Magnesium-A central player in obesity

Robb Wolf-Blast from the Past

The above video is a presentation that Robb Wolf gave at SUNY New Paltz in 2012.  There are a ton of nuggets on why an ancestral diet is the best choice for human health, but there is one particular construct I would like to focus on for this blog.  At 52:50 in the presentation Robb discusses the relationship between sepsis and insulin resistance.  The basic gist is that obesity is caused via sepsis induced insulin resistance.  Lipopolysaccharide (LPS) enters the blood via a leaky gut caused by the dissolution of the tight junctions between enterocytes (Cells of the intestinal wall).  This basically poisons the blood which, in turn, induces insulin resistance which progresses to both diabetes and the metabolic syndrome.  According to Robb, this is to spare glucose for the brain.  If you think about it, given the fact that most of our ancestors died of some sort of infection, it would make sense that when infection of the blood occurs there is an evolutionary advantage conferred to the host by sparing glucose for the brain.  However what is the mechanism that causes this advantage and is there any way to exploit it?

Interestingly enough, you don't even need to dig too deep in to the literature to find some pretty strong relationships in this scenario of sepsis-induced insulin resistance.  In fact, when we look at these relationships, one thing seems to contribute to insulin resistance, diabetes, obesity, sepsis, and even early death due to sepsis.  I am talking about the 4th most abundant mineral in the body and one that has gotten little play from scientists up until recently, magnesium.

Magnesium is critically important in over 300 enzymatic reactions in your body.  Both the secretion of and effectiveness of insulin are dependent on adequate magnesium.  In the presence of insulin, cells require magnesium in order to take in glucose from the bloodstream(1).  In children, serum magnesium has been shown to be lower in obese children than lean controls(2).  In adults, lowering serum and intracellular magnesium via a diet low in magnesium has been shown to reduce insulin sensitivity.  Evidence from the study suggests this was via reduced insulin action(3).  Oral magnesium intake has also been shown to improve insulin sensitivity, even in people who have normal magnesium levels(4).  This could be due to the fact that serum magnesium is a terrible indicator for magnesium status given that magnesium is primarily an intracellular cation and serum magnesium levels are tightly controlled.  If they weren't you would die with the slightest variation outside of the normal range.  When compared to normal controls, people with the metabolic syndrome tend to have lower intakes of magnesium(5).  Mirroring the results of this study, a prospective study performed in 2012 found an inverse relationship between the intake of magnesium and incidence of diabetes.  What makes this study more interesting than the others is the fact that they also found an inverse relationship between magnesium intake/serum magnesium and markers of inflammation(6).  It is widely known that chronic inflammation is correlated with diabetes and metabolic syndrome, the fact that both magnesium intake and serum magnesium levels correlated with the level of chronic inflammation in this study strengthens that notion.  It is even possible that this relationship could be stronger if intracellular magnesium was measured.  But how does a magnesium deficiency lead to chronic inflammation?

When we look at the effects of sepsis on insulin sensitivity, the strength of the relationship between the 2 is as strong as the relationship between magnesium deficiency and insulin resistance.  In a study on rats, progressive magnesium deficiency increased the rate of mortality in rats induced with endotoxemia(7).  The longer the rats were magnesium deficient the more likely they were to die from endotoxemia.  In addition, rats that were treated with magnesium had a 300% increased likelihood of survival compared with control rats.  In another study on rats, sepsis induced a drop in magnesium over time that eventually recovered during the later part of sepsis(8).  In a study in humans, 52% of patients entering the ICU unit had hypomagnesemia.  Patients with hypomagnesemia were almost twice as likely to die (58% vs 32%), required more care, and were twice as likely to experience sepsis (38% vs 19%)(9).  As menioned above, one of the problems with measuring serum magnesium is that it is tightly controlled in the body, if it gets too out of whack you die.  Since magnesium is primarily found within cells, Red Blood Cell magnesium seems to be a better indicator of magnesium status.  In studies that have measured RBC magnesium instead of serum, the incidence of hypomagnesemia in critically ill patients is much higher which may confound the results(9).

Given that hypomagnesemia leads to both an increased risk of sepsis as well as poorer outcomes, there must be some mechanism by which magnesium inhibits sepsis.  In a study examining rabbits rendered endotoxemic with LPS, histamine levels quickly increased to 50x greater than baseline values and remained that high throughout the 6 hour study period(10).  A study on humans performed in 1996 found multiple relationships between sepsis and histamine levels.  None of the patients with low histamine levels as determined by criteria in the study experienced sepsis while 45% of the patients with sepsis had high histamine levels.  Of the patients with sepsis, the non-survivors had higher plasma histamine levels than survivors and all of the subjects with a high sepsis score AND high plasma histamine levels died(11).  All of this begs the question, is there some relationship between histamine and magnesium?

Two studies in humans have shown a decrease in intracellular magnesium levels during increased histamine levels in asthmatic patients(12,13).  In the first study, magnesium and histamine levels were measured during asthma attack.  When compared to asymptomatic levels as well as control subjects, histamine levels increased during asthma attack while plasma and intracellular magnesium levels dropped(12).  In the second study, patients were given histamine to induce an asthma attack.  While plasma magnesium didn't change, there was a significant decrease in intracellular magnesium levels(13).  One of the likely mechanisms by which histamine reduces magnesium levels is via Diamine oxidase (DAO) production.  DAO is an enzyme secreted by cells of the intestinal mucosa that enters the circulation via the lymphatic system.  DAO inactivates histamine and is dependent on magnesium for production.  Therefore, when histamine levels increase, magnesium is used to create DAO to metabolize the histamine.  As magnesium levels drop due to sustained histamine release, DAO levels drop and histamine levels increase. In a study performed on rats, rats fed a magnesium deficient diet for 8 days had a decrease in duodenal DAO activity which led to an increase in blood histamine levels. Feeding the rats a diet high in magnesium for 2 days decreased blood histamine levels to that of controls(14). 

The relationship between histamine levels and magnesium appears to be multi-faceted.  In another study on rats, magnesium deficiency led to an initial increase of histamine levels reaching a maximum of 5x the control level by 14 days on a magnesium restricted diet with a subsequent decline to control levels as the magnesium deficiency continued(15).  The mast cells (cells that secret histamine) that remained or were produced after magnesium deficiency had a reduced capacity to store and secrete histamine.  This implies that magnesium is necessary for the manufacture and secretion of histamine as well as the inactivation of it.  Judging from the results of both experiments, priority is given to histamine production over histamine metabolism.  This underscores the importance of histamine release to the immune response.

One hormonal player in the obesity/insulin resistance game that we have yet to discuss is leptin. Leptin is an inflammatory hormone secreted by fat tissue that suppresses appetite.  Basically, you eat food and when you start making body fat, leptin is secreted by fat cells to tell the brain that you are in a fed state.  In obesity and the metabolic syndrome, people become resistant to the effects of leptin. This causes them to never receive the fed signal which causes them to overeat.  While there is no good evidence linking leptin to magnesium, there is very strong evidence linking leptin to histamine in mice.  In a study on rats, the administration of leptin caused an increase in hypothalamic histamine that lasted 4 hours in anesthetized rats(16).  The same dosage of leptin given to non-anesthetized rats significantly reduced food intake.  In another study, mice treated with leptin had an 84% reduction in food intake when compared to controls 24 hours after being treated(17).  In mice treated with FMH(an inhibitor of histamine) prior to leptin, appetite was not significantly different.  In a study using mice bred to lack the histamine H1 receptor(H1KO), injection of leptin did not significantly change appetite in comparison to control mice.  These findings were confirmed in another study on rats(18).  Finally, in a study that looked directly at the effect of histamine on feeding behavior and fat deposition, injecting leptin resistant obese and diabetic mice with histamine reduced food intake and bodyweight(19).  In addition, histamine treatment in the experimental group reduced body fat, ob gene expression, and leptin levels to a greater degree than that seen in pair-fed controls.  The histamine treated H1KO mice also saw greater improvements in blood glucose and insulin sensitivity than pair-fed controls.  Interestingly enough, the effect on body fat reduction was only significant in visceral fat, the type of body fat associated with insulin resistance and the metabolic syndrome.

The sum of all of the evidence discussed above points to very strong relationships between sepsis, insulin resistance, histamine, and leptin.  It seems as though control of sepsis may be given priority over blood glucose control and magnesium may mediate this.  Since both biological functions are dependent on magnesium for proper function, preference has to be given to one function over the other.  Over the course of evolution, natural selection would have favored those animals that gave precedence to control of sepsis over blood glucose control since infection was the primary cause of mortality and blood glucose levels were controlled by the availability of food and energy required to attain it.  In addition, system-wide insulin resistance during sepsis would confer an advantage to the host via conserving blood glucose for the brain.  It appears there is a very strong relationship between magnesium intake and levels, histamine levels, sepsis, and insulin resistance.  One potential idea is that a diet high in foods that increase intestinal permeability and blood levels of LPS increase the body's need for magnesium to both produce and metabolize histamine. Since the body naturally gives precedence to control of sepsis over that of blood glucose, people who experience endotoxemia from LPS will have reduced magnesium availability to both produce insulin and allow glucose uptake by cells.  If magnesium deficiency reaches the point of negatively impacting the production of DAO, histamine levels will increase.  At some point, either histamine levels decrease, possibly due to magnesium deficiency, or histamine receptors downregulate and become resistant to histamine in the brain.  This reduces leptin signaling and leads to an inability to control appetite.  These could be the initial stages of insulin resistance that eventually progress to Type 2 Diabetes and the metabolic syndrome.

It appears that special care should be taken to manage magnesium status both by increasing intake as well as limiting lifestyle activities that increase magnesium depletion to prevent the metabolic syndrome.  Examples of lifestyle activities that are known to deplete magnesium are poor sleep, high carbohydrate diets, smoking, alcohol intake, excess stress, and eating foods that increase intestinal permeability and blood levels of LPS (1).  Interestingly enough, all of these activities have been shown to be correlated with the metabolic syndrome.  This is not to say that magnesium is the sole cause of the entire problem, only that it is a major player in it and a potential target for therapy.  This also presents a competing paradigm that contrasts with the energy balance paradigm for weight management.

In my next blog I will explain this in plain English and give actionable steps to improve the metabolic syndrome and how those steps contribute to a healthy magnesium status.  Here's a hint, it involves a lot more than taking magnesium supplements.


REFERENCES


1)Magnesium miracle
2)http://www.ncbi.nlm.nih.gov/pubmed/15855585
3)http://hyper.ahajournals.org/content/21/6_Pt_2/1024.short
4)http://onlinelibrary.wiley.com/doi/10.1111/j.1463-1326.2010.01332.x/abstract;jsessionid=8F71CE49763637EE8FA0805916869F81.d04t02?deniedAccessCustomisedMessage=&userIsAuthenticated=false
5)http://onlinelibrary.wiley.com/doi/10.1038/oby.2007.628/full
6)http://care.diabetesjournals.org/content/33/12/2604.short
7)http://journals.lww.com/ccmjournal/Abstract/1995/01000/Progressive_magnesium_deficiency_increases.19.aspx
8)http://link.springer.com/article/10.1186%2F2110-5820-1-53?LI=true#page-1
9)http://www.japi.org/january_2011/oa_%20hoyponagnesemia.pdf
10)http://link.springer.com/article/10.1007%2Fs00210-002-0651-x?LI=true
11)http://journals.lww.com/ccmjournal/Abstract/1996/10000/Histamine_release_in_sepsis__A_prospective,.12.aspx
12)http://europepmc.org/abstract/MED/749826

13)http://erj.ersjournals.com/content/16/4/621.short
14)http://www.ncbi.nlm.nih.gov/pubmed/3111814

15)http://jn.nutrition.org/content/110/5/851.full.pdf
16)http://www.sciencedirect.com/science/article/pii/S0006899300023258
17)http://cat.inist.fr/?aModele=afficheN&cpsidt=1201182
18)http://diabetes.diabetesjournals.org/content/48/12/2286.short
19)http://diabetes.diabetesjournals.org/content/50/2/376.short

Health, wellness, and framing the statement properly...

When you look at health news today you may see statements such as, "Fiber reduces your risk of colon cancer", "Get more Vitamin D3 to boost immunity", or "Exercise your way to a healthy heart".  This approach to health is ridiculous and one of the primary drivers of our current healthcare problem.  The way these statements are phrased is completely wrong, they are phrased in a manner that essentially assumes poor health is the default condition.  It is not the normal course of events to grow old, get sick, and die.  In fact, a few thousand years ago if you made it to 40 years old and didn't get killed in the normal manner of getting a wound that got infected, you had a far greater chance of making it to 75 than you do today.  Let's look at what's wrong with all three of these statements one by one.

Fiber reduces your risk of getting colon cancer
Correct me if I'm wrong, but I just don't remember that many people dieing of colon cancer when I was a kid.  And while it may have been present a few thousand years ago, I highly doubt cavemen were doubling over and dieing of colon cancer.  While we would never know for certain, we do know that modern hunter gatherers have little to no incidence of colon cancer unless they adopt a westernized diet high in processed foods.  While fiber is something you should get, you should get it from whole, unprocessed foods as it is these very foods that shaped our genome over 2 million ears of evolution.  We literally evolved to run on them.

Vitamin D3 to boost immunity
There have been multiple studies looking at Vitamin D3 and immunity with mixed results.  In my opinion, the mixed results come from poor controls in clinical studies.  Vitamin D3 probably isn't a helpful supplement to someone who is not deficient in it.  Someone who is outside in the sun regularly with a significant amount of skin exposed probably won't have much use for supplementing with it unless they live on the east coast and it's winter (UVB rays that carry D3 are reflected back toward the sun so we don't get them during those months). In other words, Vitamin D3 doesn't improve immunity, a Vitamin D3 deficiency compromises it.  Those are 2 different things, the first one states your immune function will be improved with Vitamin D3, the second that proper functionality of your immune system is dependent on it.  Again, poor immunity isn't the default condition, it's the pathological one.

Exercise your way to a healthy heart
My roots are in exercise.  I love to exercise and it is more or less my job.  However, exercise in it's current form is ineffective for preventing heart disease or improving health in general.  Given what we know about evolution and natural selection, sitting at a desk all day is not the default condition.  If it were we wouldn't be here because food doesn't find itself.  Regular, daily physical activity is the default condition and we are not talking about 2 hours at the gym 3-5 days a week.  We are talking about being on your feet for a majority of the day and not sitting for stretches of 4-8 hours without getting up.  Your 6-10 hours a week at the gym are not going to make up for the 158 hours you spend lying around.  Couple that with a bad diet and a reliance on insulin to shuttle glucose in to cells and you are basically destroying your cardiovascular system.

Conclusion
The way we view health in the US is terrible.  We assume that the default condition is to sit in an air conditioned room out of the sun in a chair for 8 hours a day.  If you buy in to the notion that we evolved via natural selection (I hope you do or you've found the wrong blog), it makes perfect sense that we are optimized for whole foods high in fiber, constant movement and plenty of sun exposure.  We spent 99.999975% of our time here getting just that, to assume that you can undo the fine tuning that occurs over the course of 1,999,950 years of evolution with a few supplements and a couple of hours of activity is foolish.

Stop the Insanity: What’s the deal with Crossfit, P90x and Insanity?

I don’t think I go a week without someone asking me about Crossfit, P90x, or Insanity. My response most of the time is that if it’s something you want to do, do it. Personally, I think all 3 of them are insanity and wouldn’t recommend them to your casual fitness enthusiast or weight loss client, and people often want to know why I think that. Listed below are my primary reasons.

1. For the vast majority of people, they are overkill. You can get the same or better results doing less than half as much total work. Dealing with the general population as much as I do, I can tell you the number of people who have asked me what is the most amount of work they need to do to lose fat is zero. Most, if not all, want to know the quickest, easiest way to lose fat. These 3 methods are none of the above. They require a ton of work and the results you get really aren’t any better than what I’ve seen with my clients who train 3-4 times a week for 30 minutes at a time with tons of rest between sets.

2. Pushing your stress response to the level these people do day in and day out almost always leads to more injuries or illnesses. The last thing someone who is trying to lose weight needs is a reason to quit and both of these reasons are probably the greatest contributors to quitting a fat loss plan.

3. Most people who need to lose fat are coming from sedentary lifestyles. While over time you can certainly prepare them for these types of activities, it would take at least a year just to correct movement dysfunction and learn proper exercise technique, let alone improve their stress response to the point this activity leads to positive adaptation.  If you get sore in very specific areas chronically this is almost always due to either over-stressing that tissue or a movement dysfunction.

4. People who are more prone to obesity and Type 2 Diabetes tend to have higher percentages of Type II muscle fibers. These fibers fatigue more easily than Type I fibers and take longer to recover. In order to activate these fibers they cannot be in a fatigued state, they need full recovery. If organized properly you can do higher intensity exercise in a compressed time window while getting full recovery. None of these modalities do that.

5. I agree that intensity is key, but what these programs do isn’t intense by definition. While they are physically draining, intensity is defined by percentage of max force output. If I sprint as fast as I can for 30 seconds, get full recovery, and then sprint as fast as I can for 2 minutes, the second sprint will be more exhausting but the first will be more intense because it will be at a greater speed which requires more force. Also, if I sprint for 30 seconds, get partial recovery, and then try to sprint for 30 seconds again, the second sprint will not be as intense as the first because I will not be able to produce as much force. This is the primary drawback of these types of exercise; partial recovery means partial muscle recruitment. We want total muscle recruitment, not partial.

6. If you have problems regulating your appetite with no exercise, you are going to have a hell of a time regulating it by doing all of this work.

7. Muscle confusion does not exist.  Don't get me wrong, I'm not about to compare sports science to heart surgery, but I don't intend on going to a heart surgeon who calls my heart the "Blood pumpy thing".  I expect the people I pay to provide a service to know what they are doing and talking about.  A muscle cannot be confused any more than a hammer can.  Muscles are tools your brain uses to accomplish a task, they don't get confused.  If they get used and haven't been used in a while they get sore via inflammation and waste products they are not capable of disposing of.  This can both be a positive adaptation or a negative one depending on the magnitude of the soreness.


Don't get me wrong, if your goal is to become a Crossfit athlete you obviously need to join a Crossfit gym.  Of the 3, Crossfit is obviously superior because you are getting instruction.  I've noticed quite a push in the Crossfit community to develop bridge programs so that sedentary people who want to do crossfit can work their way up to doing it safely.  This is a very good move and is causing me to soften on it, I would endorse a gym that does it properly.  If you are interested in doing a crossfit program I highly recommend going to one that uses a Functional Movement Screen to drive corrective exercise and has a good bridge program.  Realize that most programs that do this are going to be more expensive than ones that don't, but you get what you pay for.  It is well worth it to take care of any movement dysfunction up front rather than deal with it after you have learned the movements and need to re-learn them after fixing the problem.  As for the other 2 programs...fix your diet, go for walks, and foam roll and strength train 2-3 times per week for 45 minutes at a time.  The rest is just overkill.

Poor health? Look at your gut bugs! (Video)

 Man the Fat Hunter from AHS '12

The video above is a presentation given by Dr. Miki Ben-Dor, MBA, Ph. D entitled "Man the Fat Hunter: Animal Fat Shortage as a Driver of Human Evolution and Prehistory" at the Ancestral Health Symposium in 2012. I found quite a few little nuggets in this video that I found interesting. Most countries ignore the importance of evolutionary biology in their Health/Nutrition paradigm which is a big mistake. Dr. Ben-Dor makes a pretty compelling case as to why what the past shows us is important. Dr. Ben-Dor's primary assertion is that we evolved to eat animal fat.

On the surface it seems as though it would be very difficult to prove such an assertion since it's not really a testable hypothesis given the technology we have today. It is true that, at this point, we could never prove this theory. However, you can't prove that carbohydrate is the preferred fuel source for humans either. We can make some guesses based on things we know, but at the end of the day we could never prove that. In fact, the notion that carbohydrate is our preferred fuel source is based on faulty logic discussed in the blog titled, "Myths, Metabolism, & Appetite". Yet somehow this myth continues to be repeated time and time again.

One thing that seems to run counter to Dr. Ben-Dor's hypothesis is that our closest genetic relatives, the Chimpanzee and other primates, live on a diet fairly high in carbohydrate and low in fat. However, while primates may eat a lot of vegetation high in carbohydrate, by the time it enters their bloodstream most of it is not glucose, it's fat. Dr. Ben-Dor goes on to explain that most of the energy from food on the planet is locked away in fiber we cannot digest.  He explains that while we are unable to break most of this fiber down, our chimp brethren can. The gut of a primate is filled with bacteria that digest this fiber in to fatty acids such as butyric acid that gets absorbed in to circulation while our digestive systems lack this bacteria in significant amounts.  In humans, some soluble fiber gets fermented in to butyric acid which is used to repair the gut lining, but other primates have a much higher capacity to do so.  So while a chimpanzee's diet may not appear to provide a high amount of fat, by the time the substrate hits the bloodstream 50% is fat and only 30% is glucose/fructose.  Why is this important?

Approximately 70% of the human brain is fat. We need fat to rebuild cell membranes, insulate nerve fibers, as well as a host of other processes in brain function and development. In fact, the greatest source of DHA, the most plentiful fatty acid in our brain, is human breast milk. If fat is so necessary for brain development, why would we lose some of our ability to ferment fiber in to fatty acids in our gut? Because we didn't have to.

The human genome, as well as the genome of every living thing on the planet, is constantly changing. Life forms tend to shed genes that no longer serve a purpose to them. Obviously a life form that is capable of providing a resource to itself is no longer in need of a gene that manufactures that resource. The bacteria in our gut actually serve as a secondary genome often referred to as the human microbiome. In fact, there are more genes in the bacteria in our gut than there is in the entire human genome. While the mechanism by which the human genome sheds genes is not known, understanding why we shed bacteria that make up our microbiome is as simple as understanding real estate and basic biology.

If you were to place a bowl of cat food outside of your house every night, you would eventually have some feline company. You provided a fuel source and the kitties started showing up. If you then removed the cat food and started placing a bowl of dog food on the porch, cats may show up for a couple of nights, but once the dogs start showing up there won't be a cat in sight.  You would no longer be providing fuel for the cats and a competing animal would keep them away.  In much the same way, a bacterial organism will make a significant presence in your gut when you provide food and an environment friendly to it's proliferation. In our gut that means real estate low in competition. When you don't provide food for that bacteria it eventually dies and gets replaced with bacteria that is being fed and, also, serving a purpose. This process, when reiterated over millions of years, will eventually remove bacteria that were once crucial for our survival.  Is there any evidence that this is happening?

In a recently published study from the University of Oklahoma, scientists looked at the microbiome of ancient human fecal samples including Otzi, the well preserved remains of a man who lived 5500 years ago.  The authors found that the microbiome of the remains from ancient humans more closely resembles those of non-human primates and modern hunter gatherers than those of westernized people¹.  They believe that our current diet as well as the widespread use of antiobitics and overuse of antiseptic practices is driving this change.  Of course, now the question shifts to whether or not this change can fuel changes in health status.  The authors of the study believe the change in the microbiome could be what is fueling the increase in autoimmune disease and other negative health states.  It makes sense since one of the functions of the microbiome is to train the immune system, 70-80% of which is housed in your gut.  Other studies looking at different health problems have found fairly good correlations between health status and changes in the microbiome.

There have been many studies showing the correlation between the gut microbiome and obesity.  Specifically, in both mice and humans, changes in the amount of 2 bacterial species found in the gut, bacteroidetes and furmicutes, correlates very well with obesity.  In mice, transplanting the microbiome from lean mice to obese mice results in the obese mice becoming lean.  Implanting the microbiome of obese mice in to lean mice causes the lean mice to become obese².  One of the drivers of this phenomenon is that the microbiome of obese animals makes more energy available from the diet³.  In humans, it is believed that this change can make 150 more calories available to the host per day.  While this may seem like a small number of calories, over the course of a single year it would lead to the accumulation of 10-15lbs of weight.

The effects of the microbiome on human health don't stop there.  In a study recently published in Nature Communications, researchers found that changes in the gut microbiome appear to play a role in stroke and atherosclerosis⁴.  It has long been theorized that carotenoids play a major role in prevention of diseases of the cardiovascular system, which has lead to the use of supplements as a preventative measure with mixed results.  The interesting finding of this study is that the microbiome of healthy subjects contained more bacteria that contain the genes to manufacture carotenoids than those who had suffered a stroke.  This could potentially explain the mixed results seen in the use of carotenoids as a supplement for prevention of cardiovascular disease as not all carotenoids are created equal.

These are just a few of the examples where your gut microbiome affects your health.  In my opinion, the future of health and medicine is in manipulating the microbiome to provide a truly symbiotic relationship between host and symbiont.  In order to do this effectively, we need to look at not only evolution as it pertains to the human genome, but also the evolution of our partners in the gut.  It seems, based on Dr. Ben-Dor's video and evidence from these studies, that the evolution that is occurring in our gut is happening at a much faster rate than the evolution happening to our bodies and the evolution of the bacteria in the gut is driving evolution of our bodies.  This mismatch in evolutionary symbiosis may be one of the primary drivers of poor health seen today.  This can be particularly problematic when bacteria that were once used to manufacture a resource that we need are selected away because we provide that resource directly through diet and then stop providing it as is the case in the modern era of fat phobia.



References

¹Raul Y. Tito, Dan Knights, Jessica Metcalf, Alexandra J. Obregon-Tito, Lauren Cleeland, Fares Najar, Bruce Roe, Karl Reinhard, Kristin Sobolik, Samuel Belknap, Morris Foster, Paul Spicer, Rob Knight, Cecil M. Lewis. Insights from Characterizing Extinct Human Gut Microbiomes. PLoS ONE, 2012; 7 (12): e51146 DOI: 10.1371/journal.pone.0051146

²Vaibhav Upadhyay, Valeriy Poroyko, Tae-jin Kim, Suzanne Devkota, Sherry Fu, Donald Liu, Alexei V Tumanov, Ekaterina P Koroleva, Liufu Deng, Cathryn Nagler, Eugene B Chang, Hong Tang, Yang-Xin Fu. Lymphotoxin regulates commensal responses to enable diet-induced obesity. Nature Immunology, 2012; DOI: 10.1038/ni.2403

³Peter J. Turnbaugh, Ruth E. Ley, Michael A. Mahowald, Vincent Magrini, Elaine R. Mardis & Jeffrey I. Gordon.  An obesity-associated gut microbiome with increased capacity for energy harvest.  Nature, 2012.  444,  1027-1031.

⁴Fredrik H. Karlsson, Frida Fåk, Intawat Nookaew, Valentina Tremaroli, Björn Fagerberg, Dina Petranovic, Fredrik Bäckhed, Jens Nielsen. Symptomatic atherosclerosis is associated with an altered gut metagenome. Nature Communications, 2012; 3: 1245 DOI: 10.1038/ncomms2266

Meal Frequency, metabolism and the mythical stress mode: Why eating 5 times a day is stupid and more than likely counterproductive

Most of you have probably heard the old saying, “You need to eat every 3 hours or your body will enter stress mode and your metabolism will grind to a halt!” You’ve probably heard this from friends, trainer, and maybe even Doctors. When I hear people state this myth it drives me nuts. For one, it shows a complete lack of understanding of the stress response. Secondly, it shows a complete misunderstanding of how the human body works in general. So let’s see where we can shoot this thing down.

To start off, the Thermic Effect of Food (TEF), the mechanism by which you are trying to increase caloric expenditure by eating 5 times a day, accounts for about 10% of calories. That’s right, TEF is related to the calorie load, not the number of times you eat. So, if you eat 2000 calories a day, the TEF will be around 200 calories whether you eat 3 times or 5 times. Now, if you lower calories to 1800, your body will eventually adjust metabolism to that rate and you will stop losing weight. However, if you increase consumption to 2200 calories, your body will actually increase metabolism. The point here is that there is no stress mode, the body just adapts to the number of calories you put in to it by increasing and decreasing efficiency as well as increasing fidgeting and non-exercise related energy consumption. This is fairly common knowledge outside of the Muscle and Fitness crowd.

Now, does your metabolism grind to a halt when you fail to eat every 3 hours? Given that studies of fasting have actually shown INCREASES in resting energy expenditure during fasts of 84 hours (1), I’m going to go out on a limb and say that skipping your mid morning snack should leave your metabolism pretty well intact. Oddly enough, given that the Autonomic Nervous System (ANS) partitions resources based on eating and physical activity, eating 5 times a day may be a bad idea for energy levels. Your ANS controls most of the automatic processes in your body. You know, things like heart rate, blood pressure, digestion, breathing rate, etc. Most people have heard of the fight or flight, or stress, response. The fight or flight response is controlled by your ANS. You don’t need to know the specifics of it, but your ANS is a continuum from rest and digest to fight or flight and is handled by 2 branches of the ANS, the Sympathetic and Parasympathetic Nervous Systems.

When you encounter a stressful situation, your ANS increases blood flow to your muscles, floods your bloodstream with stress hormones, and increases heart rate, blood pressure, and breathing rate so that you can either fight what is coming at you, or flee and live to fight another day. This is handled by an increase in Sympathetic Nervous System activity. When you are resting or eating, your ANS directs blood flow to the organs of digestion while also lowering heart rate, blood pressure, and breathing rate. This is accomplished by an increase in Parasympathetic Nervous System activity.

This is why irritable bowel syndrome is so tightly linked to stress. If you are highly stressed, blood is shunted away from your organs of digestion and towards your muscles, preventing you from digesting your food properly. In the same way, if you are constantly digesting the food you’ve eaten, blood is shunted away from your muscles and toward your organs of digestion. This is why most people tend to feel sluggish after they eat. Optimally your body should switch between the two easily so that you have energy and you can digest your food properly. As such, it’s probably a good idea to give your organs of digestion a rest every now and again by eating 3 times a day or less. In fact, the above referenced study showed the increase in caloric expenditure during fasting was due to an increase in norepinepherine, one of the stress hormones secreted in response to fight or flight.

According to most accounts, we evolved by eating a very small meal in the morning followed by a large meal at night with no lunch in between. To say eating 5 times a day is necessary for fat loss shows a thorough misunderstanding of rudimentary human physiology.

References

1. Zauner, C. et al. Resting energy expenditure in short-term starvation is increased as a result of an increase in serum norepinephrine. Am J Clin Nutr. 2000 Jun; 71(6): 1511-5.

Human Food Project article on fat and gut bugs

http://humanfoodproject.com/can-a-high-fat-paleo-diet-cause-obesity-and-diabetes/?utm_source=Human+Food+Project&utm_campaign=b344ab05c9-Human_Food_Project6_30_2012&utm_medium=email

This article is awesome for 2 reasons.  For one, I have been discussing with clients how the Paleo diet doesn't tend to work if you don't eat loads of vegetables.  Secondly, I am halfway done a blog post on a presentation at the Ancestral Health Symposium on why we have evolved to eat fat.  So what is the interesting tidbit about this article?

The author of this article discusses an interesting link between eating fat and a species of gut bacteria called bifidobacterium.  In mice fed a high fat diet in the absence of bifidobacterium in the gut, obesity ensued.  In mice with bifidobacterium fed the same diet, they remain lean.  So what is this link and how does it work?

A high fat diet leads to low grade inflammation that correlates with an increase in an endotoxin called lipopolysaccharide (LPS).  The LPS leaks from the gut in to the serum and can lead to a whole host of problems including obesity and diabetes.  But how does the LPS get from the gut to the serum?  One study tested this out.

Researchers fed one group of mice a high fat diet and another group a high fat diet and a prebiotic that feeds bifidobacterium.  They found an increase in serum LPS in the group fed only the high fat diet while the group fed the prebiotic with the high fat diet had normal LPS levels.  The theory is that the prebiotic feeds the bifidobacterium which then increase in number and produce fatty acids that heal the gut lining, preventing LPS from entering the serum and causing problems.

So what foods do these prebiotics come from?  The soluble fiber found in plants such as onions, garlic, leeks, and dandelion greens just to name a few.  This explains why a paleo diet that focuses only on meat fails in some people, especially people who are obese and have low levels of bifidobacterium in the first place.  Fix the gut imbalance and fix the problem.

With diet it's "what", not "how much"..

The human body is a complex machine. We like to think we have it all figured out, but at the end of the day my guess is that we probably DON’T understand a thousand times more than what we do. We like to simplify things to make them easier to understand, but a lot of times this actually ends up gumming up the works more than it does in helping us understand a construct. A perfect case of this is the energy balance equation of weight loss. In the past, I made the mistake of telling clients that they should make sure that they are burning more calories than they are taking in and that this should be the core of their weight loss efforts. For the most part, this was a mistake of ignorance. At the time, I didn’t have a thorough understanding of how the human body works. Now that I have a better grasp of human physiology, I would like to take the time to tell you why counting calories shouldn’t be the primary concept you use to lose weight, maintain it, or just be healthy.

1)Energy or raw materials? Your body is made up of trillions of cells, approximately 50 trillion of them. Each of these cells is surrounded by a plasma membrane made up of fat. While it is true that these cells are microscopic, if you were to line them up end to end you would circle the planet 4.5 times. Given that the membrane surrounds the cell, cutting a cell open and stretching the membrane out would more than double that length. In addition, your brain is approximately 60% fat and the sex hormones you make on a daily basis are made from fat. Not to make this point all about fat, your body produces enzymes from the amino acids in the protein you consume that catalyze the chemical reactions within the cells of your body. When these proteins and fats are used for raw materials like this, they may contain calories, but they aren’t being used for energy. If they aren’t used for energy, the calories really don’t count, do they? In the same way, if you had a stack of 100 $50 bills, you would have money to purchase something. If you were out in the wilderness with nothing to make a fire with and used those bills to make a fire, you no longer have something of monetary value, do you?

2)The bugs in your gut… It has been long established that the symbiotic bacteria inside the gut of obese people is different than the bacteria inside the gut of lean people. This makes sense because if I had 2 petri dishes colonized with the same bacteria and fed each dish with different food sources, over time they would have different proportions of each type of bacteria. Studies have shown that these bacteria cause obese people to extract more energy out of their food, approximately 150 calories a day. Over the course of a year, this would lead to the accumulation of 15.6lbs. Underscoring this notion, studies in mice have shown that taking the gut bacteria from obese mice and implanting it in to lean mice cause the lean mice to become obese. The inverse is true as well, taking the gut bacteria from the lean mice and implanting it in to the obese mice cause the obese mice to shed their weight and become lean. Which bacteria proliferates has nothing to do with how much you eat because each bacteria type eats a specific type of food. It’s not how much, it’s what.

3)Appetite The human body is very machine-like. However, unlike a machine, humans can provide themselves with fuel. Given that there are multiple fuel sources for the human body, the type of fuel you select is very important. The fuel you select will influence performance and appetite. If a machine could provide itself with fuel and it provided itself with the wrong fuel, there would be dire consequences. If a diesel engine provided itself with jet fuel, the engine would overheat and blow up. While we don’t blow up, there are metabolic consequences to the food we choose to eat. These consequences affect our appetite, how we feel, how we perform, and future food selection. In study after study, lower carbohydrate diets have been shown to reduce the number of calories you eat by 25%. In addition, life and it’s effect on stress can influence these food choices and how we perform.

4)Sleep Multiple studies have shown that not getting enough sleep not only causes your blood glucose to run higher, it also causes you to make poorer food choices and typically leads to weight gain. If it were as simple as calories in and calories out, less sleep should increase the calories you burn since you would be spending less time sleeping. However, less sleep leads to poorer food choices and less energy throughout the day, which would actually lower the amount of calories you burn. In addition, applying exercise in a dose that is too high for your body to respond effectively to will cause you to lose sleep via overtraining. While you are hammering away on the elliptical machine during that hour at the gym, the lack of sleep will cause you to be less active throughout the day, more or less countering the hour you just spent trying to lose weight.

While it may be more or less true that weight loss is a product of eating fewer calories than you burn, you will never be able to figure out calories in or calories out. In fact, in many instances what you eat has a direct effect on how much you eat.  It is far more complex than we make it out to be. In order to effectively use the energy balance equation, we need to know far more than the calorie content of the food. In fact, there are more factors that we don’t know than we do. What we do know is that some foods will keep you satiated and more likely to stick to the plan than other foods. In addition, certain types of activity lend themselves better to weight loss than others via the influence of hormones, something we will discuss in another blog post.

Myths, Metabolism, & Appetite Part 3

Part 3-Appetite

In part 1 and parts 2a and 2b of this series we went over what some of the research shows and how this runs counter to what most people are told and end up doing to lose weight.  Here’s a recap:

A calorie is indeed a calorie, but your body doesn’t use calories.  A Calorie is a measure of things your body uses, namely carbohydrates, protein and fats.  However, what you eat is not merely energy, it is raw materials for cell membranes, hormones, enzymes and a host of other important chemicals and structures

As you lose weight by lowering calorie intake, your body lowers your metabolism making the calorie you burned when you started much easier to burn than the calorie you burn after dropping 50lbs.  Conventional wisdom is that this is a result of your body protecting body fat stores for times of famine.  However, if you overconsume calories, your body will actually increase metabolism and in both instances it is capable of altering metabolism by 25%.  If your body truly was trying to conserve energy, why would the rules change when you are eating to excess?

Obviously your body adjusts metabolism to the energy intake you provide it with.  This is your body adapting to the environment it is in.  If you provide too much energy, your body increases energy output and when you decrease energy your body lowers energy output.  Looking at it in terms people can understand, which car do you have more faith in, one that can go 500 miles on a tank of gas or 400 miles?  Assuming they are identical, you have to wonder where all of the extra energy is going in the less efficient car since it is not being used for driving further.  In humans, it’s quite possible that the extra energy is speeding up all of your body processes, which is not good.  Efficiency is good, especially when you are dealing with your body, cell division, and repair processes.

While some of your cells will only run on glucose, it is not the preferred fuel for your body.  Your body’s preferred fuel is based on what you put it through via the day, i.e., your environment.  If your job or life is filled with a lot of high force activity, glucose is your body’s preferred fuel.  If you are part of the 99% of people in the United States that sit for hours at a time, drive an hour to work, and only bend over to pick up the piece of donut they dropped, this doesn’t apply to you and fat is your guy.

Mismatching fuel to both what you are engineered to run on (Your genes) and the type of activity you perform drives obesity and diabetes.

Diet is not the only player in this story, exercise is a significant player as well.  When your diet doesn’t match your activity type and level, insulin is used to shuttle glucose in to your muscle and liver cells for storage.  It isn’t that insulin is a bad thing, if you look at Type 1 Diabetics who don’t produce any, you can clearly see how important it is.  The problem with insulin is when we rely on it as the primary way of getting glucose out of our bloodstream and in to our cells.  Once your cells’ glycogen stores are full they stop listening to insulin and you begin to convert the glucose to fat.  High levels of insulin help shuttle this fat in to your fat cells.  Exercise also shuttles glucose in to the cells but instantly burns it.  Provided the intensity of exercise is sufficient, exercise also empties glycogen out of muscle cells and improves their sensitivity to insulin, making it less likely glucose will be turned in to fat and stored.  In the long term, exercise also increases the amount of glucose your body can store as glycogen, allowing a higher consumption of carbohydrate before conversion to fat.

Control of appetite

Now that we have gone over the way our muscles use fuel, we need to direct our attention to appetite.  The primary difference between us and a machine with regard to energy is that we are capable of providing ourselves with energy, and the signal to do this is via appetite.  Appetite is dictated by the interplay between the hypothalamus in the brain, the gastrointestinal tract, and adipose (Fat) tissue.  Both hormones as well as circulating levels of glucose and fatty acids provide information to the hypothalamus so that appetite can be adjusted.  The primary hormones that deal with regulating appetite are Ghrelin, PYY, Leptin, and insulin.

Ghrelin is a hormone secreted by the empty stomach to stimulate food uptake.  Once you eat and the food enters your stomach, ghrelin release is stopped, signaling you to stop eating.  PYY, on the other hand, is released after you eat to signal that you are in a fed state and can stop eating.  Both of these hormones work by controlling the secretion of appetite stimulating Neuropeptide Y and AgRP; ghrelin by increasing secretion and PYY by inhibiting it.  Leptin, on the other hand, is a completely different animal.

When you consume too much food, whether it is from fat or carbohydrate, the excess energy is converted in to fat.  As you starting making triglycerides, the storage form of fat, they move to adipose tissue where they are stored.  This releases the hormone leptin from the adipose tissue, which signals the hypothalamus to decrease appetite.  In the short term, insulin tends to signal the hypothalamus to curb appetite in a similar way.  In the long term, high levels of insulin seem to have the opposite effect, increasing appetite.

Leptin resistance

As your body fat increases, it secretes more leptin to signal a fed state.  While body fat increases you become insulin resistant, and as this body fat continues to secrete leptin, you actually become leptin resistant.  In a healthy individual, the hypothalamus gets the signal that high levels of leptin mean you no longer need to eat, but in the leptin resistant individual, the cells within the hypothalamus either don’t get the signal or ignore it.  Despite having high levels of circulating leptin, obese individuals that are leptin resistant do not get the fed signal and their appetite remains high.  It’s not that they are always hungry, it’s that they never get the signal to stop eating.  As you can see, leptin resistance and insulin resistance run hand in hand with one another.  If you can control insulin resistance you can control leptin resistance, allowing your hypothalamus to properly control appetite.

This is by no means a comprehensive list of hormones within the body that control appetite, but these are the major players.  As mentioned above, circulating levels of glucose and fatty acids also play a major role in the regulation of appetite.  In fact, if you are insulin resistant, the nutrient partitioning (Fuel selection) effects of insulin can boggle this signal and not only inhibit fat loss, it can also make the effects of cutting your caloric intake unbearable.

Trappings of caloric restriction

Anyone who has undertaken a weight loss program by either reducing calories or exercising away the pounds has at one time felt voraciously hungry, irritable, dizzy, brain fog, or just a complete lack of energy.  Eventually you reach a tipping point and go on a food binge, undoing most of the weight loss progress you have accomplished up until that point.  Most of this can be very easily explained when you look at what you eat, not how much.

When most people decide to tackle a weight loss program, they will cut their calories to some number, let’s say 1500, and begin exercising.  For the most part, people will keep their carbohydrates at 50% of their calories which leaves them with 187.5 grams of carbohydrate.  It has been established that when the brain and central nervous system use glucose as their primary fuel, they need approximately 150g for proper functioning.  This leaves 37.5g of glucose for the rest of your body to use.  The problem with this situation is that even just taking resting metabolism in to account, this is not enough.  So, not only are you already starting out in a hole, once you exercise you have depleted some of the glucose that would be later used for the brain. 

A 130lbs woman will burn approximately 60g of glucose during an hour long run at a pace equivalent to a 10 minute mile.  Increasing the intensity you run at not only increases the amount of carbohydrates you burn via an increased calorie burn, it also increases the percentage of carbohydrate you burn, a double whammy.  This energy is taken out of the system as it is performed, so the brain will eventually enter a low energy state unless you provide it with more fuel.  Just taking in to consideration total daily carbohydrate intake and not accounting for the fact that this exercise may have been done while you have only consumed 1 or 2 meals, this leaves you with 127.5g of carbohydrate for a system that needs 150g.  Interestingly enough, this system also contains the appetite center.

Your brain on ketones

As you can see, a single exercise session of an hour can cause your brain to enter a low energy state while carbohydrate is the dominant fuel source, leaving you hungry and negatively impacting brain function.  This doesn’t even take in to account the glucose that is used for other parts of the body that can only run on glucose as well as other physical activity you may take part in.  It is very easy to see how this could leave you feeling hungry, irritable, preoccupied with food, and a little off mentally.  All is not lost, however.  While it was thought for many years that the brain could only run on glucose, there is actually another fuel the brain can use.  The best part about this fuel is that you will not run out of it until you run out of body fat.  This fuel is a byproduct of fatty acid metabolism called ketones.

Most people familiar with the Atkins diet have heard of ketones or ketosis.  Ketones are essentially the leftovers once a fatty acid has been metabolized for energy and can be metabolized for energy by the heart and the brain.  With ketones provided as an energy source, the brain can function on less carbohydrate, allowing the rest of the body to use what it needs without negatively impacting brain function.  As a substitute for glucose, ketones can provide up to 70% of the brain’s energy needs, lowering the amount of glucose necessary for proper function from 150g to 45g.  Provided you have a good amount of fat to lose, the brain will not enter a low energy state until those fat stores are gone, which is more or less the point of a fat loss program.

The question now becomes, “How do we get the brain to run on ketones?”  In a healthy individual who has good insulin sensitivity and who exercises regularly, ketones probably provide some energy for the brain.  In an insulin resistant individual, high levels of insulin prevent ketones from being formed by blocking the release of body fat stores AND inhibiting fat burning.  In addition, having a high level of carbohydrate in the diet while at the same time eating every 3 hours will cause insulin to be secreted for a couple of hours after every time you eat, which brings us to another myth.  Eating every 5 hours is foolish and will not dramatically impact your metabolism.  In fact on a moderate to high carbohydrate diet it will do more harm than good.

The thermic effect of food, the number of calories used to process what you eat, is related to the amount of food you eat, not how many times you eat.  For comparison’s sake, the thermic effect of food only accounts for 10% of the calories you consume.  In someone who eats 2000 calories, that effect is 200 calories per day, so we are probably only dealing with a 50 calorie per day difference between eating 5 times a day instead of 3 times.  However, if you eat 5 times a day and get insulin secretion for 2-3 hours after every time you eat, this will lead to 10-15 hours per day that you cannot access body fat stores or burn fat effectively to make ketones for the brain.  This will certainly affect appetite, talk about putting your eggs in the wrong basket.

Becoming keto-adapted

So, how do we get the body to become keto-adapted?  First, you have to repair insulin sensitivity to lower the amount of insulin coursing through your veins so that ketones can be made.  The most effective way to do this is to reduce the amount of carbohydrate you consume for a few days.  The amount of carbohydrate you should consume is variable from person to person, but a general recommendation is under 50g of carbohydrate for 2 weeks followed by a gradual increase to tolerable levels based on activity level (1).  Once you’ve done this and things start working properly, keeping insulin levels low via carbohydrate restriction and properly programmed exercise will allow ketone bodies to be formed.  In the initial period following this adaptation, your brain is not very efficient at using ketones.  People who have done the Atkins diet are probably familiar with ketosis and measuring ketones in your urine.  If you are dumping a significant amount of ketones out of your body via urine, your brain can’t possibly be using them effectively.  In fact, once your brain does start using them, urinary ketone levels should start to drop.

There is another way to get ketones to the brain without consuming a low carbohydrate diet.  Coconut oil contains medium chain triglycerides(MCTs) which are instantly metabolized for energy.  As a result, ketones are formed and can be used by the brain as energy, which may be the mechanism by which coconut oil suppresses appetite.  However, this effect will probably only work on someone who is fit and has a properly operating metabolism.  In other words, if you are insulin resistant, it probably won’t work.  If you are an athlete with good insulin sensitivity, MCTs may be something you want to look in to. 

The benefit of ketones to the brain may be far greater than the effect on appetite and body composition.  It has been hypothesized that the protective effect calorie restriction has on the brain may be related to the use of ketones as a substrate.  Increases in brain-derived neuroptrophic factor (BDNF) that occur during fasting may be triggered by the ketogenic energy pathway as are multiple other protective factors (2).  BDNF is a potent driver of brain neurogenesis, the ability to form new connections in the brain.  From an evolutionary perspective this would make sense, it is obviously beneficial for brain function to be enhanced when food is scarce, and for the greater part of our evolution fasting wasn’t a choice it was more or less forced upon us.  This is all speculation at this point, there have been no good trials looking directly at ketones and neurogenesis in humans.  The fact that the neuroprotective effects of calorie restriction seem to be mirrored during a ketogenic diet provide some support that it is not merely the reduction in calories that are the primary driver.

Conclusion

Hopefully this 3 part series has given you an idea as to how complex the science of weight loss and nutritional intervention is.  While I agree that calories do matter, looking at calories in vs calories out is far too simple of an algorithm to use for weight loss, which is probably why it rarely works when you take in to account all of the factors, including appetite.  We not only have to take in to consideration energy, we have to look at the type of energy, the type of activity being performed, the machinery doing the activity (Fiber type and cell type), as well as appetite.  Taking a comprehensive approach is far more effective than the generalist approach of using the energy balance equation, especially when we are dealing with tissues and organs that can alter which substrate they use for fuel depending on the fuel you provide.  Improving insulin sensitivity via the appropriate exercise and diet as well as getting the brain to run on ketones puts more tools in your tool box.  Whether or not you are improving insulin sensitivity directly via carbohydrate restriction or via calorie restriction is irrelevant, they both will work and through basically the same mechanisms.  However, given appetite is a major consideration that will be negatively impacted by calorie restriction and positively impacted by carbohydrate restriction, the scales easily tip in favor of carbohydrate restriction.

References

1.       Volek, JS & Phinney, SD.  The Art and Science of Low Carbohydrate Living: An Expert Guide to Making the Life-Saving Benefits of Carbohydrate Restriction Sustainable and Enjoyable (2011).

2.       Maalouf M., Rho J. M., Mattson M. P. (2009). The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. Brain Res. Rev. 59, 293–315.

 

Myths, Metabolism, & Appetite Part 2b

Continued from part 2a...

Muscle fiber type distribution in Type 2 Diabetics

One of the more intriguing attributes of people with obesity and Type 2 Diabetes is that they have a higher percentage of Type IIx muscle fibers and a lower percentage of Type I fibers (5, 6, 7, 8, 9, 10).  When we look at the 3 muscle fiber types, the IIx fibers are the most insulin resistant, followed by the IIa and, finally, the type I fibers are the least resistant to insulin(11).  Obviously a person with a higher percentage of muscle fibers that are insulin resistant will be more prone to insulin resistance and the conditions associated with it.  Looking at this merely on the surface, one would be inclined to believe that people born with a higher percentage of Type IIx muscle fibers may be particularly prone to these conditions.  While the data shows that genetics probably plays a large role in your percentage of Type I vs Type II fibers, it probably has little to do with Type IIx fiber distribution.  When you look at all of the information that is out there, it appears more likely that this is an adaptive response by the body to the environment presented to it.  In other words, it is a classic gene/environment interaction that develops within people who have a higher percentage of Type II muscle fiber types.

Muscle Fiber Type Conversion

It has been well established that all training, whether it be cardiovascular/aerobic or resistance training/anaerobic, causes a change in type IIx muscle fibers by either converting them to type IIa fibers or causing them to take on the characteristics of the more intermediate IIa fibers(12,13).  This is a positive adaptation in that it allows you to do more work before fatigue sets in by increasing the amount of energy the fiber can store and the amount of energy it can make.  In addition, once training ceases for more than a week, the IIa fibers revert back to IIx fibers.  In fact, all sedentary people experience this conversion whether they are prone to diabetes/obesity or not. 

Knowing that the IIx fibers are primarily driven directly by ATP and have low glycogen, it makes sense that they would be insulin resistant because they fill up with glycogen faster.  As an adaptive response to training, they increase glycogen storage and mitochondria content while at the same time receiving an increase in blood flow via an increase in capillaries serving the fiber, which is basically the same thing as taking on IIa fiber characteristics.  This improves their insulin sensitivity both by using the glycogen content of the fibers as well as increasing their capacity to store glycogen, improving their ability to dispose of glucose from the blood.  It also improves their ability to generate ATP from fatty acids given that is the primary role of the mitochondria.  In other words, they burn more fat.

So, what drives this adaptation, is it simply a use it or lose it scenario or is it caused by some environmental factor?  Interestingly enough, it appears this adaptation may be driven hormonally, specifically by our good friend insulin.  In a study performed on rats, induced hyperinsulinemia caused IIa to IIx conversion (14).  In another study performed on humans, inducing hyperinsulinemia on 10 young male subjects for 3 hours increased MHC IIx gene expression by 40% when compared to control conditions in each subject (15).  This means the subjects were beginning to make Type IIx muscle fibers as a response to high insulin levels.

It makes sense that this could be the body adapting to the environment you are providing it, insulin only gets high when you secrete a lot of it.  If you eat a ton of carbohydrates and don’t exercise you will create tons of insulin to deal with that glucose.  If you eat the same amount of carbohydrates and exercise a lot you will be using exercise as your method of getting glucose in to cells, insulin will stay low, and this conversion will not happen.  This provides support for the notion that Type 2 diabetes is a reversible metabolic state.  If you activate IIx muscle fibers they convert to IIa fibers, become more sensitive to insulin, and are capable of disposing of more gulcose in the event blood glucose gets too high.  If you stop using them they will convert back to IIx fibers, become more insulin resistant, and become relatively worthless with regard to disposing of glucose.  The end result is elevated blood insulin levels to force the glucose in to the lower threshold Type I fibers and eventually, fat cells.  A high percentage of Type II fibers in general is a very strong risk factor for Type 2 Diabetes, and it makes sense since they will switch from IIa fibers to the more insulin resistant IIx fibers with disuse. 

Type IIx fibers have often been referred to as the default fiber type, but this is not something that has been studied extensively.  Given that the modern diet is, by default, high in carbohydrate, it would be interesting to see the effects of a high fat diet on muscle fiber type conversion.  Would a high fat environment induce the opposite effect?  In other words, if you consumed more fat would this cause fiber type changes that favor fat oxidation, a conversion to Type I fibers?  While the effect of a high fat diet on fiber type has not been studied directly, there have been studies that show physiological adaptations via gene expression to burning fat from a high fat diet (16) and endurance exercise (17).  It is highly unlikely that eating a high fat diet would induce a fiber type change from Type IIx to I given that IIx fibers have a very limited blood supply, but the latter study did show an increase in genetic expression of genes responsible for the creation of mitochondria from exercise.  A limited blood supply means ingested fatty acids probably wouldn’t make their way to the IIx fiber, but if these fibers converted to IIa fibers via exercise the blood supply may become sufficient enough to go from IIx to IIa to I. 

There is the possibility that a high fat diet could induce a Type IIa to I fiber conversion given the good blood supply to IIa fibers.  The general consensus is that fibers may convert in the following ways:

Type IIx<------------>Type IIa<------------>Type I

There is plenty of evidence of IIx to IIa and IIa to IIx conversion in multiple studies, but the lack of studies on conversion of either Type II fiber types to Type I fibers makes any notion that this conversion is possible speculative at best.  In addition, given that fiber type is dictated by the type of nerve that fires the muscle fiber, this conversion is unlikely.

Since we know people who are prone to obesity have a higher percentage of these Type IIx fibers, getting them to convert to IIa fibers is a potentially good intervention.  In order to get IIx fibers to take on the characteristics of the IIa fibers, you have to activate them on a regular basis, which means meeting their force activation threshold or fatiguing the muscles recruited before them to the point the IIx fibers need to kick in.  Given the high force threshold for activation of IIx fibers, this is not likely to happen with distance running or aerobics, the exercise should be glycolytic and short in nature with appropriate rest between exercise sets.  The best options that meet these criteria are high intensity resistance training, plyometrics, and sprints.  While it is certainly possible that you could eventually activate IIx fibers via endurance exercise once the Type I and IIa fibers run out of fuel, the speed you would need to run at or the amount of time you would need to run for make it an unappealing option.  However, no matter which dietary approach you decide to use, low carbohydrate or low calorie, diet will have no effect on increasing the blood supply to IIx fibers, underscoring why it is so difficult to get rid of insulin resistance once you have it.

When we look at what happens to people as they age, we see the same adaptation as we see in sedentary people, a conversion from IIa to IIx muscle fibers and eventual atrophy of the IIx fibers, making them even insulin resistant.  As a result, the risk of Type 2 Diabetes doubles when you reach the age of 65 and doubles again when you reach 80.  When we look at studies involving older people and resistance training, we see nearly identical improvements in muscle fiber type characteristics and measures of insulin resistance as we do in younger people (18, 19, 20) that we would not expect to see in endurance training unless it were progressive in nature.  In other words, if you can run 5 miles at a pace of 10 minutes/mile, your fiber type characteristics will improve a little and then stop unless you increase your speed to 9.5 minutes/mile.  Then, the adaptations would stop until you increase your speed even further.  This is something that a competitive endurance athlete does that your typical gym-goer does not.  A much better option is to induce this fiber conversion via high intensity resistance training, which takes less time, is more pleasant, and is unlikely to cause an overuse injury provided it is done properly and progressively.

Glycogen depletion during exercise

During high intensity exercise, glycogen is depleted equally among the muscle fiber types.  This makes sense given that during high intensity exercise, all muscle fiber types are recruited.  During aerobic exercise, most of the glycogen depletion during the onset of exercise comes from the Type I muscle fibers.  Given that these fibers have a low glycogen storage capacity, they run out of glycogen relatively quickly.  Once this happens, the Type II fiber types will start to kick in to allow exercise to continue.  But wait, we mentioned above that Type II fibers have a high contraction threshold, why would they be activated at a lower threshold?  To provide fast acting glucose to the Type I fibers which will fatigue without it, and the process is actually pretty cool.

Recall that the glycogen within a muscle fiber has to be metabolized by that fiber.  If this is the case, how can the Type II fibers provide glucose to the Type I fibers?  The answer, aka loophole, is lactate.  If you have ever exercised for a long period of time, you have probably felt the burn associated with lactate/lactic acid.  This burn actually comes from the high levels of hydrogen ions that are created alongside lactate.  While glycogen cannot be passed on from fiber to fiber, lactate can.  As lactate accumulates in a muscle fiber, it is shuttled out of the fiber and in to the blood where it goes to the liver and is converted to glucose.  Now, this glucose is free to go wherever it is needed.  But what happens once exercise ceases?

Glycogen Storage

One concept that is important to grasp with regard to exercise and it’s effect on insulin sensitivity is that the improvements in insulin sensitivity are not permanent, they only last for a limited period of time.  This is probably variable based on the amount of exercise you do, the type of exercise, and the amount of carbohydrate you consume afterwards, but is typically about 36 hours following exercise.  During the recovery period following exercise, the body preferentially stores glycogen while increasing fatty acid oxidation, even when it is primarily carbohydrate being consumed.  The hormonal environment post-exercise primes the muscles to store glucose rather than burn it (21, 22, 23). 

The body’s drive to replenish glycogen is so great that even during fasting after exercise it tries to replenish muscle glycogen stores, provided they were used during the exercise period(22).  What the body uses to replenish glycogen stores post-exercise in the absence of food is primarily dictated by the intensity and duration of the exercise.  If the exercise was intense and of short duration, the lactate generated during exercise is used to replenish glycogen.  If the exercise was of moderate intensity but long duration (Long distance running anyone?), amino acids are the fuel, i.e., your muscles (22).

In addition, even if you are performing physical activity, your body will replenish glycogen in the muscle fibers you are not using (22).  Active recovery is a recovery modality where you continue to do low intensity activity like walking or lower intensity exercise after a period more of intense exercise.  During active recovery following exercise, even though Type I fibers are still using glucose, some of the glucose being made in the liver from lactate is actually shuttled to the Type II fibers that are not being used to replenish glycogen stores (22).  This is, of course, contingent on those fibers depleting their glycogen stores first.  If the intensity of exercise prior to the recovery was not sufficient enough to engage the higher threshold IIx fibers, they will not need glycogen.  However, the Type IIa fibers, which have a lower contraction threshold, are probably being activated to provide the lactate that is converted in the liver to glucose to fuel the Type I fibers, so their glycogen content would be depleted to some extent.

The science vs “conventional wisdom”

The evidence appears to support the notion that we are dealing with a mismatch between the primary type of fuel consumed and the type of activity performed, at least in obese people and Type 2 Diabetics.  Given that obese/diabetic people have more IIx fibers and that glycogen is preferentially directed to these fibers even during fasting and physical activity, these fibers will typically be insulin resistant unless used regularly.  In people with a higher percentage of these fibers that also tend to over-consume carbohydrate and not perform physically demanding activity, it appears that we are seeing a classic gene/environment interaction that is driving the obesity epidemic.  This same interaction occurs in non-obese people as well via a conversion of IIa fibers to IIx.

Taking all of this data in to consideration, performing intense physical activity on a regular basis is obviously something important for anyone who wants to maintain insulin sensitivity throughout life.  In people who are Type 2 Diabetic or obese as well as their children, it is absolutely critical while carbohydrate is a significant part of the diet.  It is also important to make sure this activity is performed with both the lower AND the upper body as well as with a full range of motion.  In order to improve insulin sensitivity even further, it would also be smart to vary your exercises frequently to make sure that you are hitting as many muscle fibers in as many muscle groups as possible.  So, let’s compare what the science shows to the route most people are recommended to take by the medical establishment.

If you go in to the Doctor’s office and get a diagnosis of Pre-diabetes or Type 2 Diabetes, you are told that you need to change your diet and start an exercise regimen.   The general theme of the discussion will center around the fact that you need to lose weight.  While this is true, the extra weight doesn’t cause Diabetes, the extra weight is an effect of Diabetes caused by insulin resistance.

If you lose some fat you are improving insulin sensitivity via exercise and diet because if you weren’t you wouldn’t be able to release or burn body fat.  The problem is you are doing it indirectly by focusing on creating an energy deficit.  More often than not the exercise portion of creating this deficit is long distance running, a spin class, or some other aerobic activity.  This will take forever and require a massive amount of effort given the IIx fibers are not recruited for this type of activity so they can’t convert to IIa fibers.  Given that you would still have a higher percentage of insulin resistant muscle fibers, the insulin resistance is probably still there, and unless your diet is spot on and very low carbohydrate you will continue to have problems with your blood glucose. 

In fact, you may be able to maintain normal blood glucose levels as long as you keep your carbohydrates low or exercise for hours per day.  If you go wild and hammer in to carbohydrate-heavy food or stop running, your blood glucose will shoot through the roof along with your insulin levels.  This doesn’t even consider the fact that very few people who run long distances do so with a full range of motion, progress it properly, and that running and spinning do little to nothing for the upper body.

At this point you are probably going, “Wait a second, I know a bunch of people who do long distance running or spinning and they aren’t overweight.”  While this is certainly true, chances are these people aren’t prone to Type 2 Diabetes or obesity.  They probably have a higher percentage of Type I fibers so they are better suited to distance running, or they may not have the genetic predisposition to store body fat.  While the former would make them far less likely to develop Type 2 Diabetes, neither prevents them from developing insulin resistance.  Anybody can become insulin resistant at any time, and you don’t have to have an outwardly obese appearance to have either Type 2 Diabetes or insulin resistance.  It would certainly be much more difficult for a person with a high percentage of Type I fibers to become insulin resistant, but it is possible.  Whether you are Type 2 Diabetic or not, insulin resistance is a bad scene.  A small list of the diseases/issues associated with insulin resistance includes cancer, heart disease, high blood pressure, stroke, fatty liver disease, metabolic syndrome, Polycystic Ovarian Syndrome, and Type 2 Diabetes/Obesity.  So, don’t think you’re safe just because you are lean.

Conclusion 

If you get anything from part 2 of this series, it’s that insulin sensitivity is NOT a 1- trick pony.  With exercise, you have something you can do that mimics the primary effect of insulin while at the same time lowering your resistance to insulin provided you do it properly.  In the context that most people approach exercise, I agree with Gary Taubes, that it has little effect on fat loss.  But, in the proper context with the proper modalities it not only helps improve insulin sensitivity in a way that diet cannot (You will not empty glycogen from a muscle fiber with diet, only activating it via activity will do that), it gives you leeway in the event you want to consume some higher carbohydrate meals.

Now that we have looked at the science behind obesity and diabetes, it seems the exercise prescription given by the medical establishment is way off base.  While capable of attaining short-term success, it comes at the expense of long-term health.  At the end of the day, this approach is unsustainable.  You will be exercising 8 days a week and eating rice cakes all day which is not even remotely necessary.  You will be hungry, irritable, and won’t be able to think straight.  You will be constantly preoccupied with food and tired until you just give up.  You will also enter an overstressed state and become either sick, injured, or not be able to sleep.  Does this sound familiar?  There are very specific reasons why all of this happens, and most of it is dictated by hormones.  

In Part 3 we will answer why all of this occurs and how to adjust your diet to prevent it.

(Having problems publishing the references, I'll plug them in later today)

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