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The Standard American diet and the Immune System

By Renata Trister DO
The Standard American diet and the Immune System
Review current literature

The Standard American or Western 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 of refined sugars, salt, and saturated fat. In addition to many illnesses, this diet has an impact on the gut microbiome, these dietary choices are encoded into our gut, our genes, and are passed to our children. Although the modern diet has successfully prevented many 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.

The Western diet is characterized by a high intake of saturated and omega-6 fatty acids, reduced omega-3 fat intake, an overuse of salt, and too much refined sugar. This type of eating can damage the heart, kidneys, and cause obesity/metabolic disorders. Increasingly, it has become apparent that this diet damages the immune system also. The modern lifestyle, reduced exposure to microorganisms, increased exposure to pollutions, heightened levels of stress, and a host of other exceptionally well reviewed variables that likely contribute to immune dysfunction.

Intake of adequate calories and micronutrients is vital for optimal immune function. Deficiency in total calories and/or protein, with starvation, severely reduces the immune system’s ability to respond. The Western diet is plagued with obesity. Adipocytes release inflammatory substances including interleukin (IL-) 1, IL-6, and tumor necrosis factor (TNF). These act as signals in infection, but when they are released without an actual infection, the system wears out. When an actual infection comes along, the response may be delayed.

Obese individuals have fewer white blood cells to fight infection and those cells they do possess have reduced phagocytosis capability. While a complex interplay of hormonal, metabolic, and immunologic processes contribute to the biologic responses in the obese the resultant immune dysfunction increases the risk of infections of the gums, respiratory system, and post op infections.


Processed, simple sugars reduce white blood cell phagocytosis and possibly increase inflammatory cytokine markers in the blood. The impacts of artificial sweeteners are less clear; provocative, yet highly limited, evidence implicates saccharin and sucralose as contributors to Crohn’s and Ulcerative Colitis via interference with homeostatic inactivation of digestive proteases. More studies are being conducted to investigate this.

Saturated fatty acids

One potentially harmful effect of fat is enhancement of the prostaglandin system as it feeds into the arachadonic and prostaglandin E2 (PGE2) pathways. PGE2 is pro-inflammatory, increasing IL-17 production and macrophage activation. Additionally, dietary fats alter the lipids of the membranes of immune cells, disrupting the immune functions. Modern produced dietary fat can also directly trigger the inflammatory process. This is most troubling.

One of the first-line weapons the immune system deploys against infection are molecules called Toll-like receptors (TLR). This is a very complex aspect of the immune system; when these receptors come across a potential pathogen, they are designed to evaluate if it is bacterial, viral, or fungal. If the body finds evidence of any of these organisms, the immune system can begin its attack immediately while the adaptive immune system assesses what specific pathogen it is facing. One of the TLR weapons, TLR4, is designed to sense bacteria. Unfortunately the part of the bacteria TLR4 binds, lipopolysaccharide (LPS), contains mostly saturated palmitic and steric fatty acids. Meaning that TLR4 can generate inappropriate signaling when exposed to certain saturated fats if in too great of frequency, amount, or homogeneity rather than in a more biological balance and dosage. Any resultant, abnormal signaling may lead to a misguided attack upon saturated fat when it is perceived as a bacterial invader. The resulting inflammation in the gut can lead to a break down of barriers, allowing harmful substance to leak from the gut into the blood stream and contribute to immune dysfunction that worsens infection control.

Omega-6 fatty acids

While saturated fats are the most inflammatory, overabundance of omega-6 (n-6) poly-unsaturated fats, such as those found in most cooking oils, have also been implicated in immune response through several mechanisms including effects on TLR4 [53] and serving as precursors for inflammatory mediators

Omega-3 fatty acids

The immune impact of trans unsaturated fatty acids (trans fats) have gone under investigated whilst researchers focus on their deleterious cardiovascular effects, Another possible contributor to modern diet-induced immune dysfunction may be the increased consumption of omega-6 in lieu of omega-3 fatty acids.


Recent animal and cell-culture models have found that elements in gluten can stimulate inflammation through TLR4. This is a possible explanation of the current gluten-free dietary trend.
The microbiome and inheritance

Diet, stress, and environment can have a big effect on the gastrointestinal system. Recent studies have determined some of the mechanisms by which our lifestyle impacts our microbiome and leads to dysbiosis. In the gut (and on the skin), there is an optimal balance of bacterial species. Some strains of bacteria are needed to digest fiber while others produce valuable nutrients like vitamin K. Beneficial bacteria also competitively in habit the microenvironment thus preventing harmful bacteria from taking over. The current understanding on how dietary fats alter the microbiome include TLR4-dependent induction of local inflammation leading to altered host environment, shifts in immune cell membrane functions, and changes in nutrient availability favoring some organisms over others. Dietary simple sugars can to lead to dysbiosis directly through changes in local nutrient concentrations. Interesting some preliminary research has shown the gut microbiome to possess the ability to metabolize the artificial sweeteners considered otherwise non-caloric for humans. While results must be interpreted cautiously, gut bacteria can process sweeteners into various short-chain fatty acids (SCFA) that hold a wide array of potential consequences; while some SCFA may be beneficial, their production may shift the bacterial balance, may be processed into absorbable byproducts that provide calories, and may activate the TLR4 pathway.
Another concern is that the harmful effects of diet can actually stretch across generations. A mother’s diet may potentially shape her child’s flavor preferences even before birth, potentially skewing their palette towards anything from vegetables to sugary sweets in ways that could influence subsequent propensity for obesity and/or unhealthy dieting. Children inherit their microbiome from their mother mostly through parturition but also during breast-feeding and development until the bacterial balance matures around two to four years of age. However, recent evidence suggests that the microbiome may also be seeded into the unborn fetus while still in the womb. When the mother’s diet causes a harmful imbalance of her bacteria, she can pass this imbalance on to her child. This developmental dysbiosis may have an impact on the baby’s immune system.

In addition to altering TLR-mediated inflammation and potentially DNA epigenetics, a mechanism by which alteration in microflora may drive immune-mediated disease involves the gut bacteria’s effect on regulatory T-cells (Tregs), the cell tasked with keeping the immune system in balance during both inflammation and homeostasis. Alterations in the microbiome have been shown in both mice and (to a less extensive degree) humans to affect Treg development, and reduction in Treg signal is associated with worse outcomes in infection control, autoimmunity, and allergic sensitization Therefore, dietary choices that alter gut microbiome likely alter systemic responses through changes in the number and function of regulatory T cells.

Determining which specific bacterial strains are either the protectors or pathogens is not yet fully clear. The desire to foster a healthy microbiome is the driving force behind the therapeutic use of probiotics. Supplementation with various Lactobacillus, Lactococcus, and Bifidobacterium has proved to be beneficial but they are not a cure –all. Our microbiome is far more complex than what is found in a supplement bottle. Simply taking supplements creates a very homogeneous microflora that lacks diversity.
Palmitic acid (found is certain processed fats) may potentiate iron-mediated toxicities and increase the rates of DNA mutations. Dietary intake of the saturated palmitic and steric fatty acids as well as the omega-9 oleic acid, may be independent risk factors for the development of colon cancer. Simple sugars were thought to heighten cancer risk through several well-reviewed in vitro mechanisms.

The exact mechanism of how any individual dietary element impacts cancer development is far from fully understood. Many of the reportedly protective vitamins and minerals share anti-oxidant properties, suggesting a mechanism more related to protection of DNA from damage than altered immune function.

In summary, there is enough quality, direct human evidence to conclude that many of the dietary choices in today’s modern society appear to have harmful impacts on our immune system and likely on the immune system of our children. Although promise remains, it also appears unlikely that synthetic supplements or probiotics will be able to fully heal the damage of our diet. Lifestyle modifications are a must. The greatest negative consequence of our poor diets can be encoded into our DNA and gut microbiome. These harmful immune modifications are passed to our offspring during the time of critical development. This can affect the health of many generations to come.