Thursday, March 7, 2013

You are what you eat... and then some


 Gennarina Riso 

Figure 1. What if we really looked like what we eat? I might be waddling around like a big container of peanut butter, or even worse… a big tall beer. (

We’ve all heard the saying “you are what you eat”. As well educated, young, and reasonably active individuals, most of us don’t need to worry too much about this – we do eat fairly healthfully on a daily basis, and even when we don’t, we have the resources and know-how to better our food choices.

But what about people who don’t have access to knowledge about nutrition? Since having my job in the ER, I have thought a lot about how (seemingly) close the correlation is between having a healthy diet, remaining active, and avoiding chronic illnesses. It seems to me that most of the cases we see in any given day would be nonissues if people adopted some serious lifestyle changes. In America, poor diet and sedentary behavior are of epic proportions. And while it’s no news to us that being chronically overweight and eating a typically high-fat Western diet contribute to incidence of Type II Diabetes, high cholesterol, and high blood pressure (just to name a few), the cumulative effects of having a poor diet are much more convoluted and additive than they appear. But how many people truly understand what lifestyle choices to make? And further, can they afford to do so?

In addition, I got to thinking about how exactly Americans became so unhealthy – what is it about our society in particular that leads to such overabundance of excess? According to my research, much of the “spike” in obesity in this country is due to the increased availability of meat and oil products after World War II (not to mention plastic and other conveniences). In addition, the concept of “super sizing” or “economy sizing” (in other words, getting more product for less money) played greatly into the spike in calorie consumption that took place. Families who once barely had enough food or resources to survive could now buy more food than they could ever dream of, so self-control was really not at play here, and with good reason. In addition, where families once made their own food from scratch, grew their own vegetables, and owned one family car, suddenly streamlined products appeared on the market that greatly changed the dynamics of the American household. Suddenly, America was more focused on productivity than ever – and while there are thousands of such examples, TV dinners are particularly symbolic in terms of this topic, as cooking and eating meals together became less common than heating up a frozen meal in the microwave and sitting in front of the television. 

Figure 2. An example of a classic Swanson TV dinner from the 1950’s. Very convenient, but how much nutritional benefit is there? (

But what is it exactly about eating poorly that contributes to such physiological mayhem down the line? And how is it that our diet can play into our immune function and cause inflammation?

The answer is surprisingly straightforward, as I learned this quarter in BMED 545. When the endothelial cells that line our blood vessels become activated (which can happen in response to turbulent blood flow, or even simply increased blood flow), they express adhesion molecules that allow monocyte extravasation into the subendothelial space. They also secrete chemokines (such as MCP-1) that help activate leukocytes. So, when macrophages are present in the subendothelial space, they secrete cytotoxic superoxides in order to prevent infection. If there are high plasma LDL levels, once they filter through the space between contracted/activated endothelial cells, they react with these superoxides, which is a very bad situation, as this contributes to the positive feedback loop that involves more and more immune activation and eventually leads to the formation of a plaque that contains cholesterol, LDLs, macrophages, and other immune cells (such as helper T cells, which secrete INF-g, causing macrophages to secrete TNF-a, both of which are common proinflammatory markers). Obviously plaque formation alone is dire, but if that plaque ruptures, endothelial cells are exposed to many combinations of factors that can lead to a blood clot quite easily, most commonly leading to MI, but also seriously increases risk for stroke and pulmonary embolism.

Figure 3. A simple schematic of how eating a poor diet can lead to coronary heart disease (CHD), just to name one deleterious side effect. 
 These days, a widely used term to describe individuals who are ailed with many of the above pathologies is “metabolic syndrome”. Of note, in 1988 when the term was becoming more common, obesity was not one of the criteria when classifying whether or not someone had metabolic syndrome. As the instance of obesity continues to climb in this country, much controversy has ensued between researchers and clinicians about who does and does not have metabolic syndrome, and moreover, what tests should be routine in determining presence or absence of the syndrome. In 2001, a person with three of these five criteria was classified as having metabolic syndrome: obesity, high blood pressure, raised triglycerides, low HDL levels, and fasting hyperglycemia. Today, some healthcare professionals think that presence of visceral body fat, biomarkers of adipose tissue, insulin resistance, inflammatory markers, and thrombotic markers should also be considered.

As if all of this isn’t scary enough, research has shown that increased emotional and psychological stress can promote some of the oxidative and proinflammatory pathways (even in the absence of physical injury) that having a high fat diet can – so imagine how dangerous it would be to be stressed and eat poorly! Because depression is also correlated with poor sleep patterns, which further increase our risk for infection and immune response, it is easy to see how this situation could spiral out of control. Janice Kiecolt-Glaser (2010) cites longitudinal studies that explicitly show that people who are chronically stressed over a 6 year period have significantly higher amounts of proinflammatory cytokines circulating through their bodies at a given time than those without chronic stress. Further, postprandial lipemia can also increase expression of inflammatory markers, and while the spike in lipid levels may be short-lived, the positive feedback loop associated with some of this inflammation could be much longer lasting and cumulative, especially if a high fat diet is the “norm”. Similar research also indicates that one single meal high in fats can lead to endothelial cell activation and increased expression of adhesion molecules that are necessary for the monocyte extravasation that I mentioned above.

Figure 4. Even the autonomic nervous system is involved! Although, that is a subject for another day. 

 Before I begin to talk about some of the ways we can combat having metabolic syndrome ourselves, I just have to share one more thing… Pistell et al. (2010) performed fascinating study using a mouse model that showed that mice who were fed a high fat diet (in particular, a “high lard diet”) showed cognitive impairment when compared to mice who ate a regular diet. Further, these same mice were also shown to have significantly higher levels of proinflammatory markers in their brains (Fig 5)! If that won’t make you stop hitting up Jack in the Box, I don’t know what will.

Figure 5. Mice fed a high-fat lard diet showed significantly higher levels of the above mentioned proinflammatory cytokines and markers when compared to mice fed a control diet. 

The good news? As discussed in BIO 502 lab last week, eating a Mediterranean Diet has been associated with lower instance of heart disease and many of the pathologies I described above. In 2011, Kastorini et al. did a metanalysis on 50 past studies involving the Mediterranean Diet (MD) and metabolic syndrome, and they showed that not only is the MD negatively associated with metabolic syndrome as a whole, but also with all of its separate components! Luckily, eating like an Italian is no punishment; all you have to do is eat a well-balanced diet of fruits, vegetables (flavonoids!), whole grains, healthy fats (olive oil!) antioxidants (salmon!), and even some dark chocolate and red wine. They key to adopting the healthy Mediterranean style is moderation. For example, studies that show lower instance of heart disease, obesity, inflammation, and high cholesterol in people who comply with a MD also note that they have a relatively lower dairy intake than a Western Diet, and the dairy that they do consume is generally low-fat. After all, we must take into account inflammation in the animals we consume and how that may manifest in our own bodies. But that is a subject for another day.

Essentially, the take-home message is that our grandparents and great-grandparents would have been better off (I will argue) from a health perspective if they did not change their dietary habits in such a drastic manner.

Figure 6. A Mediterranean Food Pyramid. Note that it gives you information about what you should be consuming on a daily, weekly, or monthly basis! (

Mangiate, bevete e sopratutto divertitevi! (Eat, drink, and be merry!) In moderation, of course; at least in regards to the eating and drinking J


Pistell, P., C. Morrison, S. Gupta, A. Knight, J. Keller, D. Ingram, and A. Bruce-Keller. 2010. Cognitive impairment following high fat diet consumption is associated with brain inflammation. Journal of Neuroimmunology 219:25 – 32.

Nicklas, B., W. Ambrosius, S. Messier, G. Miller, B. Penninx, R. Loeser, S. Palla, E. Bleecker, and M. Pahor. 2004. The American Journal of Clinical Nutrition 79:544 – 551.

Giugliano D., A. Ceriello, and K. Esposito. 2006. The effects of diet on inflammation. Journal of the American College of Cardiology 48:677 – 685.
Esposito, K., and D. Giugliano. 2006. Diet and inflammation: a link to metabolic and cardiovascular diseases. The European Heart Journal 27:15 – 20.

Chrysohoou, C., D. Panagiotakos, C. Pitsavos, U. Das, and C. Stefanadis. 2004. Adherence to the Mediterranean Diet attenuates inflammation and coagulation process in healthy adults. Journal of the American College of Cardiology 44:152 – 158.

Kastorini, C., H. Milionis, K. Esposito, D. Giugliano, J. Goudevenos, and D. Panagiotakos. 2011. The effect of Mediterranean Diet on metabolic syndrome and its components. Journal of the American College of Cardiology 57:1299 – 1313.

Alberti, K. and J. Shaw. 2005. The metabolic syndrome – a new worldwide definition. The Lancet 366:1059 – 1062.

Kiecolt-Glaser, J. 2010. Stress, food, and inflammation: psychoneuroimmunology and nutrition at the cutting edge. Psychosomatic Medicine 72:365 – 369.


  1. Physiological Mayhem! Great post Gennarina

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