Strategies to Upregulate Autophagy to Maximize Peptide Therapy Benefits

Kelly Halderman, M.D., CCN

Zero.

Matthew Cook, M.D.

Oh, that’s the way you do it, I remember that. People always used to say when I was a kid, “Oh, it’s pretty warm, it’s like 18 degrees.”

Kelly Halderman, M.D., CCN

Oh my, yep.

Matthew Cook, M.D.

So we both grew up near the Highline. And in Minnesota, she has her own clinical practice and services as director of research and product development for Professional Health Products and Randal Optimal Nutrients. So I’m delighted to have you here for a fireside chat at my house.

Kelly Halderman, M.D., CCN

Awesome, I am so happy to be here, Dr. Cook. Thank you so much for having me.

Matthew Cook, M.D.

Yeah, it’s gonna be right. So then tell me, I know we had a little delay, something happened to you and so we had to reschedule. Today’s a couple days after Christmas, what happened?

Kelly Halderman, M.D., CCN

So after I returned from a fabulous educational experience at a forum in Vegas, in the middle of December, that be 2021, I came down with a nasty case of COVID. And I am a sharer, I like to share things. And so I gave it to my whole family. When I got home, I just shared the love, took everyone down in my entire house, so thank you for rescheduling. I was pretty sick, but my story’s really interesting because of the topic, because this is the Peptide Summit and I used a lot of different peptides. I got a lot of guidance from really great colleagues, such as Jim LaValle on getting myself over COVID really fast and I will attribute the peptides I used to really helping me recover and my family recover. Although I didn’t, you know, my kids weren’t really that sick, it was just my husband and I were pretty sick. So really have to thank peptides for this.

Matthew Cook, M.D.

Oh, good, yeah, I like Jim a lot. Tell me what protocol did you use to, well, maybe start, tell me what’s sort of symptoms did you get from COVID?

Kelly Halderman, M.D., CCN

Sure, so I got home on Sunday and then on Monday I started to feel a little bit achy and just kind of had a little bit of malaise. And I went to bed that night and woke up in the middle of the night with a pretty significant fever, which honestly I was pretty excited about. I don’t know about you, but when my body, when my immune system is healthy enough to kick off a really nasty fever, I was almost cheering my body on. So I did feel rather terrible, but at the same point I was not suppressing my fever because that’s one thing that I really wanna drive home is that was an important piece, is that I wasn’t taking a much of Advil or anything to like suppress the fever. I had a raging headache, you know, I was just nesting. I had some mood changes, which were like, I was just really like angry just to be honest. And I think my brain was so inflamed and we know that Daniel Aman was doing some before and after SPECT scans and I’ve actually had a SPECT scan, it shows that COVID is more affecting the limbic system so. It lasted about two or three days. I was, you know, I was throwing the kitchen sink at what was going on and peptides that I did use, I used Ta1, I used Tb4, I used BPC, I used LL-37 and I also use a fragment of the Tb4 when I ran out of the Tb4, ABP, what I wanna say, for maybe five or six days I used high doses and then after that, and I think I was well, symptom free on day five. I just continued it for another two days, so that was my regimen.

Matthew Cook, M.D.

Okay, good, so then take me through what, how many milli, what dose of BPC did you do each day?

Kelly Halderman, M.D., CCN

I’d have to, I’d have to look that up. I would have to look up at the exact doses.

Matthew Cook, M.D.

So I’ll go through, I’ll tell you some of the dosing that-

Kelly Halderman, M.D., CCN

Sure.

Matthew Cook, M.D.

It’s interesting, some people will take, so then BPC, normal dose might be 500 micrograms to one milligram and then a lot of people I’m hearing will take, you know, maybe one to one and a half milligrams a day and I’ve heard people taking up to two milligrams a day for COVID.

Kelly Halderman, M.D., CCN

Pretty sure I took one milligram a day.

Matthew Cook, M.D.

That would sound perfect. For the Ta1, do you remember how much you took of that? I’ll ran you through all of my dosing that I’ve heard of. We, you know, the range will go from two to 10 milligrams a day in divided dosing, and then you can do IV infusions of Ta1 and I’ve seen that be quite helpful for COVID as well in the ball park of five milligrams in a slow infusion. And then if you do that in the afternoon, do some Ta1 in the morning and at night to add up to a total of 10 milligrams. Some people don’t have Ta1 and then, and if they have, if they do high dose Ta1, I have them do low dose Tb4, like one to two milligrams of Tb4. If they do no Ta1, then I’ll have them do high dose Tb4 in the ballpark of five to 10 milligrams of Tb4. And then the dose for LL-37 is a 100 micrograms twice a day.

Kelly Halderman, M.D., CCN

That’s what I was on, yeah.

Matthew Cook, M.D.

Okay, perfect. And so then did you get much of a pneumonia?

Kelly Halderman, M.D., CCN

No, I did not, I was nebulizing hydrogen peroxide iodine the minute on Monday when I started to feel ill. So that could have been a part of it, but I didn’t have any lung involvement.

Matthew Cook, M.D.

Okay, that’s amazing, so then that is, so A, you had a fever, B, you took all the right things and then C, this is the sort of new conversation that’s been coming out, you know, over this last month, which is, is that we need to probably wash our hands, but more importantly, we gotta do a lot of hygiene of, you know, mouth washing and nebulizing and kind of those upper airways ’cause it sounds like basically you prevented it from getting into your lungs.

Kelly Halderman, M.D., CCN

I will say that a 100% Matt is that I also made my poor husband go get, before he had symptoms, he didn’t have ’em, I said, “Go get a neti pot.” So he went and we did, everybody in the whole house did neti pot rinses with the same solution and I’m, I really do credit that to, you know, keeping my lungs healthy is that we had to keep these cavities and I was gargling with it, yeah, so I totally agree.

Matthew Cook, M.D.

Which solution did you use in the neti pot?

Kelly Halderman, M.D., CCN

I used normal saline with a, I think it was what, 12%. I had a little table that I was using, that I was using to draw everything up and then I would just put a drop of glucose, iodine in there.

Matthew Cook, M.D.

Okay, yeah, that’s a great, that’s a, that’s a.

Kelly Halderman, M.D., CCN

I’m still doing that because there’s still flu out there, right?

Matthew Cook, M.D.

Right, yeah, so then this, you nailed it, which is super awesome that goes to show you that, you know, that’s one person affected three and I think that, you know, that may be an indication that that was Omicron because it’s so contagious and I’m hearing, I’ve heard this story like a 100 times in the last week and a half of, oh yeah, somebody got it and then they were really conscientious and careful, and then everybody in the family got it. Like, I can’t tell you how many times I’ve heard that.

Kelly Halderman, M.D., CCN

Right, right, I have a 16 year old daughter and, you know, she spends 99% of her time in her room and I had very little contact with her whatsoever and she actually tested positive as well. So I do believe that yes, that we had the Omicron variant.

Matthew Cook, M.D.

That’s interesting, well, we’re gonna talk about COVID a little bit later, but tell me, you know, you have a very, it was, that was awesome to read your bio. And it’s also awesome for me that we have in our journey gone through some of the same certifications and gone through some of the same study, because I think probably talking to you I realize, boy, we probably agree on a lot of stuff and think about things similarly. Tell me what happened and that started you on this journey from being a straight laced primary care doctor into learning all of these new interesting ways to help people.

Kelly Halderman, M.D., CCN

Yeah, well, it really wasn’t my plan. I absolutely loved the practice of medicine. I was doing well and very successful and, you know, was able to match up symptoms with medication, pill for every ill, I mean, like I was on my A game until I myself became very ill. I was on call one night delivering a baby and I remember having a giant scotoma out of nowhere. Now, if you rewind at this time of my life, I was a collegiate level athlete, you know, I was still in great shape, I had just birthed two wonderful healthy babies. I mean, I was very healthy and just in a period of six months, I got really ill. And so, the crescendo of that was delivering this baby, not being able to see, having to go grabbed my nurse to catch this baby and thinking what is going on with my health?

Matthew Cook, M.D.

What does scotoma, tell ’em what a scotoma is?

Kelly Halderman, M.D., CCN

Oh, scotoma, so a hallmark of a migraine. In some people is that you’ll get a flashing blinding light in one of your visual fields and it’ll it, depending on where it is, it can almost blind you. And so, this flashing light, like someone’s running a strobe outta nowhere when I’m gloved up and gown and ready to deliver a baby and it was like this moment of like, I can’t do this anymore. I need, the doctor needs to go get evaluated. So I was evaluated and I was diagnosed with MS. I mean, I wasn’t even 30 years old and I was shuffled to the, not shuffled, escorted to the best neurologist in town at the Mayo clinic. And I was given the diagnosis and I was given the right medications, but I wasn’t given any hope, I wasn’t given any anything, but what I felt was a death sentence and so-

Matthew Cook, M.D.

What did they say? What did they say was your plan?

Kelly Halderman, M.D., CCN

My plan was to basically wait and watch and see, you know, what symptoms that I would have. I don’t recall exactly what medications I was put on, but I remember at that moment thinking, oh, you know, this whole paradigm that I’m in of you’re prescribing medications for symptoms, I’m like, yeah, that’s not gonna work for me because it’s not the answer, it’s not the answer to how I’m gonna get out of this, right? Because I had little kids, I had a two and three year old. And, you know, basically being told to go home and be with my children that was not an option for me. And so, I loved my allopathic career, I loved my colleagues, but I was out of resources. The tools in my toolkit were not helping me. I had to step away, I still have an amazing husband that supported me and supported me for stepping away and trying to learn something new. Now I come from a line of, well, a lot of lawyers and, you know, and a lot of allopathic practitioners who would think I’m crazy for stepping outside of the norm and going to naturopathic school, but I did. And I started to learn about detoxification and nutrition and I started to apply it to this body, this sick body and I just slowly, slowly started to regain my health. 

Now, we had this conversation yesterday, Matt, where we talked about like, well, what was going on? Well, at that time now in retrospect that six months where I just was declining, we had a dishwasher that we didn’t know was leaking, so we had some mold issues in our home and I also lived in an area that was endemic for Lyme disease and so that was my actual root cause. I went to a Lyme literate physician who said the root cause of what’s going on is probably Lyme disease, coupled with mold, you know, that’s probably what’s going on, so let’s go after that and she saved my life. Thank you Dr. Vacoda. And from that point on, when you realize that there’s another way that there’s root causes, it’s almost hard to go back. It’s hard to go back and just practice covering up symptoms. And so, one of the ways this is why I’m so passionate about what we’re gonna talk about today about autophagy, is because autophagy, a word that I didn’t know about until probably about five years ago, looking back, this is one of the central things that I did, I optimized I think to get myself back to 110% better than I ever was. And that’s why I’m so passionate about it.

Matthew Cook, M.D.

Okay, that’s a good one that, you know, reminds me of like myself and everybody that I knew, you know, you go through medical school and you get to that moment when in residency and, you know, I remember I used to try to figure out that I would try to spend like $10 a day on food, you know, so you’re just scrambling through staying up all night and you may have had Lyme in the background, but then a little bit of mold triggers your immune system, and then you’re staying up all the night. Actually, I think the most stressful job on the planet is maybe the most inspirational job at delivering babies is what a, and so then you’re going, and it’s interesting because then, and I’ve seen this a 1000 times ’cause I used to do epidurals for labor and delivery back in my old life and there’s this moment when you see people that are compromised because it was four in the morning and you’ve been up, you know, 22 hours and trying to kinda manage your way through not making mistakes and you’re getting and then having anything going on and there’s an expectation of everything being perfect, 24 hours a day, seven days a week. And so, I’m empathetic for that, but now we’re gonna, and go through some of the biochemistry, ’cause you wanted to talk about autophagy, and I think, you know, this is a Peptide Summit, but maybe one of the important things is to understand the biochemistry of what’s happening and then how can we optimize cellular functioning ’cause if we can do that, then we, that’s almost like the platform that things are running on, then we can kinda put on these other things on top of that. So then tell me what is autophagy, why is it important and how do you think about it?

Kelly Halderman, M.D., CCN

Sure, so autophagy is so important that in 2016, Dr. Yoshinori Ohsumi was awarded that Nobel prize in Physiology or Medicine. And at that time I don’t think any, anyone really thought that it was gonna be this big of a deal. We really didn’t, but we built on it. Like all good things that we, well, I wish I didn’t say all good things, but like some things that we find in science were like, this could be potentially a big deal. So, you know, 2016, we’re learning more and more. And so autophagy, the process of it is the cellular cleaning in your body. So I describe this to my patients as these little tiny cellular vacuums that go around and they clean up old cellular debris, autophagy is also relevant to help us get over viral infections as well, so autophagy is cellular cleaning in that respect too. So, you know, like looking at what autophagy is, it’s an important mechanism and it’s been conserved across a billion years, I’m not being hyperbolic here, a billion years of evolution we have this autophagy pathway and is that its so important. And so since 2016, we’ve done studies, you can look at the literature and see that impairments in autophagy can lead to disease processes, chronic disease processes, cardiovascular, immune dysfunction issues. And so we know that upregulating this autophagy is extremely important.

Matthew Cook, M.D.

Well, yeah, I know that too because you sent me 18 articles about it, which was awesome that that helped me get ready for today. How do we upregulate autophagy?

Kelly Halderman, M.D., CCN

You see, you can’t talk about autophagy without talking about the pathway that opposes it and that is called mTOR. So mTOR stands for mechanistic target of rapamycin. Okay, so what is rapamycin? Well, rapamycin is a drug and it was actually discovered in Easter Island in 1972 and it was passed on to two drug companies and it was eventually cleared for renal, for transplants. I say renal transplants because my father actually was a recipient of a kidney and he was actually on rapamycin. So the drug was discovered first. And then in 1991, Hall, the researcher Hall found this TOR pathway in yeast. And in 1994, David Sabatini found that we mammals also have this TOR pathway. So this to pathway is extremely important again, because it’s a billion years pretty much of having this same pathway. So what is this mTOR pathway? It is the master regulator of all the inputs that are coming in and deciding if we’re gonna grow or not. So when you think of a baby being, like the sperm and the egg coming together, if you didn’t have mTOR, if you didn’t have that process, you’d have no baby. 

So the inputs can be amino acids, glucose, growth factors, and things, but again, it’s the pathway that promotes growth just to kinda keep it pretty granular for all people to understand. Now, when mTOR is upregulated by all kinds of things, it can be upregulated by insulin, glucose, just think growth, right? Amino acids, some hormones, it shuts down autophagy. It’ll shut it down. So the problem is, this is the central paradigm, is that we are living in a world that is over driving mTOR. We are over driving this process, that’s fine and dandy, but when you think about the implications of cancer and autoimmune disease and other diseases, we’re not giving our bodies a chance to do the cellular cleanup that is so vital. And there’s also genetic mutations that can have a person be more at risk of having really impaired autophagy. Now, looking back, that was me. I actually have some genetic SNPs that were probably expressing because I was so sick where my autophagy was impaired. So I was a like biological traffic jam of old cells and things not being able to be recycled, and how’s your body supposed to heal, how’s your body supposed to get back to a normal homeostasis allostasis when you’re you’re full of debri.

Matthew Cook, M.D.

Okay, that’s a good one. One way, I heard one description of autophagy is cellular efficiency.

Kelly Halderman, M.D., CCN

Yeah, right.

Matthew Cook, M.D.

So then, what in your experience or maybe from the literature are the most important strategies for optimizing autophagy in cell efficiency?

Kelly Halderman, M.D., CCN

Sure, so I call that easing up on our mTOR, right? There’s an article on that on my website, drkellyhallerman.com, easing up on our mTOR means balancing our blood sugar. You know, you’re gonna go back to foundational things, but again, if you want, if we wanna get the maximum benefits out of peptides, if we wanna get the maximum benefits out of any anti-aging, you know, senolytic therapy that we’re doing, we have to get our cellular biology right. And this master control, this mTOR and this autophagy, we have to make sure that we’re in balance. So the mTOR, again, insulin, glucose make sure that you’re monitoring that, that you’re trying to be on a diet that has less, you know, peaks and valleys of glucose that’s really hard, that’s pushes mTOR. A lot of things that are contaminated with xenoestrogens, there’s a paper that I send you, Matt, that, that shows that xenoestrogens can actually upregulate TORC1, so that’s one complex, that’s the one complex of the mTOR. So it’s upregulating that, again, growth, growth, growth. Now, we have an epidemic here where 82% of the population above the age of 80 will die of cardiovascular disease, cancer, Alzheimer’s and the downstream effects of uncontrolled blood sugar from diabetes, right? So we’re thinking if those are the things that we’re succumbing to, right? Those coincide to me with too much mTOR, too much pushing on this growth, growth, growth, not enough cleanup. So again, you can overdo amino acids, so if you had a real high protein diet, methionine, leucine, they really push on mTOR. 

There’s also, you know, hormonal imbalances. But again, I think the strategy should be a foundational one, so we’re looking at diet and lifestyle, but the one thing that is really important that can actually upregulate your AMPK, so adenosine monophosphate protein kinase, so kinases, phosphorylases, so that pathway AMPK will activate autophagy. How do we do that? We can do it by fasting. Fasting is one of the most potent tools that you have in your toolkit to optimize all these things and the strategy, this is where I get myself up, the strategy of anti-aging is not to reverse your chronic disease, it’s that you never get one or we elongate the time until you get one, okay? So if you’re in the anti-aging world and you’re trying to push anti-aging, your goal is not to reverse all these chronic diseases, it’s to get your patient far as you can down the line, right? So this is all about prevention, prevention, prevention. Again, go back to the things that we know, how many, fasting has been in history. It’s in all kinds of texts and things for years and years, since you know, like the dinosaurs were around that, fasting is very important, right? So we wanna take advantage of that. The caveat is, is that we don’t spend enough money, in my opinion, we don’t spend enough money on research to know the dose response nor the timing of fasting, we do not have a good answer. So when people look at you, if you’re a physician, if you’re a practitioner and say, “Tell me exactly how long I have to fast and I’ll do it. Do I have to fast seven days, every quarter, do I have to fast every other day?” We don’t know, we really don’t know. We know that after seven days your autophagy is gonna be kicked on high gear, we do know that, but fasting shouldn’t be undertaken by, you know, it’s something that you should probably be medically directed because a lot of people’s blood sugars and things like that. So exercise can also upregulate autophagy, there’s nutrients too that can upregulate autophagy, lithium, berberine, resveratrol. And then we can also talk about rapamycin and rapalog if you want to.

Matthew Cook, M.D.

Okay, we’ll go into that. How are, how, what type of fasting protocols are you having people do right now?

Kelly Halderman, M.D., CCN

Sure, so it depends on the person who’s sitting in front of me and their phenotype and what else they have going on, what they’re willing to do. Again, I don’t have a lot of data, to hard test data to say, “Okay, well, this clinical study showed this and this.” So, you know, we’re really, we’re applying empiric treatment and knowing that the, that, you know, fasting in and of itself is a good thing. So what I’m doing is I’m having people kind of dabble in what they’re comfortable with. And I do like Valter Longo’s, five day fasting mimicking diets, so that if someone wants to get the effects of, and we don’t know how much effects they’re getting by the away, but it’s better than nothing, right? And if you can’t do a water fast, if you’re unable to do it, you know, there’s data on intermittent fasting. So one of the things that I started to do when I was ill is that I tighten my eating window and there’s a lot of good data on tightening the eating window and upregulating autophagy, but again, setting autophagy is extremely hard, it’s difficult, the Achilles’ heel of medicine because we don’t have, we don’t have objective measures. We can’t say, okay, Dr. Cook, I want you to go on this and we’re gonna measure this autophagy marker, I want you to go on this fasting protocol, and then we’re gonna measure that autophagy marker, you know, 25 days later, we don’t have that. We don’t have that yet.

Matthew Cook, M.D.

The, so when I was, you know, I was doing a lot of yoga in my early journey of studying integrative medicine and I found out about fasting and this was back when I was still doing anesthesia full-time and so I said, “Okay, I’m gonna do it.” And so then about a year, I fasted, I did a 24 hour water fast, one day a week. And so then what I did is I did, and I would do it on like Tuesdays or Wednesdays just ’cause it was kind of impossible-

Kelly Halderman, M.D., CCN

It was goal or something?

Matthew Cook, M.D.

No, I would just do it and, you know, interestingly, my mental clarity, those were all my best days, because-

Kelly Halderman, M.D., CCN

Right, if the BPM goes, yep, way up.

Matthew Cook, M.D.

And interestingly, what, and for people who haven’t done it, you’re fasting and so then all of a sudden you get really hungry, and so then all of a sudden, you’re hungry, you’re hungry and you think you’re gonna die of hunger and you feel almost kinda shaking. And then next thing you know, all of a sudden it’s like, you felt just like this, totally fine. So then you go for a couple more hours and then it would happen again, at least this is what happened to me.

Kelly Halderman, M.D., CCN

Me too.

Matthew Cook, M.D.

And so then that happened for about a month and then I broke through that. And then now if I like didn’t eat till tomorrow night, I’d be totally fine and it, so something reset my metabolism through that experience, so that I think I got much more efficient from a liver perspective of glucogenesis, but then I probably turned autophagy on and so then just the things just started to work better.

Kelly Halderman, M.D., CCN

Right, right and then you’re probably cleaning up your senescent cells too that’s what I find with people is that when they embark on starting to fast, they go through those, you know, like starting today I’m gonna eat my hand and then, you know, I’m okay that, and then something flips for them where I really do think it has to do with senescent cells. So senescent cells are when your normal cells get to a point where they’re marked because they shouldn’t replicate anymore, right? So they’re frozen and they’re called zombie cells, but, and really the it’s not that, it’s a hermetic where, you know, you have a lot of senescent cells that they give off, especially the SASP, the SAS version of them, that are spewing cytokines, right? So if you have too many of those, if you haven’t even ever dabbled in autophagy because if you are just pushing so hard on your mTOR because you live on planet earth, you know, and you’re just doing the standard American diet, when you start cleaning up those senescent cells, your inflammation is gonna go down, right? And so not only are you fixing your biochemistry, you’re also like cleaning up that biological environment to have more cellular of processes going on. There’s things that go on during fasting, during autophagy, during the AMPK activation that we haven’t even named, we don’t even know, but again, I know that it’s tangible for me as well in a lot of my patients.

Matthew Cook, M.D.

Okay, so then two questions. Your thoughts on intermittent fasting and autophagy and then in relation to that, are you using the continuous glucose monitors to help people as they go through that process?

Kelly Halderman, M.D., CCN

So I am a big fan of both. I think that intermittent fasting, again, we took a Hippocratic Oath to do no harm and I see no harm in having people tightening their eating window down and seeing how they do. And to guide them, I do like the continuous glucose monitors. In 2022, I’m going to excise from my vernacular go keto, because what I’m gonna say to people instead is slap a CGM on your arm and what you put in your mouth, make sure it’s not spiking your glucose because it could be popcorn for some people. I mean, it’s the strangest thing, watermelon for me just, I mean, makes my glucose go off the charts. So learn about your body, don’t attach any, you know, any concepts or any, you know, buzz words to it, learn about what your body does with the energy, the food that you deliver to it. And I do, I find that completely, and it’s very helpful with getting someone to be more metabolically, they’re, you know, not burning, they’re into the fat burning because they can actually see, they can actually see what the things they’re eating are doing to their blood sugar and then they learn. And then they don’t necessarily have to wear a CGM the rest of their lives, it’s that they’ve learned with their bodies how their bio-individuality and that’s really the, you know, I think that’s personalized medicine, right? Right there, right there, you can do it all by yourself.

Matthew Cook, M.D.

So then for people who are not aware or are new to this conversation, it used to be that we would have to do a finger prick and then take a little glucose and then monitor, and then check that and then look to see what the blood sugar was. So the idea is, well, I don’t feel like doing that right now. And so then what happens is people would have kind of no idea how their blood sugar is going up and down throughout the day, and this monitor comes on, and then you can just take your phone, and then there’s also some Bluetooth, I just got, connect just people that have a Bluetooth enabled version of it, so it just tells you real time what it is.

Kelly Halderman, M.D., CCN

Oh, nice.

Matthew Cook, M.D.

Yeah, which is kind of amazing because then suddenly you realize, and probably not too surprisingly, which is why maybe we all love watermelon so much that if you eat watermelon, your blood sugar may go sky high, but then now we can control that, which is super interesting. Of the supplements to improve autophagy, what are your favorites, what do you use in your clinical practice?

Kelly Halderman, M.D., CCN

So my new favorite since coming home from A4M is spermidine and I think that is an amazing compound. It’s been a while that we’ve been waiting for an actual, correctly harvested or what, you know, whatnot. So spermidine finally, I have one that I really like and the data behind it’s really good. I like, there’s a product called Autophagy Assist from Professional Health Products has pterostilbene, berberine, resveratrol, so those are some of the nutrients that I like, EGCG, curcumin, those are really important, lithium and vitamin D is known to also upregulate AMPK. But again, it’s, you know, it’s not like we’re gonna take these pills and we’re still gonna continue to overdrive our mTOR, right? So you can’t do both, like they’re opposing mechanisms, on a granular level they’re opposing mechanisms and we wanna make sure that we’re not just taking these pills and continuing our crappy lifestyle, is that we have to implement some things and exercise, you know, oxygen hypoxia is a very potent of regular autophagy, but so is exercise. So I’m looking at exercise and reframing it as like, what can your body do? Your beautiful body, what can it do for you? Instead of like a punishment, it’s that it’s a celebration of any which way you wanna move your body, it’s going to help you with your autophagy, it’s help you, again, get rid of these zombie cells that are secreting inflammatory compounds, it’s gonna help clean up that cellular components. And again, it’s going to help with possible viral infections or some, there’s some data on there as well.

Matthew Cook, M.D.

That’s a good one and we are gonna have to keep talking about viral infections for the rest of our lives. It seems like the, you know, as you’re talking the balance between mTOR and autophagy, it reminds me almost, you know, some of these conversations, I feel like maybe we’ve been having since the dawn of time, you know, it’s almost like yin and yang. yin feminine, nurturing, supportive, yang growth expansion, yin clean up, you know? And so the, from a Chinese medicine perspective, this sort of, this conversation falls in kinda right in line with I would say a lot of ideas of health that have been promoted.

Kelly Halderman, M.D., CCN

100% and it also falls in is that we don’t just drive autophagy all day long, right? I mean, mTOR is very important, protein synthesis, bio lipid synthesis, I mean, we absolutely need this. It’s all about balance, it’s absolutely all about balance. And that’s, again, it’s Chinese medicine, the balance.

Matthew Cook, M.D.

Right and so then the, so autophagy cleanup and then mTOR is basically anabolism and growth. And so then, there’s this drug rapamycin, which is an inhibitor of anabolism, what, tell me your thoughts on that, how you’re thinking about that and what’s happening with that.

Kelly Halderman, M.D., CCN

So it’s really interesting. So again, discovered in 1972, finally became a drug to help patients not reject their transplant, so immunosuppressive, right? So that’s what we really thought of rapamycin for a long time and then along came Joan Mannick, brilliant Joan Mannick, who started to think about, well, what if we use it at a different dose? What if we brought it on down to a different dose? In 2014, she published a paper with Klickstein that showed that indeed, if you bring down the dose of rapamycin that, actually they used RAD001, which is a rapalog, okay, so they’re using RAD001, and I will say this, is that RAD001 is approved for renal cell carcinoma, right? So it’s approved for that, but what they did is they took it in healthy volunteers and they wanted to know if it would help upregulate the immune system and indeed it did have some positive effects. So, you know, I think that, I think again, when you’re looking at the population of people who have renal cell carcinoma, the safety data, right? FDA is concerned about safety is that we’re not so concerned about people who are dying, right? The safety margins are much wider now, we’re talking about prevention, we’re talking about using something to prevent, you know, I guess anti-aging to prevent aging, prevent the spurring on of mTOR. There’s a lot different, there’s a narrower window because it’s not a necessarily a need. So right now I think that’s kind of where we’re at is that there’s not a lot of money that’s wanting to be spent in pharmaceuticals on these long term, oh, you know, it takes so long to get the data that that would show safety, right? And so we’re kinda stuck and that’s why the jury’s out for me, and we had this discussion yesterday Matt, is that I see, I can read the literature in that their rapalogs and rapamycin, it does some press mTOR, right? So, yes and there’s a certain dose response we can see that, but am I comfortable using ’em at this point? Not really, no, I’m not comfortable. I think there’s other things that we can use at this point. Now, if I had a very increased risks of a neurodegenerative disease, I may think differently. I may end up, may change how I feel about it, and I have to be more aggressive on that end, but right now, the jury’s kind of out for me.

Matthew Cook, M.D.

They read an article that said rapamycin was a little bit unlucky because if it would’ve come out as a low dose in the first place, it would’ve been considered an immunomodulatory drug and it would’ve been the darling of integrative medicine because everything that we tried to do is to regulate and balance immune function. And so then the major levels that we’re pulling is either trying to improve autophagy or potentially in certain ways balance and decrease ’em tolerance. And we’ve got supplements, lifestyle all of those things as factors to begin to do that. And interestingly, when we do that right, the side effect is that we tend not to be plagued by the, the diseases of the day, which have been traditionally the obvious sort of big metabolic conditions, diabetes, stroke, coronary artery disease, fibrovascular disease, and then all of the neurocognitive degenerative things, but then now we’ve got COVID, you know? I was very, you sent me an article and I thought it was about post COVID syndrome. And, you know, I think that that’s a good conversation to go into a little bit, because I thought it was a fantastic article. Take me through your thoughts on how you think about long COVID, COVID long haulers and then the immune expression of those people compared to a normal cohort.

Kelly Halderman, M.D., CCN

Well, up until about September, I think it was a black box that we all were wondering what is going on here? You know, we have dealt with chronic infections, Epstein-Barr, CMV for a long time, but this was throwing a curve ball at us and then Andy Heyman handed me this brilliant paper that I handed you yesterday. And it talks about the similarities between CIRS, so Chronic Inflammatory Response Syndrome and post COVID syndrome and how they are very much alike in their signatures with a hypometabolism, with the transcriptomics. So how Dr. Heyman will look at a person with CIRS is that he uses a test called the GENIE, and he looks at the expression of the DNA, brilliant, right? Like the messenger RNA, like what is going on, what is being expressed? Not just your DNA, not just your blueprint, but what’s being expressed. And you can see signatures of a person who has chronic inflammatory response syndrome. And then they have created a treatment plan, a treatment protocol based on a person with CIRS. And again, so it’s based on the transcriptomics, the diagnosis is based on transcriptomics, symptom survey, the visual contrast test, which I would say visual contrast test is one of the most underutilized tools in our toolkit, it is $13, it can be repeated, it’s been validated since 2010 that is something I would-

Matthew Cook, M.D.

Tell me how you do it.

Kelly Halderman, M.D., CCN

I go to visualcontrasttest.com and I pay my $13, and, you know, you’ll pass/fail. And we could probably do a whole entire lecture on that, but I will just say, it’s worth people’s time to go explore that, it’s worth practitioner’s time to just go and look at this test. And it’s in this paper by Dr. Heyman, they talk about the evaluation, I digress. So what they’re saying is that there is a similarity between the CIRS presentation and the presentation with people’s long haul and Dr. Heyman and Dr. Shoemaker have found water damaged buildings are really a key factor in people who have a long standing that chronic inflammatory response. Like they cannot get out of it. There’s genetic susceptibility that has to go along with that, but very interesting because it’s a paradigm where then you can think, okay, if they have the, they have the secret sauce for how we understand and treat CIRS, and these are very much alike in their signatures and what’s going on biochemically, the TGF-beta increase, like all these things are similar that maybe we can take what they’re saying and apply it to our patients who are struggling with long haul. So now I’m gonna turn this question to you, Dr. Cook and say, “Okay, well, how did you feel about the paper?”

Matthew Cook, M.D.

Okay, I loved it and I thought it was very appropriate for this moment. So then I’m gonna echo what you said just to, and so then we can go back and forth on this, ’cause I think this is a crucial thing for people to understand. And so there was two stories, so one, is this person that just is in a water damage building and they got exposed to mold. Hypothetically, that person they breezed a mold and they had a biofilm in their nose. And then next thing you know, they’ve got mold in their body that, but it’s not just mold, is mold and then actinomyces and gram-negative rods, this is the Heyman Shoemaker literature. And thank you to them ’cause I think they’ve, they’re very important in furthering this line of thought. So then that basically those mycotoxins and then the bacterial byproducts causes inflammation, particularly in the central nervous system, and so then what does that inflammation do? It makes it so you have problems with your visual fields and so you can’t see well, so you, and as, and there’s a past fail on this test that you mentioned the VCS, which I think is very important. And so then when that happens, it’s almost incapacitating for some people because of inflammation in the brain. 

And so then this, I think very interesting work done by, with the GENIE test is that they look and they see that we’re printing the inflammatory side of the genome. And so then that, the inflammatory genes are all upregulated and so they’re all in red on that GENIE test. Now, when I heard, when I first heard this literature and I go, “Oh, that’s exactly the same thing that’s happening in long COVID and Epstein Barr and CMV and Lyme disease.” And then we know that so many people with Lyme disease end up having a bunch of those other things or so many people with mold have those other things. I remember that, I think God bless all of those residents that are living in moldy apartments right now like we were. And so, but so then, so then interestingly long COVID looks just like that and the people who get, the COVID long haulers, so then the question is, did they already have that in the background or does long COVID all by itself without any of those things cause a similar mechanism?

Kelly Halderman, M.D., CCN

That’s the jugular question. That is it right there, that’s it and I don’t know.

Matthew Cook, M.D.

I’m gonna say it’s a little bit of both because when I test, when we’ve been diving into this, some people have a bunch of those things or all of them and some people don’t.

Kelly Halderman, M.D., CCN

Interesting.

Matthew Cook, M.D.

And so then, you know, are you familiar with the Bruce Patterson research? So then, what he’s saying is that your, another white blood cell, the monocytes, can come in and then they pick up the spike protein and then that dysregulated them. So now we’ve got multiple aspects of the immune system getting dysregulated and potentially spinning outta control and they can go all over the body cause symptoms wherever they go.

Kelly Halderman, M.D., CCN

Right, right.

Matthew Cook, M.D.

Now, my, now, guess what is the final common pathway that fixes these people who were exposed to water damage building that have mold and chronic mold symptoms? A peptide, VIP.

Kelly Halderman, M.D., CCN

That’s right, that’s right, VIP, that’s great.

Matthew Cook, M.D.

So, and so then that one, and so then suddenly you begin to say, oh, okay, what we really need to do is we need to take all of those other conditions, look at mold, look at the COVID long haulers, the reality that I’m seeing is they’re having a similar immune signature with their blood testing, so they’re having high TGF-beta, they’re having high IL-6, they’re RANTES. And so they’re, you have all of these aspects that are getting triggered up and they’re fairly, if they’re not the same, they’re like brothers and sisters and cousins and so then what we need to do is down regulate and start to balance immune function. And interestingly, when you do that, then a lot of the side effects and, you know, for these chronic mold people a lot of times they will have POTS or they’ll, postural orthostatic hypertension where they stand up and pass out, so then what will happen is that with many of these people, they also have mass vacuolization and postal orthostatic hypertension, which are common side effects across all of these populations. And interestingly, traditionally we haven’t really used peptides early in any of these CIRS patients because we use VIP at the very end.

Kelly Halderman, M.D., CCN

Sure.

Matthew Cook, M.D.

But the bio regulators have an opportunity to come in sooner and start to support people both on the immune peptide side, and then the bio regulator peptide side.

Kelly Halderman, M.D., CCN

100%, I mean, that’s very key and I think that’s something that, you know, we should lead the movement in that because I see no reason, you know, looking back at the cause of my illness, I mean, I use on a daily basis or weekly basis, I still use about four different peptides. They’re extremely important to why I stay healthy. And I think looking at the pathogenesis, implementing in Cmax, some LL-37, like those would be extremely effective right out of the gate.

Matthew Cook, M.D.

Okay, so tell me, so then when you got your diagnosis, what, so then peptides helped, so we gotta go into that, and then what do you really credit? How did you, I mean, because maybe we buried the lead, like we gotta like dive into how did you do it? Like what worked for you?

Kelly Halderman, M.D., CCN

Yeah, and I think that that’s a question I get asked all the time and my answer is I did a 100 different things. I completely overhauled my metabolism, I will say that, is that I stopped drinking Mountain Dew in the middle of the night, delivering babies, you know, I balanced my blood sugar, I just implemented intermittent fasting, I think I really upregulated my autophagy, I started to get into sauna, I did hot and cold therapy, you know, I started to exercise as tolerated, I was already exercising, but I mean, like more of a strategy of like longevity, you know, I wasn’t going to a gym like killing myself. And so, and then I started nutrient that I tried to really optimize my nutrients, like making sure my body had the correct nutrients. I really never respected the, you know, vitamins and things. I thought I was kind of like, well, you know, we get that from our food, but, you know, the, it’s nutritional biochemistry, it’s all biochemistry. Your machinery of your body works using these vitamins and minerals. So now I take that very seriously, the status of my electrolytes and things. And again, it wasn’t one thing, but I will say this is that, you know, I’ve used stem cells, the ozone therapy, you know, every IV that I could do I tried it on myself and, you know, peptides have really given me an edge I’ve never even dreamt that I would have. And that’s probably in the last two years of using them. And I’m just so impressed and that’s why I’m like, yes, I’ll be on this summit, I absolutely love peptides, I apply them to my patients, I apply them to myself, they save my life from COVID, you know? I mean, well, they save me a lot of more days I think-

Matthew Cook, M.D.

More days.

Kelly Halderman, M.D., CCN

Yeah.

Matthew Cook, M.D.

You use Cmax and that’s a, for the MS conversation, I think that that’s an interesting one. Very, what was your, how do you feel when you take it? Tell me about your thoughts about how it works and-

Kelly Halderman, M.D., CCN

You know, having chronic Lyme and mold for so long, I think because I really didn’t get like an accurate diagnosis for about like three or four years. It really took a toll on my neurological system. And I remember at one point being so ill that I couldn’t figure out when someone was trying to tell me their phone number, I couldn’t figure out what a seven was. So I had some major neurological impairment. And so I think that even using Cmax 12 years or how many years later, that I’m getting a benefit because of the neurological pathways. And you could, I might turn this question to you, back to you in the mechanism, but tangibly, I feel sharper, I wear an Oura Ring so I watch my sleep. My deep sleep in particular has gone up, so I think my glymphatics are actually draining my brain at night. And so I’m not sure if the mechanisms Cmax increases BDNF, but I sure feel sharp as a cat.

Matthew Cook, M.D.

It does, it does, yeah.

Kelly Halderman, M.D., CCN

And that’s what I’m feeling definitely.

Matthew Cook, M.D.

The, the, I’ll see, I have seen a lot of people, Cmax increases BDNF. However, I see a lot of people will tell me that they sleep better with it. And then sometimes they’ll sleep better with Cmax, sometimes they’ll sleep better with Cmax and Clank.

Kelly Halderman, M.D., CCN

Okay.

Matthew Cook, M.D.

Which has a GABA mechanism. It’s interesting to think about your story with the whole conversation of MS. And I think it’s important also to echo this idea of the diagnosis of Lyme disease, which is this fact this caused by a bacteria called Borrelia, but it’s a tick born infection, and a lot of that in Western Montana where I come from.

Kelly Halderman, M.D., CCN

Oh, yeah.

Matthew Cook, M.D.

But when I hear that somebody has MS, then it’s like, do not pass going into that, collect $200, you’ve gotta go figure out if they’ve got mold, figure out if they’ve got Lyme, ’cause typically almost always they’ll have one of those two.

Kelly Halderman, M.D., CCN

Agreed.

Matthew Cook, M.D.

Almost always. Well, it’s a total 100% delight to interview you. And I’m so happy with how well you’re doing and all of the work that you’re doing and keep up the good work because we need it.

Kelly Halderman, M.D., CCN

Thank you so much, Dr. Cook, it was a pleasure and like I started our conversation out yesterday by saying like, I’m your number one fan right here and that, you know, the contributions that you make, I apply them and I help people. And so there’s no better compliment than utilizing your knowledge and actually putting it into action. And I’m just, I’m very thankful for your work.

Matthew Cook, M.D.

Aww, thanks so much, have an awesome day.

Kelly Halderman, M.D., CCN

All right, you too.