Monday, January 31, 2011

Autism and Ketogenic Diets

I had forgotten that the good Dr. Su sent me a link to a dietary trial of ketogenic diets in kids with autism a few months ago. He reminded me of this himself when he quoted some comments I made in a recent blog post, but then "Paleo Guy" extraordinaire earned bonus margarita mixes for his machine by reminding me yet again and sending me a link to a complimentary paper that is an excellent review of ketosis in general.

I will get back to posting on sleep. It's just the continuing sleep deprivation I've been experiencing makes the reading of the sleep textbook a bit too painful. However, I'm committed to restoring good sleep hygiene habits and no more twitter at 3am. In addition, each little beastie now has an LED nightlight play toy thingie that switches off after 30 minutes. They get huggable freedom from fear of the dark, and we all get blessed nighttime blackness. Win win. We'll just ignore the shutting down of the melatonin with the 30 minutes of LED glow. It's better than leaving the hall light on all night.

Right. Dr. Su's paper. It is a study of 30 kids from Crete with autism who were placed on a ketogenic diet for 6 months in 1999. They went on a "John Radcliffe" version of a ketogenic diet, consisting of 30% medium chain triglyceride oil, 30% fresh cream, 11% saturated fat (oops! overshooting the USDA 2011 guidelines by a bit), 19% carbohydrates, and 10% protein along with vitamin and mineral supplements. The kids were placed on the diet in 4 week intervals, followed by 2 weeks of anything goes, so on and off. The kids' urine was tested with ketostix and their serum checked for beta hydroxybutyrate (a ketone) to measure the amount of ketosis. After 6 months, the diets were discontinued, and the kids were evaluated monthly for another 6 months.

At the beginning of the study, 2 of the 30 kids met criteria for mild autism, the rest were more severe. Interestingly enough the premise of the study was to presumably improve mitochondrial efficiency in the brain via ketosis (using ketone bodies as fuel rather than glucose). 11 years later a small study did in fact confirm that kids with autism often have problems with mitochondrial efficiency.

23 kids tolerated the diet beyond the initial 4 weeks, and of those, 5 more discontinued the diet due to lack of improvement during the first few cycles. Of the remaining 18 kids, two boys improved enough in symptoms to be taken out of the special school and placed in mainstream education. Overall the 18 ketogenic kids "presented with improvements in their social behavior and interactions, speech, cooperation, stereotypy, and... hyperactivity, which contributed significantly to their improvement in learning."

The kids who did not stay on the diet were the most severely affected by autism, and the ones who had the best response were ones most mildly affected. Another interesting fact from the study is that the kids maintained their improvements through the two week washout periods and in the 6 months after the study was over. None of the kids had any complications (such as poor weight gain or selenium deficiency) seen in other trials of ketogenic diets in kids with epilepsy.

Overall (using the original sample size of 30), 26.66% of the kids benefited significantly from the diet. The researchers also have a nice explanatory paragraph about the biochemistry of ketosis and how it favors the relaxing inhibitory neurotransmitter GABA over the excitatory, and in excess, neurotoxic glutamate:

"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."

Couldn't have said it better myself!

Well, this wasn't a large study or a blinded study and there was no control, but for some kids, the improvement was exceptional, and ketosis didn't have to be strictly maintained. My personal preference is not to live in ketosis, but rather to dip in on occasion via 16 or 24 hour fasting and some very low carb breakfasts after overnight fasts. This study seems to suggest that dipping into ketosis can have benefit for brain energetics, though the kids went through a larger scale "dip" than I ever have.

And, once again, dietary therapies prove to be exceedingly beneficial for some, but won't do much of anything for others. It would be important for any parent of an autistic child to know that ahead of time before pinning one's hope on a ketogenic diet. On the other hand, autism is currently incurable, and a ketogenic diet seems like a nice weapon to have in the arsenal against this disease.

(Put in the links and fixed some of those bizarre sentence structures.  I shouldn't be allowed to blog when sleep-deprived.)

Edited to add links to the rest of my posts on autism.  I cover gluten-free diets, inflammation, mitochondria, vitamin D, theories about the pathology:

Diet and Autism1
Diet and Autism 2
Autism and Vitamin D
Autism 4 - Inflammation Speculation
Brain Efficiency, Pediatric Edition
Autism and Interpregnancy Interval

10 comments:

  1. It takes twice as much red light as white light to suppress melatonin (http://www.ncbi.nlm.nih.gov/pubmed/8586959), so I would think the night lights would do little. Win win indeed.

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  2. More evidence that burning fat points in the direction of health. Why does the woman that discovered the genes that control aging eat a low carb diet? “I did it because we fed our worms glucose and it shortened their lifespan.”

    The USDA guidelines manufactures artificial demand for healthcare services. There's a lot of money to be made in sickness and disease. With a government like that, who needs terrorists, eh? ;-)

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  3. Very interesting.

    However it is hard to attribute the improvements to the ketosis specifically given the prevailing theory that some kind of immune system disorder may relate to some cases of autism... it's possible the improvement in those kids was merely the result of eliminating 99% of allergic food and going low protein. It would have been nice to see a third group of the ketogenic diet done where levels of common dietary allergens were maintained (e.g. casein and gluten and such).

    Speaking personally, I seem to have a mild/subclinical bipolar condition, and my depression responds quite well to carbohydrate restriction. I was extremely nonfunctional and depressed prior to discovering low carbohydrate eating. I slept 12+ hours a day, lost all sense of time, did not/could not leave the house, did not shower or tend to hygiene, dropped out of school and life in general. I was a total wreck. In march of 2001 I began a very deep ketogenic diet, and like a miracle my whole mental state changed within days. I stopped sleeping excessively and only slept 6 hrs a night. I no longer felt hopeless and depressed and for the first time I could find/feel meaning in life. It was such a strange experience to feel like things actually had importance and meaning as I had been so used to my miserable state.

    I still go through depressions, but I have tools to deal with them now and they are not as severe chronic or enduring as they were. Over all my mental health is far better the more ketotic I am.

    Given the overlap between antiepileptics and mood stabilizers, and the similarities between epileptic disorder and bipolar disorder variants, it stands to reason this diet may be effective for a subset of patients with mood disorders (probably those who also have primary blood sugar/insulin disorders maybe, as that is a sign of mitochondrial, energy using abnormality).

    I have never tried ketosis while experiencing manic symptoms... because while I am high I feel fine and do not actively try to stop it (although I know I am not totally right). My appetite is very poor while high, but eating excessive carbohydrate while high seems to shift my mood from euphoric to very irritable and angry. It also makes me very nauseated because my appetite is poor. So it is at least true that the ketosis and very low carb eating will prevent my up symptoms from being chaotic/angry/dysphoric/disorganized and paranoid and instead I feel euphoric and grand and excited.
    It should also be mentioned I only started having manic symptoms at 23... so I do not have as much experience with it as I do depression (which became tangible at my preteens and quite severe by 16). I also do not get as much mania as I do depression. I am 28 now.


    For many many years I have tried to figure out why food seems to affect me the way it does. All I can do is accept that I am much more stable and normal if I eat this way. It doesn't matter why that much, I'm just glad it helps. I am 100% certain I would be a psychiatric case if I did not eat this way. I would be extremely depressed and nonfunctional.

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  4. Interesting. I have a high functioning 18 year old on the spectrum, and have often wondered about this kind of diet for him. A few problems emerge:
    --In our family's experience, obsessions and perseveration often extend to food choice. Past a certain age, one cannot manipulate any child's diet (autistic or typical). They can always refuse to eat, filch what the rest of the family is eating. Such a plan would only work in a "normal" family (ie: one where a spouse and other siblings might mutiny at being put on a special diet to make it more likely that the afflicted one might improve. My own son had about half a dozen foods he was willing to eat at all at one point, and only years of badgering, bribing, reinforcing, and more maturity broadened his gastronomic horizons to the point where he was even willing to let foods touch each other or try them. The issue of preferences also arises. Also of cravings. Tho I feel rather sure that the ravenous cravings for carbs, candy, soda, and other scrumptious junk beloved by all ages of children might actually be an indicator of sorts. I remember somewhere reading that kids who craved even more soda than the norm, and candy (how can there ever be too much candy for a kid???) often grew up to become substance abusers. Impulsivity and inability to delay gratification, or something related to things like serotonin and glutamate balances...

    My point is, I think such a diet might well work, but implementing it might prove difficult. My own children, two typical, as well as the one on the spectrum ate healthily by my standards only til elemenary school broadened horizons "Mom, I traded lunch with a frien and her sandwich was made with this great soft, fluffy WHITE bread, and had white marshmallow fluff in it and it was the best thing I EVER had!)

    But if one could overcome rebellion, the kid's personal tastes and habit, I can see that it might help all the kids like mine who are kept fairly stable despite cooccurring disorders with meds that promote weight gain. Autistic kids are often overweight, because even without psych meds, they may eat more than most. So if you give them a less tempting diet (hard to want more meat, chees, eggs, etc. than one needs as they fill one up and sate one) they will do better...

    I agree on the iPad/computer thingey. I can write posts, comment, etc from mine (during work lunch hours and when we travel to a family place with no landline or internet) but setting up lots of links can be cumbersome on it.

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  5. Paul - I consider it a nice evolutionary "campfire glow."

    js290 - It is puzzling that a rather large body of decent evidence that came out in 2010 seems to have been ignored. Well, more grains to be peddled, I suppose.

    ItstheWoo2 - I'm not sure if autism is due to allergies - it could be they are more vulnerable to allergies because they are in a state of general inflammation. There are two case studies in the literature (that I know of) of ketogenic diets and bipolar disorder - one didn't do squat and the other (though it was Atkins, so likely high in omega6) made the guy much, much worse. However, I keep coming up to these little studies of ketogenic diets and Alzheimer's, autism, and of course the evidence for childhood epilepsy, and there is clearly something there. Exactly what and in what way it should be "prescribed" is still unclear to me. I will typically fall back to an ancestral diet paradigm (+ modern veggies and dairy fat or high-fat fermented dairy in my personal version) as it seems like a safe fallback - we aren't smart enough to know with scientific certainty what is best - so let's go to what we are more likely to be designed for, with some common sense. I do love to hear about people improving mental health conditions with diet.

    Retriever - I cooked eggs for the kids this morning. The 21 month old immediately demanded "chicken" and the older one said, "No, I'll only eat popcorn and candy." And these are toddlers and pre-preschoolers! They both ended up eating the eggs (and chicken), and no popcorn or candy... but the daily battles are tiresome. With autistic kids the battles can quickly get out of hand, and parents need to be able to pick their battles! I think the good news from this study is that you don't need to be perfectly ketogenic all the time to get benefit, and the benefits lasted for 6 months after the diet was discontinued.

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  6. Perhaps I jumped the gun when I said "prevailing" theory... however there is evidence that some kind of immune system problem is present in some cases of autism. It may be that the inflammation is causing the immune system disorder, but I tend to think the immune system disorder is the common link among autistics. There are many people who are inflammatory but do not have autism, there are many people who are inflammatory with no allergies. It seems as if autistic people's immune systems just work differently.
    Anecdotally speaking, I've found that most people who are autistic, or "neurotypical" people who exhibit autistic-like personalities, often seem to have multiple allergies.

    http://www.ucdmc.ucdavis.edu/newsroom/releases/archives/mind/2005/immune_sys5-2005.html

    http://www.jleukbio.org/content/80/1/1.full


    -------------------------------------

    Regarding ketosis and mood disorder... given the overlap between epilepsy and bipolar, as well as the fact metabolic disorder / glucose intolerance is more common in bipolar people (even after meds considered), it stands to reason ketosis will help.

    More compelling is the fact that depression (endogenous) is common in epilepsy, and epileptics using a ketogenic diet experience a reduction of symptoms.

    Many of the effects of depakote and lamictal and others are found in ketosis.

    I was hoping to hear that you have tried it or recommended it in some of your patients. I do very strongly believe a subset of patients could reduce or eliminate medications if they used a ketogenic diet. If antiepileptics work for bipolar d/o, and if ketosis is a powerful antiepileptic, why not? The brain boo boos in bipolar are quite similar to epilepsy.

    My life would be unlivable if I didn't know what I know. I think of the depressions and it terrifies me to think that I would be feeling that way more / most of the time. It's so horrible, and for no reason at all. I can't describe how bad it feels. You cannot function, or you can only function minimally. You see no point in living at all. I always think to those times and try to understand how I could think/feel that way, but ultimately I cannot conjure it with my rational mind. It is a brain problem.

    Anyway.

    I wonder what you think of the role of stress hormones in mood disorders. I tend to think I would never have developed manic symptoms if I did not have an eating disorder. Prior to the onset of my highs, I had been very low weight and eating very little food for months on end. By the end of that year, in summer, was the first time I ever had manic symptoms. I do not think this was incidental. I think the stress of chronic malnourishment damaged my brain, likely via cortisol.

    The second time I had another bout (more severe) with manic symptoms I was 25. It was the end of spring and I had just graduated from school, which was an extreme stressor for me. I went pretty nuts, stayed up at night pacing and laughing and felt like I was on drugs. My family watched me like you would a crazy person. I thought I was losing my mind. By the end of summer I saw a psychiatrist, due to my family history of insanity (schizophrenia) I was worried I was cracking up. They told me I was bipolar.

    Every time I have had an extreme, enduring stressor I have gotten crazier permanently.

    Rambling, sorry.

    My point is I think that in my case stressors have been influential in triggering the brain damage leading to it. What's your take? Are stressors common prior to the onset of a first episode or a very severe episode?

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  7. It'stheWoo - allergies are a type of inflammatory repines, so I don't think we disagree on that piece at all. As to your question about stress - yes, it will absolutely be the straw that breaks the camel's back likely in combination with genetic vulnerability and underlying inflammation of some kind. I have a couple of posts "chronic stress is chronic illness" and "stress is metabolic syndrome" with some details. I also discuss ketogenic diets and bipolar disorder in more detail in a couple of posts (called ketogenic diets and bipolar disorder 1 and 2).

    I find there are three sorts of people willing to undergo the dietary change of a paleo diet (and the low carb ketogenic angle would be a step up from that so far as big change and need for adherence, if used as treatment) - vain, know-it-all anti-authoritarian types like myself, folks struggling for years with vague (and not so vague) autoimmune disorders, and young adults with acne. Outside those cohorts there is less interest. But it would be interesting to see a cohort of folks with bipolar go ketogenic.

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  8. Emily, In your reading of these studies about the therapeutic use of ketogenic diets for autism, epilepsy, or other neurological disorders, is there ever any discussion of exactly what the diet is composed of? I am asking because I have seen some references to a possible linkage between ketogenic diets in the treatment of epilepsy and a heightened risk of the development of pancreatitis, which can be quite serious. But if these studies are more focused on macronutrient proportionality rather than on nutritional quality, I wonder if what goes by a "high-fat" diet is in fact loaded with PUFAs and therefore highly inflammatory and that this might be the cause of the pancreatitis or is this a danger regardless of what fats are eaten? It would be helpful to know if these studies remark at all on the specific sources of dietary fat. I am thinking here also of Dr. Harris's current series on "no such thing as a macronutrient."

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  9. Ann - I have to say a lot of the papers are a bit vague about the specifics. If you look at some of my previous ketone posts (your brain on ketones being the most read), I mention some of the drawbacks. Also the Ketogenic Diet and Bipolar Disorder posts have more information too. The worst outcome I saw was in case studies of kids who developed arrythmias and died due to selenium deficiency. Strict ketogenic diets are not to be taken lightly, and anyone who eats a lot of fat should take care as to the quality of the fat consumed and to make sure all the needed nutrients are accounted for. I think that is why most weight loss programs, even Atkins, just have an induction phase and keep you out of ketosis after an initial phase. Primal diet followers and IFers will dip into ketosis from time to time (that's what I do), and this likely resembles what our ancestors did.

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