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Let me introduce myself. My name is Mark Sisson. I’m 63 years young. I live and work in Malibu, California. In a past life I was a professional marathoner and triathlete. Now my life goal is to help 100 million people get healthy. I started this blog in 2006 to empower people to take full responsibility for their own health and enjoyment of life by investigating, discussing, and critically rethinking everything we’ve assumed to be true about health and wellness...

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July 19, 2016

The Fat Burning Brain: What Are the Cognitive Effects of Ketosis?

By Mark Sisson
39 Comments

The Fat Burning Brain FinalAlthough mainstream sources still mistake “the brain needs glucose” for “the brain can only run on glucose,” regular MDA readers know the truth: given sufficient adaptation, the brain can derive up to 75% of its fuel from ketone bodies, which the liver constructs using fatty acids. If we could only use glucose, we wouldn’t make it longer than a few days without food. If our brains couldn’t utilize fat-derived ketones, we’d drop dead as soon as our liver had exhausted its capacity to churn out glucose. We’d waste away, our lean tissue dissolving into amino acids for hepatic conversion into glucose to feed our rapacious brains. You’d end up a skeletal wraith with little else but your brain and a hypertrophied liver remaining until, eventually, the latter cannibalized itself in a last ditch search for glucose precursors for the tyrant upstairs. It would get ugly.

That’s adaptation. But is there an actual cognitive advantage to running on ketones?

Maybe. It depends. It certainly helps people with neurodegeneration.

People whose brains suffer from impaired glucose utilization see cognitive benefits from ketones. In Alzheimer’s disease, aging-related cognitive decline, epilepsy, and Parkinson’s disease, brain glucose uptake is depressed—even before any actual cognitive decline appears. Despite high glucose availability, the aging, epileptic, Alzheimer’s, or Parkinson’s brain can’t utilize enough of it to handle cognition. Enter ketones. Ketones act as an alternative energy source for the glucose-starved brains. It’s no coincidence that ketogenic diets can improve symptoms (and in some cases abolish them) and cognitive function in all four conditions.

Okay, but those are in unhealthy people with existing (or looming) neurological deficits and disorders. What about healthy people? What about you?

Anecdotes certainly suggest that otherwise healthy people can experience cognitive benefits from brain utilization of ketones. The entire butter/coconut oil coffee movement is predicated on ketone production—from morning fat bombs (especially medium chain triglycerides in coconut oil, which convert directly into ketones regardless of carb intake) and very low carb intakes—improving mental clarity, focus, and performance.  In people with “mild cognitive decline” rather than full-blown Alzheimer’s, a ketogenic diet improves memory. It hasn’t been validated in controlled trials of healthy subjects, but the fact that it’s a “movement” and shows efficacy in “unhealthy” brains suggests it’s worth exploring.

There are some interesting studies, to be sure, albeit not in totally healthy people. Such is the way of medical research.

  • Type 1 diabetics who experience reduced cognitive function because of low blood sugar see those deficits erased by increasing BHB through dietary medium chain triglycerides (the same fats found in coconut oil).
  • In memory impaired adults, some with Alzheimer’s, BHB improved cognition. Scores improved in (rough) parallel with rising ketones.
  • A ketone-elevating agent (purified medium chain triglycerides) improved cognition in patients with mild to moderate Alzheimer’s.
  • A very low-carb diet improved memory in older adults. Again, ketones tracked with improvements.

If there are benefits, what’s going on?

Brain mitochondrial biogenesis

Ketosis upregulates mitochondrial biogenesis in the brain. It literally creates new power plants in the brain that are good at burning fat-derived fuel. This upregulation is actually responsible for the anticonvulsant benefits in patients with epilepsy, and, likely, the benefits seen in other brain disorders with glucose uptake problems. By providing an alternate source of brain power, brains that don’t run so well on glucose can begin burning fat. There’s no indication that ketosis only induces mitochondrial biogenesis in “unhealthy” brains. It simply hasn’t been studied yet, but I don’t see why it wouldn’t also build mitochondria in healthy brains.

There’s reason to believe ketone-induced mitochondrial biogenesis in the brain will improve its function.

For one, extra energy sources are always nice to have. That they might improve the way your brain works makes intuitive sense.

Two, exercise, perhaps our most reliable and potent booster of mitochondrial biogenesis in the brain, is downright nootropic. Exercise increases blood flow to the brain, which provides more oxygen and energy but also reduces free radical damage and enhances memory. It stimulates the creation of new neurons and the production of brain-derived neurotrophic factor (BDNF), a chemical that is instrumental in neuron preservation and formation. Exercise also promotes gene expression that supports plasticity, the brain’s crucial power to alter neural pathways.

If exercise promotes mitochondrial biogenesis and better functioning in the brain, perhaps ketosis does, too.

Brain fog clearance

Elevated ammonia levels and depressed GABA levels contribute to a condition called “brain fog.” We’ve all had it. Everything is muffled. Your synapses fire blanks, your neuronal communication medium is cold molasses. Works suffers, nothing gets done.

According to a very interesting post from Dr. Bill Lagakos of the always interesting Calories Proper blog, ketosis has the potential to alleviate brain fog. There’s a lot of biochemistry thrown around, so geeks are advised to read the post in full, but two big, relevant takeaways are these:

Ketosis increases brain glutamine synthetase, and brain glutamine synthetase mops up extra ammonia.

Ketosis increases GABA signaling. GABA is the “chill-out” neurotransmitter. It opposes glutamate, the excitatory neurotransmitter. We need both for cognitive function (or else we wouldn’t make both), but too much glutamate can lead to neuronal injury and neurodegeneration. GABA is the counterbalance.

Euphoria infusion

Ketone bodies are known to increase feelings of euphoria in some people.

Of course, that isn’t always good for productivity and mental performance. If you experience high “affect intensity”—if euphoria hits you hard—then it might actually decrease your mental performance.

I know that the first cup of coffee after a great night’s sleep foments a heady dose of optimism tinged with focus that always leads to a productive morning. Maybe being a fat-burning beast in mild ketosis from the overnight fast is an additive.

I’m not surprised by any of this. For most of human history, a regular person would be regularly exposed to ketosis. Mostly light and transient, sometimes more protracted. But they were never far from a mildly ketogenic state for many reasons.

Long breastfeeding: Breastfed infants are in a mild state of ketosis (this is different from being on a very low carb diet, which babies are not!).

More meals, less snacking: Light ketosis in between meals, assuming fat-adaptation.

More structured meal times, less eating late at night: More nighttime ketosis.

Occasional fasting (the tribe going hungry, the hunter coming up short, the free range pre-1990s child being out all day and forgetting to eat): Full-blown ketosis.

This was “enough” to keep things in check and, likely, hold off neurodegeneration. Most of us are only learning about ketosis after a half or quarter lifetime of standard Western eating patterns. We’ve been snacking, overweight, unable-to-skip-a-meal sugar-burners, and we probably need a stronger intervention. That’s where ketones, ketogenic diets, and fasting come in.

You don’t even have to start counting the carbs in your leafy greens. There are ways to cycle between ketosis and higher-carb days, outlined in this post. There are also other ways to set up a meeting between ketones and your brain without changing your overall diet.

Here are a few.

Fasting: A fast quickly induces ketosis. You’re not eating anything, so your only option is to consume your own body fat. And to offset the lack of incoming glucose, your brain will run partially on ketones. It helps to be a strong fat-burner already, as you’ll start dipping into your body fat stores right away and everything will go more smoothly. Anyone who’s fasted without being fat-adapted can attest—it’s not easy.

Don’t eat too late: Even just a “fast” from dinner to breakfast is enough time to induce a little ketogenesis. Ketosis is a spectrum, not a binary. By eating earlier and avoiding midnight snacks, you allow your body to start burning fat and converting it into ketones. You’ll know it when you have funky ketone breath in the morning; it’s a sign of a good metabolism (PDF).

Eat medium chain triglycerides: Adding MCTs, found in coconut oil or isolated MCT oils, to a regular diet spurs the creation of ketones. You don’t even have to reduce carbs, although I probably wouldn’t recommend trying a high-carb, high-MCT oil diet. Might get weird (see the next section).

Eat ketone esters: “Eat” may be optimistic. “Do everything in your power to mask the flavor” is more accurate. These things are foul. But man do they quickly induce ketosis. I’ve taken them to experiment. Pretty hard on the digestive tract. They require a ton of taste alteration to get past the nastiness. I swear I get some funky stomach effects from some of them almost instantly, but I do notice I can play two hours of hard Ultimate with no other fuel.

I think they are awesome for a fat-adapted athlete. I doubt their efficiency and wonder about their safety in a sugar burner. In nutritional ketosis, or during fasting, both free fatty acids and ketones are elevated. This is normal. It’s physiological. When you add ketone esters to a regular diet, free fatty acids are low. This is unprecedented. Peter over at Hyperlipid is suspicious. He doesn’t like “faking ketogenic diets.” Tread lightly.

Primal Endurance training: Low-level aerobic activity is awesome for starting ketosis. 180 minus your age = the heart rate you need to stay at or under to maximize fat burning efficiency, lay your aerobic base, and upregulate mitochondrial biogenesis. Do this on an empty stomach and you’ll kickstart ketosis.

I don’t think we all need to be on a ketogenic diet, nor do we need to remain in ketosis for long periods of time. I do think we need to slip into ketosis every once in awhile, because we seem to be built for doing it and derive benefits from it. We know in the short term (and probably longer term) it’s safe. We know it seems to stave off neurodegeneration, as well as improve the brains of people already suffering from it. What we don’t know is if it will provide nootropic benefits to healthy individuals.

I suspect the occasional foray into ketosis will help you think, perform, and produce. I’ve felt it myself.

How about you? Has the fat-burning brain been a boon to your business?

Thanks for reading, all. Take care.

Prefer listening to reading? Get an audio recording of this blog post, and subscribe to the Primal Blueprint Podcast on iTunes for instant access to all past, present and future episodes here.

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39 Comments on "The Fat Burning Brain: What Are the Cognitive Effects of Ketosis?"

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Rich
Rich
10 months 6 days ago

I’ve heard of the issue with ingesting ketone esters (MCT oil and the like) to enter Ketogenesis. The dose seems important to warding off a quick trip to the bathroom.

Bryan
10 months 4 days ago
Take two tablespoons of apple cider vinegar in a tall glass of water before you take your mct oil and you will have no issues with GI probelms. I discovered this by accident and thought I was one of the lucky ones that didn’t get GI probelms from mct oil. Well one day I didn’t take the apple cider vinegar before my mct oil and I discovered that mct oil would give me GI problems without the apple cider vinegar. Can even put the mct oil in with the apple cider vinegar. With enough water it’s not a bad drink… Read more »
Wenchypoo
Wenchypoo
10 months 6 days ago
brain glucose uptake is depressed—even before any actual cognitive decline appears. Despite high glucose availability, the aging, epileptic, Alzheimer’s, or Parkinson’s brain can’t utilize enough of it to handle cognition Why is that? It’s because once you’ve passed through your respective “pause” (meno or MAN-O), the blood-brain barrier tightens itself to help defend against the onslaught of sugar that’s now in the blood (pick your reason: low exercise, not lowering carb intake to match, etc.) Sugar used to pass easily through this barrier to the brain because the sugar molecule was once wrapped in estrogen, and the barrier recognized it… Read more »
Ruth
Ruth
10 months 5 days ago

This was really fascinating to read! Are you in a medical/scientific field that deals directly with this, or do you perform your own research? This is by far the best description of Alzheimer’s that I’ve ever read.

Alice
Alice
10 months 6 days ago

I wonder if ketosis, or supplementing with certain ketogenic fats, would be helpful as a preventative if you’re at higher risk for nuerodegenerative disorders? For example, folks with the Apoe 3/4 or 4/4 mutations? I have the former, so maybe just a daily pinch of MCT (and some occasional dips into ketogenesis via general healthy low carb eating/fasting) would be something to add to my regimen. I suppose it’s worth trying out if fasting and intermittent ketosis already have other benefits.

David
David
10 months 6 days ago

For APOE 3/4 or 4/4, 1) eat fish / DHA 2) avoid sugar / refined carbs 3) exercise

Keto and extended fasting have so many preventive and maintenance benefits that it’s worth doing on a regular basis. It’s easy to do once you’re fat adapted. Dom Dagastino at University of South FL is one of the leading researchers in keto. He’s done many podcasts – Google him.

Casey
Casey
10 months 5 days ago

Thanks for posting because I had a similar question. Alzheimer’s runs rampant in my family. Every elderly person has died from it. Not to mention strokes and mental illness… I’ve wondered if I should switch to a ketogenic diet younger in life to stand a chance against it.

Simon
Simon
10 months 5 days ago

You should probably get genetic testing first to see if you are an APOE 4/4. After that assuming you are are a 3/4 or 4/4, you could try a ketogenic diet. However I’m a 4/4 myself and the problem is that we are slow cholesterol recylcers so you have to balance fat intake with brain function. Personally I currently just do a daily cyclical approach and fast in the morning and save carbs for the evening. I get into ketosis before lunch time. This forum is a great resource if you are APOE E4/E4

http://www.apoe4.info/forums/index.php

Diane
Diane
10 months 5 days ago
ALZ runs in my family, too; so I spend a lot of my free time reading the latest research on it. From what I’ve read, I completely believe it is preventable through a low-carb/moderate protein/high fat diet (occasionally going into ketosis!), exercise, quality sleep and other lifestyle choices (get plenty of sunshine, enjoy nature, learn to diffuse stress healthily, limit chemical exposures, etc.). Check out writings by Dr. Perlmutter. Also, Max Lugavere (while not a scientist) reports on the latest research (follow on FB) and does a great job of it – he has a vested interest due to family… Read more »
Tim
Tim
10 months 6 days ago

Intermittent euphoria, eh? Who needs recreational drugs when you have a jar of mayo and a slab of Kerrygold in the house.

barry
barry
10 months 6 days ago

IDK, I sure do enjoy a cup of kava and a bowl of cannabis. I’m not going to justify their usage, but, I like them haha. I do enjoy grassfed butter and primal kitchen mayo though haha.

Paleo Bon Rurgundy
10 months 5 days ago

Maybe not “need”, but why limit ones options.

Tina
Tina
10 months 6 days ago

I’m all about using compressed eating windows as an easy way to dip into ketosis. The best way to do it is to eat dinner early and wait to eat until late morning or lunch time the next day. Sleep is a great buffer between meal times. 😉

Kira
Kira
10 months 5 days ago

Wow, I had to read that about 5 times before I didn’t read “I’m all about eating windows as an easy way to dip into ketosis.”

That is not recommended! Stick to food :).

Susan
Susan
10 months 6 days ago

Ah, mitochondrial biogenesis! I’m all about building new factories for my body to keep humming along. Maybe all those fresh new mitochondria contribute to the extra feelings of energy you get when you’re in ketosis.

barry
barry
10 months 6 days ago

I prefer to stay right outside of the ketosis range. Anywhere from 85-125 carbs a day, depending on my activity level. I enjoy fruit too much to go full blown ketosis.

Jessica
10 months 6 days ago

I’ve been eating a Primal Ketogenic diet for 6 weeks+ and have found I can include berries and/or a serving of seasonal fruit daily with no problems. Granted, I haven’t yet tried adding in tropical fruits. Interestingly, when I started using keto-strips to check my urine for ketones, I was already showing a presence on the first day…evidently all this Primal stuff made me fat adapted well before I went full Ketogenic. I’ve read in Dr. Phinney’s writings, that most people take a full six weeks to become fat burners. Once again, Primal for the win!

Rivah
Rivah
10 months 6 days ago

Awesome that you’re feeling great on a Ketogenic diet, but be aware that urine test strips aren’t a good metric for tracking your level of nutritional ketosis. What you are excreting is not necessarily reflective of what your body is using as fuel. A blood meter (I use the Precision Xtra) is much more informative, with levels exceeding around 0.5 to 0.8 mmol/L (depending on who you ask!) indicating that you are in nutritional ketosis. Only downside is that the test strips are quite a bit pricier.

Enjoy the fat burning!!

rubiyatta
rubiyatta
10 months 6 days ago

Here’s a link to an article in the NY Times reporting on interesting research that may provide a plausible physiological explanation for the oft-reported increase in mental clarity/cognitive benefits derived from nutritional ketosis:

http://well.blogs.nytimes.com/2016/06/15/how-exercise-may-help-the-brain-grow-stronger/?_r=0

Of course, they attribute the presence of ketones in the brain to low blood sugar levels resulting from strenuous exercise; however, we know this is a natural result of LCHF diets and nutritional ketosis. In short, ketones preclude the accumulation of molecules that bind to (and down regulate) the gene responsible for regulating the production of BDNF, thereby resulting in increased production of BDNF.

Terry
Terry
10 months 6 days ago

I did not see mentioned the positive affect on those with migraine headaches. I have significantly reduced my headaches. See: http://www.mymigrainemiracle.com/the-diet/. Looks pretty primal to me.

Lisa in Northern California
Lisa in Northern California
10 months 5 days ago

Terry, I was going to mention the same thing. Ketosis has helped my migraines tremendously. I also discovered this while reading “The Migraine Miracle.” 🙂

Lori
Lori
10 months 6 days ago

I find I can often go quite a while with out eating even if my stomach is growling. I used to be hungry all the time and had to get my next meal in quickly otherwise I’d become seriously cranky. I don’t feel that way since adopting a primal diet. It’s good to know that’s it’s probably due to my body getting other energy sources while it patiently waits on me to eat some food.

Elizabeth
10 months 6 days ago
Very interesting. I have definitely become a fat burner rather than a sugar burner over the past five or six years. And as a result I feel much more stable…clearer thinking and even when I’m hungry I don’t get that shaky miserable feeling. I do like the idea of the shorter eating windows and have done that successfully at times when my schedule allows. The biggest difference I notice since becoming fat adapted is how focused and clear I feel in the morning. Even on very little sleep I don’t feel all groggy. I start every day with coconut oil… Read more »
Becky D
10 months 6 days ago

I feel fantastic in ketosis. For a good while I was in the habit of having a keto shake in the morning then waiting until 6 pm to eat anything else. I worked out 5 days a week at 1 or 2 pm. I was alert without any caffeine, focused, never felt hungry, and put on muscle easily.
I’ve gotten out of the habit unfortunately, we moved and changed jobs which threw me off. I’m getting back into it now though, just working out in the morning 🙂

David
David
10 months 6 days ago
Dr. Dana Leigh Lyons
10 months 5 days ago

Though I don’t recommend it for everyone, my body and mind thrive on a two-meal-a-day, no-snacking, low-carb, high-fat eating plan with an eating window between noon-ish and 7/8pm at night (aside from my bulletproof breakfast around 7am).

Before going paleo-primal, I was totally opposite–needing regular infusions of sugars and carbs to fuel my body and mind. Sure don’t miss the energy highs and lows, fatigue, bloating and brain fog I experience from that way of eating.

Hr
Hr
10 months 5 days ago

What about keto flu? I can barely remember my own name the first 3 weeks, and that’s a major barrier for me. Could it be too much protein?

Ruth
Ruth
10 months 5 days ago
In my experience, it’s all about making sure you have proper levels of electrolytes! The first time I went keto, I also had terrible keto flu for several weeks. Then I received some advice regarding using extra salt for the first few weeks, as well as making sure I’m getting adequate levels of potassium and magnesium. The next time I started keto (because life happens and I fell off the wagon) I made sure to drink some bone broth every day and just eat whenever I was hungry so long as they were keto-appropriate foods, and it made a HUGE… Read more »
LM
LM
10 months 5 days ago

I hope this is not a dumb question, but what is the magical primal figure for remaining in ketosis? Is it under 20 grams of carbohydrates or less per day, like the Atkins approach?

Robert
Robert
10 months 5 days ago
Has anyone any thoughts on protein intake and optimizing ketosis? I’ve personally found that staying low carb but not worrying about ketosis, ie eating plenty of protein, provides the most stable, calm moods and energy throughout the day. I also feel I sleep easier. Although I do wonder if I’m not eating optimally for ketosis by eating ?200g protein per day? I find if I decrease protein and increase fat I’ll sometimes be ravenously hungry after meals as I’m not satisfied, and also find it harder to wake up in the mornings. I also think it’s important to make sure… Read more »
Jacob
Jacob
10 months 5 days ago
I am wondering about two things: first, this magical “under 50 grams of carbs” number. It doesn’t make sense to me as it surely depends on the size of a person and the amount of muscle mass they carry? wouldn’t a perentage of calories coming from carbs be more accurate? It’s a bit like alcohol, a 5 foot woman can’t drink as much as a 6’2 250lbs muscled dude before she collapses? Just curious if the “grams” approach is used because it’s easier than calculating percentage? the other thing I am wondering about is if ketogenic diet and ketones could… Read more »
SpottedChui
SpottedChui
10 months 5 days ago

Hi Mark,

I wish you would talk to the Harvard School of Public Health, who think that breakfast and snacking is all important for weight loss, and are still pimping whole grains. Looks like they could use a challenge to their paradigm: https://www.hsph.harvard.edu/nutritionsource/healthy-eating-plate/

Your (excellent) article makes one wonder why you are not promoting IF more than you are. Surely full daily ketosis is the way to go?

SpottedChui

Nick
Nick
10 months 5 days ago

Unless something goes seriously wrong I start my day with 4 scrambled eggs in coconut oil. Kicks off the ketones and leaves me feeling awesome for the rest of the day.

Kyle
10 months 5 days ago

This is an excellent article! Love all of the references to studies and your acknowledgement that there is still research to be done. I think it is especially interesting to know a diet centered around ketones can improve cognitive function in the Age-related Disease population. Thank you for the great post and I look forward to reading more of your articles!

Senza
10 months 4 days ago

We made an app to help people try the ketogenic diet. Free, available for beta now on iOS: http://www.senza.us

Josh
Josh
10 months 1 day ago
I certainly do not doubt the potential benefits of low carb and ketogenic diets, especially for people with neurodegenerative conditions, however they certainly have their downsides as well. I’m not an anti-keto zealot by any means but after being dogmatic about them for the past couple of years, my experience has definitely reminded me of BIOINDIVIDUALITY. What works for one may not work for another. I’m a healthy 27 year old male RN. I was low-carb (I even ate tons of green veggies but excluded starchier veggies). Long story short, I gained almost 20 pounds, drove my thyroid hormone through… Read more »
Animanarchy
Animanarchy
9 months 28 days ago

This reminded me, I think MSG might actually have the potential to temporarily increase mental performance and maybe happiness. After eating foods laced with it I’ve sometimes felt more excited, happy, and had a bit of a racing, more active mind. Then again, studies show it’s a neurotoxin and makes your synapses fire excessively to the point they burn themselves out, thus literally frying your brain.

Animanarchy
Animanarchy
9 months 28 days ago

When I read “free range” child it reminded me of Mark saying he ate sunflower seeds all day roaming as a kid, and it makes me wonder if he was out running around like Merry and Pippin, executing agricultural raids.
Personally I get satisfaction helping myself to produce from gardens and fields. I hope one day I’ll find out where Farmer Maggot grows his mushrooms…

Kimberly
Kimberly
9 months 24 days ago

This is an excellent article and I have read a lot on the subject; but, I am wondering what Ketone Esters would you suggest for getting started to get into a state of ketosis. I am struggle with getting through the brain fogs and headaches.
I follow Mark’s Daily Apple and listen to the podcasts and have read both Primal Endurance and The Primal Blueprint, cover to cover….Thanks for the inforamtion!

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