People with a genetic mutation that leaves them with an LDL cholesterol level of 30 mg/dL live very long lives. Can we replicate that effect with drugs?
Data from large-scale cholesterol-lowering trials using statin drugs suggest that the incidence of cardiovascular events such as heart attacks can approach zero if LDL cholesterol can be forced down to less than 60 mg/dL for primary prevention and around 30 mg/dL for those trying to prevent another. But is lower really better? And is it safe to have LDL cholesterol levels that low?
We didn’t know until PCSK9 inhibitors were invented. Are PCSK9 Inhibitors for LDL Cholesterol Safe and Effective? I am testing that problem on mine video of the same name. PCSK9 is a gene that has been altered to give people lower LDL cholesterol, and that’s how Big Pharma has come up with the idea of trying to disable PCSK9 with drugs. After a heart attack, significantly lowering a person’s LDL cholesterol above the target of 70 mg/dL appears to be more effective than moderate lowering. There were fewer cardiovascular deaths, heart attacks, or strokes at LDL below 30 mg/dL compared to 70 mg/dL or higher, and compared to below 70 mg/dL. There is consistent risk reduction even when starting as low as an average of 63 mg/dL, and pushing LDL down to 21 mg/dL, remarkably, showed “no marked elimination” of negative side effects.
Perhaps that shouldn’t be surprising, because that’s about the level at which we begin to live. And there’s another type of genetic mutation that leaves people with LDL levels around 30 mg/dL for life, and they’re known to have unusually long lifespans. So, where did we get this idea that cholesterol can be so low?
The common claim that lowering cholesterol can be harmful due to the reduction of molecular cholesterol is not supported by evidence and does not take into account the good measurement methods used by our body. After all, that’s how we came about. Until recently, most of us had LDL levels around 50 mg/dL, so that’s normal for the human race. The lack of evidence that low or low cholesterol levels are somehow bad for us is compared to overwhelming evidence that lowering cholesterol reduces the risk of coronary heart disease, our number one killer.
However, what about hormone production? Since the body needs cholesterol to synthesize steroid hormones—such as adrenal hormones and sex hormones—there are concerns that it may not be enough. You never know, though, until you put it to the test. For decades, we have known that women taking cholesterol-lowering drugs have no problem with estrogen production and that lowering cholesterol does not affect adrenal gland function. Also, it does not interfere with testicular function by causing testosterone levels to fall below normal. If anything, statin drugs can improve erectile function in men, which is what you would expect from lowering cholesterol. But you’ll notice that these studies only look at lowering LDL to 70 mg/dL or less. What about really low LDL?
On PCSK9 inhibitors, you can find many people with LDL below 40 mg/dL and some below 15 mg/dL! There is also no evidence that adrenal, ovarian, or testicular hormone production is impaired, even in patients with LDL levels below 15 mg/dL. The risk of heart attack goes down in a straight line as LDL gets lower and lower, even below 10 mg/dL, for example, without any obvious safety concerns, but that’s over time of exposure to these drugs. The longest follow-up to date has been for those with LDL, on multiple medications, maintained below 30 mg/dL for six years.
Now, we can take solace in the fact that those with extreme PCSK9 mutations, which lead to lifelong reductions in LDL levels to less than 20 mg/dL throughout their lives, remain healthy and have healthy children. Changes in cholesterol are what cause so-called “longevity syndromes,” but that doesn’t mean the drugs are safe. The bottom line is that we should try to lower our LDL cholesterol as much as we can, but long follow-up data is needed whenever a new class of drugs is introduced. So far, so good, but we’ve been tracking the data for almost 10 years. For example, we didn’t know that statins increased the risk of diabetes until decades after they were approved and millions were exposed. And it’s worth noting: PCSK9 inhibitors cost about $14,000 a year.
Doctor’s Note
How can you reduce cholesterol with food? Look Trans Fat, Saturated Fat, and Cholesterol: Zero Tolerable High Diet.
For more on statin drugs, see the related post below.
