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“Obesity and often associated metabolic syndrome and inflammatory diets have emerged as a major cause for low grade activation of the immune system.”

As we hit our 50s and beyond, our immune system may begin to work against us. It might be difficult to notice however, as chronic inflammation, unlike acute inflammation, doesn’t show obvious signs. When a joint swells up after an injury, it is a clear sign that acute inflammation is at work, but chronic inflammation is sneakier—it acts kind of like high blood pressure, remaining silent and physically unnoticeable. To fully understand the impact of chronic inflammation on our health, it is crucial to identify its root causes. Obesity and often associated metabolic syndrome and inflammatory diets have emerged as a major cause for low grade activation of the immune system (“metabolic endotoxemia”) . In most cases, chronic low grade systemic immune activation occurs without being triggered by a specific disease, but rather because of our immune system is simply working to defend us.

So, what exactly is inflammation anyways? To put it simply, because it is in fact very complex, acute inflammation is the body’s natural response to infection or injury. It is initiated by our innate immune system, our first line of defense against all bacteria or viruses, to unleash proteins and hormones that promote healing. However, its role is not always protective – researchers are finding that it can be both a marker and a driver of a growing list of chronic diseases, including heart disease, memory loss, colon cancer and liver disease, acting much like a double-edged sword.

“… [patients] with elevated levels of inflammation—despite appearing healthy—experienced heart attacks and strokes at significantly higher rates than those with lower inflammatory markers.”

Paul M. Ridker, MD, MPH, the Eugene Braunwald Professor of Medicine, Harvard Medical School and Director, Center for Cardiovascular Disease Prevention Physician, Brigham and Women’s Hospital is a cardiologist who has reshaped our understanding of the link between inflammation and heart disease. In the mid-1990s, he observed a puzzling trend: many of his patients had suffered strokes and heart attacks despite having normal levels of cholesterol, which was long considered the main culprit of heart disease. Intrigued by these results, Dr. Ridker and his team delved deeper and discovered that these patients exhibited elevated markers of inflammation in their blood. He noted that those with elevated levels of inflammation—despite appearing healthy—experienced heart attacks and strokes at significantly higher rates than those with lower inflammatory markers. This revelation sparked a new hypothesis: rather than being a byproduct of heart issues, inflammation may actually play a role in the development of heart disease. This inflammation hypothesis of heart disease has also provided an explanation for the clinical observation that anti-inflammatory medications like Aspirin were protective against heart attacks. His work has opened new avenues for research and treatment, challenging conventional wisdom and paving the way for more effective interventions in cardiovascular health.

“The co-occurrence of central obesity, type 2 diabetes and elevated blood pressure is referred to as metabolic syndrome, which is a major risk factor for chronic disease.”

There is increasing evidence that systemic inflammation is closely linked to obesity. An extensive body of evidence has shown that obesity leads to chronic inflammation and can lead to insulin resistance (IR) and ultimately, type 2 diabetes (T2D). The co-occurrence of central obesity, T2D and elevated blood pressure is referred to as metabolic syndrome, which is a major risk factor for chronic disease. Not surprisingly, the underlying mechanism again seems to be chronic inflammation. The general idea for this mechanism is that inflammatory mediators produced by cells in the gut associated immune system and by macrophages (a specific type of white blood cell found in fat cells produces a variety of protein molecules called chemokines and cytokines that stimulate tissue inflammation in many organs, including the brain. Therefore, circulating chemokines are likely to be found in obese individuals and act as a marker of tissue inflammation. Interestingly, anti-diabetic drugs like Ozempic, have been shown to help with weight loss and may even have benefits for several of the chronic diseases associated with the current chronic disease epidemic. The emerging connection between weight management, inflammation and chronic disease highlights the intriguing potential of the new weight loss drugs to transform health outcomes in unexpected ways. However, more research is needed to study these connections.

“Gut dysbiosis—a disruption in the gut microbiome—has been linked to several inflammatory conditions…”

Another key factor driving low-grade inflammation, often influenced by lifestyle choices, is the impairment of gut microbiota. The composition and function of our gut microbes are often impacted by aging and dietary changes. This decline in microbial diversity is particularly evident in older adults and those with obesity. Gut dysbiosis—a disruption in the gut microbiome—has been linked to several inflammatory conditions, including obesity, diabetes, cardiovascular diseases, and neurodegenerative disorders. As often discussed in this newsletter and described in detail in The Mind Gut Immune Connection This dysbiosis can contribute to chronic low-grade inflammation, as the gut microbiome is closely connected to the gut associated immune system and thereby tied to innate immune responses. Lifestyle interventions play a crucial role in this relationship; for example, different types of intermittent fasting, including time restricted eating have been shown to increase levels of the molecule secretory IgA, which may correspond with shifts in gut microbiome composition.

Why is this important?

The good news about these findings, is that lifestyle changes are currently the most effective and practical way to reduce inflammatory markers and prevent the progression of non-contagious inflammatory diseases. Increasing the consumption of a variety of foods rich in fiber and polyphenols, while eliminating ultra processed foods, including sugar from your diet can lower or reverse systemic inflammation.