Alzheimer's: Type 3 Diabetes?

Recently, our family has had some experiences with dementia and Alzheimer's as my wife's family recently lost one of their beloved matriarchs.  She was a lively woman, who was outgoing and caring, with a personality that many described as "loving" and "feisty".  But towards the end of her life she had lost the capacity to take care of herself, to communicate, and perform the simplest of activities like eating.   This was a horrible experience for my wife's family as it would be for anyone.  After having been exposed to several accounts of such tragedies, it serves as a reminder of why I want to do what I do.  It strengthens my resolve to rid the world of these terrible and preventable diseases.  NOBODY should have to suffer through an experience like this, and there's no reason anyone should have to.  

As of some recent studies, many experts in health research are leaning towards a new paradygm in Alzheimer's research.  It's the idea that the disease is actually the result of insulin resistance in the brain, hence the new moniker "Type 3 Diabetes", aka "Diabetes of the Brain" [1].  It seems, in the case of Alzheimer's, many folks in conventional medicine have resorted to nutritional therapy.  This is a fantastic example of how powerful the effects of food and nutrition can be in the treatment of some pretty serious and life-threatening diseases.  

So a little elementary physiology and anthropology is in order here to better understand why this works.  We'll keep it simple so a), I don't confuse myself, and b), you don't get too bored.  Using the Grok meme, you have to imagine early man had instances where food wasn't plentiful.  From an evolutionary standpoint, it would make sense that people who's physiology was unfit to cope with such stresses would eventually be selected out.  How did man cope with these thin food times?

As discussed previously, the body was designed to run on a relatively low-carb diet as compared to modern diets.  True there were several examples of hunter-gather diets that were relatively high in carbohydrates such as the Kitavans, however, generally speaking most paleolithic people ate a higher fat, low-to-moderate carb, moderate protein diet.  That macronutrient composition is just how it usually worked out with the types of food available to be gathered or hunted in most climates during that time [2].  

On such a diet, one's body shifts from burning glucose to burning fat as its primary source of fuel, specifically Free Fatty Acids (FFA).  The end product of FFA metabolism are ketone bodies, which end up providing more ATP per molecule, but at the expense of more oxygen.  This means that, while at rest or during mild activity, your body is more efficient when running on ketones as it's primary energy source.  This was base-line for early man [3].  However, due to the high O2 demand, ketones become less efficient in times of extreme physical exertion (ie, crossfit, marathons, MMA, running from predators).  In the event that great physical exertion or stress is necessary, for example "Flight" during a fight or flight moment, epinephrine is released and the body turns to glucose which is supplied by the liver in the form of glycogen.  Large amounts of glucose is then dumped in to the blood stream so that energy is more quickly available for use by the exerting muscles.  While not baseline, such a glucose spike is useful when fending off a lion for example, or hunting a gazelle.  In other words, ketones could be seen as "gasoline", while glucose could be thought of as "nitrous oxide."  

Remember however, that chronic or prolonged sugar spikes throughout the body are toxic and associated with metabolic derangement.  So, while one would want glucose available in case of an emergency, he'd not want to depend on carbs as his primary source of fuel.  Doing so could lead to chronic conditions, and insulin resistance (as has happened to modern humans).  It's starting to be understood that such insulin resistance is happening in the brain as well.  It occurs when insulin receptor sites are down-regulated (meaning there are less receptors) which retards glucose transport into the cell.  This, coupled with inflammatory processes and resulting oxidative damage are thought to cause the disease.  Enter the Ketogenic Diet.  A ketogenic diet treats both pathways, increasing insulin sensitivity and reducing inflammation in the tissues of the brain.  

Going back to Grok, we'd think of him as a guy who would have occasion to go without food every now and again.  Fasting, unintentionally, was a logical consequence of early man's environment.  They had no Safeways, Starbucks (the horror), KFC, or Costcos in which to gather supplies.  And typically, there was no refrigeration (with the exception of winter) in which to store food for long periods of time.  Man was an opportunistic eater, and even scavenged meat when possible.  He probably ate meat when available via hunting or scavenging and probably ate his fill [4].  But what happened when the hunters returned without meat, or the gathering of edible vegetation returned fruitless?  Protective mechanisms were evolutionarily put in to place to deal with food variations in terms of the types of macronutrients ingested, and the overall calories taken in.  

"The classic ketogenic diet is a high-fat diet developed in the 1920's to mimic the biochemical changes associated with periods of limited food availability." (Kossoff, 2004) [5]

During times of fasting or starvation glucose is in dearth supply, either due to a lack of dietary carbohydrates or a lack of dietary proteins which can be converted to glucose via gluconeogenesis.  In this case the human body is built to operate at low-carb (LC), very low carb (VLC), or even zero carb (ZC) levels.  Your most important organ, the brain, runs on ketone bodies in the absence of glucose, and can do so with efficiency.  In this case, the fuel is typically supplied by fat stores but can be obtained from dietary fat as well.  While your brain still requires a small amount of glucose in order to function, it actually runs more efficiently on a higher ketone to glucose ratio, with research reporting improvement in memory, decision-making, problem-solving, and various other brain-related activities. [8]

Healthy brain (left) vs. Alzheimer's brain (right)

So why the big long explanation about ketones and how the body (and specifically the brain) uses them?  Because high-fat ketogenic diets not only improve brain function in healthy people, but are hugely effective in preventing and treating many neurological diseases, including Alzheimers.  For an explanation of how cholesterol DOESN'T cause Alzheimer's disease, I couldn't even begin to explain it better than Chris Masterjohn.  Go here for his article on why that's not an issue.  

For a while now ketogenic diets have been used to treat a slew of neurological diseases as described in this article here. [7] 

Ketogenic Diet Therapy uses OTHER than epilepsy:
Brain tumors2003
McArdie's Disease2005
Traumatic brain injury2005
Sleep disorders2007
Post hypoxic myoclonus2007
Post anoxic brain injury2008

In summary, diet is a major player in the treatment of many diseases.  It's important not to overlook the dietary component of any disease process, and while conventional medicine is starting to see the value of nutritional therapy in neurological instances, it severely lags behind in that regard concerning many other areas in medicine.  Preventative medicine IS after-all, bad for business.  Just ask your friendly neighborhood pharmaceutical sales rep. 

--The Japsican 


[2] Kaplan HS, Hill KR, Lancaster JB, Hurtado AM. A Theory of Human Life History Evolution: Diet, Intelligence, and Longevity. Evolutionary Anthropology 9:156-185, 2000.http://www.unm.edu/~hkaplan/KaplanHillLancasterHurtado_2000_LHEvolution.pdf.

[4] Aiello LC, Wheeler P (1995) "The expensive tissue hypothesis: the brain and the digestive system in human and primate evolution." Current Anthropology, vol. 36, pp. 199-221.

[5] Kossoff EH, "More fat and fewer seizures: dietary therapies for epilepsy."  Lancet Neurol. 2004 Jul;3(7)415-20  http://www.ncbi.nlm.nih.gov/pubmed/15207798

[6] Maciej Gasior, Michael A. Rogawski, Adam L. Hartman.  "Neuroprotective and disease-modifying effects of the ketogenic diet Behav Pharmacol. 2006 September; 17(5-6): 431–439.

[7] Kossof EH, "Ketogenic Diets: Not just for epilepsy any longer" http://www.epilepsy.com/epilepsy/keto_news_aug08
[8] Joseph C. LaMannaNicolas SalemMichelle PuchowiczBernadette Erokwu and Smruta Koppaka, et al. "Ketones Suppress Brain Glucose Consumption"  Advances in Experimental Medicine and Biology, 1, Volume 645Oxygen Transport to Tissue XXX, Pages 301-306, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874681/


Nice information, many thanks to the author. It is incomprehensible to me now, but in general, the usefulness and significance is overwhelming. Thanks again and good luck!
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