medicine,
and private practices as neurologist and director of research at Razignol Medical Center
and Neurodevelopmental Precision Medicine where he sees international patients
(01:20):
and nonprofit appointments as principal investigator at Southwestern Autism Research and Resource Center.
And in 2022, he co-founded the Autism Discovery and Treatment Foundation where he serves as president.
I am lucky to have Dr. Fry on today to discuss mitochondria.
(01:45):
Dr. Fry is an incredible individual and he will take us through the process,
this very complex process of the mitochondria.
He will talk about what happens within our biology here, this little tiny organelle,
(02:06):
this so-called powerhouse of the cell when processes such as the glycolysis or the TCA cycle
breaks down and gets backed up and what happens with disease and mitochondrial functioning because of this.
Now, it appears to me that the mitochondria in this diagram that he will show is like a vast mass production operation.
(02:35):
If you think maybe like Henry Ford or assembly lines, producing cars or just manufacturing cars,
there are hundreds or even a thousand components all feeding into this kind of assembly line with precise space and time considerations.
(02:57):
This clocked timing of this mitochondrial, these molecular levels going on here, if the pyruvate for instance from glycolysis gets backed up,
what happens then or the TCA cycle that we discussed in the previous episode?
He will take us on this journey and explain the mitochondria.
(03:20):
We also learned that how sensitive the mitochondria are.
Not only to latitude, but altitude.
And this is something that modern humans can kind of create more problems with now,
with our ability to navigate the world a little bit easier.
(03:41):
We will also discuss some environmental risk factors and the implications to or the potential implications to the mitochondria.
And we discuss light, thankfully, and I'm very pleased that we got a discussion in about light.
Dr. Frye shares some information that I was unaware of about using photobiomodulation for autism and seizures.
(04:08):
Now, as a neurologist, he has a high interest with the seizures.
So this is wonderful data with extreme promise, something that we should look forward to.
We also talk about how light, as a light to me seems like a hot topic or a logical topic here,
(04:32):
because with all of the environmental changes and environmental risk that are now present in, let's say 2024,
autism predates most of these.
So autism was here before all of these other environmental factors.
Now, it is not up to me to say which of these factors may cause a risk or more of a risk even.
(05:01):
But with the discussion of light, I'm happy to say that this really interests me.
Light predates the autism, meaning the shift from the sunlight to the artificial light.
Now, remember the discussions on the differences with wavelengths of light.
(05:26):
If light, the artificial light predates autism and autism predates these other environmental factors.
I think it's something that research can get around and maybe build on something with this.
You will find out that we have a little bit of technology issues around minute 18 or so.
(05:53):
Now, we were able to shift and continue on.
So hopefully it was not too much of a distraction.
But finishing up my rambling here about the episode that I'm happy to announce,
here is my discussion with Dr. Richard Fry.
(06:14):
Dr. Fry, let's start with just explaining a little bit about mitochondria.
Yeah, so the mitochondria, so they're very interesting parts of your cell.
So there you have many mitochondria in almost every cell of your body, anywhere from hundreds to tens of thousands.
(06:39):
And they're most well known for making energy.
So depending on the energy of the cell, you have more or less mitochondria.
So for example, the skin cell will have maybe 100 mitochondria.
Whereas each muscle cell will have tens of thousands of mitochondria.
(07:00):
And the mitochondria are very unique because they're the only other part of the cell that has its own DNA.
So most of your DNA you think of as in the chromosomes in the nucleus of your cell.
But the mitochondria has its own DNA.
And what makes it even more complicated, it has many copies of that DNA.
(07:25):
So we find that sometimes there can be problems with a certain percentage of the DNA and not with all the DNA with the mitochondria.
So it can cause somewhat milder disease than other times in it, you know, puts into the idea that mitochondria disease varies quite a bit.
(07:48):
And that's one of the challenges with mitochondrial disease is because it doesn't always affect the same organs.
It doesn't always have the same symptoms.
You know, in general, it tends to affect the higher functioning of the areas of your body that need high energy.
(08:12):
And those particularly include the nervous system, the immune system, and the GI system.
So those are common symptoms that we see in individuals with mitochondrial disease.
And there's another, and so one of the things is I'll say that really mitochondrial diseases were first described in the late 80s.
(08:37):
So for really medicine, that's really kind of a blink in time.
And so that's why we're just really learning about the mitochondria because it's so complex and all the things that it can do.
Then we have what we, you know, kind of originally, you know, found mitochondrial diseases.
(08:58):
We found that they were mostly due to genetic disorders, problems with genetics in the DNA in the mitochondria or DNA on the chromosomes.
It ends up that there's 150 genes on the chromosomes that also control the mitochondria.
But your mitochondria are inherited from your mother.
(09:21):
So they're in the egg.
And so certain genes in the nucleus have to play well with the genes in the mitochondria.
And sometimes when you have a baby, now they have new genes in the nucleus, new chromosomes, like you have the chromosomes now are changed.
And it may not play well with the DNA in the mitochondria, so things may not work all that well.
(09:47):
So one of the things that we talk about a lot is that original mitochondrial diseases are defined by very low functioning mitochondria that have a genetic disorder.
So some type of genetic issue with them is one of the major criteria for genetic, for mitochondrial disease.
(10:11):
What we see in many other diseases is that the mitochondria isn't working at the level of mitochondrial disease.
That is about 20% of normal.
Maybe it's working at 50% of normal, which isn't great.
We find mitochondria that actually working overtime at 200% of normal.
That may not usually don't have genetic components in the mitochondrial pathway that we can find.
(10:37):
And we call this secondary mitochondrial dysfunction.
And this can happen with other genetic diseases.
For example, individuals with muscular dystrophy, their muscles tend to get very inflamed, and that inflammation causes mitochondrial dysfunction.
And so you have that secondary mitochondrial dysfunction.
The mitochondria is in the center of all metabolic pathways in the cell and in your body.
(11:04):
So it is affected by and affects most of metabolism in your body.
So it's really the central player there that makes it so important.
Okay.
So this mitochondria DNA being separate from our other DNA, and it's in the cell nucleus kind of alongside.
(11:32):
What is it within our biology that connects these two?
So the mitochondrial DNA has kind of different properties than the chromosomal DNA.
Most of the genes that control the nucleus are actually on the chromosomes, but some of it is in the nucleus.
(12:00):
The DNA is in the mitochondria.
And the DNA in the mitochondria actually can change much more rapidly than your genes in your nucleus.
So you have a lot of pair mechanisms to keep your nuclear genes just as they are.
Whereas in the mitochondria, we know that it tends to vary in what we call haplotypes.
(12:25):
And that is how the mitochondria has adapted to different environments.
It's very sensitive to the environment.
So actually different regions of the world, the mitochondria is adapted based on climate and also altitude.
And so that also means though that it's very sensitive.
(12:46):
It's very sensitive to our environment.
And so we can actually think of it as the environmental sensor.
One of the other things that we worry about is that if your cells are under stress and you have a lot of what we call oxidative stress in your cells, this can damage DNA.
(13:07):
And the DNA in the mitochondria is very sensitive to that oxidative stress.
Okay.
So the ROS is involved.
This sounds like.
Is the mitochondria DNA.
What I know about other DNA sequencing in the cell nucleus, it's a, it's kind of a chroma for it absorbs, it peaks at 260 nanometer light.
(13:37):
Is this the same mechanism that the mitochondria DNA uses?
I'm sorry, as far as what?
Does it absorb the 260 light or is it also a chroma for whereby it activates only on specific wavelength of light?
(13:58):
No, I don't think the light, I mean, it may activate at certain, you know, wavelengths of light, but for the most part, you know, it is, is activated by other types of systems in the.
In the cell.
Now, one of the really interesting things is that the nuclear DNA, as you may know, is regulated by epigenetics.
(14:27):
And that's the, the methylation and, and other signaling that's put onto the DNA to turn it on and off.
So one of the really interesting things is that the mitochondria actually regulates that epigenetic landscape as it being the environmental sensor and the nutrient sensor.
(14:48):
You know, how much food you have, how many nutrients it have.
It actually sends signals to the nucleus and turns whole sets of genes on and off, depending on what it feels your body state is.
Okay.
So, okay, so there's like a back and forth communication there.
Interesting.
(15:10):
So, with the with that mitochondrial DNA.
And it's having significantly less amount of genes creating it.
I know, I know in neurobiology of disease, a paper just released a review and meta analysis, I believe there were, it seems like a lot of different findings that can that informs us of a lot of different things.
(15:46):
Let's start with just understanding the, I have noted here lactate 17% and then pyruvate the fourth.
Yeah, yeah. So let me, let me give you a before we go into that.
Let me show you a couple of slides here that I think we'll, you know, talk about these biomarkers because, you know, in that paper where we try to do was really kind of set things up so you understood where these are coming from.
(16:17):
We talk about these, you know, biomarkers all the time.
And, you know, a lot of times people don't know, oh, why are we actually looking, you know, at these specific biomarkers.
So I'll just share my screen here.
And so this is a, this is a picture of the mitochondrial pathways.
(16:49):
And this is actually a simplification that can even show you more of a simplification than this.
But you can see that it's very, very, very complex in the, the machinery in the mitochondria.
The main part of the mitochondria is, is this thing called a citric acid cycle here.
(17:13):
And glucose, the major source we think of is carbohydrates in the form of glucose going down the glycolysis and making pyruvate.
So we can see pyruvate here.
Pyruvate, the next step is to go into the mitochondria.
(17:39):
And the machinery in here is in working what's going to happen.
Pyruvate is going to get backed up.
And pyruvate, if it gets backed up, has to go somewhere.
And it's either made into lactate or alanine.
These are three of the biomarkers that we use to just tell us in general that the mitochondria is not working.
(18:11):
Also, let's say pyruvate does come into the mitochondria and goes to acetyl-CoA and then into the citric acid cycle.
We can see there's many little offshoots here and a lot going on.
So if there's something that stops, if there's a problem somewhere in the cycle, then we'll build up these things called citric acid cycle intermediates,
(18:37):
which we can measure in the urine as urine organic acids.
And that can tell us where this cycle may have stopped.
So that's really important.
Once you go around the cycle, you make these things called energy carriers, NADH and FADH2, which go to the electron transport chain.
(19:03):
And that's what a lot of people talk about where we see problems.
The electron transport chain are these five enzymes up here, labeled 1, 2, 3, 4, 5, which are called complexes,
which sit on this inner membrane and take the energy produced from the citric acid cycle in other places and turn it into energy in the form of ATP.
(19:30):
ATP is your energy molecule of the cell.
If there's any type of backup here, sometimes we can see that in intermediates in the citric acid cycle,
but we can also measure the activity of many of these complexes to see which one may not be working.
(19:55):
One of the other really important things is that what I essentially call the wires in the mitochondria from complex 1 to complex 3,
and complex 2 to complex 3, is something called CoQ10, which you can think of, a lot of people think of it as a vitamin.
They take what big went all for art health, which is CoQ10.
(20:16):
And CoQ10 is really important because it's an antioxidant, so it will protect the mitochondria.
This inner membrane here is very crucial electron transport chain from oxidative stress, but then it gets used up.
It gets used up. You don't have the wires to connect complex 1 to complex 3 or complex 2 to complex 3.
(20:39):
So that's another really important concept there.
To look at the mitochondria and how it's working,
it's up by acne as an antioxidant.
The other complex that's really important is this complex 4, because it's the one that uses oxygen.
(21:02):
The whole reason we breathe actually is to allow the function of complex 4.
And one of the ways we see how the mitochondria may be working is we use something called Respirometry,
where we measure oxygen consumption at complex 4 here.
(21:24):
One of the important aspects is that the mitochondria is also important for fatty acid oxidation.
And that's to break down fats.
So your fats come in very long chains of carbons, and we determine, we characterize them by how many carbons they have.
And what the fatty acid oxidation cycle does is it takes off two carbons at a time and shortens the chain.
(21:52):
And that goes around and around and around until we either have two or three carbons left.
And that goes right into the citric acid cycle.
There's special fats need to be brought into the mitochondria in a special way, and so we need cornutine.
Cornutine is very important for transporting those fats,
(22:14):
but it's also very important because it hangs on to any type of organic acids, maybe any toxic organic acids that may build up,
and eliminates them for the kidney.
So it's very important for that.
The other thing we measure many times is something called creatine kinase,
(22:35):
because the muscles have so many mitochondria that if there's any damage to the mitochondria, the mitochondria isn't working well.
We see that the muscles break down a little bit and release this enzyme called creatine kinase.
So it's kind of another way of measuring what's going on.
(22:56):
Yeah, bodybuilders, people that exercise will supplement with creatine.
And I think just to accelerate those nutrients to build the muscle.
Yeah, so that's in the whole another area.
So the importance of creatine is that it is kind of like the batteries of the cell.
(23:22):
So ATP, that important energy molecule, is kind of fleeting.
It can only around for a short period of time.
So the only way we can store that is by making phosphocreatine.
So that's why you take creatine, it builds up your muscles, and it also stores up energy like a battery.
So people can do weightlifting for longer periods of time, because they have more ATP.
(23:50):
And my understanding is it also quenches ROS, that creatine supplement.
It may, it may, yeah, that's not the primary thing we use it for, but that's definitely possible.
We usually use other things for quenching ROS that are a little bit better.
One of the things that's kind of our concept is to build up the ROS regulatory system of the body.
(24:19):
So that the body is able to handle it rather than giving antioxidants.
Okay.
It's my understanding that complex for cytochrome c-oxidase, I have a couple of questions on this complex in general, if we can.
Yeah.
(24:40):
This complex actually makes water.
Is that correct?
It does.
Okay.
And then it kind of breaks down the H2O into separate hydrogen and oxygen and then some electrons.
What seems interesting to me is the production of water at complex four, the less water that it's producing will kind of show up in disease.
(25:15):
Or cell health or mitochondrial damage even.
So if cytochrome four isn't producing right, in other words, this is where like even hetero plasma will show up and our overall health will begin to decline.
(25:39):
This is like at the very upstream of senescence even is, can you confirm or correct any of that?
As far as complex four and senescence of the cell or.
Yeah, just if, as soon as cytochrome c-oxidase is the water production is decreasing.
(26:04):
That's when cell health begins to kind of is become implicated.
Well, the, you know, I don't know that the water production itself has any major issue.
It's not thought to here's here's a diagram here where you can see oxygen, right, made into water.
(26:30):
The other really important thing is concept of the electron transport chain is you take hydrogen ions, protons, and you pump them across the membrane to create this gradient.
And then gradient comes down to make ATP.
So sometimes what happens, and I think we have that in this picture here, is that we can make.
(26:59):
We can have many types of oxygen radicals.
Okay, and that's something that's really important to be able to deal with in the cell.
So if you have a superoxide, so that's an oxygen with a negative charge here.
(27:22):
We have superoxide dismutase, which is very important.
And that makes hydrogen peroxide.
And you have to get rid of hydrogen peroxide through either catalase or by with glutathione.
You can make then you come back and make water and just regular O2.
(27:46):
So water does build up as you start to quench all these toxic oxygen radicals.
And so this is really important.
The other important thing for help is we've heard a little bit about the certuents.
(28:07):
It's the SI-RT genes, which all up-regulate these defensive mechanisms.
And we know that NAD+, and there's a lot of supplements out on the market seem to up-regulate these important areas to actually protect the mitochondria.
Yeah, a lot of aging and longevity research is centered around NAD+, rapamycin and certuents.
(28:36):
And I suspect it's because of the to keep the cell healthy, the way you explained it.
Now, yeah, so right. So that's what's important about the certuents.
Yeah, and NAD, and NAD also is very important as an intermediate.
That's where we usually think of it as like a vitamin.
(29:00):
But the important part is that it's also, and we see this in biology a lot, it's also a regulator of metabolism because how much of it is in a specific state tells the cell something about metabolism.
And so that's really something that's very important.
Now, mTOR is a really interesting central hub for regulation of growth and of metabolism.
(29:30):
And it has many pathways coming in, and it does many, many things to the cell and it controls the mode of growth of cells.
So if it doesn't regulate growth, that's where you can actually get certain types of cancers that grow.
(29:51):
Yeah.
So it's kind of off topic of autism, but the idea that mitochondria is now a hot spot or in large part where melatonin is made.
And melatonin is likely our number one antioxidant, which also goes with that cancer story too, I think.
(30:17):
And I guess the reason why I bring that up is it seems to me that autism is just a downstream phenotype of our new environment.
And you know, we know that the mitochondria DNA are very sensitive to the environment.
(30:42):
And I don't want to, I don't know, I'm going down a complete bad path here for our conversation.
But autism just shows up apparently around the 1930s, maybe a little bit in the 20s.
I don't know. Eugen Bueller and even Piaget and some like experienced with children with very autistic phenotypes.
(31:11):
But something in the environment caused it.
And I've been hitched on that.
I don't know where I want to take that, this rant for the last two minutes, but maybe I should just get back on path here about.
So let me show you another kind of theme that we have.
(31:34):
So, you know, the mitochondria, we talk about something called the terrible trio.
Yeah, oxidative stress, mitochondrial dysfunction and immune dysfunction.
And when we find these all feedback on each other to create a vicious cycle of disease.
(31:56):
So, you know, sometimes it's not clear where you start, oxidative stress, immune dysfunction, dysfunctional mitochondria.
But all of these things tend to feedback on each other and make things worse.
So the mitochondria itself, when it becomes dysfunctional, it can send out dangerous signals called damps, which start inflammation.
(32:21):
Also, the really interesting thing is that when you look at regulatory cells in the immune system, they're usually more what we call oxidative.
They use mitochondrial function to function.
Whereas the inflammatory cells, many of them just use glycolysis and don't use the mitochondria.
(32:42):
So when you mitochondria becomes dysfunctional, you really have a deficit in this regulatory aspect of inflammation.
And so that potentiates inflammation many times.
Of course, inflammation and also not being able to regulatory the immune system leads to immune dysfunction in both ways.
(33:09):
Autoimmune disease and also not being able to successfully get rid of infections or having prolonged infections, having sensitivity to infections.
Inflammation and the immune cells actually send out messengers to the mitochondria, which actually turned down its ability to work.
(33:37):
So there's a vicious spike will spiral there.
Both of these cause oxidative stress.
And oxidative stress can cause more mitochondrial dysfunction, can cause, again, mutations, especially on the mitochondrial DNA.
And the important thing here, another way that oxidative stress in the mitochondria interact is the major antioxidant of our body is glutathione.
(34:04):
And glutathione can be made of the mitochondria.
It's made in the cytosol outside of the mitochondria.
But to make it de novo, you have to have ATP.
So if you don't have glutathione to combat the oxidative stress in the mitochondria, you're not going to making it making ATP and you're not going to be making glutathione.
(34:25):
So there's a vicious cycle here too.
So we think that many diseases, complex diseases are caused by some cascade in these three different areas, which kind of end up in this vicious spiral.
And the idea is how to get the body out of that and support it so it can get back to a normal state.
(34:47):
And of course, as our environment changes, not only a lot of people like to talk about toxins and things like that.
But the other thing we're finding is that probably the major influence of your body is really the maternal environment during gestation.
And it's so, so, so important to make sure that prenatally the fetus gets the nutrients that it can because we find that there's some predisposition in a because of a lack of certain nutrients.
(35:24):
And to be exposed the least to certain types of pollutants and other types of toxic material.
The prenatal. And there's a lot of vitamin B's associated with autism.
The prenatal is it based off of some work at UC San Diego and even the the paper released in neurobiology of disease that you're you're on it.
(35:57):
Are you comfortable with kind of thinking that autism is in the embryo.
I think it may be predisposed in the embryo. You know, yes and no. So, you know, and that makes what makes it so difficult.
It's how certain factors come together, you know, environmental and genetic factors, how they come together to predispose and then usually think of some type of trigger that is can cause this.
(36:31):
So, one paper we actually were able to correlate air pollution prenatally with long term mitochondrial function.
So, we show that if you measure, you know, the mitochondria anywhere from six to 12 years old was most of our kids that you can link that function to air pollution exposure.
(36:56):
And, and this the pattern dependent on whether you have regressive type autism or non regressive type autism.
That is whether you develop to a certain point and lost all your skills or you were at just a you had symptoms from early on, or you had a plateau phenotype.
(37:21):
But what's also interesting, we went through and we said, well, the regressive, you know, type phenotype is very interesting.
We've linked the regressive phenotype with a specific type of mitochondrial dysfunction where you actually see overactivity of the mitochondria by about 200%.
But what that does, we found is make the mitochondria very vulnerable to any type of physiological insults.
(37:49):
So, sometimes you know the trigger when a child regresses, you know, whether it be an illness or a seizure or so.
But many times you don't. And so what we looked into is whether, you know, that air pollution, you know, we know that it affected the child prenatally.
(38:11):
If it, it could be the trigger postnatally to regression. And we found out there was some evidence of that, you know.
So, it's all these things that, you know, you may have the luck or the unlucky of getting exposed to them in some type of vulnerable state.
You know, so the really the thing we want to do is reduce that vulnerable state.
(38:32):
So, you reduce that vulnerability to have some trigger not to develop well.
And that starts, yeah, that starts in the embryo. So, we have to be sure to start very early on.
You know, the JAMA paper that looked at when there was sensitive periods for folate supplementation found out that it extended into the preconception timeframe.
(38:59):
So, that also is so important to know that you have to get your body ready for pregnancy.
And it's not just the pregnancy itself.
Yes.
I have an episode on that. And the environment of the birthing mother, the mother has drastically changed from the time that autism wasn't here.
(39:31):
And I just don't understand why we can't mimic that environment before autism to see if there's any change to the rates.
Yeah, it's very complex because we don't know all the factors that go into it.
(39:52):
So, there's a nice paper by the Mount Sinai School of Medicine group where they actually looked at the sigiwis teeth, that is, baby teeth.
They start to develop at the end of the first trimester and they record everything that the baby has been exposed to.
And with that, they found that, yeah, that very in twin studies, they were able to differentiate the twin that developed autism, which the first is the one that didn't, by the manganese and zinc levels.
(40:28):
So, those are really important, you know, nutrient metals.
And then we actually looked at these various types of metals, both nutrient and toxic, in kids with autism, and looked at how it may regulate their mitochondrial function.
And we found that, yes, prenatally zinc and manganese actually modulated long-term mitochondrial function in those that had regressive type autism.
(41:00):
So, those are just probably examples of two nutrients, but there's many other nutrients that are probably really very critical.
Of course, we know that thyroid, iron, folate is very important.
Carnitine is something that seems to be reduced during pregnancy, which is usually not recognized.
So, the problem with metabolic systems is they're complex, right?
(41:25):
They're not just one thing or another. All these things kind of play on each other and are correlated.
So, that complexity of it makes it hard to study.
Yeah.
The role of melanin, like neuromelanin now, is very fascinating, whereby it works as a protector of the cell.
(41:47):
And it takes these metals or these toxins, I should say, just to be general, and kind of protects the cell.
I think there's going to be something to come out of that, the role of melanin within the cell.
Yeah, we're knowing, especially melatonin, is, you know, we think of it as a sleep initiator, but it actually has many different roles as far as an antioxidant.
(42:22):
It regulates the immune system and it supports mitochondrial function.
And there's some studies are using high dose melatonin to as a treatment for mitochondrial dysfunction.
(42:43):
Okay.
I have a question about NAD. Is that synthesized through tryptophan or is that a different acid?
It has several different pathways. But tryptophan, yeah, definitely that's one of them.
But there is other ways that it can be produced.
(43:09):
So, you know, definitely many different aspects of that. So again, being complex, yeah.
And the idea is, yeah, how do you get it into your body?
I find actually that the nasal sprays work pretty well rather than the oral form.
And that's a problem with all of these kind of supplements, you know, they're not at the level where they've been tested as medications.
(43:36):
So we don't have those same ideas of how they optimally get into the body for certain individuals.
One of the problems with, you know, at least kiddos with autism and other diseases is that they have issues with GI system.
(44:05):
Yeah, which is kind of hits with the tryptophan and serotonin, I think too, because of the enteric and enterochromathin cells.
Yeah. So you're absolutely right there. Most of our neurotransmitters, we always think we're in their brain, but most of it is in the gut as you point out.
(44:28):
So, you know, it may very well be that, you know, that the gut, these things also regulate the gut, not only these metabolic systems are extremely important in that metabolism.
(44:54):
Yeah. So here's an NAD production.
Can you or can people differentiate the amount of NAD coming from tryptophan versus, yeah, the nicotinetic acid?
(45:15):
Yeah. So you can see that here can come from tryptophan or nitinic acid. Exactly.
And so there's two pathways that converge to make the NAD.
And or you can take some of these other products that come right into this cycle and make NAD downstream.
So there's many ways of getting in there. Yeah.
(45:38):
I was curious because of with everything that we've talked about with the environment and the protein sequencing, DNA sequencing.
Because tryptophan being an aromatic amino acid that absorbs, it peaks at 280 and anywhere from 2 to 280 nanometer light.
(46:02):
And I'm just, I'm kind of everything to me saying that autism developed as a biological adaptation from our shifts in light.
We're less involved in the sunlight, which we evolved under and that we're under this artificial light, which is very isolated.
(46:28):
And I guess a simple way of explaining it is if I go by a baby, if I go by a tree, like from Home Depot, and I plant it in my yard, even if it's optimal environment, optimal soil.
And I cover the tree with or from the sun. It's not going to develop the way that it should.
(46:53):
And so that is kind of like a neuro development of the tree.
Yeah. And in contrast, or in addition, if I take a grown tree and block the sun and it accelerates death.
That I just gave that tree kind of Alzheimer's, which is also new in medical literature.
(47:22):
I don't know if I'm far out, but this biological adaptation to our environment, especially with how sensitive it is and how we evolve for, I don't know how many years as mammals.
Under the sunlight, I think we neglect the fact that the sun and light, especially light as an electromagnetic field.
(47:50):
And as we talk about mitochondria and the electrons and proton balance.
I'm just, I'm just so curious and interested if how much light has a is in play here.
Yeah, I mean, light itself, sunlight, especially is extremely important.
(48:11):
One, you know, actually say to get the cycle, you know, one of these things we know that in autism, we have the, the melatonin sleep cycle is that diurnal cycle is broken down quite a bit.
And some one of the first things we really have to fix.
And your body doesn't repair itself very well.
If you don't have that cycle, if you don't sleep well, that's why we look at sleep.
(48:36):
That's so important because that's when you actually integrate everything you learn during the day into your brain.
If you don't sleep, you don't learn.
Also, we're learning, of course, about the lymphatic system that washes out the brain, almost like a washing machine of all the junk, you know, at nighttime.
So if you don't sleep well, you don't wash out your brain really well.
(48:57):
So sleep is so important and getting into that cycle is so important.
And then you have the effects that we're learning about how light is therapeutic, you know.
And so you wonder about light itself, if it's actually getting into our body and actually physiologically, you know, helping our body function.
Absolutely.
Red light for sure penetrates bones.
(49:21):
So red light is getting in.
Robert O'Becker is really good on that.
And with cytochrome c-oxidase, having four red light chromophores is very telling to me like something is going on here.
And the complex, the mitochondrial complex has VDR receptors.
(49:50):
Yeah, you know, they're absolutely right.
Yeah, that's why vitamin D is so important also, people underestimate it too.
And it's amazing these days how many low vitamin D levels I find.
I always check vitamin D and I would say most of the time it's low, you know, and I live in Phoenix where it's hot to sunlight.
(50:11):
Yeah, people avoid the sun and whenever they go out to the sun, they now cover up the sun quite a bit.
And it's like vitamin D to me connects, you know, our skin is obviously the largest organ and endocrine organ in our body, but it connects our body to the central nervous system.
(50:37):
It's not like it's a bloodstream or whatever, but it's a healthy dance there, vitamin D and the central nervous system.
It's just so bizarre to me that maybe it is this simple, but yet human biology being so complex.
(51:01):
It's why don't we look at the environment before autism got here.
And I think the rates of how many things that's changed, that's the problem, right?
Yeah.
And so we have the really good research.
It's hard to know, right?
(51:22):
Because you can, you know, blame it on almost anything, you know, TV, you know, yeah.
Absolutely.
It's, you know, it's just that certain way to invite even in a lot key kids, you know, it's just, it's amazing how much our society has changed.
So it's so hard to figure out those variables.
(51:43):
Yeah.
If it goes back to the 1930s, though, and this maternal genetic implication.
If it is a source of artificial light being invented in the 1880s, and then the power grid really taking off in 1893,
(52:06):
it hit the autism.
That's about one and a half to two generations later that it slowly came of all.
But then the rates of autism kind of follows this shift of reducing sun and replacing it with LED lights, which is blue light, 440 to 480 nanometer light.
(52:30):
And like with tech light, the rates of autism and quite frankly, the rates of Alzheimer's and metabolic health, obesity, they're, they are, they're all following.
They're all following this, this shift of the light source.
(52:52):
And I don't think it's not autism, but I don't think obesity is a food problem or even a calories in calories out problem.
I think they, people with obesity just lose energy to the environment because they're not getting the electrons is what I'm leaning towards.
And this is off topic and I know I'll wrap that up right now, but obesity is just like the autism where there's a lot of factors, but just that this one factor of the sunlight or artificial light and the implications,
(53:31):
because Melotinopsin wasn't discovered until 1998 and that's a blue light chromophore.
And so everything here is telling me that, well, maybe it is as simple as our energy source, light as an electromagnetic field.
(53:53):
Yeah, no, I think light has a lot to do with it. I always tell my, my patients, you know, my family is to, to wake the kid up and take a walk around the block in the sunlight.
If I'm wanting to get the day started, because really wakes you up and it gets you going.
That circadian cycle is starts as soon as, as soon as you need light as soon as possible, because of the signaling and the implications or benefits to the hormones in our physiology.
(54:27):
And we've, we've kind of neglected that as a modern society.
Yeah, it's complex. That's, that's nothing. It's not simple. Our bodies are not simple. And nature is not simple.
Yeah.
Yeah, we, we, we took ourselves out of nature.
And when we were in nature, though, we didn't have so many of these modern complex diseases.
(54:53):
What is something you're working on now that is your most excited about or something that you can share for us that to look out for?
Well, I mean, what we're doing, you know, we have a bunch of clinical trials. We're still doing our work on leukovorn, which is certain folate that seems to help many kids with autism.
So we're continuing those.
(55:14):
We're doing a project on photobiomodulation for seizures. So there's some good evidence that it seems to work well for autism symptoms.
But we're also seeing, we think theoretically by looking at how it works in the brain and how it changes certain brain waves, that it should actually improve seizure, seizure activity.
(55:36):
You know, and many kids with with autism are very sensitive to anti-epileptic medications where they don't respond.
So it's really nice to have, you know, a another, you know, tool to treat them.
We're also doing a trial on a brand new drug that is not even on the market yet that regulates microculele cells.
(56:04):
So we think that could be a real game changer.
And then for, you know, mitochondria, you know, and other types of metabolic systems, what we're finding is that that they may that they seem to run in families.
And so something that might be affecting the whole family.
(56:26):
And if that that's important in many ways, one, you know, the rest of the family might have disorders that are treatable in similar ways.
But if you can identify those abnormalities early in the mother and father, you may be able to do something about it, you know, in the prenatal period or preconception period that will reduce the risk of having any type of chronic disease.
(56:52):
Yeah, I think that's I think that's the future. I think that's that's I'm set aside and I'm pleased that you shared that with me because I think this is the way.
So yeah, so we have our foundation, the autism discovery and treatment foundation is what we started to do all of this research.
So we're on Facebook, you can, you know, follow, like and share and all do that stuff. We try to put videos out every week on something new, some new information, just a short video to keep people up to date.
(57:24):
Yeah, good. I'll put all your links in the show notes and I think modern medicine misses this bio physics. And I know you have a PhD in bio physics.
I think bio physics and biochemistry must meet together for the cell development or the cell functioning.
Yeah.
(57:45):
That's for sure.
Dr Fry, thank you so much. And I'm sure you have to talk to you. It was amazing.
You're talking to you.
Thanks.
Bye bye.
Before we wrap up today, I just want to kind of mention again that the podcast stands on the cause of autism and how critical light as an electromagnetic field has evolved living organisms on Earth, including humans.
(58:19):
It seems to me that eventually something will come out about this shift in light source, removing ourselves from the sun and supplementing it with artificial light in the various forms of artificial light.
But before you understand that, you need to understand that the sun spectra 280 to 3100 nanometer light, the sun spectra is much different than artificial light in the light that we have now surrounded ourselves in or suffocated ourselves even.
(58:58):
It's much different light and the energy source and the wavelength.
Humans have this capacity because humans have this capacity to think.
Now we are the only creature that will change our environment like this because of the frontal lobes because of our capacity to think.
(59:24):
I don't want to sidetrack on Dr. Fry's information and the amount of work that he is doing to one understand autism and two, even as you've heard him say, the treatment with the photo bio modulation and the the spray of the NAD.
(59:49):
This is very critical in our understanding of autism and allowing autistics to kind of thrive and have a different environment have a different option.
And we're very much appreciative of Dr. Fry's work. I know he's he's very different kind of dynamics I was searching for.
(01:00:19):
He's it's very impressive how dynamic this individual is, especially for our topic autism.
If you are listening to the episode or listening to the podcast, please feel free to leave a review or rating.
In podcasting reviews, ratings and downloads are huge.
(01:00:41):
And I very much appreciate your feedback.
You can contact me on X at rps 47586 or email info dot from the spectrum at gmail.com.
And you can click on the hop link to have access to all of the platforms of podcasting and contact information.
(01:01:08):
Thank you for listening to from the spectrum podcast.
My guest today is Dr. Richard Fry.
(00:05):
Dr. Fry received an MD and a PhD in physiology and biophysics
from Georgetown University and a master's in biomedical sciences
and biostatistics from Drexel University.
Dr. Fry holds board certifications in pediatrics and neurology
(00:28):
with special competence in child neurology.
Dr. Fry is a leader in autism research with over 300 publications
in leading journals, book chapters, and he serves on several editorial boards.
He has held numerous academic appointments and most recently of Professor of Neurology
(00:53):
at Phoenix Children's Hospital and Creighton School of Medicine,
Professor of Pediatric Neurology at Mayo Clinic Alex School of Medicine,
and private practices as neurologist and director of research at Razignol Medical Center
and Neurodevelopmental Precision Medicine where he sees international patients
(01:20):
and nonprofit appointments as principal investigator at Southwestern Autism Research and Resource Center.
And in 2022, he co-founded the Autism Discovery and Treatment Foundation where he serves as president.
I am lucky to have Dr. Fry on today to discuss mitochondria.
(01:45):
Dr. Fry is an incredible individual and he will take us through the process,
this very complex process of the mitochondria.
He will talk about what happens within our biology here, this little tiny organelle,
(02:06):
this so-called powerhouse of the cell when processes such as the glycolysis or the TCA cycle
breaks down and gets backed up and what happens with disease and mitochondrial functioning because of this.
Now, it appears to me that the mitochondria in this diagram that he will show is like a vast mass production operation.
(02:35):
If you think maybe like Henry Ford or assembly lines, producing cars or just manufacturing cars,
there are hundreds or even a thousand components all feeding into this kind of assembly line with precise space and time considerations.
(02:57):
This clocked timing of this mitochondrial, these molecular levels going on here, if the pyruvate for instance from glycolysis gets backed up,
what happens then or the TCA cycle that we discussed in the previous episode?
He will take us on this journey and explain the mitochondria.
(03:20):
We also learned that how sensitive the mitochondria are.
Not only to latitude, but altitude.
And this is something that modern humans can kind of create more problems with now,
with our ability to navigate the world a little bit easier.
(03:41):
We will also discuss some environmental risk factors and the implications to or the potential implications to the mitochondria.
And we discuss light, thankfully, and I'm very pleased that we got a discussion in about light.
Dr. Frye shares some information that I was unaware of about using photobiomodulation for autism and seizures.
(04:08):
Now, as a neurologist, he has a high interest with the seizures.
So this is wonderful data with extreme promise, something that we should look forward to.
We also talk about how light, as a light to me seems like a hot topic or a logical topic here,
(04:32):
because with all of the environmental changes and environmental risk that are now present in, let's say 2024,
autism predates most of these.
So autism was here before all of these other environmental factors.
Now, it is not up to me to say which of these factors may cause a risk or more of a risk even.
(05:01):
But with the discussion of light, I'm happy to say that this really interests me.
Light predates the autism, meaning the shift from the sunlight to the artificial light.
Now, remember the discussions on the differences with wavelengths of light.
(05:26):
If light, the artificial light predates autism and autism predates these other environmental factors.
I think it's something that research can get around and maybe build on something with this.
You will find out that we have a little bit of technology issues around minute 18 or so.
(05:53):
Now, we were able to shift and continue on.
So hopefully it was not too much of a distraction.
But finishing up my rambling here about the episode that I'm happy to announce,
here is my discussion with Dr. Richard Fry.
(06:14):
Dr. Fry, let's start with just explaining a little bit about mitochondria.
Yeah, so the mitochondria, so they're very interesting parts of your cell.
So there you have many mitochondria in almost every cell of your body, anywhere from hundreds to tens of thousands.
(06:39):
And they're most well known for making energy.
So depending on the energy of the cell, you have more or less mitochondria.
So for example, the skin cell will have maybe 100 mitochondria.
Whereas each muscle cell will have tens of thousands of mitochondria.
(07:00):
And the mitochondria are very unique because they're the only other part of the cell that has its own DNA.
So most of your DNA you think of as in the chromosomes in the nucleus of your cell.
But the mitochondria has its own DNA.
And what makes it even more complicated, it has many copies of that DNA.
(07:25):
So we find that sometimes there can be problems with a certain percentage of the DNA and not with all the DNA with the mitochondria.
So it can cause somewhat milder disease than other times in it, you know, puts into the idea that mitochondria disease varies quite a bit.
(07:48):
And that's one of the challenges with mitochondrial disease is because it doesn't always affect the same organs.
It doesn't always have the same symptoms.
You know, in general, it tends to affect the higher functioning of the areas of your body that need high energy.
(08:12):
And those particularly include the nervous system, the immune system, and the GI system.
So those are common symptoms that we see in individuals with mitochondrial disease.
And there's another, and so one of the things is I'll say that really mitochondrial diseases were first described in the late 80s.
(08:37):
So for really medicine, that's really kind of a blink in time.
And so that's why we're just really learning about the mitochondria because it's so complex and all the things that it can do.
Then we have what we, you know, kind of originally, you know, found mitochondrial diseases.
(08:58):
We found that they were mostly due to genetic disorders, problems with genetics in the DNA in the mitochondria or DNA on the chromosomes.
It ends up that there's 150 genes on the chromosomes that also control the mitochondria.
But your mitochondria are inherited from your mother.
(09:21):
So they're in the egg.
And so certain genes in the nucleus have to play well with the genes in the mitochondria.
And sometimes when you have a baby, now they have new genes in the nucleus, new chromosomes, like you have the chromosomes now are changed.
And it may not play well with the DNA in the mitochondria, so things may not work all that well.
(09:47):
So one of the things that we talk about a lot is that original mitochondrial diseases are defined by very low functioning mitochondria that have a genetic disorder.
So some type of genetic issue with them is one of the major criteria for genetic, for mitochondrial disease.
(10:11):
What we see in many other diseases is that the mitochondria isn't working at the level of mitochondrial disease.
That is about 20% of normal.
Maybe it's working at 50% of normal, which isn't great.
We find mitochondria that actually working overtime at 200% of normal.
That may not usually don't have genetic components in the mitochondrial pathway that we can find.
(10:37):
And we call this secondary mitochondrial dysfunction.
And this can happen with other genetic diseases.
For example, individuals with muscular dystrophy, their muscles tend to get very inflamed, and that inflammation causes mitochondrial dysfunction.
And so you have that secondary mitochondrial dysfunction.
The mitochondria is in the center of all metabolic pathways in the cell and in your body.
(11:04):
So it is affected by and affects most of metabolism in your body.
So it's really the central player there that makes it so important.
Okay.
So this mitochondria DNA being separate from our other DNA, and it's in the cell nucleus kind of alongside.
(11:32):
What is it within our biology that connects these two?
So the mitochondrial DNA has kind of different properties than the chromosomal DNA.
Most of the genes that control the nucleus are actually on the chromosomes, but some of it is in the nucleus.
(12:00):
The DNA is in the mitochondria.
And the DNA in the mitochondria actually can change much more rapidly than your genes in your nucleus.
So you have a lot of pair mechanisms to keep your nuclear genes just as they are.
Whereas in the mitochondria, we know that it tends to vary in what we call haplotypes.
(12:25):
And that is how the mitochondria has adapted to different environments.
It's very sensitive to the environment.
So actually different regions of the world, the mitochondria is adapted based on climate and also altitude.
And so that also means though that it's very sensitive.
(12:46):
It's very sensitive to our environment.
And so we can actually think of it as the environmental sensor.
One of the other things that we worry about is that if your cells are under stress and you have a lot of what we call oxidative stress in your cells, this can damage DNA.
(13:07):
And the DNA in the mitochondria is very sensitive to that oxidative stress.
Okay.
So the ROS is involved.
This sounds like.
Is the mitochondria DNA.
What I know about other DNA sequencing in the cell nucleus, it's a, it's kind of a chroma for it absorbs, it peaks at 260 nanometer light.
(13:37):
Is this the same mechanism that the mitochondria DNA uses?
I'm sorry, as far as what?
Does it absorb the 260 light or is it also a chroma for whereby it activates only on specific wavelength of light?
(13:58):
No, I don't think the light, I mean, it may activate at certain, you know, wavelengths of light, but for the most part, you know, it is, is activated by other types of systems in the.
In the cell.
Now, one of the really interesting things is that the nuclear DNA, as you may know, is regulated by epigenetics.
(14:27):
And that's the, the methylation and, and other signaling that's put onto the DNA to turn it on and off.
So one of the really interesting things is that the mitochondria actually regulates that epigenetic landscape as it being the environmental sensor and the nutrient sensor.
(14:48):
You know, how much food you have, how many nutrients it have.
It actually sends signals to the nucleus and turns whole sets of genes on and off, depending on what it feels your body state is.
Okay.
So, okay, so there's like a back and forth communication there.
Interesting.
(15:10):
So, with the with that mitochondrial DNA.
And it's having significantly less amount of genes creating it.
I know, I know in neurobiology of disease, a paper just released a review and meta analysis, I believe there were, it seems like a lot of different findings that can that informs us of a lot of different things.
(15:46):
Let's start with just understanding the, I have noted here lactate 17% and then pyruvate the fourth.
Yeah, yeah. So let me, let me give you a before we go into that.
Let me show you a couple of slides here that I think we'll, you know, talk about these biomarkers because, you know, in that paper where we try to do was really kind of set things up so you understood where these are coming from.
(16:17):
We talk about these, you know, biomarkers all the time.
And, you know, a lot of times people don't know, oh, why are we actually looking, you know, at these specific biomarkers.
So I'll just share my screen here.
And so this is a, this is a picture of the mitochondrial pathways.
(16:49):
And this is actually a simplification that can even show you more of a simplification than this.
But you can see that it's very, very, very complex in the, the machinery in the mitochondria.
The main part of the mitochondria is, is this thing called a citric acid cycle here.
(17:13):
And glucose, the major source we think of is carbohydrates in the form of glucose going down the glycolysis and making pyruvate.
So we can see pyruvate here.
Pyruvate, the next step is to go into the mitochondria.
(17:39):
And the machinery in here is in working what's going to happen.
Pyruvate is going to get backed up.
And pyruvate, if it gets backed up, has to go somewhere.
And it's either made into lactate or alanine.
These are three of the biomarkers that we use to just tell us in general that the mitochondria is not working.
(18:11):
Also, let's say pyruvate does come into the mitochondria and goes to acetyl-CoA and then into the citric acid cycle.
We can see there's many little offshoots here and a lot going on.
So if there's something that stops, if there's a problem somewhere in the cycle, then we'll build up these things called citric acid cycle intermediates,
(18:37):
which we can measure in the urine as urine organic acids.
And that can tell us where this cycle may have stopped.
So that's really important.
Once you go around the cycle, you make these things called energy carriers, NADH and FADH2, which go to the electron transport chain.
(19:03):
And that's what a lot of people talk about where we see problems.
The electron transport chain are these five enzymes up here, labeled 1, 2, 3, 4, 5, which are called complexes,
which sit on this inner membrane and take the energy produced from the citric acid cycle in other places and turn it into energy in the form of ATP.
(19:30):
ATP is your energy molecule of the cell.
If there's any type of backup here, sometimes we can see that in intermediates in the citric acid cycle,
but we can also measure the activity of many of these complexes to see which one may not be working.
(19:55):
One of the other really important things is that what I essentially call the wires in the mitochondria from complex 1 to complex 3,
and complex 2 to complex 3, is something called CoQ10, which you can think of, a lot of people think of it as a vitamin.
They take what big went all for art health, which is CoQ10.
(20:16):
And CoQ10 is really important because it's an antioxidant, so it will protect the mitochondria.
This inner membrane here is very crucial electron transport chain from oxidative stress, but then it gets used up.
It gets used up. You don't have the wires to connect complex 1 to complex 3 or complex 2 to complex 3.
(20:39):
So that's another really important concept there.
To look at the mitochondria and how it's working,
it's up by acne as an antioxidant.
The other complex that's really important is this complex 4, because it's the one that uses oxygen.
(21:02):
The whole reason we breathe actually is to allow the function of complex 4.
And one of the ways we see how the mitochondria may be working is we use something called Respirometry,
where we measure oxygen consumption at complex 4 here.
(21:24):
One of the important aspects is that the mitochondria is also important for fatty acid oxidation.
And that's to break down fats.
So your fats come in very long chains of carbons, and we determine, we characterize them by how many carbons they have.
And what the fatty acid oxidation cycle does is it takes off two carbons at a time and shortens the chain.
(21:52):
And that goes around and around and around until we either have two or three carbons left.
And that goes right into the citric acid cycle.
There's special fats need to be brought into the mitochondria in a special way, and so we need cornutine.
Cornutine is very important for transporting those fats,
(22:14):
but it's also very important because it hangs on to any type of organic acids, maybe any toxic organic acids that may build up,
and eliminates them for the kidney.
So it's very important for that.
The other thing we measure many times is something called creatine kinase,
(22:35):
because the muscles have so many mitochondria that if there's any damage to the mitochondria, the mitochondria isn't working well.
We see that the muscles break down a little bit and release this enzyme called creatine kinase.
So it's kind of another way of measuring what's going on.
(22:56):
Yeah, bodybuilders, people that exercise will supplement with creatine.
And I think just to accelerate those nutrients to build the muscle.
Yeah, so that's in the whole another area.
So the importance of creatine is that it is kind of like the batteries of the cell.
(23:22):
So ATP, that important energy molecule, is kind of fleeting.
It can only around for a short period of time.
So the only way we can store that is by making phosphocreatine.
So that's why you take creatine, it builds up your muscles, and it also stores up energy like a battery.
So people can do weightlifting for longer periods of time, because they have more ATP.
(23:50):
And my understanding is it also quenches ROS, that creatine supplement.
It may, it may, yeah, that's not the primary thing we use it for, but that's definitely possible.
We usually use other things for quenching ROS that are a little bit better.
One of the things that's kind of our concept is to build up the ROS regulatory system of the body.
(24:19):
So that the body is able to handle it rather than giving antioxidants.
Okay.
It's my understanding that complex for cytochrome c-oxidase, I have a couple of questions on this complex in general, if we can.
Yeah.
(24:40):
This complex actually makes water.
Is that correct?
It does.
Okay.
And then it kind of breaks down the H2O into separate hydrogen and oxygen and then some electrons.
What seems interesting to me is the production of water at complex four, the less water that it's producing will kind of show up in disease.
(25:15):
Or cell health or mitochondrial damage even.
So if cytochrome four isn't producing right, in other words, this is where like even hetero plasma will show up and our overall health will begin to decline.
(25:39):
This is like at the very upstream of senescence even is, can you confirm or correct any of that?
As far as complex four and senescence of the cell or.
Yeah, just if, as soon as cytochrome c-oxidase is the water production is decreasing.
(26:04):
That's when cell health begins to kind of is become implicated.
Well, the, you know, I don't know that the water production itself has any major issue.
It's not thought to here's here's a diagram here where you can see oxygen, right, made into water.
(26:30):
The other really important thing is concept of the electron transport chain is you take hydrogen ions, protons, and you pump them across the membrane to create this gradient.
And then gradient comes down to make ATP.
So sometimes what happens, and I think we have that in this picture here, is that we can make.
(26:59):
We can have many types of oxygen radicals.
Okay, and that's something that's really important to be able to deal with in the cell.
So if you have a superoxide, so that's an oxygen with a negative charge here.
(27:22):
We have superoxide dismutase, which is very important.
And that makes hydrogen peroxide.
And you have to get rid of hydrogen peroxide through either catalase or by with glutathione.
You can make then you come back and make water and just regular O2.
(27:46):
So water does build up as you start to quench all these toxic oxygen radicals.
And so this is really important.
The other important thing for help is we've heard a little bit about the certuents.
(28:07):
It's the SI-RT genes, which all up-regulate these defensive mechanisms.
And we know that NAD+, and there's a lot of supplements out on the market seem to up-regulate these important areas to actually protect the mitochondria.
Yeah, a lot of aging and longevity research is centered around NAD+, rapamycin and certuents.
(28:36):
And I suspect it's because of the to keep the cell healthy, the way you explained it.
Now, yeah, so right. So that's what's important about the certuents.
Yeah, and NAD, and NAD also is very important as an intermediate.
That's where we usually think of it as like a vitamin.
(29:00):
But the important part is that it's also, and we see this in biology a lot, it's also a regulator of metabolism because how much of it is in a specific state tells the cell something about metabolism.
And so that's really something that's very important.
Now, mTOR is a really interesting central hub for regulation of growth and of metabolism.
(29:30):
And it has many pathways coming in, and it does many, many things to the cell and it controls the mode of growth of cells.
So if it doesn't regulate growth, that's where you can actually get certain types of cancers that grow.
(29:51):
Yeah.
So it's kind of off topic of autism, but the idea that mitochondria is now a hot spot or in large part where melatonin is made.
And melatonin is likely our number one antioxidant, which also goes with that cancer story too, I think.
(30:17):
And I guess the reason why I bring that up is it seems to me that autism is just a downstream phenotype of our new environment.
And you know, we know that the mitochondria DNA are very sensitive to the environment.
(30:42):
And I don't want to, I don't know, I'm going down a complete bad path here for our conversation.
But autism just shows up apparently around the 1930s, maybe a little bit in the 20s.
I don't know. Eugen Bueller and even Piaget and some like experienced with children with very autistic phenotypes.
(31:11):
But something in the environment caused it.
And I've been hitched on that.
I don't know where I want to take that, this rant for the last two minutes, but maybe I should just get back on path here about.
So let me show you another kind of theme that we have.
(31:34):
So, you know, the mitochondria, we talk about something called the terrible trio.
Yeah, oxidative stress, mitochondrial dysfunction and immune dysfunction.
And when we find these all feedback on each other to create a vicious cycle of disease.
(31:56):
So, you know, sometimes it's not clear where you start, oxidative stress, immune dysfunction, dysfunctional mitochondria.
But all of these things tend to feedback on each other and make things worse.
So the mitochondria itself, when it becomes dysfunctional, it can send out dangerous signals called damps, which start inflammation.
(32:21):
Also, the really interesting thing is that when you look at regulatory cells in the immune system, they're usually more what we call oxidative.
They use mitochondrial function to function.
Whereas the inflammatory cells, many of them just use glycolysis and don't use the mitochondria.
(32:42):
So when you mitochondria becomes dysfunctional, you really have a deficit in this regulatory aspect of inflammation.
And so that potentiates inflammation many times.
Of course, inflammation and also not being able to regulatory the immune system leads to immune dysfunction in both ways.
(33:09):
Autoimmune disease and also not being able to successfully get rid of infections or having prolonged infections, having sensitivity to infections.
Inflammation and the immune cells actually send out messengers to the mitochondria, which actually turned down its ability to work.
(33:37):
So there's a vicious spike will spiral there.
Both of these cause oxidative stress.
And oxidative stress can cause more mitochondrial dysfunction, can cause, again, mutations, especially on the mitochondrial DNA.
And the important thing here, another way that oxidative stress in the mitochondria interact is the major antioxidant of our body is glutathione.
(34:04):
And glutathione can be made of the mitochondria.
It's made in the cytosol outside of the mitochondria.
But to make it de novo, you have to have ATP.
So if you don't have glutathione to combat the oxidative stress in the mitochondria, you're not going to making it making ATP and you're not going to be making glutathione.
(34:25):
So there's a vicious cycle here too.
So we think that many diseases, complex diseases are caused by some cascade in these three different areas, which kind of end up in this vicious spiral.
And the idea is how to get the body out of that and support it so it can get back to a normal state.
(34:47):
And of course, as our environment changes, not only a lot of people like to talk about toxins and things like that.
But the other thing we're finding is that probably the major influence of your body is really the maternal environment during gestation.
And it's so, so, so important to make sure that prenatally the fetus gets the nutrients that it can because we find that there's some predisposition in a because of a lack of certain nutrients.
(35:24):
And to be exposed the least to certain types of pollutants and other types of toxic material.
The prenatal. And there's a lot of vitamin B's associated with autism.
The prenatal is it based off of some work at UC San Diego and even the the paper released in neurobiology of disease that you're you're on it.
(35:57):
Are you comfortable with kind of thinking that autism is in the embryo.
I think it may be predisposed in the embryo. You know, yes and no. So, you know, and that makes what makes it so difficult.
It's how certain factors come together, you know, environmental and genetic factors, how they come together to predispose and then usually think of some type of trigger that is can cause this.
(36:31):
So, one paper we actually were able to correlate air pollution prenatally with long term mitochondrial function.
So, we show that if you measure, you know, the mitochondria anywhere from six to 12 years old was most of our kids that you can link that function to air pollution exposure.
(36:56):
And, and this the pattern dependent on whether you have regressive type autism or non regressive type autism.
That is whether you develop to a certain point and lost all your skills or you were at just a you had symptoms from early on, or you had a plateau phenotype.
(37:21):
But what's also interesting, we went through and we said, well, the regressive, you know, type phenotype is very interesting.
We've linked the regressive phenotype with a specific type of mitochondrial dysfunction where you actually see overactivity of the mitochondria by about 200%.
But what that does, we found is make the mitochondria very vulnerable to any type of physiological insults.
(37:49):
So, sometimes you know the trigger when a child regresses, you know, whether it be an illness or a seizure or so.
But many times you don't. And so what we looked into is whether, you know, that air pollution, you know, we know that it affected the child prenatally.
(38:11):
If it, it could be the trigger postnatally to regression. And we found out there was some evidence of that, you know.
So, it's all these things that, you know, you may have the luck or the unlucky of getting exposed to them in some type of vulnerable state.
You know, so the really the thing we want to do is reduce that vulnerable state.
(38:32):
So, you reduce that vulnerability to have some trigger not to develop well.
And that starts, yeah, that starts in the embryo. So, we have to be sure to start very early on.
You know, the JAMA paper that looked at when there was sensitive periods for folate supplementation found out that it extended into the preconception timeframe.
(38:59):
So, that also is so important to know that you have to get your body ready for pregnancy.
And it's not just the pregnancy itself.
Yes.
I have an episode on that. And the environment of the birthing mother, the mother has drastically changed from the time that autism wasn't here.
(39:31):
And I just don't understand why we can't mimic that environment before autism to see if there's any change to the rates.
Yeah, it's very complex because we don't know all the factors that go into it.
(39:52):
So, there's a nice paper by the Mount Sinai School of Medicine group where they actually looked at the sigiwis teeth, that is, baby teeth.
They start to develop at the end of the first trimester and they record everything that the baby has been exposed to.
And with that, they found that, yeah, that very in twin studies, they were able to differentiate the twin that developed autism, which the first is the one that didn't, by the manganese and zinc levels.
(40:28):
So, those are really important, you know, nutrient metals.
And then we actually looked at these various types of metals, both nutrient and toxic, in kids with autism, and looked at how it may regulate their mitochondrial function.
And we found that, yes, prenatally zinc and manganese actually modulated long-term mitochondrial function in those that had regressive type autism.
(41:00):
So, those are just probably examples of two nutrients, but there's many other nutrients that are probably really very critical.
Of course, we know that thyroid, iron, folate is very important.
Carnitine is something that seems to be reduced during pregnancy, which is usually not recognized.
So, the problem with metabolic systems is they're complex, right?
(41:25):
They're not just one thing or another. All these things kind of play on each other and are correlated.
So, that complexity of it makes it hard to study.
Yeah.
The role of melanin, like neuromelanin now, is very fascinating, whereby it works as a protector of the cell.
(41:47):
And it takes these metals or these toxins, I should say, just to be general, and kind of protects the cell.
I think there's going to be something to come out of that, the role of melanin within the cell.
Yeah, we're knowing, especially melatonin, is, you know, we think of it as a sleep initiator, but it actually has many different roles as far as an antioxidant.
(42:22):
It regulates the immune system and it supports mitochondrial function.
And there's some studies are using high dose melatonin to as a treatment for mitochondrial dysfunction.
(42:43):
Okay.
I have a question about NAD. Is that synthesized through tryptophan or is that a different acid?
It has several different pathways. But tryptophan, yeah, definitely that's one of them.
But there is other ways that it can be produced.
(43:09):
So, you know, definitely many different aspects of that. So again, being complex, yeah.
And the idea is, yeah, how do you get it into your body?
I find actually that the nasal sprays work pretty well rather than the oral form.
And that's a problem with all of these kind of supplements, you know, they're not at the level where they've been tested as medications.
(43:36):
So we don't have those same ideas of how they optimally get into the body for certain individuals.
One of the problems with, you know, at least kiddos with autism and other diseases is that they have issues with GI system.
(44:05):
Yeah, which is kind of hits with the tryptophan and serotonin, I think too, because of the enteric and enterochromathin cells.
Yeah. So you're absolutely right there. Most of our neurotransmitters, we always think we're in their brain, but most of it is in the gut as you point out.
(44:28):
So, you know, it may very well be that, you know, that the gut, these things also regulate the gut, not only these metabolic systems are extremely important in that metabolism.
(44:54):
Yeah. So here's an NAD production.
Can you or can people differentiate the amount of NAD coming from tryptophan versus, yeah, the nicotinetic acid?
(45:15):
Yeah. So you can see that here can come from tryptophan or nitinic acid. Exactly.
And so there's two pathways that converge to make the NAD.
And or you can take some of these other products that come right into this cycle and make NAD downstream.
So there's many ways of getting in there. Yeah.
(45:38):
I was curious because of with everything that we've talked about with the environment and the protein sequencing, DNA sequencing.
Because tryptophan being an aromatic amino acid that absorbs, it peaks at 280 and anywhere from 2 to 280 nanometer light.
(46:02):
And I'm just, I'm kind of everything to me saying that autism developed as a biological adaptation from our shifts in light.
We're less involved in the sunlight, which we evolved under and that we're under this artificial light, which is very isolated.
(46:28):
And I guess a simple way of explaining it is if I go by a baby, if I go by a tree, like from Home Depot, and I plant it in my yard, even if it's optimal environment, optimal soil.
And I cover the tree with or from the sun. It's not going to develop the way that it should.
(46:53):
And so that is kind of like a neuro development of the tree.
Yeah. And in contrast, or in addition, if I take a grown tree and block the sun and it accelerates death.
That I just gave that tree kind of Alzheimer's, which is also new in medical literature.
(47:22):
I don't know if I'm far out, but this biological adaptation to our environment, especially with how sensitive it is and how we evolve for, I don't know how many years as mammals.
Under the sunlight, I think we neglect the fact that the sun and light, especially light as an electromagnetic field.
(47:50):
And as we talk about mitochondria and the electrons and proton balance.
I'm just, I'm just so curious and interested if how much light has a is in play here.
Yeah, I mean, light itself, sunlight, especially is extremely important.
(48:11):
One, you know, actually say to get the cycle, you know, one of these things we know that in autism, we have the, the melatonin sleep cycle is that diurnal cycle is broken down quite a bit.
And some one of the first things we really have to fix.
And your body doesn't repair itself very well.
If you don't have that cycle, if you don't sleep well, that's why we look at sleep.
(48:36):
That's so important because that's when you actually integrate everything you learn during the day into your brain.
If you don't sleep, you don't learn.
Also, we're learning, of course, about the lymphatic system that washes out the brain, almost like a washing machine of all the junk, you know, at nighttime.
So if you don't sleep well, you don't wash out your brain really well.
(48:57):
So sleep is so important and getting into that cycle is so important.
And then you have the effects that we're learning about how light is therapeutic, you know.
And so you wonder about light itself, if it's actually getting into our body and actually physiologically, you know, helping our body function.
Absolutely.
Red light for sure penetrates bones.
(49:21):
So red light is getting in.
Robert O'Becker is really good on that.
And with cytochrome c-oxidase, having four red light chromophores is very telling to me like something is going on here.
And the complex, the mitochondrial complex has VDR receptors.
(49:50):
Yeah, you know, they're absolutely right.
Yeah, that's why vitamin D is so important also, people underestimate it too.
And it's amazing these days how many low vitamin D levels I find.
I always check vitamin D and I would say most of the time it's low, you know, and I live in Phoenix where it's hot to sunlight.
(50:11):
Yeah, people avoid the sun and whenever they go out to the sun, they now cover up the sun quite a bit.
And it's like vitamin D to me connects, you know, our skin is obviously the largest organ and endocrine organ in our body, but it connects our body to the central nervous system.
(50:37):
It's not like it's a bloodstream or whatever, but it's a healthy dance there, vitamin D and the central nervous system.
It's just so bizarre to me that maybe it is this simple, but yet human biology being so complex.
(51:01):
It's why don't we look at the environment before autism got here.
And I think the rates of how many things that's changed, that's the problem, right?
Yeah.
And so we have the really good research.
It's hard to know, right?
(51:22):
Because you can, you know, blame it on almost anything, you know, TV, you know, yeah.
Absolutely.
It's, you know, it's just that certain way to invite even in a lot key kids, you know, it's just, it's amazing how much our society has changed.
So it's so hard to figure out those variables.
(51:43):
Yeah.
If it goes back to the 1930s, though, and this maternal genetic implication.
If it is a source of artificial light being invented in the 1880s, and then the power grid really taking off in 1893,
(52:06):
it hit the autism.
That's about one and a half to two generations later that it slowly came of all.
But then the rates of autism kind of follows this shift of reducing sun and replacing it with LED lights, which is blue light, 440 to 480 nanometer light.
(52:30):
And like with tech light, the rates of autism and quite frankly, the rates of Alzheimer's and metabolic health, obesity, they're, they are, they're all following.
They're all following this, this shift of the light source.
(52:52):
And I don't think it's not autism, but I don't think obesity is a food problem or even a calories in calories out problem.
I think they, people with obesity just lose energy to the environment because they're not getting the electrons is what I'm leaning towards.
And this is off topic and I know I'll wrap that up right now, but obesity is just like the autism where there's a lot of factors, but just that this one factor of the sunlight or artificial light and the implications,
(53:31):
because Melotinopsin wasn't discovered until 1998 and that's a blue light chromophore.
And so everything here is telling me that, well, maybe it is as simple as our energy source, light as an electromagnetic field.
(53:53):
Yeah, no, I think light has a lot to do with it. I always tell my, my patients, you know, my family is to, to wake the kid up and take a walk around the block in the sunlight.
If I'm wanting to get the day started, because really wakes you up and it gets you going.
That circadian cycle is starts as soon as, as soon as you need light as soon as possible, because of the signaling and the implications or benefits to the hormones in our physiology.
(54:27):
And we've, we've kind of neglected that as a modern society.
Yeah, it's complex. That's, that's nothing. It's not simple. Our bodies are not simple. And nature is not simple.
Yeah.
Yeah, we, we, we took ourselves out of nature.
And when we were in nature, though, we didn't have so many of these modern complex diseases.
(54:53):
What is something you're working on now that is your most excited about or something that you can share for us that to look out for?
Well, I mean, what we're doing, you know, we have a bunch of clinical trials. We're still doing our work on leukovorn, which is certain folate that seems to help many kids with autism.
So we're continuing those.
(55:14):
We're doing a project on photobiomodulation for seizures. So there's some good evidence that it seems to work well for autism symptoms.
But we're also seeing, we think theoretically by looking at how it works in the brain and how it changes certain brain waves, that it should actually improve seizure, seizure activity.
(55:36):
You know, and many kids with with autism are very sensitive to anti-epileptic medications where they don't respond.
So it's really nice to have, you know, a another, you know, tool to treat them.
We're also doing a trial on a brand new drug that is not even on the market yet that regulates microculele cells.
(56:04):
So we think that could be a real game changer.
And then for, you know, mitochondria, you know, and other types of metabolic systems, what we're finding is that that they may that they seem to run in families.
And so something that might be affecting the whole family.
(56:26):
And if that that's important in many ways, one, you know, the rest of the family might have disorders that are treatable in similar ways.
But if you can identify those abnormalities early in the mother and father, you may be able to do something about it, you know, in the prenatal period or preconception period that will reduce the risk of having any type of chronic disease.
(56:52):
Yeah, I think that's I think that's the future. I think that's that's I'm set aside and I'm pleased that you shared that with me because I think this is the way.
So yeah, so we have our foundation, the autism discovery and treatment foundation is what we started to do all of this research.
So we're on Facebook, you can, you know, follow, like and share and all do that stuff. We try to put videos out every week on something new, some new information, just a short video to keep people up to date.
(57:24):
Yeah, good. I'll put all your links in the show notes and I think modern medicine misses this bio physics. And I know you have a PhD in bio physics.
I think bio physics and biochemistry must meet together for the cell development or the cell functioning.
Yeah.
(57:45):
That's for sure.
Dr Fry, thank you so much. And I'm sure you have to talk to you. It was amazing.
You're talking to you.
Thanks.
Bye bye.
Before we wrap up today, I just want to kind of mention again that the podcast stands on the cause of autism and how critical light as an electromagnetic field has evolved living organisms on Earth, including humans.
(58:19):
It seems to me that eventually something will come out about this shift in light source, removing ourselves from the sun and supplementing it with artificial light in the various forms of artificial light.
But before you understand that, you need to understand that the sun spectra 280 to 3100 nanometer light, the sun spectra is much different than artificial light in the light that we have now surrounded ourselves in or suffocated ourselves even.
(58:58):
It's much different light and the energy source and the wavelength.
Humans have this capacity because humans have this capacity to think.
Now we are the only creature that will change our environment like this because of the frontal lobes because of our capacity to think.
(59:24):
I don't want to sidetrack on Dr. Fry's information and the amount of work that he is doing to one understand autism and two, even as you've heard him say, the treatment with the photo bio modulation and the the spray of the NAD.
(59:49):
This is very critical in our understanding of autism and allowing autistics to kind of thrive and have a different environment have a different option.
And we're very much appreciative of Dr. Fry's work. I know he's he's very different kind of dynamics I was searching for.
(01:00:19):
He's it's very impressive how dynamic this individual is, especially for our topic autism.
If you are listening to the episode or listening to the podcast, please feel free to leave a review or rating.
In podcasting reviews, ratings and downloads are huge.
(01:00:41):
And I very much appreciate your feedback.
You can contact me on X at rps 47586 or email info dot from the spectrum at gmail.com.
And you can click on the hop link to have access to all of the platforms of podcasting and contact information.
(01:01:08):
Thank you for listening to from the spectrum podcast.
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