Thursday, July 26, 2012

Of soda bans and neural strands

A lot of comedic energy has been recently focused on New York City's ban on extra large sodas. Nowhere is this more so than  at the Daily Show, where Jon Stewart recently pointed out the irony that marijuana is practically legal, buyer beware if you want 32oz of your favorite beverage.

Yet it is interesting that Mr. Stewart chose this particular comparison.

Years ago, social and political pressure mounted on science to show that chronic marijuana consumption could damage brain cells.  The story was to be that toking up meant killing neurons.  Well despite decades of federally funded research, there has been no definitive link between the consumption of marijuana and brain cell death.  Sure,  there is a slight possibility that the ink is there and we haven't found it, but it hasn't been for lack of trying.  

Now let's flash forward to today, with over 1/3 of the US population is obese and, as a population, we just keep getting bigger.  This is mainly due to a decrease in physical activity and an increase in high caloric diets like the nefarious "super-sized" sodas.

"So what?" you might say,  "It's not like that soda is killing my brain cells."

Actually, a growing body of evidence suggests that it might be doing just that.  Well to be clear, not that single soda per se, but the obesity that such high caloric intake can lead to.

From the waistline to the brain

Most people, even scientists that I talk to, assume that if there is a relationship between the brain and obesity, it is only in the sense that certain people's brains drive them to eat more and that's why their obese.  Maybe you've got a more addictive personality to begin with, so you're hardwired to seek reward and your drug of choice ends up being doughnuts and soda pop.

Now I wont argue that there might very well be a case for this argument and, in fact, there is some data to justify this hypothesis.  But let's step back for a minute and consider some general facts.  The brain needs a lot of energy to do its thing.  In fact, you can think of the brain as the United States of the global energy supply of the body.  It occupies only about 2% of the total tissue volume in our body, but it uses almost 15% of the output from the heart, 20% of the body's oxygen, and 25% of the circulating glucose.  

Now everyone knows that obesity is linked to all sorts of metabolic problems (e.g., diabetes, high blood pressured, cardiovascular disease, etc.).  So if we stick with our metaphor of the brain being like the United States of energy consumption, then think about what happens when energy prices skyrocket in this country.  The cost of doing things incrementally goes up and the overall productivity of the country pays a price. In fact, there are many studies showing that the brains and cognitive processes of obese individuals function differently than lean counterparts.

But emerging evidence suggests that obesity may be much more nefarious to the brain than simply raising the metabolic gas prices.  It might actually be, that's right... attacking brain tissue itself.

Okay, I'll admit that last statement seems to be quite hyperbolic, but emerging research is giving us a very startling picture on the relationship between the size of your gut and your brain health.  

Take for example a recent study my colleagues and I did that will be coming out in the journal of Psychosomatic Medicine.  We looked at how the underlying architecture of the brain itself was different in obese individuals compared lean counterparts. We took a group of neurologically health adults who spanned a range of body mass index (BMI) scores.  Higher BMI means, generally speaking, greater obesity.   We then used MRI to measure the integrity of the physical connections in the brain.  Remember that the two fundamental tissue types in the brain are gray matter (the cell bodies) and white matter (the long strands that connect cells together).  The type of MRI we used, called diffusion tensor imaging, looked at this latter tissue type (by measuring something called fractional anisotropy, which a very basic measure of white matter integrity).

We found that with every point increase on the BMI scale, there was an incremental decease in the integrity of white matter throughout the brain.  Now other studies also show this relationship between obesity and white matter, but our findings point to a global and pervasive effect throughout the brain.

As if that wasn't scary enough, in another study, recently published in the journal Cerebral Cortex, my colleagues and I used the same MRI approach to look at how social factors relate to neural health.  We found that lower social status (i.e., lower family income, fewer years of education and living in poorer communities) predicted a reduced integrity of the physical connections in the brain.

Let me repeat just to drive the point home: Socioeconomic status could actually predict the microscopic architecture of the connections in the brain

How can this happen?  Well it turns out that this relationship is mediated by an increase in unhealthy life-styles like smoking and, that's right, increased obesity. So life-style factors and access to resources that affect physical health may be directly influencing the physical structure your brain itself.  That means this health-to-brain relationship has vast societal implications that we are only just beginning to comprehend.

A molecular link between physical health and the brain

Okay, if you've stuck through this far, you are probably wondering how the heck changes in the body can influence the brain?  Well in the study I just described my colleagues also measured levels of a molecule called C-reactive protein (or CRP) in the blood.  This little protein reflects inflammatory  activity, which is an immune system reaction and is the reason why recent cuts turn red and flushed.  It turns out that, the link between both smoking and obesity and the brain could be mostly explained by increased CRP levels.  

Let's put it together.  Lower socioeconomic status lead to reduced physical health which led to increased inflammation which, in turn, led to reduced integrity of the white matter in the brain.

Schematic of the relationship between social and lifestyle factors the brain (adapted from Gianaros et al. Cerebral Cortex 2012)

Does this mean that cells are dying?  Well not necessarily.  

Remember, I said that white matter is the long fiber strands that connect neurons together.  So far all we can say is that the signal we use to measure this tissue is reducing.  However, adding one more fact into the equation leads to some very scary hypothesis as to what might be happening.

It turns out that the fat around your gut is actually an organ that secretes inflammatory molecules.  As that "organ" expands, it secretes more inflammatory chemicals (called cytokines). Many of these chemicals can cross the blood brain barrier that protects the brain from a lot of bad things.  Once in the brain they can induce a local inflammation of the support cells that basically serve as the scaffolding for the axons in the brain.  After a while, this scaffolding may collapse and break the underlying axons.

How do we know this can happen?  Well because this is precisely what happens in multiple sclerosis (MS) and we know that MS definitely damages physical tissue.

Now I should be up front.  The scientific evidence isn't there yet to suggest that obesity physically kills brain cells the same way MS does.  The emerging evidence nonetheless convincing that there is a troubling link between obesity and the same systems as MS.  This evidence keeps mounting every month as more scientific studies come out.

Food for thought

So while comedians and politicians may poke fun at Mayor Bloomberg's decision to ban extra-large soda drinks in an effort to curb obesity, we should take a step back and look at the science.  Increased obesity not only reduces your physical health, but it's becoming readily apparent that obesity is also interfering with the organ that sits as the root of all thinking.  Our work, along the studies from many other labs, shows that this has dramatic implications that extend into social issues as well as medical issues.  

Will banning 32oz sodas solve the problem?  Absolutely not... not even close.  But is it taking a problem seriously that we have, thus far, only been talking about tongue-in-cheek?  You bet it is. Brogan A, Hevey D, O'Callaghan G, Yoder R, O'Shea D. (2011). Impaired decision making among morbidly obese adults J Psychosom Res DOI: 10.1016/j.jpsychores.2010.07.012

 Brogan A, Hevey D, Pignatti R. (2011). Anorexia, bulimia, and obesity: shared decision making deficits on the Iowa Gambling Task (IGT) DOI: 10.1017/S1355617710000354

Gianaros PJ, Marsland AL, Sheu LK, Erickson KI, Verstynen TD. (2012). Inflammatory Pathways Link Socioeconomic Inequalities to White Matter Architecture. Cerebral Cortex DOI:

Stice E, Spoor S, Bohon C, Small DM. (2008). Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele Science DOI: