Diet, Fasting & Supplements for Autophagy

Dr. Kelly Halderman

Yeah, definitely. If you would have seen me in 2012 bedridden, you wouldn’t have said the same thing about Dr. Kelly at that point. I was practicing medicine and loving it. However, I started to come down with some very strange symptoms. I developed foot drop. I developed migraines, just debilitating migraines out of nowhere. I was on call delivering a baby, and all of a sudden I got this scotoma from the migraine came out of nowhere. I had to grab my nurse to grab the baby. And I thought this is not working, right? So I was shuffled to the best neurologist at the Mayo Clinic, was told that I had MS, multiple sclerosis, and I needed to get my affairs in order, go home and be with my children. I was in my late 20s and that diagnosis of a death sentence did not work for me whatsoever.

All the tools that I had learned that were in my allopathic pocket at that time, they didn’t serve me well. And I needed to go and learn more. I needed to learn about detoxification and nutrition. And so I did. I went and got a naturopathic medical degree and I used those principles. And one of the principles we’re gonna talk about today is autophagy which is so critically important as to why I’m still here on this earth, why I still get to do these really neat podcasts. And I can’t wait to share with you and our listeners about autophagy and how it was one of the central tenants that took me from illness to wellness.

Joseph M. Raffaele, M.D.

Well, I’m looking forward to that. That’s quite a story. You left and got a naturopathic degree, and then, oh, you currently work in clinical nutrition. Tell us about, excuse me, excuse me, about why autophagy is such an important part. I know it’s often mentioned in the hallmarks of aging and it’s sort of an integral part of things in the aging process. Why don’t give our listeners a little bit of an introduction to it?

Dr. Kelly Halderman

Sure, so the Nobel Prize in Physiology or Medicine was actually given to Dr. Yoshinori Ohsumi in 2016. So, guys, this wasn’t that long ago. He discovered the principles that underline autophagy and what autophagy is. So I’m gonna give you the scientific version, and then I’m gonna give you the version that I can communicate to my teenagers. Okay, scientific version is autophagy is the process where cytoplasmic components, whether that be old mitochondrial parts, old vacuoles and things, or viral components, pathogen components, they are engulfed in double membranes, vesicles, they’re engulfed in vesicles, and they’re delivered to the lysosomes of the cell. And the lysosomes will then degrade these old parts. And what’s interesting about that is that that process, which sounds rather simple, is implicated in many disease processes in PubMed. Go ahead and type it in. It’s cardiovascular disease and autophagy, cancer and autophagy impairment, autoimmune disease and immune diseases in autophagy impairment. 

And so when I described this to my teenagers, I say, it’s like this, guys, it’s like your body is full of little vacuums, but you need to turn on the switch of the vacuum and you need to turn that switch on and actually move the vacuum. A lot of things that you’re doing when you’re eating all those Doritos, when you’re slamming all that high fructose corn syrup, guys, it’s not turning your vacuums on, and your cells are becoming full of debris, right? And that’s why we talk about this in the context of anti-aging. And as we age, our autophagy process naturally, unfortunately, slows down a bit. 

So we have to do everything we can right here right now to upregulate the autophagy process in our bodies, and that starts with knowing what is autophagy, what turns it on, but it also has to do with a process called mTOR. So mTOR is the opposing process to autophagy. So autophagy is turn on the vacuums, get vacuuming, get that cellular debris out of there, get those viral components out of there. The opposing mechanism is called mTOR, your mTOR pathway. Neither one is good or bad. So this is where the whole autophagy thing gets butchered. When people try and teach about it on the internet, what you’ll learn is autophagy, we have to have, everything we do has to be autophagy, we have the cellular cleaning. Yes, of course we do. But mTOR is exquisitely important in our body. mTOR is the building block. It stands for mammalian target of rapamycin, which is a mouthful, but it basically means that we are building. When the egg and the sperm come together, if we didn’t have mTOR pathways, we’d have no baby, we’d have no pregnancies. Muscle people, bodybuilders rely on mTOR. They rely on the process of mTOR to build that muscle. And as we age, as you know, Dr. Rafaelle, it’s so important that we not overdrive either one of these. We wanna keep our muscle mass. We wanna definitely keep the autophagy going.

Joseph M. Raffaele, M.D.

I think that’s a really important point. We hear a lot about inhibiting mTOR, cleaning up cells, but there’s two sides of the equation really. I mean, we also hear about growth hormone and IGF-1 being bad for you and you wanna lower that. And that’s obviously a complicated nuanced discussion, but it’s sort of a balance between longevity and keeping the cells healthy, but also performance. I mean, we know that mTOR, like you said, you’re not gonna go very far if you wanna be a big, strong functioning athlete or, and we know that maintaining your muscle mass over a lifetime is very important ’cause sarcopenia is a really bad thing. So balancing the two of those, you have to clean the junk up, but also make sure that the growth factors are actually working to maintain health, but that often gets lost in the discussion. So I’m glad you brought that up. But what are some of the strategies that can help to turn on autophagy? You mentioned high fructose corn syrup and other sort of junk foods that could cause a problem, but how do you go about using it in your practice and what do you do to turn on autophagy?

Dr. Kelly Halderman

Sure, so I think one of the important things is to look at what actually is overdriving mTOR first, and then we’re gonna go into the autophagy. So the overdriving of mTOR, again these two processes shut each other off in essence. If you really wanna make it pretty tangible for people, just think of them as shutting each other off. Okay, so if we’re going to turn on mTOR, what are the types of things that turn on mTOR? Well, I already mentioned high fructose corn syrup. It’s gonna turn on your mTOR, decrease your ability to cellular clean. Iron-enriched foods. So when you’re overdriving, when you’re consuming too much iron-enriched foods, which are your processed foods, that’ll turn on your mTOR. Too much methylfolate, too much methylated vitamins and things can actually turn on mTOR. Glutamates, so think of people who are drinking copious amounts of bone broth all day long. That can turn it on. 

Overconsumption of protein. So methionine is something that will turn on the switch with mTOR. Unfortunately, pesticides and plastics are really something that our environment we’re living in right now, we’re really at risk of just living on this planet earth of overdriving our mTOR, and so does EMF. There’s some papers that suggest that EMF is actually overdriving the mTOR. Now again if you’re a child and you want to be in a growth pattern, like this is where the nuance comes in, right? We’re not trying to avoid all things that turn on mTOR. And certainly again when we’re talking about having someone in front of us who may be 60 years old and wants to go down the anti-aging pathway, but again we have to take into account we don’t want them to muscle waste, right? We don’t want them.

Joseph M. Raffaele, M.D.

Right.

Dr. Kelly Halderman

We want them to be able to still continue to build muscle. So I think of it as some of these are dietary factors, right? So across the board, let’s get rid of that high fructose corn syrup. Let’s have a very balanced diet. So the Mediterranean diet is known and has really good research and longevity research behind it. And one of the reasons they think is that the polyamines are actually very helpful for turning off mTOR or turning on autophagy. And one of the components people are talking about a lot now turning on autophagy is spermidine. So spermidine is naturally found in a lot of the dietary components in the Mediterranean diet. So that’s my plug for the Mediterranean diet. Just eat whole foods, right? So I learned a lot personally because I had genetic weaknesses in some of the genes that are responsible, I had some SNPs responsible for those mTOR pathways. So I have iron processing issues, the HFE genes. I have some PON1 issues with how I deal with pesticides. So it’s like a double whammy, right? It’s like if 

I actually met MS, the root cause was mold and Lyme. I mean, the usual. So I was at risk because not only did I have Lyme and mold, which I didn’t know about, but my body couldn’t clean up the cellular debris. Well-intended doctors, brilliant doctors were putting me on bone broth and having me take copious amounts of methylfolate and methyl B12, and not recognizing that my body was actually, it was backfiring in a way. So when I read about the studies correlating Lyme disease with people with genetic weaknesses in mTOR, I took a step back and I went, wow, all right, I have to really make sure that I’m getting in my sauna. 

I’m sweating out all these pesticides, that I’m really making sure that I’m taking nutrients to help my body flush out any of the residual pesticides in my diet. I need to make sure I’m getting a handle on how much processed foods with iron enriched, iron in there. I need to make sure I’m not consuming the high fructose corn syrup. Dairy can actually, and it’s just intuitive. Like baby cows drink the milk so they can get bigger, right? So dairy I had to give that up too, because it was overdriving the mTOR. So it wasn’t anything where it was like one magic thing that I was doing, but I will say is that looking at the autophagy. 

So let’s go right into there. So what did I do to strengthen autophagy? Well, again, I dampened down on my mTOR pathway, and then I implemented in time-restricted eating. So those little vacuum switches, they really are sensitive to when we’re eating, and they are best turned on, autophagy is best turned on when we’re in a fasted state. So I say to people, try and get into a tighter eating window, right? So Valter Longo did a talk that I just listened to that said that over 18 hours of time-restricted eating, people had a higher amount of gallstones. So be careful, right? Make sure your bile is flowing. I’ve also done a lot of work on bile, making sure that that’s flowing. So you wanna make sure your detoxification system is working. But, again, to go back to it, so I tightened my eating window with autophagy to incite the process of autophagy. I also made sure that I exercise. And again it’s something we all have to do. 

We have to get that strategy in our lives. And I noticed when I started doing these things and I started taking things like resveratrol, quercetin. I love a product called Autophagy Assist from Professional Health Products. When I took that especially in the fasted state, I noticed, I mean, okay, so there’s three signs that I use to look at someone to know that they might have some autophagy issues. So look at the backs of your hands. If you have little age spots all over your hands, that’s a sign that you might have some impaired autophagy. Now it’s not perfect, but I will say this is that my hands, I looked like I was 10 years older than I really was. I was, like, well. Well, I had Lyme. It started rapidly. Just my skin was just looking terrible. I started to implement in this balancing of autophagy versus mTOR. My hands are like almost completely clear. So that’s just a really

Joseph M. Raffaele, M.D.

That’s interesting.

Dr. Kelly Halderman

Neat time where you can kinda look at someone and go, oh. And then during the holidays when I kinda slipped off the wagon, I really do see it. Like I take pictures and I see a little bit of spots coming back. Another way you can know without doing your genetics if you’re at risk for someone who needs to upregulate your autophagy is how are your liver enzymes doing? How is your GGT? How’s your muscle mass? And finally are you obese or overweight? Those are some signs that your autophagy can definitely be impaired.

Joseph M. Raffaele, M.D.

It’s interesting, right? But I guess one of the problems with trying to clinically manage autophagy, ’cause those are interesting pearls that you gave, but there really isn’t any blood test particularly. I guess for telomeres, there’s telomere length. You can even do a telomerase activation. For other hallmarks of aging, there are things. But mitochondrial function and autophagy, it’s difficult. And you mentioned the time-restricted eating. That’s a great thing to do. I do do that as well. But there’s some controversy about how long you really need to be in a fasted state before autophagy kicks in. Some people think it’s really actual fasting of 48 hours, 36, 48 hours before autophagy really kicks in. But how do we know? We don’t have a marker for it.

Dr. Kelly Halderman

Right, and we know that it does take at least three days, I think, of water fasting to get stem cell activation. So we do have that data.

Joseph M. Raffaele, M.D.

Right.

Dr. Kelly Halderman

So I’m completely not against fasting. I think it needs to be under the care of a licensed healthcare practitioner because of all like the blood sugar issues and other things like that. But with autophagy, we just don’t know at this point, but there’s a lot of other good data that says that like really getting down to a time-restricted feeding, and these are a lot of mirroring studies that we have to do, but improvements in blood sugar. I typically wear a CGM, a continuous glucose monitor. So I’m really looking at what the autophagy, what that time-restricted eating is doing to that. 

So I think that is a really important point. We’re not quite sure but the data is leaning toward it. And again typically in medicine, we have to wait 17 years to get really good clinical outcome and data and things that we should do into the doctor’s offices. So 2016 wasn’t that long ago. And that was the New England Journal of medicine who says that, oh, hey, it takes 17 years to get this into your doctor’s office. So these are the types of things where if it walks like a duck and quacks like a duck, it probably is, but we really don’t have the study to kind of like show everyone, but again it’s looking better and better. And I mean, look at all the data that Valter Longo is coming out with the fasting-mimicking diet. It’s really phenomenal.

Joseph M. Raffaele, M.D.

Yeah, I wanted to just go back to a couple things you said. One was, I mean, I think mTOR is kind of a nutrient sort of intermediate nutrient sensor. So you mentioned being overfed, high fructose corn syrup, high protein. And so I know that those are all things that increase mTOR. I didn’t know, how do pesticide do that?

Dr. Kelly Halderman

So there’s papers that show that pesticides will just drive the mTOR, the mTOR pathway. Yeah, we can link to those. For everything I said, there’s studies to everything that I said.

Joseph M. Raffaele, M.D.

Yeah, I was just curious what it was.

Dr. Kelly Halderman

Yeah.

Joseph M. Raffaele, M.D.

And then also just for our listeners, can you just describe what spermidine is since

Dr. Kelly Halderman

Yeah.

Joseph M. Raffaele, M.D.

Not everybody knows what it is. I know it’s like a hot molecule right now.

Dr. Kelly Halderman

Spermidine polyamine.

Joseph M. Raffaele, M.D.

So to speak.

Dr. Kelly Halderman

So spermidine is a polyamine. It’s found in wheat germ is the number one place that it is found. It’s also found in mushrooms and soy. So again there’s a company I believe that now sells spermidine, but it is from wheat germs. You have to be careful if you’re gluten sensitive. If you have celiac, definitely be very careful. And so that’s pretty new. We didn’t have that, but we do have the data again from the Mediterranean diet which we know that is very high in the polyamines. And I will say this is that spermidine goes beyond autophagy. I mean, in mirroring studies, we’re looking at lung fibrosis reversal. I mean, it’s really, the data is very copious when it comes to spermidine. So I think it kinda drives home where, sure, we can go after all these fancy nutrients and things. And if I didn’t say berberine, that is literally one of my favorite nutrients.

Joseph M. Raffaele, M.D.

Yeah, me too.

Dr. Kelly Halderman

Yeah, absolutely. I mean, it’s like metformin where the anti-aging data is really, really great. But again so there are select nutrients where I think they’re really important. Berberine is one of them. But, however, I think it goes back to lifestyle, and I think it goes back to the epigenetic influence of the things that we choose to put on our plate.

Joseph M. Raffaele, M.D.

Yeah, for sure. So autophagy is cleaning up junk in your cells. There’s also mitophagy which is, I guess, cleaning up mitochondria. Talk about the difference between those. And then I guess, but mitochondria are also very much involved in the whole process of apoptosis which is another way of cleaning up the cell by actually getting rid of it if it’s damaged beyond repair, and that gets into the whole field of cell analytics. A lot of things you’ve mentioned, quercetin, I don’t know if you mentioned fisetin, but other things in that field, in that category, can move it from beyond cleaning up the cell to actually getting rid of the cell. And in that regard, you wanna be a little bit careful about it. I mean, I know that senolysis is often done in cycles because of the stuff

Dr. Kelly Halderman

Sure.

Joseph M. Raffaele, M.D.

That you mentioned. So let’s talk a little bit about that and how you approach that clinically. I mean, like, certain things you would take all the time, perhaps berberine, but other things maybe you don’t wanna take all the time. You don’t wanna be, like you said, you don’t wanna be inhibiting mTOR when you’re doing muscle building cycle or doing it sort of an anabolic cycle of trying to put on muscle. So how do you approach that in your practice?

Dr. Kelly Halderman

Absolutely, it is so specific to the person who is sitting in front of me and their goals and where they’re at and their age and their risk factors. So if I have a person in their 30s who’s looking to continue to build muscle and they really want to increase that, I mean, they’re gonna have a whole different balancing protocol than let’s say like a 70-year-old with prostate cancer where we really look at them as, okay. we have to really go hard on the autophagy, go hard on that end, whereas the mTOR, we don’t really need. It’s kinda like what’s the most emergent at this point? Like what are we gonna deal with? So that again for our listeners too, there’s no hard and fast rule to this at all. I think of myself because I’ve had chronic illness. I find every day really hard to stay healthy. I do about a million things it feels sometimes to stay in this and live in the environment we live in and maintain. So my strategy for myself is more of a lifestyle of managing my mtor and then promoting my autophagy. Now I will cycle through. That’s a great point, Dr. Rafaelle, is I will also cycle through. 

So if I’m going to do, I do a quarterly water fast. And so when I’m doing that water fast, I’m definitely going to make sure that I’m really promoting all hands on deck with the autophagy, make sure that that’s really optimized. But again when you get off of that, because it was so heavy on the autophagy, I wanna make sure I’m not losing any of my muscle mass. Maybe I’ll go into more a training protocol where it’s harder so I will balance in the mTOR. And again, it can be difficult because there’s no magical lab test. 

I can’t draw my blood and go, oh, okay, so we need to go seven points below on your mTOR, and we need to go five points above. You need to have a savvy practitioner who is reading the literature, who is learning, who is listening to things like the summit, right, to get all this cutting and data information again, because we don’t wanna do this. We don’t wanna hurt anyone. Of course that’s our Hippocratic oath. In fact, so I would say that it, again it’s depending on who’s sitting in front of me. So if I have someone who’s gonna be in a bodybuilding competition, we’re not gonna really worry. They have no chronic disease. We’re not gonna really worry so much about the autophagy. I don’t even know if I’d have them take down their eating window because we’re trying to accomplish a different goal for them.

Joseph M. Raffaele, M.D.

Yeah, I mean, that’s a great point personalizing to each patient and their goals. Just out of curiosity, how long a water fast do you do? How does it feel? What’s your experience of it? You’ve obviously seen different stuff.

Dr. Kelly Halderman

Well, the first three days are awful. To be honest, it’s just awful. You just don’t wanna be, just don’t call Dr. Kelly in the first three days of the water fast. Then on day three and four and five, I usually can get to five. I try and get to seven depending on what’s going on in my life. I feel amazing. My BDNF and my brain is just rocking. And I mean, like, I feel like my little cellular vacuums, my autophagy is just going after. And again I have genetic weaknesses, so if I didn’t mention those specific SNPs, I want to right now, so it’s the ULK1. I mean, I have them all. It’s almost like I have to do this so.

Joseph M. Raffaele, M.D.

What is the ULK1 again?

Dr. Kelly Halderman

ULK1, ULK2, ATG, and MAPK3 and 8.

Joseph M. Raffaele, M.D.

And those are SNPs that do, I mean, I recognize these as autophagy ones in the MAP kinase pathways, but the ULK1 is? What is that?

Dr. Kelly Halderman

The ULK, they’re definitely, they’re definitely genes that have to do with the process of autophagy. There is a wonderful paper that we can link to in PubMed where it talks about, it even groups them into the known autophagy-related SNPs. And then they go into the studies on cardiovascular disease. We’re starting to think about this. We’re starting to go, okay, the literature is robust with the studies that show autophagy linked to, again, cardiovascular disease, cancer, immune issues. So if they’re linked, what can we do again? Now we’re thinking probably in the pharmaceutical mindset, looking at like the studies in PubMed, but again so we’re like, what drug can we use to promote autophagy? Well, I’ll tell you this, guys, there’s no better drug out there than fasting, exercise at this point. There’s no better drug than this. And then these natural compounds, berberine again, resveratrol, quercetin. Quercetin is an ANO4. We could all use a little more ANO4 in our life in this pandemic right now.

Joseph M. Raffaele, M.D.

For our listeners, what doses are you using of those? And are you modulating them based on goals? I mean, quercetins are around 500 milligrams. Maybe sometimes people do 1,000. There was a study published where they looked at quercetin, this and quercetin study, and they cycled it though. So it’s kind of interesting. What doses do you normally use?

Dr. Kelly Halderman

I use five, about 500 milligrams. And again it depends on is this person did they have an illness right now? Or are we doing maintenance? And berberine is completely specific to the person that I’m working with as well. I mean, there’s a lot of studies showing like what ranges and things but, and I’m always searching literature. I’m always like, okay, do we have any clinical studies? Do we have any studies in people? Like what are we looking at the doses? And so I look to people, at you, and I’ll see you next week at A4M. I grab people like you and say, hey, what do you know about this? What do you know? And I’ll always looking to my colleagues to help refine what I’m doing. I’m very grateful for minds like yourself.

Joseph M. Raffaele, M.D.

And then what company do you use to or how did you get your SNPs? These specific ones? And is there something, a company you like that gives us sort of good annotation of them so that people know what to do with it?

Dr. Kelly Halderman

Sure, so I use functional genomic analysis and that has to be ordered by a licensed healthcare practitioner. I am on the fence right now with a couple non-licensed companies. So I’m not gonna mention the name, any of the names quite yet because I’m just not satisfied. I’m trying to actually help them really, really get a really good test. So there’s a lot out there, but I would say that if you’re searching for a direct-to-consumer, we call a DNA test, see if they have autophagy SNPs, see if they have what we’re looking at and make sure that they do. I think it’s important that we have that. It’s just more information. 

And again it made sense to me why I got Lyme disease and I ended up bedridden. There’s a lot of more genetics behind that. We could talk for hours about that. But one of the things I just had such weakness in my body’s ability to clean up cellular debris. And it makes sense. If you’re drowning in cellular debris, the chronic illness might be chronic for you, and then this other person, it could just be, oh, I had Lyme and I got over it. Again there’s a lot of things that go into that, like work of Andy Heyman and the HLA and all those things. But, yeah, I really, really, I think of my autophagy everyday.

Joseph M. Raffaele, M.D.

It’s kinda like the differential vulnerability to COVID. People

Dr. Kelly Halderman

Yes.

Joseph M. Raffaele, M.D.

Some people have senescent immune systems, they have overreaction from their inflammatory pathways, and typically they’re older people. They’re not always older people, same things. I’ve had obviously quite a few patients that had Lyme and chronic Lyme. Some people, I live in the East Coast here, so people get Lyme all the time. And many patients sort of get Lyme, they take doxycycline and they’re fine. And they do that over and over again.

Dr. Kelly Halderman

Yeah.

Joseph M. Raffaele, M.D.

And other ones get it once and they’re done. They need chronic Lyme doctors. So it obviously has something to do with genetic predisposition, lifestyle, other things. So it’s a really interesting point that you make there. I’m just curious, not having myself actually done a multi-day fast, are you able to work when you do that? Probably not the first few days. Do you go back to the office when you’re feeling better? The fourth through sixth days or what do you do?

Dr. Kelly Halderman

I will say this is that when I started to implement back in I think it was 2015 time-restricted eating, I thought I was gonna die in the morning when I didn’t have like coffee with the creamer. And I mean, I felt horrible. I was so in the fermentation process, right? So we have oxidative phosphorylation, which is what we should be in, we should be able to burn fats. And I was terrible at it because I was sugar addicted. So when I was in that state, it was so hard to even get a 12-hour feeding window. So overtime getting my eating window tighter, so now it’s around eight hours. And again don’t just do it because I’m doing it. Really you have to be very careful ’cause it can backfire. What my point is is that now when I’m doing the water fast, I’ve trained my body. It’s like I didn’t just jump out of bed and just decide to run a marathon. I have been doing these mini-marathons for years now.

Joseph M. Raffaele, M.D.

So you increased from a one-day fast to then try a two-day fast and then a three-day fast. You didn’t just all of a sudden I’m gonna do a seven-day fast, right?

Dr. Kelly Halderman

That’s right. That’s a very important point.

Joseph M. Raffaele, M.D.

I mean, I totally echo your experience with that. I was for a long time somebody had to get up and have something to eat. And then I started about two years to do intermittent fasting. And now it does take, your body has to, you have to adjust to it, changes in pathways, and how your mitochondria work. And now I haven’t eaten since eight o’clock last night and I’m sitting here perfectly fine and happy. I’m not dying for lunch to show up. So for the listeners and for talking to their patients, when I tell patients this, I say, “Look, “it’s not gonna be that easy. “And maybe don’t do it, start doing it every day. “You do the days that you feel like you can do it.”

Dr. Kelly Halderman

Right.

Joseph M. Raffaele, M.D.

You will gradually acclimate to it. I think it takes like a month or two, something like that before it starts getting easier. Each time it gets easier. But it is really pretty fascinating how those changes take place. And I guess that the first few days suck no matter what in a long-term fast, but I guess you get better at it. So pretty interesting.

Dr. Kelly Halderman

Yeah.

Joseph M. Raffaele, M.D.

We touched on quercetins, berberine, all these interesting molecules.

Dr. Kelly Halderman

Dr. Rafaelle, you did say something about COVID. So I wanted to bring up a study

Joseph M. Raffaele, M.D.

Okay, sure.

Dr. Kelly Halderman

That I’ve.

Joseph M. Raffaele, M.D.

Oops, hold on a second there. I lost you, Kelly. Can you?

Dr. Kelly Halderman

Anyone?

Joseph M. Raffaele, M.D.

Yeah, okay, here we go.

Dr. Kelly Halderman

Oop, did I cut out?

Joseph M. Raffaele, M.D.

You’re back, you’re back.

Dr. Kelly Halderman

Okay. So this article is recently published. It was October 2021. And it’s called “Harnessing Autophagy to Fight SARS-CoV-2.”

Joseph M. Raffaele, M.D.

Interesting.

Dr. Kelly Halderman

So this article, again, we’re living in these times where we have to really, we’re in the fight of our lives. We need to have our bodies working in the most optimal state that we can every single day. And I think this is a really great study that points home that we’re thinking about how important, again, I started off this conversation talking about what autophagy is and how it’s responsible for cleaning up viral debris as well. And so looking at that and then bringing that in as another strategy to help have our best health during this pandemic, I think that’s worth mentioning because we wanna do everything we can.

Joseph M. Raffaele, M.D.

And so what did the paper said? Was there sort of a theoretical paper about it or was there?

Dr. Kelly Halderman

So the paper mentioned that autophagy is linked to all these chronic diseases. And so potentially we wanted to use something that could up-regulate autophagy because there’s papers showing that autophagy impacts the immune system. It’s the start of the conversation of, it’s again this is probably they’re looking at making a drug, right? They’re looking at trying to make a drug that would upregulate autophagy to help with COVID. But again we have a lot of strategies that we can use right now. And like I said, all those things that overdrive mTOR, a lot of them start with your fork. You just

Joseph M. Raffaele, M.D.

Right.

Dr. Kelly Halderman

Use it better with what you’re putting in your body. Your environment, being really cautious about the pesticides and things. So just making the best choices that you can day by day, and then looking at the benefits down the line, because, again, if you know something is correlated, so we know we got autophagy, when we have genetic weaknesses, we’re seeing that that we have increased risk amount of cardiovascular cancer, all these things. So I don’t think it’s a bad strategy to just look at the overall 30,000 foot view, look down, and say to yourself, like, have someone look at your hands, have someone do your LFTs, a practitioner look at your liver enzymes, your GGT, have someone do your body mass index. And again if everything points to the fact that you could use some upregulation of this very important system, this very important mechanism, and this is a highly conserved mechanism, meaning it’s biologically so important. Some of these mechanisms, I mean, the mTOR pathway, the autophagy, they’re highly conserved because they’re important that we’re still around here as a species.

Joseph M. Raffaele, M.D.

Yeah.

Dr. Kelly Halderman

And we really, yeah.

Joseph M. Raffaele, M.D.

So since we’ve covered, as I mentioned, quercetin and the other ones, did you use, I never know how people say it, fisetin or faisetin?

Dr. Kelly Halderman

Fisetin.

Joseph M. Raffaele, M.D.

Did you use that? And what’s your experience with it?

Dr. Kelly Halderman

So, Dr. Joe Cleaver recently this summer turned me on to fisetin. So I’ve just started getting my experience with it. I think it’s a fantastic nutrient. I know it’s naturally found in strawberries I wanna say.

Joseph M. Raffaele, M.D.

Right.

Dr. Kelly Halderman

But, again, my experience with it is pretty fresh. I put myself on it and the TA-65, and I felt like I had some good results. When I say good results, I always think, well, what does that mean for someone? Well, I had a brighter brain fog. I just feel like my brain is just so locked on. My sleep is on point. I wear an aura ring. I tract my sleep. I mean, like, if I don’t get a good night’s sleep, I’m like what did I do wrong? So I use objective data when I’m trying things. I feel like the combination of the fisetin with the TA-65 really, really helped. And then I’m also upregulating my Nrf2 pathway. 

So the Nrf2 pathway is the anti-aging pathway in the body, the antioxidant pathway in the body. Upregulation of it will increase your levels of glutathione, SOD, hydrogen peroxide downstream. So what you’re doing is you’re increasing your antioxidants, protecting your mitochondria. You don’t wanna overdo that pathway either because you can’t just flood your body with antioxidants. It’s actually gonna backfire, right? You need things that are supposed to degrade to degrade. So I do cycle the Nrf2 upregulation in that pathway. I cycle that one for sure.

Joseph M. Raffaele, M.D.

And what dose of fisetin do you use?

Dr. Kelly Halderman

Whatever Dr. Cleaver recommended.

Joseph M. Raffaele, M.D.

I don’t know off the top of my head, I’m just curious. It’s interesting that you mentioned TA-65 and fisetin, or fisetin is supposed to be one of the strongest sort of natural cytolytic molecules. And the reason that I think it’s interesting is because T-65 is important for mitochondrial biogenesis, I mean, not T-65, telomere length, and then T-65 through augmenting telomere length, or maintaining it, in some cases improving it, it improves your mitochondrial biogenesis. On the other hand, you wanna get rid of the mitochondria that are not functioning and damaged. And so those two together, people often take care of the sort of housekeeping side of things, but forget about the other side of things.

Dr. Kelly Halderman

Yeah.

Joseph M. Raffaele, M.D.

I kinda maybe liken it a little bit to bones where you have the osteoclast that come in and clean up damaged bone, but you have to have the osteoblast come in, so it’s estrodiol for the class and testosterone and other growth factors, progesterone, growth hormone through IGF-1 increasing. And that’s sort of the same thing that you’re kind of doing. You have to look at both sides of the equation which is I think really good. I’m glad that you got that interesting sort of clinical improvement in yourself. I’ll have to see about that. I’m gonna give it a try myself. Speaking of giving things a try, I mean, we’re talking about mTOR, which is mechanistic or mammalian target of rapamycin. Do you use rapamycin? Do you have any?

Dr. Kelly Halderman

I have a lot of thoughts on rapamycin. Let me just get on my soapbox here. Rapamycin has a lot of side effects, right? One of those side effects is immune system dampening. When you are living in a pandemic, do you want to be cycling in rapamycin at this time? I don’t think so. I think we should hold off. And also some of the side effects can be extremely unpleasant, like very large bulk ulcers. I’ve heard that one that are very, very painful. I think that this time again, because of the mechanisms of rapamycin, and it’s just a tough drug to get ahold of. I myself have never tried it. I’ve got a lot of autoimmune things. I just don’t wanna rock the boat. I do have close personal friends who have tried it, but as soon as this pandemic started, it was we’re not gonna do this. And again we have berberine, we have metformin. 

Metformin does shut down complex 1 of the oxidative phosphorylation chain. So I mean, there’s a lot of data on it, but again, guys, like we’re still learning, we’re still learning. That’s our promise to our patients. And really we’re making sure what we’re doing is as safe as we know, but we have strategies better than I think at this point of rapamycin. How about your thoughts?

Joseph M. Raffaele, M.D.

Yeah, so I’ve kind of evolved on it over time. I think that what you say is true at the doses that are used in chemotherapy and transplant medicine, but in the low doses that people talk about now, once a week, three to eight milligrams, it may not be immunosuppressive. Of course if you’re getting aphthous ulcers and other things like that, then perhaps you need to lower the dose. And Joan Mannick published a study on sirolimus, looking at improvement actually in vaccination response in elderly people in flu vaccination response with it. So it’s kind of like–

Dr. Kelly Halderman

With half the dose.

Joseph M. Raffaele, M.D.

It’s hard to know for sure. Matt Kaeberlein talks a lot about these excessive worries about immunosuppressive and even potentially being slightly immunostimulant vis-a-vis what Mannick published. So I haven’t tried it myself. I do have some patients that have tried it, physician patients that wanted to do it on their own. And we’re looking at biomarkers, epigenetics, DNA methylation clocks, looking at their telomere length, looking at their senescent cells in a lymphocyte subset panel to see whether or not they’re having, we know what direction we want those to move in, so it’ll be interesting to see. I haven’t gotten any results back from that yet, but I know there are people who are using it clinically in sort of low dose once a week and talking about some pretty good results. So it’s interesting. I think, and Matt Kaeberlein, who’s done a lot to talk about this, he’s sort of one of the mTOR mavens out there and the head of the Dog Aging Project, he’s talked about it’s being beneficial. So I don’t know, I mean, I think I just wanted to get your thoughts on it. I mean, I definitely hear you. And that’s sort of where I was. And I’m now sort of not sure yet whether–

Dr. Kelly Halderman

Yeah.

Joseph M. Raffaele, M.D.

I’m just watching for the science to advance.

Dr. Kelly Halderman

That’s great and that’s kind of the boat I’m in right now. A lot of the colleagues who took a step back, they’re people that are my mentors. And so again, I myself, I like to think for myself. I like to gather a lot of data. So it’s really interesting that research. I’m gonna definitely hit you up for that to take a look at it.

Joseph M. Raffaele, M.D.

Yeah, so, yeah, it is interesting ’cause you want to have a good vaccination, but I think the important point that you make earlier and that we should emphasize is that if you haven’t tried time restriction, if you haven’t tried fast potentially, regular exercise and all those things, you don’t need to be jumping on rapamycin. Once you’ve done all those things–

Dr. Kelly Halderman

Right.

Joseph M. Raffaele, M.D.

You wanna get sort of the really top top stuff. I mean, Peter Attia has talked about, he does all those things and then he does do rapamycin. I think he has in the past. And he regularly fasts. And so you add that as sort of the cherry on top to get your–

Dr. Kelly Halderman

Yeah, I think the low hanging fruit for the majority of people, I mean, Peter Attia is way up there at the top, right? So really I think that the low hanging fruit is the most, actually the most important again. It’s not sexy to say like, hey, lay off all the dairy and all the protein. And again I don’t eat a plant-based diet. I definitely have a well balanced diet. I try to eat more Mediterranean. But again all the low-hanging fruit will really pay off in dividends, and of course we’re always looking at things. But that’s a really excellent point. It’s like we’re not stuffing Cheetos in our mouth and then try and find something to–

Joseph M. Raffaele, M.D.

Take rapamycin, right. That would be very American though I think.

Dr. Kelly Halderman

That would be very American, wouldn’t it? So that’s not what we’re saying here.

Joseph M. Raffaele, M.D.

Right. And so in terms of the genetic testing, SNP testing, do you do that on all patients when they come in or is that sort of targeted?

Dr. Kelly Halderman

I do. No, I do, I love it. I definitely can go through and I don’t treat SNPs. I look to see if there’s something that could be a weakness that’s contributing to what I’m seeing phenotypically in front of me. So I like to use the functional genomic analysis because it also has all the SNPs related to everything I went through for the mTOR. It has the HFE. It has the PON1. It has all your methylation. It has the CACNA1C which is related to possible EMF oversensitivity with your calcium gated voltage channels.

Joseph M. Raffaele, M.D.

So I guess you don’t have AirPods in right now.

Dr. Kelly Halderman

I don’t, but I have a pair, but I use the wave block and I have an EMF meter. I tested out these little wave block there, and you put them around your AirPod and they show that the EMF goes down. But I definitely try to mitigate the EMF. It’s so very difficult especially when there’s so many bad products. Just put your tinfoil on your head. 15.99 . It’s a racket and it’s really frustrating. I’m sure for you as a doctor as well it’s very frustrating when people get taken advantage of, so buyer beware. The best thing you can do is just buy a timer or use your phone to turn your wifi off at night. I mean, that should be the minimum you’re doing absolutely. It’s just to have that wifi shut off at night so you’re not baking in it when you’re–

Joseph M. Raffaele, M.D.

You’re talking about your router or in your phone?

Dr. Kelly Halderman

I would prefer that someone turn off their router. And some people have apps where they can set, okay, turn this off at 12:00 a.m. and turn it back on at 6:00 a.m. That’s what we have in our house where it’s just timed to go to off.

Joseph M. Raffaele, M.D.

Cool, but the problem with me is live in an apartment building. I gotta get everybody else to turn them off around me.

Dr. Kelly Halderman

Oh my God, that is tricky actually.

Joseph M. Raffaele, M.D.

Because I get on the WiFi and there’s like 13 of them sitting there that I could log on to, and so they’re all around me.

Dr. Kelly Halderman

Right, right. Yeah, that’s a little bit–

Joseph M. Raffaele, M.D.

That’s the hassle of living in New York City.

Dr. Kelly Halderman

Yeah, magnesium is our best calcium channel blocker, right, that we have, so.

Joseph M. Raffaele, M.D.

So you have patients on magnesium regularly, yeah. So the HFE, is that the hemochromatosis gene you’re talking about or?

Dr. Kelly Halderman

Yep, hmm-mm.

Joseph M. Raffaele, M.D.

Yeah, I mean, that is the most common genetic disorder amongst Caucasian populations. People don’t really appreciate it that much. It’s Northern Caucasian population I suppose I should say, but it’s about 1%. And I’ve seen quite a few in my practice. And I think it’s great to screen for it. But doing ferritin is a good start. Do you try to keep the ferritin in a window?

Dr. Kelly Halderman

Yeah, definitely. I think that we could, again we could do a seminar on the HFE pathway and the HFE SNPs, but I would say this is that please be mindful that in medicine we like to do black and white, we like to do you don’t have hemochromatosis or you do. However, if you’re looking at your HFE genes, you can have a hemochromatosis light. I like to tell people where you’ll have this upregulation of, the iron in your body will be more so, and then you’re looking at your ferritin and all these other. Some things look normal and they’re not. It’s very nuanced. But again some of what we are diagnosing as iron deficiency anemia, that’s not true. Iron is not being properly utilized. It’s being stored in the tissue. It’s very difficult. But again just having somebody take a look at your HFE genes especially if you are Caucasian can be really important.

Joseph M. Raffaele, M.D.

Well, listen, this has been a really fantastic discussion. I’ve learned a lot myself and I just wonder if there’s any parting comments you’d like to make before we wrap it up.

Dr. Kelly Halderman

No, I’m just very thankful that you invited me on. I’m so excited like we started off this conversation and I was telling you how excited I am to learn more about telomeres and all the other things that, the wonderful guests you have, their topics are fantastic. So kudos to you for putting this on. And I’m just really excited to learn myself.

Joseph M. Raffaele, M.D.

Thank you very much. I mean, it’s been fantastic having you on, and I look forward to seeing you in Vegas in I guess just a week or so.

Dr. Kelly Halderman

Yep, sounds good.

Joseph M. Raffaele, M.D.

Thank you very much.

Dr. Kelly Halderman

Thank you very much.