Ketosis, Epigenetics, and the Brain

It’s long been understood that ketones, specifically beta-hydroxybutyrate (BHB), are a brain superfuel. It’s easy to explain the evolutionary reasons for this. Hunter-gatherers spent much more time in ketosis. This metabolic state tends to occur during periods of low food access. That happens in winter but also throughout the year, as hunter-gatherers tend toward a feast and fast pattern.

After a period of plenty, it might be a while until the next big kill. Some hunting expeditions could take days or weeks. They needed their brains working in top form for a successful hunt. Many hunter-gatherer tribes purposely fast on a regular basis as a demonstration of their toughness, to show that they can go long periods without food, a very important ability for hunters. Even tribal people living amongst food abundance will fast for no particular reason other than it’s part of their culture.

The Piraha, for example, can procure food easily and yet will go without, sometimes simply because they’d rather socialize around the village or are in the middle of communal dancing that can go on for days. They have better things to do than eat all the time. Besides, on a low-carb diet that is typical among hunter-gatherers, it takes little effort to fast. That is one of the benefits of ketosis, one’s appetite is naturally suppressed and so it effortlessly promotes caloric restriction.

Along with improving brain function, ketosis increases general health, probably including extending lifespan and certainly extending healthspan. Some of this could be explained by creating the conditions necessary for autophagy, although there are many other factors. An interesting example of this was shown in a mouse study.

The researchers exposed the rodents to influenza (E. L. Goldberg et al, Ketogenic diet activates protective γδ T cell responses against influenza virus infection). Most of the mice on a high-carb diet died, whereas most on the keto diet lived. In this case, it wasn’t the ketones themselves but other processes involved. Giving exogenous ketones as a supplement did not have the same effect as the body producing its own ketones. We typically think of ketosis only in terms of ketones, but obviously there is much more going on.

Still, in the case of neurocognitive functioning, the ketones themselves are key. It’s not only that they act as a superfuel but simultaneously alter epigenetic expression of specific genes related to memory. On the opposite side, research shows that feeding people sugar literally makes them dumber. Ketosis also decreases inflammation, including inflammation in the brain. Through multiple causal mechanisms, ketosis has been medically used as an effective treatment for numerous neurocognitive conditions: mood disorders, schizophrenia, autism, ADHD, Alzheimer’s, etc.

If ketosis is a biological indicator of food scarcity, why does the body expend extra energy that is limited? This seems counter-intuitive. Other species deal with food scarcity by shutting the body down and slowing metabolism, some going into full hibernation or semi-hibernation during winter. But humans do the opposite. Food scarcity increases physiological activity. In fact, ketosis is actually inefficient, as it burns more energy than is needed with the excess being put off as heat.

Benjamin Bikman, an insulin researcher, speculates this is because ketosis often happens in winter. Hibernating creatures lower their body temperature, but humans don’t have this capacity. Neither do we have thick fur. Humans need large amounts of heat to survive harsh winters. In ketosis, everything goes into overdrive: metabolism, immune system, and brain. This alters the epigenome itself that can be passed onto following generations.

* * *

You Are What Your Mother and Father (and Grandmothers and Grandfathers) Ate
by Mark Sisson

Epigenetic Explanations For Why Cutting Sugar May Make You Feel Smarter
by Caitlin Aamodt

High Fat, Low Carb Diet Might Epigenetically Open Up DNA and Improve Mental Ability
by Bailey Kirkpatrick

Epigenetics May Provide Relief for Fragile X Syndrome and Intellectual Disorders
by Tim Barry

Fiber or Not: Short-Chain Fatty Acids and the Microbiome

A common viewpoint among both conventional and alternative health practitioners is that fiber is good for you. Not only good but necessary. Millie Barnes, as an example, identifies her expertise as a chef and nutrition coach. She apparently comes from a functional medicine approach, common among those advocating traditional foods diet that is plant-based and fiber-heavy (another example is Dr. Terry Wahls).

Barnes wrote a post about fiber and short-chain fatty acids (SCFAs), Why Short-Chain Fatty Acids Are Key To Gut & Overall Health, Plus How To Get More — her position is typical: “SCFAs are produced when bacteria—the good kind—ferment fiber in the gut, thereby providing your body with energy, keeping your metabolism humming, and even thwarting a wide range of digestive disorders.” There is nothing necessarily wrong about this position, although the scientific evidence is severely limited and highly contested. The problem is in treating the science as settled.

I’m not against fiber. I eat some high-fiber vegetables, especially fermented, along with other cultured foods. I used to eat even more fiber and vegetables, back when I was doing a paleo diet. And there was benefits to it, at least in comparison to my prior high-carb diet of processed foods. But I’ve also tried the carnivore diet and felt freaking awesome! I never realized how hard to digest are most plant foods (Like water fasts, meat fasts are good for health.).

I’m much more cautious about the plants and hence plant substances, including toxins and anti-nutrients, I allow into my body. Still, I have nothing against plants on general principle and I’m persuaded by Siim Land’s argument for hormesis and antifragility, that is to say beneficial stress (in case you’re interested, there is an intriguing scientific paper to check out: Hagen, Roulette & Sullivan, Explaining Human Recreational Use of ‘pesticides’). I now think of plants as more medicine than food, but nonetheless quite useful as medicine.

SCFAs are a complex topic, as is the microbiome of which we know little. As aside note, while some SCFAs (acetate and butyrate) are ketogenic, others (propionate) is glycogenic. They play an important role in health. That much we can agree on. What is less understood or at least less acknowledged is that SCFAs can come from other sources besides fiber. Butyrate, for example, is found in dairy fat. The cow eats the fiber and makes the butyrate for us.

So butyrate deficiency shouldn’t be a problem for anyone on a reasonably healthy diet, plant-based or animal-based. That is assuming they are getting plenty of high-fat dairy, pasture-raised all the better, and most Westerners tend to consume tons of dairy. As for myself, I get plenty of ghee (clarified butter) which means I’m probably fine on butyrate levels. By the way, my preferred mode of ghee delivery is through coffee and tea, what has been made famous as Dave Asprey’s Bulletproof Coffee, but he got the idea from a Tibetan woman who served him tea with yak butter. This maybe is not such a foreign practice. My mother recalls her Kentuckiana grandmother regularly pouring coffee over butter, although she also mixed in saltine crackers — that latter part probably less traditional and certainly not low-carb.

To get back to our discussion of SCFAs, I’m not as familiar with acetate, but apparently you can get it from apple cider vinegar (ACV), something I also take on a daily basis. I assume that the microbes in the ACV produced the acetate and so bypasses the need of the microbes in your own gut to do the work. No fiber is required, at least not in the diet. Furthermore, one can get acetate from ketosis as well and ketosis is my preferred state. Acetate/acetoacetate sometimes is what is measured for ketone levels. Some amino acids such as leucine and lysine can be converted into acetoacetate through fatty acid synthesis. Acetoacetate then is reduced to beta-hydroxybutyrate and the latter gets turned into acetone and acetate.

Now on to propionate, even more fascinating. It is a food additive that the modern person is getting overdosed on and appears to be a causal factor behind such conditions as autism (The Agricultural Mind). Those on the autistic level tend to have high levels of the bacteria that produce propionate and tend to crave foods that are high in it. Rodents injected with propionate express autistic-like behaviors. And those on the autistic spectrum show decreased behavioral problems when propionate is removed from their diet or when an antibiotic kills off some of their microbiome. SCFAs are a key part of a health diet, but they are powerful substances not to be taken lightly. They potentially can do harm as well.

As a last comment, no studies have been done on the microbiome of those on a carnivore diet or near-carnivore diet such as the Inuit. Heck, there has been no research even on a more general healthy omnivore diet including meat — the studies on the Standard American Diet (SAD) don’t count. But from what we do know about biology in general, it appears humans have multiple pathways of producing or obtaining SCFAs. The microbiome, in particular, is probably extremely adaptable to a wide variety of diets that were necessary during evolution (e.g., the microbiome of some hunter-gathers completely alters from season to season). Dr. Paul Saladino has talked a lot about this kind of thing — take what he had to say in an interview with Geoffrey Woo (Nose-to-Tail Carnivore Diet: Organ Meat, TMAO Implications, & Reaching Ketosis ft. Dr. Paul Saladino; & video):

“There are many bacteria which can metabolize fat, protein and animal-based collagen. That’s the thing I think that most people are missing. That our gut microbiome can shift. There’s a study where they put people on what I would consider to be a very poor version of a carnivorous diet and they compare it a plant-based diet. What they see is a divergence in the gut flora within a week. The animal-based eater, again, it’s not an ideal diet. The animal-based eaters had more bile acid tolerant organisms and more organisms to ferment fat and protein. They made isobutyrate and they made acetate and they made propionate as short chain fatty acids.

“The plant-based eaters made butyrate as a short chain fatty acid and had different colonic and small intestinal microflora. The investigators in that study jumped to the conclusion. Look, we know what’s going on with the gut because they have this organism. What’s worthy of biophilia or they don’t have this organism. They clearly have an unhealthy gut microbiome and I think that is an extrapolation. We do not know that. Clinically, nobody is assaying anything clinically in that study. They didn’t do inflammatory markers. They didn’t follow those people moving forward. It was almost like a setup. They were just trying to prove that these bile acid tolerant organisms would show up when they gave people a bunch of foods, which promote the formation of bile.”

Dr. Paul Saladino was on the paleo diet before trying carnivore, but Dr. Will Cole went from vegetarian to a more paleo-style diet. Dr. Cole wrote a book, Ketotarian, about how to do a plant-based keto and so he is right in line with the likes of Millie Barnes. That didn’t stop him, in an interview with Vanessa Spina, from pointing to evidence that a high-fiber diet may not be necessary, even going so far as to mention the carnivore diet:

“Because we have an epidemic of gut problems in the United States and around the world and Europe as well that this is going take time. Sometimes some people can have it right out of the gate. Some people can’t. It’s important to know what’s right for your body and what’s not right for your body. But as you heal, what you used to not be able to have the goal is to be able to reintroduce these things as your body heals.

“So the carnivore diet, for example, it’s the ultimate elimination die because it’s removing a lot of these fibers. But the goal isn’t to be carnivorous forever and ever, even though maybe some people would prefer that. But the goal is to use something like that to drive down this inflammatory cascade to bring things back in, as long as it’s nutrient-dense. And there are studies to show like the Hadza tribe in Tanzania they have good bacterial diversity during those months where they are eating less vegetables. But they’re eating more raw meat or getting like drinking blood and doing things that most people that are on the carnivore diet in the West are not doing today.

“So there are other there are other ways to get back to our diversity beyond fiber. I would just say it is the most common, most well researched way to get back to our diversity.”

Vanessa Spina, in that interview, then added an important point, not all prebiotics are fiber or necessarily come from plants at all: “I found this list of prebiotic foods that were non-carbohydrate that included cellulose, cartilage, collagen, fructooligosaccharides, glucosamine, rabbit bone, hair, skin, glucose. There’s a bunch of things that are all — there’s also casein. But these tend to be some of the foods that actually have some of the highest prebiotic content. So it’s interesting, I think, if someone has less tolerance for fiber, they can also explore some of these other product prebiotics.” That is something I never hear anyone talk about.

This might explain why so many people do so well on a carnivore diet. They are still getting prebiotics. And we know those on entirely or mostly meat diets retain functioning microbiomes. But there has been so few scientists looking into this.

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3/2/20 – The first video below is a quick overview by Dr. Paul Saladino. And for more detail, see the second video (time mark 77:00-84:00) where he talks with Dr. Joseph Mercola. But to get his full argument, you’ll have to read his book that just came out, The Carnivore Code.

 

Getting Into Ketosis

Here is some information about ketones, ketosis, and ketogenic diets. The focus is on treating Alzheimer’s, although the topic applies to many other conditions as well. Let me begin by explaining the basics.

Ketosis is the primary burning of fat, dietary fat or body fat, to produce ketones that the body uses. A ketogenic diet is sometimes called nutritional ketosis, as opposed to ketosis through other means such as fasting. When ketone levels are high enough, it is called ketosis — the term being used more strictly for medical purposes. The body has two main options for fuel, glucose and ketones. With Alzheimer’s as type 3 diabetes, insulin resistance in the brain decreases the ability to use glucose and so the brain slowly starves. Ketones can mostly replace glucose, especially for brain cells. Some argue they’re the preferred source of energy, since for most of human evolution there were limited amounts of carbohydrates in the diet. This is shown in how, when both glucose and ketones are available, the brain prioritizes the latter. Ketones are a more efficient and steady source of energy because few people have to worry about running out of dietary or body fat to make ketones.

Ketones are a superfuel that allows the brain function at a higher level. In ketosis, not only does metabolism change but so does brain functioning. This is why ketogenic diets have been medically used to treat diverse neurocognitive conditions: epileptic seizures, autism, ADHD, depression, multiple sclerosis, Alzheimer’s, etc. Part of this has to do with inflammation, as ketosis is anti-inflammatory. This is important because inflammation is often involved in problems with brain health and many other problems as well (arthritis, autoimmune disorders, etc). I can vouch for this in my own experience when my depression disappeared after going low-carb. Partly that is because my glucose, insulin and serotonin levels would have stabilized, but cutting back my carbs further to go into ketosis definitely made a difference. I generally feel better.

Immediately below is a chart comparing ketogenic strategies and the resultant increase in ketones. If multiple strategies are combined, ketone levels can be higher still. Ketoacidosis is thrown in the chart below for comparison, but it only happens to diabetics and it is harmful — it’s an entirely separate condition from ketosis, although both involve ketones. People sometimes confuse ketoacidosis with ketosis, but what causes each is separate. As you can see below, ketoacidosis raises ketone levels to a degree that nothing else does. Unless one is diabetic, that isn’t a concern.

Ketogenic Strategy                             —>               Ketone Levels (mmol/L)

Caffeine                                                    —>               0.2 to 0.3

Coconut Oil                                              —>               0.3 to 0.5

Vigorous Exercise                                  —>              0.3 to 0.5

Overnight Fast                                        —>              0.3 to 0.5

MCT Oil                                                      —>             0.3 to 1.0

Branched Chain Amino Acids            —>             0.3 to 1.0

Ketone Mineral Salts                            —>             0.5 to 1.0

Classic Ketogenic Diet                          —>             2 to 6

Starvation/Long-Term Fasting       —>             2 to 7

Ketone Esters (Oral or IV)                   —>             2 to 7 or higher

Diabetic Ketoacidosis                           —>            10 to 25

This chart and most of the other info I share here comes from Mary T. Newport’s book, The Complete Book of Ketones. There is also good info available in Dale E. Bredesen’s The End of Alzheimer’s, Amy Berger’s The Alzheimer’s Antidote, and Bruce Fife’s Stop Alzheimer’s Now. All I’m discussing below is the most basic info. For a more in-depth approach, I’d recommend checking out Dr. Bredesen, the author mentioned above, who is an Alzheimer’s researcher and clinician at UCLA. He has a complex protocol, going beyond ketosis, that requires working with a doctor trained in it. The clinical trial he did is the only confirmed reversal of Alzheimer’s. But back to increasing ketones and suppressing mental loss.

How to get into ketosis:

The most dependable method of entering into ketosis and maintaining it is through diet. Put in the simplest terms, there needs to be strict limits on starchy carbs and sugar (bread, crackers, noodles beans, potatoes, fruit, fruit juice, pop, candy, most processed foods, etc) combined with moderate amounts of protein and lots of fat/oil. Specific details can be found below. It is not necessarily easy, since those are some of the foods we enjoy most. Even so, it still allows a fair amount of diversity. Many foods are low in carbs: non-starchy vegetables, fruits like olives and avocados, most nuts and seeds, etc. The difficult part is that many convenience foods aren’t allowable other than as occasional foods eaten in limited amounts.

Of course, there are simpler methods of increasing ketones. Here are three:

(1) Exogenous ketones can be taken directly and will give a quick mental boost that doesn’t last long, but it is easy for the body to use since it is already in the needed form. A single dose peaks out in 30-60 minutes with the body fully eliminating them in a few hours. Exogenous ketones would need to be regularly taken in smaller amounts throughout the day to maintain higher ketone levels. One thing to keep in mind is that as ketone levels go up blood sugar and insulin levels drop. This can be an issue for people with diabetes or pre-diabetes. There are two options of exogenous ketones: ketone esters and ketone salts. The former are more easily used by the body, but the latter are more available on the market. I haven’t found ketone esters in any local store. They can be obtained online, though. I’d probably stick to the ketone salts, as there is much more research done showing their safety. Exogenous ketones are of more limited use since most people can’t safely handle more than one or two servings a day.

(2) Or one can use MCTs (medium chain triglycerides) which turn into ketones without much effort. MCT oils and powders can be added throughout the day and the body uses them fairly quickly. There are also MCTs in coconut oil and Mary T. Newport found that, in treating her husband’s Alzheimer’s, that coconut oil had a longer lasting effect. She used a combination of all three: exogenous ketones, MCT oil, and coconut oil. This gave a more steady level of ketones throughout the day. Her husband showed improvement despite her not doing anything else initially, not otherwise changing his diet. As a side note, Newport says to use cold-pressed coconut oil for reasons of general health. The main advantage is that greater amounts of MCTs and coconut oil allow the body to produce ketones even when carbs aren’t as restricted, not that one can eat carbs unlimited.

(3) An even simpler way is fasting, although easier still if one is already in ketosis (trying to go from a high-carb diet to fasting can be a challenge). A person is guaranteed to go into ketosis by not eating. Even a full night of sleep is enough to begin increasing ketone levels. Skip a meal or an entire day of eating and ketone levels will keep going up to a much more noticeable degree. If you break your fast with a ketogenic meal of low-carb and high-fat, that will extend ketosis into the rest of the day. Starting your day with fat in your coffee can be even better, as caffeine will also boost ketones (I add ghee and MCT oil to my coffee and mix it up with a battery-powered frother). In fasting for ketogenic purposes, one can do a fat fast by eating only fat, such as drinking fat-filled coffee all day. Without starches and sugar, the body is forced to burn fat and produce ketones. There isn’t anything easier than a fat fast nor as satiating.

The only potential downside is not everyone digests and metabolizes fat equally well. MCT oils, in particular, can require some adaptation. Too much can cause diarrhea for those sensitive to it. It’s best to start off with small amounts (1/2 to 1 tsp or less at a time, once or twice a day) and build up a tolerance (upwards of 1 to 2 tbsp or possibly higher, two to four times a day). If sensitive, take MCT oils with other foods, such as mixing it into cottage cheese or Greek yogurt. Coconut oil is easier for the body to handle, as it is a mix of other fats such as lauric acid that has some of the traits of MCTs. There is evidence that lauric acid works as a ketogenic fat directly in the brain. Coconut oil also helps with the thyroid and Alzheimer’s patients often develop thyroid problems.

By the way, here is what Mary T. Newport writes: “When Steve [her husband with Alzheimer’s took just coconut oil in the morning, his ketone levels peaked at about three hours but had returned to nearly normal after eight to nine hours, just before dinner time. With just MCT oil, Steve’s ketone levels went higher, peaked at about ninety minutes, but were gone within three hours.” So, she used both in a 4:3 ratio (MCT to coconut oil) to maintain stable ketone levels throughout the day. Newport suggests gradually increasing coconut oil (and MCT) intake up to 4-6 tablespoons a day or even as high 8 tablespoons, but gradually is the key part.

If one wants to ensure ketosis, there are ways to measure ketone levels. I’ve never done this, but I keep my carbs so low that there is no way for me to avoid ketosis. Without a ketogenic diet, it will be more difficult keeping ketone levels elevated and stable. Still, any greater amount of ketones is better than nothing when it comes to how the brain is starving for fuel in Alzheimer’s or in relation to many other conditions. If you want to try a ketogenic diet, here are some variations explained in detail and with good visuals about what the macronutrient (carb, protein, & fat) ratios should look like as a plate of food: Diet Plans – Charlie Foundation. Also, keep in mind protein levels, which can be an issue for with diabetes, pre-diabetes, etc: Too Much Protein?

Eating in such a way that ketosis is frequent is not always easy, although it can be the easiest diet in the world. It is not easy for many people because such diets reduce the foods they ‘love’ (sugar and carbs), reduce the foods they know how to prepare, and reduce the food options found in most restaurants. Further, these diets run contrary to the traditional food pyramid that we have been trained on for years. They seem downright unhealthy, when in fact, current research is showing they have been healthier all along. It requires changing how one thinks about food. In short, one must be very intentional. One cannot coast along and provide optimal brain nutrition. The first step for most people is breaking their food addiction, but it’s worth the effort.

Too Much Protein?

A ketogenic diet is any diet that puts you into ketosis. The issue isn’t only what raises your ketone levels but also what lowers them. It is glucose that keeps you out of ketosis and that generally means restricting carbohydrates. But glucose can come from other sources. This is where protein come in. It has been a common view that too much protein would keep you out of ketosis. The theory was that gluconeogenesis, the process that turns proteins into glucose, could interfere with ketosis. So, some have worried that too much protein was basically no different than too many starches and sugar.

That view has been challenged by more recent research. The newer understanding is that gluconeogenesis is mostly demand-driven, not supply driven. That said, it’s more complicated than that. There are conditions that can alter demand or else signaling. Benjamin Bikman, an insulin researcher, advocates a higher protein ketogenic diet. He says that initially it might matter when someone first goes onto a ketogenic diet, if they have hyperglycemia and hyperinsulinemia, a problem for far too many Americans. But as insulin levels are normalized, which can happen quickly, gluconeogenesis is not a problem.

So, it depends on how healthy you are. With insulin resistance, high protein intake might spike insulin and cause the insulin glucagon/ratio to become imbalanced. Yet for a person with a healthy metabolism, the glucose/insulin ratio might not change at all. As Ben Wagenmaker explains it, “Studies do show that GNG affects obese people and diabetics, in that excess protein produces measurable spikes in blood glucose levels, although this same effect has not been observed and quantified in non-diabetics that are not obese” (Gluconeogenesis, Chocolate Cake, and the Straw Man Fallacy).

Considering that most Americans are obese, diabetic, pre-diabetic or insulin resistant, it might be advisable to limit protein until one has become fat-adapted and metabolically flexible. It’s easy to figure out for yourself, though. You can simply measure such things and see how it is affecting you. Or you can go by an even simpler method. Once your body is regularly in ketosis, fasting should become easy. If you can skip meals or go a day without eating at all and not be particularly bothered by it, then you know you’re body has fully adjusted to ketosis. At that point, protein should no longer be a concern.

This is good to keep in mind, considering most people turn to specific diets later in life. Bikman points out that, as people age, the body requires more protein for health. That is because the body becomes less effective at using protein. And if you don’t get enough protein on a keto diet, the body will cannibalize muscle.  A lack of protein, in general, can be problematic — look at how lacking in musculature are many vegans with limited protein and lower quality protein. Muscle loss is a major health hazard for senior citizens, but muscle loss can begin much earlier in life.

* * *

Dietary Proteins Contribute Little to Glucose Production, Even Under Optimal Gluconeogenic Conditions in Healthy Humans
by Claire Fromentin et al

Dietary Protein and the Blood Glucose Concentration
by Frank Q. Nuttall & Mary C. Gannon

The relationship between gluconeogenic substrate supply and glucose production in humans
by F. Jahoor, E. J. Peters & R. R. Wolfe

More Than You Ever Wanted to Know About Protein & Gluconeogenesis
by Amy Berger

If You Eat Excess Protein, Does It Turn Into Excess Glucose?
by L. Amber O’Hearn

Protein, Gluconeogenesis, and Blood Sugar
by L. Amber O’Hearn

Ketosis Without Starvation: the human advantage
by L. Amber and Zooko Wilcox-O’Hearn

The Ultimate Guide to the Carnivore Diet:
How can carnivore diets be ketogenic when they have so much protein?
by L. Amber O’Hearn and Raphael Sirtoli

What is gluconeogenesis? How does does it control blood sugars?
by Raphael Sirtoli

the blood glucose, glucagon and insulin response to protein
by Marty Kendall

why do my blood sugars rise after a high protein meal?
by Marty Kendall

Gluconeogenesis – The worst name for a rock band ever
by Tyler Cartwright

Protein Over-consumption in Ketogenic Diets Explained
by Ken Adkins

Will This Kick Me Out Of Ketosis?
by Dustin Sikstrom

Keto Problems: Too Much Protein?
by Keto Sister

Dietary protein does not negatively impact blood glucose control.
by Bill Lagakos

 

Ketogenic Diet and Neurocognitive Health

Below is a passage from Ketotarian by Will Cole. It can be read in Chapter 1, titled “the ketogenic diet (for better and worse)”. The specific passage is to be found on pp. 34-38 in printed book (first edition) or pp. 28-31 in the Google ebook. I share it here because it is a great up-to-date summary of the value of the ketogenic diet. It is the low-carb diet pushed to its furthest extent where you burn fat instead of sugar, that is to say the body prioritizes and more efficiently uses ketones in place of glucose.

The brain, in particular, prefers ketones. That is why I decided to share a passage specifically on neurological health, as diet and nutrition isn’t the first thing most people think of in terms of what often gets framed as mental health, typically treated with psychiatric medications. But considering the severely limited efficacy of entire classes of such drugs (e.g., antidepressives), maybe it’s time for a new paradigm for treatment.

The basic advantage to ketosis is that, until modernity, most humans for most of human evolution (and going back into hominid evolution) were largely dependent on a high-fat diet for normal functioning. This is indicated by how the body more efficiently uses ketones than glucose. What the body does with carbs and sugar, though, is to either to use it right away or store it as fat. This is why hunter-gatherers would, when possible, carb-load right before winter in order to fatten themselves up. We have taken this knowledge in using carbs to fatten up animals before the slaughter.

Besides fattening up for winter in northern climes, hunter-gatherers focus most of their diet on fats and oils, in that when available they choose to eat far more fats and oils than they eat meat or vegetables. They do most of their hunting during the season when animals are the fattest and, if they aren’t simply doing a mass slaughter, they specifically target the fattest individual animals. After the kill, they often throw the lean meat to the dogs or mix it with fat for later use (e.g., pemmican).

This is why, prior to agriculture, ketosis was the biological and dietary norm. Even farmers until recent history were largely dependent in supplementing their diet with hunting and gathering. Up until the 20th century, most Americans ate more meat than bread, while intake of vegetables and fruits was minor and mostly seasonal. The meat most Americans, including city-dwellers, were eating was wild game because of the abundance in nearby wilderness areas; and, going by cookbooks of the time, fats and oils were at the center of the diet.

Anyway, simply in reading the following passage, you will not only become more well informed on this topic than average American but, sadly, also the average American doctor. This isn’t the kind of info that is emphasized in medical schools, despite it being fairly well researched at this point (see appended section of the author’s notes). “A study in the International Journal of Adolescent Medicine and Health assessed the basic nutrition and health knowledge of medical school graduates entering a pediatric residency program and found that, on average, they answered only 52 percent of eighteen questions correctly,” as referenced by Dr. Cole. He concluded that, “In short, most mainstream doctors would fail nutrition” (see previous post).

Knowledge is a good thing. And so here is some knowledge.

* * *

NEUROLOGICAL IMPROVEMENTS

Around 25 percent of your body’s cholesterol is found in your brain, (19) and remember, your brain is composed of 60 percent fat. (20) Think about that. Over half of your brain is fat! What we have been traditionally taught when it comes to “low-fat is best” ends up depriving your brain of the very thing it is made of. It’s not a coincidence that many of the potential side effects associated with statins—cholesterol-lowering drugs—are brain problems and memory loss. (21)

Your gut and brain actually form from the same fetal tissue in the womb and continue their special bond throughout your entire life through the gut-brain axis and the vagus nerve. Ninety-five percent of your happy neurotransmitter serotonin is produced and stored in your gut, so you can’t argue that your gut doesn’t influence the health of your brain. (22) The gut is known as the “second brain” in the medical literature, and a whole area of research known as the cytokine model of cognitive function is dedicated to examining how chronic inflammation and poor gut health can directly influence brain health. (23)

Chronic inflammation leads to not only increased gut permeability but blood-brain barrier destruction as well. When this protection is compromised, your immune system ends up working in overdrive, leading to brain inflammation. (24) Inflammation can decrease the firing rate of neurons in the frontal lobe of the brain in people with depression. (25) Because of this, antidepressants can be ineffective since they aren’t addressing the problem. And this same inflammatory oxidative stress in the hypothalamic cells of the brain is one potential factor of brain fog. (26)

Exciting emerging science is showing that a ketogenic diet can be more powerful than some of the strongest medications for brain-related problems such as autism, attention deficit/hyperactivity disorder (ADHD), bipolar disorder, schizophrenia, anxiety, and depression. (27) Through a ketogenic diet, we can not only calm brain-gut inflammation but also improve the gut microbiome. (28)

Ketones are also extremely beneficial because they can cross the blood-brain barrier and provide powerful fuel to your brain, providing mental clarity and improved mood. Their ability to cross the blood-brain barrier paired with their natural anti-inflammatory qualities provides incredible healing properties when it comes to improving traumatic brain injury (TBI) as well as neurodegenerative diseases. (29)

Medium-chain triglycerides (MCTs), found in coconuts (a healthy fat option in the Ketotarian diet), increase beta-hydroxybutyrate and are proven to enhance memory function in people with Alzheimer’s disease (30) as well as protect against neurodegeneration in people with Parkinson’s disease. (31) Diets rich in polyunsaturated fats, wild-caught fish specifically, are associated with a 60 percent decrease in Alzheimer’s disease. (32) Another study of people with Parkinson’s disease also found that the severity of their condition improved 43 percent after just one month of eating a ketogenic diet. (33) Studies have also shown that a ketogenic diet improves autism symptoms. (34) Contrast that with high-carb diets, which have been shown to increase the risk of Alzheimer’s disease and other neurodegenerative conditions. (35)

TBI or traumatic brain injury is another neurological area that can be helped through a ketogenic diet. When a person sustains a TBI, it can result in impaired glucose metabolism and inflammation, both of which are stabilized through a healthy high-fat ketogenic diet. (36)

Ketosis also increases the brain-derived-neurotrophic factor (BDNF), which protects existing neurons and encourages the growth of new neurons—another neurological benefit. (37)

In its earliest phases, modern ketogenic diet research was focused on treating epilepsy. (38) Children with epilepsy who ate this way were more alert, were more well behaved, and had more enhanced cognitive function than those who were treated with medication. (39) This is due to increased mitochondrial function, reduced oxidative stress, and increased gamma-aminobutyric acid (GABA) levels, which in turn helps reduce seizures. These mechanisms can also provide benefits for people with brain fog, anxiety, and depression. (40)

METABOLIC HEALTH

Burning ketones rather than glucose helps maintain balanced blood sugar levels, making the ketogenic way of eating particularly beneficial for people with metabolic disorders, diabetes, and weight-loss resistance.

Insulin resistance, the negative hormonal shift in metabolism that we mentioned earlier, is at the core of blood sugar problems and ends up wreaking havoc on the body, eventually leading to heart disease, weight gain, and diabetes. As we have seen, healthy fats are a stronger form of energy than glucose. The ketogenic diet lowers insulin levels and reduces inflammation as well as improving insulin receptor site sensitivity, which helps the body function the way it was designed. Early trial reports have shown that type 2 diabetes symptoms can be reversed in just ten weeks on the ketogenic diet! (41)

Fascinating research has been done correlating blood sugar levels and Alzheimer’s disease. In fact, so much so that the condition is now being referred to by some experts as type 3 diabetes . With higher blood sugar and increased insulin resistance comes more degeneration in the hippocampus, your brain’s memory center. (42) It’s because of this that people with type 1 and 2 diabetes have a higher risk of developing Alzheimer’s disease. This is another reason to get blood sugar levels balanced and have our brain burn ketones instead.

Notes:

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I came across something interesting on the Ketogenic Forum, a discussion of a video. It’s about reporting on the ketogenic diet from Dateline almost a quarter century ago, back when I was a senior in high school. So, not only has the ketogenic diet been known in the medical literature for about a century but has even shown up in mainstream reporting for decades. Yet, ketogenic-oriented and related low-carb diets such as the paleo diet get called fad diets, and the low-carb diet has been well known for even longer, going back to the 19th century.

The Dateline show was about the ketosis used as treatment for serious medical conditions. But even though it was a well known treatment for epilepsy, doctors apparently still weren’t commonly recommending it. In fact, the keto diet wasn’t even mentioned as an option by a national expert, instead focusing on endless drugs and even surgery. After doing his own research for his son’s seizures, the father discovered the keto diet in the medical literature. The doctor was asked why he didn’t recommend it for the child’s seizures when it was known to have the highest efficacy rate. The doctor essentially had no answer other than to say that there were more drugs he could try, even as he admitted that no drug comes close in comparison.

As one commenter put it, “Seems like even back then the Dr’s knew drugs would always trump diet even though the success rate of the keto diet was 50-70%. No drugs at the time could even come close to that. And the one doctor still insisted they should try even more drugs to help Charlie even after Keto. Ugh!” Everyone knows the diet works. It’s been proven beyond all doubt. But there is a simple problem. There is no profit to be made from an easy and effective non-pharmaceutical solution.

This doctor knew there was a better possibility to offer the family and chose not to mention it. The consequences to his medical malfeasance is the kid may have ended up with permanent brain damage from seizures and from the side effects of medications. The father was shocked and angry. You’d think cases like this would have woken up the medical community, right? Well, you’d be wrong if you thought so. Yet quarter of a century later, most doctors continue to act clueless that these kinds of diets can help numerous health conditions. It’s not a lack of information being available, as many of these doctors knew about it even back then. But it simply doesn’t fit into the conventional medicine nor within the big drug and big insurance framework.

Here is the video: