Thursday, October 16, 2014

Spanish Fries

Ingredients

2 TBSP of bacon grease
1/2 large onion, diced
1 large jalapeno pepper, cut in half length-wise and sliced into half discs
2 peeled potatoes, cut with a fry cutter
Garlic powder to taste

Directions

Preheat oven to 425F.  Place large cast iron skillet on low heat and add bacon grease.  Place cut potatoes in a container with a lid, pour half of grease over fries, add garlic powder, cover, and shake.  Place fries on a baking sheet and put in preheated oven.  Add onions and peppers to the skillet once its hot and stir.  At 10 minutes, shake the fries and put back in for 10 more minutes.  When the fires are finished, dump on plate and put onions and peppers on top.  Salt to taste.

Nutrition information

Makes 2 servings
270 cals
13g fat
35g carbs
3g fiber
4g protein
669mg potassium
10mg sodium

Monday, October 13, 2014

Candida albicans and its effect on hormonal balance

In my previous blog, found here, I went over some of the research on Candida albicans.  This opportunistic fungus is the leading cause of fungal infection in humans and can cause issues ranging from mild skin and connective tissue irritation to vaginal yeast infections and hormonal disturbances in those with a candida overgrowth.  In this blog I will show the connection behind all 3 of these issues.

To better understand how Candida albicans can cause a hormonal imbalance, it's important to understand the basic physiology of the stress response.  The stress response is carried out by the HPA axis.  HPA is an acronym for Hypothalamus-Pituitary-Adrenal.

Stress 101

The stress response begins when stress is perceived, which causes the hypothalamus, a part of your brain that is essentially the master control center, to release something called corticotropin releasing hormone(CRH).  CRH, in turn, triggers a projection off of your hypothalamus called the the pituitary gland to release adrenocorticotropic hormone (ACTH).  ACTH travels in the bloodstream until it reaches an area on top of the kidneys called the adrenal glands and signals them to produce corticosteroids such as cortisol and aldosterone.  In turn, as cortisol is pumped out by the adrenals, it eventually makes its way back to the hypothalamus via the bloodstream and shuts off CRH production, which causes the pituitary to reduce production of ACTH which reduces cortisol production by the adrenal glands.  This is called a negative feedback loop as higher levels of cortisol help tell the hypothalamus to chill out with requesting more cortisol.  While the stress response is far more complicated than this, this is all you need to know to understand Candida albicans' role in causing hormonal disturbances.

Recall from my last blog that Candida albicans possesses a corticosteroid receptor capable of binding corticosterone and cortisol.  When Candida albicans binds cortisol, it prevents cortisol from binding to cells that need it, while at the same time blocking the negative feedback loop cortisol has on CRH production by the hypothalamus.  This can cause the hypothalamus to pump out more and more CRH as it never receives the "Cool it" signal which, in hormonal terms, means the perception of chronic stress.  It doesn't end here for the impact on hormonal balance, however.  By causing something called pregnenonlone steal, HPA axis mis-signaling due to Candida albicans can cause problems with sex hormones and, therefore, reproductive success.

Pregnenolone-hormonal stem cell

As far as hormones go, pregnenolone is the last common ancestor of all hormones.  All steroids begin as pregnenolone and are created based on the body's needs.

Pregnenolone is synthesized from cholesterol and becomes whichever steroid the body needs based on hormonal signaling. When cortisol is bound by Candida albicans and the negative feedback loop it has on the HPA axis is broken, CRH sends the signal to the adrenal glands via ACTH that pregnenolone should be converted in to the corticosteroids, particularly cortisol.  As pregnenolone is directed towards the corticosteroids, less can be used for formation of sex/reproductive hormones causing a hormonal imbalance.  In men, this can cause low testosterone and in women it can cause low testosterone and low levels of estrogens.  Estrone, estriol, and estrogen are estrogens and Candida albicans can directly bind estrogen.  Ironically, you really don't have to learn anything else to understand how Candida albicans can affect the skin and GI tract because it is by the same mechanism.

The HPA axis in the skin

In addition to the central HPA axis that regulates the stress response, humans have a peripheral HPA axis within the skin and hair follicles that actively produce the same hormones and contains the same negative feedback system of the central HPA axis(1, 2, 3, 4) with the only difference being that the end product of the skin HPA axis is corticosterone instead of cortisol.  The skin and hair follicles are also rich sources of collagen which is high in the amino acid L-Proline, the amino acid of choice for the conversion of yeast to hypha in Candida albicans.  When you look at the effect of unmitigated CRH secretion in the skin and GI tract, you can see how Candida albicans can wreak havoc in these tissues.

By binding corticosterone in the skin, Candida albicans can break the negative feedback loop in the skin's HPA axis which may cause CRH levels in the skin to increase.  CRH causes mast cells in the skin to release histamine, an immune compound that increases inflammation and the primary target of antihistamines, pharmaceuticals used to decrease allergic responses(3, 5).  Unfettered stimulation of mast cells by CRH could cause skin inflammation to grow out of control and cause major skin hypersensitivity reactions.  Increased levels of CRH in the skin are thought to play a role in skin conditions such as eczema, psoriasis, hypersensitivity to chemicals, poison ivy reactions, urticaria, acne, and certain types of hair loss.

Effects of CRH outside of the skin

High levels of CRH activate mast cells and cause them to release histamine in the intestinal tract, increasing intestinal(6, 7) permeability.  CRH is thought to have a major role in IBS(8, 9) which would jibe with the relationship between a exaggerated stress response and IBS.  Finally,  CRH activates mast cells in the brain and increase permeability of the blood brain barrier(10).  An additional effect of chronically high CRH levels in the brain is impaired function of the hippocampus(11), an area of the brain crucial for consolidating information from short-term to long-term memory as well as spatial memory. It is interesting that brain fog is often listed as a potential symptom of candida overgrowth as impaired hippocampal function would certainly be a mechanism for brain fog.

Conclusion

Above I have laid out possible mechanisms for the symptoms associated with overgrowth of Candida albicans.  It is important to point out that this doesn't mean that if you have one of these symptoms that you have an overgrowth of Candida albicans.  If Candida were disrupting signaling within the HPA axis, you wouldn't have a single symptom, you would have a suite of them.

It is interesting to note that many of the symptoms of a Candida overgrowth overlap with symptoms of what was once referred to as adrenal fatigue and is now more appropriately labeled HPA axis dysregulation.  Another interesting thing that pops up is that many of the symptoms of HPA dsyregulation are caused by an electrolyte imbalance.  It is important to note that the adrenal hormone aldosterone is one of the chief regulators of electrolyte balance, and corticosterone is the precursor to aldosterone.  Candida could only play a role here if it invaded the adrenal gland directly.

If these mechanisms turn out to be correct, overgrowth of Candida albicans causes HPA axis dysregulation.  That is not to say it is the only cause or even the most common cause, other commensal organisms could potentially bind hormones that are part of the HPA axis and could, therefore, cause it to function improperly if they grow out of whack.  The important thing to realize if this is the case is that nutrient deficiencies aren't causing the problem, blocking steps in a tightly regulated system is.  Therefore, taking high doses of nutrients that are used to manufacture cortisol won't fix the problem until you fix the signaling issue.

***I will likely follow this up with a blog on therapeutic approaches to fixing the problem.  However, I need a break from writing these super long, heavily referenced blogs as they take a ton of time and I am currently working on something work related.  Please stay patient and hopefully I will get to it soon if that was what you were waiting for.  I know, it sucks, but there are only so many hours in the day.

Thursday, October 9, 2014

Candida Albicans: Fact vs Fiction



The internet is filled with tons of information on the fungus Candida albicans.  While I love that information is much more accessible now than it has been in the past thanks to the internet, there is a problem with being able to put out and receive any information you like: It's difficult to determine fact from fiction.  In this blog I will go over some of the intricacies of Candida albicans and help create a better understanding of what this crazy commensal critter is up to.


What is Candida albicans?

Candida albicans is often referred to as a yeast because overgrowth in the vaginal wall is referred to as a yeast infection, but this is a misnomer.  Candida albicans is a fungus that can grow as either single cell yeast or multicelluar filamentous cells.  Since it's found in 80% of the human population(1) and more often than not causes no harm to us, it's considered a commensal organism.  Candida albicans can convert back and forth between both yeast and hypha depending on the environment it's in, thus it is highly adaptable.  The yeast form of Candida albicans is typically benign, it's the filamentous cells that more often than not tend to become problematic, but conversion to filamentous hypha doesn't necessarily have to occur for Candida albicans to cause problems.  It is believed that the ability to switch forms and, therefore, adapt to the environment may be the most important factor in the ability of Candida albicans to infect a host rather than just one specific form(2).

Since the yeast form is unicellular, it typically spreads out within an environment which causes cells to compete with daughter cells as well as other bacteria found there for real estate and nutrients.  Filamentous cells, on the other hand, form hypha that are able to invade host tissues, find nutrients, and help grow biofilms(3).  This allows the cells to grow out in to what is more or less a root network, meaning real estate isn't as big of an issue and it can acquire resources in remote areas where other bacteria can't.  Even though Candida albicans is considered a commensal organism, it is a frequent cause of infection in patients with a compromised immune system.  Below is a picture of Candida albicans in yeast(L) and hyphal(R) form.



Yeast to hypha conversion

While conversion from yeast to filamentous hyphae is not necessary for invasion, this is the most common route due to high expression of the hyphal wall protein-1 gene.  When activated, this gene allows the filamentous cells to bind heavily to host tissues, providing stability so that they can form filaments that can puncture and invade host tissues, primarily to scrounge for nutrients.  Think of it like outriggers on a drill, without outriggers the drill will topple as it tries to drill in to the ground.  When anchored to the ground, stability allows the drill to puncture the ground and the same happens with Candida hyphae.  Without adhering to tissue, the hypha would merely push itself away from the tissue rather than puncture through it.  Hyphal wall protein-1 is either non-existent or barely expressed in the yeast form of the fungus, but highly expressed in the hyphal form(4).

Many people believe high sugar/carbohydrate intake to be the primary culprit in Candida albicans invasion, but the science doesn't support this.  In fact, high levels of glucose tend to prevent conversion of yeast to hypha while increased amino acid availability tends to promote it(5).  Another factor that tends to promote yeast to hypha conversion is an increased environmental pH, which is promoted through the formation of ammonia when hypha metabolize amino acids.  When the yeast form metabolizes glucose, this increases acidity which lowers pH and makes the environment less hospitable to the hyphal form.

If sugar intake is involved at all, it may increase the amount of yeast found within the GI tract.  This could indirectly increase the risk of hyphal conversion if the proper conditions present themselves by providing more yeast that could turn in to hyphae, but it doesn't in and of itself promote virulence of Candida albicans under most conditions. Another indirect way sugar intake can promote virulence is through inflammation, which animal models show promotes colonization of Candida albicans(6).  This wouldn't be a result of carbohydrate intake, per se, but more likely caused by specific types of food. 

Gluten and Candida

When you look at potential dietary issues that may promote Candida albicans invasion, carbohydrate intake does not appear to be directly linked.  However, something often found in foods that contain carbohydrate may have a direct effect on Candida albicans yeast to hypha conversion, which increases the likelihood of invasion.  Gluten, a protein found in grains, is not completely digested by humans because of it's high content of the amino acids L-Proline and L-Glutamine.  This allows gluten to interact with the resident flora within our digestive tract, of which Candida albicans is a member.

Studies have shown L-Proline(7, 8) and L-Glutamine(8) to be potent drivers of yeast to hypha conversion, with L-Proline having the biggest effect of any amino acid(9).  Candida albicans is also able to bind to free amino acids as well as amino acids that are part of larger proteins(10), as would be the case for a large protein like gluten.  Since Candida albicans makes the enzyme needed to break apart proteins high in L-Proline, it could bind to larger proteins and take in L-Proline to induce conversion from yeast to hypha.  In addition, gluten is also known to cause inflammation in the GI tract which is another way it may promote the virulence of Candida albicans. 

Candida and the immunocompromised

For the most part, the assumption has been that people who are not immunocompromised don't tend to have issues with Candida albicans or other Candida species.  However, this is not necessarily true.  First, Candida albicans may team up with Streptococcus mutans to form biofilms and cause cavities in the mouths of children(11).  Second, a recent study looking post mortem at people who died of heart disease found fungi of the species Candida in plaques from the blood vessel walls during autopsy(12).  Another study found significant levels of Candida albicans in the healthy wall of the aorta in patients with coronary artery disease and in the aorta of those with aortic valve stenosis (13).  This by no means implies that Candida albicans causes any of these issues, but to say that it is benign in people with a functioning immune system isn't quite true.

Up until recently, the model for Candida albicans invasion has required the host to be immunocompromised.  However, in 80% of people with disseminated Candida albicans, there is no evidence that they are immunocompromised.  In most people, Candida disseminates due to a break down in the permeability of the skin or GI tract or via a change in the gut microbiota.  These changes can come about due to surgery, nutrition, and/or antibiotic/antimicrobial usage(14). Even within the GI tract, Candida can become problematic if it overgrows due to its ability to alter hormonal status.  This is due to its ability to bind endogenous hormones. 

Candida and hormones

Candida albicans can bind female sex hormones, including estrogen(15, 16), and possesses a receptor for corticosteroids that can bind endogenous hormones as effectively as the native corticosteroid receptor(17, 18).  Corticosteroids are steroid hormones such as cortisol, corticosterone, and aldosterone that play a significant role in human physiology.  Cortisol and corticosterone are glucocorticoids, hormones that prepare the body to deal with stress by increasing blood glucose and suppressing the immune system, among other things.  While cortisol is the primary glucocorticoid in humans, corticosterone has a limited role in the human stress response but plays a role in human skin physiology that is just recently being explored.  It is also a precursor to aldosterone, a mineralocorticoid that helps regulate electrolyte balance by causing sodium and water to be retained.  In addition to binding corticosteroids, the same receptor is capable of binding to progesterone, a precursor to aldosterone and cortisol(19). 

Conclusion

The ability of Candida albicans to bind to hormones indicates it may have the ability to alter hormonal balance if it overgrows and invades a host.  In part 2 of this blog, I will go over how an overgrowth of Candida albicans can cause symptoms ranging from:

  1. HPA axis dysregulation
  2. Skin sensitivity reactions(Cosmetic sensitivities, hair loss, fungal nail infections)
  3. Digestive issues
  4. Hormonal issues
 From there, we will explore therapeutic strategies for fixing an overgrowth of Candida Albicans.  

Monday, October 6, 2014

Chicken Kima

 

 

Ingredients

1 lb of ground chicken
1 large onion, diced
2 medium tomatoes, diced
2 purple sweet potatoes, diced
2 orange sweet potatoes, diced
2 cups of asparagus, cut 2" long
2 TBSP coconut oil
5 cloves of garlic, diced
1 1/4 tsp curry powder
1 tsp of salt, pepper, ground ginger, and turmeric
3/4 tsp of cinnamon

Directions

Place large cast iron skillet on medium heat and add coconut oil.  Once the oil is hot, add the onion and garlic and cook until soft and pliable.  Add in ground chicken and spices and stir.  Once the chicken is browned, add in the tomatoes, asparagus, and sweet potatoes and cook covered until desired firmness, typically no more than 10-15 minutes.

Nutrition information

Makes 2 servings
511cals
22g fat
52g carbs
11g fiber
33g protein
2115mg potassium
934mg sodium

Thursday, October 2, 2014

Chicken Tikka Masala (Grain-free, dairy-free)

Paleo Chicken Tikka Masala

Ingredients

4 chicken thighs, pre-roasted and chopped
2 tbsp coconut oil
1/8tsp ground ginger
1tsp turmeric
1tsp ground coriander
1tsp cumin
1tsp cayenne powder
1tsp chili powder
dash of cinnamon
5 cloves of garlic, chopped
2 medium vine ripe tomatoes, pureed
1 medium onion, chopped
1 yellow bell pepper, chopped
1 orange bell pepper, chopped
4oz baby bella mushrooms, chopped
1/2 can of lite coconut milk
2tbsp shredded coconut
Salt to taste

Instructions

Place a large cast iron skillet on medium heat and add the coconut oil.  Once the oil is melted, add the yellow pepper, onion, garlic, and mushrooms to the skillet and cook until the onions are caramelized.  Mix the spices and add to the skillet.  Stir the contents of the skillet for a couple of minutes and add the pureed tomatoes, continue to stir.  Add the coconut milk and shredded coconut and let simmer for a few minutes.  Remove the contents, puree in a blender, and add back to the skillet.  Add the chopped chicken thighs and let simmer for 5-10 more minutes.

Nutrition information

Makes 2 servings
495cals
25g fat
37g carbs
8g fiber
38g protein
1515mg potassium
478mg sodium

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 tantrum...is 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.

Conclusion

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.