Several years ago, I did a post on a study that looked at the COVID pandemic measures taken to reduce the risk of viral spread. One of the biggest social projects during the pandemic was the replacement of air-conditioning filters in most urban buildings (especially hospitals, schools and government) with filters that have a much finer mesh and were thought to be able to stop viral particles from coming into the internal air circulation system. Well, as usual, rash and thoughtless decision carry many unintended consequences and the situation in all those building was arguably made much worse since the finer mesh in the new filters disintegrated Gram-negative bacteria in ambient air, which allowed the endotoxin present in said bacteria to freely float in the air. Given that endotoxin is highly inflammatory, several studies from the pandemic era discovered that these new filters dramatically worsened asthma symptoms in people diagnosed with that condition. I just posted about another study showing that even tiny elevations in blood endotoxin have powerful blood clotting effects that likely drive the high mortality rates seen in sepsis as well as the clotting events seen in people with cardiovascular disease (CVD), ultimately leading to heart attacks and strokes.
The study below sort of combined these prior findings and discovered that endotoxin in ambient air, despite being present in exceedingly tiny amounts, is by the far the most inflammatory component of so-called fine particulate matter (PM), which is the dominant factor in air pollution. It was long-thought that other components of PM (metals, petrol byproducts, ash/smoke, etc) are bigger culprits in the known pulmonary, vascular and systemic negative effects of air pollution, but now it looks like the old adage that “big things come in small packages” is very, very true. The bad news here is that the findings of the study make it very hard to implement protective countermeasures. Namely, if one sits in a building somewhere in a Western country, the ambient air inside would probably be loaded with endotoxin due to the new air filters installed, as described above. If one decides to limit indoor time and spend more time outdoors, then one would be exposed to the endotoxin in PM, at least in most Western countries. So, short of moving to a remote place in the wilderness (and even there, air pollution may be present), the only tools available for us to address the risk from the (apparently) ubiquitous endotoxin are substances that limit as much as possible the downstream inflammatory cascade triggered by endotoxin, as well as substances that may be able to bind and neutralize said endotoxin before it can do much damage. Aspirin, niacinamide, fat-soluble vitamins, and flavanoids are probably the most widely available examples of the former, and pregnane steroids (especially progesterone) are good examples of the latter due to the ability of said pregnane steroids to directly bind and deactivate endotoxin.
https://dx.doi.org/10.1021/acs.est.5c07255
https://phys.org/news/2025-09-bacterial-endotoxins-high-potency-mass.html
“…Endotoxin, a toxic chemical found in bacteria, makes up only 0.0001% of PM2.5 fine particles but packs a serious punch when it comes to its bioactivity. According to a study by researchers from The Hong Kong Polytechnic University, endotoxin drives 0.1–17% of the inflammatory responses triggered by these airborne particles, with its toxicity contribution being three to five orders of magnitude higher than its mass contribution. The findings are published in Environmental Science & Technology. Air pollution is now the world’s leading environmental health threat, linked to more than three million premature deaths every year. One of the key culprits is PM2.5, which refers to airborne particles smaller than 2.5 micrometers, small enough to slip deep into the lungs and even seep into the bloodstream. Scientists have long been focusing on PM2.5 because evidence consistently links it to respiratory illnesses, such as asthma, chronic obstructive pulmonary disease, and airway inflammation. Studies suggest that the damage caused by PM2.5 could be due to oxidative stress and the triggering of immune responses in the lungs following exposure. PM2.5 is a complex atmospheric cocktail of natural and anthropogenic particles containing biological, inorganic, and organic constituents. For decades, researchers have extensively studied the impact of chemicals—including transition metals, polycyclic aromatic hydrocarbons, and industrial smoke—produced by human activities. These components, however, contribute to less than half of the respiratory damage inflicted by PM2.5, leaving roughly 60% of its impact still unexplained.”
“…Endotoxin concentrations were measured using the Limulus Amebocyte Lysate (LAL) assay, then researchers used DNA sequencing and source tracking to identify the Gram-negative bacteria they came from. Finally, they applied mixture-toxicity modeling to estimate how much these endotoxins contributed to the overall harmful effects of PM2.5 exposure. They found that despite making up only a minuscule fraction of the total PM2.5 mixture, it drove about 0.1 to 17% of the IL-8 release triggered by PM2.5. Among all reported PM2.5 components, endotoxin demonstrated the highest toxicity-to-mass contribution ratio, 10,000:1 to 100,000:1, establishing its extreme biological potency. These findings show that less is indeed more.”
