Lipitor, a member of the cholesterol-lowering drug class of statins, is the #1 top selling drug in the United States. Statins have long been hailed as protective against cardiovascular disease by lowering cholesterol levels.

But these popular drugs are not without controversy.

How Statins Work

Statins block the production of cholesterol. But in the process of doing so, they also block everything else downstream that gets made by that same pathway. This includes all cholesterol-based hormones, which include the sex hormones: testosterone, estrogen, and progesterone. It also includes the hormones produced by the adrenal glands: cortisol, aldosterone, and DHEA.

Statins also block production of CoQ10, one of the most important nutrients for mitochondrial support: the powerhouse of your cells. Since every cell in your body except for red blood cells rely upon the mitochondria for energy production, this has far-reaching implications.

They block production of Vitamin D from sunlight as well. Vitamin D is critical for immune function, and also correlated with many other important physiologic functions—not the least of which, for the purposes of this discussion, is protection against metabolic syndrome.

Statins also block production of bile acids, necessary for absorption of fat and maintenance of the microbiome.

Cholesterol itself is also a major component of cell membranes, along with phospholipids. Cell membranes are critical for the health of the cell, allowing transmission of signals (such as insulin, for example—or neurotransmission in nerve cells), as well as letting nutrients in, and letting metabolic waste out.

Side Effects of Statins

Given these effects, the best-known side effects of statins are predictable.

The most common is certainly muscle soreness, ranging from mild to severe, and affecting some 10-15% of statin users. The primary cause of this is likely mitochondrial dysfunction secondary to low CoQ10. Since the heart is also a muscle, statins have also been associated with cardiomyopathy, leading to heart failure. This effect is reversible upon discontinuing the statins and initiating CoQ10 therapy.

It’s also now established that statin therapy increases the risk of Type 2 Diabetes, though there is some controversy on whether this has to do with the specific statin or the dose. This study states that mechanisms involve decreased insulin sensitivity and secretion, and increased insulin resistance. I suspect statins may cause this due to decreased testosterone in men (since low T is associated with insulin resistance and metabolic syndrome), as well as due to lower Vitamin D production (also critical for metabolism), and poorer insulin signaling, secondary to lower cholesterol levels to form healthy cell membranes.

This study demonstrates an association between statins and neuropathy, though this is controversial—other studies have not demonstrated this effect. It does make sense, though, again, since decreased cholesterol production will lead to less fluid cell membranes, which could impair transmission of nerve signaling. Statins have likewise been associated with cognitive impairment, probably for the same reason, though studies conflict on this side effect as well.

Do Statins Protect Against Heart Disease?

We might be able to make a cost/benefit argument for statins despite all this, if they still dramatically lowered the risk of cardiovascular disease and mortality, as heart disease is still the #1 killer in America.

But do they?

The risk for Type 2 Diabetes is especially concerning here, since diabetes itself is a significant risk factor for heart disease. Even webmd.com writes, “statins raise the risk of diabetes in about the same number of people who might avoid a first heart attack or stroke on the drugs. And they don’t lower a person’s overall risk of an early death. What’s more, studies show 140 low-risk people would need to take statins daily for 5 years to prevent just one heart attack or stroke.” (source)

The concerns stack up from there. This study suggests that statins “may be causative in coronary artery calcification,” from several possible causes: the inhibition of synthesis of Vitamin K2, necessary to put calcium in the bones rather than to allow it to deposit in the arteries, and the inhibition of glutathione peroxidase production, necessary to protect the arteries from oxidative stress.

This study shows no correlation between LDL-C levels, the calculated “bad cholesterol,” and cardiovascular disease in the elderly: there is little difference in risk between those with high or low levels, and even some association with increased longevity in those with higher levels. Does this suggest that the obsession with lowering cholesterol levels might be misplaced?

This study suggests that this might be the case: it showed that 75% of patients who had a heart attack had “normal” cholesterol levels.

Clearly, there’s something else going on here.

What’s the Real Culprit?

Cardiovascular disease is a real threat, of course, but it appears at the very least that a focus upon lowering cholesterol alone, independent of other factors, is not the answer.

Elevated cholesterol can be a sign of the problem, but it isn’t usually the problem itself. The real culprit is whatever caused the damage to the blood vessel lining in the first place. In far more cases than not, the constellation of causes are all part of metabolic syndrome.

Even if cholesterol management is a part of a larger treatment approach, there are better ways to do it.

The Dark Side of Statins