Monday, October 8, 2012

Ketogenic Diets and Bipolar Disorder: New Case Studies

Researching the viability of ketogenic diets for therapeutic usage was one of the original interests that launched this blog. And while there is growing data for brain cancers and even a Cochran review for the use of ketogenic diets in epilepsy, the bipolar story has always been theoretical.

Churchill: Change (song starts at about 30 secs)

Ketogenic (very low carbohydrate and low protein) diets should work a bit like the mood stabilizer depakote in regulating unstable moods in bipolar disorder, making them an interesting option, should the research pan out. I explore the research and details in this post:

A Dietary Treatment for Bipolar Disorder?

But, as I stated in that article, there were no randomized controlled trials, not even a pilot trial, and the only two case studies I had unearthed had one guy getting psychotic on Atkins induction and another one where a hospitalized bipolar woman showed no benefit (but despite reported enthusiasm and being in an inpatient unit where her food was supposedly entirely controlled, she never acheived ketosis).

But the other day PubMed emailed me a new paper with links to the following article: The ketogenic diet for type II bipolar disorder.  Thanks to the good Dr. Eades I was able to see the full text without getting a librarian to request it for me.

And here we have not one, but two rather well documented cases of bipolar II disorder in women, beginning in youth with some hypomania, in one person predictable seasonal depressions in the summer and a bit of mania in the spring. Both women had bad responses (such as suicide attempts and suicidal thoughts) to antidepressant trials and one gained weight on quetiapine.  They were tried on lamotrigine, an anticonvulsant and mood stablizer, with okay results (one woman was finally able to maintain a job and be functional).  One tried a ketogenic diet to help with some irritable bowel symptoms, the other just wanted to try the diet. One woman ate raw cream, grassfed beef, organic pork, free range chicken, and seafood. The other ate mostly chicken, fish, and coconut oil with 2-3 cups of vegetables a day.  Both monitored their urine with ketostix or Ketone Care Test Strips most days for several months, achieving mild to moderate ketosis on most days. Both women eventually discontinued the lamotrigine and reported better symptom control with the diet than with medication.

One woman described her irritability going away and a sense of calm.  Also "having my head screwed on straight--well, it's definitely worth giving up pie." She said her symptoms seemed better with a ketone level of 15mg/dl vs 5 mg/dl in the urine. The other woman noted that if she remained gluten-free, she felt much better, even though she had never been diagnosed with celiac disease.

Neither woman had any adverse consequences and they remained stable on the diet for 2-3 years at the time the paper was published.

The paper details how a slight acidosis achieved with a ketogenic diet results in decreased intracellular sodium accumulation, which is the mechanism by which all anticonvulsants which are also mood stabilizers appear to work. In addition, the paper details some possible pitfalls of a ketogenic diet, such as difficulty maintaining it in a world of twinkies and coca-cola, and the risk of kidney stones. The author recommends >2.5 liters a day of fluids and a potassium citrate supplement to alkinilize the urine, which is done routinely in pediatric clinics where ketogenic diets are used for seizures, but may not be be necessary in adults. There is a long-term review of the ketogenic diets in kids (though I'm not a fan of the ingredients in some of the formulas used for tube-feeding some of these kids - soybean oil, soybean oil and more soybean oil) talking about complications over 6 years. Since these kids were often very ill with many other debilitating conditions, it is hard to attribute the complications (sepsis, cardiomyopathy, lipid pneumonia) to the diet itself.

Lipids were measured in one woman from a vegetarian to an omnivorous to a ketogenic diet.  As is expected her trigs dropped and her LDL and HDL went up on the ketogenic diet. Total cholesterol to HDL ratio (the best cheap test I know of relating to total LDL particle number, with a lower ratio being better) on the vegetarian diet was 4.47, 3.78 on the omnivorous diet, and 3.74 on the ketogenic diet.

All in all, the paper is a nice illustration of two motivated patients acheiving remission of their bipolar symptoms (which they had dealt with for decades) with a free-living ketogenic diet (and some other supplements, though each woman took different ones, for example, probiotics and omega 3).  Two anecdotes isn't a huge amount of data, but it is intriguing, and I would say the time for a randomized controlled trial of ketogenic diets in bipolar disorder is way overdue.

(Final note as I was in a bit of a hurry when I wrote the post at first… I did want to say there is a *lot* about these case study diets that could be therapeutic. No processed food, no sugar, lots of nutrients, lots of omega 3, low in gluten or gluten-free, likely low in histamine. The tracking of the ketones and one women's experience that the 15mg/dl ketone level felt more calming to her along with the sensible biologic mechanism makes the ketosis part plausible, but it is important to note these other possible factors).


  1. Hi.

    I have commented on an old post of yours. Could you look at the question please? Sorry for this irrelevant post.

    Many thanks

  2. Thanks for reviewing this paper. A few months after I started Protein Power in 2007, I knew my state of mind was somehow much different than it had been. I was on both Celexa and Depakote, having been diagnosed first with clinical depression, and then with Bipolar II disorder. I had been taking that cocktail for a few years by the time I started low-carbing. Over a period of eight weeks, I was able to wean myself off the meds, and I've never taken them again.

    And like the woman in the study (I'm going by what you said, above; I haven't had access to the paper), gluten seems to make a big difference. When I added some rye bread back into my diet (during an experiment with Kwasniewski's Optimal Diet), the depressive symptoms returned, only to disappear when I got rid of the bread.

    I didn't start eating this way to improve my depression; I had no idea this was even possible. Like most people, I started low-carbing to lose weight. This was just one of several non-scale improvements in my health that happened after changing my way of eating.

  3. This comment has been removed by the author.

  4. Another mechanism by which ketogenic diets might produce effects is by reducing the abundance of a dysfunctional microbiotia, resulting in less pro-inflammatory signalling and more immune tolerance. After a suitable (fairly long) period, the re-introduction of resistant fibre from "safe starches" (but not grains or sugars) might actually create further improvement along these lines, in such cases.
    Looking at the microbiotal response might offer a way to resolve this particular paleo schism...

  5. Sorry ItsTheWooo I deleted your comment when I tried to approve it on the tiny phone screen--here is the text imported from my email:

    ItsTheWooo has left a new comment on your post "Ketogenic Diets and Bipolar Disorder: New Case Stu...":

    People at work ask my why I take the bun off my hamburger. LOL WHO EATS HAMBURGERS LIKE THAT.

    I need to think of a more socially acceptable answer other than "so I can feel normal, wake up on time for work, and my body doesn't feel like lead and I don't think about jumping off a bridge".
    Weight control excuses are usually met with an assumption I am vain/neurotic. ANY IDEAS???

    1. I was in class yesterday and the psych department supplies soda, juice, water, and cookies for the students for our three hour class. Everyone was eyeing the leftover cookies and I mentioned I don't do gluten. Student asked me if I had celiac. I said no, gluten affects my skin and I'm vain. Fortunately psychiatrists are presumed to be neurotic.

    2. I use the skin excuse too. I say that dairy gives me acne and grains give me reflux, which is true but I want to be shouting a million other reasons at them too.

  6. What I find so amusing in these reports is the idea that food does so much more than just supply "calories," as if in the normal paradigm the human (or often, in experiments, mouse) body is using food as a "fuel" like a car uses gas, or as if the human body just needs "energy" as a fire needs fuel. Instead, obviously, on some reflection, there is clearly no fire inside people, and combustion inside a person would be a bad thing. Calories in v. calories used is overly simple and only part of the analysis.
    Instead what is taking place inside people in terms of food is not combustion but at least two layers of extremely complex "chemical" reactions, one layer being the obvious "digestion" that an organism is capable of, sort of by itself, and the other layer being the results of the interaction with the various small creatures that are also exposed to the food passing through us. It is complex chemical interaction, not really a "burning" of calories. Clearly there is more to obesity and depression than simple consumption of excessive calories.

    What if more than a few of the drugs used to make lives better for those with "diseases" were simply unnecessary if proper nutrition was the rule, rather than the exception, and known triggers for some of the bad results were avoided with proper nutrition? I know that not all bad results could be avoided, but maybe a lot of marginal cases would be a lot better off.

  7. That's really great to hear that ketogenic diets might work for bipolar. My boyfriend has just been diagnosed with bipolar ll and is being trialled (starting tonight) on Epilim 200mg, working up to 800mg. He told the doctor that he didn't want anything strong and that he wanted to be able to go off it at any time. I started searching for bipolar in conjunction with ketogenic diets because I knew epilepsy could be treated that way and since Epilim is for epilepsy.... well yeh, that's how I found your article. I wish there were evolutionary psychiatrists like you here in Australia!!

    He and I are almost 100% paleo and low-ish carb (between 50-150g/day). We eat pastured butter, sometimes tamari soy sauce, some 85% (dairy free) chocolate and he drinks coke zero 5 times a week- ew, but otherwise we're strict. He has been told that Epilim is pretty safe and from what I've found on the internet, it seems to be, especially at such a low dose. Would you agree with that? One of the side effects seems to be increased appetite and weight gain- any idea what the mechanism for that would be and if anything could specifically be done to combat that? He's planning to take MCT oil on an empty stomach between meals and decrease any aerobic activities in favor of more weight training. He's not overweight at the moment but he still wasn't at his absolute ideal weight and he CERTAINLY doesn't want to gain >4kg which seems to be very common in the research.

    1. The day after taking only 200mg, he's so nausea he can barely stand or move. This sucks. I hope it'll subside.

    2. Your boyfriends condition may well improve if he were to give up the Coke Zero. That stuff is bad news - specifically the sweetening they add

  8. Great post! Nice to see an MD that understands gluten sensitivity beyond the intestinal tract and Celiac Disease. I'll have to find the papers that correlate gluten-free diets and remission of Bipolar.

    1. Would love to see the papers that correlate gluten-free diets and the remission of bipolar disorder....I am soooo tired of the switching meds every month route.

  9. (Final note as I was in a bit of a hurry when I wrote the post at first… I did want to say there is a *lot* about these case study diets that could be therapeutic. No processed food, no sugar, lots of nutrients, lots of omega 3, low in gluten or gluten-free, likely low in histamine. The tracking of the ketones and one women's experience that the 15mg/dl ketone level felt more calming to her along with the sensible biologic mechanism makes the ketosis part plausible, but it is important to note these other possible factors)

    YES... I would probably be categorized as experiencing cyclothymic bipolar disorder and I have noticed the same sense of calm, and less irritability being completely off of sugar ( even ketchup, honey, etc)alcohol,caffeine, gluten and dairy ( which I don't tolerate). I also try to exercise when I get the chance(mother of two young ones) and get some sunlight in. I eat a ton of fat. Feel good when my meal is meat/whole grains and vegetables with plenty of oils,butter,avocado,etc. Feel not so great with any kind of flour (even gluten free) Do it anyway for convenience. Take a multi, fish oil, and experiment with amino acids. I did all of this before and noticed minimal difference until I WENT 100% SUGAR FREE AND THAT IS WHEN I STARTED FEELING IN MY BODY AND HUMAN AND CALM AND LESS IRRITABLE. Not that I don't have times that I get snappy ( lack of sleep,etc) and not that I don't need to change habits of getting angry quickly but it is more the habit now than my body! amazing! No stimulants for me. The only thing is I am feeling more of a very mild down side now(no suicidal thoughts! no intense negative thoughts!, just some apathy). I am now trying to figure out how to get some energy and focus. The winter weather is taking its toll on me, but I want to be able to be motivated...

  10. Without going into detail, I just want to say thank you for this post, and for distilling a PubMed article that could really help a lot of people who haven't found a solution elsewhere. Thank you, really.

  11. I really like the gluten or even flour free idea. Ezekiel bread is purely sprouted grains with no flour, all grown organically. Any studies on primrose oil and bipolar? I seem to remember it repairs the myelin sheath of nerve cells that may be irritated and misfiring in some way.

  12. Don`t talk even more this blog and comment is for sure enough to read and learn something new....


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