Can Fasting Improve Your Brain Health?

Episode Intro:

Welcome to Dr. Ruscio Radio, providing practical and science-based solutions to feeling your best. To stay up to date on the latest topics, as well as all of our prior episodes, make sure to subscribe in your podcast player. For weekly updates, visit DrRuscio.com. The following discussion is for educational purposes only and is not intended to diagnose or treat any disease. Please do not apply any of this information without first speaking with your doctor. Now, let’s head to the show.

DrMichaelRuscio:

Hey, everyone. Today I spoke with Dr. Matthew Phillips about fasting and its impacts on brain and neurological health. What I really appreciate about Matt is that he’s both a clinician and a researcher. This provides one with very valuable insight, partially skewed toward academics and partially skewed toward clinical results. One of the noteworthy things that we discussed is Matt’s hypothesis that mitochondrial dysfunction is really the chief hallmark that fasting helps to rectify – this underlies the myriad of neurological benefits that ensue from fasting. We unpack his mitochondrial hypothesis for brain health, we review what testing he feels has merit for mitochondrial function and we also go into quite some detail about how to find the optimum balance of carbohydrates, as he’s advocating for a predominantly ketogenic state for an individual to be in.

DrMR:

We explore this nuance of ketosis and fasting, which will potentiate ketosis and can be helpful for many things. However, what about this cohort of underweight individuals – due to having IBS or sensitive gut? How do we find the optimum balance there? We touched briefly on post-concussion syndrome. We also discussed what you can/cannot or should/should not have in terms of coffee, tea and milk when you are trying to have something while you’re fasting to take the edge off, but not come out of your fast. We discussed what ketone monitoring device he prefers, a short tangent into sleep/sleep health and how that impacts brain health. It was a really enjoyable conversation and I am very appreciative of Matt’s perspective. With that, we will now go to the interview with Dr. Matthew Phillips.

DrMR:

Hey, everyone. Welcome back to another episode of Dr. Ruscio Radio. I am here today with Dr. Matthew Phillips. I recently came across his excellent interview with Dr. David Perlmutter about the impacts of fasting on neurological health. Matt – One of the things that really struck me about your work was the fact that you’re both a clinician and a researcher. I find this to be such a prized balance where you have part of your foot in academia, research, literature or data tracking, but you’re also staying sensitive to what patients are saying and what patients can do; what might be attractive in theory, but then in practice falls apart for whatever reason. I feel this is a really valuable perspective we can bring to people. So, I was really excited and keen to get you on the show. It’s a pleasure to have you here today.

DrMatthewPhillips:

Thanks, Mike. Likewise.

DrMR:

Can you tell our audience a little bit about your background before we get into some of the nitty-gritty on fasting and brain health?

DrMP:

Sure. Essentially, my training is in clinical neurology. So, I’m a clinical neurologist and I’ve tried to stay as a general neurologist, so not over-specialized too much in any one particular area. So, that’s my background in a nutshell. However, in the last few years, I’ve also done quite a lot of clinical research, mainly trying to apply different kinds of therapies like fasting to people with neurological conditions. So, I really do try to strike a balance between clinical neurology and research.

DrMR:

With fasting, how did you find your way into recommending this as an intervention? It doesn’t seem to be something that’s largely endorsed by mainstream neurology – or at least from my last check-in. So, how did that transition come about?

DrMP:

Your last check-in is correct. It’s a long story. Basically, when I finished my neurology training in Melbourne in 2012, I had been wanting to specialize in some kind of a therapy. Yet, the only options were diseases. To be honest, since I was a very small guy, I thought doctors healed. However, when I was in my second year of medical school, I realized doctors do something a little different – they mask symptoms in no small part. I wanted to heal. I didn’t want to specialize in a disease.

Mitochondrial Health

DrMP:

So, at the end of the training, I just took a year off and bought a one way ticket around the world. I went to a distant country. I was exploring and letting my mind wander away from mainstream medicine. I was looking at all kinds of things to see what could potentially act as a therapy in a number of neurological conditions. It actually took about three years. After that time, I realized that fasting was one potentially very powerful tool that could allow us to do things that medications could not.

DrMR:

Was some of this spurred by European and Middle Eastern countries? Fasting is incorporated as a religious part of their practice. Is that how that initial light bulb flickered?

DrMP:

Yes, I think it probably was. The first year, I was in South America. The second year, I worked in Northern Australia. In the third year, I was in Asia. It was really in Asia where I started to think seriously about fasting. I was in countries like Sri Lanka, Myanmar and Cambodia. I was doing some volunteer work in Cambodia, and a lot of these countries have fasting as part of their religious practices. It goes back a few thousand years. I think that being in that whole environment of not just fasting, but getting a chance to try other things like meditative practices really made me wonder about a flip side to mainstream medicine where we tend to attack diseases. The flip side is maybe instead of attacking diseases, we should try and restore something. I think fasting appealed to me because it was aimed at restoring mitochondria health and health in general, rather than attacking a disease. We don’t talk about restoring health much in modern medicine. We talk a lot about suppressing, attacking or targeting diseases.

DrMR:

You mentioned mitochondria. This is one of the mechanisms that fasting can become a hormetic stressor to. What do you feel are some of the most impactful mechanisms that underlie the benefit of fasting on neurological health?

DrMP:

Well, I think you said it. To my mind, fasting – and other metabolic strategies, such as keto diets – the main benefit is not weight loss, not even improved insulin resistance, not even gut health or any of those things. I know some people might disagree, but it’s mitochondria health. At the end of the day, research shows that of the top ten lifestyle-related disorders killing people today, most have mitochondria dysfunction underlying those – excluding accidents and suicide, of course. If there’s one great thing that fasting does, it is that it allows mitochondria to undergo hormesis, whereby they get used to small stressors, reactive oxygen species and so on. They can get more efficient in the long-term, but the fasting essentially allows them to crucially undergo mitochondria biogenesis and renewal.

DrMP:

When people on a normal, non-fasting related modern diet are ingesting tons of carbohydrates – three or more times a day – the mitochondria never get a breather from the onslaught of carbohydrate. It’s particularly carbohydrates because they crank up glycolysis so much and throw so many reduced intermediates into the TCA cycle – hence, the electron transport chain, which the mitochondria have to deal with. It’s really that lifestyle that hurts the mitochondria. Fasting just takes the foot off the gas pedal and allows them to recuperate. To me, that is the main strength of it. There are other benefits of fasting, of course, but that’s the main one to my mind.

Mitochondria Dysfunction & Inflammation

DrMR:

I think you hinted on my follow-up question – So, what’s happening in the mitochondria? Do you feel it’s essentially inflammation? Or this reactive oxygen species that are a by-product of the high level of carbs in the diet? Or just never being in fasting physiology, leading to this inflammation? Is it this accrual of inflammation that’s damaging the mitochondria and a mitochondrial associated aging that underlies the deterioration of brain health? Would that be an accurate portrayal of part of your thesis?

DrMP:

Somewhat. I think one of the hardest things when we’re interpreting studies and research is we get all these correlations, but it’s figuring out causation. So does the mitochondria dysfunction cause inflammation? Or does inflammation cause mitochondria dysfunction? Or is it both? We know they’re correlated where mitochondria dysfunction is located in a particular tissue. Chronic inflammation is probably going to be there, too. I have thought about this over a long period of time – hundreds, if not thousands, of hours of writing and thinking – and I believe the mitochondria dysfunction is the core problem and the inflammation is secondary to that. Now, that is contestable.

DrMP:

For example, let’s take the modern diet. You’ve got an onset of carbohydrates coming into the blood as glucose and maybe fructose, and that has to be dealt with. So, insulin goes up to push it into cells and mitochondria have to deal with it. There’s basically a creation of two things. The first is you get these advanced glycation end products – AGE’s – and they cause damage and produce free radicals. The second thing, which I think may be more important, is that glycolysis in the cells has to go up so much that you get all these electrons overflowing along the electron transport chain, and they have to go somewhere. They end up producing a lot of reactive oxygen species – or free radicals – in cells along the chain. So, the mitochondria are dealing with a lot of oxidative stress. The oxidative stress, if it exceeds their capability (which it does with the modern diet), the free radicals end up causing the damage. The damage eventually becomes inflammation. Then, you get other responses following that. The main problem to my mind is that we’re throwing an abnormal dietary lifestyle at the mitochondria. Over 2 million to 3 million years of human evolution, we have never seen a diet like this, which has only been around for maybe 50 years.

DrMR:

I certainly agree that anytime we can restore a human’s natural operating system, we will likely see a high degree of benefit. I think one of the most stark evidence points we can point to is disruption of day/night sleep cycles, even if people are getting adequate sleep. In our night shift workers, all-cause mortality goes up – and unless there’s something else there that’s driving this – it just seems deviation from the normal rhythm is enough to really lead to changes in sleep that are enough to lead to all-cause mortality spiking up. This could be akin to where your diet is such a large shift – it’s almost like being a night shift worker,

DrMP:

100% agree, Mike. If we’re grading them, I think the modern dietary lifestyle would be the most responsible thing for poor health today. I would put #2 as sleep deprivation/sleep timing. There are other things such as chronic work stress, lack of exercise, etc.

DrMR:

This is something we’re doing much more with at the clinic. Maybe we’ll circle back to picking your brain on some sleep stuff in a moment.

DrMP:

Sure.

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DrMR:

I do want to ask you one or two more things central to the mitochondria. We had a guest on the podcast three years ago – Dr. Jon Kaiser – who is on mitochondrial research. He did some early work with AIDS populations and found that some of the AIDS cocktails were – I believe it was a presumption on his part – causing mitochondrial dysfunction. So, he used cocktails with carnitine, alpha-lipoic acid and CoQ10. He was finding in this cohort a lot of success. So, he came up with essentially a multivitamin with some mitochondrial supports added to it and reported good results with that. I believe he also mentioned there was this coming test for mitochondria that could be done simply in a doctor’s office. I think it may have even been with a buccal swab. As someone who is a researcher and pretty plugged in here – Are there fairly routinely available clinical tests that a clinician can use to assess mitochondrial function? Or is this more of a presumption based upon symptoms and how someone may improve from an intervention like fasting?

DrMP:

That’s a very good question. Mitochondria really are at the heart of cell metabolism. They do so many things. They don’t just make energy. Measuring what they do and their actual health status is a major challenge. To answer your question, there’s nothing readily available as a quick clinical test. You can do assays on certain enzymes in glycolysis and certain enzymes in the TCA cycle; look at the complex activities in the electron transport chain. You can assess all that. I’ve done that in my master’s research degree and that’s basically what we did for two years. However, even if you measured the energy production, mitochondria fuse and fission; they divide and re-form together. They move around cells and they’re constantly moving. So, that wouldn’t tell you about their mobility. It wouldn’t tell you about how their population of mitochondria and how that health is. They have a lot of signaling functions. It wouldn’t tell you much about that either. It’s very tricky and you have to read into a lot of these studies. A lot of people do measure certain facets of mitochondria health that’s helpful, but a lot don’t. That’s probably one reason why mitochondria health has stayed under the radar for so long in mainstream medicine. There are other reasons, but that’s probably one big reason – it’s very challenging to actually measure them.

DrMR:

I just pulled up the podcast notes for that episode. This is known as the ‘Seahorse Mitochondrial Stress Test.’ Have you heard of this?

DrMP:

No, I haven’t.

Lab Testing Issues

DrMR:

Okay. When we checked it a couple of years ago, it was still pre-clinical. So, I think my audience is pretty used to me having a fairly circumspect position on testing. I’ve noticed in the field of integrative medicine, there’s a clear influence from lab companies that have contorted the practice model because they provide so much education. I don’t think the clinicians are suspicious enough that perhaps a test hasn’t gone through proper validation. So, because clinicians don’t have enough circumspection, many tests permeate their way into the care model. Sadly, somewhat of a mainstay of functional medicine is an initial lab bill anywhere from $2000 to $4,000, which I find to be egregious. This is part of the reason I ask these questions on the podcast, so that the consumer and the clinician can be protected against using testing that’s really pre-clinical and more based upon speculation.

DrMP:

I really like that you say that, Mike. I fully agree that tests have to be validated. It’s not just a problem I suspect in integrative medicine, but of course in mainstream medicine, too. There’s a lot of funding of medications by pharmaceutical companies. One has to be very critical of the evidence, especially when studies are published whereby some or most of the investigators received funding by a company product that they’re investigating. So, I fully agree with what you said.

DrMR:

What about the organic acids? This is something that’s touted as being a multi-utility test in functional medicine circles. For example, D-arabinitol can tell you about candida and other organic acids can be used to purportedly give you insights into mitochondrial function. I’m assuming this may not be something that you have experience with either – and that might be a good thing – telling us in terms of what’s been validated as on your screen/not on your screen. Any comments on organic acids?

DrMP:

No. I don’t use them routinely. I would be lying if I said I knew a lot about them. I’ve heard of them, but I don’t think I would be the best person to comment on them.

DrMR:

Sure. It’s not a problem at all. In my experience with organic acids, they’re not incredibly informative when you really ask the tough question of, “Does this tell me something I would otherwise not know or change treatment in a in a measurable way?” Normally my answer has been no.

The Ketogenic Diet

DrMR:

So, shifting out of testing for a moment, there’s another potential balance point here. I want to see if we can try to give people some guideposts regarding the sweet spot for carbohydrate intake. There are extremes. There’s the person who is having a bunch of processed sugar through soda and processed food, but then the other extreme could be the person who is doing keto, even though it’s putting them in this almost severe metabolic deficit – insomnia, fatigue, thinning hair. They may have read so much about how therapeutic the ketogenic diet can be. They’re kind of shoehorning themselves into this keto diet. Do you see a range for someone who does better on more of a Mediterranean diet? How do they reconcile the fact that carbs can be a problem, but they need to eat some carbs. How do you approach this general issue?

DrMP:

So to my mind, the ketogenic diet is not a diet like any other diet. So we talk about, for example, Mediterranean, vegetarian, carnivore diets – as long as they’re keto, it doesn’t matter to me. I’ve put patients on all of those and they all do well, at least in the short term, over months. So to my mind, the only thing special about the keto diet is that it is putting the body into a semi-fasted state. You’re activating many of the metabolic mechanisms induced by fasting, not all of them and not certainly to the same extent, but you are. So that’s the power. It doesn’t matter if it’s vegetarian or carnivore or Mediterranean, as I said. Most Mediterranean diets are fairly high in fat, but when people say Mediterranean, that’s quite a diverse word. The carbohydrate content can vary wildly, as can the fat content.

DrMP:

So, I prefer to use the term ketogenic and strictly define it as under 50 grams a day as a reasonable term. That’ll get most people fairly ketogenic. Why that’s important is because I do think ancestors evolved in different parts of the world. Obviously, some were closer to the equator and some were more near the poles. From the evidence, I’ve read that people whose ancestors were near the poles tended to have a higher meat content and might have leaned more towards carnivorous. The Inuit of Canada would be a classic example of basically a meat and fat diet with very little, if any, fiber. Whereas, other people who evolved in the temperate or tropical zones, would have had a much higher fiber content and some of them were mainly vegetarian. They would have taken most of their food as plant-based products – not all of it, but most of it. I think that also has to be considered when you’re looking at the person in front of you, but it doesn’t matter either way, as long as they get ketogenic, I’m happy. Keto can be done wrong, as you say, but I think people usually make the same mistakes over and over, and they are simple things to fix. A lot of people think they’re keto and they’re not, and they’re most importantly doing it for the wrong reasons, which often is weight loss. That’s not a reason to do keto.

DrMR:

Would you say it’s the total load of carbohydrates in the day – the 50 gram threshold you provided a moment ago? Or is it the fasting? Or is it the combination that tends to be the best way to get someone into ketosis?

DrMP:

Awesome question. I think a combination strategy is best. There’s very little evidence for this because people tend to focus on keto diets, low-carb diets or fasting. There’s not even much research in the latter, as you said earlier. In terms of combined strategies, those are very rare. Now, that’s what I do as a rule for my patients – combined strategies – because I think it’s good to combine keto and fasting. For example, one common strategy that I use is a 2 meals/day ketogenic diet, where there are no snacks and every other time is fasting. You’re allowed to pick the two meal hours. You have two hours – one hour to eat each meal and you can pick it. So, it creates flexibility and self-empowerment for people. Yet, it’ll make sure there’s 22 hours of fasting every day.

DrMP:

Then, you can throw in multi-day (3, 4 or 5 days) prolonged fasts if you want once in a while. Combined strategies are the way. It depends on the person’s starting point as to how much benefit they’ll get from just a keto diet or just fasting. People who are metabolically very unhealthy – and that, unfortunately, is most people in the west- will probably improve their health on either strategy. So, that’s okay. People who are healthier at the baseline can get healthier still, but I think they might need to use more combined strategies to fully optimize a metabolic function to their mitochondria health.

DrMR:

Do you find that the degree of – for lack of a more tactful term – metabolic derangement makes it harder for someone to transition to this diet initially? For example, a low-carb flu or other negative symptoms when someone’s coming in? Let’s say, frankly, a Type 2 diabetic and also at an obese BMI?

DrMP:

No. I find the people that are more obese/more insulin resistant – so like worse diabetes – find it the easiest. I did a Zoom call with one fellow a few weeks ago who just launched into a 66 zero day fast – he’d never done one before and he was quite overweight. He really didn’t have a problem doing it. So I would never advocate that off the top. I would never advocate that period, but he just did it on his own accord and he wanted to tell me about it. I find that people who are more overweight/more insulin resistant actually have an easier time with the keto diet and the fasting.

DrMP:

It’s the people who are thin that have a harder time. I do it on a BMI as low as 18. So, if someone’s got a BMI of 20, they tend to have a harder time. I’ve noticed the keto flu, in my opinion, is a bit of a misnomer. Most cases of the “keto flu” that I have encountered on a personal experience level, is basically that they’re dehydrated or don’t have enough salt. If you take care of those two things – water and salt – the keto flu is very rare and I don’t think it should be called a flu. I think it should be called dehydration or low salt status in the body. There are other things that you can do to produce adverse effects, but those are the two main things I find that are quite easily correctable.

DrMR:

That was one of my next questions. What do you find to be the most effective to reduce any of this dehydration? Low salt syndrome may be a better term. You also mentioned the cohort I wanted to ask a question about. Framing some of my practice, we will see a subset of patients that may have a bit of orthorexia because they’ve had IBS or IBD for so long. They’ve directed toward under eating. It might have started as gluten-free… and then dairy-free… and then gluten-free, dairy-free, low FODMAP. Now you’re looking at an individual who has a little lower vitality… a low BMI. Sometimes I have a hard time reconciling that with these individuals, sometimes getting them on more carbs is a godsend for them – better energy, better sleep, hair stops falling out, they gain weight…

DrMR:

I agree with you foundationally in the sense that we should be trying to get people to the point where they can fast and be ketogenic. It might just be that I’m not going deep enough into all the dietary recommendations. I’m just trying to get their GI functioning and get them at a normal calorie intake that’s not flaring their IBS or IBD. We then hold them there for a little while and move on, but we don’t necessarily always circle back months and months later to try and get them keto.

DrMP:

I absolutely respect that – gotta respect your clinical experience.

DrMR:

Do you have any other thoughts? It’s kind of interesting to compare notes here. There does seem to be this – albeit smaller – cohort who does better on upping their carb intake. This is where I really came to that observation because I emanated from more of a paleo diet background. Over time, there just seemed to be this small group of people that when we upped their carbs, it was very helpful for them. Do you have any insights that you’ve seen in the clinic? Any notes we can compare here to try to figure out how to give people a list of options they can work through?

DrMP:

It’s difficult because all my evidence is anecdotal, but it is through experience and I think that’s very important. So, definitely, I think some people do better with higher carbs, but the key is not consistently higher carbs. To my mind, a cycling ketogenic diet – where you introduce punctuated periods of natural carbohydrate intake – probably would be better for people. Going back to evolution, people whose ancestors evolved near the equator would probably do better with that strategy. Do I see that in my clinic? Maybe, but it’s difficult to say without doing the formal data testing on that. What I’ve gradually realized over the last couple of years is that being ketogenic most of the time is probably the best way to go, but not necessarily all the time. That’s only in the west.

DrMP:

It just so happens that 75% of people in western countries are overweight or obese. That means 75% of people will probably benefit from being ketogenic close to all the time – until their metabolism is reset and they’ve lost the weight. This is a side effect of the keto diet. The 25% that aren’t overweight or obese – but, many of which still have metabolic health that can be improved – don’t need to be ketogenic all the time. Maybe punctuated carbohydrate intake is better there. It’s all context. If I went to a country that had an average BMI of 20, I would not be recommending keto diets. Clearly, these guys are probably ketogenic because they don’t have enough food and protein intake as it is most of the time. In that case, you’d want to do a different strategy.

DrMP:

So, yes, I agree with you. Some people would do better on carbs, but I wouldn’t say a consistent carb intake. I think everybody evolved on the planet to go without food for a few days – everyone, no matter what part of the planet you came from, everyone knows how to fast and go ketogenic. It’s a good state to be in, as long as you don’t overdo it. However, overdoing it is hard. I think in the west, we definitely overdo the carbohydrate intake a lot more than we do the state of ketosis.

DrMR:

Hard to argue that.

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Post-Concussion Syndrome

DrMR:

One other thing I wanted to transition to… We’ve discussed post-concussion syndrome in the past with some various chiropractic neurologists who have pretty interesting thoughts and protocols to help with it. Titus Chiu wrote a book called ‘BrainSAVE!’ He also had a clinic in Berkeley, but I believe he now moved to Sacramento. This has been very helpful for some patients, for whom their history throws up a flag for post-concussion syndrome. Everything was going pretty good and then they got into a motor vehicle accident. IBS plus some depression starts in the patient and then they say “I’ve done a whole bunch of stuff and it’s gotten some better, but I’m still very sensitive to stress in my life.” You’re getting this scenario of inability to handle stress and this neurology that’s teetering on the edge. There have been a handful that have either done his book’s self-help plan or gone to see him and the responses have been very hard to ignore clinically. I’m wondering – Do you have any thoughts on post-concussion syndrome? I’m sure you’ve found fasting helps with this to some extent, but just wondering if you’d share any thoughts you have on this entity.

DrMP:

Sure. Well, I’ve never tried fasting in a patient with post-concussion syndrome. I’m trying to think if anyone’s tried it, but no one comes to mind. I’m not surprised that irritable bowel syndrome, fibromyalgia and other sorts of disorders like that might improve if you treated post-concussion syndrome. From a neurological point of view, a lot of disorders are probably partly or even mainly caused by brain dysfunction. The brain can influence all of the body, including the gut microbiota itself and vice versa. However, if the brain is damaged, you can get funny symptoms popping up all over the place. It’s possibly due to the brain misinterpreting things. The way the brain works is it creates a reality of the world that people use to guide themselves day to day. If you mess up that projected reality, it can result in lots of “problems” arising in different parts of the body. I wouldn’t be surprised if you treated post-concussion syndrome by treating the brain that it would improve other things.

DrMP:

Now, that being said, post-concussion syndrome is not a well-defined entity itself. It’s kind of a loosely applied term in a lot of cases. I like to have reasonable definitions of things when I’m treating them so I can measure them. It’s hard to do that with post-concussion syndrome. So, I think I might’ve answered your question partly.

DrMR:

I can totally appreciate the vague nature of post-concussion syndrome. This is one of those on the border of my radar. It’s not squarely within my radar, but I like to know enough to refer someone to a plan that can help them rather than just not giving them any advice. Admittedly, my nuanced understanding of post-concussion syndrome – or the acknowledgement that it’s a broad finding – I would fully agree with you on. Just to reiterate for the audience, if you’ve had a head trauma in the past, and you have some symptoms that are neurologically-based or others that started after that head trauma, you may want to look into getting some support for that. There are things that can be done. It seems that there are some pretty good tools on both sides of the fence in terms of integrative and conventional medicine. Matt – maybe you can speak more to what kinds of tools are being used for this.

DrMP:

In mainstream medicine, I don’t think we have good tools for treating post-concussion syndrome at all, other than recommending things like rest, exercise and sleep – these are pretty obvious lifestyle measures. I think integrative medicine probably is ahead of the game with that particular disorder. If I knew someone with that, I would have no problem mentioning what you just said to them about seeking help from that avenue.

DrMR:

I’ll just echo this one more time for the audience – Titus Chiu – He’s been on the podcast two times. He’s a chiropractic neurologist and he wrote the book ‘BrainSAVE!’ I’ve had at least six patients to date go through the self-help protocol in the book with good results and a few others who went and worked with Dr. Chiu directly. So, there’s a resource for people.

Neurological Conditions & Fasting

DrMR:

So, this is a ‘can of worms’ question admittedly, but what neurological conditions do you think should really chiefly consider fasting? I’m asking this for the person who maybe has a family member or a friend, and they’re watching them go down the medication management of symptoms road, and they’re trying to pull them out of that. Here we have a neurologist who can speak to this from more of an authoritative position. What conditions would you say this person should definitely think about other integrative interventions for Alzheimer’s, Parkinson’s, etc?

DrMP:

Sure. I think it’s always good if you can catch these things earlier, rather than later. The answer would be most neurological conditions because most neurological conditions are lifestyle related. You look at something like Alzheimer’s, which is doubling every 20 years. There was much less Alzheimer’s a hundred years ago – much, much less than there is today. If you could catch someone in the early stages – a subjective or mild cognitive impairment, some memory issues, etc. – but it’s not totally interfering with their work or social life yet, they would be a prime candidate. Another disorder would be Parkinson’s caught in its early stages. So again, the evidence for this is not here with humans – with animals it is, but, not humans – so you have to be careful. We have done studies with keto diets in both those conditions – Alzheimer’s and Parkinson’s – and they had improvements, but keto just mimics the fasted state.

DrMP:

Another one would be brain cancer, like glioblastoma multiforme. At the moment, we’re doing some work there with people with that condition. That’s very late stage. By the time the tumor is the size of a tennis ball, you’re dealing with something that’s very end stage and difficult. However, if you want to prevent those things, fasting would be useful for a host of reasons – prevention of strokes, for example. If you take animals and fast them every day for three months (even just time-restricted feeding) and then you give them a stroke compared to animals that are not fasted, the final stroke size is less than half the size of the ones that are not fasted. The body does something to really mitigate the size of the stroke. Again, no data in humans, but maybe that would be very helpful and that would almost certainly be helpful in preventing the stroke from occurring in the first place.

DrMP:

Epilepsy is another common neurological condition. So, we know ketogenic diets help people with epilepsy and those are the hardest epilepsies that it helps with – the so-called drug-resistant epilepsies. There is some study of introducing fasting alongside ketogenic diets in epilepsy. In humans, it did improve it a bit more, which is not surprising. So, I think if you had epilepsy, throwing a combined strategy of fasting and a keto diet added would probably be optimal. I have some patients doing this and getting good results – not all but, most.

DrMP:

Multiple sclerosis is another one, which as I’m sure you know, has been associated with altered microbiota – as are some of the other disorders I mentioned. We know that fasting of MS models in animals improves clinical symptoms. I think there is some evidence in the Fasting Mimicking Diet, which is essentially a diet that really mimics fasting. It has a totally reduced calorie intake and it’s got fiber and stuff, so it makes the body go into a very closely fasted state that has improved symptoms in pilot studies of people with multiple sclerosis.

DrMP:

Those are just some of the examples that I mentioned – basically the most common neurological disorders. With almost all of those, a major risk factor for them is metabolic syndrome – the combination of being overweight and/or type 2 diabetes and/or hypertension and/or an altered blood cholesterol profile. With all of those things, you can reverse them if done correctly. So, if you had anyone with those things before they even had a neurological condition and they got on a healthy fasting practice, you could probably prevent or delay all those neurological conditions before they even happened.

DrMR:

Right. Well, there you have it folks. There are so many to choose from in that list. Hopefully, none of those are things that you or a loved one are dealing with, but if they are, something to consider here. Also, great point on prevention. I think that’s what we’re ultimately after as much as we can.

Breaking the Fast

DrMR:

As you’re mentioning this, a thought occurred to me. Patients will often ask me, “If I have some coffee, does that break the fast? If I put some creamer in there, does that break the fast?” My position has generally been, as long as there’s little to no sweetener, some fats won’t be a big deal. Some proteins won’t be a big deal. Try to mitigate as much as you can. Obviously, a Starbucks mocha or Frappuccino is going to have 30 to 100 grams of sugar in it. However, it’s different if you’re talking about a black coffee with some half and half. What I do midday to get me further in my fasting window is I have an electrolyte pack – which is essentially salt, potassium, magnesium, one fresh squeezed lemon and a little bit of whey protein. That’ll buy me another three hours of fasting on days when I’m trying to do one meal per day. At least, the way I’m doing the math is that’s going to lead me in a net beneficial, metabolic state. Curious where you draw the line with how much we can get in to help buffer that fasting window we’re trying to get through.

DrMP:

That’s a really good question. I just want to prelude it by saying, I think what you do sounds really good. I think that it’s very difficult because when I say, “You can have a coffee” and then someone else might think, “Oh, that means I can have a Starbucks.” I never go to Starbucks so I wouldn’t know. You look at how people make flat whites, lattes, etc… there’s a heck of a lot of carbs in there. You have to make sure you’re communicating correctly and that you both have the same idea.

DrMP:

You can fast in different ways. The first way we divide it is by time. Do you do one meal a day? Or OMAD (One Meal a Day)? Or do you do 16:8 time restricted feeding (16 hours a day fasting, 8 hours a day eating)? Or a five day multi-day fast? The other thing is the intensity of the fast, if you will. So, you can do a water-only fast, which is the purest way, but I’m also a fan of the water/coffee/tea fasts. You can go to a Fasting Mimicking Diet, where you introduce bits of food. Or you can do what you’re doing. Introduce a little bit of protein periodically if you want to minimize muscle breakdown. I think when it comes to how much coffee and tea, I get all of my patients who are doing this safely, to measure their blood ketone and glucose levels every day with a blood monitor. I give them a range of ketones to be in, dependent on the disorder and dependent on the person. However, let’s say it’s 1-2 mmol/L. Then, they just do that. If they’re out of the range consistently, then they get in touch with me and we go, “Okay, so what are we doing that’s wrong? Okay, well maybe it’s because we’re adding too much milk to the coffee and we’ve got to stop doing that.” Most of the time, I would say black coffee and tea are best. If you must have anything, add cream – go for up to 1 tablespoon or so of cream in your coffee. Certain types of almond milk are okay. When you start getting into milk, I generally say none at all. A teaspoon of milk isn’t going to do too much if you’re doing a five day fast, but people can get carried away and suddenly they’re having 6-7 cups of coffee a day with a teaspoon of milk. Then, you might be doing some damage. So I limit the coffee to 2 or 3 cups/day. Those are the guidelines I give. How much of that is evidence-based? Very little, but, with some people, the coffee alone can elevate the glucose not by much, but it can. I guess context really matters and that’s one of the beautiful things about fasting. You can tailor them to people, their lifestyles, their physiology and the neurological disorders they have.

Ketone Measurements

DrMR:

In regards to monitoring, obviously there’s the finger lancet – prick sticks where you can do glucose and ketones. I know that there’s recently been a breath ketone meter, which I haven’t had a chance to experiment with, but it sounds a lot easier for people to be doing routine measurements with. I’m pretty motivated, but I do find the finger pricks just get annoying after a while. Do you have any idea about accuracy? Any ideas in terms of the utility of the breath ketone monitoring? What is your preferred method?

DrMP:

The only exposure I’ve really had to them is trying them at conferences. Last year, I was in Los Angeles and had a chance to look at the breath monitors, but we use the blood monitors routinely. The main reason for that is the brain is what I’m most interested in. What the brain is exposed to in terms of ketones and glucose levels is the blood that’s saturating it. So, I want the blood levels because that’s what the brain is being exposed to at that particular moment. So in the breath, you’re measuring a slightly different ketone and the urine you’re measuring what the state of the blood might’ve been potentially a few hours before, so it’s not relevant to right now. It’s because the blood is containing the level of ketosis that the brain has been exposed to right now that I prefer it. It just gives me the most physiologically relevant indication of ketosis. That’s the most important thing to make sure of.

DrMR:

I suppose it’s important to acknowledge that this wouldn’t ostensibly be forever. It would be someone acclimating their diet, feeling out where that line is and once they have that, they can generally maintain that eating pattern. Maybe they do a check every once in a while, but I’m assuming people are not needing to be perpetually checking their ketones. Right?

DrMP:

Absolutely. Typically, I’ll say do it every day for at least two months until you’re confident. Then, you can do it 2-3 times/week. Once people are good at that (if I’m not asking them to measure it for data collection purposes), then they don’t need to. They can check it once in a while, but it’s really about making sure you’re doing it right. The ketones have benefits themselves, but they’re a good marker of how well one is doing a keto diet or fasting. I think it’s very useful to have that feedback so you can self-correct. As soon as you know you have experience to do it, then you don’t need to measure them very frequently at all.

DrMR:

That makes sense.

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Sleep Quality & Ketosis

DrMR:

In terms of one thing that may lead you to poor food choices, thus taking you out of ketosis, poor sleep quality would be one of them. That brings us back to sleep for one of the final couple of topics here. So, we’ve been doing a lot more at the clinic with home sleep tests and trying to determine if people are having significant nighttime desaturation events or apneic events. We’ve been finding some of the home sleep test measures are adequate and was actually shocked to find that physical therapy for the mouth – also known as myofunctional therapy – was shown to be as effective as CPAP, according to a meta-analysis. This blew my mind. So, we’ve been doing some of these home sleep tests and having patients perform myofunctional therapy. We have a series of patients now who are waiting back to do the post-test and pre-assessment of their symptoms. I’m wondering – In your clinic, I’m assuming there’s a fair number of people with decently high BMI’s and therefore, at risk for apnea. Is sleep medicine something you fall right into at all? If so, just wondering if you have any thoughts there.

DrMP:

Well, it’s really an interesting topic. I make it a point to ask two questions with pretty much any patient. I ask them about chronic fatigue and I ask them about their sleep because they’re probably not going to introduce you to those things unless I ask for them. When you think about it, chronic fatigue affects 2/3 of your life all the time you’re awake and insomnia or sleep problems affect the other 1/3. So, these are two massive issues. I do find that sleep problems in general are the rule rather than the exception. Obstructive sleep apnea, which generally is from some kind of anatomical thing – too much weight on the chest from being too overweight, anatomical changes in the throat and jaw that predispose them to it – is one of the major things underlying poor sleep. I look out for it. I think we under treat it. I think it’s very common. If we treated it better, that would be good for everyone’s health. That being said, instead of CPAP – so using a machine at night to improve it – fasting and keto diets are two much better strategies. For most people, it’s too much weight. That’s the problem. If you lose the weight and get the body into a more healthy place, you can work on the insomnia in other ways. Chronic anxiety is a very common thing that underlies insomnia. You can work on that, too. You can improve sleep without needing the machine. As for the other technique you mentioned, that’s interesting to me. I think I’d want to wait and see what you guys find.

DrMR:

Well, thank you. I’m very curious to see if we can publish it. We’re pretty much collecting data via peer reviewed symptom inventory on everything that we do at the office now, which makes it so easy to spin up a retrospective chart review. Once we’ve had hopefully a pilot of six people go through this, we can write something up and put that out there. It seems to be such a ‘low-hanging fruit’ – home sleep test: inexpensive, some validation data, patients will do it rather than dragging their feet at doing the overnight attended and physical therapy for the mouth. It’s much easier to get people to swallow rather than using a CPAP machine. I just see the compliance being much higher and probably allow the healthcare provider to reach people that they wouldn’t otherwise be able to reach. That’s my hope, but, I always say with anything new – There’s a big chunk of salt I’m going to lick on just to make sure I don’t get too swept up in the excitement accompanying whatever new hypothesis I’m currently working on.

Episode Wrap-Up

DrMP:

Well, I’m just going to say – Good on you for doing that, Mike. In my opinion, you’ve got the right approach. You have to approach these studies with the combination of optimism and doubt. You want to be hopeful, but you have to be skeptical and make sure that you’re doing things correctly and not interpreting things in a biased fashion. That’s done far too often. If you feel that combination of “I’m hopeful, but I really don’t know if this is going to work…” then that’s good. To me, you’re on the right path.

DrMR:

Well, thank you. Part of how I’ve come to that position is I’ve just seen so many patients who have wasted so much time and money. So now, I really don’t care if my hypotheses are the ones I “want” to be right. I just want to do what’s going to help people and get the dogma out of the way.

DrMP:

Excellent. I fully agree. You’ve got to keep your mind open to real-world data. If the data is telling you that maybe what I love so much – maybe it’s a therapy or something – isn’t working, you have to be receptive to that. Otherwise, you’re going to be chasing the wrong thing for decades. It’s not easy because you want to believe, but to be a proper scientist, you do have to maintain that doubt part of the equation and not just be fully optimistic.

DrMR:

Right. That’s why I like the clinicians who are also researchers because publishing the research forces you to look your data in the face and say, “Hmm, when we put this into mathematical terms – even though I was really excited about the 2 in 10 who responded – when we map it out, it was only 2 in10. My mind was focusing on those 2 so much it felt more like 8 in 10.”

DrMP:

Exactly so. You are basically mirroring my thought processes of the last few years. When I was making thoughts about how this would work and how that would work, and then you get into the real experience of real patients, you realize some of that stuff may be true, but a lot of it was my imagination. Researchers have wonderful, imaginative ideas, but as a clinician, you can apply them. People who are just researchers – I am generalizing here – get these wonderful, imaginative ideas, but they have no hope of working in a clinical setting with real patients. Conversely, for people who just do clinical practice, they know how to work with patients, but their imagination wanes over the years. They don’t want to try anything new. So, they get stuck in these ruts – “Well, this is how it’s done because this is how it’s always been done.” So clinician-researchers all the way. I fully agree.

DrMR:

So, where can people find you online? Is there anywhere you’d want to point them if they wanted to learn more about you and your work?

DrMP:

Sure. I had a patient start a website for me. It is metabolicneurologist.com. Pretty simple. If you go there, you can see the videos I’ve done, podcasts, key publications. Your podcast will go up there, I’m sure. I’ve also got some metabolic plans that people can download and try. They can contact me as well if they need to. So, it’s metabolicneurologist.com.

DrMR:

Awesome. Well, Matt, I had a feeling this was going to be a really enjoyable and insightful conversation, as it was. Again, I really appreciate your perspective and taking the time to share some of your thoughts with us today.

DrMP:

Well, thank you very much for offering to do it with me and for the work you do in spreading this kind of information. I think it’s really admirable.

DrMR:

Absolutely. It’s been a pleasure.

DrMP:

Likewise.

Outro:

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