Monday, November 15, 2010

Ketone bodies protect neurons from stress hormone-induced damage

[Part 1 of 2]

This is inspired by this video presentation:

Robert Sapolsky: Stress, Neurodegeneration and Individual Differences

Scrolling to minute 26 of the video, reveals a slide summarizing the results of an experiment, where neural tissue was exposed to an "insult" (damage cause) equivalent to hypoglycemia.

The degree of damage to the neurons was asessed in volume units (vertical) while the 4 cases are represented by color bars:

green - damage caused solely by the original "insult"
yellow - damage caused by the "insult" in the presence of glucocorticoid (stress hormone)
red - damage caused by the "insult" in the presence of glucocorticoids and mannose sugar
white - damage caused by the "insult" in the presence of glucocorticoids and ketone bodies (beta-hydroxy-butyrate)

What do I make out of that? Basically, it shows that not only ketone bodies work better as the energy source than mannose sugar, but also protect against the damage caused by both factors combined: hypoglycemia and glucocorticoid: - the white bar is smaller than the original green bar on the left!

[part 2 essay inspired by the same video will be titled "Lack of social skills made us human!" ]


john said...

Wow, this is cool. It would seem from epilepsy studies that ketones themselves do not directly provide "protection," but of course things are inconclusive, and this is an interesting study.

Stan (Heretic) said...

Hi John,

No, it is not a proof but it does give us a hint of what the damage mechanism is (energy deficit) and what is the nature of the protection mechanism: ketones are just the super-fuel!

I find all of Sapolsky's lecture highly thought-provoking. Well worth watching.

cavenewt said...
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twitchyfirefly said...
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twitchyfirefly said...

cavenewt said...
I'm interested in this because I've been diagnosed with a rare neurodegenerative disease, MMN (multifocal motor neuropathy), which is thought to be autoimmune. It affects motor nerves and appears to involve more axon damage than demyelination. IVIg is the main treatment, which I've been on since May 2010 (15 months.) Dunno if it's helping, it might slow it down. In Jan 2011 (8 months ago) I put myself on a ketogenic diet, hoping to encourage axon regeneration (my Mayo neurologist is humoring me in this.)s I'd be very interested in anything else which might encourage nerve health.

dav0 said...

Hi cavenewt. Firstly, I must stress that I'm not a doc. I'm an engineer. I'm not able to give you medical advice. My own amateur interest comes from the fact that I myself suffer from a 'myopathy/neuropathy' syndrome, the exact cause of which is still not known. As I'm sure you know, MMN can be clinically very similar to ALS and is often mistakenly diagnosed as such. One distinguishing factor that supports the MMN diagnosis is the presence of anti-GM1 antibodies. IvIG is indeed the only conventional course of treatment recommended for MMN. There appears to be a growing body of evidence that a significant amount of neuropathy can result from the triad of ' Excitotoxicity, Oxidative stress and Neuroinflammation' These mechanisms have been observed in Alzheimer's, Huntingdon's, Parkinson's and ALS. (Facheris et al., 2004; Farooqui and Horrocks, 2007b). Some theories exist suggest that one underlying cause could be relatively recent shifts in dietary ratios of n-6(arachidonic acid) : n-3 (docosahexaenoic acid). The paleolithic diet we evolved on had a ratio around 1:1 but modern Western diets are more like 15:1 due to agricultural development, changed eating habits and abundance of processed foods.

A substantial amount of data supports the use of n-3 fatty acids as anti-excitotoxic, antioxidant, and anti-inflammatory agents
(Högyes et al., 2003; Mori and Beilin, 2004; Calder, 2004, 2006;
Roland et al., 2004; Farooqui and Horrocks, 2004).

In short, I'm not advocating any particular diet, just providing some references that you might like to quote to your smug neurologist.

I got most of these refs from the book: Neurochemical Aspects of Excitotoxicity, Farooqui, Ong and Horrocks. Springer, ISBN: 978-0-387-73022-6.

HTH Dave.

Some Refs:

Calder P. C. (2004). n-3 Fatty acids, inflammation, and immunity - Relevance to postsurgical and
critically ill patients. Lipids 39:1147–1161.

Calder P. C. (2006). n-3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am.
J. Clin. Nutr. 83:1505S–1519S.

Roland I., de Leval X., Evrard B., Pirotte B., Dogne J. M., and Delattre L. (2004). Modulation of
the arachidonic cascade with omega 3 fatty acids or analogues: Potential therapeutic benefits.
Mini-Rev. Medicin. Chem. 4:659–668.

Horrocks L. A. and Farooqui A. A. (2004). Docosahexaenoic acid in the diet: its importance in
maintenance and restoration of neural membrane function. Prostaglandins Leukot. Essent. Fatty
Acids 70:361–372.

Högyes E., Nyakas C., Kiliaan A., Farkas T., Penke B., and Luiten P. G. M. (2003). Neuroprotective
effect of developmental docosahexaenoic acid supplement against excitotoxic brain damage in
infant rats. Neuroscience 119:999–1012.

Marszalek J. R. and Lodish H. F. (2005). Docosahexaenoic acid, fatty acid-interacting proteins,
and neuronal function: breastmilk and fish are good for you. Annu. Rev. Cell Dev. Biol. 21:

Mori T. A. and Beilin L. J. (2004). Omega-3 fatty acids and inflammation. Curr. Atheroscler.
Rep. 6:461–467.

Angeline Pacy said...

Hi friends,
I was really touched by your stories. I always say that it takes a village of therapies to heal these complex neuropathies (aka the cocktail). Part of what I have picked up on my journey is that a System's Theory approach is needed with any neurodegenerative disease.

First, I'd like to say that the Deana Protocol from Winning the Fight is a great place to start. They do emphasize ketones for neurometabolism / anti-inflammatory / alternate energy source. Next, tweak everything to your genome. There is a detoxigenomic test kit that tests for several genetic risk factors that impaire the body's ability to detox, particularly in the central nervous system.

Or, you can go with the common defects and address them (clinical diagnosis) because breaks in these metabolic pathways are a given and common in these types of diseases, not just from genetic risk but from environmental stressors that break down the body. I would start with chelation. It's a must. Try everything from tri-weekly methyl cobalamin injections to cilantro to glutathione intravenously, to Trimethylglycine. Don't be shy. This is your life to live and these methods do work as part of a cocktail.

Once toxicity is addressed, its time to activate endogenous anti-oxidant pathways. Lipid-soluable cur using in high doses is a must. It also doubles as an anti-inflammatory and anti-microbial. Glutathione also turns on endogenous anti-oxidant pathways.

Then, you must break out the big guns with anti-oxidants to address oxidative stress. Get the best on the market for lipid-soluable anti-oxidants. I like Astaxanthin in that it also doubles to remove neurotoxins from the CNS. Therapeutic dose of astaxanthin begins at 80mg per day. Remember that this speeds up the Kreb's cycle by improving ATP production for the brain. So, remember that caloric needs increase with the lipid-soluable anti-oxidants. This is key: Start ripping through GeroNova Research's materials because we have a lot to learn from them too! Anti-oxidant experts with ethics.

Please remember the bases. . . Adrenal support with DHEA and vitamin C. I like intravenous because absorption is a major issue in the chronically ill.
Then, replacing the cell walls / lipid membranes is vital to healthy energy output and restoring function. Phospholipids and essential fatty acids are crucial. Don't take a wimpy product and expect to get anywhere. EPA/DHA needs to be at a starting base of 3-5 grams (no milligrams a day). Krill oil is great too because it does assimilate directly into the phospholipid bilayer. Molecularly distiller is a must. Try Nordic.

A mitochondrial cocktail is a must and should be tweaked to your needs. People are finding success with acetyl-L-carnitine, lipid soluable anti-oxidants like ubiqinol (don't confuse with CoQ10) and PQQ (I highly recommend in high doses).

Some benefit from increasing nitric oxide in the brain. I do. Some research suggests that it oxidizes into something unhealthy in ALS models, so keep that in mind. It's great for the other neuropathies. Increasing nitric oxide in the CNS is tricky because you don't want it elevated indiscriminately. I like rotating schitzandra, scalenium and Phenolethylamine (found in chocolate). These do target the CNS and will ultimately protect motor neurons.

That is all. I have spoken.

Angeline Pacy said...

Oops. That should have read: turn on endogenous anti-oxidants with lipid-soluable curcumin in high doses.