Systemic Inflammation

Inflammation is the body's biological response to harmful stimuli, designed to eliminate threats and initiate repair. It is driven by immune signaling molecules called cytokines, including IL-1β, IL-6, and TNF-α. These cytokines coordinate immune cells, increase blood flow, and trigger protective reactions. While short-term (acute) inflammation is essential for healing, chronic inflammation becomes harmful and contributes to metabolic dysfunction, autoimmune activation, and hormonal disruption.

Cytokine-driven inflammation: IL-1β and TNF-α activate immune cells and raise inflammatory signaling throughout the body, while IL-6 links the immune system to metabolic stress and often rises in response to blood sugar instability, visceral fat, and gut-derived endotoxins. When these cytokines stay elevated, they chronically stimulate the HPA axis, increase oxidative stress, and disrupt normal tissue function.

Carbohydrates, insulin resistance, and inflammation: High-glycemic and refined carbohydrates rapidly spike blood glucose and insulin. Over time this leads to insulin resistance, where cells respond poorly to insulin and require higher levels to clear glucose. Elevated insulin activates inflammatory pathways like NF-κB and increases oxidative stress. Fluctuating glucose levels drive IL-6 and TNF-α release. As insulin resistance progresses, the body enters a state of persistent low-grade inflammation driven by metabolic stress and cytokine output from adipose tissue.

Leaky gut as a driver of systemic inflammation: A weakened intestinal barrier allows bacterial fragments (endotoxins such as LPS) to enter the bloodstream. These endotoxins strongly stimulate inflammatory cytokines and activate Toll-like receptors (TLR4), causing the immune system to treat gut-derived molecules as threats. This elevates IL-1β, IL-6, and TNF-α and can trigger autoimmune mechanisms. Carbohydrate-heavy and processed diets worsen gut permeability, while low-carbohydrate, ketogenic, and carnivore diets often improve barrier integrity and reduce endotoxin load.

Walking and inflammation reduction: Walking is one of the most effective natural interventions for reducing chronic inflammation. Rhythmic low-intensity movement lowers circulating IL-6, TNF-α, and CRP, increases anti-inflammatory cytokines such as IL-10, and improves glucose disposal without triggering stress hormones or sympathetic activation. Walking enhances lymphatic flow, improves blood circulation to tissues, and accelerates the clearance of inflammatory byproducts. It also strengthens vagal tone, which directly suppresses inflammatory signaling through the cholinergic anti-inflammatory pathway. Ancient humans routinely walked 6–10 km per day, meaning our inflammatory and metabolic systems evolved to expect this steady, rhythmic movement as a baseline regulator.

Metabolic inflammation: When chronic inflammation, insulin resistance, and leaky gut coexist, the immune system remains continuously activated. This disrupts the HPA axis, increases cortisol demand, creates fatigue, worsens metabolic health, contributes to mood disorders, and drives chronic disease. Reducing inflammatory signaling therefore requires stabilizing blood sugar, improving gut integrity, lowering dietary carbohydrates, reducing endotoxin exposure, and engaging in consistent low-intensity movement such as walking.