Thursday, February 25, 2010

11. Statins and Lung Disease

The statin industry has tried to promote the idea that statins might be beneficial in treating pneumonia. They came to this erroneous conclusion through retrospective studies, where the observed benefits come, I suspect, from the fact that those who took statins had benefited from high cholesterol for probably many years before introducing statin therapy. The industry was sufficiently encouraged by preliminary positive indications to then conduct placebo-controlled studies to try to legitimize their claim. However, the studies backfired, because they clearly showed that statin therapy not only wasn't helpful, but actually led to a significantly worse prognosis [26][12] (see ( Statins Increase Pneumonia Risk) . For pneumonia severe enough to require hospitalization, the increased risk incurred by taking a statin was an alarming 61% [12].

Statins' effects on muscles apply to the respiratory muscles as well, leading to difficulty in breathing and subsequent oxygen deprivation, which, of course, further aggravates both pneumonia and heart failure. Furthermore, it is now well known that, in rare cases, statin drugs cause severe lung disease, so-called "interstitial lung disease" (ILD) [24][44][15]. ILD is now listed as a rare side effect for all statin drugs.

In an excellent review article published in 2008, Fernandez et al. [15] identify several possibilities for how statins might cause interstitial pneumonia. They begin their discussion by drawing an analogy with amiodarone, a drug which is known to cause a very similar kind of pathology, which includes the accumulation of lysosomal inclusion bodies, i.e., lipofuscin, the cell-membrane debris that was described previously in the section under heart disease.

Amiodarone belongs to a very common class of drugs known as "amphiphilic" drugs: they have both a hydrophilic (water soluble) and a lipophilic (fat soluble) component in their chemical structure. This property allows them to cross through the membranes of cells in order to achieve their desired biochemical influence. However, the process by which they enter the cell involves degrading the lipids in the cell membrane [2] . Membrane fragments break away from the cell wall and carry the drug along with them into the cell. As a consequence of cell wall deterioration, sodium leaks will cause the cell to lose energy, with all the negative consequences that have been described before.

Fernandez et al. argue that, like amiodarone, statins have an amphiphilic structure, since they contain an apolar (lipophilic) ring and a hydrophilic side chain. A really disturbing observation they make is that, over time, amphiphilic drugs are known to become more efficient at entering cells. It seems logical that a deteriorating cell wall would allow better permeability to the drug molecule. But this then means that whatever effect the drug has on the cell will be increased, leading to accelerated damage and a destructive cascade.

Amiodarone is a potent antidysrhythmic agent, i.e., a drug used to try to correct an irregular heart beat during heart failure or post-operative. It has numerous side effects, but probably the most serious side effect is interstitial lung disease. An article written in 2001 [3] explored the likely mechanism of pulmonary damage. The authors conducted in vitro experiments on cells in lung tissue extracted from hamsters. They noted that exposure to the drug decreased the mitochondrial membrane potential (H+ ions leaked out of the mitochondria) and subsequently the amount of ATP in the cell dropped by 32 to 77%. Even with the addition of glucose, the mitochondria were not able to regenerate the depleted ATP; i.e., the mitochondria were not functioning properly to generate energy from glucose. Ultimately, the cells died. They concluded that mitochondrial dysfunction was the path by which the drug induced cell death.

What they describe is essentially the exact same process by which statins lead to problems in muscle cells. Fernandez et al. agree with my argument that, like amiodarone, statins may cause interstitial lung disease through their disruption of the mitochondrial electron transport chain and subsequent depletion of ATP. Lung cells are particularly vulnerable to oxidative damage, because they are tasked with capturing oxygen from the air and transporting it to the blood. I also suspect that, although the number of cases of reported interstial disease is small, there is a much larger number of people whose lungs have been compromised by statins, but whose pulmonary function has not yet deteriorated to a catastrophic point. Instead, they experience some difficulty breathing and a perceived inability to get enough oxygen. As with muscle weakness, such symptoms may go unreported, as the patient has no way of knowing that what he is experiencing is not a normal aspect of growing old. Certainly an increased susceptibility to viral pneumonia would be anticipated when the lung's cells are suffering from insufficient energy and a degraded cell wall.


condoline said...

Yes. I had two chest X-rays in five years showing normal lungs, then I was prescribed Pravachol. Six months after the second normal X-ray, I got an X-ray in the Maui Memorial ER that showed pulmonary fibrosis in all four lobes of my lungs. I wish they had let me know this at the time - but I suppose I wouldn't have made the statin connection anyhow because I was so totally brainwashed into thinking statins are safe. Now I'm on supplemental oxygen.

Anonymous said...

I don't know why doctors are making a big fuss over this. I frequently pay attention to medical blogs like this most of all when it has to do with the benefits of the Generic Viagra.

Anonymous said...

of course, anything except Buy Cialis, that affect the level of fat, nutrients and other sustance that are need in the blood, can affect lungs, beside this kinb of inhibitors are totally useless.

tareq alkholifi said...

thats one of the best articles i read about statins .

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