Friday, June 10, 2011

Fat Loss, Mood, and Cognition Part 1

Perhaps a month ago, Zooko tweeted me some papers - one of which I had seen before.  Both papers were done on the same group of obese dieters (half eating low carb and half eating an isocaloric low fat diet) for 52 weeks.  Zooko presented a puzzle and links to the free full text - notice anything about the data?

Paper Number 1 (I'm adjusting the name for simplicity's sake): Low Carb vs. Low Fat - Cardiometabolic and Weight Loss Effects

Paper Number 2: Low Carb vs. Low Fat - Mood and Cognitive Function

So, have you taken a look and found the interesting thing about ketones?  Yeah, Zooko had to point it out more explicitly to me as well - though to be fair I was distracted by some issues I have with the second paper's conclusions.

All right, here's the important bit.  The first graph is from the first paper, showing levels of ketones in the low carb and isocaloric low fat dieters over the 12 months.  (The low carb dieters were advised to increase carbs a bit after 8 weeks, which is no doubt part of why their ketones drop at that point):

Note also that both the low fat and low carb dieters have higher plasma levels of ketones in the first 8 weeks than thereafter.

Now here's a graph from the second paper, showing Beck Depression Inventory scores at the same time points (a higher score corresponds to a more depressed individual - though none of these scores are high enough to indicate even a mild depression):

Those first eight weeks, with more ketones for both sets of dieters (and since they were losing weight, ketones in the low fat group especially would have been from burning stored fat), corresponded to a 4 point drop on the BDI for both sets of dieters.  I have no idea if the correlation between the two sets of data in that first 8 weeks (or later) is statistically significant, so don't run to the bank or anything - it's just rather interesting.  Most obese dieters will be pretty happy to be losing weight, especially at first.

Now the distracting thing I find objectionable about the second paper is that, even though both groups had identical depression scores at baseline, 24% of the low carb group were on antidepressants compared to 12% of the low fat group at the beginning of the study.  The authors discounted that bit of data somewhat, saying it was non-significant.  They go on to suggest that on explanation of the low-carber's tendency to move back toward baseline levels of depression as opposed to the low fat dieters is that low-carbers are more isolated in society as the eating patterns are far from the norm.

The low-carbers were instructed to consume no more than 20% of their calories from saturated fat.  That means they had to be downing a bit of olive oil or lots of PUFAs, so you do wonder about a massive omega 6 load over time.  The low fat dieters, on the other hand, were consuming the palmitic acid from all the stored carbs of yore and presumably not adding as much dietary omega 6 to the party as they were instructed to eat low fat.

Cognition-wise, though the authors had found some problems with cognition measures in the low-carb group in the first 8 weeks compared to the low fat group, there was no difference between the groups after 52 weeks, suggesting the adaptation period may have led to some temporary cognitive problems in the low carb group that then resolved.  ("Low carb flu?")

Personally, after 16 hours of fasting (which I am quite adapted to at this point), I find my thinking is sharper, I'm less distractible, and more motivated for the next several hours (I've never fasted longer than 24 hours).  Anecdotally, others have shared the same experience.

What I'm trying to sort out here is what the ketones are doing.  In order to achieve seizure control by changing oxaloacetate concentrations with a ketogenic diet, you need to be in pretty deep ketosis and it would take more than a 16 hour fast to get there.  Glucose is preferentially sucked up in the brain as it is the last place in the body to become "insulin resistant" in starvation or high-fat conditions.   While some folks seem to love deep ketosis and thrive there, I have always wondered if the more evolutionary model of intermittent fasting (though there may have been high fat seasons also) would have a beneficial effect via ketones, despite the fact that most IFing does not leave us in ketosis deep enough or long enough to change the amino acid handling in the brain in a way that lowers seizure threshold.

In cells of the brain with mitochondria, I'm still assuming one would get boosts in energy efficiency from partial utilization of ketones, as I've discussed before.

There's a lot to sort out and a gazillion variables, but I thought the graphs were cool enough to put them out there for your perusal.  Thanks Zooko!

Here's the weight loss, in case you were interested:

(While we are discussing ketones, Zooko also tweeted news that a young man who started a ketogenic diet after being diagnosed with brain cancer is now in remission.  Happy news indeed!  Zooko noted in a later tweet that we can't know the ketogenic diet helped bring on remission, but it is certainly plausible that it may have helped.)


  1. I have had some pretty amazing cases make an abrupt turn around after starting them on ketogenic diets for many neurosurgical indications. I really think we need to do it a lot more. Sometimes technology brings us further from the truth and close to an edge.

  2. "technology brings us further from the truth and close to an edge" That's one I'll "leverage" for future use! Thanks, John.

    Thanks, Dr. Dean, for this post. We desperately need research in the realm of nutrition and emotional/mental health. Have you read Robert Whitaker’s “Anatomy of an Epidemic?” Your thoughts? Here’s a link to an article from Ethical Human Psychology and Psychiatry, Volume 7, Number I , Spring 2005 I wonder about the dietary influence …


    Pete B

  3. John - I agree - keto diets have very plausible and scientific possibilities of a lot of conditions - there is no reason to be afraid of them. It is absolutely a travesty that they are not studied more for brain conditions. The research is heating up, though - hopefully the next 10 years will be fruitful.

    Pete - Whitaker has a flawed premise, and I think he is particularly wrong about schizophrenia, based on quite detailed accounts i have read of the natural history of these disorders prior to the invention of medication (lithium is first in the 1940s, then Thorazine I believe in 1949). BUT Fred Goodwin, author of the best textbook on bipolar disorder, strongly believes that bipolar disorder has changed quite a bit very recently, and he blames antidepressants. I have to say, though, it is only very recently that there was this free-for-all with respect to medication. Only 10 years ago it was pretty shameful to prescribe more than one medicine at a time for psych disorders (basically it meant you weren't working hard enough at therapy)- now I will literally get intakes with people on 7 or 8 meds. Worst thing is, try to take away any, and you end up with a bad situation... I could go on and on... The thought leaders in the field are heading two directions.

    On one hand, you can use the evidence to say meds reduce relapses, and relapses represent damage to the brain, the more episodes, the harder the illnesses become to treat, the more damage is done to the brain, as symptoms represent active inflammation. Using that paradigm, it becomes folly and damaging NOT to throw everything you can at it - thus the most respectable hospitals sending me people on 8 meds including 2 or 3 for side effects from the other meds - this path obviously leads us to expensive nowhere land pretty quick, but no one seems to look ahead. The frightening trend is occurring in young people - the idea to treat aggressively in order to prevent long term damage. This same paradigm (which can seem completely reasonable and moral if you look at it in a certain light) leads childhood obesity experts to put the green light on for gastric bypass for teenagers. Literally removing half their insides - there are 300 lb teenagers with diabetes and the long term outlook is not good - bariatric surgery is the only successful evidence-based treatment for morbid obesity.... But... I'm given to thinking our guts are awfully short compared to other primates to begin with, right?

    On the other hand, Andreasan's recent work, and Goodwin, and great studies comparing unpublished and published data for antidepressants have dampened the pharmapalooza enthusiasm. To my mind this is a very good thing. It is an untenable position to be a psychiatrist trying to help people using bad data and addressing long-term conditions with short-term data. I personally was so frustrated with the situation that it has been incredibly refreshing to dive into the nutrition aspects. None of the thought leaders in psychiatry are addressing that much, though the scientific reasoning is quite sound and I have every reason and a pile of evidence to suspect that nutrition, sleep, and stress are the biggest issues, piled on top of genetic vulnerability.

    As I see it, psychiatry runs aground if we keep heading the same old direction, but we need data, not hand-wringing.

  4. Interesting post and comments Dr Deans
    In my continuing n=1 experiment I have made another adjustment (in the last 6 weeks), so in the last 18 months I have dropped grains, legumes, added sugar, I restrict my fructose to a few berries (and stay very low carb around 50 g a day) and now the most recent change do not include dairy (other than a very small amount of butter). Dropping dairy occurred after I did a lot of research into the insulinogenic effect of dairy proteins.

    I'm am now the most well I've been mentally in 25 years, and physically have the best body composition I've ever had (I've leaned down further since the dairy went even though I have consciously kept the fat content of my diet at a similar level along with the overall caloric intake). And that after a decade of hardcore triathlon training - I arrived at Paleo the classic skinny fat vegetarian compulsive eating disordered exerciser . I now do embarrassing little; lift heavy weights and sprint (pool or bike) once a week, swim for fun and cycle when I fancy, I also do some yoga. Not bad at 44. Most impressive (to me anyway) I can get up and ride 5 hours if I fancy, without 'training for it' - guess that's Art De Vany's (Evolutionary Fitness) principle of metabolic headroom achieved through the intermittent lifting and sprinting.

    I IF once or twice a week by skipping breakfast (and occasionally lunch 16 - 24 hours) and train heavy/sprint in a fasted condition. My mental processes during a fast are excellent, sharp and focussed. This makes evolutionary sense to me. A fast is replicating limited/no food supply so very important that the brain be highly focussed in order to make the next kill etc.

    I was interested and heartened to read your 'take' on medication, particularly multi-meds. Until a year ago I struggled with bipolar since my teens. In part due to my Grandmother's experience (and my own distrust of the medical profession) I have avoided the conventional psychiatric services (and their approach and meds). Instead I muddled through 2 - 3 decades with some intermittent unconventional therapies (of the cognitive, talking variety), self education and many, many manic episodes which bordered (and occasionally tipped into) the bizarre and dangerous. The only medication during that period was the occasional temazapam to enforce sleep during the worst of the mania. Now, I guess I could have had an 'easier' more 'normal' life had I been medicated, and my family would certainly have been spared some of the trauma, however it would only have been treating symptoms.
    What I have discovered, quite by chance, is that all my issues were rooted in the wrong fuel. My particular genotype (along with many others it would appear - especially in the areas of addiction and eating disorders) is highly sensitive to the effects of insulin-triggering foods/events. I'm convinced my recovery is down to the low insulin enviroment I now operate within (insulin sensitivity/resistance is in my history as a gestational diabetic). Once I began to understand the effect of insulin/IGF pathways in the endocrine system essentially highjacking the superhighway and knocking dopamine/serotonin et al out of whack the penny really dropped as to why I am well now and wasn't before. I personally believe diet can solve just about everything.

  5. continued ...

    I have a friend who has been under the 'care' of conventional psychiatric services for the last 25 years, she's been bounced about from one med to another, misdiagnosed and now on multiple meds for anxiety. She has gained huge amounts of weight and is constantly tired. I wish I could get her to try Paleo living for a month or two. Her treatment seems to consist of trial and error (mostly the latter) that has simply produced insulin resistance and myriad other problems because the treatment is symptomatic not causal. My definition of insanity is doing the same thing over and over and expecting a different result.

    The sooner diet and nutrition (lifestyle) are considered more seriously within the context of serious mental health disorders the better - more power to you and your questing.


    (I have tried so many times to post this comment, not sure if it's your system or mine that is creating problems)

  6. Cavegirl - I had problems posting comments, even on my own blog. It's a "known issue," but Blogger states it's "fixed." Not by my experience when using IE. I switched to Chrome and I can now post comments using the Google profile.

    Pete B

  7. Dear Emily, very interesting comment on schizophrenia and medication. I would find it difficult to decide how to treat a person. Maybe the problem is to use drugs in cases of hallucinations in non psychotics?

    I would like to read a post on how you treat other conditions like social phobias or obsessive personalities. I understand diet in depression can help with inflammation but what can help with anxiety?

  8. Google bought Blogger but never put much effort on it. With posterous you can post almost any file by mobile, email, whatever, and it is displayed. Tumblr is also good. The only good point is that one can assume Blogger service will last.

  9. Hi Emily! Thanks for mentioning me! If I knew more graphing package foo I would recast those two graphs to have the same X axis and to be overlaid on one another nicely.

    The young man who went on a ketogenic diet was not *recently* diagnosed with brain cancer. He was actually at the end of a struggle--drugs and radiation had failed to stop it and the oncologists had offered him no further ideas besides to do his best to enjoy the remaining six to twelve months.

    He had been suffering from frequent debilitating headaches and had started talking about euthanasia. Shortly after he started the ketogenic diet the headaches were reduced in severity (but not in frequency) from debilitating and quality-of-life destroying to "just like normal headaches".

    Of course the real test is how long this remission lasts. The case studies by Nebeling 1992 describe one (out of two) patients surviving and thriving and staying cancer free until the present day (in other words, the entire childhood of that patient, who was 3 at the start, which was more than 10 years ago).

    But of course we might not be so lucky. At this point we can only hope.

  10. Hi Emily,

    Martin (from as well as Matt Stone and others have noted that the cognitive/emotional stimulatory effects that result from fasting are due to the rise in stress hormones (catecholamines); which in turn are provoked by the slight hypoglycemia caused by fasting (and calorie restriction).

    Whilst transient euphoria is no doubt a pleasant sensation, the constant secretion of catecholamines can lead to problems (e.g. anxiety, digestive issues).

    The severity of this issue is mediated by the length of the fasts, the regularity of the fasts, the extent of calorie restriction, and the extent of carbohydrate restriction.

    Bottom line, catecholamines make you feel great in the short term, but it is a case of "too much of a good thing" if the secretions continue for too long and/or occur too regularly.


  11. Stress hormones are no doubt involved - it is partly why I don't fast for more than 24 hours (usually it is more like 22 hours).