Saturday, January 8, 2011

Alzheimer's, Mild Cognitive Impairment, and Ketosis

Funny thing is, not even a month ago I was commenting over at Dr. Parker's Diabetic Mediterranean Diet blog that there weren't really any studies about ketogenic diets and Alzheimer's and dementia.  There were a few case reports that it was helpful, to be sure, but nothing much on Pubmed. Which is disappointing, because if you know anything about (very low carb or coconut oil heavy) ketogenic diets, you know that they should reduce inflammation, enhance energy efficiency, and decrease hyperinsulinemia, all of which are implicated in the pathogenesis of Alzheimer's. 

Thank heavens I follow Dr. Eades' twitter feed.  In December 2010 and January 2011 not one, but two academic papers have come out related to dementia and ketogenic diets or glucose metabolism.  So here they are:


Dietary ketosis enhances memory in mild cognitive impairment

In this study, researchers did the obvious thing and put 23 older folks with mild cognitive impairment (MCI, a type of early dementia) on a very low carbohydrate diet or their normal diet for 6 weeks.  Most people with MCI will progress to Alzheimer's, and MCI is important, because at this point your brain still has more than a fighting chance.  Interventions at this point, if they work, might mean you don't progress to Alzheimer's.

Oh dear, here is a depressing quote from the article:

Contemporaneous with the developing dementia epidemic
is an epidemic of obesity and associated metabolic disturbance.
Currently, 64% of the USA adult population is overweight and
34% obese (Flegal et al., 2010). It is projected that by the year
2030, 86% will be overweight and 51% of adults in the USA
will be obese (Wang, 2008). Likewise, diabetes prevalence is
accelerating, particularly in the aging population (National
Institute of Diabetes and Digestive and Kidney Diseases,
2008). Hyperinsulinemia, which is a precursor to type 2 diabetes,
occurs in more than 40% of individuals aged 60 and
older (Craft, 2005; Ford et al., 2002).

So the elders were recruited, given a battery of cognitive tests, then randomized to either a high carbohydrate diet (>50% of calories) meant to mimic an ordinary older American's diet, or a very low carbohydrate diet (10-20g of carbohydrate daily) for six weeks.  Protein, fat, and calories were not restricted.  "All subjects were advised to choose monounsaturated fats when possible, although this was not controlled." 

At the beginning of the studies, the subjects were pretty ordinary older Americans (though anyone with frank diabetes was excluded).  They tended to be overweight, had normal fasting glucose, but were at the high end of fasting insulin levels.  Fasting insulin levels correlated with waist circumference.

After six weeks, the ketogenic diet group got skinnier waists, lower fasting glucose and lower fasting insulin (which shouldn't be a surprise for anyone).  Ketone bodies were measurable in the urine of the very low carb subjects, and total calorie intake was also lower - fat and protein were not significantly different than the high carb group, however.  Basically the low carb folks ditched the carbs and didn't replace them, resulting in lower calories overall.

And the brain effects?   Memory was improved in the low-carb subjects, but not the tests of executive functioning (like trailmaking tests), suggesting a specific hippocampal and parahippocampal effect of ketones in the brain.  Very interesting!

On balance, these preliminary data provide evidence that
dietary ketosis by means of carbohydrate restriction can provide
neurocognitive benefit for older adults with early memory
decline and increased risk for neurodegeneration.

Got it!  Moving on.

Second paper is Brain fuel metabolism, aging, and Alzheimer's Disease from the January 2011 edition of Nutrition.  This paper is a review article rather than a study, with lots of interesting evidence for shoddy glucose metabolism in animal and human studies of Alzheimer's disease.  I like this paper because it targets every piece of dietary insult on our brain that a Kitavan avoids just by being a horticulturist and not subsisting on a diet of *insert the vast majority of foods in the middle aisles of the modern Western grocery store here* - and the Kitavan happens to avoid dementia at the same time.  Poor glucose metabolism, poor omega 3 (DHA status), and poor mitochondrial function are all found time and time again in folks with Alzheimer's, especially those with the ApoE4 allele or a maternal family history of Alzheimer's dementia.

This paper is 18 pages long and rather amazing, but I'll skip to the ketogenic part here:

Nevertheless, two observations in particular support the notion
that the neurons affected in AD are still functional: (1) in AD,
brain ketone uptake is apparently normal or at least less
impaired than is glucose, and (2) there is a functional
response to nutritional supplements that increase brain fuel
availability, particularly ketones. Hence, if brain fuel metabolism
could be optimized or even partially returned toward normal, the
risk of further cognitive decline may diminish. Raising plasma
ketones to 0.4-0.5 mM would contribute to 5-10% of the brain’s
energy requirements (Fig. 3), which is equivalent to the early
cortical glucose deficit in those genetically at risk AD. Such
a mild, safe level of ketonemia is achievable with ketogenic
supplements, so if implemented before symptoms develop, it
seems plausible that they could diminish the risk of further
metabolic deterioration and clinical onset of cognitive decline.

Ketogenic supplements would mean medium chain triglycerides, such as coconut oil, which the Kitavans eat in spades

I know, the prescription is very nearly always the same on my blog.  The scientific explanation to get to the prescription in different disease states are often very different.  Avoid the neolithic dietary agents of disease (I count them as many paleo types do as wheat, fructose, and vegetable oils), not to mention other novel fake foods we were never designed to eat, just to be safe.  Ratchet down the carbs if you have love handles or metabolic syndrome.  Dabble with ketosis by intermittent fasting, coconut oil, very low carb, or all three depending on your own personal brain status.  There's plenty left to eat that is gorgeous and yummy.  And you get to keep your brain.

23 comments:

  1. Wow, great stuff here. I was hoping to find something on this subject.

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  2. There had to be something to the keto diet when they use it to treat epileptic kids. Like Dr. Rosedale says, you have to burn fat to be healthy.

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  3. Unfortunately, Nursing Homes in the UK feed their residents on the SED. I suspect that on your side of the pond, they all get the SAD. They also don't get any sun exposure.

    Without the right kind of Power of Attorney (which I don't have), you don't have any authority to specify your parents' diet or supplement regime once they're institutionalised. :-(

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  4. Dr. Deans, thank you very much for this post. It will be of great interest to many.

    I hope you don't mind a question:

    If someone is already on a ketogenic diet, free of the Neolothic agents of disease, how important is the coconut oil?

    Is improvement on coconut oil a "try it and see if anything improves" scenario? Or is coconut oil a vital supplement such as magnesium and D3 for older folks?

    Thank you very much.

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  5. Hi H - Coconut oil just makes it easier to stay in ketosis. A bit of coconut oil allows you to eat more carbs and protein and stay in the strict ketogenic state required for epilepsy treatment, for example. Coconuts most likely *weren't* a staple food for humans for much of human history so there's no reason to think we are symbiotic with coconuts. But coconuts and fish (and non-toxic starchy carbs, for the Kitavans) seem to make for good brain food, at least from a dementia standpoint. I would say there is no evidence coconut is a "vital" supplement - and one can certainly dip into mild (or deep, if you cut carbs and protein enough) ketosis without it.

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  6. Hi Nigel - a friend of mine is a geriatric psychiatrist and she puts everyone on the ward on 2000 IU vit D straight off. But hospital/institutional food is organized by nutritionists on staff to meet the food pyramid, more so for the "heart healthy" or diabetic diets, at least when I worked in hospitals. It is unfortunate you can't help prescribe your mother's food, however. Sometimes one can develop a relationship with the staff and they will allow you some liberties.

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  7. Dr. Deans,
    I found your blog via the shout-out at PaleoNu by Dr. Harris. My father died of aspiration pneumonia secondary to advanced AD at the age of 68, so I am quite keen to do whatever I can to ward off early-onset AD. I've really enjoyed reading your series of AD-related posts. I adopted a strict Paleo diet (+ high fat dairy) back in September. So, basically, what you've posted on so far indicates that Paleo/Primal should help preserve brain function via suppressing systemic inflammation, supplying adequate cholesterol to the brain for myelin sheaths etc., correcting glucose dysregulation, and occasionally supplying ketones as fuel. In your view, is it necessary to be permanently in ketosis, or is occasional ketosis via a low-carb diet and intermittent fasting likely to be as effective? Thanks again for your great posts and insights.

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  8. Clarissa - sorry to hear about your Dad. As to how much ketosis is enough ketosis? I think we can safely say nobody knows. If you already have a condition where the brain is short-circuiting, such as epilepsy, pretty strict ketosis seems to be required (more studies are coming out with less and less strict ketosis with epilepsy - at first kids were fluid restricted, calorie restricted, and severely carb and protein restricted. The latest studies (in epilepsy) have added coconut oil so there can be more carbs and protein and the diet is more palatable, and also used a "modified atkins" approach which starts out with 5g carbs per day and increases to 20 as tolerated.). They used a low key 20g carb approach with the MCI patients, and it seemed to help, but again, they already had issues and likely active inflammation and damage going on. I would like to think that with a healthy brain, plenty of dips into ketosis is good enough (and certainly the Kitavans tend to eat a high carb diet but have no dementia - but they have no obesity and no diabetes and low low fasting insulin). But there is no data for this - it is all off the grid (hopefully common sense) speculation.

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  9. Dr. Deans, thank you for taking the time to answer. I will enjoy reading further about fish and coconut as brain food.

    The subject of staying on a ketogenic, Paleo diet for the rest of one's life and the best choices for nourishment are areas of keen interest for some of us.

    Would you consider addressing the following?

    1) Optimal protein amounts:

    Peter Dobromylskyj, who writes "Hyperlipid", keeps a low protein intake, and made a comment about being concerned about elevated brain cortisol if one stays ketogenic. He follows Dr. Kwasniewski's recommendations for protein and carb intake.

    2) If one keeps protein and carbs low, with a high fat intake, does this withhold necessary nutrients from the brain? I am thinking of middle-aged and late-middled aged people, or older, who wish to improve brain function and improve overall health, rather than the children with epilepsy. Is it risky to eat low protein when one is under 20 carbs per day?

    3) Some of us prefer eating fewer than 20g of carbs per day, which means ketosis, unless, as has been posted on the low carb forums, that after some months, the body adapts and is no longer in ketosis at under 20 grams of carbs per day. After this adaptation, is it wise to do something, additionally, to improve brain nourishment, or to better support what Dr. Harris calls the evolutionary metabolic milieu?

    4) The advantages and disadvantages of staying in ketosis, for brain health, and what changes occur on a ketogenic Paleo diet, which might require additional steps of nourishment or supplementation.

    Thank you very, very much.

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  10. Axona is a medical food for Alzheimer's that is 20 grams of 8 carbon chain Caprylic acid per packet. This costs about $90 for 30 packets.
    http://www.accerapharma.com/
    http://www.about-axona.com/

    This product works by raising the blood ketone levels.

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  11. A much cheaper approach to Axona is to buy pure MCT oil. You can get it in 32 oz bottles for about $15 + $5 shipping over the internet.

    For a ketogenic drink, mix about 100 calories worth of coconut milk with about 4 teaspoons of mct oil with maybe about 1/4 teaspoon of Lecithin to help the mct oil mix with water. Add enough warm water to make this drink about 8oz. Add artificial sweetener of choice.

    For protein, you might add a few grams of Branch Chain Amino Acids. BCAAs appear to make the ketogenic diet work better. It takes several minutes for BCAAs to dissolve in warm water. BCAAs can also help with muscle wasting.

    Someone not use to drinking this might get diarrhea. Try smaller doses first.

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  12. Hi H - a lot of questions! First off I learn a lot from Peter, Kurt, and the rest all the time, and I am less an actual metabolism expert than I am trying to figure out how our neolithic lifestyle and foods affect our brains. My general take is that we are optimized for a wide variety of foods and energy sources - just especially not the horrendous industrialized foods - and my personal preference is NOT to count calories and weigh things. So keep that in mind for my biases.


    1) Optimal protein amounts:

    Peter Dobromylskyj, who writes "Hyperlipid", keeps a low protein intake, and made a comment about being concerned about elevated brain cortisol if one stays ketogenic. He follows Dr. Kwasniewski's recommendations for protein and carb intake.

    I still have not looked too much into the Optimal Diet. Paul Jaminet over at Perfect Health Diet has a lot of information about some specific ratios and a specific ketogenic diet. Ironically, protein seldom comes up in the psych literature, and there is much, much more about minerals, vitamins, fats, and dietary patterns. A classic epilepsy ketogenic diet is protein restricted, I believe, due to gluconeogenesis. I'm used to seeing hypercortisolism associated with hyperglycemia, not protein.

    2) If one keeps protein and carbs low, with a high fat intake, does this withhold necessary nutrients from the brain? I am thinking of middle-aged and late-middled aged people, or older, who wish to improve brain function and improve overall health, rather than the children with epilepsy. Is it risky to eat low protein when one is under 20 carbs per day?

    I think you have to be careful as to your fat sources and watch the omega 6. And there is some suggestion that we need a certain amount of glucose for making mucous, etc, and perhaps a cancer risk without enough mucous, but I've just read the secondary sources on that, not the primary sources.

    3) Some of us prefer eating fewer than 20g of carbs per day, which means ketosis, unless, as has been posted on the low carb forums, that after some months, the body adapts and is no longer in ketosis at under 20 grams of carbs per day. After this adaptation, is it wise to do something, additionally, to improve brain nourishment, or to better support what Dr. Harris calls the evolutionary metabolic milieu?

    My understanding is that you better utilize ketones so you don't spill as many in the breath and urine (typical signs of ketosis), not that you are no longer in ketosis.

    4) The advantages and disadvantages of staying in ketosis, for brain health, and what changes occur on a ketogenic Paleo diet, which might require additional steps of nourishment or supplementation.

    The disadvantage to strict ketosis is that cheating is difficult and in general you need to prepare your own food *all the time* if you are on a paleo ketogenic diet. Frankly I haven't bothered to try a strict ketogenic diet - I seem to be metabolically healthy. No signs of metabolic syndrome. I don't need to be in ketosis to lose weight, either. I personally appear to maintain a set point without trying (meaning no counting, no ratios, eating as much as I want when I want to, fasting when I want) as long as I don't go off-paleo too much and I get enough sleep, and I feel good, so I don't really have a great deal of incentive to dial it down to ketosis all the time. Also, Paul Jaminet at Perfect Health Diet has a new series about "dangers of a very low carb diet" with some suggestions and interesting questions. Advantages are as I suggested in the first paragraph - they seem to reduce inflammation, enhance energy efficiency (which is more important in the neurons than pretty much anywhere), and decrease hyperinsulinemia and hyperglycemia. Ketogenic diets as many know are being studied for people who are fighting off cancer and I'm looking forward to more literature on that.

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  13. Dr. Deans,
    Thank you for your reply. Good incentive to keep up with the intermittent fasting! Thanks again for such informative and interesting posts.

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  14. Dr. Deans, thank you so very, very much.

    Your generous answers are a great help.

    Your answer to Clarissa fills in some of the pieces as well.

    I quite appreciate your taking the time to write so specifically.

    With best wishes.

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  15. H - I forgot that I did look into protein and cortisol before - most studies I looked at were with casein, and the results were contradictory and confusing, so I wasn't able to wrap my head around it...

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  16. I can't wait to dig into that first article you mention, Emily. Too bad they couldn't extend it beyond six weeks.

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  17. Dr. Deans, thank you for checking on the cortisol. I will keep "sleuthing".

    I appreciate very much your taking the time to help.


    All best wishes to you.

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  18. Have you seen Dr. Mary Newport's case study with her husband, showing improvement with coconut fat for Alzheimer's?

    http://www.coconutketones.com/whatifcure.pdf

    Chris

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  19. Hi again Emily.

    Well, I did what I thought I couldn't do and persuaded the nursing home to change mum's breakfasts to cooked ones and also change her bread to Burgen Soya & Linseed (12g carbs/slice, GI=32), supported by the two studies you linked to above. Mum's much more alert in the mornings now. I've also asked the staff to not give mum too much carbohydrate at lunchtime.

    I'm also in discussion with mum's GP re: Vitamin D3 supplementation etc. See Polite Requests. Sometimes, asking politely but insistently does work.

    I'm considering making mum some tasty treats out of flavoured whey powder and coconut oil, based on Branched chain amino acids as adjunctive therapy to ketogenic diet in epilepsy: pilot study and hypothesis.

    Nige.

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  20. To really work a lower carb diet, and reintroduce good carbs bck into the lifestyle, one with Metabolic Syndrome must work with the liver & pancreas. It is becoming more popular with the American Dietetic Assoc Weight Watchers Jenny Craig and Gary Taubes to say lower carb, lower glycemic scale diet for those with Metabolic syndrome. The one thing they are all missing is the proper amount of carb and the TIMING of carb intake. This is the key component of Diane Kress' work and published almost 2 years ago now!!!!

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  21. The research is now indicating that Alzheimer's is an insulin insensitivity of the brain. Two other non-glucose neurone fuels exist, key tones, and glutamate. Glutamate is also the only way to remove excess ammonia from the brain of Alzheimer's victims.
    By utilizing these and cutting carbohydrate consumption to zero brain energy is restored. It is also interesting that this same diet with no carbs will kill cancer swiftly and effectively.

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  22. Hi Dr. Deans,
    First off thank you for the research on this topic, it is encouraging to me. In 2006 I was working 1700 miles away from home and rushed to the hospital with searing abdominal pain and I just overall had been feeling foggy and lethargic for quite a while, although the excitement of a new job was perhaps masking that feeling, what I found out in that hospital answered many questions for the way I had felt for years. I was diagnosed with acute pancreatitis and found to be type II diabetic. I was 350 lbs at the time I was admitted. My blood glucose was 480 and my triglycerides were 4700. Doctors came in with their students as if I was on display talking about the patient who had been ignoring signs of Diabetes and was really lucky to be alive after been found in the condition I was when admitted. My doctor at home couldn't believe that he'd missed the signs but it had been roughly a year since I'd had blood drawn. They starved me for a week, I lost 30 lbs and I recovered from the pancreatitis but I have struggled with my weight and the diabetes ever since. I'm currently on a couple of injection medications, a 75/25 insulin twice per day and a once a week injection of Bydureon. I've been to several different doctors and all of them promote a diet of 45-60 grams of carbs per meal to include breads and grains which to me seems counter productive, because I always feel tired after a meal with any type of grain or bread or starch. A couple years ago I got my weight down to 217, which I was very happy with, however I ignored what my doctors had outlined for my eating plan and went with a very low carb diet and felt great for that time, like I was on top of my game in every aspect of my life. I honestly don't know how I did it, I was off of insulin for a short time, but for some reason my blood sugars crept back up and because of that I had to go back on insulin. Insulin seemed to be my agent of regression. The hunger and cravings came back followed by the weight, and with the weight came the lethargy, which is difficult for me to deal with as I am a technical manager by day and a student by night, so while I don't have the time to be tired and mentally dragged down, I am, and I clearly see that it is because of the cereals, breads, grains basically all the bad carbs that we as a society have been pushed, prodded and primed for over the last few decades even at times by our own doctors. Somehow I got through 24 credit hours last year and I am headed for at least that much this year, compounded with my work which keeps me on the clock 10-12 hours per day as I have engineers that report to me on east and west coast, makes me a desk jockey for 14-16 hours a day when it's at the worst. When I was younger I had no problem doing this, but as I'm about to turn 43, I'm tired and the weight has crept back up to 277. I know that keeping an active brain is good for helping to ward off Alzheimer's, but I have seriously noticed changes in my mood and a decline in my mental acuity over the last couple of years and I'm concerned that I'm putting myself at higher risk of falling to Alzheimer's later in life because of all this. We've only recently come across Paleo diets which sound like the way for us to go to include using coconut oils, but it doesn't seem to come without some adversity to our schedules and of course, our pocketbook. Among a few other thoughts that I don't need to drag out on here, what I want to be sure to know is, will it be safe for me to take on this new adventure in diet that seems against the advice of my doctors and as such, is it a risk I take on my own or are there people out there to help me through this? Any help and guidance to starting and maintaining this would be GREATLY appreciated!

    Warm Regards,
    Jamison LeBlanc

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