I know I already wrote a blog post about why the ketogenic diet (keto) seems to be everywhere right now, but this article is going to give you tons more information from a ketogenic expert (Dr. Matthew Taylor has studied the ketogenic diet in people with Alzheimer’s disease). To catch you up on the basics of what’s going on with keto: the ketogenic diet is popular because a lot of people are finding it helpful for weight loss. In reality, it’s a new version of the Atkin’s diet, or at least the Atkin’s approach is based on the idea that our bodies will shift into burning fat when we deprive it of high amounts of carbohydrates. It’s an adaptive response our bodies have when we are faced with famine. It’s normal, natural, and generally safe… with a few asterisks, of course.
There was quite a bit of buzz around my blog post, so I wanted to follow up with some additional, in-depth background on the therapeutic use of the ketogenic diet.
So, I interviewed one of my former classmates and friend, Dr. Matt Taylor, who is a ketogenic diet expert and studied the diets (and did a keto diet intervention) among patients with Alzheimer’s disease (I’ll refer to as AD). His research used the ketogenic diet to see if it would improve cognitive symptom changes in patients with AD, and/or result in any measurable cognitive outcomes. Spoiler alert! Even though his study population was only 11 people, 10 of them had measurable improvements in their cognitive symptoms. That’s unheard of in comparison to AD medications. Typically AD meds will help with slowing the decline, but none of them actually result in improvement. Well, participants in Dr. Taylor’s study had actual improvement.
He's published a couple papers on the topic: the first found that a high glycemic (refined carbohydrate/likely processed food) diet was associated with higher burden of alzheimer's disease markers and the second study showed that putting people with mild (early) AD on a ketogenic diet was feasible.
I sat down with Dr. Taylor a few weeks ago and picked his brain about many of the questions you have about the ketogenic diet, both related to cognitive health and AD, but I also asked him about who should and shouldn’t follow the diet.
Before I dive into the interview, a little background on the ketogenic diet. The keto diet is a very high fat (80-85% of calories), very low carb (5-10%), and moderate protein (~15%) diet. The idea behind it is that the body can shift, from burning primarily carbohydrates, into burning fat into what are called “ketones” or “ketone bodies.” Thus, the “ketogenic” diet.
Historically, the ketogenic diet has been used for epilepsy in kids when medications don’t work for them. Over time, the diet has been studied in brain cancer, and more recently there has been interest in its use for conditions involving cognition. Dr. Taylor’s study, as I already mentioned, is related to the ketogenic diet’s use in patients with Alzheimer’s Disease.
Here is my interview with Matt, condensed for readability and to avoid redundancy. I also made the more publicly relevant questions at the top and left the more science-heavy (nerdy) stuff at the bottom. Enjoy!
Leigh: So, why is keto so popular right now?
Dr. Taylor: Many researchers, physicians, practitioners, or people involved in the “keto movement” have seen improvement in weight or health conditions by following keto. Then, they encourage others to try it, and it spreads from there.
I think keto is most popular because of weight loss but I’ve also heard from many that follow the diet that they are following it because they believe it is best for their brain health. For weight loss, it’s a diet where you can eat and feel full most of the time – it consists mostly of fat, so it can be very satiating. Sometimes the diet causes people to eat fewer calories and feel satisfied. There is also evidence that some people can eat more calories and still lose weight. From a brain and focus perspective, ketones tend to give a sense of euphoria, so some people just like the way it feels and potentially feel like they have better focus.
Leigh: What are common misconceptions of the ketogenic diet?
Dr. Taylor: The biggest misconception is that this diet is a fix-all approach.
Also, there are many products touted to enhance ketosis, help with symptoms, or help with weight loss. Some of these may or may not actually work. The product consistently shown to be beneficial in this area is MCT (medium chain triglycerides). There is a lot of marketing for beta hydroxybutyrate (BHB) supplements, which research has shown that many don’t actually help raise ketones UNLESS given with MCT oil. With that said, a certain formulation of exogenous ketones has been effective at raising blood ketone levels after administration. I’ve seen posts on social media push products as “you have to be on these supplements follow the ketogenic diet properly” which is not true, some of it is gimmick.
Leigh: So what’s being portrayed in media that IS or ISN’T accurate?
Dr. Taylor: Once again, just the misconception that the keto diet is a panacea. Keeping focused on research, I try to stay away from what media is pushing out, but I do see what’s being marketed on social media. I’ve been asked to talk at conferences and seminars that companies have put on, but I haven’t taken those gigs, so can’t say for certain.
It’s funny, I know several people who research the keto diet that are surprised to learn how many people are following it. Listening to people who are actually DOING it and articulate some of the benefits and obstacles can be helpful for scientific messaging. Sometimes there is good info in the keto communities, but not always.
Side note: here’s my (Leigh’s) previous post about keto that explains more.
Leigh: Who would benefit from following keto?
Dr. Taylor: We use the ketogenic diet very successfully in childhood epilepsy. Evidence has shown potential for people with adulthood epilepsy, Alzheimer’s disease and other neurological conditions, Diabetes, and even Polycystic Ovarian Syndrome (PCOS). There is emerging evidence around people with malignant tumors (specifically Glioblastoma – brain cancer) on keto with a potential shrinking effect and improvement in symptomatology. Individuals who have those types of conditions may benefit from keto. The ketone metabolism research shows us that many of these conditions are metabolic in nature, which we haven’t always known. Where we’re seeing an effect of the ketogenic diet is on conditions driven by metabolic changes impairing our body’s ability to use glucose for fuel. Once that condition has occurred, it doesn’t matter how much sugar you provide, there it seems there is a preference for ketones instead of glucose for fuel. Even in situations when glucose isn’t as usable anymore, such as in Alzheimer’s, ketone metabolism stays intact. Traumatic Brain Injury (TBI) is another condition that I’m researching with the keto diet.
Leigh: Ok so this sounds like it has potential for a lot of different situations right?
Dr. Taylor: In science, we’re conservative about using approaches that are this extreme because we’re concerned about any possible negative outcomes. It’s interesting, many people have started this diet for many different conditions, and so we’re sort of letting the population do tests on themselves. Healthcare professionals can see the results from an anecdotal standpoint and we can then use this as rationale for future studies.
Leigh: Who shouldn’t follow keto?
Dr. Taylor: First, people with carnitine deficiency should not follow keto (you would have discovered/been diagnosed with this in childhood if this were an issue for you). This deficiency means that it’s harder to get fat into the cell for fuel, and you no longer are providing glucose as fuel either, so this could be a problem. There is some evidence that supplementing with carnitine may be helpful. Really, it comes down to personalizing the diet, because there are different ways to do keto, and it’s not for everyone.
Secondly, people with an APOE4 mutation may want to stay away from keto diet. These people don’t seem as able to handle high amounts of fat, especially saturated fat. This can be tested via genetic testing. It’s suggested that following the keto diet can have adverse cardiovascular effects like increase cholesterol levels and many with the ApoE4 gene don’t seem to have the same cognitive response in research studies.
If you’ve given it a try, consider how you feel. There is an adaptation phase to diet that many people experience, often called “Keto Flu”. The symptoms while adapting vary by individual, I’ve seen people go on the diet and feel great immediately, and other people go a handful of days and feel kind of bad, and others that feel horrible. For many, they adapt and feel good after a few days. Some never adapt at all and never feel good, once again it’s about individualizing the diet for each person. There is some really interesting evidence that feeling this way mostly comes down to low sodium intake to replete the high amount of sodium excreted by following the diet. I recently saw data from a study that put several hundred people on the diet. By ensuring that those individuals consumed plenty of sodium, they were able to attenuate many of the side effects associated with “keto flu.”
Another individual component to consider is insulin level before starting Keto. People with higher insulin levels may take longer to shift into ketosis and possibly feel bad. Also, what is your nutrient status coming in? Many people already lack electrolytes and hydration and this diet requires more hydration. Burning more fat makes you excrete more fluid, so people who aren’t hydrating or replenishing electrolytes will likely feel awful. The diet isn’t for everyone, if you follow this diet and feel awful on it (and continue to feel awful) more personalization may be necessary, or it just may not be right for you.
Side note: people with history of (or current) eating disorder should definitely consult with their healthcare provider and eating disorder recovery/healthcare team before taking on any dietary changes or restrictions.
Leigh: On a basic level, can we get people to follow keto long term? Should that be the goal? Can we see changes, metabolically, with just macronutrient changes (without focusing on fruits and veggies)?
Dr. Taylor: After the study of metabolic change builds more evidence, then we can ask that more complex questions. We see overall improvement in condition, but what we also want to consider personal experience? I think diet quality could play a part, but that hasn’t been studied yet.
Leigh: What would you tell someone who is thinking about starting keto?
Dr. Taylor: Seek out advice from someone with experience or background in this area, like a Registered Dietitian Nutritionist (RDN). You may run into RDNs who are hesitant to comment or advise on this diet if they don’t have experience with it. However, those with experience would be more apt to provide objective help.
Leigh: What’s one thing you would tell someone to expect?
Dr. Taylor: First, following a ketogenic diet is usually a big change from most people’s typical way of eating. It’s really counterintuitive for many to eat as much fat as is required to follow the ketogenic diet and carbohydrate restriction can be difficult for people who have carbohydrate food cravings. It’s also possible that you may feel crummy for a period of time while your body adjusts to a different type of fuel (shifting from carb-burning to fat-burning).
Leigh: How does one know if they’re just adapting to fat-fueling or that the ketogenic diet isn’t working for him/her?
Dr. Taylor: It could be either, but there are steps you can take in preparation for starting keto that can help you to know if it’s a feasible option before getting fully invested. It could be helpful to know your APOE status, personally I’m a proponent of genetic testing, but I realize that some people are hesitant to that for various reasons. It may be helpful to do blood work from a PCP or other physician who could look at APOE status because we’ve seen people with APOE4 who don’t respond as positively as others. If you don’t know your APOE status and go on this diet, it’s advisable to get your cholesterol checked periodically to make sure you aren’t doing more damage than good.
Another helpful tip is to be proactive with hydration and electrolytes like potassium, phosphorus, and sodium. Bone broth has been helpful for adaptation phase, patients have been using bone broth to feel better and it is becoming more widely available. In my research, we provided participants a multivitamin and a potassium/phosphorus supplement. My current study in patients with traumatic brain injury (TBI) with a small sample size provides a multivitamin but not phosphorus/vitamin D. I’ve never used exogenous ketone supplements in my research.
Leigh: Is it bad to abrupty start or stop following a ketogenic diet?
No! Actually, with the research we’ve had some interesting findings. The researchers determine “compliance” as following keto about 70-80% of the time. This means that ¼ – ⅓ of the time not following keto, which is a way of cycling, whether it happens intentionally or organically. This indicates cycling or abrupt stopping would be ok. People who have stopped the diet can pick it back up and resume. Once you’ve started making ketones, there’s an idea (among keto experts) that ketone adaptation, where you switch over to ketone fuel metabolism, becomes easier. There isn’t really a concern unless you’re just generally yo-yo’ing (dieting) bouncing back and forth between ketogenic and Standard American Diet (SAD), which is not healthful. This is a lifestyle/behavior change that is so important, and moderation is also important. Extreme shifts may be problematic, but we don’t know because we don’t have the evidence. Variation is important, cycling with a plan is probably a good approach, but we still need evidence on this as well. All these assumptions are also focused on diet quality. If the shift is on keto I eat bacon, eggs, vegetable oil, cheese (not high quality) then shift to bacon, eggs, oil, cheese + carbs, this is a problem no matter what because in both cases the fats are unhealthy.
Another interesting area of research is in athletes and performance. If you wanted to look into it more, Jeff Volek has discussed the concept of cyclic ketosis, which is the idea that if you’re keto-adapted you can be a more efficient athlete because you’re good at using 2 different fuels whenever they’re available.
Leigh: Are there actual benefits to being in ketosis or burning ketones?
Dr. Taylor: Ketones are not only providing energy but are also powerful messengers that are important for metabolism. A bunch of animal studies have also shown that ketones are anti-inflammatory. Inflammation is necessary for healing an acute injury, but long-term chronic inflammation is linked to chronic disease. So, ketones have been shown to suppress pro-inflammatory pathways over a long period of time.
Leigh: Tell me about your study/work for your dissertation or any of your other keto-related research? Summarize your findings (high level) any surprises? conclusions?
Dr. Taylor: My original exposure to this was a pilot research study with Alzheimer’s disease. One of the key findings in Alzheimer’s patients is that their brains refuse to use glucose as an energy source, so we’ve started to shift our thinking of AD as more of an energy crisis. Amyloid and tau proteins are involved, but it’s more that brain metabolism has changed. Most basic thought behind research was to provide the brain with alternative fuel source. One study he did put Alzheimer’s patients on keto for 3 months, there were 15 participants at the start and 10 of them completed the study. Of those 10, 8 of the patients had improvement in cognition and decreases in Alzheimer’s symptoms. One person worsened, but he had other variables with his health, so it’s difficult to know what was going on, or if it was related to the diet change. With our study, the ketogenic diet education focused a lot on diet quality. Actually, I’m currently writing a paper regarding the positive changes in nutrient density of this study’s ketogenic diet vs. the standard diet that participants were following. I’m convinced that this type of keto diet is very different from a diet that only focuses on macronutrient ratios.
I remember from the research, a story about a patient that would read the newspaper multiple times a day but wouldn’t retain any of that information. About 2 months into the diet/study, the study partner reported that the patient had started reading the paper only once per day and retained some of that information later in the day. This type of story gives me optimism that it might be helpful for Alzheimer’s patients.
Leigh: What surprised you from your studies?
Dr. Taylor: I was surprised that older adults would follow it! To be honest, it was a challenge because these people have grown up through a low fat marketing era, and people are hesitant to increase fats to the level they needed on the study. Throughout, I had several shifts in perception. I had gone into it thinking it wouldn’t be too big of a challenge, but as I got feedback I realized how ingrained the low fat messaging was for these people. Also, I had no anticipation for the type of cognitive results that we saw. We saw improvements in patients that really compete with, or surpass some of the most successful Alzheimer’s research in the past. In Alzheimer’s research, a drug is considered to be successful if cognition decline is slowed, whereas in this study there was actually cognition improvement.
Leigh: What about the ketogenic diet for non-brain cancers such as Prostate and bladder cancers?
Dr. Taylor: There is some real interest in using it in these conditions, but there is currently not enough research to draw a conclusion. Based on results of other research it wouldn’t surprise me if it might help.
Leigh: Weight loss?
Dr. Taylor: Keto is one of the ways to do it. From experience of putting individuals on the diet, people have been able to eat a higher caloric amount and still lose weight. It has a thermogenic effect in that it boosts fat metabolism, which makes it effective for losing weight. After weight loss, like most other diets, you can’t go back to eating haphazardly because you’ll regain the weight. Surprisingly, it takes a lot of work for our bodies to store the fat that we eat as fat. Eating fat does not make you fat. (mic drop)
Leigh: So, would people with diabetes benefit?
Dr. Taylor: There is evidence that supports the use of keto in diabetes. Ketones are safe; it’s ketoacidosis that is dangerous.
Leigh: How can one be safe as a diabetic on a ketogenic diet?
Dr. Taylor: First, we should talk about the difference between type 1 and type 2 diabetes. Briefly, type 1 diabetes is an autoimmune disorder where the beta cells (cells that make insulin) in the pancreas have significant impairment or completely stop making insulin in response to sugar in the blood. Type 2 diabetes is when the cells of the body become resistant to insulin, meaning that the pancreas must produce much more insulin in response rises in blood sugar in order to transport it into the cell.
There is a very serious condition that can occur in uncontrolled type 1 diabetics known as ketoacidosis. Because of this condition, ketones are commonly thought of as bad or dangerous, but there is a big difference between ketosis and ketoacidosis. As we’ve discussed, our cells can burn either glucose (sugar/carbohydrates) or fat (in the form of ketones) for energy. Ketoacidosis is dangerous in uncontrolled type 1 diabetes in which blood levels of both glucose AND ketones are well above normal. This is a dangerous, potentially lethal, combination as high levels of glucose and ketones overwhelm the body’s ability to keep pH levels in a normal range. Ketoacidosis in type 1 diabetes is induced by the following:
- Ingestion of carbohydrates elevates blood glucose (sugar) levels.
- The pancreas does not produce insulin to drive the glucose into the cells, causing the body to think it is in a starved state.
- To compensate for the body’s perceived starved state, fatty acids are converted to ketones to use as an energy source.
- Because glucose is high and ketones are also being produced, the signal to shut down ketone production is severely impaired, resulting in extremely high production of ketones (~20+ mmol/L) and an overly acidic blood environment.
On the other hand, ketosis from following a ketogenic diet (without having type 1 diabetes) involves an elevation of ketones from what is normally ~0.1 mmol/L to anywhere between 0.3 to 1.5 mmol/L in the blood. The ketogenic diet provides a substrate that our cells can use and doesn’t result in the perceived energy crisis seen in DKA. Because ingestion of carbohydrates is low, glucose levels remain mostly normal while the brain and other tissue happily use the ketone bodies for energy. Ketones are more acidic than glucose, but that is okay at these levels since we are generally good at buffering the blood to normal pH levels.
It appears that the ketogenic diet may be safe and helpful in both type 1 and type 2 diabetes. First, a case study published a few years ago reported successfully treating type 1 diabetes in a 19-year-old male (Tóth & Clemens. Int J Case Rep Images. 2014). The patient previously utilized an insulin injection regimen and short-acting insulin for sporadic high glucose. Through 6.5 months on a vegetable-rich ketogenic diet, this participant maintained very tight glucose control and was able to incrementally reduce insulin usage until he came off of his insulin injections. (that’s insane, and unheard of) There were no adverse events reported. Interestingly, he also improved C-peptide production, which suggests that his pancreas regained some ability to naturally produce insulin. Similar findings have recently been published in a cohort of 11 type 1 diabetes patients (Leow. Diabetic Medicine. 2018). Disclaimer: This was all under STRICT supervision by a medical team. It is very important for an insulin-dependent diabetic to follow the recommended carbohydrate intake for their insulin dosage. Changes in eating patterns can affect insulin needs; therefore, making dietary changes like this must be done with a medical professional.
There was also this really cool study published by Stephen Phinney and Jeff Volek this year (Hallberg. Diabetes Therapy. 2018). Out of 349 type 2 diabetes patients, 262 patients were treated via a continuous care model that included a vegetable-rich ketogenic diet and 87 received usual care for type 2 diabetes. The patients on the ketogenic diet produced a blood ketone range of 0.5-3.0 mmol/L, demonstrated better diabetic control, and had significant reduction in diabetes medications when compared to the usual care group. The overall care model was labor intensive for the practitioners and researchers, but this study showed some pretty cool results for potential use of the ketogenic diet in diabetes treatment. They also, really focused on diet quality, which makes me think that there is long-term feasibility for the style of diet that the patients followed.
Leigh: So if someone is concerned about ketoacidosis, is it important to monitor ketosis and shift more slowly?
Dr. Taylor: I can’t say that I’m currently a proponent for keto in type 1 diabetes as I feel there much more need for research, but the ketogenic diet itself should not induce ketoacidosis. However, if people with insulin-dependent diabetes did want to pursue this as a potential treatment, it would be imperative that they do so through a medical professional with significant knowledge in the area. Following a ketogenic diet will require adjustments in insulin dosage and strict adherence to the diet protocol.
There’s a line of thinking that if you’ve become unable to use glucose (sugar) as a fuel, which is what diabetes IS, then the ketogenic diet may be an alternative. Think of it like this: why give your body more fuel that you can’t use? In type 1, perhaps keto could serve as a therapy that would alleviate the need for insulin injections. In type 2, it seems that it is effective in bringing abnormally high insulin levels down due to decrease in need.
Leigh: Does the ketogenic diet contradict the idea that a calorie is a calorie?
Dr. Taylor: On keto, the machinery used for getting glucose metabolism are reduced because you start using more of the fat and ketone metabolism machinery. Therefore, everything that we know about metabolism when we are primarily using glucose is turned on its head. One of the effects of the diet could be that we increase the number of mitochondria available, which is where the body makes energy.
Leigh: Is there a thermogenic effect?
Dr. Taylor: Ingesting more fat for energy makes you more likely to burn more of your stored fat as energy. Think of it this way: fat burning machinery is at its peak, so stored fat in our bodies become available as an energy source.
Leigh: Why do ketones make us make more mitochondria?
We still aren’t exactly sure why. Some theories include that ketogenic diets cause less metabolic stress allowing for more mitochondrial biogenesis or perhaps that ketones themselves have a signaling effect. It’s very important to keep in mind that all of the research available has been done in humans/animals with health conditions, not those that are generally healthy.
Leigh: Is there any evidence about the quality of the diet and efficacy of keto or is it all about the macronutrient balance?
Dr. Taylor: Right now, research outcomes have all been about macronutrient balance. I’d really like to see research go toward diet quality, which is coming. From a clinical standpoint (non-research), I’ve observed it is more feasible when people focus on quality, especially when following long term. A keto diet based on high quality foods would include beneficial fats, vegetables, and generally more of a whole food approach. These people seem to tolerate the diet better. They likely could go long term and have success, but we still need to learn if it’s feasible to follow a strictly ketogenic diet long term.
Leigh: Is there any effect on the gut while doing keto?
Dr. Taylor: Interesting new research about gut flora modulation suggests that some benefits of the ketogenic diet may be mediated/modulated by gut flora changes.
Leigh: What are the changes in flora?
Dr. Taylor: I’m not sure how it may affect people with an “optimal flora” but if you take, for example, epilepsy, MS, etc. it is suggested that the gut flora may be altered. In epilepsy, those changes in gut flora have associations with changes in seizure control. There are some animal studies where changing the gut flora can help halt seizures. This poses an interesting question: does diet quality in the ketogenic diet matter? Now we have to ask: do the microbes change by the macronutrient distribution, or does the food type matter (e.g. do veggies/fruit matter)?