Tuesday, December 09, 2008

Alzheimers and ketones

I was interested in the post Stan put up about medium chain triglycerides and Alzheimers Disease. I particularly like the pictorial record of the clock faces, showing memory improving quite markedly within 37 days.

One of the first posts I ever put up on Hyperlipid was the use of the full blown ketogenic diet for the partial reversal of Parkinsons Disease. As far as I can see AD, PD and ALS are all essentially the same disease, but the genetics of your glutamate receptor subtypes or quirks of your glutamate processing enzymes determine which you get. They're excitotoxin diseases, and Russell Blaylock has the most self consistent hypothesis of their generation that I've come across.

According to Blaylock the glutamate neurotransmitter receptor sporting cells can be driven to a catastrophic energy failure under certain conditions. Adding ketones as an alternative to glucose appears to supply energy to allow both survival and improved function of neurones which are doing very badly on glucose.

Having read Vanitallie's abstract and Marilyn Deaton's account of eating an extreme ketogenic diet, I'd imagined that we would be needing ketones ++++++, ie. off the top of the scale, as for the rather problematic ketogenic epilepsy diet (especially if designed by a cholesterophobic nutritionist).

But Dr Mary Newport got a detectable effect within 24 hours from 40ml, or 350kcal, of coconut oil. Without carbohydrate restriction. That's pretty impressive. BTW, if anyone else has already read this account, are you as puzzled as me as to how Mr Newport could stay in a drugs trial while confounding the outcome, admirably so, with MCT derived ketones? I think this is what the article says, correct me if I am wrong.

So the neuroprotection appears to kick in at very low levels of ketones. It might not even be necessary to go to Atkins induction. Something as mildly ketogenic as the Optimal Diet might just do the job. Although 0.8g/kg/d of carbs will keep you out of ketosis, you certainly have elevated ketones compared to the average person on a modern industrial diet... Plus once you start eating real food without excitotoxins the rate of progress might just slow too. I like to have a few ketones on tap.

And now here comes a complete tangent (that's just how stuff goes sometimes):

While I was googling to find out how ketogenic eating about 10% of calories from MCTs is, when added to a standard diet, I came across this gem from 1984. They fed their rats 5%, 15% or 25% of calories from MCT or long chain fats and measured all sorts of things including weight gain and calorie intake. Look at the calorie intake of the diabetic rats!



For normal rats diet composition made no difference to food intake. For diabetic rats (streptozotocin induced) see how appetite skyrocketed on low fat but virtually normalised with increasing fat content (any fat) by the time fat got up to 25% of calories. The lower the fat content, the more hyperphagic (read HUNGRY) the rats became, the fatter they became too. It just reminded me of the cruelty of telling human diabetics to eat a low fat, high carbohydrate diet and then berating them for their gross gluttony.

People keep inventing the wheel but it keeps getting lost!

BTW 15% of calories from MCTs produces about 0.3mmol/l of ketones in the plasma of a rat. My Ketostix would show 0.3mmol/l in urine as a faint trace. Seems quite modest compared to a ketogenic diet, but certainly delivers something.

Peter

22 comments:

Half Navajo said...

So coconut oil is ok again...i am still confused weather coconut oil is good or bad? I know you don't use it. Maybe i shall stay away from it still for the time being. Time to drink some raw cream and milk...mmmm...

t r o y

Sue said...

"Deaton says her Parkinson's symptoms improved during the original trial, which was conducted in 2003. And losing 26 pounds was a bonus, she says. But even with a more lenient menu on the table, she doesn't plan on signing up again.

She's trying a more conventional weight-loss plan. It lets her eat carrots."

These kind of comments always surprise me. Geez, having her carrots is more important than stopping her parkinson's symptoms.

ItsTheWooo said...

Peter,
I just wanted to thank you for this post because it inspired an experiment that i think has proven very helpful.


Let me preface this post by saying that I have some kind of affective disorder. The disorder I have is possibly a form of bipolar, but most definitely involving depression.

For as long as I have been "regular" low carbing (vs ketogenic) there have been these episodes that seem to plague me. The episodes come on especially at night, especially if I do things that would compromise my level of ketosis during the day. The worst episodes are expected if I stay inside and eat a lot of calories and protein with moderate or higher carb. Staying inside hurts because less activity translates into more blood sugar. Protein and carbs are obvious and do not need explanation.

Well I was having one of those episodes tonight. I didn't go out today and I ate a ridiculous amount of calories and too much protein... I was miserable, agitated, ranting, and hungry, the sort of state I know so well. It's like a knife twisting, it's excruciating, it's impatience and rage, it's fire-like misery... imagine being told something tragic, the shock and activation and anger you would feel. It's somewhat similar to that, except it's precipitated by nothing at all.

I thought of your post and I decided to do an experiment. I made a big bowl of leaves, and I drizzled a bunch of coconut oil and vinegar (vinegar seems to help similar to fat). If these symptoms are caused by too much sugar/not enough fats in my brain, then the coconut oil should help, right? Vinegar should help too since vinegar acts somewhat like a fatty acid/ketone.


Well within minutes of eating this, I felt "sane" again. My thoughts calmed, the dysphoria dissolved into emotional neutrality. The hunger disappeared.
I also experienced a sharpening of senses (vision especially) and increased energy.

It very well could be placebo, but if not I want to thank you so much for this post... these episodes I have are so miserable and painful, if a little bit of coconut oil can help stop it, then my life just improved about 500%.

Peter said...

ItsTheWoo,

A mix of ketones and acetate... I have vague memories of acetate being a short acting GABA precursor or something of that ilk, probably off of Emma's blog. At work at the moment so no time to chase. But might be real...

Peter

darwinstable said...

Great post!!! I was just googling for positive effects of ketones too and found that birds prefer ketone bodies over glucose as it is a far more energy efficient fuel. Of course when your flying around all the time you need to be energy efficient.

Peter said...

Hi ItsTheWoo,

Full post is here

http://blog.plantpoisonsandrottenstuff.info/2008/10/29/gaba-and-diy-for-bipolar-disorder/

Interesting bit is here:

"Raising GABA levels

Ultimately, the way to fix bipolar disorder is to raise GABA levels.

Firstly, a ketogenic diet or low carbohydrate diet can do this. This creates ketones, and the ketones increase several calming neurotransmitters in the brain, particularly GABA levels. This is why a ketogenic diet can help people with epilepsy, which is also caused by too much glutamate/too little GABA.

You can induce some of the effects of a ketogenic diet without having to be on one by taking vinegar. Believe it or not, the main ketone produced on a low carb diet is acetic acid, i.e. vinegar. A tablespoon or two of vinegar before every meal actually produces similar effects to low carbing, and will raise your GABA levels. Unfortunately vinegar is digested and destroyed very quickly, so the effect doesn’t last very long"

Tecnically I guess acetoacetate is a vingar derivative rather than vinegar per se, but you get the idea...

Peter

JB said...

Peter,

I am glad to see the new information on MCTs and coconut oil. I actually brought some to work with me today. I will have to see where I bought it and post it. I purchased about a gallon of it in a tub and I keep it in the fridge. I take a knife and pry loose a chunk, put it in a small jar and drink it at lunch. It looks like white candle wax until I melt it by submerging the little jar in warm water to dissolve it. Tastes great, and what an easy way to get some extra fat calories.

I'd like to see a bit more on this topic if only for this very reason... in addition to butter, cream, and animal fats, it's always nice to find another source of fat for the diet, one that is inexpensive and easy to work with.

Brad

Peter said...

Overall I think I stay about neutral on MCTs. Nothing against them per se, but it just struck me that very mild ketosis was all that is probably needed in the excitotoxin diseases. The other slight caveat I have is that using ketones is not getting at the hyperactivity which leads to cell damage and death. But as a sticking plaster they seem to knock spots off of any current pharmaceuticals.

Peter

ItsTheWooo said...

Hi Peter,
Thanks for that, I completely believe that vinegar helps like a ketone because I always feel better for taking vinegar. It helps both my blood sugar and my crazy.


Today I did another higher fat/lower carb day, and all day I had 0 signs of craziness of any sort. The only side effects were those related to withdrawal, i.e. anger/irritability and headaches (NOTE: sane anger feels a lot different than crazy anger; in sane anger your mind is organized and calm yet irritated; in crazy anger you're just like ADF;LJAER all over the place).

The other side effect is that my moods were just flat, numb, but this may very well be normal. I usually feel like this while fasting (flat and numb). I don't know if it's normal and I'm not used to it. Could be. I'm used to some sort of extreme and irrational mood state being present. I'm not used to feeling nothing at all. Is it normal to feel nothing most of the time?


Another effect is that I have a huge desire to sleep. But I am very sleep deprived so this makes sense. This is the first time in a long time where I feel like I'll actually be able to sleep.


I feel like myself when I used to restrict calories a lot, except I"m not super hungry... but I have all the other signs of being flat, calm, sane, except I'm eating enough food.


This is very exciting for me. I can fix this problem simply by eating less carbs/restricted protein and more fats. Wonderful.

Honestly, though, I don't like this flat feeling. While this is preferred to agonizing misery and extreme almost psychotic horrid thoughts... I feel kind of bummed at the prospect that I won't be able to trigger an amphetamine-like reaction in my brain anymore if I'm deeper ketogenic. I think I'm addicted to that hope of staying up late and experiencing mildly detached thoughts, irrational excitement, chattering away as I furiously do whatever I'm doing. Or, like, the late night dancing sessions, feeling "vast"... I hate to give that up but if it involves getting rid of the really painful torturous crazy type depressions then maybe it's worth it.

Connie said...

Itsthewoo, have you read the beta endorphin chapters of Potatoes not Prozac?

People report "the flat" for about 6 months after quitting carb highs, staying up late highs, feeling vast.

The theory is that when you stop those, your endorphin receptors are still highly upregulated but the endorphins are not there to light them up. Result, flat.

However, over time, IF you do endorphin raisers that are more moderate like dancing, music, great food, then your body will re-regulate. Endorphin receptors go down because there's more endorphin around.

Then instead of "flat" you have a life that is more even and more joyful than ever before. Without the crashes and panics.

Richard A. said...

A discussion about using MCTs for Alzheimer's can be found at --
http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/6111003923

Peter said...

Hee hee ItsTheWoo,

You remind me of Witty Ticcy Ray in Oliver Sacks' book The Man Who Mistook His Wife For a Hat. WTR was a Touretteur who took his haloperidol through the week but took the weekend off, dropping back in to Tourette's syndrome to supercharge his drumming in a jazz band.

Life's a trade off all the time, I certainly don't feel particularly normal, though mood swings are not one of my oddities...

Peter

_flo said...

:)
I kind of experience that too. ON/OD style of eating sets me on a geek mode (or Road Runner at times). I rather retire into reading and studying than take part in social intercourses, which I don't find that enjoyable. Still, better intuition, more in control and ready to please whomever I'm talking to, but it's not that much fun any more. I'm not sure I'm perfectly fine with this.

And it all kind of fits well into JK's historical study on the diet:
- ON => suitable for the sage,
- Eades' => more like the warrior's way of eating,
- USDA food pyramid => well, slaves?

The answer here would be perhaps boosting adrenaline when needed - up the protein and maybe gulp on ethanol (carefully though, so that the liver doesn't shut down)?

ItsTheWooo said...

Hi Connie -
I thought I would clarify that I am not new to a low carb diet and the mood problems are not related to sugar abuse. For years I've been eating 60ish - 70 carbs. The mood changes (chattering/dancing/singing/vastness) I was speaking of were not sugar highs, they were bipolarish-type nuttery. If I eat carbs, I become WICKEDLY depressed so I have no idea what a sugar high even feels like. I honestly have a conditioned fear response of carb food. Mood wise it can only possibly screw me up.

Here's an example. Prior to thanksgiving my mood was sailing higher and higher every week, every day... I was happier than I ever have been in my life, I had stopped having depression and the only mood problems I was having were exacerbation of hypomania (e.g. being unable to concentrate enough to read a paper, feeling so restless I wanted to rip my arms off and beat myself with them lol).
I started drawing again, I started covering my walls with drawings... I was like a different person. It was wonderful.

Then thanksgiving came and I ate a ton of food.

After thanksgiving I was in a coma pretty much, it totally knocked me out for a day afterward. This comatose-like state persisted for about 2-3 days after. Slowly I recovered, and was alert again by day 3 post TG. However, I was not the same. Since that day the happiness died. I am MUCH hungrier, I am often depressive again, I am rarely if ever hypomanic and when I am hypomanic it is not purely euphoric the way it was before. I was really, visciously horribly depressed for a long time after that, and I gained a ton of weight because my hunger was out of control.

Slowly I have been getting better, but that single solitary day of out of control blood sugar/insulin seemed to have an affect on my brain that has persisted for weeks now.
Just one day of severe food intake was enough to shut my brain down. For weeks.

Food has never, ever done anything good for my moods. Other than staving off the unhappiness caused by hunger/starvation, it is impossible for me to actually experience a mood elevation from food, and carbs are the worst offenders.

Prior to finding the LC diet, I was completely insane and non-functional. I had social phobia to the point where I couldn't answer the phone. I could not leave my house. I was constantly excruciatingly depressed. I thought I would die, everyone gave up on me. It was purely a miracle that the diet I selected to lose weight was exactly the sort of diet I needed for both my metabolism and my nuttery.


Ugh, rambling... point is that I'm not going low carb for the first time, but rather I am supplementing with HIGHER fat, lower carb, and lower protein as a means to help control my nuttery.

High fat/low carb/low protein has always helped my mood, both to lift it as well as stabilize it. It pulled me out of the hole I was in at 20 years old, it consistently helps symptoms either become more favorable (i.e. turning dysphoria into euphoria) OR it makes them go away (i.e. turning unstable moods into more consistent/stable).

Since making this change, I seem to be having a much easier time with all forms of nuttery (both depression and hypomania are better, and my sleep is better/less insomnia). This is only day 3, so that's not much time, but I am hopeful.




Regarding the downregulation of receptors... I sure hope that didn't happen because those few weeks were the first time I have ever consistently felt good at all. It would not surprise me if my brain is all screwed up from the unstable moods. The flat feeling could entirely be because my brain is overstimulated from the hard bursts of stimulation caused by nuttery (so my receptors are screwed up). It's kind of like I have an internal source of amphetamines that goes off randomly. Users of amphetamine have screwed up brains that don't respond to normal brain chemicals right, maybe I do too. Even though I felt like crap a lot of the time, perhaps the episodes where I was buzzed were contributing to that.

ItsTheWooo said...

Hi Peter,
That's a really interesting story, I wish I could predictably "turn on" my moods like that. As it is, it seems a toss of up whether or not I get almost psychotic unhappiness, paranoia, guilt, and fear of the future *VS* the most profoundly amazing feeling of insight, inspiration, vastness, energy, motivation, etc. I know certain conditions make one state more likely than the other but it's never absolutely predictable (eating more + no activity = crazy depression... eating less + more activity = euphoric high). No sure way to trigger it, other than really obvious stuff like "not sleeping will help" and "eating too much will make me feel on fire with pain and unhappiness" and "if I eat less and fast and do physical activity I'll probably go crazy in a good way"... there's no guarantees.


It would be nice to be able to 100% reverse-medicate myself though :D.

Stan (Heretic) said...

And it all kind of fits well into JK's historical study on the diet:
- ON => suitable for the sage,
- Eades' => more like the warrior's way of eating,
- USDA food pyramid => well, slaves?


This is fascinating topic. I have no doubts that one's diet does affect the mood. I used to dismiss Kwasniewski's theory re: "slaves" etc but now, after many years, I found that this is most likely true!

My reaction to stress are totally different now, much more benign. On a high carb diet stress used to paralyze me, "deer in the headlight" behavior. Now, on a very high animal fat diet (OD), my reactions are more like that of a warrior. Cold and calculated.

On a high carb diet, strees used to bring total panic. My moods would often oscillate between euphoric (and irrational) and panicky (though much less severe than ItsTheWoo's).

When I talked to an optimal doctor (Dr.Pala) on this subject he said that the effect of OD on schizophrenic patients are very positive. There is a theory on attention-deficit-hyperactive disorder as being a milder form or a precursor of bipolar disorder, and bipolar being a milder form or a precursor of schizophrenia. I have heard of so many stories of OD helping reduce hyperactive disorder that it is IMHO very likely that we are dealing with the entire chain of brain metabolic disorder that has the same underlying common physical cause which responds very favorably (if not curing it totally) to any kind of ketogenic diet.

Rant & Prediction:

When the current generation of dysfunctional "baby boomers" doctors and scientists eventually retire (or die of their unhealthy high sugar diets), we shall see new research developping very effective cures for many psychiatric dsorders, cancers, coronary and auto-immune diseases that all seem to have the common roots. It all will happen very fast. You may have an insight of what is to come by looking at this blog and similiar boards, and by listening to people.

Stan (Heretic)

ItsTheWooo said...

Stan,
Very interesting! It's always fascinating when I meet another person sane-ified by eating LC.

I think bipolar is often related to schizophrenia, but I think it also represents a distinct disease. This sounds paradoxical but, consider it like the obesity/diabetes-heart/vascular disease link. They go together but it is not always true that diabetes/IGT precedes heart disease... or that obesity precedes diabetes. Or that they are even found together always.


On a somewhat related note (to your last paragraph)...
Does anyone else find it ironic that the increase in obesity/diabetes is considered a "real" epidemic by all rational people, but the increase in mental disorders is considered a "fake" one mediated by evil psychiatrists/pharma industries?

The fact that more people today have weight problems and blood sugar problems is obvious... but the increase in depression, bipolar disorder, that's all bullshit made up by industry to pathologize normal human experiences and profit off of your naivete.

Peter said...

Stan, yes, I have more and more time for JKs ideas on national nutrition and behaviour. It was good to see Stephan and Robert Brown put some flesh on it with the omega six data. I look at people and tend to make mental notes about how they eat and what problems they might have. Talking to my boss about a case the other day I went on something like: "Do you remember the labrador with such and such, belonged to Mr Jones, the owner with metabolic syndrome..."

Retort: "do you look at everyone in those terms?"

Err, well, yes. I'm a clinician. I use the data my eyes give me all the time. Well before the lab numbers come in... That's just how my brain works.

ItsTheWoo,

I think the diseases are all real enough. I think SSRIs can be life saving for a very small percentage of people. For most they are placebos. There are, as you probably know better than most, enormous influences of diet on mental state. Have you seen the ancient stuff on fasting and schizophrenia? Whether this acts through ketosis (AKA B3 at pharacologic doses), gluten withdrawal, casein withdrawal or all three plus other things I don't know, but it does something.

Peter

ItsTheWooo said...

Peter,
Very interesting about fasting and schizophrenia. I would assume it worked because starvation depletes dopamine, similar to antipsychotic medication. This would be primarily a symptom-based approach.

For some people food restriction actually increases dopamine (e.g. people vulnerable to compulsive starvation and anorexia nervosa). For MOST people, it will lower dopamine.



I feel like food restriction changes where and how dopamine acts in my brain... when eating very excessive calories/carbs / protein I'm attacked by these extreme feelings of guilt and the most desperate unhappiness and self hatred... the extreme and irrational nature of these thoughts imply some sort of dopaminergic root. Yet, paradoxically, I lack "good" signs of higher dopamine in terms of creativity, novel thinking, motivation, energy, lower appetite etc. I only experience THOSE when eating very high fat, moderate protein, low carb, with moderately restricted calories.



Lately I've been wondering about the use of insulin shock to treat psychosis before thorazine was invented. I can't help but notice that all meds which treat psychotic nuttery seem to induce hyperinsulinemia directly (e.g. insulin shock) or indirectly (e.g. antipsychotic medications). It's been shown in studies that the disease of obesity involves suppression of the action of dopamine in the brain. In animals dopamine levels determine metabolic state, dopamine in the brain tells the animal what season it is and how to use nutrients/how fat to get. This is also true of melatonin (that is, melatonin lowers dopamine and raises insulin; insulin tends to raise melatonin by turning more tryptophan into melatonin as opposed to serotonin).

Hyperinsulinemia is a depressant. It turns off the brain. It bugs me when people say they eat to treat their depression. This is neurochemically impossible. Eating for stress makes perfect sense (insulin depresses brain activity) but eating for depression is like taking a benzodiazapine to try to reduce depression... nonsense.

Anyway... rambling. Perhaps there is a mutual feedback relationship between insulin and dopamine... the higher the insulin, the lower the dopamine, and the lower the dopamine, the higher the insulin.




So it seems that starvation OR high insulin can help suppress dopamine action. Makes sense, since dopamine tells the metabolism "work really well", high insulin and starvation should terminate any signal that tells metabolism to use food / fat for energy.

cavenewt said...

This whole discussion is very interesting to me. I've been having strange symptoms for about 10 years (increasing asymmetric tremor, fasciculations, muscle cramps) that were misdiagnosed as various benign things. Last year when I suddenly (as in overnight) lost the ability to extend 3 fingers, and then spent a week at the Mayo, they diagnosed me with MMN (multifocal motor neuropathy), a rare condition where your immune system attacks peripheral (mostly motor) nerves. It's known as an ALS mimic, but is not generally fatal and only involves peripheral nerves. The only real treatment for it is IVIg (intravenous immunoglobulin) which will only prevent it spreading, if I'm lucky. IVIg costs $thousands per semimonthly treatment.

So after running across the coconut oil/Alzheimer's article, and the New York Times pediatric epilepsy article recently, I have gotten interested in ketosis and how it might protect the nervous system. Various threads led me to your blog.

Coincidentally, I read Good Calories Bad Calories a couple of years ago and have been fairly low-carb for that amount of time. I have never been obese or prediabetic, rather was skinny my whole life. But I used to enjoy a pound of Cheetos as an evening snack :)

Three weeks ago I decided to try ketosis to see if it makes any difference in my condition. I try for about 6g or less of carb per day. The involuntary muscle twitches that could keep me awake at night seem to have calmed down, but of course it's impossible to say if it's the diet or the latest round of IVIg kicking in. My last treatment was 2.5 weeks ago, next one in 1.5 weeks.

What bothers me is the immunoglobulin they give me is d-sorbitol based. I knew some brands were glucose-based and I requested NOT to be given that. But now I wonder if sorbitol can sabotage ketosis? Especially to have it dumped directly into the bloodstream?

My Mayo neurologist seemed pretty generally open-minded, and I'll talk to him about this when I go back in three months. In the meantime, I would be interested to see what you think about either the ketosis/MMN, or the d-sorbitol/ketosis, or both.

George Henderson said...

Scientists should have this tattooed on their foreheads:
"REMEMBER THE WHEEL"

BTW, the acetate info makes all the cider vinegar sceptics look a bit premature. It may not be what the enthusiasts say it is, but it is something after all.

TJ Melville said...

I am also trying ketogenic diets to help with possible bipolar (or really bad PMS). I tend to the more depressed side which expresses itself as rage episodes. I tried getting into ketosis but without much luck. I'm pre diabetic with a high baseline blood sugar level, try as I might I could not seem to produce ketones above 0.4. Now I'm going to try again with MCTs and vinegar. I get massively depressed and flat on moderate carbs. Thing is when on a KD my blood sugar levels goes into diabetic range and the higher the fat, the longer my BS levels stay elevated, the worse the FBG level etc etc. so it's a trade off, diabetes vs bad moods...which to choose ?