A Ketogenic Diet for Parkinson’s Disease: Shaking Up the Science

Can a ketogenic diet help treat Parkinson's disease? Let's cut to the chase. My answer is a cautious but confident yes. However, it's not that simple. In this video, I'll break down why I believe this is the case, what you can realistically expect. We'll dig into the nitty-gritty of the science, the gaps in the science, and how you can start a ketogenic diet. Whether you have Parkinson's disease or not. And here's why this video is personal. I spent years studying Parkinson's disease at Oxford, conducting clinical trials for my PhD, and working with incredible patients who inspired me to push harder for solutions. Because current treatments help manage symptoms but do little to nothing to stop the disease's relentless progression. This video is for them and for anyone looking for hope and actionable steps today. But first, what is Parkinson's disease? How common is it? And why this video now? I gave you a little prelude, but I'm going to delve a little deeper. Parkinson's disease is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. The motor symptoms are what most classically stand out and include the cardinal features of a tremor, usually a resting tremor, in one hand worse than the other, bradykinesia, which literally means slowness in movement, rigidity that can make it really hard to walk, write, speak, or express facial expressions, and postural instability, which leads to falls. There's also usually a shuffling gait. And in terms of non-motor symptoms, patients often experience issues with smell, gastrointestinal upset, and sometimes mood disturbances like depression. There's also the related phenomenon of Lewy body dementia, which is characterized as a distinct disease but with similar underlying pathology. It's what afflicted Robin Williams. And if you want, just as an aside, a sobering and incredible documentary, see Robin's Wish. It brought me to the edge of tears. Now, how common is Parkinson's disease? Well, I call Parkinson's disease the sad middle child of neurodegenerative diseases in that it's the second most common neurodegenerative disease. Behind Alzheimer's. Thus, it gets less attention and fewer research dollars, which is really important. But it still impacts over 10 million people worldwide and is actually growing in prevalence much faster than Alzheimer's disease. If it were an infectious disease, Parkinson's disease would be labeled as a global pandemic. For example, in the United States alone, almost 100,000 people per year are diagnosed with Parkinson's disease. And now, why this video? Why now? And I'm going to get a little sentimental, so warning on that before we get more sciency. Well, I did a large portion of my PhD on Parkinson's disease. I was running clinical trials at Oxford, and during my studies, I really got to know quite well lots of patients and volunteers with Parkinson's. And ever since then, it's been a disease that touches my heart deeply. The Parkinson's community is truly a community of incredible, resilient, generous people for whom I'll be forever grateful. And they honestly deserve better than the lot they're afforded insofar as current treatments only manage symptoms but do little to nothing to slow the progression of disease, the underlying disease. Thus, I feel like there's a special flavor of psychological trauma that accompanies this diagnosis. The knowledge that there's nothing you can do to prevent it from progressing. At least not proven yet, but that's what we're here to talk about. And yet the patients I met somehow thrived on the hope that either disease-modifying treatments would arise, or that in their time, whatever time they had, they would turn their lemons into lemonade by contributing their time and bodies to advancing the research by contributing as study volunteers. That mindset takes a special type of person, and incidentally was one of the things that got me motivated to work my butt off conducting research. Not because I really desired more publications or academic prestige, at least not primarily, for the patients and volunteers themselves. Their commitment fed my commitment. And I mean this as a genuine sentiment of inspiration from the researcher to the test subject to the test subject to the researcher. Clinical research volunteers can be a huge inspiration for us researchers. They're not only subjects, but they're cheerleaders and coaches that put the fire in our belly, the fire in the belly of scientists, and thereby propel us to get the hard work done together so these people can be helped. Sorry for being sentimental. I'll pause on the feelings for now and get back into the physiology. Okay, what causes Parkinson's disease? Parkinson's disease is caused by the death of dopamine-producing neurons in the brain's substantia nigra. This actually translates to black substance,— and is a little patch of brain in the midbrain motor system. It's black because of a pigment called neuromelanin in the neurons there. And specifically, Parkinson's disease is characterized by the aggregation of misfolded proteins, misfolded alpha-synuclein proteins, the hallmark of Parkinson's disease, leading ultimately to the death of these dopamine-producing substantia nigra neurons and the motor and also non-motor symptoms of Parkinson's disease, including those we already reviewed. And as more neurons die, the disease gets worse. And as I've already said, I think twice now, the current standard of care is basically replacing missing dopamine with dopamine supplementation of some form. However, as more neurons die, the underlying disease will progress. The medications become less effective. And the disease typically gets worse until— well, that's why we really need better treatments and disease-modifying treatments. And if you want more on the pathophysiology of Parkinson's, I'm going to link a bunch of references below. But here's something interesting and really important about these dopamine neurons in the midbrain that die off as Parkinson's disease progresses. They are huge neurons with many branches. This is called arborization, and they're also very few in number and super, super energy hungry. They have a distinct calcium pacemaking activity that gobbles up energy like a hungry teenager. And all this means these substantia nigra dopamine-producing neurons are particularly metabolically active and therefore especially susceptible to energy deprivation. And when these neurons are starved of energy, they die. This pathology is important to understand because one can envision the cause of Parkinson's disease and the progression of disease as largely an energy metabolism problem, where the neurons that need a lot of energy don't get enough, and as a result, they can't do their jobs, and they die off until the disease manifests once a bunch of neurons are dead and then progresses as more neurons die, as the army of dopamine neurons in that midbrain region, substantia nigra, dwindle. But what if we could rescue energy metabolism in substantia nigra neurons? Could we actually slow or stop Parkinson's disease? In theory, the answer is yes. So enter ketones and ketogenic diets. Ketogenic diets are very low carbohydrate diets that force the body to turn fat— this can either be body fat or dietary fat— into something called ketone bodies, molecules, primarily one called beta-hydroxybutyrate, which is amazing fuel for organs and especially the human brain. Typically, the brain's neurons run mostly on glucose, but the brain also loves ketones. And ketones have special properties that make them better brain fuel, especially when the brain's metabolism is impaired, as in most neurodegenerative diseases, including both Alzheimer's and Parkinson's disease. Now, I'm not going to hit on every energetic mechanism, but here are a few to give you a flavor of what I mean. And brace yourself now because there is going to be some scientific jargon. All right, number one, let's talk about mitochondria, the powerhouse of the cell. They make energy using something called the electron transport chain, where high-energy electrons are passed along the chain in the inner mitochondrial membrane. To produce energy as they transition from higher to lower energy states. You can think of it like a waterfall being used to turn a hydroelectric turbine. That would be called ATP synthase. Now, if you can increase the height of the waterfall, you can get more energy to spin the turbine more. And that is more or less what ketones do. They can do so for— ready for some of the jargon? Increasing the redox span between the NAD and NADH and Q and QH2 electron carrier couples. This is biochemically analogous to increasing the height of that waterfall so you can spin the turbine faster and get more energy. Or for a little bit of a comic analogy, increasing the height from which a bowling ball is dropped to the floor. Dropping the ball from 1 foot high and it makes a clunk. Drop that same bowling ball from 4 feet high and it makes a smash. But here the smash is more energy for the brain, which is great. A lot better than breaking your toes with a bowling ball. Okay, moving on. Two, ketones also provide the advantage of generating relatively more electrons, energy electrons, to feed into a back door in the mitochondrial electron transport chain called complex II to make more energy via going in the back door than the front door, complex I. This is important because Parkinson's disease is actually characterized by a front door, complex 1, defect which impairs energy production. So if you can go to the back door, you can generate more energy. And actually poisoning complex 1, blocking the front door with a compound called MPTP, is a way to generate animal models of Parkinson's disease. This is how we actually study Parkinson's disease in animal models. So this microscopic approach whereby ketones sneak electrons in the molecular back door, complex 2, is logical insofar as that it may help rescue energy production and slow the death of Parkinson's disease dopamine neurons in the substantia nigra region. And indeed, studies do show that ketones, beta-hydroxybutyrate, can successfully protect against the death of dopaminergic neurons in the substantia nigra, and in so doing, slow the progression of Parkinson's disease, at least in animal models. We'll talk more about the human momentarily. But moving on, 3, in addition to directly boosting energy production, ketones can help protect neurons from being harmed by the stress of generating energy by boosting antioxidant defenses. You see, as a function of normal energy production by mitochondria, sometimes these high-energy electrons, they can escape their normal path and go rogue and generate what are called reactive oxygen species. And if these overwhelm antioxidant defenses, it's called oxidative stress, it can lead to progressive damage to mitochondria in neurons and ultimately neuron death. Now, the antioxidant defenses of the body depend on something called NADPH, not to be confused with NADH, which simply put is the foundation for replenishing and refueling the antioxidant defenses of the body, including those intrinsic to the body like glutathione and thioredoxins and those related to exogenously consumed nutrients like vitamin C and vitamin E. And what's more, this NADPH system not only supports antioxidant defenses, but may also directly support dopamine synthesis in the brain since NADPH supports the reduction of what's called dihydrobiopterin to tetrahydrobiopterin, a critical coenzyme in the synthesis of dopamine. I know, I know, that is a ton of jargon, probably went over your head. The keep it simple, stupid version is that in the same way ketones support antioxidant defenses to protect neurons against harmful reactive oxygen species, they may also boost the brain's own dopamine synthesis. So kind of a one-two punch for brain health and Parkinson's disease. And this may be a mechanism whereby ketogenic diets can improve the symptoms of Parkinson's disease, as they've shown in human trials. In addition to slowing Parkinson's progression, which I think is even the more interesting thing. And honestly, I can go on for hours, but I'll spare you and instead link a bunch of references below, including mechanism papers and textbook chapters I've written. And if you want more nitty-gritty on the neurobiology, just go delve into there. It's a super rabbit hole. But now, what about human studies? Well, there's some really promising data, starting with early small-scale studies in 2005, where researchers did a 28-day pilot trial in just 5 patients targeting a 90% fat by calories ketogenic diet, and they found that all 5 patients exhibited symptom improvements on what's called the Unified Parkinson's Disease Rating Scale, with an average decrease Higher scores indicate worse symptoms, so a decrease is good. Average decrease of 43.4%, ranging from 21 to 81. Among symptoms that improved were resting tremor, freezing, balancing, gait, mood, and energy levels. Furthermore, we at Oxford conducted a randomized placebo-controlled crossover trial for exercise performance in Parkinson's disease. And we found that supplementation with ketones, exogenous ketones, improved participants' ability to sustain a certain level of exercise by 24% with statistical significance as compared to a calorie and taste match carbohydrate control drink, which is really, really promising. And I'll just put in there, there was one larger-scale clinical trial being conducted in 2020, with some really promising early results. But unfortunately, some respiratory virus that created a big stir around 2020 got that Oxford-based trial being run by some bearded 25-year-old Boston-born Marvel-loving researcher shut down before he had to matriculate to medical school. So that study got put on pause, unfortunately. Wonder who could have been running it. Now I want to talk about a complexity of the research, which is that the major benefit of ketosis and ketogenic diets may not be in immediate symptom relief, but in delaying or stopping Parkinson's disease progression. Remember, patients with Parkinson's disease usually get dopamine replacement therapy, but the underlying disease still progresses over many years. That said, once neurons are dead, they're dead. So until we advance stem cell therapy, and some people are really working on that, those neurons are gone. And the disease won't go into complete remission. It won't reverse. The key point is we don't have therapy to properly stall or reverse Parkinson's disease. However, if we could offer patients something to halt or slow disease progression in combination with dopamine replacement drugs for symptoms, that would be a massive win. And I do believe a ketogenic diet Ketogenic diet can be that option, even today. But it's really hard to prove, since the sort of human-controlled trials that you need to conduct would take years, and it simply hasn't been funded and conducted. Thus, I can't cite any human randomized controlled trials proving that ketogenic diets slow or stop Parkinson's disease progression. And that's not because it wouldn't work or couldn't work, but because the study hasn't been done for logistical and funding reasons. We'd honestly need tens of millions of dollars. So I can speculate, but until we as researchers get honestly a boatload of money to do the study, all we can do is guess based on physiology. But honestly, that's something. And I still think this is a hopeful message, and I've seen it spark hope in the eyes of many patients with Parkinson's disease who have chosen to adopt a ketogenic lifestyle some under my informal guidance, and some with really dramatic improvements and honestly slow disease progression as far as we know, because their disease hasn't progressed. For example, I recall one text message I received from a past research subject where she told me she could dance again with her children and her husband. She previously loved to dance. She was a dancer and thought she'd lost that part of her life forever. But after several months on a ketogenic diet, she regained that ability. Her Parkinson's did not disappear. We did not reverse her Parkinson's disease. But various elements did improve, including her depression. And we hope the disease slowed. But since she doesn't have a way to test this, she doesn't have a clone of herself, I guess we don't know yet. And as a quick comedic aside, I previously shared this story with someone in the past, and they said, "how do you know if this wasn't just a placebo effect?" Because this individual's n=1 story was just that, an n=1 story. It's not an RCT. But to that I replied, "I don't think the patient would care if it were the ketones or the hope that brick-walled her disease progression and improved her symptoms." Bottom line, while the research is outstanding, hope really matters. Now I want to transition to a quick how-to on a ketogenic diet for Parkinson's disease. And bear in mind, this is completely based on extrapolating from basic physiological principles rather than rigorous human data on different types of ketogenic diets for Parkinson's disease. That study certainly has not been done, but I can still give you my best guess tips, starting with number 1 of 9. 1. Get into deep ketosis by keeping carbs very low and protein moderate. I suggest eating at least 75% of dietary calories as fat with carbs below 10 net grams per day. And you can see the video notes if you don't know how to calculate net grams. I'll explain it there. 2. Get a ketone monitoring device like Keto Mojo device to check ketone levels from your blood and target ketone levels between 1.5 and 5.0 millimoles. 3, while I have nothing against saturated fat-rich foods like butter, cream, dairy, red meat, they're delicious and they can be healthy, targeting unsaturated fats and particularly polyunsaturated fats may have some advantage in that the unsaturated and polyunsaturated fats are easier to convert to ketones. They promote more ketogenesis. Thus, foods like sesame, tahini, raw walnuts, and raw pecans may be a good choice if you're trying to optimize for ketone levels. Okay, 4. In addition, you can use coconut oil, which is rich in medium-chain triglycerides, MCTs. And yes, coconut is almost all saturated fat, but the MCTs have a special metabolism where they can get into the mitochondria more quickly and be used to make ketones more quickly. This is due to their smaller chain size. They don't need a certain carrier system. Additionally, you can get a pure C8, meaning 8-carbon, 8-carbon chain length, or a C8/C10 MCT oil or powder to help boost ketones in line with the coconut oil approach. Okay, 5, and related to that, there are also some exogenous ketone supplements you can try. This is a whole different topic in terms of the species of exogenous ketones, but I suggest esters over salts since they can be a lot more potent, although they can also be very expensive and you certainly don't need exogenous ketones. They can just help get your ketone levels higher. All right, 6, to help with ketosis and Parkinson's disease symptoms and possibly progression, try to remain active. Exercise is super important in Parkinson's disease. Exercise at least 5 times per week, including a mix of cardio, resistance training, and balance and mobility work. These are really important. Okay, 7. Intermittent fasting couples beautifully with ketogenic diets and can get you into deeper ketosis. You can try to start with a 16:8 pattern, which means 16 hours of fasting per day and eating in an 8-hour window. This can look like eating 2 meals per day, one at 10 AM and noon, and one at 6 PM and 8. I realize this can be tricky for some patients given certain medications and how they're administered. This is not a must, but it can help if you can intermittent fast. Okay, 8, make sure to get omega-3 fats. They're really important for brain health. This means ideally including fatty fish in your diet like sardines, salmon, or mackerel at least twice per week. Or if you're a vegetarian or vegan, an algae oil supplement with DHA can also be used. And 9, in terms of vegetables, stick to very low-carb vegetables like leafy greens. Given the connection between the gut and the brain and the potential role of gut health in Parkinson's disease, it's also possible that very low-carb fermented foods like sauerkraut or kimchi or fermented pickles could have some advantages. I don't think this is a big lever, but if you like these foods, they're more likely to help than harm your health anyway. Those are my 9 tips to start, but if you have more questions or specific questions, things I didn't address, drop your questions in the comments. I'll really try to monitor the comment board extra hard on this one. Anyway, the message I want to leave you with, if again sentimental, is one of gratitude and hope. We don't always get dealt a fair hand in life, and sometimes it's just a losing hand. But from what I've seen in the research subjects and patients I've met who live with Parkinson's disease, is a lot of them realize it's just about playing the hand the best you can. And acknowledging it's more about who the people are around the table with you than winning this round. So thank you. And I hope in coming years we'll have a lot more to say and report from the research front. Stay curious. Stay hopeful. I appreciate you all. Hope you learned something.