The Evidence Continues to Mount Against Statins

Pill BottleAlthough statins get a lot of flak in the Primal health community, you have to hand it to them. They may not cure cancer, or single-handedly save the economy and bring back all the jobs, or render entire populations totally immune to cardiovascular disease, but they do exactly what they’re meant to do: lower cholesterol. And they’re very good at what they do. You want lower LDL without changing what you eat or how much you exercise, or trying that crazy meditation stuff? Take a statin. Do you want to hit the target lipid numbers to lower your insurance premium? Take a statin.

Except that statins lower cholesterol by inhibiting HMG-CoA reductase, a crucial enzyme located upstream on the cholesterol synthesis pathway. If that were all HMG-CoA reductase did for us, that’s one thing. At least we’d know what we were getting ourselves into when we filled the prescription. But the “cholesterol pathway” isn’t isolated. Many other things happen along and branch off from the same pathway.

Some would deem those other products of the pathway inconsequential when you have the opportunity to lower cholesterol. Okay; that’s a normal reaction given the widespread hysteria surrounding blood lipids. Still, I maintain that we should give the benefit of the doubt to our physiology and assume the unfoldment of the body’s processes happens for a reason, even when we’re unaware of the “benefits” or existence of a particular process. There are a lot of moving parts in the meat sack your consciousness calls home. Probably a good idea to let them happen, or at least know what’s going on down there.

What else is downstream of HMG-CoA reductase?

CoQ10: Statins block CoQ10 synthesis. Because CoQ10 production is downstream from HMG-CoA reductase, statins interfere. This is a problem, for CoQ10 is an endogenous antioxidant and vital participant in the generation of cellular energy. It helps us generate ATP to power our cells, tissues, and structures. Muscle contractions require it. Deficiencies in CoQ10 have been linked to heart failure and high blood pressure. Luckily, supplemental CoQ10 is both widely available and, according to many studieseffective at countering some of the muscle-wasting effects of statins.

Squalene: Since squalene is the precursor to cholesterol, blocking squalene production is an expressed purpose of statin therapy. Good if you want to lower cholesterol at all costs, bad if you enjoy the antioxidant effects of squalene.

Vitamin K2: Statins interfere with vitamin K biosynthesis. The pathway inhibited by statin use is the same pathway used to convert vitamin K into vitamin K2, which is protective against cardiovascular disease. Interestingly, the sites in the body where statin-related adverse effects predominate – the brain, kidney, pancreatic beta cells, and muscles – also happen to be typical storage sites for vitamin K2.

Vitamin D: Since vitamin D synthesis in the skin upon UV exposure requires cholesterol, statins may impair it. This hasn’t been studied yet, save for one short term study where statin users’ vitamin D levels were monitored for a month. Although no changes were noted, changes in CoQ10 production take months to appear after statin therapy and vitamin D production may require a similar time frame to show changes.

Testosterone: Steroid hormone production is also dependent on cholesterol, and statin therapy is associated with a small but significant reduction in circulating testosterone levels in men.

What are some possible side effects of statin therapy?

Statins may cause myalgia, or muscle pain. If you listen to anecdotes from people who’ve taken statins, this is probably the most common side effect. On the other hand, most clinical trials suggest that muscle pain is rare. What can explain this discrepancy? Mild symptoms… such as fatigue, myalgias, or mildly elevated CK (creatine kinase, a marker of muscle damage), are usually not reported to the US Food and Drug Administration in a drug’s postmarketing period,” suggesting that “clinical trial estimates of these adverse events are an underestimation of the real world event rate.” In some cases, statins even lead to rhabdomyolysis, a severe, often fatal type of muscle damage which overloads the kidneys with broken down muscle protein.

Statins impair adaptations to exercise. When you add statins to an aerobic exercise routine, the normal improvements in cardiovascular fitness and mitochondrial function are attenuated (PDF). Furthermore, due to the possibility of musculoskeletal pain and/or injury, exercise also becomes less attractive and enjoyable. It’s no fun working out – or even going for a walk – when you ache all over.

Statins increase the risk of musculoskeletal injuries. In a recent study, statin users (characterized by use of a statin for at least 90 days) were more likely than non-users to develop musculoskeletal pain, injuries (dislocations, strains, tears, sprains), and diseases. Another study found similar results for statin use and osteoarthritis, rheumatoid arthritis, and chondropathies.

Statins increase fatigue. In one recent study, a group of over 1000 healthy men and women aged 20 and older took either statins or placebo. Those taking statins reported reductions in overall everyday energy and the amount of energy they were able to muster during exercise. These effects were more pronounced in women taking the drug.

Statins increase the risk of diabetes, with stronger statins having a greater effectThree mechanisms have been proposed. First, statins reduce glucose tolerance and induce both hyperglycemia and hyperinsulinemia. Second, certain statins change how insulin is secreted by pancreatic beta cells. Third, the reduction in CoQ10 impairs cellular function all over the body, leading to dysfunction. These are features of statins. They may not all lead to full blown diabetes, but these mechanisms occur uniformly across statin users to varying degrees, and the longer you adhere to your statin therapy the greater the risk.

Statins may increase the risk of certain cancers. Amidst flashy, misleading headlines claiming that statins could lower the risk of breast cancer based entirely on an association between high cholesterol levels and breast cancer from a study that didn’t even examine statins, we have long term usage of statins actually increasing breast cancer rates in women and overall cancer mortality in the elderly enough to offset the reduction in cardiovascular mortality.

Everything we know we only know because the pharmaceutical companies deign to provide it.

They control the flow of information. They have the raw data and release only the published research that’s been picked clean and gone over with a fine tooth comb. Actually, we don’t know what’s happening, what’s been removed, and what’s been omitted because we don’t have access to it. Seeing as how pharmaceutical companies have both the opportunity and motive to omit or downplay unfavorable results, I’m not confident we’re getting the whole story on statin side effects. For one thing, large statin trials will often have a “run-in period” where people who show poor tolerance of the drug are eliminated from inclusion in the full trial. That’s just crazy. We need trials specifically looking at, or at least including, the statin-intolerant. Side effects certainly are rare when you exclude the people who are most likely to have them.

Okay, okay. Even with the potential for side effects, surely the benefit to heart health makes it all worthwhile. Right?

It depends.

Even though statins can reduce mortality from heart disease in certain populations, they consistently fail to reduce all-cause mortality in everyone but people with an established clinical history of heart disease. For primary prevention in people without prior history of heart disease, even those considered to be at the “highest risk” (high LDL and such), statins do not reduce all-cause mortality. Same goes for the elderly (who seem to suffer more depression and cognitive decline when taking statins). Nor do statins lower the total number of serious adverse events (PDF), which include death (from any cause), hospital admissions, hospital stays, permanent disability, and cancer.  That’s the story, time and time again. You might be less likely to die from a heart attack, but you’re more likely to die from something else. It’s a wash in the end – unless you have prior history of heart disease/attacks. 

What does this mean for you?

If you’re currently on statins and notice any of the possible side effects listed above, talk to your doctor about cycling off. Your doctor works for you, not the other way around. Express your concerns, come armed with a few studies printed out, and suggest a trial period without statins to see how you respond under his or her guidance. Keep them apprised of your status with frequent updates. Turn it into an N=1 self experiment. Maybe it becomes a case study, even. Maybe you change your doc’s mind about the realities of statin side effects; good documentation tends to do that. Or maybe you realize that statins weren’t the problem after all.

Statins may not hurt you. They may even help, if you’ve already had a heart attack and you’re not elderly. I’m not saying you shouldn’t take them. I’m only suggesting that if you’re experiencing any of the issues mentioned above, you should probably consider not taking them with the help of your doctor to see if they resolve. And if your doctor is pushing you to take statins because of some mildly elevated cholesterol numbers, think about all the important physiological processes that occur along the same pathway whose inhibition you’re considering.

The narrative seems to be changing, though. Yeah, they want to give statins to pregnant women and there’s been chatter for years about putting them in drinking water, but things are getting better. The pill-pushers have overreached. Their latest curated guidelines for the primary prevention of cardiovascular disease, which looks suspiciously similar to the guidelines you’d come up with if your primary goal was getting as many people taking your drug as possible, are receiving considerable push back from physicians in the UK. Mainstream doctors who write for are publicly questioning the utility of statins.

Statins have their place. I won’t deny that. But they’re not for everyone and there are consequences, and I think people deserve to know that.

What do you think, folks? Got any statin experiences? Good, bad? Let’s hear about them!

TAGS:  Big Pharma

About the Author

Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending three decades researching and educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates Primal/paleo, keto, and Whole30-friendly kitchen staples.

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