Thursday, September 25, 2014

Movie Review: Fed Up

I think my feelings towards this movie can be summed in 2 words:

While I think the central message given at the end of the movie is a strong one, that people should be primarily eating home-cooked meals made from fresh and local meats and vegetables while limiting or avoiding processed foods, there is too much of what I find to be a recurring theme in most of these movies.  This theme is that personal responsibility is not a central part of the answer to our obesity epidemic.

To begin with, there are some parts of this movie that I agree with.  The government is certainly making the problem worse by subsidizing bad food, proposing terrible, confusing, and oftentimes conflicting recommendations, and essentially being a puppet for the food industry.  Advertising junk food to kids is also a pretty hot button issue that certainly makes a parent's job much more difficult.  Finally, bringing the food industry in to school cafeterias is also a pretty troubling move that even the most staunch proponent of liberty would have to question.  In the movie they put up clips from the usual bozos from Fox News that decry the nanny state that is reinforced when any form of government regulation on food is proposed.  This is a false dichotomy, one can be for personal responsibility/liberty as well as intelligent regulation within the food industry, the problem is intelligence in this country is lacking.  If you don't believe this, realize that if you feel that television advertising is damaging to children, you could always turn the TV off.  Or, if you still want them to watch television, you could remove the commercials from the program and let them watch their shows a day late.  

The movie interviews many children who are dealing with the many health and social complications associated with obesity.  You can't help but feel for these children as they tell their stories of being ostracized by classmates and feeling like they are different from their peers.  While I believe personal responsibility is going to play a central role in fighting the obesity epidemic, you really can't blame the kids for the problems they face.  When dealing with children, I don't believe the lack of personal responsibility lies with them, it lies with their parents.  It's not a far cry to say that children that were raised in a household of violence are more likely to raise their kids that way, why is it groundbreaking to think that an adult who is raised to become obese and that becomes obese would raise children that would have the same problem?  It's interesting to note that every parent of these children was either very overweight or obese.

This is probably not a popular belief, especially with parents, but it's certainly my belief.  While I believe the food advertising directed at kids likely plays a large role in the obesity epidemic, my question is why are the kids spending so much time watching television if the ads are damaging?  The answer is simple, it's easy.  Likewise, why do parents feed their children processed food or have them purchase lunch in school?  Simple, because it's easy.  Why don't parents tell their kids no when they ask if they can have cake on a random Tuesday night.  The answer, because they know they'll throw a fit.  Avoiding a easy.  This reminds me of a great stand-up routine by Louis CK.  (Warning, NSFW)

Convenience is coveted here in the United States and living a healthy lifestyle is anything but convenient.  It's also inconvenient to miss parties with your friends while studying in medical school, but the payoff is certainly worth it.  In most instances, delaying instant gratification for long term goal accomplishment tends to be quite satisfying and leads to greater success in the long run.  While most parents are fortunate enough to not have to witness the death of their children, is it really any more comforting to know that you're laying down patterns that will likely cause them to die early of something preventable after 5-10 years of suffering that will likely be painful and dramatically impact their quality of life?  Go in to a hospital or retirement home and take a look at the patients, each one of those patients was someone's child too.

The movie almost made up for it's shortcomings at the end where it more or less told people the power is with them to make the right choices.  However, after spending the whole movie telling people personal responsibility won't cut it and that the government has been screwing everything up, the end essentially promotes personal responsibility and asks for the government to step in.  The mom of Brady, one of the kids interviewed for the movie, summed it up best.

"You have to be willing to put forth the effort, it's a matter of priority."

While Brady made tremendous progress when the family followed a diet low in processed food, once he stopped he gained all of the weight back.  So when his family prioritized health and put forth the effort to make better decisions, they were able to make incredible health improvements.  When they stopped prioritizing and working at it they went back to the way they were.  Imagine that.

Overall, I did not like this movie.  I believe the message to eat mostly whole, unprocessed food is on target.  I believe they dropped the ball on several points.  First, exercise was an afterthought and seen as a way to be a scapegoat for the food industry.  News flash, exercise is important, that is undeniable.  Second, there is universal agreement within the science community that spending time seated in front of a television is one of the worst things for your health.  If you reduce the amount of time you sit in front of a television, you will see a lot fewer advertisements and will be much less prone to eat mindlessly, which is another thing with universal consensus as being unhealthy.  Finally, I personally believe telling people, particularly children, that they can't do something because the cards are stacked against them is inherently demoralizing.  Rather than making them out to be victims of the food industry, how about we raise them to make better decisions and lead by example.  Telling a kid they can't do something but then doing it right in front of them really doesn't reinforce the argument that eating bad food is a poor decision, it just reinforces that it's something they will be able to do when they are adults and they will put it on a pedestal.  Sort of like drinking alcohol, and we all can see how well telling kids they can't drink until they are 21 has worked to prevent underage drinking.

Monday, September 22, 2014

Endurance exercise, heat tolerance, and gut health

GI disturbances are a frequent complaint in those competing in endurance and ultra-endurance competitions.  In addition to GI disturbances, many athletes must cope with heat tolerance issues as well as heat stroke.  While many researchers focus on the detrimental effects of endurance exercise on the heart, heat stroke is a much more common occurrence, especially in warmer climates(1).  While most endurance athletes probably attribute an intolerance to heat or heat stroke to other mechanisms within the body, the research to date points to immune disturbances caused by increased intestinal permeability as a casuative and/or major contributive factor.  In other words, the body's inability to cool down isn't because heat isn't being dissipated properly through sweating, it's because the immune system is being activated.  In this blog I will go over the science of what causes this and other factors that can contribute to the problem.

Heat as an inducer of heat stroke

The classic model of heat stroke was centered on the notion that once a critical core temperature is reached that is damaging to cells, the hypothalamus decreases the neural drive to muscles.  This decreases heat production and, therefore, core temperature.  So, in essence, there is a safety mechanism built within the hypothalamus that prevents core temperature from exceeding a certain point that could be detrimental to the cells of the body.  While this is true, there are a couple of issues that contradict this model.  First, people often experience heat stroke at workloads they have previously tolerated, both in terms of performance and heat stress.  Second, core temperature doesn't seem to share a relationship with the severity of symptoms experienced once heat stroke is triggered, but there is a strong relationship between symptom severity and circulating inflammatory cytokines(2).

The immune system as an inducer of heat stroke

These factors have caused researchers to propose a dual model of heat stroke that has a heat induced pathway and an immune system induced pathway.  There doesn't appear to be a specific core temperature at which heat stroke is induced between individuals or within the same individual, and many of the clinical manifestations of heat stroke are identical to those found in sepsis, a whole body inflammatory response to infection.  It is believed that endotoxemia, the leakage of lipopolysaccharide(LPS) from the gut in to the circulation due to increased intestinal permeability, drives this inflammatory process.  This has led scientists to develop an endotoxemia model of heat stroke where hyperthermia initiates heat stroke by increasing intestinal permeability, but endotoxemia drives the clinical progression.  It is believed that this model of heat stroke is the primary cause as the vast majority of people who experience heat stroke are not reaching the critical core temperature that is damaging to cells(2).

When an endurance athlete competes or performs an intense training run, blood is diverted from the gastrointestinal tract and toward the muscles to power the activity and toward the skin to dissipate heat via sweat.  In addition to these changes in circulation, the immune system is also suppressed.  This combination of physiological changes, in addition to mechanical jarring of the area, increases intestinal permeability and causes LPS to leak in to the circulation(2, 3, 4, 5).  These issues are exacerbated when runs are prolonged, in the heat, and under conditions of dehydration(3).  Since LPS drives the immune system nuts, and the immune system is suppressed, it is believed that pushing through causes LPS levels to increase further, and sepsis occurs.

The immune system and chronic endurance exercise

This may sound like a whole bunch of doom and gloom for people undertaking endurance exercise, but the body adapts.  A chronic adaptation to long term endurance training is an increase in anti-LPS antibodies(2, 4).  This means training at or above the threshold that causes LPS to leak from the GI tract in to the circulation causes the body to deal with LPS better.  However, this brings up a couple of interesting questions.  Why would a well trained, experienced runner experience heat stroke during a run of tolerable intensity?  Also, how can some trained athletes tolerate levels of heat that induce heat stroke in others?

Internal vs. external environmental conditions

Obviously external environmental conditions, especially in extremely hot environments, could be at play, but what about internal environmental conditions?  In other words, maybe it isn't the state of the environment that is causing the problem, maybe it's the physiological state of the athlete.  One potential contributing factor is obvious; training during an infection.  The trio of an existing infection, an acutely depressed immune system, and LPS leaking from the gut in to the circulation could negatively impact heat tolerance causing once manageable workloads to cause unmanageable levels of LPS.  There is data to support the evidence that immune disturbances can lead to transient heat intolerance(2).  Furthermore, many animal studies show that heat tolerance is improved and heat stroke can be averted up to a point when animals are given therapies to help deal with LPS.  Animals given therapy to bolster LPS clearance are better able to tolerate heat and do not succumb to heat stroke until temperatures exceed 43.8C, which is considered the critical temperature for cell damage(2).  In a small study, all monkeys who were given anti-LPS antibodies were able to survive at 43.5C but only 16% of control monkeys lived as the rest succumbed to heat stroke(6).  When core temperature was raised to 43.8C, all of the monkeys died but the treated monkeys lived 5 times longer than the controls.

Gut health as a contributing factor

Another avenue worth exploring is the health of the gut.  Many factors affect intestinal permeability under what would be considered resting conditions including the use of anti-inflammatory drugs, antibiotic use, and diet.  A recent study looking at the use of ibuprofen found that intestinal permeability after exercise was greater when an athlete took ibuprofen than when they did not(7).  This is important because many athletes use anti-inflammatories as a training tool to help reduce inflammation, and this study shows that there may be drawbacks to using this approach.

Antibiotic use is known to change the ecology of the gut by modulating gut bacteria.  Changes in gut bacteria can lead to alterations in intestinal permeability as many of the byproducts of bacterial fermentation are known to help maintain intestinal barrier integrity.  Elimination of a keystone species may impair an athlete's ability to maintain intestinal barrier integrity and lead to greater levels of LPS during exercise and, thus, decreased heat tolerance.  This is not to say you shouldn't take antibiotics, but you should only take them when needed and maintain a diet high in fiber when doing so because it will support the bacteria that are responsible for maintaining intestinal barrier integrity.

Diet as a preventative therapy

This brings us to diet, one of the most important "therapies" a person can use to maintain optimal intestinal barrier integrity.  A proper diet helps maintain intestinal barrier integrity by optimizing gut bacteria, providing nutrients that gut bacteria can use to uphold the intestinal barrier, and limiting the types of food that can increase intestinal permeability.  Under optimal conditions, the intestinal barrier is maintained by tight junctions, areas between cells that don't allow contents of the intestine, including LPS, in to the bloodstream.  These tight junctions can be dissolved under certain conditions, and the fermentation of soluble fiber and resistant starches by resident bacteria generate short-chain fatty acids that reseal these tight junctions.

Certain foods can increase intestinal permeability, particularly ones that contain gluten.  Gluten causes the release of zonulin, a protein that causes the tight junctions between cells of the intestine to dissolve.  All humans secrete zonulin in response to gluten, but most people reseal the tight junctions rapidly, before significant levels of LPS enter the circulation.  People with Celiac disease or a sensitivity to gluten have a delayed response which allows more LPS to enter the circulation and increase inflammation.  Researchers believe that this delayed ability to reseal the tight junctions is due to local changes in gut bacteria.

Despite the mass hysteria surrounding gluten, I don't feel that everyone should avoid gluten.  In limited quantities in an otherwise vegetable/fiber heavy diet, gluten is likely harmless for most people.  However, there is nothing nutritionally novel about gluten that makes it a necessary part of your diet, and most people are likely overeating it while undereating higher quality foods like vegetables. 

Chronic alcohol intake is another thing that can increase intestinal permeability and cause damage to the cells of the intestine both directly and as a result of bacterial fermentation(8). The concern here isn't that people are getting loaded before their runs and this impacts their ability to regulate core temperature.  The primary concern is that people who chronically ingest alcoholic beverages, particularly beer, may be changing their gut ecology over time in a way that may reduce their ability to reseal tight junctions after distance runs.


As research on the topic of gut health progresses, we find more and more physiological processes that gut health affects.  This blog presents compelling evidence that gut health can directly impact performance in endurance competitions through modification in heat tolerance.  If you take one thing from this blog, it should be that it is in your best interest to pay attention to the quality of your diet.  While research on gut bacteria and gut health is in it's infancy, the one common thread in all of the data is that a diverse microbiome is best for gut health, and a diverse diet is what's best for a diverse microbiome.  Including as many different fruits and vegetables as possible will help build a diverse microbiome and provide enough fiber to help maintain intestinal barrier integrity as you train throughout the year.  In addition, the use of anti-inflammatories should be used with caution and diet quality should be tightened up during an infection that requires the use of antibiotics.

Thursday, September 18, 2014

No free lunch: No calorie sweeteners shown to cause gut changes that induce glucose intolerance

No-calorie sweeteners have proven to be relatively useless in the fight against obesity, despite what the food industry may tell you.  In a new study published in Nature, researchers provide evidence that no-calorie sweeteners can induce metabolic changes that lead to glucose intolerance in both mice and humans.  This study found that the changes in glucose tolerance come about from shifts in gut bacteria.

The mouse arm of this study started by feeding mice a 10% solution of either saccharin, aspartame, or sucralose in place of drinking water and comparing their glucose tolerance to control mice given either water alone or a 10% glucose solution.  After 11 weeks, the glucose tolerance in the mice given the artificial sweetener was worse than the mice given water or even glucose.  Previous research has shown that certain no calorie sweeteners can alter the gut microbiome, so the researchers gave mice a 4 week course of antibiotics to wipe out the microbiome.  The result...Glucose tolerance returned to normal.

To make certain that the effects were due strictly to changes in the gut microbiome, researchers transplanted feces from the mice given saccharin in to germ-free mice who had not had the sweetener.  Within a week, the germ-free mice had the same changes in glucose tolerance as those who consumed the no-calorie sweetener.  Looking at the fecal samples, researchers found changes in the microbiome that mirrored changes in the microbiome of humans that eat no-calorie sweeteners.  Furthermore, a follow-up with 7 humans with no history of using no-calorie sweeteners who were fed saccharin at the maximum daily limit allowed by the FDA found that 4 of the subjects had poorer glucose tolerance after 7 days and an altered gut microbiome that, when transplanted in to mice, resembled the one seen in mice fed saccharin.

This study brings up a few important points.  While the dosage of no-calorie sweetener was high, it was within FDA limits.  So while you may not consume these sweeteners at the level seen in these studies, the point is that they aren't entirely benign.  Furthermore, relying on these sweeteners as a crutch to kick a sweet tooth may not be in your best interest, especially if you are diabetic.  Secondly, some people did not respond negatively to the no-calorie sweetener.  An important question to answer would be whether or not Type 2 diabetics, who have poor glycemic control in the first place, are more likely to be susceptible to poorer glycemic control from these sweeteners due to their microbiome.  I would be willing to bet that people with Type 2 diabetes are more likely to rely on no-calorie sweeteners because they "have no direct effect on blood glucose".  Unfortunately, they apparently have an indirect effect on blood glucose that is just as bad as a direct one.

Finally, even though the people who weren't affected by the artificial sweeteners were in the minority, the fact that their glucose tolerance wasn't affected, nor was their microbiome, points to no-calorie sweeteners being benign for them.  As is a frequent topic in this blog, an individualized approach to health and diet is always the best approach.

Thursday, September 11, 2014

Why Lebron James needs (the right kind of) carbs

The world is abuzz with Lebron James' recent decision to undertake a low carbohydrate Paleo diet and the more svelte physique that followed.  While the aesthetic change to his decision is readily apparent, the performance ramifications wait to be seen.  As someone who has used principles of the Paleo diet for my own personal nutrition as well as those of my clients for the past 5 years, I am familiar with the ins and outs of this type of nutrition program.  While paying more attention to the quality of one's diet can improve performance, cutting carbohydrates is not always the best idea for someone in a sport like basketball.

The type of fuel a person uses is dependent on the type of activity they partake in.  Someone who sits at a desk and does low level physical activity throughout the day doesn't need a large amount of carbohydrate because this type of activity predominantly uses fat.  If this person were to get up and sprint on and off for 30 seconds at a time they would shift to burning glucose, which is what the body turns carbohydrates in to.  In the event this person decides not to eat carbohydrate and still tries to perform physical activity that requires glucose from carbohydrates, they will eventually "bonk".  This means they will not be able to produce energy fast enough to keep up with demand.  While they will be able to make glucose from non-carbohydrate energy sources, the body cannot produce it fast enough to keep up with the demands of a sport like basketball.  My prediction: Either Lebron starts eating carbohydratess or his game will suffer.

So if slashing carbohydrates isn't going to give a performance advantage, how can following principles of the Paleo diet improve athletic performance?  To better understand how this works, it's important to get a basic understanding of how the immune system works.  I promise this won't get too technical.  Monocytes are essentially immature white blood cells, they roam around the bloodstream like a couple of high schoolers looking for something to do.  Just like a high schooler, they have no specialized skill because they haven't received instruction yet.  When monocytes encounter an area of the body in need, they quickly receive a PhD in what needs to be done from the environment and differentiate in to a more specialized type of cell that can carry out a more specific task in that tissue.  This could be to identify invaders, fight an infection, or repair damage from exercise.  An important point to understand in this process is that it is often inflammation that gives the monocytes the instructions and, thus their PhD in what to do.  Once a monocyte has been given instructions on what to do by a certain tissue, they are essentially useless to any other tissue in the body.

Neutrophils are another type of white blood cell, the most numerous.  Neutrophils act and move quickly to sites of inflammation to help battle invaders by engulfing them, secreting antimicrobial proteins that help digest invaders, and increasing inflammation to signal there is an infection.  The function of monocytes and neutrophils is important to understanding how the principles of the Paleo diet can improve athletic performance.

The Paleo diet avoids refined sugars/processed foods, grains, legumes and dairy and replaces them with fruit and vegetables.  Many people elect to eat large quantities of meat as well, but since most people eat large quantities of meat regardless of whether they eat a Paleo diet or not, we'll skim past that part(FYI, I recommend a moderate level of meat consumptions).  The gluten in grains and casein in dairy are two proteins that can increase inflammation in the GI tract.  An inflamed GI tract could hijack monocytes that would be better served helping you recover from exercise induced damage to muscle tissue.

In addition to tying up monocytes that could help recovery, GI inflammation also increases intestinal permeability to lipopolysaccharide(LPS).  LPS drives the immune system nuts and induces insulin resistance in muscle and fat tissue to preserve glucose for the immune system.  Since insulin sensitivity is the primary dictator of an athletes ability to replenish glycogen stores after training or competition, causing insulin resistance at any point in the recovery process can be bad for performance.

One final piece of the puzzle is how neutrophils respond to refined sugars.  Ingestion of large amounts of refined sugars has been shown to reduce the ability of neutrophils to engulf invaders for up to 5 hours post-ingestion while starches had not effects(1).  While this effect likely has a modest direct effect on exercise recovery, it will have a greater impact on susceptibility to infection which, over the long term, can negatively impact performance by taking an athlete away from training.

While many people attribute the benefits of a Paleo diet to a low carbohydrate content, most of the positive benefits of the diet occur because the quality of the diet changes.  By improving the quality of your diet, you can improve athletic performance by improving recovery through better immune system function.  Furthermore, if you participate in a sport that primarily relies on glucose for energy, cutting carbohydrates will have a deleterious effect on performance.  My prediction for Lebron James is that he will either increase his carbohydrate intake during the season, or you will see at least a minor drop in his performance.

Thursday, September 4, 2014

Would you take that drug if you knew the whole story? Context matters.

Let's say you've gone to your doctor for your annual check-up.  The Dr. comes in and tells you that he sees something in your bloodwork that is troubling to him, and he'd like to put you on a drug.  At this point the vast majority of people will just take the drug, but a few may question the Dr. more, as they should.  Let's just assume you are one of those people, and the conversation carries on.

"Well, I'm a little concerned about your bloodwork.  You have an elevated risk for cardiovascular disease, I'd like to put you on one of 2 drugs.  The first one will reduce your future risk of death from cardiovascular disease by 30%, and the second will only prevent death for 1 out of 30 people."

As the shock sets in, you begin to think about the prospects of having to take a drug for the rest of your life.  Of course, cardiovascular disease has always been on your mind.  Your father had a heart attack at 55.  You've done your best to get regular exercise and eat a healthy diet, and at 45 years of age feel 10 years younger.  Despite feeling well and never having had a heart attack, you decide it's likely in your best interest to take a drug.

Which drug would you take?  Assuming that you are generally good at math, most people would choose the first one.  The problem is, the first and the second drug are the same drug.  Of course clinical research studies often have different outcomes depending on how they are designed, but this data is not only for the same drug it's from the same study, I just worded the outcome differently(1).  This illustrates an important point; when research results are worded in a way that inflates the results, people are more likely to take a drug.

When you look at the "30% decreased risk", that is something termed relative risk. This is used often despite the fact that it presents the data in a deceptive way that makes you more likely to take the drug.  Let's say you perform a study with 100 people in the treatment group and 100 people in the placebo group.  Of the people who received the treatment only 1 person died, while in the group not receiving the treatment 2 people died.  This would seem to be a very small effect since the absolute difference is only 1.  However, stated in relative risk terms, the treatment reduced the risk of death by 50%.  This is where numbers like the number needed to treat(NNT) come in handy.  In this fake study, the NNT is 100.  In other words, you need to treat 100 people with the drug to prevent one death, the other 99 who are taking it will not live any longer with or without the drug.  Yay!

This is problematic for many reasons, not the least of which being that most pharmaceutical drugs have a laundry list of side effects that could affect the 29 out of 30 people not experiencing a benefit from the drug.  For statins, this means an increased risk of neurological problems, muscle pain, an increased risk for Type 2 diabetes, liver damage, and more.  Another reason this is problematic is that they have recently revised the guidelines for prescribing statin drugs which would increase the number of people eligible to take the drugs to 56 million.  This would potentially prevent 1.87 million deaths over the course of 5-6 years, while 54.13 million would be taking the drug with no benefit from a mortality standpoint.  The interesting part is that these numbers are for people who have had a previous heart attack, if you've never had a heart attack, the picture is worse.

For primary prevention, the NNT is a lot worse.  Primary prevention essentially means using statins to prevent a heart attack or stroke in someone who has never had one before.  The NNT in these people is 1 in 60 to prevent a heart attack and 1 in 268 to prevent a stroke.  Side effects, on the other hand were seen in 1 in 50 people(Type 2 diabetes) or 1 in 10(muscle damage)(2).  The NNT to prevent 1 death from cardiovascular disease in primary prevention trials fluctuates but is typically around 1 in 120.  Taken together, this means that in 600 people you would prevent 10 heart attacks and prevent 5 deaths, while creating 12 new cases of diabetes, which increases your risk for a heart attack.  In fact, people with Type 2 diabetes have the same risk of experiencing a heart attack as someone who has had a heart attack before and are twice as likely to die from a heart attack than non-diabetics(3).  So, of the 600 people who took the drug, 10 will prevent a heart attack and 12 will substantially increase their risk for one.  Does that sound like something you would sign up for?

When you look at the data this way, it makes the decision on whether or not to take something like a statin a lot more difficult.  I can't tell a person whether or not they should take a drug, that's between that person and their doctor.  Looking at the total picture from a numbers standpoint makes the decision a lot more difficult than, "You're the DR, whatever you say".  On top of the numbers issue, they are finding new therapeutic effects from these drugs every day and so many of the results conflict with one another.  Recent evidence has shown that statins may be protective against cancer when taken for 4 years(4), but they may also double a woman's risk of breast cancer when taken for over 10 years(5).

While many of the researchers who come to positive findings on these drugs hail them, one has to wonder how they know the drugs are totally safe when they are finding new ways to use them every day.  If you are looking for therapeutic uses for a drug and are just now finding new ones, how can you get a complete handle on the total range of side effects when they are more of an afterthought and may not pop up until 10 years down the road?  The point of this is not to prevent you from taking pharmaceutical drugs, the point is that you should ask more questions, research these drugs, and weigh the pros and cons before you decide that's the route you're going to take.  Just for the sake of comparison, 300 minutes of exercise per week for the use of primary prevention of heart disease can reduce your risk by 20%(6) and regular exercise for secondary prevention can reduce the risk of death from heart disease by 27%(7).