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Ketosis makes your brain work better

Butter_melted

Every morning for the last four and a half months, I’ve broken off a large chunk of grass fed butter (usually around 50 grams or just over three tablespoons) and a couple tablespoons of coconut oil and thrown them in a blender with my morning coffee. You might have heard of this idea, dubbed ‘bulletproof coffee’ and created by a guy called Dave Asprey.1 You might ask why the hell somebody might want to put butter in their coffee, but all you’d be proving is that you haven’t tried it (because it tastes amazing) and according to Dave Asprey, apparently will help make you healthier, feel better, perform better, think better – everything short of give you superpowers.

Now, I didn’t want to like Dave Asprey… he’s just a little bit too charming – especially once you realize he’s created a whole line of supplements and other consumables that meet his extra-special toxin-free super-executive standards. I tried his upgraded mycotoxin free coffee beans and didn’t notice any difference between them and any other local fancy-shmancy coffee I’ve purchased since – not that I doubt that some people are more sensitive to these toxins, I just didn’t notice a difference. Nevertheless, I do like him. He does a good podcast and he clued me into something that I previously would have thought was completely insane, but now am starting to think is key to keep my brain working optimally – eating a high fat diet.

A diet that is high in fat (60-70% of calories), is almost by definition low in carbs, and this means that when eating a high fat diet, it is likely that one is at least partially and some of the time in a state of ketosis. For those of you who don’t know, ketosis is what it is called when the body switches over from burning glucose (the kind of sugar our body uses as fuel) to burning an alternate fuel called ketones, which are made from the breakdown of fatty acids in the liver when glycogen (how the body stores glucose) levels are depleted.2 Basically, the body starts burning fat for energy when we don’t consume very much sugar or foods that readily break down into sugar — carbohydrates. While glucose is metabolically preferred by the body (meaning that if glucose is present, the liver produces only small, baseline amounts of ketones),3 it is interesting to note that ketones are a principal source of energy during early postnatal development,4 5 when our brains are growing and developing at the most rapid pace of our lives.

Ketosis, not to be confused with ketoacidosis (a harmful out-of-control state of extreme ketosis associated with type-1 diabetes in which the pH balance of the blood becomes upset),6 is an entirely normal and healthy state for the body to be in – in fact, most people will be in some amount of ketosis every single morning after ‘fasting’ while they sleep (you can often smell the acetone – a ketone – in your pee when you wake up), which is a sign of metabolic health.7 There is quite a lot of debate, however, about whether or not prolonged ketosis is in some way damaging to the body. While some studies suggest that there may be long term problems with low carb diets,8 9 other studies suggest contradictory results.10 11 Given that most long term diet research is done with what are called observational studies these contradictory results are not surprising. Observational (or epidemiological) studies are inherently problematic because they are unable to isolate experimental variables or determine causation – they can only report correlations.12  Nevertheless, as the jury is still out, it is possible that long term states of deep ketosis may have the potential to cause some harm. Luckily, one need not be continually in deep ketosis to enjoy some benefits from this metabolic state.

One area in which the ketogenic diet is completely uncontroversial is as a relatively effective non-pharmaceutical treatment for a set of common neurological disorders called ‘epilepsy’.13 14 15 It is often effective in cases in which epilepsy drugs are not, as well as in severe infant and childhood epilepsy syndromes like ‘West Syndrome’, ‘Lennox–Gastaut Syndrome,’ and ‘Dravet Syndrome’.16 17 18  A systematic review found that “all studies showed 30‐40% reduction in seizures compared to comparative controls”19 and other studies have found that a single high carb meal can rapidly reverse the antiseizure effect of the diet.20

You may have heard about Mary Newport. She is a medical doctor who makes the controversial claim that she actually reversed her husbands Alzheimer’s disease using coconut oil.21 Coconut oil is a uniquely ketogenic food in that it contains a high percentage of Medium Chain Triglycerides (MCT’s), which are metabolized directly by the liver into ketones22 (hence the inclusion of MCT’s in the bulletproof coffee recipe). Claims of a cure notwithstanding, there is some evidence in the medical literature to back up what Newport is saying about ketogenic diets as a treatment for Alzheimer’s. Single doses of MCT heavy meals have been shown to improve memory performance in Alzheimer’s patients.23 Preliminary work with patients at-risk for Alzheimer’s has also shown potential cognitive benefit24 and another pilot study has shown promising, yet ultimately inconclusive results. 25 Also, similar to what was found with epilepsy patients, a single high carbohydrate meal has been shown to worsen cognitive performance and behavior in Alzheimer’s patients 26 27. When somebody gets Alzheimer’s, their brain has trouble metabolizing glucose, and while it is sometimes claimed that the brain can only run on glucose, this isn’t true. Research shows that ketones cross the blood-brain barrier28 29 30 and are actually a more efficient fuel than glucose31 32 33 which might help explain the cognitive benefits some Alzheimer’s patients report (since their brains no longer have to rely on a damaged glucose mechanism for fuel).

In addition, preliminary data has also shown potential benefits for other well known neurological disorders such as Parkinson’s disease34 35 and Autism.36

But what about for people who aren’t sick? Well, epilepsy researchers noticed that the anti-seizure effects are not the only benefits shown in children who follow the diet – they also seem to have improved attention, alertness, and social functioning37 38. Obviously, these are improvements that anybody could benefit from, and they match the anecdotal experience of large numbers of people who try ketogenic diets (often for weight loss) and report feeling clearer, sharper, generally cognitively faster, and even euphoric!39 40 Unfortunately, there isn’t really any direct research into the cognitive effects of ketosis in healthy people, but there are quite a few biochemical reasons to believe that it could positively impact brain function.

Things are about to get even more technical, so hold on to your hats (I assume you are wearing more than one).

When the liver breaks down fatty acids there are three principal ketones produced: β-hydroxybutyrate, acetoacetate, and acetone. When cells burn fuel (either glucose or ketones), it does so in the mitochondria, which convert the fuel to ATP (adenosine triphosphate), the substance that our cells use for fuel. β-hydroxybutyrate has been shown to improve cellular respiration (the process in which the mitochondria produce ATP) in the brain,41 which is consistent with studies with demonstrated that β-hydroxybutyrate increases ATP production42 43 and that ketogenic diets increase ATP levels in the brain.44 Ketogenic diets also upregulate mitochondrial biogenesis – the process by which new mitochondria are formed inside of cells.45 46 So we have a more efficient fuel producing more energy and stimulating the growth of even more fuel engines (the mitochondria) – no wonder people report the effect of a high fat diet being like ‘the lights were turned on’. The increase in the formation of mitochondria is especially beneficial when we take into account that mitochondrial damage and energy production failure are central components of many neurological disorders.47 48 49

Another way the ketogenic diet improves brain function is through several kinds of antioxidant effects. Oxidative stress can cause harm all throughout the body, and the brain is no different – oxidative damage has been implicated in a wide range of neurodegenerative diseases as well as simple brain aging50 51 52 Glutathione is our body’s master antioxidant substance, and ketogenic diets have been associated with increased mitochondrial glutathione levels53 and glutathione peroxidase activity in the hippocampus.54 In animals eating a ketogenic diet, mitochondria have been shown to produce fewer free radicals,55 which are chemically reactive molecules that can cause oxidative stress.56 Ketones have also been shown to reduce the amount of coenzyme Q semiquinone, which also decreases free radical production.57 The combination of upregulating our bodies natural antioxidants as well as downregulating our bodies production of free radicals is quite spectacular. As we might expect from all this, studies show ketosis reducing oxidative damage within the body58 and having a potential benefit from in multiple neurological disorders that are directly related to free radical damage.59 60

Some of the neuroprotective effects from ketosis could be related to polyunsaturated fatty acids (PUFA’s). In people following a ketogenic diet, blood and brain levels of PUFA’s, such as docosahexaenoic acid, which have anticonvulsant and neuroprotective properties61 62 63 are increased.64 65 66 PUFA’s have also been shown to increase the survival of neurons in the aftermath of traumatic and toxic brain injuries.67 68 69

The last mechanism through which a ketogenic diet may confer cognitive benefit is through the increase of γ-aminobutyric acid (GABA) levels in the brain. GABA is the brain’s major inhibitory neurotransmitter70 while glutamate is the most abundant excitatory neurotransmitter.71 Too much glutamate in the brain can be neurotoxic.72 73 Glutamate toxicity can lead to neuronal injury and even death by creating free radicals and inhibiting mitochondrial function.74 75 Ketogenic diets may protect against this damage by increasing the levels GABA in the brain – though the studies at this point are unclear, showing an increase in GABA in some, but not all, patients.76 Studies in rats have likewise been mixed.77 78 There is, however, a plausible mechanism through which ketogenic diets might increase GABA levels, and this is through the increase of glutamic acid decarboxylase (GAD),79 80 81 which is a substance that facilitates the conversion of glutamate into GABA.82

So don’t feel too ashamed next time you reach for that stick of butter – think of it as a brain vitamin. Personally, I can’t maintain ketosis too often because I am absolutely in love with carbohydrates, but I do try to often limit my consumption of carbs until later in the evening. First, I’ve found that eating them at night gives carbs an almost sedative-like effect which puts me to sleep nicely, and second, it allows me to spend most of the day in some amount of ketosis. My energy levels and brain function thank me.

And I thank you for reading, if you got this far.

If you just scrolled to the bottom it doesn’t count.

Additional sources:
- The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies
- Neuroprotective and disease-modifying effects of the ketogenic diet
- The Neuropharmacology of the Ketogenic Diet
- Your brain on ketones – Psychology Today

Author’s note: I am not a doctor, and have no credentials in any relevant field discussed in the article. The entire post is my interpretation and synthesis of the information I’ve found on the topic. It’s quite possible I’ve made a mistake, small or large, somewhere in the post. If you find one, feel free to point it out to me, either in the comments or through an e-mail via the contact page.

  1. How to make Bulletproof Coffee  (back)
  2. Wikipedia – Ketosis  (back)
  3. The synthesis and utilization of Ketone Bodies  (back)
  4. Ketone Body Transport in the Human Neonate and Infant  (back)
  5. Brain uptake and metabolism of ketone bodies in animal models  (back)
  6. Wikipedia – Ketoacidosis  (back)
  7. Ketonuria after Fasting may be Related to the Metabolic Superiority  (back)
  8. Low-carbohydrate-high-protein diet and long-term survival in a general population cohort.  (back)
  9. Low carbohydrate-high protein diet and incidence of cardiovascular diseases in Swedish women: prospective cohort study.  (back)
  10. Four-Year Follow-up after Two-Year Dietary Interventions  (back)
  11. Low-Carbohydrate-Diet Score and the Risk of Coronary Heart Disease in Women  (back)
  12. The problems with Observational Studies  (back)
  13. A multicenter study of the efficacy of the ketogenic diet.  (back)
  14. Dietary approaches to epilepsy treatment: old and new options on the menu  (back)
  15. The ketogenic diet. Neurologist  (back)
  16. Lennox-Gastaut syndrome.  (back)
  17. Infantile spasms and Lennox-Gastaut syndrome.  (back)
  18. Ketogenic diet in patients with Dravet syndrome.  (back)
  19. Ketogenic and other dietary treatments for epilepsy  (back)
  20. Ketonemia and seizures: metabolic and anticonvulsant effects of two ketogenic diets in childhood epilepsy  (back)
  21. Alzheimer’s Disease: What If There Was A Cure?  (back)
  22. Absorption and distribution of dietary fatty acids from different sources  (back)
  23. Effects of beta-hydroxybutyrate on cognition in memory-impaired adults  (back)
  24. Dietary ketosis enhances memory in mild cognitive impairment.  (back)
  25. Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial  (back)
  26. High carbohydrate diets and Alzheimer’s disease.  (back)
  27. A randomized, crossover trial of high-carbohydrate foods in nursing home residents with Alzheimer’s disease: associations among intervention response, body mass index, and behavioral and cognitive function.   (back)
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  30. Monocarboxylate transporters in the central nervous system: distribution, regulation and function.  (back)
  31. Ketoacids? Good medicine?  (back)
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  35. D-beta-hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease.  (back)
  36. Application of a ketogenic diet in children with autistic behavior: pilot study  (back)
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  39. Euphoria on the Ketogenic Diet  (back)
  40. Forum Post – Ketosis, mental energy, and euphoria  (back)
  41. D-beta-hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease.  (back)
  42. Effect of beta-hydroxybutyrate, a cerebral function improving agent, on cerebral hypoxia, anoxia and ischemia in mice and rats.  (back)
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  44. Effects of ketogenic diet on electroconvulsive threshold and brain contents of adenosine nucleotides.  (back)
  45. Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet.  (back)
  46. Chronic ketosis and cerebral metabolism  (back)
  47. Oxidative stress, mitochondrial dysfunction, and stress signaling in Alzheimer’s disease.  (back)
  48. Mitochondriopathy in Parkinson disease and amyotrophic lateral sclerosis.  (back)
  49. Mitochondrial respiratory chain and free radical generation in stroke.  (back)
  50. Mitochondrial oxidative damage in aging and Alzheimer’s disease: implications for mitochondrially targeted antioxidant therapeutics.  (back)
  51. Evidence of increased oxidative damage in subjects with mild cognitive impairment.  (back)
  52. Oxidative stress in brain aging, neurodegenerative and vascular diseases: an overview.  (back)
  53. The ketogenic diet increases mitochondrial glutothione levels  (back)
  54. Ketogenic diet increases glutathione peroxidase activity in rat hippocampus.  (back)
  55. The ketogenic diet increases mitochondrial uncoupling protein levels and activity.  (back)
  56. Wikipedia – Reactive Oxygen Species  (back)
  57. The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism.  (back)
  58. Effect of Short-Term Ketogenic Diet on Redox Status of Human Blood  (back)
  59. A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis.  (back)
  60. The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism.  (back)
  61. Anticonvulsant effect of polyunsaturated fatty acids in rats, using the cortical stimulation model  (back)
  62. Neuroprotective effect of docosahexaenoic acid on glutamate-induced cytotoxicity in rat hippocampal cultures.  (back)
  63. Docosahexaenoic acid: brain accretion and roles in neuroprotection after brain hypoxia and ischemia.  (back)
  64. Elevated polyunsaturated fatty acids in blood serum obtained from children on the ketogenic diet.  (back)
  65. Despite transient ketosis, the classic high-fat ketogenic diet induces marked changes in fatty acid metabolism in rats.  (back)
  66. Omega-3 fatty acids, pro-inflammatory signaling and neuroprotection.  (back)
  67. Polyunsaturated fatty acids modify mouse hippocampal neuronal excitability during excitotoxic or convulsant stimulation.  (back)
  68. Docosahexaenoic acid inhibits synaptic transmission and epileptiform activity in the rat hippocampus.  (back)
  69. Omega-3 fatty acids improve recovery, whereas omega-6 fatty acids worsen outcome, after spinal cord injury in the adult rat.  (back)
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  71. Wikipedia – Glutamic Acid #Neurotransmitter  (back)
  72. Glutamate neurotoxicity and diseases of the nervous system.  (back)
  73. Glutamate Neurotoxicity in Cortical Cell Culture  (back)
  74. Neurodegenerative diseases and oxidative stress.  (back)
  75. Ageing and neuronal vulnerability.  (back)
  76. In vivo measurement of brain metabolites using two-dimensional double-quantum MR spectroscopy–exploration of GABA levels in a ketogenic diet.  (back)
  77. Diet-induced ketosis does not cause cerebral acidosis.  (back)
  78. Regulation of GABA level in rat brain synaptosomes: fluxes through enzymes of the GABA shunt and effects of glutamate, calcium, and ketone bodies.  (back)
  79. Caloric restriction augments brain glutamic acid decarboxylase-65 and -67 expression.  (back)
  80. The ketogenic diet influences the levels of excitatory and inhibitory amino acids in the CSF in children with refractory epilepsy.  (back)
  81. Ketogenic diet, amino acid metabolism, and seizure control  (back)
  82. Wikipedia – Glutamic acid decarboxylase  (back)
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