Friday, July 11, 2014

Neuron fuel and function

In the comments following a previous post Dustin linked to this rather lovely paper from the early 1970s, back when I was still at school and marathon racing my kayak.

This is one of the nicest figures:

























The lower section is the interesting part. CJ had not eaten for 50 days and had a (very) fasting blood glucose of 4.0mmol/l when he received around 0.1 IU/kg of insulin by intravenous injection. Please don't try this at home. You can see that a) he is still insulin sensitive and b) his blood glucose bottomed out at around 0.5mmol/l by 60 minutes. Throughout this period he was asymptomatic. No hypo.

CJ was not running his brain on glucose. The upper section shows a rapid and sustain increase in B-OHB extraction (the dark hatching between the arterial line and jugular bulb line for B-OHB)  by his brain through this period of time. Ketones, at levels in excess of 11.0mmol/l, can sustain apparently normal brain function. Given an alternative fuel source this would seem to put the level of blood glucose needed for normal neural function at some (non determined) value of less than 0.5mmol/l.

Drenick et al did not look at fatty acid extraction by the brain. That's a pity, but understandable. No one expects the brain to metabolise palmitic acid. Well, perhaps we should say that neurons should not metabolise palmitic acid. Astrocytes do. Astrocytes are ketogenic and are in a perfect position to supply ketone bodies to neurons using the monocarboxylate transporters ubiquitous on them. I hope to come back to this by the end of the post.

Of course, a 50 day starvation period is not exactly the normal human predicament and we could argue that the normal human brain is glucose dependent. This too, I think may be a very debatable point.

Work has been done with humans under hypoglycaemia with brain function supported by either lactate or pyruvate by intravenous infusion. They're fairly effective, not perfect, but there are limits in how far you can push the metabolism of human volunteers.

Rats are not so fortunate.

If we go to Figure 1 from the rather nice paper emailed to me by Edward

























we can see that, under the influence of a massive 20 IU/kg of insulin, there is an almost complete loss of plasma glucose and a slightly more complete loss of brain response to limb stimulus in the insulin-only, profoundly hypoglycaemic group, top row of  section A. This has occurred by two and a half hours. The next row has had the hypoglycaemia corrected with glucose (i.e. it's essentially a control group) and has a normal response to stimulus at 4 hours. The lower row shows the effect of lactate in supporting brain function during four hours of persistent, profound, uncorrected hypoglycaemia. You have to note that progress from left to right is time in milliseconds after stimulus and that there is a clear cut delay of about 10 ms in the response time under pure lactate compared to under glucose. This is reiterated in section D, where the response can be seen to be delayed and blunted when compared to the glucose supported data of curve C.

This has led the authors to speculate that, heresy of heresies, there may actually be an absolute need for some glucose by the brain! Strange I know, but... They're not sure of this, just speculating. There are other potential explanations.

Now, most people do not walk around with a blood lactate of 9.0mmol/l. Perhaps most people really do run their brain on glucose?

This seems very unlikely. Or, rather, it seems very unlikely that the neurons in the brain run on glucose. Astrocytes certainly do. But one of the main functions of astrocytes appears to be to manufacture lactate from glucose (directly or from stored glycogen) and deliver it to neurons as a one step conversion fuel giving pyruvate, which can enter the TCA as acetyl-CoA without any messy glycolysis. There is an awful lot of information in this paper.

I put up this nice illustration previously, in the Protons thread:























Neurons are spared glucose. Why?

Mitochondrial glycerol-3-phosphate dehydrogenase. Glucose, during glycolysis, is quite able to input to the electron transport chain through an FADH2 based input at mtG3Pdh, which can reduce the CoQ couple and set the ETC up for reverse electron flow through complex I, with the generation of superoxide as this occurs. Modest superoxide is a Good Thing, especially if you want to signal for mitochondrial biogenesis or cell division. Excess superoxide is a potent signal for apoptosis. Apoptosis is verboten for CNS neurons because any information stored in their synaptic connections will be lost along with the cell. Replacing the cells will hardly replace the memories and appears equally forbidden. There is a need for immortality without reproduction in neurons, for their survival in excess of the lifespan of an organism needing a functional memory in a learning brain.

Feeding lactate through pyruvate to acetyl-CoA does not drive CoQ pool reduction "ahead" of the throughput of electrons coming in from complex I. Neurons do not want to generate insulin resistance. Avoiding glycolysis looks (to me) to be the way they do this. Generating hyperglycaemia looks like a way to overcome the normal lactate shuttle and of forcing glucose directly in to neurons. Enough apoptosis and eventually neural loss just might show as memory loss.

Hyperglycaemia and Alzheimer's...

Generating large amounts of superoxide in astrocytes during glycolysis is not damaging to the neurons supported by the derived lactate. Astrocytes are certainly replaceable, although there seems to be some debate about cell division vs stem cell recruitment. Astrocytes are also able to divide unreasonably rapidly and form various grades of brain tumour. They are common and frequently aggressive. Neuron derived tumours are much rarer and are usually derived from embryonic cells giving medullablastomas rather than being derived from mature neurons. That seems to fit the metabolic arrangements in the brain rather neatly.

This takes us back, eventually, to palmitate as a ketogenic energy supply to the brain via astrocytes. Again, an FADH2 input through electron transporting flavoprotein dehydrogenase can couple with hyperglycaemia to generate reverse electron flow through complex I giving excess superoxide generation. I consider this to be why free fatty acids are excluded from neurons. It's not that FFAs generate excess superoxide per se, they don't. But combined with hyperglycaemia they certainly do, especially palmitate and the longer of the saturated fatty acid series. You really don't want this happening in a cell whose remit is immortality.

Ketones and lactate do not drive reverse electron flow through complex I. Glucose can. Palmitate certainly can. What you want from a metabolic fuel depends on the remit of your cell types. Neurons within the brain preserve information by their continued existence. This is best done by burning lactate or ketones. NOT glucose and, of course, not FFAs. Anyone who claims that glucose is the preferred metabolic fuel of the brain has not though about what a neuron has to do and what an astrocyte actually does do. Or much about the electron transport chain.

Peter

40 comments:

gallier2 said...

Wow, this is huge. It feels like a 7-1 in half-final of the WC with Peter being Germany and the mainstream researchers being as clumsy as Brasilian players, i.e. good football players with no vision of the game.

I

valerie said...

Little typo towards the end of the post:

"You really don't want this happening in a cell who's remit is immortality."

"Who's" should be "whose".

Lowcarb team member said...

Jeez

Why Rome burns, Valerie fiddles.

Eddie

raphi said...

this is the crux of the argument nutrition science needs to come to terms with if is to progress at all.

small bellies easily digesting high-kcl nutrient dense foods provide great fuel for an animal who doesn't eat for days and has a big brain with a lot of memories, kept in cells who like to live in a goldie-locks ROS equilibrium.

Ned Kock said...

Hi Peter. Posts like this remind of the variations in glucose and ketone levels in the child with glycogen synthase deficiency discussed by Williamson, which I think you mentioned here in a previous post:

http://bit.ly/hqOTCY

Nigel Kinbrum said...

Hmmm,

Do you want low fasting glucose, insulin, cholesterol etc, as per http://www.ncbi.nlm.nih.gov/pubmed/10535381?
"For example, the mean insulin concentration in 50-to-74-year-old Kitavans was only 50% of that in Swedish subjects."

Well, just do this:- http://www.staffanlindeberg.com/TheKitavaStudy.html!
"The residents of Kitava lived exclusively on root vegetables (yam, sweet potato, taro, tapioca), fruit (banana, papaya, pineapple, mango, guava, water melon, pumpkin), vegetables, fish and coconuts. Less than 0.2% of the caloric intake came from Western food, such as edible fats, dairy products, sugar, cereals, and alcohol, compared with roughly 75% in Sweden. The intake of vitamins, minerals and soluble fibre was therefore very high, while the total fat consumption was low, about 20% E, as was the intake of salt (40-50 mmol Na/10 MJ compared with 100-250 in Sweden). Due to the high level of coconut consumption, saturated fat made up an equally large portion of the overall caloric intake as is the case in Sweden. However, lauric acid was the dominant dietary saturated fatty acid as opposed to palmitic acid in Sweden. Malnutrition and famine did not seem to occur."

It was a high-carb (about 70%E), low-fat (about 20%E) diet, but with no Western junk. Food for thought, eh?

G'night!

Peter said...

Many thanks valerie, fixed.

Peter

Nigel Kinbrum said...

Hat-tip to Paleo & Zone Nutrition for posting this on Facebook...

http://www.ncbi.nlm.nih.gov/pubmed/24365581
"CONCLUSIONS: These data suggest that a dietary pattern characterized by a low amount of carbohydrate, but reciprocally higher amounts of fat and protein, is associated with poorer vascular reactivity in patients with Metabolic Syndrome and T2D."

Any comments, Peter?

Michael Frederik said...

"Individuals in the lowest LCDS quartile (Q1; 45% carbohydrate, 19% protein, 31% fat) had higher saRHI values than those in the top quartile (Q4; 30% carbohydrate, 25% protein, 43% fat) (1.84±0.42 vs. 1.55±0.25, P=.012)."

30% carbohydrate, 25% protein, 43% fat. Hey, that's the Perfect Health Diet (TM).

ItsTheWooo said...

This is great Peter.

I have read seizure control in epilepsy reflects lactate elevation, which is part of the end goal of obtaining ketosis for neurological conditions like epilepsy . If palmitic acid is ketone delivery vehicle for brain via astrocyte metabolism this explains so much like why cal restriction and fasting is can be superior to calorie replete hf keto diet. It is often observed calorie restricting epileptic children may control seizure better than cal adequate keto, perhaps body fat is more ketogenic in the CNS than dietary fats.

It also explains paradox like why plant based cultures live long with great memory...plant based is almost always hypocaloric more palmitic acid use via low energy consumption of dietary energy. It appears carbs are okay if you starve yourself every once in awhile or every day so taht you force your body to use palmitic acid to feed your brain.

Perhaps the reason there is a lactate elevation in ketosis is because of increases palmitate ketogenesis in brain? This might ironically be glucose sparing in brain , more glucose metabolism into lactate by astrocytes. So, the keto diet is not great for CNS because it reduces glucose but ironically it increases glucose metabolism into lactate specifically in CNS via palmitic acid and ketones in the serum .

I think this explains a lot like why serum ketones are pretty much useless for predicting nervous system response to ketogenic diet. A serum ketone of 0.6 is extremely low, but in the CNS, this might be highly ketogenic with flourishing lactate if that 0.6 is achieved via a fast and ample palmitic acid-> ++lactate/ketones superior CNS energy, less seizures, better mood/memory.

raphi said...

https://db.tt/LbVUiIQD --> "Low-carbohydrate, high-protein, high-fat diet alters small peripheral artery reactivity in metabolic syndrome patients" in full-text (ssshh!)

Consider 1, 2 & 3 so you don't waste too much time:

1) LCDS (low-carb diet scores) divided into quartiles; LCDS1=45%CHO, LCDS2&3=36&, LCDS=30%...once again LC = 30-45% CHO. Rationale for such a division?
===> "LCDS has successfully been employed to show that a low carbohydrate diet is positively associated with the risk of type 2 diabetes (T2D) in a large cohort of healthy men after 20 years of follow-up" --> citing ref. 25 = which is a prospective cohort study arguing "high animal protein and fat was associated with an increased risk of T2D") = old weak blablabla..


2) "While differences in endothelial function biomarkers did not reach statistical significance, they varied in the same direction. In essence, patients consuming carbohydrate-poor diets had the worst vascular and risk profiles" = underwhelming so shake the statistical wand for scarier outcomes/markers

3) "Errors associated with completion of food diaries are possible, such as undisclosed supplemental use of omega-3 fatty acids and polyphenols. Although undescribed, either the pharmacological agents that our patients were taking themselves, or interaction with macronutrient changes, could have influenced small artery vascular reactivity. Last, a cross-sectional study cannot establish causality. In view of the strength of our main finding, the quantitative importance of these limitations appears small." = so, lets presuppose OM3's & meds aren't worth controlling for when assessing VASCULAR FUNCTION (give me a break...)

raphi said...

- back to the subject at hand -

@Woo,

"Perhaps the reason there is a lactate elevation in ketosis is because of increases palmitate ketogenesis in brain?"

They (PMID: 11043913) say "brain BHB rises significantly with 2- & 3-day fasting-induced ketosis. The lactate increase likely results from ketones displacing lactate oxidation without altering glucose phosphorylation and glycolysis".

Furthermore, based on (PMID: 22078747) I'd add the role of Lactate signaling to say '''what's up''' via:
"Although hippocampal mitochondria have been found to produce less ROS in animals fed a KD for at least 1 week, substrate-driven H2O2 production was observed to be increased in hippocampal mitochondria from KD-fed rats compared to controls after only 1 day on the diet. Acute production of H2O2 may play an important role in the KD, as it has been shown to serve a redox signaling role, in addition to its more
notable role as a damaging species (Fig.1 --> https://db.tt/gC67eYyd)

Bob said...

"small bellies easily digesting high-kcl nutrient dense foods providing great fuel for an animal who doesn't eat for days and has a big brain with a lot of memories, kept in cells who like to live in a goldie-locks ROS equilibrium." (edited ever so slightly)

raphi, that is almost poetry!

Nigel Kinbrum said...

raphi,

So you don't think much of that study I posted a link to?

Would you like to take a close look at the 28 studies at the end of http://nigeepoo.blogspot.co.uk/2014/06/ultra-high-fat-80-diets-good-bad-and.html?

Cheers, Nige

Dustin Sikstrom said...

You did a far better job of explaining that paper than I could have, plus more. Thanks Peter. Glad to have been able to contribute something to your knowledge that is far larger than mine.

Also:

> Anyone who claims that glucose is the preferred metabolic fuel of the brain has not though about what a neuron has to do and what an astrocyte actually does do. Or much about the electron transport chain.

Excellent point that will stop most people in their tracks. It may go over their heads so you might not get the point through, but at least they stopped. Haha.

Side note: in the reddit /r/keto community we talk about adaptation taking 8-12 weeks for physical performance. Any comment on how long you think mental performance may take? 3 weeks seems to be when people feel better running on ketones. Rat studies show the brain soaks up any present ketones (in vitro, sorry no citation right now, I could find it if you're not sure which one I'm referring to, apologies for vagueness). Perhaps the brain prefers ketones over everything else but it requires carbohydrate restriction to produce ketones? If that's the case, supplemental ketones may be the next big thing. Dr. D'Agostino seems pretty excited about them considering they have supplemented navy SEALS and got great results without carbohydrate restriction:

http://www.bengreenfieldfitness.com/2013/10/deep-dive-ketosis-navy-seals-extreme-athletes-busy-executives-can-enhance-physical-mental-performance-secret-weapon-ketone-fuel/

And more including PubMed:

http://highsteaks.com/forum/topicseen./health-nutrition-and-science/ketone-esters-supplements-557.msg3192.html

Either way, it almost looks like ketones are metabolized before glucose in the brain and that they provide many benefits there. Any thoughts?

Larcana said...

Thanks for the great post! As an anecdote, I've noticed on my nursing home rounds, that many a demented patient is placed on Namenda but continues to eat a very high carbohydrate based diet.
Namenda was marketed to doctors under the indication of moderate to severe dementia. But even mild memory impairment can get them placed on it.
At that point it's like a bandage over a surgical dehiscence, eh? Patients and their families are not aware of the benefit of ketones and would likely chose diet change over yet another drug.

ItsTheWooo said...

It kills me knowing that a keto diet would likely arrest and even reverse some dementia...but instead they are given statins, aricept/namenda, insulin and lots of refined glucose.

ItsTheWooo said...

We need a Facebook group for medical professionals disgusted by lack of keto diet application watching ppl disabled by strokes and diabetes of the brain into invalid status

Nigel Kinbrum said...

I can only comment on Lewy Body Dementia (an α-synuclein protein disease) & the related Parkinson's Disease Dementia, but putting my mum on a ketogenic diet (which had a lot of initial problems, due to some care staff not understanding terms like "No sugars & starches". "This rice pudding's O.K, isn't it?" SMH.) gave her a dual-fuel brain.

Although a ketogenic diet improved her mental faculties, it didn't halt the progression of her disease. It only "turned back the clock" for a while.

Jack Kruse said...

Parkinson's is a prion like disease Nigel and that is why she did not get full benefits. DHA is the key to the brain's keto template. Peter is knocking a real big door here. I hope it wakes up some people. Not all ketotic templates are thermodynamically the same. People seem not to understand this. This is why mitochondria in brain and heart resist apoptosis and live for autophagy.

Nigel Kinbrum said...

Jack Kruse said...
"Parkinson's is a prion like disease Nigel and that is why she did not get full benefits. DHA is the key to the brain's keto template."
She was being given 10ml/day of Seven Seas high-strength Fish oil with EPA & DHA. See http://nigeepoo.blogspot.co.uk/2009/03/look-after-your-brain.html and http://nigeepoo.blogspot.co.uk/2011/02/mums-proposed-ketogenic-diet-for.html

Some broken things can't be fixed.

Nigel Kinbrum said...

I nearly forgot...

See http://paleozonenutrition.com/2011/10/12/my-current-view-of-the-zone-diet/#comment-31414
"But, your blog post explains to me why this happened and I very much appreciate that. You get fed so much “carbs are evil” from the paleo world to the point that you feel like a failure when you don’t lose weight/sleep perfect/turn into a fitness model just “doing paleo.” I don’t ever lose weight eating paleo, feel like I’m starving even after eating a ton of protein or fat, and then I crash and burn every couple of months into a huge sugar binge that goes on for weeks or months."

The correct answer to the question posed at the top of your blog is:-
Both. As to the amounts of each, it all depends.

Tod Rosenthal said...

Eddie/lowcarb team member--

While Rome burns... vs. Why Rome burns....

$20 says Peter appreciates the Who's Whose catch.

Jane said...

Peter, I'm not sure what you say about neurons and glucose is quite right. Here's what Wikipedia says about it.

"The central role of [glucose transporter] GLUT3 in cerebral metabolism has been challenged by the astrocyte-neuron lactate shuttle (ANLS) hypothesis,[6] which proposes that astrocytes play the key role in the coupling of neuronal activity and cerebral glucose utilization. In this hypothesis, the astrocyte, which relies on GLUT1 for glucose transport, is the primary consumer of glucose in the brain, providing lactate as the primary energetic fuel for neurons. However, by modeling the kinetic characteristics and glucose concentrations in neurons and glia, it was concluded that the glucose capacity of neurons via GLUT3 far exceeds that of astrocytes via GLUT1.[7] Additionally, demonstrations of increase in GLUT3 expression associated with increased cerebral glucose utilization provides further confirmation of the central role of GLUT3.[5]"
http://en.wikipedia.org/wiki/GLUT3

My understanding is that neurons only use lactate because they need most of their glucose for the pentose phosphate pathway to produce NADPH and keep their glutathione reduced.

ItsTheWooo said...

Nigel - my understanding is LBD is not like alzheimers or cardiovascular dementia which is by FAR the most common types, LBD is more like an autoimmune disease and is progressive and often rapid onset in nature, which is why a keto diet would not help in this instance. LBD is more like prion disease like Jack Kruse stated. It's a death sentence and often is rapid.

OTOH the vaaast majority of elderly dementia patients have common alzheimers (which is related to insulin deficiency in the brain and neurodengeration that is slow steady and progressive) or they have cardiovascular dementia, which involved plateus and rapid sudden declines in cognition which is secondary to vascular insults/mini strokes in the brain that occur randomly. IN these cases, ketogenic diet has way more potential to help as it will help the brain heal from insults and provide alternative/superior fuel sources in insulin deficiency (alzheimers) or from vascular trauma (vascular dementia).

ItsTheWooo said...

http://en.wikipedia.org/wiki/Dementia_with_Lewy_bodies Not offically autoimmune but this clearly different from common alzheimers/vascular dementia.

IT appears to specifically attack cholinergic system (dementia) and substantia nigra (parkinsons) and seems more of an autoimmune like process in comparison to the other dementias that clearly destroy the brain as an entity.

Galina L. said...

I really wish keto diets would be used more for mental conditions, but at the moment the step #1 should be the hard look at statines as a significant contributer to mental impairments especially for old people. Recently another person thanked me for bringing his attention a year ago to sertain side effects of Lipitor which was prescribed to his dad for preventive purposes. The old guy started to age faster, developed memory and speech problems. After the discontinuation of Lipitor, he feels much better - his speech is back to normal, muscles weisting got reversed, memory improved.

Galina L. said...
This comment has been removed by the author.
Nigel Kinbrum said...

ItsTheWooo said...
"Nigel - my understanding is LBD is not like alzheimers or cardiovascular dementia which is by FAR the most common types, LBD is more like an autoimmune disease and is progressive and often rapid onset in nature, which is why a keto diet would not help in this instance. LBD is more like prion disease like Jack Kruse stated. It's a death sentence and often is rapid."
Hi. I'm glad we're on speaking terms again. I don't visit your blog any more, which is why I don't annoy you any more! :-D

My response to Jack Kruse was to refute his suggestion that DHA would have made all the difference. He assumed (as per usual) that I'm some kind of idiot who doesn't know what I'm doing. Can you sense the sarcasm oozing from my words?

LBD is in-between Alzheimer's & new variant Creutzfeldt–Jakob disease in terms of life expectancy, with a MTTD of 6 years.

Cheers, Nige

Praveen RS said...

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Lechuza Planters

Jack Kruse said...

This came from my forum regarding ketosis: Momma28 says, "Truly the brain does HEAL in Ketosis! Testimony of a Two Year old!
The story begins in January of this year when I am given custody of a 16 month old nephew lost to the system by a drug abusing, alcoholic mother. I'd only seen him once before this. He made no eye contact or any attempts at physical connection. He had jerky, palsy-like movements and seizures intermittently throughout the day. He weighed 18 pounds and was 28 inches tall; just 46th percentile on the growth charts. He would only eat bananas, white bread toast and commercial milk that was being microwaved and put in a bottle, oh, and of course, soda. He had by this time been given 22 vaccines.

His first week here I let him choose what he would eat to ease him in with the other 6 kids and let him acclimate. The second week it was on....nothing was offered but what I wanted him to eat. Three days later and lots of tantrums and shed tears and he was eating meats for the first time in his life. He was given watered down Welch's with D3, Iodine, a multivit liquid and probiotics in it throughout the day. He was also given a B12 transdermal patch. His diet was fresh veggies all loaded with organic butter or bacon fat. Meats were offered with each meal and he soon grew to love them. All seizures halted within the first week most likely due to lack of dietary fats. His palsy-like movements have gradually ceased as well and have become much more normal. In fact, his balance has more than improved, its incredible.

It took him 6 weeks to learn his name. Since then, he has learned so much more...body parts, animals, fruits and veggie names and songs. His cognitive function, that was about an 8 month old, is now just slightly behind his 2 years that he turned last week. He has been on a ketogenic diet for 8 full months now and today is 30 (77th%) pounds and 34 (87th%)inches tall. He has grown 6 inches and gained 12 pounds in 8 months! Unheard of! He makes eye contact, responds to facial...

Jack Kruse said...

Nigel Kinbrum said...
ItsTheWooo said...
"Nigel - my understanding is LBD is not like alzheimers or cardiovascular dementia which is by FAR the most common types, LBD is more like an autoimmune disease and is progressive and often rapid onset in nature, which is why a keto diet would not help in this instance. LBD is more like prion disease like Jack Kruse stated. It's a death sentence and often is rapid."
Hi. I'm glad we're on speaking terms again. I don't visit your blog any more, which is why I don't annoy you any more! :-D

My response to Jack Kruse was to refute his suggestion that DHA would have made all the difference. He assumed (as per usual) that I'm some kind of idiot who doesn't know what I'm doing. Can you sense the sarcasm oozing from my words?

LBD is in-between Alzheimer's & new variant Creutzfeldt–Jakob disease in terms of life expectancy, with a MTTD of 6 years.

You must upgrade your game Nigel. Not all versions of ketosis are thermodynamically the same. Those with DHA alter CNS pathologies. I dont think you're a moron. I think you suffer from poor thoughts on some things. Humans are social creatures. We are born physically, neurologically, and epistemologically dependent on others, for evolutionary reasons. Therefore, we do not build our worldview directly from nature as all other animals do. We learn primarily from elaborate symbolic communication with other humans.Many ideas are put in our heads by others with out you thinking much about it.It is a great shortcut that allows advanced knowledge to be additive across many lives and lifetimes. A uniquely human neurological adaptation. But our greatest asset is also our greatest blind spot. Since much of our knowledge is predominantly “absorbed” in this way, through language and concepts, rather than fully experienced and verified firsthand, it leaves us extremely vulnerable to potential manipulation by other humans, whether intentionally or unintentionally. The most useful piece of learning for the uses of life is to unlearn what is untrue.
Truth happens to individuals not to crowds.....http://www.sciencedaily.com/releases/2014/07/140722091603.htm

CITES:
http://www.lipidworld.com/content/pdf/1476-511X-12-16.pdf
http://www.nature.com/.../v35/n11/full/npp201098a.html
http://www.ncbi.nlm.nih.gov/pubmed/22057807
http://www.ncbi.nlm.nih.gov/pubmed/22316559
Guess how this mechanism works? DHA. DHA breaks down into protectins resolvins and maresin's. The more DHA you have in cell membranes the better you respond. http://onlinelibrary.wiley.com/.../j.1471-4159.2007.../full

Jack Kruse said...

The key is what an electron does to a protein. All foods ae broken down to electrons. DHA captures electrons on cell membranes to assimilate and move them properly. Electrons ionizes protein 3D molecular size and shape to change its function. This is how all prion disease begin. Read about Stanley Prusiner and his Nobel. That is why the movement of electrons can take 20 amino acids and 23,000 genes made from those amino acids and make millions of different proteins. The addition or subtraction of said electrons determines the proteins final chemistry by bending it and shaping it to give it is function. This is the beauty of thermodynamic compliant design. It is the quantum mechanism that all life uses to function. When you realize this you see how physiologic function changes as the environment of electrons around it changes. Nature is the driver of nurture. The building blocks are the template we alter with the information from the environment. This is why circadian biology determines the function of how a mitochondria can and can't work. The size and shape change determine the virulence of the prion disease. Your family members disease was due to this mechanism. You just refuse to scale you knowledge to the quantum scale to understand it. I am under no obligation to make sense to people like Nigel. My obligation is elevate their thinking above where it is now by challenging their current beliefs.

August said...

It seems to me the great confusion with prion disease is not so much how it begins, but how it continues. Wasn't there some argument a while back that there must be a virus or something that hasn't been identified yet which is keeping the process going?

Amy Berger said...

This is such freaking good stuff, Peter! Really fascinating. I invite anyone who's interested in this kind of thing to read my article on Alzheimer's as type 3 diabetes, and the potential therapeutic role of keto and/or low-carb diets. (Whatever your opinion of the Weston A. Price Foundation, their publication is where my work happens to appear this time.) You can read it on their website, but their online formatting is awfully screwy. Feel free to email me privately and I can send you a pdf that is much more aesthetically pleasing in terms of where the sidebars fit in and how everything flows. (tuitnutrition at gmail dot com)

The WAPF version is also a little condensed...the original paper has slightly more scientific detail, especially regarding how the beta-amyloid plaques often seen as a "cause" of AD are actually an *effect,* and, in fact, they're a *protective mechanism* in many ways. The plaques seem to be shutting off glucose metabolism as a failsafe just to keep neurons alive in the face of tremendous glycation and oxidative stress (due to a lifetime of dietary CHO abuse), but because there is no other energy substrate available (i.e. ketones), the neurons essentially starve to death.

http://www.westonaprice.org/modern-diseases/type-3-diabetes-metabolic-causes-of-alzheimers-disease/

You can find AWESOME coverage of all this in this paper as well:
http://people.csail.mit.edu/seneff/EJIM_PUBLISHED.pdf

Really can't recommend it highly enough.

Amy Berger said...

(Hope this doesn't double-post...I think I messed up the captcha the first time.)

This is such freaking good stuff, Peter! Really fascinating. I invite anyone who's interested in this kind of thing to read my article on Alzheimer's as type 3 diabetes, and the potential therapeutic role of keto and/or low-carb diets. (Whatever your opinion of the Weston A. Price Foundation, their publication is where my work happens to appear this time.) You can read it on the website, but their online formatting is awfully screwy. Feel free to email me privately and I can send you a pdf that is much more aesthetically pleasing in terms of where the sidebars fit in and how everything flows. (tuitnutrition at gmail dot com)

The WAPF version is also a little condensed...the original paper has slightly more scientific detail, especially regarding how the beta-amyloid plaques often seen as a "cause" of AD are actually an *effect,* and, in fact, they're a *protective mechanism* in many ways. The plaques seem to be shutting off glucose metabolism as a failsafe just to keep neurons alive in the face of tremendous glycation and oxidative stress (due to a lifetime of dietary CHO abuse), but because there is no other energy substrate available (i.e. ketones), the neurons essentially starve to death.

http://www.westonaprice.org/modern-diseases/type-3-diabetes-metabolic-causes-of-alzheimers-disease/

You can find AWESOME coverage of all this in this paper as well:
http://people.csail.mit.edu/seneff/EJIM_PUBLISHED.pdf

Really can't recommend it highly enough.

Nigel Kinbrum said...

Jack,

Some things that you write about make sense. Congratulations.

When you start gong on about electrons, quantum mechanics, EMF's etc, you just sound like a total nutter. I'm a retired electronic engineer, so I know electronic BS when I see it. And I've seen a lot of it on your blog!

Stick to what you know and don't BS people with stuff you've just pulled out of your ass.

K?

George Henderson said...

Prions - mitochondrial protein MAVS activates interferon synthesis by prion generation.
In theory CNS viral infections could be a trigger for prion-type diseases if this system becomes disregulated.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179916/
That could be conceptualised as an innate immunity form of automimmune disease, as opposed to auto-antibodies.

Stan (Heretic) said...

Fascinating! Many interesting implications.

1. Blood glucose below about 60mg/dl must thus be risky only for people on high carb diet, not on ketogenic diet.

2. Long term diet high in both fat and carbohydrates damages the brain - which is exactly Dr. Kwasniewski's thesis! His way of putting it was describing a syndrome of some "fat middle aged men with psychopatic brains".

3. Fat+glucose=accelerated apoptosis, that must also apply to mitochondria! If accelerated mitochondrial apoptosis is the cause of long term mitochondrial degeneration then diabetic doctors were right all along, telling patients to avoid eating too much fat (on their usual high carbohydrate diet). They were right for the wrong reason! 8-:)

4. As both of us have already found out, brain not only can live on ketone bodies but works much better than on glucose! Now I know why!

Thanks for posting it, best regards,
Stan (Heretic)

Matthew said...

"Long-Term Low Carbohydrate Diet Leads to Deleterious Metabolic Manifestations in Diabetic Mice"

http://www.ncbi.nlm.nih.gov/pubmed/25170869

As a reader of this blog and non-medically trained person reading the paper abstract, I think I see:

1) "Crap in a bag"
2) More protein than fat, making it a bad high protein diet more than a bad low carbohydrate diet: "severely carbohydrate restricted (SR, C∶P∶F = 18∶45∶37)"

Awaiting your deconstruction of the study :)