People with genetic mutations that leave them with LDL cholesterol of 30 mg/dL live extremely long lives. Can we duplicate this effect with drugs?
Data from large trials of cholesterol lowering using statin drugs recommend that the incidence of cardiovascular events such as heart attacks would approach zero if LDL cholesterol could be reduced below 60 mg/dL for first-time prevention and around 30 mg/dL for those trying to prevent another. But is lower really better? And is it still safe to have LDL cholesterol that low?
We didn’t know that until it was PCSK9 inhibitors invented. Are PCSK9 inhibitors safe and effective for LDL cholesterol? I am exploring this topic in mine video namesake. PCSK9 is a gene that was mutated to give people such low LDL cholesterol, and so Big Pharma thinking trying to cripple PCSK9 with drugs. After a heart attack, intensive care lowering of a person’s LDL cholesterol above the goal of 70 mg/dL seems to work better than the more modest reduction. There it was Fewer cardiovascular deaths, heart attacks, or strokes at LDL less than 30 mg/dL in comparison at 70 mg/dL or higher, and even compared to less than 70 mg/dL. There is a consistent reduction in risk even when starting as low as an average of 63 mg/dL, and pushing LDL down to 21 mg/dL remarkably showed “no trade-off” of adverse side effects.
Maybe that shouldn’t be it is so amazing since that’s about the level we start life at. And there is another type of genetic mutation leaves people with LDL levels around 30 mg/dL throughout their lives and are known to have extremely long life expectancies. So where did we get this idea that cholesterol can get too low?
The common claim that lowering cholesterol can it is dangerous due to the depletion of cholesterol in the cells is not supported by evidence and does not take into account the exquisite balancing mechanisms that our bodies use. After all, that’s how we evolved. Until recently, most of us were used to it have LDL levels are around 50 mg/dL, so this is pretty normal for the human species. The absence of evidence that low or reduced cholesterol levels are somehow bad for us contrasts with the overwhelming evidence that lowering cholesterol reduces the risk of coronary heart disease, our number one killer.
But what about hormone production? From the body necessary cholesterol for the synthesis of steroid hormones – such as adrenal hormones and sex hormones – there is a concern that it would not be enough. But you don’t know until you try it. For decades, we’ve known that women who take cholesterol-lowering drugs don’t have a problem with estrogen production and that lowering cholesterol does not influence adrenal function. It also doesn’t destroy testicular function in terms of testosterone levels falling below normal. If anything, statin drugs can improve erectile function in men, which one would expect from lowering cholesterol. But you’ll notice that these studies only looked at lowering LDL to 70 mg/dL or lower. What about really low LDL?
In PCSK9 inhibitors, you can take most people below 40 mg/dL LDL and some below 15 mg/dL! And there it is there is 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 it falls in a straight line as LDL gets lower and lower, even below 10 mg/dL, for example, with no obvious safety concerns, but this occurs during exposure to these drugs. The longest follow-up to date of those whose LDL, through the use of multiple medications, was maintained below 30 mg/dL it is six years.
Now, we can take comfort in the fact that those with extreme PCSK9 mutations, which lead to a lifelong reduction in LDL levels below 20 mg/dL throughout their lives, remain healthy and have healthy children. Mutations that affect cholesterol are this cause so-called “longevity syndromes”, but this does not necessarily mean that the drugs are safe. The bottom line is that you should essay to lower our LDL cholesterol as low as we can, but much longer follow-up data is needed every time a new class of drug is introduced. So far, so good, but we were alone following data for about 10 years. For example, we didn’t know that statins increased the risk of diabetes until decades after they were approved and millions had been exposed. Also worth noting: PCSK9 inhibitors cost about $14,000 a year.
Doctor’s note
How can we lower cholesterol with diet? See Trans fat, saturated fat and cholesterol: tolerable upper zero intake.
For more on statin drugs, see the related posts below.
