paleo / ketosis vs epilepsy in adults reading list?

by 902 · May 24, 2011 at 1:29 PM

My wife and I started Paleo recently (2-3 months ago). In that time, I've spent a lot of time reading and learning about metabolism, hormone pathways, good and bad science, the practicalities of paleo, and all the rest in between. I'm very much on the science and research end of the paleo spectrum, at least as far as intellectual curiosity is concerned, and my most detailed reading so far has concentrated on the specifics of the issue that brought us to paleo: PCOS.

All that changed suddenly this weekend. My wife had 3 full-on grand-mal epileptic seizures in the space of about an hour; one at home, one just before we arrived at hospital, and other in the ED. She'd had a few odd turns previously (over the space of a year, with another recently), enough that we were already scheduled for a neurologist visit as well as taking various other tests to narrow down the possible explanations. Epilepsy was one of those, and it's now clear they were petit-mal absent seizures. The specific causes and details are still to be determined, we are waiting on some test results and there are more tests to be taken.

I've seen and read with interest quite a bit about ketosis, brain function, inflammation, gut-brain-axis, etc - and even about the use of ketogenic diets with epileptic children - but all with a general view.

I'm about to have some in-depth conversations with neurologists, and want to be as prepared as possible. Understandably, I also have my hands fairly full at the moment (looking after an 18-month old is enough by itself). Please help me find the most valuable and direct research and reading that I can in a short amount of time. I need to prioritise. I will get to the rest in due course.

There are some specific questions that I intend to investigate, so papers addressing these topics would be of particular interest

1) Could a recent change to a low-carb, moderately ketogenic diet have aggravated or provoked the condition?

I hope not, and suspect it is unlikely, but will keep the hypothesis open. There are mentions that seizures can be caused by low blood sugar, mitochondrial and metabolic problems in Wikipedia that I need to follow up as possibly relevant. I have no idea what the neurologist's take on paleo and ketosis will be. If they claim it was, I want to be sure they have justification rather than just assumption based on unfamiliarity.

2) What is known about the mechanism by which a ketogenic diet helps epileptics, and is it applicable to adults (or specific to forms that arise in children)?

Once we learn more about what's going on in this specific case, this information will help us understand where to go next, in particular with respect to paleo.

3) What is the single most relevant paper or researh that you would present to a neurologist to convince them of the merits or significance of diet (and paleo / ketosis in particular) in their field.

Perhaps they will already be on board, or perhaps they will simply be unaware and there may be an opportunity to introduce the subject. Of course, it takes more than one paper and result - but I want the shortest and most compelling introduction - the paper that makes them say "oh really? has this been replicated?" and leads to the rest.

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6 Replies

424 · May 22, 2011 at 1:04 PM

Hi, uep. I normally like to research answers before posting but it sounds like this is time-sensitive so I'm going to tell you what I think off the top of my head and then get back to you with more information later.

1) Could a recent change to a low-carb, moderately ketogenic diet have aggravated or provoked the condition?

I doubt it. I don't recall seeing any warnings in the epilepsy literature about a change to ketogenic diet aggravating extant epilepsy. Many epileptics have initiated a ketogenic diet under medical supervision and much has been written about them. What I have read about the ketogenic diet for epilepsy has often had a very conservative/skeptical tone--searching long and hard for signs of harm being caused by the ketogenic diet, which is reputed among epilepsy researchers to be an unnatural, difficult, and potentially dangerous medical therapy. So if there were any evidence of ketogenic diet initiation triggering or exacerbating seizures, I think they would have emphasized it.

Nonetheless since my own bias is quite the opposite (ketosis is natural, easy, safe, and healthy), I might have missed, ignored, or forgotten any such warnings, so I'll try to find some.

2) What is known about the mechanism by which a ketogenic diet helps epileptics, and is it applicable to adults (or specific to forms that arise in children)?

Last I checked, nobody has high confidence in their theories about the mechanism, even though the efficacy of ketogenic diet as a treatment for epilepsy is well established. The theories that I have heard, which people seem to have started writing about only in the last ten years or so, focus on energy production in the mitochondria. I have heard various ideas about it. Mitochondrial energy production on ketones is more efficient than on glucose, produces fewer reactive oxygen species (see Lucas Tafur's blog http://www.ketotic.org/2011/05/bioenergetics.html ), and perhaps it is more robust against some kinds of mitochondrial damage -- if you're running on glucose and your mitochondria suffer certain forms of damage then the flow of energy is disrupted but if you're running on ketones this kind of damage won't interrupt energy production. Dr. Emily Dean's summary -- http://evolutionarypsychiatry.blogspot.com/2010/08/your-brain-on-ketones.html -- emphasizes that ketogenic diet should reduce the ratio of glutamate to GABA, if I understand correctly.

I will come back and give you more references later.

By the way, you mention ketogenic diet for adults vs. for children and this is a good example of how weirdly sophomoric this whole field is. Someone (sorry, I forget exactly who and when -- this whole "posting without researching" thing feels weird) made some observations in the early or mid 20th century which led them to believe that the ketogenic diet as a treatment for epilepsy only worked in children. Then for many decades people didn't try the ketogenic diet in epileptic adults. Then, in approximately the last decade (sorry...) people realized that there wasn't really any strong evidence that it would be ineffective in adults, and started trying it, and what do you know--it is effective in adults.

This whole pattern is really frustrating to me: for about a century the ketogenic diet as a treatment for epilepsy has been regarded as difficult, dangerous, "last resort" sort of option. Even today, after the Charlie Abrahams revival, the standard treatment is to first try two or three anti-seizure drugs and only then try the diet. This seems insane to me! Why would anyone risk taking an unhealthy and dangerous drug like carbamazepine, gabapentin, or any of the others when you could first try a nice healthy zero-carb diet instead? :-)

Anyway, even this may be changing, in large part due to the successful experiments of Dr. Eric Kossoff.

3) What is the single most relevant paper or researh that you would present to a neurologist to convince them of the merits or significance of diet (and paleo / ketosis in particular) in their field.

So it depends on the milieu your neurologist is from. :-)

a. They're from the pre-Charlie-Abrahams-revival. So basically they got their training before 1994 and haven't been keeping up. Honestly, if this happens maybe you should just get a different neurologist? I don't know how common this type is nowadays.

b. They're from the post-revival, pre-Kossoff era. I would assume this is the current standard model of neurologist. They should not require any prompting from you to know about the efficacy of the ketogenic diet. (If they do, then maybe you should get a different neurologist.) They might think of the ketogenic diet as a difficult and dangerous last-ditch option to try after drugs have failed. They might think that a ketogenic diet requires calorie-restriction, protein-restriction, drinking cups full of medium chain triglycerides, or water restriction. They might be worried about side-effects of eating a high fat diet such as heart disease or osteoporosis (haha). They might think that a "ketogenic diet" means living on a medicalized "nutritional product" such as KetoCal™ (made from corn or soy, of course) instead of eating real food.

c. They're on the cutting edge of the modern (Kossoff) era. They're well aware of the therapeutic potential of ketogenic diet, and they might think that basically just going into "Atkins induction mode" and staying there is more or less as good as the traditional, medicalized "ketogenic diet".

So your task is probably not to educate your neurologist on the efficacy of the ketogenic diet, but to navigate the subtleties of your wife's case in particular and the various options of drugs and diet that are now available.

Hope this helps!

I'll come back with more references later. Feel free, everyone, to request clarification from me or challenge what I've said. I'm no expert on these matters and I might have made mistakes above, and I would hate for my mistakes to go unchallenged and contribute to harm to uep's wife. I'll probably find it easier to come up with specific references to research papers (which is what uep asked for) if asked more specific questions.

By the way, you didn't ask for general advice (you asked only those three questions above) but there could be a world of difference between your wife's "paleo" diet of the last 2-3 months, of which you didn't give any details above, and a very strict ketogenic diet which carefully eliminates everything which isn't necessary and which might be contributing to the epilepsy. If it happened to me, I would go on a strict all-meat diet as practiced by the folks on the Dirty Carnivore forum. Well, actually, I already am on such a diet, more or less, so if it happened to me I would start by eliminating the exceptions that I occasionally indulge in. I would also take up intermittent fasting.

There are plenty of people who suffer from epilepsy and a ketogenic diet doesn't help them, or doesn't help them enough (around 50% of patients), so I'm not saying it is a cure-all. I am saying that it is the best first-line option, and that what your wife has been doing for the last 2-3 months may or may not have the same effect as a strict ketogenic diet. Note that those people who suffer from epilepsy and a ketogenic diet doesn't help them may be suffering from different types of epilepsy than your wife is, often have very bad additional complications, and are in most cases taking in the medicalized, calorie-limited version of the diet. So your wife may have a better chance than they do.

Good luck! I hope your wife heals quickly and doesn't have any more seizures.

Oh, and one more bit of advice: if my brilliant wife, Ambimorph, has anything to contribute then listen to her. :-)


uep: I just found this review article by Dr. Kossoff (whom I earlier mentioned):

  1. “SpringerLink - Neurotherapeutics, Volume 6, Number 2,” http://0-www.springerlink.com.skyline.ucdenver.edu/content/k168n1262138823w/.


This is the best thing I've seen yet as an introductory point for a neurologist. It summarizes a lot of experiments in animals, clinical reports in humans, a couple of experiments in humans, some possible mechanistic explanation (which seems to mostly emphasize the efficient energy production in mitochondria when on the ketogenic diet). It also briefly describes alternatives to the traditional (medicalized) ketogenic diet, namely "Modified Atkins" (which I think is basically just: stay in Atkins Induction Phase and try to get plenty of fat), and low-GI (about which I am modestly surprised that it is ANY USE AT ALL). It also mentions that the former beliefs that the diet is unsustainable, loses efficacy over time, and doesn't work in adults is unjustified.

Now here is "the ketogenic diet HOWTO for neurologists", also by Kossoff:

  1. “Optimal clinical management of children receiving ... [Epilepsia. 2009] - PubMed result,” http://www.ncbi.nlm.nih.gov/pubmed/18823325.


Of course, the best situation would be if your neurologist is already intimately familiar with both of these documents. :-)

Hope this helps! Please do keep us informed of how things go.



1136 · May 22, 2011 at 3:03 PM

Hi uep. I actually have a research alert for pubmed for ketogenic diets, and much of the recent studies that have been in adults are with a modified Atkins protocol (atkins induction, basically, usually with less than <10g carb per day) - they seem to be just as effective as the more restrictive, rather horrible research diets used in children previously. For epilepsy you do have to maintain strict ketosis, however. Two mechanisms are thought to be most likely - a decrease of sodium gradient (though this one is a little poo-poohed) which would theoretically make it more difficult to depolarize the membranes and trigger a seizure.

The other (more accepted) mechanism is this one (a paragraph from a study on ketogenic diets in autism- http://jcn.sagepub.com/content/18/2/113.abstract):

"The increase of ketone bodies maintains the synaptosomal content of γ-aminobutyric acid (GABA) at a higher level, a phenomenon that may contribute to the beneficial effect of a ketogenic diet in children with epilepsy and perhaps children with autistic behavior. Other researchers, in an attempt to clarify the manner in which ketone bodies increase the synaptosomal content of GABA, showed that the metabolism of ketone bodies to acetyl coenyzme A results in a decrease of the pool of brain oxaloacetate, which is consumed in the citrate synthetase reaction. As less oxaloacetate is available for the aspartate aminotransferase reaction, thereby lowering the rate of glutamate transamination, more glutamate becomes accessible to the glutamate decarboxylase pathway, thus favoring the synthesis of GABA."

In order to change the oxaloacetate levels in the brain, you really have to be pretty strict with ketosis - no cheating, high fat, low/mod protein, low carb (though you can play around with the carbs and protein a bit if you add MCT oil or coconut oil).

There are a variety of complications - for example, I have read there is some worry about combining a strict ketogenic diet with medications for epilepsy, particularly depakote (a recent paper addressed this but I didn't look at it and now I can't find it). I believe more often now keppra is used most often, but it really depends upon the type of seizure. I doubt the combination has been studied, and it is something to keep in mind. Ketogenic diets in children in the literature are generally 50% effective - however, one must realize that these studies were typically done on children who had failed medication therapy so would have more resistant disease.

Given all that it would be vital to have a neurologist who is knowledgable about these sorts of things, or one who is willing to consult with someone who is. Looks like the folks above listed the hotspots in the US. Also, looks like some good papers have been listed, so I will list some sites for your own edification:

Paul Jaminet has a good series on ketogenic diets - one of the posts is here:


Lucus Tafur has a whole blog devoted to the subject: http://www.ketotic.org/

While theoretically a low carb paleo diet should lower risk of seizures, sometimes there can be major derangements of potassium or magnesium which might affect someone who is vulnerable to seizures (but to be honest, leg cramps and heart arrhythmias ought to happen first) That's the only thing I can think of that might increase risk… there are plenty of smart people here who might be able to think of something else.

172 · May 22, 2011 at 12:42 PM

UEP - I'm so sorry that you are going through this. A seizure is very scary to witness when it is unexpected. You are an awesome dad if you are freaking out about taking care of your child. At least you are mindful that care of a child is a big deal, you will do great even if you feel overwhelmed. Just breathe and let me see what I can add/help you with.

What was going on before the seizure, was she sick, did you eat out/somewhere unusual, could she have been dehydrated, is she taking any medications/herbs, has she ever had any heart problems, any recent stress? These are things I'm sure everyone at the hospital has asked you these questions, it definitely could be a seizure, or something else. Tell me more about your wife's PCOS.

Johns Hopkins is THE place for treating children/young adults with the Ketosis Diet for seizures. They pioneered the research. Here is the link for the general info sheet on treating children with the ketosis diet, this might not help, but it will give some general information on how ketosis used.

Here is the Hopkins research article from 5 years ago where is starts it all. http://www.matthewsfriends.org/jh/KDPaviaEpilepsyResearch.pdf

And a follow up: http://www.springerlink.com/content/m7q56775745143w7/ (The PDF is on the page)

And here is one of the research articles, cut and paste this into your browser: http://site.matthewsfriends.org/uploads/images/LongTermKDGroesbeck1.pdf

Here is an article about the neuro-protective effect of the keotgenic diet: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2367001/?tool=pubmed

Here is an article about the neuroprotective properties of calorie restriction, the ketogenic diet and ketone bodies. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2649682/?tool=pubmed

These last 2 articles explain why ketones/paleo/low-carb is so much better for us. Everyone should read them.

I'll keep researching today, and see what I can come up with. But preliminarily, I don't see anything that ties ketones/low carb/paleo to causing seizures, if anything its protective. If you are willing to post more information and I will do searches with that too. Just breathe. She is under medical supervision and they will figure this out. Take care of that baby and take care of you. Let me know what else I can do to help you.

The Quilt, where are you, jump in here!

  • Wendy :)

2369 · May 22, 2011 at 12:33 PM

Dr. Seyfried is doing major research in Boston with ketogenic diets and epilepsy as well as brain cancers. Here's a link to his lab's website and I think you can find more info there. He is definitely a proponent of ketogenic diets. https://www2.bc.edu/~seyfridt/epilepsy.html

There is a paper referenced at the bottom of that page.

You might also check out this site at Johns Hopkins. They are also on the forefront of treating epilepsy with ketogenic diets: http://www.hopkinsmedicine.org/neurology_neurosurgery/specialty_areas/epilepsy/about_us/ketogenic_diet.html

40 · May 22, 2011 at 1:43 PM

Some "paleo" diets even those that are low carb, are NOT ketogenic and that may be important. Protein also short-circuits ketosis so for some people a high protein, predominantly meat diet will not induce ketosis. Ketogenic diets are high fat, moderate to low protein, zero carb. Using the strips can help determine exactly how much protein can be tolerated before knocking someone out of ketosis. Hopefully the high fat comes from good fats instead of vegetable oils.

Best wishes for your family.

9983 · May 22, 2011 at 12:42 PM

http://www.marksdailyapple.com/low-carb-epilepsy/ reviews the info and this is the reporting of the study.


My wife had petite grand mal and the treatment back 25 years ago was dilantin...which made her spacey and not in present time. She hated the feeling. Back then we had no idea about ketogenic therapy...and of course there was no internet.

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