Dr Rupy: Today I have the privilege of speaking with consultant neurologist Dr Sharok Malik. He gained his primary medical qualification from the University of London. He's a specialist in neurology obviously, trained at the John Radcliffe Hospital in Oxford and the National Hospital for Neurology and Neurosurgery, Queen Square, London, both internationally recognised centres of excellence for neurology. He's got an MSc in clinical neurology, a PhD in imaging and multiple sclerosis. Honestly, he's one of the smartest people we've had on the podcast, but also he's got interest in public health and nutritional physiology. He's one of the few neurologists in the world with such an interest and that's why I was really keen to have him on the podcast. And what I do love about Dr Sharok is that he is unwilling to talk about subjects without diving into the nuance of exactly what we mean. So we meander around certain definitions quite a lot today. And if you're willing to go the extra mile and listen very carefully to what we're saying, you will understand the subject matter a lot better. Things like metabolism, insulin resistance, these are all very nuanced topics, even the term neuroinflammation that gets bandied around quite a bit. So if you are interested in brain health and you really want to get to the crux of what we mean by brain health, this podcast is definitely for you. We dive into why people with type two diabetes have up to a 50% higher risk of developing Alzheimer's, why the brain is more vulnerable than we think, how poor metabolic health, once we've defined it, links to dementia, stroke, migraines, depression and more, as well as some evidence-based tips to protect your brain through food and movement. And I just want to start this podcast by giving you some ground ideas around what we know about how to protect our brain. The first thing is glycaemic control. So randomised control trials and meta-analyses show that better glycaemic control, i.e. blood sugar control, is associated with improved cognitive outcomes and larger brain volume. So targeting a healthy HbA1c, which is a marker of the last three months or so of your blood sugar regulation, of under 6.5% at least, but I would say, I would argue for the lower the better, is associated with better outcomes when it comes to brain protection. There's lipid management. So if you have elevated total cholesterol, LDL-C or apolipoprotein B levels, these are linked to worse brain structure and cognition. The ways in which we can reduce cholesterol, we've discussed many times on the podcast, can include dietary interventions, like the portfolio diet, which has a preponderance on plant-based proteins, legumes, and certain ingredients like flax, chia, and oat bran, but there are also pharmaceutical interventions that we've discussed at the start of this year with Professor Ray as well. And the other thing is blood pressure control. This is one of the areas that I think doesn't get enough attention. It's one of the silent killers. Many of us don't understand why we have elevated blood pressure. There are a lot of reasons that we still don't know why people, certain people have a high blood pressure, but it's really important to make sure that you check it regularly with your primary care physician and you control it with diet, lifestyle and medications if needed.
Dr Sharok: Sharok, great to have you here. I want to dive into this episode by asking how you describe metabolic health to your patients.
Dr Rupy: I mean, thanks very much for having me. I've realised we've got two of England's most wanted South Asian men in the same place at the same time. It's nothing but a gangster party, I think.
Dr Sharok: I mean, I've been watching your show for such a long time and I've been waiting by the phone for so long for you to call, to email. It's just been five years and finally we're here, so thanks very much.
Dr Rupy: I appreciate that. Mate, we've been trying to get you on the pod for a while. You know, you're a busy guy. I mean, you were saying, you know, you still work four days in the NHS, you've got the private side as well. You're you're in demand.
Dr Sharok: We're both high value men. What colour's your Bugatti?
Dr Rupy: My Bugatti, my Bugatti.
Dr Sharok: That's an Andrew Tate reference. I actually drive, I actually drive a Honda Accord most of the time. I finally upgraded from my Nissan Sunny.
Dr Rupy: I had a BMW for 15 years and the only reason why I changed it is because someone drove into it whilst it was parked overnight.
Dr Sharok: Only once?
Dr Rupy: Only once.
Dr Sharok: That's just normal. Oh my god. Okay, all right, fair enough.
Dr Rupy: Anyway, so, I don't know how to segue into metabolic health.
Dr Sharok: I mean we can just keep chatting if you want. That's what I'm here for.
Dr Rupy: Your quiff is definitely more impressive than mine. I used to, I used to have a quiff myself, but I don't think I was able to fashion it.
Dr Sharok: I mean I was bald last week, but I put some ashwagandha on my and now I'm better.
Dr Rupy: Ashwagandha, that's what, that's definitely something I want to ask you about. So there's fasting and ashwagandha. I'm going to add this to the list. All right, the people want to know about metabolic health. Let's let's dive into that first.
Dr Sharok: So how would you define it?
Dr Rupy: It's an interesting one. I mean, I kind of use the furnace analogy, even though it's kind of imperfect. So it's every cell in your body, of which there are billions or trillions, all have the need to respire, to utilise energy, and your metabolism is essentially the sum of all those different reactions.
Dr Sharok: Yeah, that's I think that's a very good way of doing it. There isn't a definition. Because the thing is in the world, if you are a neurologist, it's very clearly defined what you do. People can define that term. If you're a psychiatrist, if you are thinking about neuroscience versus neuropsychiatry. But the thing is metabolic health is very new. And what people use as a term will vary from country to country, physician to physician, things like longevity, functional medicine, preventive health, all very poorly defined. There are societies of, you know, various things, but they will have their own definition. And one of the things that I try to explain to my patients is that there's no point trying to pin it down into one thing. Because at the end of the day, you're an individual. You're not just a brain, you're not just a lungs, you're not just your gut. Everything is interconnected, whether we like it or not, it's all working together and if one part is unwell, you're going to feel it somewhere else. So we're thinking about whole systems approaches, we're thinking about cellular approaches. You talked about every single cell producing energy. There are trillions of cells in the body. And each one of them is working efficiently or inefficiently. So trying to make sure that the major organ systems, but also the cellular systems are working at their most efficient is kind of what we're about. Now, that may be part of helping someone improve their cognitive performance, maybe part of someone who has diabetes trying not to have diabetes anymore or trying to control it better, maybe part of someone who is just generally well and thinking how can I not get dementia in the future or how can I continue to walk when I'm 90 years old up and down the stairs carrying my groceries home. So these are all part of the same puzzle, but ultimately metabolic health and all the different types of health that we're talking about are aimed at trying to get people not necessarily to live longer, but to lead better quality and more functional lives into into older age.
Dr Rupy: Do you think as a function of improving one's metabolic health, they would have more years of life? I.e. increasing their lifespan as well as healthspan.
Dr Sharok: We would guess so. But, you know, I have a clinic called the London Centre for Longevity Metabolic Health. The thing I tell all of my patients when they first come to see me is that we don't really have any good evidence any of this works. It should work. We have good biological plausibility. And we have small level data in rat models, in ape models, maybe even small pilot studies in humans. There's no reason why it shouldn't work, but I can't tell you that this is proven. I mean, medicine, you know, science proof doesn't really sort of fit, but there's no incontrovertible evidence to say this is the way to live longer. The only things we know for sure are if one or both of your parents lived long lives, you have a much higher chance than anyone else, whether you smoke, whether you drink, whether you partake in other recreational activities that might otherwise, you know, reduce your lifespan, good chance that you'll live longer.
Dr Rupy: I love that. So, I mean, I knew when we were going to jump on this podcast and chat that we're going to have this nuanced conversation. And I think the audience will appreciate the fact that even within your clinic that is labelled as longevity and improving metabolic health, you're very upfront about the fact that, look, I can't actually prove that any of this stuff works. We're going to give it a go anyway.
Dr Sharok: Yeah, and the thing is there are certain types of clinics that will say, listen, let's infuse you with X and Y chemical. There may be dangers. Sure. But the approaches that we're taking, that we're talking about, there's generally no danger and if anything there should be of benefit, but whether or not they are enough benefit that they prevent heart disease and Alzheimer's and prevent you getting arthritis later on or lead you to live longer than you might have otherwise, there's no real way to know.
Dr Rupy: So when in the context of a neurologist and metabolic health, what are the things that you're looking at and how do you actually, actually let's take a step back. I don't think many people would make the connection between metabolic health and and brain health. Why don't we unpack that a bit more?
Dr Sharok: I mean, it's not dissimilar to what we talked about before. Every part of your body is interconnected. So in order for your brain to function well, you need to make sure that each cell of each different part of the brain is working to its optimal capacity. And the opposite to that would be that if certain parts of the brain are working inefficiently or less efficiently or sub-optimally or abnormally, then you're going to get symptoms associated with that part of the brain. And the theory would be, we have some data on it, that if you were to prioritise metabolic health in your body, then very good chance that your brain's metabolic health would also be affected in a positive manner. However, the brain is a little bit different. The brain, spinal cord are a little bit different to the rest of the body because they are protected from the rest of the body systems by the blood-brain barrier. So there are things to consider in that area which are quite nuanced. But it is an intrinsic concern. When people come to our clinics, what they're looking for is I don't want cancer, I don't want heart disease, I don't want a stroke, but I specifically don't want dementia. Those are the four things that they're looking for to treat. And stroke and dementia are part of the brain.
Dr Rupy: You mentioned the blood-brain barrier. Can we quickly define that for folks who are listening?
Dr Sharok: I mean, it's a very complicated part of neurology. So I think, you know, without sort of being a neuroscientist, we don't want to go into all the definition, but essentially, if you think about your skin as a barrier between the muscles and the fascia underneath and the rest of your of the world outside, it's not dissimilar. The brain, it's not just the brain, the central nervous system is brain and spinal cord mainly, but also if we're going to be very correct, the optic nerves, they are protected by a very complex set of blood vessels, which basically protect it from any of the systemic infections or other toxins that might be coming in in order to preserve brain function because objectively, we would argue, and I might be slightly biased as a neurologist, that the brain is the most important part of the body and every single resource should be spent to try to make sure that it's preserved even when other parts of the body are on fire perhaps.
Dr Rupy: Now, with the caveat that it is there's biological plausibility for poor metabolic health and disorders of the brain, how do you talk to patients about signs that their metabolic health might be array and their risk of brain conditions, specifically dementia?
Dr Sharok: Yeah, it's difficult because the thing is every single one of those terms that you've used needs unpacking. Yeah. So metabolic health, dementia, etc. You know, poor, what does poor mean? You know, who who defines what that means? So what is dementia? Dementia isn't Alzheimer's. I mean, Alzheimer's will make up a significant proportion of dementia, but Alzheimer's is actually multiple different conditions. What we're talking about when we talk about dementia is probably the typical amnestic version of Alzheimer's, but there are other types. There's language variants, there's visual processing issues, posterior cortical atrophy. Um and, you know, there's others, but what most people are thinking about is that specific type, but all the different types of Alzheimer's are a little bit different. And we very likely have good biological plausibility, even animal model and small human pilot study data to suggest that metabolic improvements may help in the typical amnestic version of Alzheimer's, but nothing really else. And outside of Alzheimer's, you have vascular dementia, you have frontotemporal dementia, you have Parkinson's related dementia or Lewy body dementia, and many others which are neurodegenerative conditions. Maybe Parkinson's, there may be some element of metabolic health being involved, but we don't really have very good data. As much as people have suggested various things, and we've got some data from using various supplements and things like that that may help in people with Parkinson's, it's very poorly defined, it's very early days. But Alzheimer's, the typical amnestic variant probably has the best hope.
Dr Rupy: When you see the amnestic variant, are you talking of specific symptoms like forgetfulness or?
Dr Sharok: Yeah, so it used to be up until 2024 that we could define Alzheimer's by its symptomatic course. Now, internationally, it's been recognised by every neurologist that we have to follow the international guidelines, which basically is defined pathologically. Okay. So if you have amyloid plaques, if you have intracellular neurofibrillary tangles with tau, with hyperphosphorylated tau, you've got Alzheimer's, whether or not you have the symptoms.
Dr Rupy: Really? So unless you have that, and how do we measure those today?
Dr Sharok: So there's lots of ways. The best way is to open the brain up, take it out of the body, you can't put it back. So that's called postmortem. We wouldn't suggest doing that on living people. Um you can take samples of the brain, brain biopsy. Again, that will lead damage, especially if you're going deep inside the brain to the hippocampus, which is where the typical amnestic variation of Alzheimer's tends to affect, you're going to lead to damage from that biopsy. You can get CSF, so lumbar puncture, taking cerebrospinal fluid, have a look at it, look at sort of typical patterns of amyloid and tau. And imaging, which is very specific for amyloid, um using PET, positron emission tomography can also be quite sensitive. And more recently, as of last year, there's been blood tests which actually see P-tau 217 in your blood. And that's quite good. And we've got it in the UK as of this year.
Dr Rupy: Really?
Dr Sharok: It's relatively cheap, 100 pounds if you are able to get it via a trial, or if you get it via sort of a subsidized service, but lots of, you know, corporate entities are charging much more than that.
Dr Rupy: So can you buy it privately?
Dr Sharok: It's only private at present or via trial. It's not on the NHS.
Dr Rupy: Gotcha. Okay. And it's quite good? There's the false positive rates and all the rest of it?
Dr Sharok: We'll have to see. Yeah, I mean, lots of these things when you go into how they derived, you know, their apparent sensitivity and specificity, you start to see it's not 100%. It never is. But we have a blood test which may give you some information. I guess the only thing that they will say about the blood test is that it's only really should be used in people who have symptoms. Because otherwise I could go and have a blood test, you know, P-tau 217 levels are abnormal. That doesn't mean anything necessarily. And the thing is histopathologically, we've known for some time that on postmortem, there are many people who have the typical amyloid beta plaques, people have the typical tau intracellularly who don't actually have the typical symptoms. So it's not a 100% correlation between neuropathology and actual clinical manifestation. But the powers that be with whatever their vested interests might well be, we won't go into it, believe that this is the best way to do it, so we're kind of beholden to that.
Dr Rupy: Not to take us too much off track here, but if there was somebody with a positive blood test for some of these proteins without symptoms, would you be worried about that? Is there any evidence that we should be worried about that?
Dr Sharok: If it were me, I'd be worried, although I don't know 10 year, 20 year data on what happens in a 35 to 40 year old person who has this in the future. We don't have that yet.
Dr Rupy: Okay. But I'd be worried, of course. I mean, I'd rather not have it than have it, yeah. So I think the argument would be don't test it unless you have some symptoms and you might be in that category. So really people over the age of 65 plus who are getting subjective cognitive impairment or perhaps objectively have cognitive impairment on their assessments.
Dr Sharok: Okay. So that would be a good way to do it. But companies will sell it to you if you want it.
Dr Rupy: Yeah, yeah, yeah, I'm sure. I mean, companies will sell everything, you know, brain scans, full body MRIs.
Dr Sharok: I mean, I went to Debenhams and they tried to sell me a push-up bra, so. I wasn't sure I needed it. But I do jiggle a bit when I run. I'm not sure that's what I need.
Dr Rupy: Okay, so Alzheimer's disease, it's around two-thirds of the dementias, give or take.
Dr Sharok: Yeah, about just under. Yeah, it's about 60%. Okay. In the Western world, it's a little bit different elsewhere.
Dr Rupy: And within that, you've got all these different subtypes.
Dr Sharok: But again, that's over the age of 65. If you go under 65, it changes a bit, but let's keep it simple. Just just let's keep it simple. Two-thirds is reasonable.
Dr Rupy: Two-thirds. Okay, fine. And and given there are so many different, you know, subtypes of Alzheimer's, different predominances in terms of symptoms, I guess that speaks to the different root causes of those presentations. If you were to like hazard a guess as to, you know, how many of those might be improved by lifestyle changes or or any changes to improve one's metabolic health, would you be able to make a ballpark figure on that or?
Dr Sharok: Typical amnestic Alzheimer's, I'd say a good amount. Whether a good amount is half or 80% or 90% is difficult. Because the thing is there are subtle genetic abnormalities or not abnormalities, variations which will increase your risk whatever you do. Gotcha. It won't make it a sort of a given necessarily, unless you happen to be one of the six to 700 families that have the three autosomal dominant genes that we know you're just going to get it at a very young age generally. So PSEN1, PSEN2, APP. Interestingly enough, APP, which is on chromosome 21, if you happen to have trisomy 21, which is also known as Down syndrome, then you're very likely going to get an Alzheimer's type disease. Um but outside of that, probably less than 1% of people have a genetically determined Alzheimer's. Um there are other risk factors which are genetic. So you're probably aware of the ApoE sort of um epsilon 2, epsilon 3, epsilon 4, and depending on how many of each you have, you could be homozygous for four, which confers the highest risk. Now, if you look at the studies, there's some variation, but between 50 to 90% lifetime risk of getting Alzheimer's disease if you have ApoE4, two copies of the epsilon 4. If you have two copies of epsilon 2, very low risk. Less than probably 1 or 2% have that. Um but it's protective. But most people have a little bit of two, a little bit of three, etc. So you're kind of in in the ballpark.
Dr Rupy: And and just to clarify, that doesn't mean that you're not going to get Alzheimer's, it just means that you're at a much lower risk.
Dr Sharok: Much lower risk and and you'd be pretty unlucky if you got it. You'd have to yeah, something else has gone wrong at a very fundamental manner.
Dr Rupy: Okay. And let's let's dive into poor metabolic health because I feel like I'm going to be saying poor metabolic health quite a bit over the course of this episode. What what would be the biomarkers of poor metabolic health to you, the things that would raise your eyebrows and say, you know, if we optimize this, we can actually improve your chances, reduce your risk of dementia regardless of your genetic burden.
Dr Sharok: Yeah, that's a difficult one because that that requires a long history, examination, ideally some blood tests, etc. Um metabolic syndrome has been well defined for a long time. You know, if you have hypertension, hypertension isn't a deficiency of antihypertensives. Something's gone wrong. Now, obviously, as we get older, the arterial wall, um the endoluminal will get a little bit stiffer. So you get less variation um in blood pressure. So that's normal aging related increase in blood pressure. But the biggest thing is hypertension. Because it's actually very treatable. Um if you have hypertension, lots of conditions, metabolic conditions become um much more likely. If you have aberrations in glucose utilization, glucose excursions from the cell, etc, that makes it much more likely. But again, that's a little bit complicated because it depends where you are in the rest of your metabolic health. If you are unhealthy, whatever that means, higher levels of blood sugar are particularly bad because of what's called polyol pathway flux.
Dr Rupy: Polyol pathway flux.
Dr Sharok: Yeah, so your intravascular, so so extracellular, let's keep it simple, extracellular blood sugar really should be around, you know, five, whatever the units are in the UK, I forget now. The minute it goes above that, 5.1, 5.5, 6, 7, you start diverting the normal metabolic processes of glucose into the sorbitol fructose or fructose sorbitol pathways, which are actually quite toxic. Fructose, even though we consume it, is actually a toxin. It's treated as a toxin by the body. So, um if there are insulin dependent cells which require glucose to enter the cell with insulin, you might be protected somewhat, but if you have certain cell types which don't necessarily require insulin for you to have glucose incursion into the cell, you get a lot of toxicity, which is why you get retinopathy, which is why you get nephropathy, which is why you get neuropathy much more because they don't necessarily require the insulin to be present.
Dr Rupy: Gotcha. I don't think I've ever appreciated that.
Dr Sharok: The first things that get damaged are that.
Dr Rupy: So the, so just to rewind for the listener, there are certain cells that require insulin.
Dr Sharok: Most of them.
Dr Rupy: Most of them, um to move sugar from your bloodstream into specifically glucose. Yeah, specifically glucose into the cell that can be used for storage or energy, whatever you need glucose for. However, there are some that are independent from requiring insulin to move glucose into the cell.
Dr Sharok: And these are the ones that are the highest risk of damage.
Dr Rupy: When you're a type two diabetic or you're you've got poor metabolic or metabolic syndrome.
Dr Sharok: That's right. I mean, you don't have to go into formal diabetes. Again, the the classification for how we define diabetes changes every once in a while. But you were mentioning being an F1, you know, some time ago. Um do you remember cannulating patients? Giving them fluids, usually normal saline. I don't know if you were ever told as an F1 that don't, if you are not sure if the cannula is in place, if it's tissued, you can give saline at a slow rate, but don't ever give dextrose.
Dr Rupy: Gotcha. Yeah, yeah, yeah.
Dr Sharok: And the reason why is because that sugar has a necrotic effect on the tissue. Yeah. So that high concentration of glucose by its nature will start to kill the tissue. It has an ischemic, has a has a necrotic effect. So much lower levels of that happen intracellularly when you have a bit too much. And a good way to determine that would be through your average blood sugar levels throughout the day. You can estimate that using HbA1c. HbA1c isn't perfect. There are things which can cause it to vary. Some people's might appear slightly high, some people's might appear slightly low. Um but it's a reasonable marker for most people most of the time.
Dr Rupy: Okay. What not to take us on another diversion, but what are your thoughts on continuous glucose monitors for those who are?
Dr Sharok: Very useful in some people. Okay. If you know why you're using it. Uh-huh. In non-diabetics or just those with?
Dr Rupy: Yeah. I mean, it's a good demonstration of what happens to your blood sugar when you eat, when you don't eat, when you exercise, etc. But just be aware that it doesn't tell you what your insulin is doing. Yeah. It doesn't tell you what your pancreatic increasing system is doing. It doesn't tell you what's happening at your leptin, ghrelin, cortisol and signal level in your hypothalamus. It doesn't tell you any of that. Because those are the steps that are being triggered before your blood sugar changes.
Dr Sharok: That was going to be my next question. Insulin. Is there a reliable way of actually seeing what your insulin is doing? I mean, almost glucose is the aftermath of of you eating something, whether it's good or bad, or whether it's, you know, negative for you. But what about the insulin response? Is there a?
Dr Rupy: You can't get that on a CGM. Sure. Um if someone did that, that would be very useful. I mean, I, you know, I've kept my eye open for the last 10 years or so to see if anyone's managed to do that. I ran into someone, did you ever go to the Swiss Re conferences in in um Zurich? Okay. Um and I ran into someone who was developing that some time ago, but I've just kept an eye on the company, but it never panned out unfortunately, which is really interesting. So I think that is an area of interest because more than just looking at your glucose, again, glucose is useful, looking behind the scenes, peeking behind the curtain as to what's going on metabolically, um in terms of insulin and not just insulin, but also glucagon and a few other things, um adiponectin, ghrelin, leptin, etc. These things are very important, but insulin would be the big thing. Yeah. Yeah. The only way to really do that would be to have a modified OGTT or oral glucose tolerance test where you also measure insulin at various points. Because a normal oral glucose tolerance test, you have a baseline, you give someone a certain amount of glucose and then you measure what happens over a certain period of time. Again, you know, tends to be done in the UK mainly in pregnancy. Um or could be used diagnostically for diabetes um if other measures haven't been useful. But if you added in measurements of insulin, even if your blood glucose levels remain constant, you may see a spike in insulin. And that may well be the earliest marker of insulin resistance for people whose HbA1c's are otherwise normal.
Dr Rupy: Yeah, this is one of my bug bears actually with the current testing that we do at the moment within the NHS. We actually intervene quite late once a lot of those systems that have maintained balance in our blood sugar have been disrupted so much so because of the fact that insulin is keeping everything looking good.
Dr Sharok: I mean, we've not really um focused on that. Um unfortunately, the thing is the nature of the NHS is such that it is a burden for the doctors and the nurses that work there. As much as we would love to be in a position to spend three hours with each patient trying to work out what's going on, we have to get through our lists. Yeah. So, unfortunately what happens is even highly qualified doctors with PhDs and interests in, you know, endocrinology, etc, um will still follow the the guidelines. And if your blood sugar levels are particularly high, even though your underlying problem is hyperinsulinemia and insulin resistance as a result of that, one of the treatments is to give you insulin.
Dr Rupy: Do you ever do fasting insulin?
Dr Sharok: Yeah. Yeah. Do you find it useful?
Dr Rupy: So there are there have been measures of insulin resistance, you know, so HOMA insulin resistance and fasting, the theory that uses fasting glucose and insulin in in various ways. So these are imputed measures of insulin resistance. Um without doing sort of like a an insulin glucose clamp, um it's quite difficult. So but these are useful. Yeah.
Dr Sharok: Yeah, yeah. And just for the listener, these these um insulin glycemic clamps, you know, these are done in research settings where you can get a.
Dr Rupy: You can pay people if you want to get it done.
Dr Sharok: Oh, really?
Dr Rupy: Yeah, it's like anything. You can pay people for anything, right?
Dr Sharok: Really?
Dr Rupy: I'm not one of those people.
Dr Sharok: Okay, yeah, I was going to say because it's pretty involved. You've got to have cannulas on each side and then you've got to have a constant infusion of insulin and then dextrose and yeah, yeah.
Dr Rupy: I wouldn't recommend it. It's not needed. It's not needed for most people. But some people like that guy Brian Johnson. Sure, yeah. You've probably heard of it, right? Not Brian Johnson, the Liver King, Brian Johnson, the other guy. The other Brian Johnson. Yeah, yeah. Um he's just doing everything to try and draw attention to himself. I know what's going to happen in a few years, but the reality is most of what he's doing is not needed.
Dr Sharok: What what's going to happen in a few years?
Dr Rupy: So he's a successful businessman. I can't remember exactly what he did, but he earned a lot of money, many hundreds of millions. Now the thing is, unfortunately, once you get to this kind of level of success, hundreds of millions of dollars or pounds is not enough. You're kind of looking like my friends are billionaires and they have yachts and they have they're going to space. So I want that. So I think he's realized, this is my guess and I'm pretty sure I'm right, that healthcare and preventive health and longevity and metabolic health and and sort of biohacking, whatever you want to call it, is the next domain where people can make money. And it's his job now over the next five years, he's been doing it for two to three years, next few years to show people, look, I'm doing this. I'm spending two million, famously he says I spend I spend two million dollars a year. But what he's doing is just garnering attention. Everybody's heard of him. Everybody knows. And he's doing it with crazy things like I'm measuring my erections compared to my son. I'm taking infusions of blood from my son. I have he says stupid things like I have the metabolic health of a 20-year-old. He doesn't. Yeah. Um but people get to know him. And in a few years, he'll say, well, I spent two million a year, but here is a plan that you can pay me 100,000 a year. And people who are very rich will say, actually 100,000 for something that costs two million, I'm happy to pay. He'll have a plan below that, which will say, it's actually, you know, if you want the lower plan, it's 10,000 a year. And if you want the really low plan, you can buy my books and my supplements and my whatever. So this is all marketing, but he's getting that attention and he's getting things in place beforehand. Almost 100%.
Dr Sharok: Yeah, yeah. I mean, I I agree with the the outcome. It's definitely heading that direction. In fact, the supplement company is already worth over 100 million or doing over 100 million in revenue.
Dr Rupy: That's not enough for him. It's probably not enough for him.
Dr Sharok: But I, you know, I think it's it's getting more people to think about preventive medicine and taking ownership of their health. That's one way you could look at it. The other way is like, well, no, you know, it's telling people to spend money on expensive infrared lights and actually they just need to clean up their diet and that's the majority of of what people need to do. But perhaps he's not really trying to influence the majority, maybe it's just the minority that can influence the others themselves in their own ways. I don't know. It's it's a it's an interesting circus to watch from the sidelines.
Dr Rupy: I mean, the thing is if you take a population of people, there'll always be people that two or 3% that take things to an extreme. So that will appeal to them. So, but the vast majority of people don't need to do that. And whether or not those things that he's doing are of any benefit, we don't know. Yeah. But there is benefit to people selling that product. So in the gold rush, the people selling the shovels are making money whether or not you find gold. You know, um and that's essentially how they're kind of looking at it. People are getting more aware of your own health and there will be people who will just do simple things, modifying diet, being a bit more cognizant of their sleep, being a bit more cognizant of their exercise and posture and things like that, mindfulness, whatever you wish. That's probably doing most of the benefit. All of these things extra, wearing rings to, you know, measure your sleep, wearing tapes to close your mouth. I mean, some people might help and, you know, having CGM monitors on all the time. I saw a chap in the airplane with two CGM monitors on. One on each arm. Two different types. One one Dexcom, one freestyle.
Dr Sharok: Do you reckon he was just trying to tell if there's a difference between the two?
Dr Rupy: He says I don't trust. Literally. I mean, he was so, you know, he was just sitting there on during the whole flight just looking at his stats. Really? Yeah, so there are people who will take things to the extreme and it appeals to them.
Dr Sharok: I'll be honest, I've done that myself. I've I've tried to tell if there was a difference between the two and I took true measurements as well of my just a finger prick.
Dr Rupy: What was it for you?
Dr Sharok: Dexcom was more accurate, but then again, Dexcom allows you to calibrate. So I think perhaps that's one of the reasons why. But it's the trends are the same.
Dr Rupy: I mean, and the thing is for most people most of the time who are using it for monitoring diabetes, it's they're all fine. You know, and I think the now the new freestyle Libra is also they they alert you when you have a hypo. Which they didn't used to do that.
Dr Sharok: There is, yeah. Yeah, yeah, yeah. In fact, the freestyle 2 plus, I think it's called, um they've actually given me one to to try. So, yeah, I'm going to but mainly to, you know.
Dr Rupy: But put it this way, and again, I'm not casting shade on anyone. I know more about metabolic health than a lot of people, a lot of doctors, etc. I don't do any of that stuff. I've used a CGM just to see. And I'm aware of my sleep, I'm aware of my diet, I'm aware of exercise. I don't believe I need to do any of that stuff. There's a few supplements I will take, but despite some evidence for lots of supplements and, you know, there've been putative benefits for all kinds of things, all kinds of things, I choose not to take them.
Dr Sharok: Okay. That's really interesting. I want to talk about supplements a bit later, as well as your fasting regime and ashwagandha for your hair.
Dr Rupy: That's a joke, by the way. It's not. I know. Squirtle application of ashwagandha doesn't grow your hair, just so you know. Not on your head at least.
Dr Sharok: I think I think the the audience got that. Hopefully anyway. Um let's bring it back to the brain. So, uh what I with the caveat that, you know, some of these mechanisms are putative, a lot of them are influenced by animal models. What is going on in the brain when you have an average blood glucose level that is high, i.e. pre-diabetic or as a type two diabetic, or even those that who have high insulin levels but the normal blood sugar levels.
Dr Rupy: You mean what is going on that's abnormal?
Dr Sharok: Yeah.
Dr Rupy: So you may well be, in fact, you probably are accelerating brain aging in various cortical regions of the brain. So the brain has lots of different tissue. Most people will probably be familiar with white matter, gray matter. Two main gray matter components. The gray matter generally, if you think about it very simple, if you think about it as a computer, your CPU, the processing units, the GPU, they're like the gray matter, and then you have the wires that connect them together, the motherboard, etc, that ties everything together, that's the white matter. Um very overly simplified, but that's just where we are for now. But the gray matter in the cortex, which is the outside of the brain, is where you do most of your processing of information. So cognitive function is from there. Um although interestingly enough, there is some suggestion the cerebellum may have some cognitive impact that we didn't realize, but we won't go there. That's these are still hotly debated. Um but the energy metabolism within your cortex, especially within your temporal lobes and the the limbic system, the hippocampus, these are the areas where you have memory retention long and short term. Um and again, memory is not the same as attention, it's not the same as registration, etc. And, you know, when patients come to me say my memory is not great, I try to really work out and we do the cognitive assessments um to see what exactly are they talking about because often they're not talking about memory at all. So pathological memory loss is pathological, whereas attention deficits are very common and not not suggestive of anything pathological. So that's a clear thing that we have to clarify. But if you were to have prolonged levels of abnormal glucose metabolism such that you have hyperglycemia in your um in your blood, um you're very likely leading to hypo metabolism in certain parts of your cortex, which is why they shrink. Everyone's brain shrinks. So from the age of zero to 25, 26, we think the brain grows and it gets to its final size.
Dr Sharok: Do you know the average size of a adult male Western European brain?
Dr Rupy: I couldn't tell you.
Dr Sharok: In litres, 1.6 litres. Now obviously if you're in South Asian, you know, smaller, if you're African, it's a little bit different, but we have lots of data. It's 1.6 litres. What about females?
Dr Rupy: Same?
Dr Sharok: 1.4. Okay. So now we have objective data that women have smaller brains than men. This is where you edit it out. But my I've had my brain volume measured, it's 1.3.
Dr Rupy: Okay. So it's it's, you know, it's not reflective of performance or anything like that.
Dr Sharok: Not at all. It's this is just one of those things, yeah. I always remind that to my um you know, academic students. But it doesn't mean anything. But from 25 to 35, you probably have peak brain. Okay. Now if you're drinking a lot of alcohol, if you're engaging in lots of illicit substances, you're probably damaging your brain to some extent. But from 35 onwards for most people, you have this very, very slow shrinkage of the whole brain tissue. Now there's billions of neurons in the brain. Exactly how many is difficult to know. The cerebrum has a certain amount, the cerebellum, which is structurally smaller, probably has more. And it's much more dense. Now, but they will all start to shrink. The typical normal rate of brain shrinkage is something like 0.1 to 0.3% per year. Okay. And it does accelerate as you get older, after 65 is a little bit quicker, after 85 it's starts to sort of decline quite rapidly. But what we would be worried is for people who have hyperglycemia and other sort of issues in addition, but also hypertension, you are very likely accelerating that rate of atrophy, which is that shrinkage, especially in your brain parenchyma, which is the gray matter in the cortex. Okay. And that's where a lot of the processing happens.
Dr Rupy: Gotcha. Wow.
Dr Sharok: Now there's other things that can happen. You can start to cause blockages in the smallest blood vessels deep inside the brain, the white matter. And even though that doesn't change the processing of data itself, the connections in between are a lot slower. So you may get increased access times. Or although you won't necessarily be incorrect like you might be if you have problems with cortical function.
Dr Rupy: Gotcha. So it just takes you longer to do things, remember things. Yeah. Yeah.
Dr Sharok: So the memory is there and you might remember that you forgot. Um but it's not quite the same as cortical dysfunction leading to cognitive abnormalities.
Dr Rupy: Gotcha. Okay. So you have this accelerated loss of brain volume that is normal, but it's just at a higher rate if you are someone who has got high levels of.
Dr Sharok: But specifically in the parts of the cortex which which are um sensitive. I mean it is quite complicated. So most of the cortex has GLUT3 receptors. Okay. So that does not require insulin. So insulin can go through relatively straightforward. Now, if you are in a position where you have hyperglycemia, which is prolonged, that's usually a sign of insulin resistance. And your blood-brain barrier that we talked about, very likely gets insulin resistance too. So it's allow it allows the glucose through into the brain, but you're not getting insulin through into the brain as much as you might do. So what you get is a relative reduction of insulin within your brain. Gotcha. Now, in GLUT3 mediated glucose transport in much of the cortex, it's not that big a deal. You're still getting glucose through. Now there are other things which may affect it, but the hippocampus is a little bit different in the sense that it has a lot of GLUT4 receptors.
Dr Rupy: Let's just describe the difference between GLUT3 and GLUT4 because GLUT4, yeah, GLUT4 tends to be the receptor that we talk about within the body that is in muscles specifically.
Dr Sharok: But it's the muscles are a little bit different though. In fact, it's quite different. Okay. Um because the thing is GLUT4 does require insulin. So insulin insulin dependent glucose incursion into the cells. However, in the muscle, if there is a very rapid contraction and and relaxation, you can open up glucose independent or insulin independent channels, which is why exercise allows you to just suck in glucose. You can't really do that with brain tissue. You can't rapidly expand and contract it in the same way. So if your GLUT4 receptors aren't able to bring in glucose because you have a relative deficiency of insulin within your brain compared to outside, you will starve your mitochondria of being able to produce energy through the, you know, the normal cycle that we love learning in medical school. Um with glucose and oxygen, yeah.
Dr Rupy: Okay. All right. Um and GLUT3, so that's independent of insulin.
Dr Sharok: Yeah, again, these are sort of over simplifications because every tissue has a little bit of different types of cells, but there's GLUT3 predominance in much of the cortex, not all of them.
Dr Rupy: Gotcha. Okay. So you you get a situation where your brain becomes awash with glucose and this is what.
Dr Sharok: Well, there's abundant glucose.
Dr Rupy: Abundant glucose, but more so and it's not getting into certain cells.
Dr Sharok: Yeah. But it doesn't necessarily have a toxic effect in the same way that it might do.
Dr Rupy: Ah, okay. That's a that's a big differentiation because when I think of excess amounts of glucose in the blood, I'm thinking of, you know, advanced glycation end products, the sort of rusting effect, inflammation, all that kind of stuff. Is that?
Dr Sharok: Yeah, I mean, you could argue that it probably does that, but much much later on. It isn't it isn't immediate. You don't get that hardening and, you know, etc. Um AGEing as it were. Um but you could probably look at people over 20, 30 years and go, actually there has been some AGEing etc. And maybe it's a contributor. Maybe it's a contributor in other parts of the cortex, but in the hippocampus, which is where you get significant reduction in volume, so atrophy in people with the typical amnestic Alzheimer's, that's a different process going on completely.
Dr Rupy: Okay. It's the lack of glucose.
Dr Sharok: The lack of glucose. And which is why what a a PET scan, which again, PET scan can can look at lots of different things. There's amyloid PET, there's there's glucose PET, but an FDG PET, which is radiolabeled glucose, one of the key things that you see in a typical amnestic Alzheimer's is you've got reduced, you get hypo metabolism of glucose in that region.
Dr Rupy: Yeah, so this is something that I think I want the listener to to really get a grip of because it's almost like unintuitive to most people to think, oh, well, I've got high levels of glucose in my blood, but I'm not getting enough glucose in parts of my brain, which is actually the reason why I might be experiencing accelerated aging.
Dr Sharok: I mean, there is data, not many people look at it, but you can measure insulin in your CSF, which is a compartment of your central nervous system. Insulin tends to be a bit less. It's not 100% that straightforward just be just to be clear. And there has been, there have been attempts at delivering insulin directly into the CSF, into the central nervous system as a way using inhaled insulin.
Dr Rupy: Yeah, so I was I was going to ask you about intranasal insulin actually and whether that's a recognized treatment or something that.
Dr Sharok: Small pilot studies suggested a benefit. There was uh I don't know if something's been done more recently. A few years ago, there was an attempt um to do it in a larger scale, but they ran into technical issues with the actual nasal sprays that they were using. So there were technical problems that they couldn't interpret the data, but it didn't work and their explanation was that the technical delivery of insulin intranasally wasn't good enough. That's how they've interpreted it. So I haven't looked at it more recently. But am I going to say to my patients now go and take some insulin intranasally?
Dr Rupy: Sure. Okay. I wouldn't. Gotcha. Is that ideas? I guess one of the things that bothers me um about this new age that we're in where we have the democratization of information, anyone can get up and get on their pedestal and talk and they can get an audience, is that the scientific process which has allowed us to get to where we are in the world, we've kind of forgotten it. It used to be that I have an idea. I think insulin is important. I'm going to give it to someone intranasally. You would then test it. Before you test it, you'd have to think about what's the biological plausibility. We're sitting here chatting about the biological plausibility now. And then we as researchers, we go and test it in cells. And then if it works in cells, we'd then test it in murine rat models. And then we'd test it in a few patients. And then after many phases of doing clinical trials, we'd then see is this actually number one, safe? Number two, is there efficacy? And then number three, number four, is there effectiveness in medium and large size? And then we'd release it out into the wild. 30-year process minimum. What happens now is you have people who are incentivized because they have products to sell, etc, to say, well, I don't know, lithium orotate has some evidence, let's give it to people and it should now be used. Or um I don't know, I mean, there's so many different things which have putative benefits. People are skipping that 30 years of work and saying this is what we should be doing. Because that's what they're selling. Doctors do that too. And that bothers me. Because I think if you are selling products which are, again, fine, if you're in clinic and you have MRI scans and you try to sort of, you know, blood tests for patients and it's appropriate, fine. But if your entire platform is, hi, I'm this doctor and I have this degree, people may not know if that's relevant to what you're talking about. And then by the way, here's my stuff that I'm selling. That raises eyebrows to me.
Dr Rupy: Yeah. To me. Yeah. Yeah, no, that's fair. That's fair. I think there there is um a perversion of the scientific method when there's money involved. I think that's.
Dr Sharok: But the perversion of the scientific method has happened even before all of this. Yeah. Because when you are a company selling products which are maybe other things. Whether that's a pharmaceutical company or a supplement company.
Dr Rupy: Yeah. So it's it's not just now. But but I think we have to as doctors be a bit more careful.
Dr Sharok: Sure, sure.
Dr Rupy: Because people need to trust us. Yeah, yeah. You know, if if we, if people lose trust in doctors, that's that's near the end of the downfall of society. You're kind of terminal stages of society unfortunately.
Dr Sharok: I I I honestly, and not to take us too much off track, but I think this is something that has occurred um post pandemic in a big way. I think, you know, coupled with the lack of satisfaction with being seen, particularly in the UK, the lack of access and the just how easily accessible information is in all different forms, misinformation and good information, um we've we've created this like massive divide between doctors and the general public where there is a lot of distrust now. So, and I don't know how we we mitigate that. I don't know how we we correct that, but.
Dr Rupy: Most doctors now, I don't know, you know, our training some time ago was a little bit different. Um we don't understand the scientific method. We don't understand its place in the Western world, in Western philosophy, etc. Um so we don't even understand what we're doing most of the time. This is the issue. So we're not really a lot of us aren't in a position to even interpret what's going on. We don't have the tools to to unpack it and say, look, what exactly is happening in patients' minds, why is this happening? And I think that's a real failing. Um but um the issue that we have is it's not just doctors that are leading this, it's not just patients or, you know, whoever the um political entities might be that are leading this. There is something else going on behind the scenes that we don't quite understand. And I think we can probably leave it at that for that. Well, that's sort of, you know, getting into Trump and everything else.
Dr Sharok: No, no, I mean, that's not why we're here, but there are things going on which are interesting.
Dr Rupy: Sure. Yeah, yeah. You know, diagnostic criteria changing, you know, things are coming out at the same time as diagnostic criteria changing. So people have plans. These things don't happen overnight.
Dr Sharok: Yeah. And that leads to more distrust, I think, because I think there's this idea that all doctors are in cahoots with, you know, those those events.
Dr Rupy: Most of us aren't.
Dr Sharok: Oh, for sure. Yeah. Yeah, yeah.
Dr Rupy: Yeah. And the thing is that the the distrust started some time ago, um but you're right. This pandemic, etc, etc. People have really started to distrust and and I see a lot of patients coming in to clinic, in NHS clinic but also privately who actively want to go against the status quo of medicine.
Dr Sharok: Gotcha. Yeah. Um I'm going to bring us back to the brain. Uh so we we talked about accelerated aging potentially. Um you mentioned the M word, mitochondria, which has has become a buzzword, I think online for basically anything, you know, increasing mitochondria. I mean, I I'm a big fan of exercise. I'm a big fan of, you know, hit training in particular. Um but let's talk a bit about mitochondria and why it it's so important to this conversation around around dementia and what role it plays.
Dr Rupy: You can't have a car without an engine. Well, I guess you have motors now with electric cars, but you you need the thing which drives the engine to produce energy essentially or the motor to produce energy. So this is your, I think the it's almost a meme now, powerhouse of the cell or the, you know, whatever. Um but that's what it does. You know, and there are multiple pathways that may allow um energy to be made. The most commonly used would be the combination of glucose and oxygen. Um but certain ketone bodies can also replace glucose in certain cell types. In fact, a lot of cell types potentially. But without um the currency of energy, of which there's a couple, but ATP is a big one, um your cells won't function. And if your cells don't function, then the organ systems they supply don't function. And if the organ systems don't function properly, then it's going to have a pretty massive effect on the rest of your body at a widespread level. So, yeah, you need to make sure your mitochondria are optimally working. How exactly you do that is quite difficult. I think if there were clear deficiencies in certain processes that allow the normal energy cycle to work to be present. So you have deficiencies replacing that may help an abnormal mitochondrial function to become normal. Can you take normal mitochondrial function and make it super physiologically normal? Like Arnold Schwarzenegger with his special milk that he has. Um I don't think so.
Dr Sharok: Okay. I don't think so. Can you can you know, if you have full optimal function, can you optimize it to 110, 120, 130% beyond by giving a shot of steroids? VTEC kicking in in your Honda engine. I don't think you can.
Dr Rupy: Okay. Um I guess the strategy then becomes protecting your mitochondria as best as possible. So one of those ways is to ensure that you're getting enough of the substrate, glucose in. So, you know, you're not.
Dr Sharok: Doesn't have to be glucose, yeah.
Dr Rupy: Yeah. The other one being oxygen. So, you know, ensuring that your vessels are patent, you know, you don't have high blood pressure, your cholesterol is maintained. Um and then any anything else that would protect your mitochondria?
Dr Sharok: Toxins, you know, smoking, alcohol, other things that people do now. Um it is too generic a question. You know, which mitochondria where? I mean, if you're exposing your lung mucosa to very toxic chemicals, the mitochondria there will be suboptimal, but it may not immediately affect your gut, it may not immediately affect your skin, may not immediately affect your eyes. Um so, you know, you just have to think what is likely to allow optimal functioning at a basic level. I don't think we can go much further than that to be honest. But you're right, if you were to exercise, if you were to make sure that you're getting the adequate nutritional supply for B12, folic acid, vitamin D, omega-3, lots of other things, which are often deficient. We are often deficient in some of these things, in many of these things, and a lot of patients, all of these things actually. Um these will allow good functioning for most of your symptoms most of the time. Everything else which are have these potential benefits of, you know, supercharging your your mitochondria.
Dr Rupy: Okay. One diet that has become very popular in through the lens of brain health is the ketogenic diet. Maybe we could just talk a little bit about ketones and why they are an alternative source of fuel for your mitochondria.
Dr Sharok: I mean, there's there's like any cycle which you're producing energy, you have like a roundabout. You have lots of roads leading to that roundabout. In order for you to get up the M1, you can enter that roundabout in multiple ways. Now, you could be coming in from the side of glucose, you could be coming in the side of ketones. And there's different types of ketones. But both allow the conversion of oxygen and that energy source into ATP and other types of energy sources. But um if we were in a position to talk about brain health, we could look at, for instance, developing children's brains because in the first few months of life, perhaps even, you know, up to year two, we would estimate that in breastfed babies, so babies who are breast human breast milk, something like two-thirds of brain metabolism is actually via ketones rather than glucose. It's very efficient. And I think, you know, I wouldn't be able to quote what test they use to measure efficiency of energy production using ketones rather than glucose, but the general understanding is at least in the brain, it's a much more efficient process. So if you're joining a roundabout rather than you having to go through four exits, you only go through two exits to get to your end product. So what may be useful for brain health, especially we've talked about insulin resistance and the blood-brain barrier and hypo metabolism of glucose, is if you could deliver an alternative fuel source. So you have a hybrid car that is petrol and electric, you run out of fuel, we've still got some electricity, you can still drive your car. We have reasonable data. It's not incontrovertible, it's not sort of beyond any reasonable doubt that if you were to be able to deliver ketones effectively to that part of the brain, you may be able to replenish it and perhaps before it has reached the point of no return because every cell can die and not come back, you may be able to restore function. Doing that is much harder than theorizing it.
Dr Rupy: Okay. Is that do you mean like doing the ketogenic diet itself?
Dr Sharok: So getting ketones into your into the relevant parts of your body, specifically the hippocampus is not straightforward.
Dr Rupy: It's not straightforward. And just because you are on a ketogenic diet doesn't necessarily mean you're delivering those ketones to that part of the brain.
Dr Sharok: What does someone mean by the ketogenic diet? Because what we say is keto, which has become a four-letter word now, um is very different to what it was decades ago. In fact, what interesting tidbit of information is ketogenic diet was mainly used by neurologists to treat difficult to manage epilepsy. Because what was happening is you got excess cortical activity in places where there was abnormal utilization of glucose. Um these are often genetic epilepsies with with glucose transporter abnormalities, not always. And what they found was rather than just trying to calm those areas of the brain down by giving them calming, let's let's use simple terms, calming types of medication that calms the neurons down, actually just delivering more energy to them using an alternative energy source often stopped them having seizures or at the very least reduced seizures significantly. Now, can we then say that the same type of diet, which is very unpleasant, it's not an easy thing to follow. It was very difficult, especially for young kids who had it. Um is the same as what people are doing online, the Instagram influencers or wherever it is now. It isn't. Yeah. It really isn't. So that therapeutic ketogenic diet that was used by neurology to treat difficult epilepsy, which is actually what the ketogenic diet was, isn't the same as keto, which is I'm not having bread, I'm not having chips, I'm cutting out carbs and I'm just eating a lot of meat. Um you're going some way to minimizing the amount of blood sugar, you're going some way to increasing ketone function, ketone production if you have your body switch over to metabolizing glucose um to the mobilization of adipose tissue, adipocytes in order to produce energy and then you get ketones as a as a sort of byproduct almost. Um but that's difficult. Yeah. And the amount of ketones produced through dietary ketogenic diets, however strict, probably isn't enough.
Dr Rupy: Really? That's so interesting. So, I mean, yeah, with the with the understanding that a ketogenic diet is a specific, it's a high fat, low protein, low carbohydrate diet, which most of the popular keto diets online are not adhering to.
Dr Sharok: That's the therapeutic ketogenic diet.
Dr Rupy: Exactly. Yeah. So, um you know, just because you're cutting out carbs doesn't mean that you're automatically on the keto diet. And so I think there's there is a lot of miscommunication around that. For folks who are on a, you know, Mediterranean style diet with good quality fats, low refined carbohydrates and good quality whole sources of protein, if they supplement that diet with exogenous ketones, is there any evidence that that potentially helps?
Dr Sharok: How are they getting the exogenous ketones?
Dr Rupy: Via um consuming them in in like commercially available drinks like.
Dr Sharok: And are they having it whilst in a calorically deprived state or they're fasting or just having it with food?
Dr Rupy: No, just like a isocaloric. So they're eating it with food.
Dr Sharok: Correct. It's just going to be converted into into um to fat probably. Yeah, yeah. Um I think you in order to truly utilize the ketones, you need to be fasting.
Dr Rupy: Okay. So it has to be in a faster state where you actually because.
Dr Sharok: Well, I mean, I can't be that, but just thinking about it in terms of the what happens to it if you were to eat it while you've eaten something, if you if you ingest it while you've eaten something, it'll probably just be metabolized into and converted to fat is my guess. Um but if you were fasting, again, how long you'd have to have fasted for exactly is difficult, but you don't have uh um other metabolism going on of food that you've recently eaten, then it probably will be utilized in a in the way that you wanted to and it probably will then maybe deliver to other parts of your body including your brain maybe.
Dr Rupy: Yeah.
Dr Sharok: Now, have we done the studies to to demonstrate that in thousands of people and compared it to people who are eating and people with fasting we haven't. Yeah. But the guess would be and some studies that could be set up from this, you know, this biological discussion would be to do it that way. My guess is if you wanted to, and I couldn't tell you it's going to work for you or not, is you'd want to do it while fasting.
Dr Rupy: Okay. Is that just purely from the first principles of energy utilization? So you wouldn't.
Dr Sharok: That's my guess.
Dr Rupy: Yeah. Yeah, yeah. Yeah, I mean, the the systematic review that I saw that had a lot of heterogeneity in that was largely looking at um MCT uh consumption as part of a therapeutic ketogenic diet, but there are all different types of ketogenic diets and it didn't actually show that there was beneficial.
Dr Sharok: Yeah, but the the I mean, there's so many issues here because how did they know whether the people were actually following ketogenic diet?
Dr Rupy: Oh yeah, exactly. Yeah.
Dr Sharok: It's self-reported. Sure. Um and, you know, how strict were they being, how much were they taking? What else was in the MCT oil that they were taking? There are so many things. Unless you institutionalize these people and you make sure that you're very clear what you're giving them and you then match the patients or match the participants for age, sex, other things, it's very difficult to do.
Dr Rupy: Yeah, yeah.
Dr Sharok: Yeah, these are. And then you can only do it for a few weeks at a time and then then what's the use of it?
Dr Rupy: For sure. Yeah, yeah. And it's very, very hard to adhere to as well. You'd have to get them in a metabolic chamber.
Dr Sharok: I mean, there may be ways of delivering ketones directly to your brain.
Dr Rupy: Really? You can do anything, right? You have enough money, you can get anything.
Dr Sharok: I'm not suggesting I offer that.
Dr Rupy: Sure, yeah, yeah. But that would be an interesting thing to explore.
Dr Sharok: Yeah, yeah, absolutely. Um neuroinflammation. When we say neuroinflammation, what what are we talking about here?
Dr Rupy: Another, you know, bug bear of mine. My PhD was in neuroinflammation. Yeah. But neuroinflammation for the last 50 years has meant MS as the archetype of macroscopic inflammation that occurs as a result of an immune mediated attack on your central nervous system. So MS being the archetype, but there could also be IgG4 disease or MOG antibody associated disease or NMO associated disease and systemic lupus or sarcoid or something like that. Now, what's happened recently, and again, this is people who aren't familiar with 50 years of literature in neurology, is people have come along and said, well, there are inflammatory processes that occur in the cells which are not macroscopic, they're microscopic, and they've congratulated themselves and said we're going to call it neuroinflammation, forgetting the fact that that term has existed for a long time. But they're talking about, you're talking about low levels of inflammation that you cannot see with the naked eye and that you cannot see using MRI imaging or other imaging modalities because MS, you're going to see lesions, you know, plaques of inflammation, but these are macroscopic. So the new type of neuroinflammation, which again, we need to think of a different name because that trademark's gone. It's not a trademark. I mean, it's like me coming along and saying I've created a new type of rice called basmati rice. Yeah, yeah. And it's existed for however many centuries. Um we need to think of something else. But yes, I know what you mean, intracellular inflammation, macrophage, cytokine, interleukin, etc.
Dr Sharok: How would you describe it if you were to rebrand neuroinflammation, the modern neuroinflammation?
Dr Rupy: I wouldn't bother. Yeah. I wouldn't bother. This is just I mean, I I've been to so, you know, when was the last time I saw you at a conference? A couple of years ago.
Dr Sharok: A couple of years ago, yeah.
Dr Rupy: I've kind of stopped going.
Dr Sharok: Really?
Dr Rupy: I mean, I haven't been to that particular conference. And it's not because I don't enjoy going there or speaking, it's because I've realized that there's two things going on. Number one, most people are just trying to promote whatever they're doing. I give a talk, um and then there'll be a queue of people waiting to ask questions, but no one's asking real questions. They're like, did you know that if you use this and by the way, I sell this product. That's kind of thing. So I was kind of like, what am I doing here? Um and the other thing is people are just trying to flex on other doctors. Look at me, I've coined this term. I mean, I remember going to a conference where they people literally gave someone a a standing ovation because they were so happy that they coined the term metabolic psychiatry. Um and I was like, that's not real. It's the same as what we've been doing for 20 years beforehand, but you've given it a new name. People literally clapping for 20 minutes because this individual had apparently given the name metabolic psychiatry to this aspect to it. It's just a name. You know, and it it bothers me as someone who believes in the science. I love what I do as a doctor. Um it it, you know, without being too skeptical, um it makes me not want to go to these conferences to be honest with you.
Dr Sharok: Yeah, yeah, yeah. Yeah, I mean, look, I've stopped going to conferences for a little while and I prefer to just read myself. Um I mean, they're great networking events. I I quite like that aspect of it. But I I share your concerns about this, particularly when terms and names are like, you know, bandied around and perhaps there's not as much um respect to the history.
Dr Rupy: Yeah, I mean, it just means that they don't really know the fact that this has been going on for 50 years and someone comes along and goes, you know, you know, it's like, I don't know, I mean, you know, there's been a technology, someone comes along and says this is OLED panel, we're going to call it something else. You know, or high high def panel, we're going to call it retina display. We're going to call wireless charging something else. It's existed for a long time, but people buy into the branding. Yeah. I tend not to do that with a lot of things.
Dr Sharok: Yeah, yeah, yeah.
Dr Rupy: Um and you know, having studied this for some time, I've been a doctor for a long time, um you start to see patterns. Uh-huh. You know, this is the thing. So but but yeah, neuroinflammation exists for a long time, but it's not what we're talking about.
Dr Sharok: So yeah, MS is not what we're talking about today.
Dr Rupy: Yeah, humor me. So let's let's rebrand uh neuroinflammation to what we're we're actually talking about.
Dr Sharok: I wouldn't even bother. So what what what just for the listener, microscopic neuroinflammation, how would you describe it?
Dr Rupy: What is it? The Malik method. The Malik method. That's what I'm going to call it. The Malik method. That's what I would rebrand it to.
Dr Sharok: Okay. So we're we're we're talking about microscopic inflammation in the brain, not what you can see on an MRI, uh demyelinating conditions. Um what is going on here? What is driving that?
Dr Rupy: Lots of things. If I were to cut my hand, I would get secondary inflammation. And that's a protective immune mechanism to make sure that pathogens don't cross into, you know, my body from the skin. If I expose my hand to heat for a long time, if I expose my body to cold for a long time, if I had a bite, there would be inflammation. Now, the type of inflammation, exactly the symptoms I have be a little bit different because it's kind of tailoring itself to that um that exposure. But if you have lack of glucose, you get some inflammation. You get uh if you have lack of oxygen, you get inflammation. If you have toxin exposure, you get inflammation. Lots of things could cause it. Um but it depends in which condition because neuroinflammation as we're talking about it now, which is microscopic, is has been linked to not just um biological organic conditions such as Alzheimer's, such as Parkinson's, but also psychiatric conditions, which by definition don't have a macroscopic organic basis. Brain scans should be normal in psychiatric conditions. Um but if you look, people with bipolar, people with schizophrenia, there's a lot of neuroinflammation. Now, this is very exciting because we talked about metabolic psychiatry, we now have approaches to conditions which we've just given people drugs to. And again, not to say, not to um um downplay the effectiveness of drugs in in the right context, that may be an alternative approach to helping people who have otherwise been very difficult to manage. Can I now go on and say, yes, now we have a cure for these things? Of course not. Of course not. And the thing is this has been an area of psychiatry which has been present for some time. There's been interest in it, but um Thomas Kuhn was a philosopher in in the mid 20th century who stated the idea of um scientific or knowledge revolutions. The idea was that you have a body of evidence that is building up. People ignore it. You have the status quo, people believe this. You know, um LDL is bad cholesterol, for instance. And then you just have at the same time as that this is established, other pieces of evidence which don't conform to that status quo. What is believed to be correct. But if that evidence then reaches a point, tipping point and overwhelming point, your supposed to look at that entire data set and say, actually, is what we believed for the last 50, 60, 70 years about LDL cholesterol, for instance, correct? And you have revolutions of knowledge or scientific revolutions that change the way we do things. But the thing is this data on the metabolic effects um of well metabolic um the micro microscopic inflammatory effects in these psychiatric conditions has existed for a long time. How we've been able to manage it, we don't know. This is the issue. But it's reaching a point where they should be explored in a more sophisticated manner. And unfortunately, unless and until you have a drug, because 60 to 70% of all research now in the Western world is conducted by pharmaceutical companies because at the end of the day, they have to invest money to sell their drugs. What tends to happen is unless you have a drug to sell, you don't invest the money in that. Um I won't go into who it was or exactly what happened, but there was a very rich person whose relative became afflicted by a particularly bad form of psychiatric health. I won't go into it. Um it's well known, so you can look it up if you wanted to, but I won't mention it here. And they were so distraught that that the normal methods of psychiatric treatment didn't help them that they tried everything. And the only thing that seemed to help was the keto diet. I'm not going to go into it. I'm not saying keto diet is the cure or whatever, but it seemed to cure them. And now because they have so much money and so much power, they've put a lot of money into it. They're not developing drugs and they're just trying to bring attention. So sometimes what happens is when you have people that are afflicted who have important family members or they are important, um you then almost um sort of by happenstance happen to get a lot of money into this. Gotcha. Um so we're lucky that that's happened. Um I wish there were other ways that we could sort of, you know, prioritize this kind of research. Keto diet is one way of doing things. There are many other interventions that one could think of. Um but I'm glad that we're making progress in that one.
Dr Sharok: Are there any other ways in which you can say hand on heart, we can reduce our inflammation that might have a knock on effect on brain health, specifically dementia?
Dr Rupy: Do the basic stuff. Uh-huh. It's I mean, if you said, you know, if you're wanting me to say drink this amount of green tea with this amount of, you know, this amount of anti-inflammatory drinks.
Dr Sharok: Yeah, that's the thing. So I mean, interestingly enough, the best way to reduce inflammation in your body isn't to drink something, it's to not eat.
Dr Rupy: It's to not eat. Let's let's unpack that.
Dr Sharok: So you you will go to lots of healthcare resorts, Switzerland, Austria, um there's a few in the UK now, and they'll be very happy to give you green milkshakes and all these kind of things. But the thing is antitoxin effects don't come from putting things in your body. The best way to remove toxins from your body is allow it to heal, especially the gut to heal, and actually go undertake a period of not eating for some time. And or drinking includes any any sort of any ingestion. And that probably has a better effect on detoxifying your body than any detox drink.
Dr Rupy: And what's going on there? What is being upregulated in terms of?
Dr Sharok: I mean, the simple stuff because food or even drink, which isn't just water, isn't inert. Everything has a slight irritant effect. Some things are much more irritant than others. Alcohol is significantly more irritant. Um you know, um I'm sure spicy food is particularly more irritant. I wouldn't know exactly what it does, but um things which are very acidic will be more irritant. But the gut lining is being irritated. And food which is more inflammatory, again, we can debate what that is, will have a significant effect on that gut lining. Now, if you stop eating, you're healing that gut just by not eating. Like if I keep rubbing my hand, I'm not going to keep rubbing it more to make it better. You stop rubbing it for a few days and it'll get better. Um that's the very basic kind of idea we're talking about. I'm not suggesting we just all stop eating and we'll get better because you're going to die from, you know, malnutrition. So there is that kind of eat less often, eat good quality foods which are less inflammatory, but when you do eat, eat highly nutritious foods.
Dr Rupy: Yeah. Yeah.
Dr Sharok: That tends to work for most people most of the time, but everyone's different. You know, there are tiny group of people who have um issues which are genetic, um where they cannot metabolize glycogen, they cannot mobilize fat, who if they were to undertake periods of fasting, they would collapse and die. Very rare. But the vast vast majority of people most of the time, um we believe human beings have existed for 400,000 years. Up until five years ago, we believed it was 200,000 years, but we then found human remains that were 200 years older than that. So we're evolving in our knowledge. But we wherever we've been, doesn't matter if you're, I mean, we all believe we probably originated from um Africa in its inception, but whichever part of the world you're from, it would be standard practice for most of our ancestors to have eaten less frequently.
Dr Rupy: For sure. Whether they were forced to or not is a different thing, but you know, that would be standard practice. So we probably have been optimized as human beings to be in periods of not eating and periods of eating. Yeah. It's like I need to sleep, but I also need to be awake. If I slept for 24 hours, I would do some harm to myself, I suspect. I mean, have you ever slept for more than nine hours, 10 hours and woke up feeling not so good?
Dr Sharok: Oh yeah, yeah, yeah. Whenever I've allowed myself to have a lie in at weekends, I always feel worse and more groggy.
Dr Rupy: At a weekend? I've got a 10 month old, so I definitely don't have that many weekends these days. But um yeah, when I when I do have weekends, which is not often, and I've had that experience, I definitely felt groggy. I've always put that down to like maybe me waking up in the middle of a sleep cycle, but it's probably just.
Dr Sharok: Yeah, I mean, even that's is difficult, but I mean, it's like anything, even oxygen too much is toxic.
Dr Rupy: Sure, yeah. Yeah, yeah.
Dr Sharok: Um so there is a an appropriate amount. What may be appropriate for you is a little bit different for me. I mean, Roger Federer famously uh would sleep 10 hours a day. If I try to sleep 10 hours a day, I wouldn't be able to function. Um but there is an optimal amount if you cross which can become dangerous. Same thing with water, same thing with with with oxygen. Yeah. So that kind of balance, I sleep the appropriate amount, I'm awake the appropriate amount. I eat the appropriate amount, I give myself enough time without food the appropriate amount. And lots of different things, you need that routine.
Dr Rupy: This is one of my bug bears about fasting though, because um for sleep, you know, we can track our sleep, whether you're using a device or whether you're using a, you know, a gold standard sleep study um setup, with food, you can determine calories, you can understand caloric burn, you can look at the macronutrient distribution. Fasting, there isn't really like a defined like measurement of success, like a metric that I can actually utilize and say, for you, eight hours of fasting is great for you, you can deal with.
Dr Sharok: You just have to suck it and see.
Dr Rupy: You just have to like experiment and see how you feel. I mean, I've never done a 24-hour fast and I'm not too sure about you, but.
Dr Sharok: I've done more than more than that, yeah.
Dr Rupy: Oh, you've done more than that? Yeah. That's probably why you look so young, Sharok.
Dr Sharok: I'm I'm 72 years old. Do you do regular fasting? No, it's Ozempic. I make I make Ozempic at home. You just take some you take some mayonnaise, you take um psyllium husk, a little bit of egg white, and you just mix it up. And you just get a 5 mil syringe. Okay. Pull it up and just put it on your face. Okay. That's it. That's Ozempic at home. But the thing is you need to let it set for a few hours. And you need to walk around, you know, go outside, go for a walk in the sun. People don't tend to talk to you much. But um I've never had a problem getting a seat in the bus. That's why I look so young, yeah.
Dr Rupy: But but honestly, from from a fasting point of view, is there something that you practice regularly? Because you're a little bit older than me and you look like half my age. That's a compliment. I mean, there's that's mainly genetic. Uh-huh. So if I were an enterprising individual, which I'm really not, I would say, well, look at me, I'm this age and I've got to a stage where I look much younger. It's because I've done this. And here's my plan and pay me money. This is what people do. This is the internet now.
Dr Sharok: Well, you can just give it away for free.
Dr Rupy: But it isn't, it's genetic. It's purely genetic. My dad is in his mid 70s, he looks like he's in his early 60s.
Dr Sharok: Really? Yeah, yeah.
Dr Rupy: Same with my mom. She's just 70 now and she looks like she's in her late 50s.
Dr Sharok: Huh, that's amazing.
Dr Rupy: So as much as we would love to say that something we did, I mean, you know, people who've known me for some time will know that there have been periods in my life where I look horrendous. Yeah, yeah, yeah. Because I'm going through difficult times, etc. You don't sleep well, you've got a really difficult night shift, long commutes, etc. But when you can optimize your sleep, your diet, you're not overtly stressed. Stress is normal. It's actually healthy. But if you don't have um what's the best way of putting it? Non-pathological hypercortisolemia. So not Cushing's disease, but like a very low grade hypercortisolemia, your everything tends to just normalize.
Dr Sharok: Yeah, yeah. Good for you. And you still work in the NHS as well, the majority of your week, which is brilliant.
Dr Rupy: If they could make us work eight days a week, they would.
Dr Sharok: Do you look at any specific markers? So I want to drill down into metabolic health here and um yeah, get get a feel for patient comes into your clinic, I come into your clinic, I want to I want to learn a little bit more about my metabolism. What what should I be looking out for? What should I be measuring to give me some guard rails as well as intuition and feeling and cleaning my diet and doing all the basic stuff.
Dr Rupy: I wouldn't see that patient.
Dr Sharok: You wouldn't see him? Why not?
Dr Rupy: It's too not it's too generic. Okay. So I you have to understand in my clinic, we have limited space. There's like a long wait, there's a long waiting list to join to see me face to face. We can do once in a while virtual consultation about basic stuff, you know, metabolic approaches to headaches, for instance, very simple. But someone just comes and says I want to learn, I'm not going to see that patient. Okay. Um so I have to have an issue going on. Or they have a very clear goal. They have a very clear specific thing. Okay. Both my parents got Alzheimer's in their 50s, what do I do? Uh-huh. Fine. That's a patient that I will spend some time with and I think it's worth them coming to see me. Okay. Um but someone just coming to chat to me for two hours, what do I do and what test should we do? They can get it done much cheaper somewhere else and they'll get the information for free. Okay. And I'm very happy to tell them that. And I'll tell them, listen, listen to this podcast, read this book, you'll get that information. And there are lots of places that will sell you blood tests for free. Do these ones, I'm not going to charge you money. I just don't have the time. So I have to be very selective. But if you as an individual wanted to improve your health, um is it important to look at blood tests once in a while? If you're in your 30s or 40s, probably a good idea to get your basic bloods done at your GP. You don't have to pay money generally and they'll be happy to do it for you. But just be aware that if you want to go to another level where you're like, I really want to try to minimize my risk of Alzheimer's, heart disease, cancer, dementia, stroke, whatever, you will need a bit more guidance. Okay. There is no lack of people who will claim to have expertise. I see lots of people who are trained MRCP physicians, who are GPs, who will just put at the end longevity doctor. Sure, yeah, yeah. How? Based on what? Now you could argue I've done the same thing because, you know, nine years ago I I started looking into this, but there isn't really a criteria. There isn't the, you know, Royal College of Physicians doesn't have a longevity program that you have to do the specialty certificate examination to get through, etc. So anyone can claim to be this because it's not regulated. It's not it's not an entity that exists in in in sort of in any observable form or any demonstrable form. So you need to make sure that you've done your own research, find a reputable set of doctors or labs that will do most stuff. And 3, 400 pounds every three or four years will probably be enough. Just be very careful of people selling you all kinds of nonsense.
Dr Sharok: Okay. Just be very careful. Because it's it's it's a wild west out there.
Dr Rupy: So the basic markers that we're talking about are ones that you can just get your GP to do or are there any add-ons that you would suggest?
Dr Sharok: So HbA1c is important because you need to know where you're, again, there are provisos to it. You need to make sure you're not anemic, you need to make sure you're not no problems with your thyroid, you have no deficiencies in your calcium. There's basic routine panel that we've all done as doctors for most people most of the time. CRP can be helpful, but just be aware that most CRP measurements, they will draw the line at normal being under eight or under four or under two, whereas really if you can get a high sensitive CRP measurement where, you know, you can go down to 0.1, 0.2, 0.3. I think in the UK we go down to 0.8. Yeah, 0.8. Um but we know from a long, long time that the difference between 0.1 to 0.2 could be worse outcomes later on in life. And 0.2 to 0.3 could be worse. So there is that almost linear progression as we go up, although it may not be immediately manifestable or immediately obvious in your young in your youth, but it may be a chronic burden of inflammation exists. And then if you wanted to get a little bit more, you probably get a, you know, OGTT with insulin. If you don't want to spend 400 pounds on that test, the best about 3 to 400 pounds, you can just get a fasting insulin, fasting blood sugar, blood glucose, and they can do a theory or HOMA IR measurement. Most labs will offer that to you.
Dr Rupy: Okay. And a lot of them will send it to you at home. And then you can find your own person to take the blood and send it off in the post.
Dr Sharok: Gotcha. And aside from that, would you say there are any other sort of, I mean, let let's imagine someone comes in and they they do say like, you know, I've got dementia in my family. I've got no idea what types of dementia. All I know is that.
Dr Rupy: Yeah, we'd have to find out. Ah, okay. Because the thing is if we all lived old enough, we'd all get dementia.
Dr Sharok: Sure. Yeah, yeah.
Dr Rupy: Um you know, that atrophy of the brain we talked about, um if you and I both got to 120, we wouldn't be having the same level of intellectual conversation now that we're doing. We'd still be chatting, but the ability to actively analyze the data and think on the spot and think, you know, what could be going on and work out, etc, would be much more slow. But and you would argue that that age related cognitive decrement, if it occurred 50 years earlier, would be typical of dementia. But there's an age appropriate decrement, um but the question is when does it become pathologically abnormal? Now you could argue that if you open up someone's brain and there's loads of neurofibrillary tangles and there's amyloid beta plaques, they're abnormal, but it isn't that straightforward.
Dr Sharok: Okay. So if they said, yes, young dementia under 65, at least one parent, then I'd my ears would prick up. I'd say this and I this is interesting. Tell me more.
Dr Rupy: Okay. And then then you would assess them based on the history of their.
Dr Sharok: Yeah, and then imaging becomes important.
Dr Rupy: Okay. Yeah. So I mean, the thing is we're very lucky. We live in a time where um we have really high quality MRI scans. Just be aware that an MRI scan in one center is not the same as an MRI scan in one center.
Dr Sharok: I don't think people realize that.
Dr Rupy: Let's unpack that a little bit. MRI uses magnets. CT uses X-rays. MRI allows a very sophisticated assessment of tissue. Doesn't have to be the brain, could be your knee, could be your prostate, could be your um another part of the body, but it's very useful for the brain. Now, when you do an MRI, you're essentially putting parameters into that scanner for what is going to be measured and for how long and, you know, under what circumstances. I don't want to go into MRI physics that much. Um but a MRI set of acquisitions have to be set up by the radiographer and approved by the radiologist. So the most basic acquisitions may only be three or four different acquisitions which look at the structure of the brain, look to see if there's any white matter lesions, that's it. But we're very lucky now to have um types of acquisitions which allow us to look at things in a lot more detail. So you can look at the CSF, you could look at blood vessels, uh you could look at metabolism in addition. So you have to be clear who is doing your MRI scan, who set it up, what is the intention of of of those tests. So certain MRI scans will be very good at looking at microhemorrhages. So if you were an athlete for some time, you're worried that you've taken a lot of blows to the head, football player, boxer, whatever, a lot of MRI scans, in fact, the vast majority of them will not be able to detect that. Whereas if you went to a specialist place that's set up to have traumatic protocols, they'll do it for you.
Dr Sharok: Gotcha.
Dr Rupy: And again, simple thing is, you know, the the the quality of the scan depends on the what Tesla it is. So 1.5 Tesla scan versus a three Tesla scan. And now you have clinical seven Tesla scans, which show beautiful images.
Dr Sharok: Really?
Dr Rupy: Beautiful images. Wow. They heat they heat you up while you're in there a lot more, so you're quite warm at the end of it. But um but beautiful images. Like you'd put it on your wall.
Dr Sharok: Really? Wow. That's awesome. Um.
Dr Rupy: But but but for um brain imaging in people who have a risk, you'd want to get high quality imaging from a specialized center rather than just walking into any Harley Street store and say can I have a brain scan.
Dr Sharok: Yeah. Well, I think this is where the accessibility becomes an issue because the vast majority of people will not be able to tell the difference between one MRI scan and another.
Dr Rupy: Your doctor won't.
Dr Sharok: And oh yeah, exactly. Yeah. Yeah, yeah. And I think, you know, it's almost by beware here because you can get a scan, I mean, you can go to a number of different websites and just book yourself in for a scan these days and you'll get a report, but.
Dr Rupy: It's useful because if you're worried about MS, almost all the scans will get rid of MS or or will confirm or exclude MS. Um I can't say confirm 100%. But anyway, let's keep it simple. Um if you're worried about a brain tumor, sure. Most scans will show you have a brain tumor. Not if you're worried that you've bled, if you've already have a major traumatic brain injury, most scans will do that. Even a CT scan will do a lot of that, not MS, but yeah.
Dr Sharok: Okay. Um look, as a metabolic um specialist.
Dr Rupy: That's unofficial.
Dr Sharok: Okay, unofficial.
Dr Rupy: That's how I would call myself. But there isn't a Royal College of metabolic medicine that says Sharok Malik is a certified in the same way that I am a neurologist. Yeah. You know, no one's going to say to me that you're not a neurologist. I mean, there was this controversy, another South Asian who's done very well. I think probably better than us, I'm guessing. There was I'm not going to name her name, but she's a South Asian lady who's become quite famous on the internet. Okay. Unrelated to medicine. She calls herself a psychologist. Okay. But it's transpired over the time that she's never been a psychologist. And it's very likely she may have doctored her. Oh, wow. But she charges 6,000 pounds an hour for consultation.
Dr Sharok: Wow.
Dr Rupy: Enterprising South Asian.
Dr Sharok: Enterprising South Asians. Yeah. Okay. Well, as you're not an enterprising South Asian.
Dr Rupy: But but I guess the reason why I brought that up is because the thing is I can't tell you who is a metabolic specialist, who isn't. Anyone can call themselves that. And the same way that you can call yourself a registered dietitian. Nutritionist in certain countries isn't.
Dr Sharok: Even in this country, you can call yourself a nutritionist and you can have like a certificate that you just bought online or you've done a little course online, but a registered.
Dr Rupy: You've got to be a little bit careful. Yeah, yeah, yeah. You've got to look for the word registered nutritionist.
Dr Sharok: So but I have qualifications elsewhere. And I've done the work and no one's going to question my credentials as a neurologist, as a physician. And then, you know, I explain to my patients very clearly, listen, this is all emerging areas of medicine. As long as you understand that I can never give you a guarantee. Don't come back when you're 80 and say I'm dying because I wanted to live to 90 and tell me that we didn't, you know. Obviously I'd like to hear from you when you're 80, but you know, but don't come and tell me I'm suing you because we have no way of knowing. So it is a quotation mark.
Dr Rupy: Sure. Gotcha. Okay. Well, as someone who's very well read in the area, um let's talk a little bit about diet. I I would love to know a bit more about like what your particular diet looks like and what you would advise for folks aside from.
Dr Sharok: My diet? No one wants to be like me, man.
Dr Rupy: Okay, maybe not your diet, but how you wish you ate, let's say. Or if you were looking to to improve a patient's diet, what would you be recommending?
Dr Sharok: It depends. It really depends. I couldn't say to you that this is the one diet that's going to help you.
Dr Rupy: No, no, no. I'm not I'm not suggesting that there's one diet. What are the principles?
Dr Sharok: So you you can assess diets in lots of different ways. So caloric value, the um the type of macronutrients that make up the diet, how frequently you're eating it. You can even probably get some surrogate markers of how inflammatory that diet is, uh-huh, um based on certain, you know, guesses, certain assumptions, maybe some objective data. You could probably have some understanding of the glycemic index of that diet. Uh-huh. The insulinogenic index, people have attempted to make an insulin index in the same way as a glycemic index. It's it's pretty poor, but it's it's not a bad start. Okay. So these are ways of looking at the diet. But if someone came to me and said, I'm diabetic, I'm overweight, I've got bad headaches, I've got PCOS, I've got eczema and I can't concentrate and I'm, you know, got these conditions, your main thing probably is going to be insulin. Uh-huh. And then you start to formulate what's the best way to bring your insulin levels down. Now insulin doesn't exist without glucagon working, adiponectin is very important, ghrelin, leptin, all of these things are important. So you need to kind of tailor it. But the big thing, and also cortisol to be fair, but the big thing would be what can we do in a simple manner to bring your insulin levels down? And there's multiple ways of doing it. Um there's evidence for uh especially the Roux-en-Y gastric bypass, there's evidence for GLP-1 drugs and GLP, GIP drugs, there's evidence for intermittent fasting or prolonged fasting, there's evidence for low carb, high fat, ketogenic diets. There's even evidence for severe low calorie restriction diets, but you'd really have to go quite low, under 800 kilocalories per day. Um there's some evidence um for um just low calorie and um low fat with unrestricted protein and carbs, but it has the least evidence. Okay. So all those ways are.
Dr Rupy: Kind of your basic, what do you choose to build your plan for your patients? There are other things, of course, you know, um but those are the things. Now, does ashwagandha make a difference? Does, you know, this make a difference? Does that make a difference? Maybe. These are but they are small.
Dr Sharok: Okay. Right. So in the in the grand scheme of things, we're looking to reduce insulin using or take your pick of any any of those diets.
Dr Rupy: Mix and match. Yeah. Yeah, yeah. If the intention is just for your general health, we believe that metabolic syndrome, insulin resistance syndrome probably is a major driver for a lot of chronic conditions. Most of the conditions mentioned, a lot of different cancers perhaps have uh an underlying metabolic basis, not all of them, just be very clear that's a controversial area still. Um certainly strokes, certainly dementia of the Alzheimer's amnestic type, you could make a good you could make a good claim. Um heart disease almost certainly. Metabolic health. So you would be reducing or mitigating some of the risks by reducing your insulin burden, by reducing insulin resistance, and you could make a good case that you're reducing that risk. And there are objective markers for insulin resistance as we say. Um but other conditions which may be less dependent on insulin is much harder.
Dr Rupy: Yeah. You mentioned um metabolic uh headaches. Did I get that right?
Dr Sharok: Sure.
Dr Rupy: What what do we mean by that? I don't think I've actually come across that.
Dr Sharok: I mean, again, these are terms which are not accepted. Okay. But put it this way, if you have significant dysfunction at a systemic level in multiple organ systems, pancreatic, your gut, heart, etc, vascular, hypertension, insulin resistance, headaches are very common. And what we tend to find, again, neurologists we treat headaches, um is people who go away and sort themselves out, whether it's through CrossFit and a specific diet or whether it's through walking a lot and swimming a lot and doing whatever it is, the headaches just disappear.
Dr Rupy: Huh. And what do we put that down to?
Dr Sharok: There's lots of potential reasons why that could be the case. Where does the pain of a headache come from? Got no idea. Could come from lots of places. Your the nerves around your head could come from the muscles around your head, could come from your skin, could come from your teeth, your sinuses. Almost never comes from your brain. I mean, now there are some people who have brain tumors. In many, many, many years of being a neurologist, I've seen in the in the clinic, not acutely, just to be very clear. I mean, for people who've had headaches for more than three months, almost certainly not something sinister. Sure. It's never zero, which is why we scan them. Um but it's very rare for there's something inside your brain causing a headache. In fact, brain tissue itself has no pain reception. It's usually the lining of the brain, the meninges stretching or sagging which causes the headache. But if the area surrounding your head are inflamed, whatever inflamed means, irritated, abnormal, metabolically unhealthy, pain may well be much more likely to occur. Okay. Whether that then leads to secondary migraines, migraines are a very specific entity which is electrical disturbances occurring in the brain. Most people when they think of migraine, they're not having a migraine. They just say they just consider migraine to be a bad headache. When they say migraine, they mean bad headache, but actually you can get migraines without headaches. In fact, probably 10 to 15% of people who have migraines never get a headache.
Dr Rupy: Yeah. I I don't want to take us down migraines because I think that's just like a real kind of.
Dr Sharok: You talked about headaches, man, so I can't not mention migraines.
Dr Rupy: I know, I know what you mean. Yeah, yeah, yeah. I have you come across that McDonald's uh migraine hack? Did you have you seen that online?
Dr Sharok: McDonald's?
Dr Rupy: Yeah, yeah, as in Ronald McDonald. People are going to McDonald's and swearing by having like a a meal with like a Coke and it cures their their migraine or takes their headache away.
Dr Sharok: Good for them. It's not it's not something I'll be putting my letters of consultation.
Dr Rupy: No, no, no, of course not. No, no, no. I it's just a phenomena that somebody asked me about because they saw it on Tik Tok and it kind of perplexed me and I had no idea what might be going on. I thought.
Dr Sharok: But but this is, you know what this is? This is these are insensible things that we cannot predict. Yeah. So think of a condition, random condition. Mention something.
Dr Rupy: I don't know, we're talking about type two diabetes for now.
Dr Sharok: Okay, type two diabetes or eczema. Okay. I will think of a random or eczema. Okay. I will think of a random intervention. Brushing your teeth with human feces. Yeah, yeah. If you did it to a million people, there will be a small proportion of people who for whatever reason, doing that insane intervention will help and they will go on Tik Tok and say, look at me. Yeah, yeah. So which is why we have to be very careful with anecdotal data. Yeah. And it needs to be studied. But Tik Tok does not respect the scientific method.
Dr Rupy: Yeah, yeah, of course.
Dr Sharok: It respects views and respects whatever Tik Tok. I never use Tik Tok, so I don't know, but.
Dr Rupy: Yeah, yeah. Yeah, yeah. I try and stay clear of all social media myself. I leave that to other people to do on my behalf.
Dr Sharok: Did you ever read um that I forget the name of that chap, The Anxious Mind? No. It's worth a read.
Dr Rupy: Oh yeah.
Dr Sharok: Um the thing is the the book came out 18 months ago looking at the effects of social media on, you know, brain, metabolic, mental health specifically. But again, this is an important part of medicine. Um but the thing is the data is all from Instagram. It's way worse with Tik Tok.
Dr Rupy: Yeah.
Dr Sharok: And by the time that book came out, Tik Tok had already overtaken Instagram.
Dr Rupy: Oh yeah, yeah, absolutely.
Dr Sharok: So, you know, as much as we try to think about toxins, there are other things which are affecting our mental health, not just that candy bar we're eating.
Dr Rupy: Oh yeah, 100%. I mean, like I've I've had first hand experience of that. I mean, I went on a silent retreat earlier this year and I just felt so much clarity when I came off it. There was no writing, reading, no email, no phone use. And at the weekends, I now have a kale phone. So I have a I have a cocaine phone, not for actually having cocaine, but it's, you know, it's got my social media on, it's got email on, it's got WhatsApp and all the rest of it. And I've got a kale phone, which has no apps. It's actually a phone that you give to seniors. It's got like an SOS button on the back of it. Um and I use that at weekends and it's just got the numbers of like close loved ones and some friends.
Dr Sharok: How long was your that retreat?
Dr Rupy: Three days. Yeah, three days.
Dr Sharok: You know what you can do is you can claim to have trained as a monk.
Dr Rupy: Oh, really?
Dr Sharok: Yeah. And start an entire podcast.
Dr Rupy: And start a whole, yeah, yeah, start a entire new. Oh, there you go. Enterprising.
Dr Sharok: I'm telling you, man. This is this is the way of the world. This is what you need to what you need to do to make money nowadays.
Dr Rupy: Uh look, I want to close this by asking you if you've changed your mind on anything over the last 10, 15 years during your practice.
Dr Sharok: Yeah.
Dr Rupy: What did you change your mind on? Give us give us an example.
Dr Sharok: At a very basic level, we're always growing. Uh-huh. You know, not necessarily height, but we're always growing in ourselves. We have to. If my medical, even life views are exactly the same as they were 15, 20 years ago, when I'm a teenager compared to my mid 20s, my 30s, my 40s, my 50s, my 60s, things have something's gone wrong. You can't be static. I'll give you a non-medical example. For a long time, I used to love Lululemon and yoga and oat flat whites. Now, I like aloe, Pilates and matcha. You have to change. And maybe in a few years, I'll be wearing Sweaty Bettys, I'll be doing CrossFit and having Coke Zero. I don't know. Yeah, yeah. You have to evolve. Yeah. Right? So same thing with medicine. We talked about scientific revolutions. Things will change. How we thought about medicine a thousand years ago versus 500 years ago, versus 100 years ago, versus 50 years ago, even 10 years ago, we have to think differently because it's evolving. The scientific method implies that the inductive method that we use to determine scientific data is always imperfect. And the highest level of evidence that we have for science, as opposed to maths, can never go beyond hypothesis. It never goes beyond hypothesis. If you look at the philosophy of science and how we've got here, nothing is proven in the same way that mathematics is proven. So we always have to assume that there is room for improvement. There's always room to further clarify. Now, certain things may become established, you know, headaches are from this and, you know, tumors cause this and this causes that. But there will always be room to further refine that, etc. So when it comes to metabolic health, diet, longevity, preventive health, whatever you want to call it, that is a very rapidly growing area of medicine. And the knowledge base that we had just 15 years ago, just 10 years ago, just five years ago, is rapidly different to what we have now. And the people who have just set up their stall and said, this is my bag, I am going to sell this way of doing things, they're not contributing. Because they've essentially said this is what I've chosen to be my way of making money or having my career, whatever. But you have to keep changing.
Dr Rupy: Yeah. Yeah. Um let's end with some quick fire uh supplements uh for brain health. Ashwagandha, skip or try?
Dr Sharok: I wouldn't try it. There is poor quality evidence for and poor quality evidence against. Okay. But the data is very poor. Okay. Um the risk of damage from ashwagandha is actually very low. So as long as you're getting this supplement or maybe others from reputable sources, and there are ways of checking to see what's in, you know, a supplement company manufacturer's supplements, um you can try it. I wouldn't try it myself.
Dr Rupy: Okay. Creatine for brain health.
Dr Sharok: Interesting because it's been it's been tested um sometimes, um going back some, you know, it's sorry, it's been in it's been tested in some form for some time. So even going back 10 years, we have some data on potentially helping people with Parkinson's. We've more recently been very excited about creatine in people who are sleep deprived. But that one study that became big on social media only looked at 15 patients, 15 subjects.
Dr Rupy: This is just 15?
Dr Sharok: Yeah. So again, you have to be very careful. It's one study. Um and more recently, there's been proof of concept in patients with Alzheimer's, 20 subjects, of which only 19 got the adequate amount of creatine. Um so tiny numbers. And just be aware, medicine is littered with all kinds of interventions where there were very promising pilot studies which never panned out. I mean, very famous, and again, I won't name the name because the chap's very litigious. Chap was a um um aging and longevity researcher and found some astonishing benefits to a compound in rat models to the extent that a very large pharmaceutical company bought his company for many hundreds of millions, almost almost a billion, not maybe two-thirds of a billion. Yeah. Um and then any attempts to reproduce that data by that company and anyone else has failed. Yeah. And they just shut it down after some time. So it's it's common. People get excited, everyone starts buying it. The people that benefit are the people that promote it because they're selling the product. That's it. So just be aware that this is the nature of medicine. And the reason why this skepticism for any diet, there are people who love the keto diet, who love plant-based diet, who love this, caloric intervention, who love whatever, is because people have been touting food and supplements for centuries, if not millennia, as being the cure to everything.
Dr Rupy: Yeah. Yeah. Omega-3 for brain health.
Dr Sharok: Potentially very helpful. I take it.
Dr Rupy: How much?
Dr Sharok: 2,000 milligrams a day, but it has to have DHA and EPA.
Dr Rupy: Gotcha. It's a fish oil.
Dr Sharok: Fish oil, yeah.
Dr Rupy: Ginkgo.
Dr Sharok: Maybe better for your PMS.
Dr Rupy: Okay, yeah. But not really for.
Dr Sharok: I mean, there's there's small level studies, but conflicting data. Okay. This is the thing. So um again, you know, is it on my list of things to suggest to people to do to optimize their brain health? No, it's not. It's not even on the list. But if someone said to me, I want to try it, sure. They can try it. Uh you know, I don't have an issue with that. Just be aware, it's a very old um compound. I think it's East Asian. Yeah. Um and historically, they used to get it from the leaves, more recently they get it from the root. It's a little bit different. Um often is mixed with other things in addition. So whether you're getting the benefit from the actual ginkgo biloba itself or from the other compounds they're using is very difficult to know. Part of the problem with trying to analyze the small studies which use usually non-randomized, non-age, sex and health matched controls or there's no controls, is you don't know what exactly is in what's being given. And so we even when you're trying to do a meta-analysis, it's quite difficult. It's quite difficult to really try and work out are we comparing like for like.
Dr Rupy: Okay. Not compelling.
Dr Sharok: Okay. Uh hyperbaric oxygen therapy for mild cognitive impairment or? Potentially. I wouldn't offer it. I wouldn't suggest it. Someone wants to try it and lots of people do offer it as a therapy. And people have used it for chronic fatigue syndrome, people have used it for um long COVID, for instance, and there are many charities I think that will, if you have a diagnosis of one of those, not not MCI necessarily, um they may help you get cheaper access to that. Um I don't think there's any evidence unless there is a visible problem. So people, there is we have some evidence in people who have had traumatic brain injury. Um there's some evidence of people with, you know, barotrauma from diving and things like that. So that makes sense. I don't think mild cognitive impairment where you don't have objective abnormalities is going to be helpful. But just be aware too much oxygen can be harmful too.
Dr Rupy: Yeah. Um okay, and finally, uh as your clinic is got longevity in the name, uh are you bullish on any geroprotective agents at all? You mean agents that you take?
Dr Sharok: Yeah.
Dr Rupy: Either ingested or infused? No. We're not there yet.
Dr Sharok: Yeah.
Dr Rupy: That is really interesting. I would dissuade anyone from going down that route.
Dr Sharok: Yeah, yeah. So and none of these agents, metformin, uh NMN, NAD boosters, none none of those.
Dr Rupy: Rapamycin.
Dr Sharok: Rapamycin, yeah.
Dr Rupy: Sirolimus in this country. Uh-huh. Um maybe. I have no idea. In fact, it has by far the best evidence.
Dr Sharok: Huh.
Dr Rupy: Resveratrol, the cert 2, very poor evidence. Um I shouldn't say very poor, it's there, but it's not great. Yeah. Um but Rapamycin, Sirolimus has data. We don't know how to use it. Yeah. Yeah, yeah. And there'll be no end of people very willing to prescribe it to you, but they don't know how to use it. Yeah. It is mainly used in transplant patients to prevent rejection.
Dr Sharok: Yeah, exactly. Just be aware. Yeah, yeah, yeah, exactly. It's not something pleasant uh that I I would recommend anyway. Um Sharok, it's been great chatting to you. I I agree with so much of what you've said and I particularly like your stance on the fact that, you know, you work within a longevity clinic. I know it's called that, but you're practicing like phenomenal medicine, evidence-based medicine and you're you're just very, very pragmatic and I I really appreciate that about you.
Dr Rupy: So thank you. I really appreciate you taking the time to have me on. I have to say, just as something, you know, you are definitely one of the top three dilfs that I always think of. You know, I do you know Rohan Francis?
Dr Sharok: Uh no.
Dr Rupy: Francis. So he's Medlife Crisis number one, my favorite my favorite dilf. Uh number two, Sanan Mir, do you know Dr Sanan Mir?
Dr Sharok: I don't, no.
Dr Rupy: World famous. Uh he is the world's most foremost authority in um preventing female urinary tract infections.
Dr Sharok: Really?
Dr Rupy: Yeah, and also unblocking noses of young babies.
Dr Sharok: Oh wow, okay.
Dr Rupy: And you're number three. You're number three.
Dr Sharok: I'm honored to be on that list.
Dr Rupy: My top three doctors I love to follow. Of course.
