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We Need More on Ketosis
Robb Wolf  |  Nutrition  |  March 27 2006

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The topic of Intermittent Fasting (IF) has drawn a fair amount of attention from the research community in the past few years. There are a few primate studies underway that should shed some light on how critters much more genetically similar to us respond to IF.

Everyone is looking for a key enzyme or cellular receptor to make a drug that can do the same thing as IF or Caloric Restriction with Adequate Nutrition (CRAN). Ironically that drug may be swirling at the bottom of wine glasses the world round: Resveratrol. However, that is a topic for another day. Right now I want to talk about this interesting phenomenon that I noticed first in my undergraduate biochemistry class but see happening still today. The phenomenon I speak of is the Teflon-like topic of Ketosis. No one seems stick to it.

In my undergrad biochemistry class I remember talking about metabolism and the topic of ketosis came up. Ketosis arises form the incomplete metabolism of fatty acids due to a lack of adequate glucose to drive the TCA/Krebs cycle. Now our instructor and textbook made the point that glucose was THE preferred energy source for all the various organs and tissues of the body but our text book Biochemistry 4th Edition by Stryer (http://www.whfreeman.com/stryer/) made the point that after a time of adaptation many tissues preferentially ran on ketones. That was very interesting to me particularly in light of the fact that ketosis was supposed to be an abnormal metabolic condition and well…everyone knew we were supposed to run on glucose, right?

 That day has stuck with me for a very long time and it has kept me alert to the story of how our metabolism really works. This story is made ever more clear with information emerging about CRAN and IF but it still appears that the topic of ketosis is something few want to talk about. In the Anson et-all paper published in the Proceedings of the National Academy of Sciences the topic of IF gets a very thorough treatment. Full text here: http://www.pnas.org/cgi/content/full/100/10/6216. One of the Key features of IF is the production of very high concentrations of ß-hydroxy butyrate…now listen to this…ketones are produced on a 67% refined carbohydrate diet! According to the biochemists and nutritionists one can ONLY be in a state of ketosis if carbohydrate is restricted. This fundamental contradiction of metabolism has received little more than a shrug from the research community. That is absolutely stunning to me.
 As a possibly interesting sideline the mouse chow used in these studies, a 67% refined carb diet that goes by the name NIH-07, is NOT recommended for long-term animal studies due to the extremely high rates of death and degenerative disease associated with the NIH-07 diet. The really telling part is that the degenerative diseases like cancer, stroke, heart disease Parkinsons and Alzheimers are being attributed to the paltry 24% protein. This is how truly clueless and disconnected most of our medical establishment is with regards to nutrition. You can read about that enthralling topic here: http://www.ehponline.org/members/1994/102-3/rao-full.html. Just to be clear, this chow is not recommended for animals in long-term studies due to the fact that most of the animals die before the completion of the study due to their NIH-07 diet. And the problem in the eyes of the researchers is the protein! (Have these researchers ever heard of hyperinsulinemia?) What is amazing to me is that mice fed on this chow manage to live a very long time on the IF protocol. IF appears to very effectively protect the animals from the National Institutes of Health recommended food. That could make a fun headline: “Mice Seek Protection From NIH Endorsed Food”.
 The topic of ketosis is a fascinating one. Search for it at PubMed sometime. I hope that the research community investigates the interplay between ketosis, CRAN and IF.  There are some redundant pathways that interlink these very separate processes. This is of significance as biology and evolution are stingy when it comes to biological redundancy. For the time being however, I need to face the reality that a drug of some sort needs to be the end product of this investigation. At present one need do nothing more than reduce carbohydrate intake or skip a few meals to achieve the state of the art in life extension and optimized health. Not much money to be made pushing that point.
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Robb Wolf is the owner of NorCal Strength & Conditioning, a co-founder of the Performance Menu journal, and author of The Paleolithic Solution. His website is www.robbwolf.com.
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6 Comments
Mary 1 | 2006-04-19
I took a grad class in metabolism in 1996 and you were lucky that you got to talk about ketones, I hardly remember the instructor gave it more attention than if glucose is not available the body would use ketone bodies. When we came to chapter on intergrated metabolism, I wanted to ask the skinny instructor on how would you go about loosing weight, but I was too shy to ask being 40 pounds heavier than I am now. If you never experience hyperinsulinemia you have no idea on what it does to your appetite. Looking back on the book we use, I have 4 points: 1. The intro to steriod metabolism mentions how important cholesterol is to our health but goes on to say that high cholesterol levels are implicated in heart disease and they don't know why. 2. On dietary starches, there is no mention of the glycemic index, just two starches amylose and amylopectin. 3. On the side bar about type II diabetes, it discusses the big mystery of beta cell failure! Why, oh, why could that be happening? 4. At the end of every chapter there was something about some type of genetic defect of metabolism but nothing about syndrome X or insulin resistance or diseases of hyperinsulinemia. In July 2002 I read Gary Taubes article in the NYT magazine and it describe me to at T. I went to that biochemistry book, looked up what hormone opened up fat cell and slammed the book shut. I went on the Atkins diet that week and lost 40 pounds in the next 5 months. It was an epiphany, for the first time in my life I could control my appetite. I was destined to be diabetic and I am glad I read that article. Looking back I could only lose weight eating a low glycemic diet but I took it from a vegetarian point of view (I ate alot of lentil soup as a poor grad student). I had no idea of the glycemic load of meat. I enjoy reading L. Cordain's research but I don't think I could have done his diet from the start with that much weight to lose. Even now when there is not enough fat in my diet I have tendency to overeat protein.
Robb Wolf 2 | 2006-04-26
Mary- The Taubbes piece certainly was a watershed moment...I honestly never thought I would live to see a piece like that and some of the research being done today. The trend is tryign to swing back to high carb land but the research community has finally gotten wind to the truth and the truth aobut hyperinsulinemia is comming out. I can not even tollerate the Zone. Too many carbs too often. Thank you for the excellent comment.
dave 3 | 2007-03-08
yes
Timothy 4 | 2008-03-19
I attended a crash course in long-term fasting over 12 years ago. After enduring the cravings on the 2nd or 3rd day of fasting, when the glycogen stores in the liver are exhausted, the body switches to ketosis and hunger goes away. This switch isn't triggered if caloric intake is not stopped, e.g. "juice fast" and the body can enter starvation state, where muscle is catabolized for energy. During ketosis, adipose tissue becomes the primary fuel source, with the brain running (better!) half on glucose and half on ketone bodies. Drinking water may become unnecessary, because water is a byproduct of ketogenesis. Physical activity should be minimized to avoid ketoacidosis, which is potentially fatal. Ketoacidosis is treated with a baking soda IV. Adipose tissue is usually exhausted after 40 days. This is signaled by the return of hunger, at which time the body has entered the starvation state, where muscle tissue is catabolized for energy. At this point, it is important to gradually reintroduce caloric intake, starting with small amounts of liquid CHO. The stomach will have shrunk, so small amounts are enough to relieve hunger. Protein and fat are gradually reintroduced later, because it will take time for digestive processes to adapt. Breaking a long-term fast suddenly by attempting to eat normally could potentially be fatal.
Chef 5 | 2009-03-30
Rob, In my process of losing 110+/- lbs of fat from my high end, I ran into a few gems of days gone by: Maura DiPasquale, Dan Duchaine, et al,. In the process of discovering the joys of CKDs and their benefit for mitigation of BF storage I was amazed at the ability to manipulate supra-maximal glycogen depletion/refeeds to drasticly ramp up strength gains while losing substantial amounts bodyfat. Tim, long term fasting would account for 'Adipose tissue is usually exhausted after 40 days' but in the average CKD follower, there is no starvation response. It would depend profoundly on how much adipose tissue you start the party with, no? The upregulation of Leptin and down regulation of Cortisol while in deep ketosis is the main angel responible for the mitigation of hunger, so keep the fracturing of triglycerides going with a minimum of 12xLBM for calories and your blood glucose at or below 50mmol and you will be bathed loads of leptin! 'Drinking water may become unneccessary...'?!?! Granted, for every gram of blood glucose/liver or muscle glycogen the body stores three grams of water, but in the nasty crap-metabolite phases of both CKDs and fasting, flushing out the acetones not expelled through your lungs, the excess ketone bodies not to mention chlorine and amonia is a big deal: both fasting and ketosis require at the VERY LEAST 1ml of water for every calorie consumed just so the machinery doesnt seize up out of warrantee! The REAL FUN begins when you use Ketosis to fuel ultra-endurance efforts and not as a 'diet'... ask the RAAM competitors and they will definitely tell you MCTs are a man/womans best friend! cheers, Chef
Vincent 6 | 2014-03-20
So what's the latest here?
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