Ask Me Anything with Dr. Putrino: May 2026

Added: 2026-05-28

[00:00:01]We are live.

[00:00:02]>> We're live.

[00:00:03]>> Um, >> good morning everyone or good day.

[00:00:07]>> Um, so we have a bank of questions from people in our stories and in our DMs.

[00:00:14]Um, our first question is, can you give an update on the first inhuman mitochondrial transplant um that your team is hoping to perform?

[00:00:24]>> Uh, yeah, absolutely. Um this is a really exciting project that that we we hope that we will be able to uh make some progress on um starting a clinical trial this year. The first thing that we're working to understand is mitochondrial dysfunction in people with longco and other infection associated chronic conditions and illnesses. So our first testing is really about studying the mitochondria of people with these diagnoses. Um so that we can really quantify how and why the mitochondria are dysfunctional. Uh so that we can make a case to the FDA and other regulatory bodies that uh there is a good rationale for doing mitochondrial transplantation uh in these folks because the procedure itself is not without risk. So this is uh something that uh our first feasibility work should start in the next couple of months just to show that there is a good faith basis for us to explore this as a potential treatment.

[00:01:30]Um as soon as we have completed that sort of initial groundwork then we hope to be able to open a clinical trial and like I said you know I'm hoping that that will be toward the end of this year.

[00:01:42]>> All right. Um and we have a question from our DMs. I am a 78-year-old senior with longcoid since 2020 and I recently got the madna vaccine in a rural area of Canada where that is the only vaccine option. Within hours I had symptoms of myocarditis, pericarditis and was directed to take an ambulance to the ER.

[00:02:01]Symptoms resolved in a couple of days with no damage observed. My question is as a vulnerable senior with long co should I stop getting vaccinated if mRNA vaccines are the only option in my province?

[00:02:12]Yeah, this is a really challenging question and and thank you for raising it. Um, your experience unfortunately is not uncommon. Um, we uh there have been studies to to link mRNA vaccines to an increased risk of pericarditis and myocarditis in most cases. Yeah, over 90% of cases.

[00:02:36]Uh and when we're when we're talking about these cases, we're talking about longitudinal studies of um millions of patients. In most cases, we we see what happened to you happened uh across the board in in terms of you get diagnosed with a pericarditis, myocarditis that was triggered by the mRNA vaccine, but thankfully it resolves fully. Um I uh in terms of whether it is worth the risk of having another vaccine reaction, um obviously this is a a a personal risk conversation that needs to happen between you and your doctor, but I understand the tough tough space that you're in.

[00:03:22]If you were a patient at the core, our clinicians would likely recommend that you look into other forms of prophylaxis such as uh drugs like incitrolv from um Shionogi uh which should be available uh the their newest sort of iteration of this postexposure prophylaxis drug for SARS KB2 should be available in June of this year. Um as well as looking into access to monoconal antibodies um you know uh invivid still uh has PMGA uh which is a monoconal that was emergency labeled for postexposure prophylaxis and they will be releasing uh VYD 2311 uh later on this year which is a monoconal that will be you know hopefully so long as the clinical trials go well labeled for postexposure prophylaxis. So, I do recognize that you're in a tough spot. Um, and I'm really sorry that this happened to you.

[00:04:21]My recommendation is to look into postexposure prophylaxis drugs.

[00:04:26]>> Um, what can we do with having severe dysotenomia flares on top of me/longcoid?

[00:04:35]>> Yeah. So, as always, when we're dealing with severe disordia flares, we're trying to understand why those flares are happening first and foremost. So you know the the process that we take at the core clinically is when when uh when people come to us often their symptoms are completely out of control. And our first step is to try to find ways to not necessarily remove all symptoms from people although that would be nice. that the first step is let's get your symptoms from out of control to controlled so you understand why you're having the symptoms you know and to that end uh you know starting off very very simple with either journaling symptoms or working with um apps like the Guava app or the Visible app that allow you to um see your physiology and try and understand why certain things are making you crash harder than others um is a really effective way of of trying to get the uh the these disordia crashes under control. If you do start to understand you know why you may be getting more disordia crashes you know maybe it's mcast related maybe it is blood volume related maybe it is uh sort of stress uh physiological stress related that is upregulating your sympathetic nervous system that's when you can start to get a little bit more targeted with IV fluids sodium supplementation uh vagus nerve stimulation breath work um you know and and other sort of disordia strategies uh that can help to stabilize disordia symptoms but first before you can go down those rabbit holes trying to get an understanding of why those disordia symptoms becomes very very important.

[00:06:37]>> Um would you recommend poxlovid in case of reinfection?

[00:06:43]Uh I think it really depends on a lot of factors. First of all, you know, um paxlovid has a lot of drug interactions. So making, you know, we're assuming that a person is not taking any medications that would interact with paxloid is is is number one. And then number two is try and understand if you're somebody who has had negative reactions to paxloid in the past or if you're someone who has experienced rebound um as a result of uh taking paxloid um in the past. If the answer is no to both of those questions, then um uh then anything that we can do to shorten the course of SARS KB2 infection in my opinion is a good idea. So anything that we can do to uh make sure that uh the virus is limited from entering cells and limited from replicating uh is is something that is going to be favorable for long-term outcome.

[00:07:47]Um is the Ellie spot Eli spot E L I S P O T um for tickborn infection sufficient for diagnostics of chronic infection.

[00:07:59]Um I think uh to to my knowledge and to my reading of the literature the the Ellie spot uh still suffers from the the same sort of limitations that we have for all tickborn testing and identific identification of chronic tickborn illness in that it can be somewhat uh hit or miss as to whether you uh you get a positive result. So I I think that um you know one of the things that we are trying to do with the polyio research foundation is to uh create uh a diagnostic testing platform that allows us to put a lot of these tick tickborn testing paradigms head-to-head with each other so that we can better understand which tests are more reliable at identifying chronic tickborn illness. um for for the different tickborn pathogens that that can be uh causing problems.

[00:09:05]And I think that that is really important research that hasn't really been done to any level of satisfaction to date. Um and I hope that we'll get the opportunity to do it.

[00:09:16]>> Um could antivirals or metformin help with high EBV IGG but negative PCR?

[00:09:27]So when we think about the high EBV, IGG and negative PCR, you know, I I think that there's a lot to sort of unpack into what that could actually mean. Um, in in my opinion, often what that could mean is that someone who has chronic EBV that has that is frequently reactivating and then going dormant again. Um, what that might mean is that you've just gone through another period of reactivation and then and then the EBV virus going dormant.

[00:10:03]It could also mean that um your immune system is uh creating antibodies for EBV due to molecular mimicry or you know or some other mechanism that uh makes the immune system think that the EBV virus uh the EBV is is either present or reactivated in in your system and so antibodies are being produced. pushing you to more toward an autoimmunity reason. Um, I think that both can occur, but I I I think that if you're dealing with the theory that perhaps um uh that perhaps you have EBV that is reactivating and going dormant and reactivating and going dormant. often when it's dormant, it's hiding in tissue and so your PCR is going to be negative, but you'll have the IGG antibodies elevated that indicate that it was recently there uh causing problems. Um and in that case we do believe that antivirals could be a viable treatment option which is exactly why we are launching a a study that we're calling shield where we're looking at the use of prolonged um herpes antiviral drugs in combination with paxloid to uh treat people with long co who we think may have symptoms related to reactivated herpes viruses. If you've had a chance to watch any of the talks from the international ME/CFS conference in Berlin, do you have any highlights or initial thoughts? Though appreciate you were extremely busy and may not have had time to watch talks.

[00:11:45]>> You your instincts are correct. I I have been sort of sadly watching some of the tweet updates of of the international conference because um uh because I sadly was unable to travel internationally to be there. Um uh I have not had the chance to sit down and watch any talks, but I do know that they get a a phenomenal collection of speakers together. Um and uh and they do a great job. Carmen Carmen's team does a really good job of of putting on a a really informative conference. Uh and I'm sad to miss it this year. I uh maybe at the next AMA I'll be up to date on some of the talks uh because I really hope to see them.

[00:12:31]>> Um will there be a new vac co vaccine in September 2026 matching a new variant?

[00:12:40]>> Um I'm honestly not sure. I I I think that uh Novivvax has just been acquired by Seni. Um, and so I would imagine that the plan is to continue creating new co vaccines. Otherwise, I I'm not sure why someone would acquire acquire the company. Um, but uh I I I can't be that which is publicly available information.

[00:13:08]I I can't be too sure of um what what their plans are at this stage.

[00:13:14]Um, why long CO left me intolerant to carbohydrates, reactive hypoglycemia?

[00:13:22]>> Yeah. Yeah. This is an interesting question that we're really trying to dig into. Um and we don't have great answers right now, but what we think is happening is that uh something that we're seeing in a lot of our longco patients who are hyper metabolic and what hyper metabolic means is that if we have them sitting in a room uh just sort of breathing and not doing not expending any energy and we measure how much energy it takes their body to just do that just sort of sit in a quiet room not expending energy.

[00:14:06]Uh there is a subset of longco patients and a fairly large you know I would say uh 60 to 70% of longco patients will be hyper metabolic meaning that they're burning more energy than they should be.

[00:14:18]Um, and when we look deeper at that subset, that hyper metabolic subset of patients, we see that they're mainly utilizing carbs for energy.

[00:14:30]And uh the reason I think that some people who have significant mitochondrial dysfunction and this is conjecture. This is the part where we're theorizing. But the reason that I think that many people with longco who have mitochondrial dysfunction are intolerant of carbohydrates is when they're overutilizing carbs for energy and then their body starts to experience sort of oxidative stress. So they're hyper metabolic. They're producing too much energy. Energy isn't free. There is uh we produce sort of exhaust fumes uh from making energy. They're called reactive oxygen species. And those reactive oxygen species place our cells under what we call oxidative stress. They're kind of like toxic fumes from that from making energy in our cells. Um and so in a body that is sort of starving for energy. um and mitochondrial function is is not working out so well. If you add more carbs in, yes, the body jumps on it because it's starving for energy, but then it produces energy with those carbs and it produces more reactive oxygen species and you feel kind of poisoned and and very unwell because of it. Um that like I said that last part is conjecture that is kind of something that we're theorizing in our our clinic because we see exactly what you've described that carbs make a subset of people feel very very unwell. Um and when we look deeper on those folks who feel unwell on carbs we see that they're o overutilizing carbohydrates for their energy source and they're hyper metabolic.

[00:16:16]Um, any update on collecting and analyzing the blood from the positive responders from the Vivgart trial?

[00:16:22]>> Um, no updates other than to say thank you to everyone who is uh donating blood. Um, we uh we have recruited a a solid number of people. We're trying to get to about 20. We're um we're we're sort of in the um uh 7 to 10 range right now, but I think that that is already enough for us to start some preliminary analysis and and and compare it to our overall data set. Um but uh these these are because of the passive transfer experiments involve live animals they you know they take a little bit of time to complete but uh we hope to give you some updates soon.

[00:17:04]>> Um please tell something about insulin and blood sugar regulation in long co.

[00:17:12]Yeah. So I mean I think that this is linked to the previous uh comment uh which is longco disrupts the way that well in a subset of longco patients not all but in a subset we see dysregulation in the way that energy is produced um for the body. And when we're uh when we're exploring that and studying that with the techniques that we have, you know, it makes sense that when you're overutilizing certain energy sources such as carbohydrates and underutilizing other energy sources such as protein or fat, um you might start to have disregulated blood sugar, disregulated insulin signaling. Um, and some people and and I'm sure that many people in the longco community will um uh you know will relate to this. Some people who have been fit and healthy all of their lives suddenly start to have blood testing that looks a little bit more like they're pre-diabetic or even diabetic. Um this is something that we've seen and we again we think it is linked to the changes in energy utilization uh that occurs in hyper metabolic longco patients.

[00:18:31]>> Um and we have a more specific question on that front. Could ailify amplify blood sugar problems even beyond the end of the therapy?

[00:18:40]>> That's a really good question. um low doseabilify to my knowledge and I will say I'm I'm limited on the pharmaccoinetics of lowd doabilify like my knowledge is limited there of you know typically when lowd doabilify is used in long co it's used to reduce neuroinflammation and it does not exceed 5 milligrams I don't know that 5 milligram gram of Ailifi has a significant enough effect on metabolic function to worsen some of uh you know to worsen some of the metabolic changes that we see. Um and but that's not me saying it is or it isn't. That's me saying I I just don't know. I don't think anyone's done the the what's called the PK testing, the pharmacocinetic testing to understand if dosages that low could affect um metabolic pathways.

[00:19:45]>> What tests should we be ordering to understand neuroinflammation?

[00:19:49]>> Oh, this is a hard one. Um you know, I would say right now the only reliable testing that we have for neuroinflammation is experimental.

[00:19:59]Uh the reason I say that is because there has been there have been numbers of studies now showing that uh blood testing using inflammatory biomarkers for for neuroinflammation are notoriously uh unreliable.

[00:20:17]Um there's even sort of spotty data on using CSF uh cerebral spinal fluid and looking for inflammatory biomarkers in cerebral spinal fluid. That is slightly more reliable um than uh than than blood testing, but it is still problematic and challenging because they take the cerebra spinal fluid from your spine.

[00:20:44]Um, and sometimes if there are issues with uh cerebral spinal fluid and and what's called glimpmphatic clearance in the brain, um, you're just not going to get some of the inflammatory cytoines out of the brain and into the spinal cord. So even that is unreliable. Some of the best work uh that has been done on this topic in in terms of showing reliable biomarkers has been PET scanning that has been done by Mike Van Alzacer at Harvard. He published a really great study uh in 2025 on this uh showing that um I'm going to butcher this but when you use a radioan tracer I think PDG28 um- which is one that shows that that sort of binds to biomarkers of neuroinflammation. you actually see the the brains of people with long co um lighting up compared to healthy controls indicating that there is more active ongoing neuroinflammation. So that's an experimental PET scan. There are also some very interesting work being done by folks like Marcelo Freyer at the J Craig Benner Institute using salivory and blood proteomic analysis uh where we we don't look for cytoines but we look for the expression of certain proteins that indicate that neuroinflammatory processes are going on but again these are experimental uh investigations and not yet ready for prime time. So that was a really long way of me saying I'm sorry but we don't have clinical tests that I would call highly reliable right now.

[00:22:23]>> Um someone asked does metformin shorten COVID infection as well?

[00:22:28]Um so the literature right now on metformin is that uh it may shorten co infection although that particular uh acute co infection although that particular data point is contentious. Some studies have shown a shorter co in acute co imper infection period others have not. Um however one of the things that it has shown quite strongly is that people who take metformin during active co infection are less likely to experience prolonged symptoms or uh receive a longco diagnosis. And we believe that has to do with metformin's ability to support metabolic processes and mitochondrial function so that your own body is able to effectively clear the virus um during the acute infection period.

[00:23:25]>> Can you talk about pmgarda as a treatment for long co? Is there any research on utilizing it that way?

[00:23:32]>> Um to date there has not been any studies uh that have looked at pega as a as a treatment for long co. However, um we are actually actively trying to curate a case series of people who have taken PMGA um for uh for their long co and try to understand the results there. Uh I would also keep an eye out for um the work that Invivid is doing on their uh with their spear study team. I I can say you know as part of the sphere study team I can say that you know we are hoping to have some some good news soon that we can start a trial not on PMGA but on their newest monoconal called VYD 2311 which is very similar to PMGA except for it has a longer halflife which means it stays in the body fighting off spike protein longer um and uh it is more potent and more effective at clearing spike protein that can data.

[00:24:37]>> Can you please repeat the name of the new Seni drug and also the name of the drug that will be launched at the end of the year?

[00:24:45]Uh so the new Seni so I think maybe uh not Seni but Shiionogi. Uh the new Shionogi drug is called Incitrovir uh and they had a very strong uh clinical trial showing that it um it uh was successful in preventing CO infections uh in people who were exposed to CO in their household. So um uh hopefully they will be releasing that drug uh very very shortly. Uh I know that they have FDA approval as postexposure prophylaxis.

[00:25:25]Um and then I don't know about the end of the year but the other drug that I was talking about in terms of postexposure prophylaxis was VYD 2311 which is a monoconal antibbody made by Invivid.

[00:25:39]Um, is it true that the FFPS I think they mean FFP2 or three masks don't help against SARS CO V2? They say the virus is too small and can pass through the mask.

[00:25:54]>> So, I I think when we're talking about uh masking, we we think about things in uh a lot of uh a lot of different contexts. So although it is true that um unless you're wearing a well a well fitted N95 mask um there are oh do you have a >> aren't the FFP one and two masks comparable to Are isn't that the European equivalent?

[00:26:25]>> Yes, >> that's what they're asking about.

[00:26:27]>> Yeah. So uh although it is true that there are pockets of of of a mask that uh even even with very well fitted um um FFP1 and FFP2 masks that theoretically a virus can pass through um it's still what the literature consistently shows us is these masks still afford protection in exposure situations.

[00:26:57]Because even if the holes are small enough to allow a virus to pass through, the virus still needs to pass through those holes, which is just much harder to do than if you are unmasked and walking around with no protection. So consistently, uh what studies have shown us is that some protection is better than no protection. In addition, you know, what what one of the things that we're, you know, frequently sort of teaching about mask usage and uh precautions is that you wearing a mask is extraordinarily effective at you protecting your community from anything that you may be carrying. And so, you know, when we talk about masking, I think a piece of the masking that is often forgotten is what are we spreading to others? not not just what are we protecting ourselves from.

[00:27:56]And so in both cases mask and then of course if if both parties are wearing a mask the person who may be carrying SARS KB2 as well as the person who uh may be exposed to SARS KB2 then exposure is highly unlikely to occur. So I think that um these are the things that we need to think about when we're uh discussing masking and risk of infection.

[00:28:23]>> Um with disregulated immune systems, low IGG and subtypes with developing autoimmunity. Is there guidance on vaccine boosters?

[00:28:35]>> Um currently I would say no. we do not have detailed guidance on uh vaccine boosters in in those situations. Um my my general advice is uh speaking to you know if you have one of these conditions you either have a clinical immunologist or a rheatologist uh monitoring your care and having conversation with a clinical immunologist or a rheatologist about your specific situation um is useful in these circumstances. Is there a link to cholesterol issues as mine has spiked since longco?

[00:29:18]>> Yeah, you know, this is a great question. Um, uh, LDL cholesterol levels, uh, have been seen to spike in a lot of people with longco. Um and uh we believe if you look at the research that has been done by Ricia Ptorius and her colleagues you'll see um a lot of the endothelial damage endothelium being the insides of our blood vessels a lot of the endothelial damage that is done by long co uh and by sorry by SARS KV2 itself the virus um can lead to the buildup of plaques and the buildup of LDL cholesterol um uh in in the blood vessels of of people with these diagnoses. And so we frequently do see a buildup of LDL cholesterol and increases and spikes in LDL cholesterol.

[00:30:14]>> Um if we think mitochondrial dysfunction is a big part of the underlying PEM, how can we test for it?

[00:30:23]Yeah, there's there's currently not the best testing available for mitochondrial dysfunction. What we typically do uh in our clinic is we do a a test called a resting metabolic rate test. This is imperfect, but conceptually um what we expect to see in people with mitochondrial dysfunction is an increased resting metabolic rate. So, we expect them to be producing more energy than their predicted resting metabolic rate for someone of their age, weight, height, and gender. Um and frequently um in the clinic when we when we see people who display this this this elevated resting metabolic rate uh which we measure using um the same uh equipment that you would use for V2 max testing or cardopulmonary exercise testing which we do not do on our patients um uh that's when we will see the elevated resting metabolic rate. Now this is us being a little bit physiologically intuitive. This is not a validated test for mitochondrial dysfunction. The validated testing for mitochondrial dysfunction is something uh is a lab test that is available. Uh you can get it done. Uh it's called seahorse testing. Um where it actually specifically measures the mitochondria and and how the mitochondria are acting.

[00:31:58]However, the problem with seahorse testing is um that depending on where your mitochondria dis are disregulated or or dysfunctional, you may not see it in the mitochondria that are found circulating in your blood. Um, and so often people who I strongly believe to have mitochondrial dysfunction because of their response to mitochondrial supplementation and their resting metabolic rate data will um have perfectly normal uh seahorse testing um if they went out and got it done. So I I would I would have a word of caution about seahorse testing. Um even though it is, you know, one of the gold standards for diagnosing primary mitochondrial disorders, >> is there a good treatment for your hyper metabolic patients?

[00:32:51]>> I would not say there's one good treatment. Um, I I think that's actually a really challenging and it's a nice question that dubtales off of our seahorse testing uh conversation because I would say that there's not one good treatment and we don't yet know enough about all of the sort of ways that the metabolic pathways get damaged or disregulated in infection associated chronic conditions and illnesses where I can look at a patient who is hyper metabolic and say this is where your KB cycle KB cycle being the the biological cycle that creates ATP which is our energy source.

[00:33:35]Uh this is where your KB cycle is breaking down. We we're not good enough to do that yet. Um but if we were good enough to do that we would be able to say well this is where it's breaking down. So, we're going to give you NAD+ or NMN or nicotenomide ribocide or your problem is oxidative stress. So, we're going to give you CoQ10 and we're going to give you alphalapoic acid. Um, because we're not able to do that with so much precision. What we typically need to do is work slowly and carefully with our patients trying out different combinations of mitochondrial supplements and antioxidants.

[00:34:14]Would you say that content of your guide is relevant for those with an iatrogenic trigger given symptom overlap with LCME, MCCAST, etc.? Please elaborate if possible.

[00:34:26]>> Uh yes, I would say that our our manual not only is relevant um because what we what we try to do in the manual is encourage providers to not treat symptoms, not treat diagnosis, but treat drivers.

[00:34:44]what what are the drivers of the symptoms in of the person in front of you? And so one of the things that we name quite clearly in the manual is the fact that many people can develop the symptoms that get them their diagnosis from non-infectious triggers.

[00:35:04]Um the extent to which prior infections were involved in getting them to a point where a non-infectious trigger started their symptoms is something that still needs to be studied and understood um in great detail. But regardless of the trigger, what becomes important after the symptoms emerge is understanding what is going wrong physiologically that is causing the symptoms. And when you take that approach, that root cause driver approach um the uh the content of the manual is highly relevant to anyone with an infection associated chronic condition or illness regardless of the trigger that started it.

[00:35:46]>> Um what oh someone has already oh what treatments are being looked into for those with neuroinflammation?

[00:35:54]So uh we are currently running a clinical trial of a technology uh that delivers what's called microtesla magnetic therapy. Um in uh in our first pilot clinical trial of this uh of this technology, we we saw that patients who were randomized to the active treatment group rather than the placebo control group experienced significant improvements in cognition.

[00:36:25]Um and the mechanism of action that was validated in animal models was that this technology is able to reduce neuroinflammation.

[00:36:34]So that's one of the uh novel treatments that we're uh attempting for addressing neuroinflammation. I think what's also important to think about is um again as we go down the the road of thinking about drivers um mass cell activation syndrome can be a significant driver of um neuroinflammation. And so uh you know when we identify mass cell activation syndrome we we will recommend combinations of H1 and H2 blockers as well as mass cell stabilizers. And we often see people's uh neuroinflammatory symptoms soothe quite significantly. And similarly when autonomic nervous system dysfunction might be at play in driving neuroinflammation because the autonomic nervous system when it's clicked into sympathetic nervous system overload. Uh that's your fightlight part of the nervous system that can also be highly neuroinflammatory.

[00:37:36]And uh so then things like vagus nerve stimulation or cold exposure or even something as simple as breath work can downregulate that sympathetic nervous system overactivity and therefore downregulate neuroinflammation. And so again when we see neuroinflammation we we're trying to understand what's behind the neuroinflammation. Why why is why is someone getting this neuroinflammation?

[00:38:02]>> The next question is just vag nerve stuff question mark. So >> yes >> my my my answer will be just as vague as the question. Yes. Vegas nerve stuff.

[00:38:14]Yes. I I think that Vegas nerve is important. um you know and and I think that in 2026 and 2027 we want to do more research into how to get more precise in stimulating the Vegas nerve, how to get more precise in assessing Vegas nerve function. Um so that's my answer to Vegas nerve stuff.

[00:38:36]>> So I was going to say let's let that person rephrase their question.

[00:38:40]>> Um but the next question is thank you for the release of the second edition of your manual. Are there any key changes that stand out for you?

[00:38:49]>> Um, I I would say there are two key changes that stand out for me. I I really think that um thanks to uh some of our amazing co-authors and contributors on the manual like um uh Amy Prowel and Charlotte Mau and Shannon Delaney, we actually were able to really beef up the tick and vectorborn illness portion of the manual in a way that I I'm hoping will just be really helpful to providers who um who understand that tick and vectorbor illness is a huge problem in in many of the patients that they see but don't quite know get a little bit stuck on like what to do about that. Um so I think that that's a really important change. The other important change I think is that we did add a section acknowledging folks who have um co vaccine injury. Um this has been a really underserved um part of the population um and part of the community of infection associated chronic conditions and illnesses and so it only felt right that we should add that acknowledgement in >> um COVID disregulation of hormones.

[00:40:06]>> This is yes >> also just a question mark. Um, >> so again, I would say yes. uh Ako Iasaki and I uh put out a preprint that is still under review but is is fascinating if you're interested that shows how CO does cause a disregulation of many of our sex hormones alongside in a subset of people disregulation of cortisol uh which is our sort of like inflammation sleepwake um hormone uh And um and so I do really firmly believe that uh people with long co uh and uh and and I believe in the ability of COVID to cause a lot of hormonal dysregulation.

[00:40:57]>> Um what are your thoughts on pentoxifil ptoxifilene for longco patients and do you think it is risky to take if you have pots? Uh, honestly, we don't have too much experience with that drug. Um, I will look into that. Um, and and see if uh uh if anything pops up from our providers about using it. Um, but I haven't seen too much on that myself.

[00:41:25]>> Do you know anything about using adenosil almethodine SAM E supplement for longcoid brain fog or fatigue?

[00:41:33]>> Uh, yes. I think that these are interesting interesting molecules like interesting supplements um that theoretically have a a good uh a good rationale for supporting brain health generally and brain metabolic processes generally. Um as always the challenge is can we make them bioavailable to the nervous system? uh do they cross the blood brain barrier?

[00:42:07]No, they don't. Uh in most of the studies that I've seen um but uh you know I I think conceptually it makes good sense, but how do we make them bioavailable is the big uh question.

[00:42:23]>> Do LDL plaques and hypertension and increased CRP go hand in hand?

[00:42:30]uh in traditional medicine typically yes uh when we start to think about longcoid physiology not always so and what I mean by that is um we have a lot of people with longco who experience increases in LDL plaques but because of their pots they do not have hypertension they have hypotension Um and uh a and certainly um uh they their CRP is often normal. Um so I think in like a typical model of heart disease like traditional heart disease you will see CRP, hypertension, LDL you know all go hand in hand. But when we when we start viewing it through the lens of infection associated chronic conditions and illnesses, that relationship is not necessarily um uh not necessarily going to hold. And I think that that tells us a little bit about how we might how we might be able to subgroup some of the people who maybe just have increased LDL plaques but they don't have CRP and the hypertension versus patients who do have those three things um who maybe have a cardiac risk that needs to be managed.

[00:43:58]>> Could you please talk about potential medications or treatments for lower leg pain associated with longcoid or POTS?

[00:44:05]Yeah. So, uh, leg pain associated with longco and pots. Uh, you know, I I think that one of the things that we're often thinking about on that front is um, uh, pelvic congestion or, uh, what we call mater syndrome. Um, so, uh, there's some really great uh, clinicians out there who have been releasing uh, content. uh Alexis Cutchins uh talks about her work with materna syndrome. Jordan Vaughn talks about their work with with mater syndrome. Uh I think even recently um uh Alberta Azola uh from Hopkins talked about the fact that maybe 10 to 15% of her patients who have leg pain uh when they do an MRV which is a uh an MRI that looks at uh Venus integrity um they they actually see um uh 10 to 15% of people you know have this diagnostic criteria for May Turner syndrome. indicating that when people are in certain positions including sitting, sitting can be a really tough one, um these pelvic veins get crimped and they can't open uh and it causes sort of swelling and leg pain uh and and that can be that can be a real issue. In addition, uh you know, um when when we see small fiber neuropathy affecting the ability of your blood vessels to sort of pump blood back into your body, um uh we we often see uh again people experiencing splotching and changes of color in their legs alongside leg pain. Uh David Cyrum and his team have published a protocol called the lift protocol um that combines logos nrexone with parido stigmine which is called methanone uh known as methanone and um uh and he has shown some good success in helping people who have POTS related um leg pain and leg discoloration uh you know and he's running a clinical trial on on his lift protocol right Um, so I think that those are some of the exciting drugs in the in the pipeline. I also think that it's worth mentioning that when you have new onset pain, uh, some of our data points us toward thinking about autoimmune causes of your POTS. Um, and so, uh, IVIG and FCRN inhibitors like Vivka should be on the table as well in in having a conversation about things to try.

[00:46:49]Do you recommend statins for high cholesterol with longcoid and would you try metformin for hyper metabolic long co?

[00:46:56]>> Um we do always recommend statins for uh uncontrolled LDL um uh in long co if other mitigation strategies have not worked. um because ultimately we we want to be cognizant of heart health and we want to do our best to sort of um uh mitigate any issues. Um uh and then in addition to that we've just also seen the benefit of uh you know in in looking at work that have been published by folks like Bruce Patterson and others we've just seen the value of using um uh statins um to help to heal and protect the endothelium um in in people with longco and other infection associated chronic conditions and illnesses. Um that being said, we always start with non-drug uh remediation approaches uh you know uh dietary changes uh that can be tolerated etc. Um and then if that's not working out we move we move into statin use. uh for metformin, you know, metformin has been a really mixed bag and and we we have a tough time identifying who benefits and who doesn't. Certainly, there have been now a number of like failed metformin trials uh for long co to my knowledge none of them broke longco patients into hyper metabolic and metabolic um and normal metabolic. But um uh I do think that um we have seen people really get a good boost off of metformin, but I can't I can't predict who's going to be a responder and who's not going to be a responder to metformin. I think more research is needed there.

[00:48:59]>> Advice on working with local providers who do not get long co dynamics, particularly when we're experiencing symptoms, but our labs are normal.

[00:49:08]>> Yeah. Uh uh my only advice there uh you know first of all I'm sorry that that's happening. Um uh my my my general advice would be to link them to our manual or some of the other manuals that have been uh emerging since we launched ours that talk uh that that are are designed to be um resources for individuals with um uh for individuals who are treating patients uh with longco and other infection associated chronic conditions and illnesses.

[00:49:44]Um so I I would say that the extent to which you can provide them with resources uh to you know better understand okay all of the blood work is coming back normal but maybe a tilt table test is indicated given the symptoms that are being experienced or maybe we should be looking for tickborne illness or maybe we should be testing for something else. Uh just giving them some some hints on what they should be testing for next. How long should lowd dose nrexone be used for treating neuroinflammation?

[00:50:19]>> So uh you know again um lowd dose nrexone is a tricky one because uh we we don't have long-term studies of its use.

[00:50:32]uh Hector Bonia's work from Stanford uh you know is is probably the best work to date out there and it it shows us that it can be used as a maintenance maintenance drug indefinitely.

[00:50:48]Um uh however you know we're still a little unclear as to how lowdos nrexone is working. Um you know if you look at um uh Sonia uh Gradis Gradisnik's work from um from uh uh Queensland in Australia.

[00:51:12]She actually shows that lotto nrexone may help to correct uh uh receptor integrity and receptor health on natural killer cells. So thereby boosting natural killer cell function and uh and and helping immune regulation and immune health. Um so it it's a and this may exper this may ex explain why many people who take lowd dose nrexone initially experience you know even at very low doses initially experience herks like reactions where it feels like their body is more inflamed not less inflamed. Um and uh a and so right now um we don't understand again the the pharmacocinetics of the drug well enough at low doses to understand why it's helping and why it may be giving giving so many patients a boost.

[00:52:11]Um but it does it does seem from if you listen to the community and you listen to what you know people who have been taking it for 20 years um tell us in the ME/CFS community it is certainly something that that can be a maintenance drug.

[00:52:28]>> I take 2,000 units of nattokinise per day. Is lumbrokinace better? In what way? I cannot get it in Europe. How is the clinical trial going? Any good news?

[00:52:41]Um we so uh nattokinise and lumbroynes work very in a very similar way. Um there is no one has tested this but theoretically if you're someone who suffers with MCCAST lumbroynes might be slightly better than nattokynise simply because um uh simply because nattokynise is formed from fermented products which are higher in histamine and so therefore um it can uh it can cause histamine reactions for people with MCCAST whereas Lumbre kynise is not you know it's it's an enzyme that is uh found in earthworms and is not a fermented product. So um uh so so those are the differences in in sort of making the choice of nanocynes versus lumbrokynise.

[00:53:41]Um uh in terms of our study uh it's going well. We have been seeing some really interesting results whereby when the lumbar does what it is supposed to do in a patient who has clotting dysfunction which we're measuring with a device called the sonoclot. Um we see the lumbrokynise is clearing up that clotting dysfunction which is not present in every one of our patients who have been enrolled into the trial and when that uh dysfunction is cleared we see symptomatic improvement. So it is a very nice mechanistic story of the lumbrokynise clearing the clotting issue and uh and causing improvement but once again not everyone is is showing that clotting dysfunction and so I think that um once you know once again we're we're advocating for subtyping patients appropriately.

[00:54:43]Um reh hormones are you routinely checking act DHEA aldoststerone etc. After 30 plus years of severe fatigue I got diagnosed with secondary adrenal insufficiency it gets overlooked or misdiagnosed as ME/CFS.

[00:55:02]>> Yeah I is a great co great comment uh and yes this is something that we are frequently doing with with our uh uh with our patients. It it is a it is a really tricky um uh you know it's a really tricky balance. Uh these are expensive tests to do a lot of the time and they require a lot of sort of carefully timed testing to occur. So sometimes it's hard to get insurance to cover them. But I totally agree that adrenal insufficiency uh that can be diagnosed um you know uh through some of these like very careful tests uh can be a significant driver of um fatigue and uh post-exertional symptoms that that we frequently see. Um, you know, and you know, for the record, more broadly, we, you know, we're we're always testing for some of the more treatable causes of fatigue and post-exertional symptoms. We're always doing a full thyroid panel to understand what is the status of someone's thyroid health. We're always making sure that our younger patients who are experiencing uh palpitations and fatigue related to you know high heart rate and and palpitations we're making sure that they get cardiac imaging and EKGs and echo cardiograms so that we we rule out some of these more commonplace and more mainstream diagnosible causes of fatigue and post-exertional symptoms. and I think it's a really good note. So, thanks for bringing it up.

[00:56:42]>> How can I eventually get rid of immune complexes?

[00:56:47]>> Oh, you know, that's a hot topic right now. Um, you know, uh, immunoparesis uh is a way of removing immune complexes from the system. Although you know there was a question 30 minutes ago or so that asked me have I watched anything from the international ME/CFS conference and as I as I said I haven't had the chance to sit down and watch any of the videos but one of the tweet headlines I saw was that imunoferesis didn't didn't um uh didn't outperform placebo in uh in a recent trial which was a bit of a bummer to see but amun amunoferis is plasma feresis. You know, the these are some of the ways that immune complexes can be removed from circulation in your body.

[00:57:43]>> Have you heard about mezenyal stem cells used for treating long co?

[00:57:48]Um I have um and you know I I I think that there is a a role for different cell therapies in in long co um uh mezzenymal stem cells uh may have a role. I haven't seen you know a whole lot of highly compelling literature. Um, uh, I may be getting this wrong, but Reenocy, I think, is is a cell product, a cell therapy that has actually had some success in reducing fatigue, uh, in people with long co um, and that's a that's a therapy that now has expanded access in the United States that we're we're looking into uh, right now at the moment actually. Um so I do think cell therapies and and I think cartis cell therapies as well um you know could have a role in treating long co um I I think that this is an area that needs to be explored.

[00:58:51]>> Um thank you for including vaccine injury in your manual. Hugely validating.

[00:58:57]Have you come across LC patients who when they experience PM instead of flu-l like symptoms have allergy symptoms?

[00:59:04]>> Yeah absolutely. Um, and I uh I I think that this is like a uh a very sort of mcastcoded response, mass cell activation syndrome uh response. Um, ex exercise or exertion um that may be pushing you into exercise like heart rate zones um causes mel degranulation. it causes an acute inflammatory response um before um uh before it causes an anti-inflammatory response paradoxically. And so um we do often see people getting flushed, getting rashes, getting um uh getting hives show up when they're exercising or even just experiencing, you know, shortness of breath uh or or air hunger uh as a result of inflammation in their airways.

[01:00:02]So this is something that we see. It's something that makes us think MCCAST and start thinking about the use of antihistamines and marel stabilizers.

[01:00:13]>> Do you have an opinion about oxalloacetate?

[01:00:16]>> Uh similar to my earlier opinion about uh mitochondrial supplementation, I think oxalloacetate is one of those mitochondrial supplements that sometimes really really help people. Um and so it's worth a try. But frankly, given the expense of oxalloacetate, I haven't found like a a a um uh I haven't found a a source of shelf stable high quality oxalloacetate that is not, you know, hauntingly expensive. Um unless it's really changing your life, um you know, we we don't recommend that people just sort of take it endlessly if they're only getting a tiny benefit. I'm sure we can find cheaper supplements to to give that benefit. That said, we have had people have extremely good benefit from it.

[01:01:09]>> Okay. Um it's 10:01.

[01:01:13]Thank you all for coming.

[01:01:15]>> Thank you everyone. Uh really appreciate the questions and uh we will be here every month. So uh let's keep them coming.

[01:01:23]>> Bye >> bye everyone.