Statins are Antibiotics…is THAT the Pleiotropic Effect?

Years ago I asked my doctor why nothing was being done to counteract the inflammation. He said statins did that also.  The problem here is that the method of action is unknown so can't be replicated, just like the method of action on neuroplasticity is unknown and can't be replicated.

Statins are Antibiotics…is THAT the Pleiotropic Effect?

Statins are Antibiotics…is THAT the Pleiotropic Effect?

Statins have pleiotropic effects, ie the ability to reduce heart disease risk and CV death via an unknown mechanism, certainly beyond the LDL cholesterol lowering that they can achieve. Researches have known for quite some time about these beneficial effects of HMG-CoA reductase inhibitors (also known as “statins,” such as atorvastatin and rosuvastatin), however the physiology behind this phenomenon remains unclear. The answer as to why statins have these pleiotropic effects is largely unknown, but let me throw out an interesting theory and you form your own opinion.

Statins are antibiotics that kill the undiscovered organism responsible for the entire process of atherosclerosis.

Lets look at some facts first. Many don’t know that the first statin, mevastatin, was discovered in 1971 in the fungus Penicillium citrinum. As the name implies, this is the same fungus from which the first antibiotic penicillin was found. What was the role of penicillin in this fungus, you ask?
To kill the surrounding bacteria so they do not invade the fungi’s space, allowing the Penicillium citrinum species to grow and spread more easily ... survival of the fittest!
Then, what is the role of mevastatin in this fungus? According to researchers, it is the exact same: To block the cholesterol synthesis in the invading bacteria and other fungi, acting like an antibiotic.
Think about this, as well: We know it takes decades for atherosclerotic plaques to form, and it is an inflammatory process. We know that the early use of statins immediately during an ACS significantly reduces mortality according to multiple clinical trials, including PROVE IT-TIMI 22 and the MIRACL trial. This benefit is thought to be from acute plaque stabilization, decreased thrombogenicity and decreased inflammation that occurs immediately after statin administration.
How does this make any sense if the only thing statins do is reduce LDL cholesterol levels through inhibition of HMG-CoA reductase? How should that short-term administration improve long-term mortality, considering the chronic nature of atherosclerosis? Why do these beneficial effects occur? Why is inflammation dramatically reduced so quickly? Again, maybe statins are antibiotics!
Quite an intriguing theory, that statins are antibiotics and kill the pathogenic cause of atherosclerosis, isn’t it? Well, of course I was not the first person to think that perhaps the process of atherosclerosis occurs from an infection. The organisms that have been implicated in contributing to atherosclerosis include Chlamydia pneumoniae (now actually called Chlamydophila pneumoniae), cytomegalovirus (CMV) and Helicobacter pylori. Here are a look at some studies that test this theory.
Interesting side note: Mevastatin caused liver tumors and severe muscle problems in animal studies, and therefore was never brought to market (although it is one of the naturally occurring statins in red yeast rice extract, which millions take ... not good).

Chlamydia pneumoniae

Chlamydia pneumoniae has the most data to show a correlation with atherosclerosis. This pathogen enters through the respiratory tract and is thought to be the 3rd leading cause of upper respiratory tract infections worldwide, with an estimated 50% of the population having been exposed. Circulating monocytes then bring the organism into the vascular wall and induce inflammation. Animal studies with both mice and rabbits show that Chlamydia pneumoniae infection, in the setting of hypercholesterolemia, can induce atherosclerosis. Moreover, giving azithromycin completely blocks this effect.
Translate this to humans. One study of 220 patients after an MI showed that positive Chlamydia pneumoniae antibody titers increase the risk of future events, and that treating those patients subsequently with azithromycin reduces the risk down to the level of patients with negative antibody titers.
The largest trials to evaluate antibiotic therapy directed at Chlamydia pneumoniae after acute MI actually failed to show any reduction in cardiac events or mortality. These include subsets in the ACES trial, WIZARD trial, and PROVE-IT trial, totaling close to 16,000 patients.
Perhaps the key is preventing the infection in the first place instead of trying to treat it after the MI has occurred.

Cytomegalovirus (CMV)

The evidence to link CMV and atherosclerosis is less robust. Certainly, in heart transplant patients there is a correlation. The studies to connect positive CMV antibody titers (serologic evidence of prior CMV infection) to CAD patients have been conflicting. Researches have postulated that CMV may play an important role in the initial endothelial cell injury starting the atherosclerotic process.

Helicobacter pylori

Once again, only a casual relationship between Helicobacter pylori infection and CAD has been shown via serologic studies. Helicobacter pylori has not been isolated from atherosclerotic plaque and the use of antibiotics to eliminate this organism with the goal of reducing CV events has not been evaluated.

Immunization for Heart Disease

How about the prospect of developing an immunization against one of these organisms? Could a cure for Chlamydia pneumoniae actually result in, essentially, a cure for atherosclerosis?
Nobody really knows the answer to that question. Researchers are indeed in the process of developing an immunization for heart disease! Interestingly, it has nothing to do with Chlamydia pneumoniae. A protein antigen that inflammatory T cells react to is being targeted in order to prevent the inflammatory response that they create. Let's see how it goes!

C-Reactive Protein, Sepsis and Statins

We know that CRP (C-reactive protein) is a measurable inflammatory marker that is significantly elevated during states of inflammation, including atherosclerosis, ACS, inflammatory arthritis and, of course, during infection (including sepsis). We know that statin therapy reduces CRP significantly, independent of reductions in LDL cholesterol. So putting these together ... infection increases CRP and statins decrease CRP. This association, of course, does not prove the antibiotic theory, but is a bit intriguing.
How about this factoid? Statins have been shown in more than one analysis to decrease the incidence of sepsis (severe infection with a systemic inflammatory response, usually bacterial) AND decrease mortality in patients with bacteremia. Other studies examining statins for community-acquired pneumonia and ventilator-associated pneumonia, however, have failed to show a benefit. Fortunately, further clinical trials are ongoing to evaluate statin therapy in patients with sepsis. Yet another possibility that statins are acting as antibiotics in this setting.

Pleiotropic Effects of Statins - So what’s the deal?

In my search to see if HMG-CoA reductase inhibitors, in laboratory models, have ever been studied to see if they eliminate Chlamydophila pneumoniae, I came up empty. Also, there are no data to see if statin therapy is more effective in those seropositive for Chlamydophila pneumoniae compared with seronegative individuals.
OK, fine, maybe it is a bit far-fetched to say that there is, perhaps, one lone organism causing all of atherosclerosis. There are likely multiple factors that contribute, causing the endothelial injury that starts the process, but infection probably plays a role somewhere along the line. However, could you imagine if there was ONE predominate infectious etiology? A potential cure for heart disease, stroke and peripheral vascular disease could be developed! I see a Nobel Prize opportunity ... discover the real reason for the pleiotropic effects of statins!
- by Steven Lome, DO, RVT