Fast food fever: reviewing the impacts of the Western diet on immunity

Abstract (provisional)

While numerous changes in human lifestyle constitute modern life, our diet has been gaining attention as a potential contributor to the increase in immune-mediated diseases. The Western diet is characterized by an over consumption and reduced variety of refined sugars, salt, and saturated fat. Herein our objective is to detail the mechanisms for the Western diet's impact on immune function. The manuscript reviews the impacts and mechanisms of harm for our over-indulgence in sugar, salt, and fat, as well as the data outlining the impacts of artificial sweeteners, gluten, and genetically modified foods; attention is given to revealing where the literature on the immune impacts of macronutrients is limited to either animal or in vitro models versus where human trials exist. Detailed attention is given to the dietary impact on the gut microbiome and the mechanisms by which our poor dietary choices are encoded into our gut, our genes, and are passed to our offspring. While today's modern diet may provide beneficial protection from micro- and macronutrient deficiencies, our over abundance of calories and the macronutrients that compose our diet may all lead to increased inflammation, reduced control of infection, increased rates of cancer, and increased risk for allergic and auto-inflammatory disease.

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Alex’s Notes: To start, I love the title of this article. It is becoming increasingly obvious that the Western diet is the poster-child for poor food choices such as too many omega-6 relative to omega-3 fats, or an abundance of processed sugars. And it has been blatantly obvious for decades that this diet can damage the body and the waistline of those who pursue these food choices. Recently, however, more interest has grown regarding the impact of the Western diet on the immune system. No doubt other civilized problems such as a sedentary lifestyle and chronic stress also contribute, but diet plays a keystone role as well.

From a functional standpoint, food is energy. Yes I know that food does a lot more than simply provide calories, but let’s stay focused for a moment; the immune system needs adequate caloric intake to function properly. But this trend is a parabola, not a straight line. Much of the world exists in poverty where nutrient intake is not sufficient, but the Western world has an overabundance of nutrition (and ironically, is still not free from micronutrient deficiencies). Fat cells release numerous inflammatory compounds that under normal conditions play a vital role in the early stages of the response to disease or infection. However, in the obese these inflammatory signals are constantly being released that causes a systemic down-regulation of the necessary receptors. When an actual infection comes along, the response may be delayed because the early warning system was silenced. Another more familiar example would be caffeine; regular exposure requires more of it to elicit the same effect. Moreover, the obese have less white blood cells and their ability to perform is reduced.

Turning our attention to a few components common in the Western diet, early research demonstrated that processed sugars reduce white blood cell function, but that it was more a result of the overall glycemic load placed on the body rather than the individual sugars themselves. This isn’t really surprising when you consider the sugar-bomb that a big-gulp soda will place on you, but still, the research is decades old and should be validated with modern techniques. Excessive salt is another issue. One study looking at the relative risk of cardiovascular disease and total mortality associated with an increase in dietary sodium intake among non-overweight and overweight participants of the National Health and Nutrition Examination Survey Epidemiological Follow-Up Study from 1971-1975 concluded that “dietary sodium intake was not significantly associated with cardiovascular disease risk in non-overweight persons.” The problem is, Westerners are fat (2/3rds of Americans), and the risks for them are substantially higher and statistically significant. Salt isn’t the problem, being fat is the problem.

Speaking of fat, the two most common dietary fats of the Western diet are saturated and omega-6 fats, both of which have the ability to trigger a direct inflammatory response. Now I completely acknowledge that, like sugars, fats are not inherently bad, but in the context of the Western diet, they are a concern. For instance, one of the pathogenic weapons in our guts is toll-like receptor 4 (TLR4), which binds to bacterial lipopolysaccharide (LPS) to generate an immune response. However, the long-chained saturated fats common in the Western diet are the same fats found within bacterial LPS, and thus when over-exposure to saturated fats or too constant of an exposure occur, TLR4 can generate inappropriate signaling of inflammation. This can lead to leaky gut and the suppressed future immune response. Then there is the excessive intake of omega-6 fats with negligible intake of omega-3 fats, the consequences of which have become so well-known that even the mainstream is catching on.

Gluten is another stimulator of TLR4. In patients with celiac disease, a receptor called HLA-DQ8 allows gluten to act as a super-antigen that by-passes normal pathogen processing, inappropriately activating the immune system and leading to inflammation and symptoms. The truly fascinating part is that about 40% of the US population carries HLA-DQ8, yet only about 1% of the population has celiac disease, suggesting that there must be some additional unknown mechanism and genetic or environmental risk factors that must be present.

And now we have the two emerging fields of interest in the modern day: the gut microbiome and epigenetics. We all have an optimal balance of bacteria, and in the gut these bacteria provide a sparring partner for the immune system that provides education for when a truly pathogenic opponent is encountered. Anything that negatively impacts our gut buddies will diminish our immune system. Of course one such compound is processed sugars, which have been shown to cause dysbiosis. More concerning, is that these effects can cross generations of offspring with a mother’s diet shaping her children’s food preferences and risk of adverse health conditions even before birth. Dads aren’t off the hook either – the child receives at least 50% of its genetic information from the sperm. Unfortunately, we don’t know what the “optimal” gut microbiota is. We do know that processed sugars and fats promote the growth of pathogenic bacteria, while phytochemical and fiber rich foods do the opposite. However, thinking that taking probiotics to get these bacteria is futile without the accompanying dietary changes. Furthermore, for all we know these beneficial bacteria may only be helpful when in the presence of a healthy diet, and may become pathogenic when exposed to the Western diet.

Another area of concern is the use of genetically modified organisms (GMOs) within the food supply chain. Annoyingly, most discussion about GMOs is conducted in absolutes (all-are-good or all-or-bad). GMOs, in theory, are an excellent idea, and this is exemplified with beta-carotene enriched rice that helps curb vitamin A deficiency in developing nations in a more economically sustainable manner than doing so through supplements. Of course, the problem is where to draw the line. While many genetic modifications simply place a naturally occurring compound from one commonly eaten food into another (such as the beta-carotene rice), GMOs are increasingly being bred to manufacture their own pesticides or develop in a manner that was never intended for the organism. Regarding the former, it encourages an overuse of pesticides on the crops; pesticides that have shown to induce cellular death in human umbilical, placental, and embryonic cells. Moreover, the GMO genes have been shown capable of being ingested by the gut microbiota with the accompanying genetic changes able to be inherited by offspring via microbiome transfer.

The debate for GMOs can go back and forth forever, but one thing is certainly clear: we don’t know enough. GMOs are too immature in practice to be as widespread as they currently are. There is a reason that the European Union and most other parts of the world have banned American GMO imports. The troubling part is that GM crops are subject to patent-law limitations, meaning that any report of findings must have the manufacturer’s approval prior to publication. Thus, the potential for conflict of interest and suppression of evidence is astronomical.

A final note of consideration is that financial costs are often presented as the primary reason for unhealthy diets. When we consider that the medical cost for obesity averages $1,152 for men and $3,613 for women per year, a vicious cycle forms in which poor dietary choices increase medical illness which increases financial burden which further promotes a poor diet. The only way to break the cycle is to fix the diet. While the bountiful Western lifestyle saves us from infectious disease and undernutrition, it simultaneously destroys our immune system and results in chronic disease. The dietary factors are compounded with a sedentary lifestyle and increased pollutant exposure. And although promise remains, it is also unlikely that medication, supplementation, or probiotics will be able to counterbalance the damage of poor dietary choices, let alone undo them, unless they are accompanied by the necessary lifestyle modifications.

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