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).

Monday, August 25, 2014

Does the Paleo diet cure X?

The link above is one of many anecdotal pieces of evidence that has shown significant health improvements from a Paleo diet.  The health conditions that are purportedly improved by a Paleo diet range from inflammatory conditions such as Rheumatoid Arthritis, digestive problems such as Irritable Bowel Syndrome, neurological problems such as Multiple Sclerosis, and the number one killer in the United States: heart disease.  Are these pieces of evidence enough to state that the Paleo diet cures any of these conditions?  Absolutely not, we are eons away from a scientific consensus on what causes these problems, let alone what we can do to fix them.  Does this mean that the Paleo diet isn't the answer?  Nope.

Science is a wonderful thing, but not a necessity for something to be true.  Science is the process we use to come to a consensus on a topic such as this because it eliminates all alternative explanations.  Truths aren't made by science, they are identified with it.  It very well could be the case that many of our modern ills are directly attributable to the lifestyle we live.  Many of the problems that have plagued human civilization throughout history can be directly attributed to things we have determined to be "progress".  The formation of cities and towns is certainly progress, but that doesn't mean that communicable disease and the rapid spread of infection isn't a product of that progress.  As Lord Helmet told us many years ago, there is an up side and a down side to every Schwartz.

This is where the evolutionary approach to health enters the picture.  You've got X, will the Paleo diet help?  help maybe, but cure?  No.  Why?  The evolutionary approach to medicine isn't a diet.  There are many aspects of today's life that are quite novel to modern humans.  Never having to go hungry, never having to experience extremes in temperature, being able to sit on your butt all day long and still procure ample food, not having to succumb to bacterial infections due to antibiotics, and the onslaught of chronic stress we experience today.  The current food environment is certainly a drastic shift to our species, but it is one of many issues that may not jibe with our genetic code.

When you look at the epidemiological research, it is universally accepted that things like poor sleep, a diet high in processed food and calories, high levels of stress, long periods of inactivity, and infrequent intense physical activity are all aspects of modern life that are problematic to health.  When you look at modern day hunter gatherers who live a lifestyle that completely eliminates these traits, we see insignificant levels of the diseases that plague us such as Cardiovascular disease, Type 2 diabetes, Cancer, and even Depression.  Multiple studies are coming out showing what many of these poor lifestyle traits do to us at a genetic level, strengthening support that many of our issues are caused by our current lifestyle.  From a scientific perspective, this doesn't prove anything. Besides, let's say being born by C-section or having to take a dose of antibiotics to kill a bacterial infection do have some ramifications, is the alternative, aka death, a better prognosis than later obesity or IBS?  Probably not, but knowing how to take steps to prevent or reduce the potential symptoms from those potential outcomes likely lies within the evolutionary approach to health.

Many people can benefit from this information, and waiting for a scientific consensus is not going to benefit most people in this lifetime because it won't likely come in that time period.  Even if the scientific consensus comes, it won't show that the Paleo diet or an evolutionary approach to health cures these problems.  What it will show is that many of our current health problems may be caused by a modern lifestyle, but that doesn't mean doing some diet for 3 months will allow you to go back to business as usual.

Thursday, August 21, 2014

Do Type 1 and Type 2 Diabetes share a common cause?

A new study recently published in the journal FASEB provides evidence that both Type 1 and Type 2 diabetes share a similar cause that differs only in the rate at which either disease occurs.  In the study, researchers found that human amylin, a hormone long associated with Type 2 diabetes, accumulates in toxic clumps that destroy the beta cells of the pancreas responsible for producing insulin.  This causes progressively worse pancreas function, leading to failure, that ultimately culminates in either form of diabetes(1).  Let's take a closer look at the findings.

When you eat a meal, insulin is secreted to help control the level of glucose in the blood by making cells in the body take in glucose.  At the same time, the hormone amylin is also secreted to help insulin regulate blood glucose by slowing gastric emptying, reducing digestive enzymes, and causing you to feel full.  When a person secretes more amylin than they can break down, clumps of the protein form on the pancreas negatively impacting beta cell function and causing cell death, thus decreasing insulin production.

In this study, researchers took mice and inserted copies of the human amylin gene, making them either homozygous or hemizygous.  Mice who were homozygous for human amylin received two copies of the gene while mice who were hemizygous only received one copy.  Mice who had two copies of the gene experienced higher levels of amylin, rapid destruction of the pancreas, high levels of insulin, a shortened stage of prediabetes, and juvenile-onset, or Type 1, diabetes.  The mice that had one copy of the gene experienced lower levels of amylin and a more prolonged period of prediabetes, which led to adult-onset, or Type 2, diabetes.

If we look at this in concert with the research on leptin resistance that shows it to precede insulin resistance, we get an interesting picture.  Leptin is another hormone that signals you to stop eating and is secreted by fat cells.  People with leptin resistance produce a lot of leptin, but the cells in the hypothalamus that help regulate food intake don't respond to it.  As a result, people with leptin resistance don't get the "full" signal and continue to eat when they don't need to.  At some point, this may cause them to overproduce amylin causing the toxic clumps associated with Diabetes.  Of course, this is an extreme simplification of a complex topic that needs further study, but it does paint a picture that both could be prevented or reversed. In addition, this study was done in mice so further studies in humans are needed.

Bonus nerd info:  Interestingly enough, amylin shares a common effect on cells with amyloid beta, the protein associated with Alzheimer's disease.  Both cause dysfunction of the mitochondria and an increase in free radical production due to interference in the activity of complex IV in the mitochondria.  The end result of high free radical production...cell death.  These mechanisms only differ in where the cells they affect are found, amyloid beta in the brain and amylin in the pancreas(2).

Monday, August 18, 2014

Paleo and remission from Multiple Sclerosis: Is there something there?

Chad Vaccarino of the music group A Great Big World and Jack Osbourne, son of Ozzy Osbourne, have both seen dramatic improvements in the symptoms they experience from Multiple Sclerosis.  In the video above, Chad discusses his history with treating the disease from taking pharmaceuticals that he felt made him sicker to his use of the Paleo Diet, which he claims has thrown him in to remission.  Chad's Paleo story began when he watched the widely viewed TED talk given by Dr. Terry Wahls, a physician who went from wheelchair-bound to perfectly ambulatory after researching and implementing what is now known as the Wahls' Protocol for Multiple Sclerosis.

While stories like this seem to be fairly common in the internet world, many people are rightfully skeptical.  As the physician in the video states, there is no evidence that diet will help with Multiple Sclerosis.  This is true from a purely scientific standpoint, but therein lies the rub.  There is no hard scientific evidence that the Paleo diet is effective for Multiple Sclerosis, yet here we have 2 people who have absolutely nothing to gain from telling you that it helped them saying that they are essentially symptom free.  As I have mentioned before, however, science doesn't make truths, it identifies them.  What I mean by this is that a lack of evidence doesn't mean something isn't true, it just means we haven't identified it as being true.  A great example of this is that at one point there was no evidence that the Earth was round, yet it has always been round.

This is where we run in to trouble.  Just like you are unlikely to find a treasure if you aren't looking for it, you are unlikely to identify scientific truths unless you search for them via research studies.  Upwards of 65% of biomedical research is funded by companies who are looking for something that they can patent and, therefore, profit from.  Since you can't patent a diet, there is no financial incentive to study the effect of diet on health.  Despite being incredibly beneficial to us as a society, research in this area is unlikely to be carried out via normal means.  While Dr. Wahls has sent numerous grant proposals to the NIH, she has yet to receive funding.  This is where crowd-sourced funding can be quite beneficial, and where you come in.  If 0.3% of the US population each donated $1 to Dr. Wahls' foundation, she would have enough funding to carry out a clinical trial.

The link below allows you to donate to Dr. Wahls' foundation to help fund her work.  If you would like to donate, that's awesome.  What may seem like an insignificant amount of money to you can be significant if enough people give.  Even if you don't wish to donate, please share this blog article with others so that they may donate to help fund research that is unlikely to be carried out otherwise.  If you donate, donate in Dr. Wahls' name and thank her for her work.  Use the mailing address in the right margin as her address.

If you are interested in learning more about the Wahls Protocol for Multiple Sclerosis. check out her book The Wahls Protocol.  Also, if you use Amazon to purchase stuff, you can use the smile program and they will donate a portion of your purchase to a charity of your choosing.  Just select The Wahls Foundation as your charity of choice.  This in no way impacts the cost of your purchases.

Thursday, August 14, 2014

Some nutritional recommendations are Bolshevik

A recent article making the rounds in Australia and New Zealand attempts to expose the dangers of the Paleo Diet by pointing to scientific advice that just doesn't exist while at the same time pointing to the paucity of clinical trials supporting the diet.  The two primary faults of the article are inconsistent logic as well as utilizing scientific data in a way that it cannot be utilized, both of which combine to make a dizzying array of non-points that make it difficult for a layperson to differentiate fact from fiction.

At the heart of the story is the notion that there is no hard scientific studies showing the Paleo diet to be more effective than the standard diet recommended by most health authorities.  This is not to say there aren't many studies that show a Paleo diet to be more healthy than a Mediterranean Diet for several populations, there are several.  What it says is that these studies do not have enough participants to make a clear determination as to whether the diet is better than what health authorities currently recommend.

In my opinion, this is a valid point.  However, when these same health authorities point to the healthfulness of processed food products such as whole grains, they are using data that cannot be used to make that determination.  One of the inherent problems with nutrition research is that you have studies that are well controlled that can be used to say A causes B. Since these studies are well controlled they tend to have a very small number of participants because they restrict external influences that may affect the results.  Theses are the types of studies that are coveted by scientists, but they are extremely expensive and hard to do and, therefore, quite rare.

On the other side of the coin are studies that can have a huge number of participants but that aren't controlled at all.  No matter how many people you have in these studies, you can never say A causes B because you aren't testing whether A causes B, you are testing whether there is a relationship between the two.  This second type of study is where most, if not all, nutritional recommendations come from.  The problem is, using these studies to say eating X improves health is essentially lying because the studies do not say A causes B or B causes A, they say A and B share a relationship that deserves further testing in a well controlled experiment.

In the very few well controlled experiments that experts use to show whole grains to be healthy, whole grains are compared to refined grains as a control group.  In effect, these studies do not show whole grains to be a healthy part of a diet, it shows them to be healthier than refined grains, which we know to be fairly unhealthy.  Of course, it's difficult to identify which type of study the health authorities are using to refute the Paleo diet in these articles since they don't post any references. 

On the logical fallacy end of things is the point that our ancestors ate seeds of grasses, which is a fair point.  However, comparing a loaf of Pepperidge Farms bread to the types of grains eaten by our ancestors is hardly a scientific comparison.  For one, the traditional way to prepare grains is to soak them, which aids in digestion and cuts back on some of the toxic properties of grains.  Secondly, grinding grains with a mortar and pestle is hardly the same as the modern processing of grains in to bread by machine.

Another logical fallacy in these arguments is that grains are somehow necessary to a healthy diet.  While this is not directly stated in these articles, it is implied by the notion that cutting out grains or specific food groups is detrimental to health.  While the authors like to point out that the diet of our ancestors varied greatly, and many included seeds of grasses(grains), this notion does not in anyway imply that grains are necessary to health.  In fact, many modern hunter gatherer societies don't eat grains and do quite well.

While I agree with many points health authorities make against a Paleo Diet, particularly that a high meat/low carb/low diversity diet is a good idea, I feel these arguments are against the lunatic fringe of those implementing the diet.  A lot of this has to do with earlier iterations of the diet and the now increased availability of the books and sources that promoted it.  Over time, the message that Paleo diet proponents have crafted has become more refined and more scientifically sound.  A great reference for what I believe to be the future of the movement can be found here.  Rather than pointing the finger at macronutrients such as carbs or fat, the modern processing of food and it's effect on the microbiota of humans is implicated.

While I don't think this will quell the influx of experts who argue against the diet, it will certainly make it more scientifically valid.  None of this is to say that a rigid Paleo diet is absolutely necessary for health.  However, making better food choices a majority of the time based on principles identified by the science being generated from principles of evolutionary health can only be beneficial in the absence of hard scientific data that shows one way or another that processed grains, whether whole or refined, are something healthful to eat.  That data, despite the insistence by health authorities, does not exist.