The Great Statin Controversy

What does the science say?
By Adam Swenson

Editor’s note: Recently our sister journal, Alternative Therapies in Health and Medicine (ATHM), convened a roundtable discussion featuring four leaders in complementary medicine. Stephen Sinatra, MD, is America’s top integrative cardiologist and a best-selling author. Andrew Campbell, MD, is an immunotoxicologist and editor-in-chief of ATHM. David Perlmutter, MD, is a neurologist and director of the Perlmutter Health Center, medical director of the Perlmutter Hyperbaric Center, and an author and popular keynote speaker. Finally, Beatrice Golomb, MD, PhD, is a professor of medicine at the University of California, San Diego School of Medicine and has published many scholarly articles and given many high-profile presentations. This feature is based on their discussion.


Statins were born out of the perceived need to lower cholesterol. Years ago, the research seemed to point to cholesterol having a big effect on heart disease, but more recent research indicates that damaged LDL cholesterol is actually the culprit.

The single goal of statin drugs is to lower cholesterol by inhibiting an enzyme called HMG-CoA reductase. This enzyme is a necessary ingredient in the liver’s synthesis of cholesterol, and this is where 80 percent of the cholesterol in your bloodstream comes from—your liver.

And statins are good at what they do: studies have found that on average they lower LDL cholesterol by 70 mg/dl, which can bring many “high cholesterol” people down into the currently recommended range.

But to assume this is a worthwhile endeavor presupposes that lowering cholesterol is going to help prevent heart disease. When deciding whether or not to prescribe a medication for a patient, a physician has to weigh the potential gains versus the potential risks, much like a cost/benefit analysis in business.

And there are some considerable risks and side effects associated with taking statins: this is not to say that statins are wholly without merit, just that, in the opinion of our roundtable physicians, they are appropriate for a much smaller patient demographic than what the current prescribing culture reflects.

Who should take statins?

Our roundtable physicians discussed this in detail and reached a consensus: statins are appropriate in non-diabetic middle-aged men who have demonstrated heart disease (particularly those that have had a heart attack or have acute coronary syndrome) and middle-aged men that are clearly at high, imminent risk. If those middle-aged men had low HDL, that would be another factor in favor of statin use.

They agreed that women should rarely take statins, people over 70 should not be on statins, and children should never be on statins. Clearly these recommendations are pretty far off from the actual statin use that is occurring today. As Andrew Campbell, MD, said during the roundtable, “Basically one in four Americans over the age of 45 now takes a statin drug.”

As Stephan Sinatra, MD said, “The proof in the pudding is that a third of cardiologists themselves take statin drugs. This belief—or this conspiracy, whatever you want to call it—goes miles deep.”

So why the revised recommendations? There are two reasons and they are ultimately interrelated. First: if the high-cholesterol-is-a-killer hypothesis is off base, then taking drugs with side effects (some severe) to lower cholesterol is nonsensical. Second: quite simply, these recommendations line up with the studies—any scientist worthy of the name must be open to re-evaluating his or her conclusions on the basis of compelling empirical evidence.

We’ll start with the general point that those who have had a cardiac event or are otherwise at risk have the most to gain. In a meta-analysis by George Daves-Smith, MD, he looked at a series of trials in which people took cholesterol-lowering drugs. Because he was looking at it after the fact, he knew which people had actually died. The high-risk group (defined as a one in four chance of dying within five years) showed statistically significant benefits from cholesterol lowering treatment. Daves-Smith writes, “A cholesterol lowering drug that reduces mortality from coronary heart disease will have a greater effect on all-cause mortality in high-risk patients with established cardiovascular disease than in asymptomatic patients with isolated hypercholesterolaemia [high cholesterol].”

To unpack the last portion of that sentence, he’s saying that “asymptomatic patients”—i.e. patients that have not had a heart attack or other heart disease, but only have high cholesterol—did not show benefits from lowering cholesterol like those who had already had a heart attack.

Regarding the low-risk demographic (with a one in 20 risk of dying of a cardiac event within five years) Dr. Golomb said, “In that group there is a [statistically] significant increase in all-cause mortality associated with lipid lowering compared to placebo … So then what happened with the statin trials is that they learned that lesson—if you want to see the benefit, you focus on a population at high risk for heart disease.”

In layman’s terms: in a big picture overview looking at many different large trials, people in the low-risk group who only had high cholesterol and no other factors were more likely to die on a cholesterol-lowering treatment than those on placebo.

Women also have not fared well on statins in these studies. In the 4S study, women showed a 12 percent increase in overall mortality compared to those on placebo.

Numerous studies have shown that the elderly do better overall with higher cholesterol, with better cognitive scores and less risk of all-cause mortality. A large 10-year study published in 1996 in the Lancet found that “each 1 mmol/L [40 mg/dL] increase in total cholesterol corresponded to a 15 percent decrease in mortality.”

Side effects

So far, I think we could say the results are a mixed bag. Statins do seem to be a help for some, but create additional mortality risk for others. To understand why that is, we’ll have to look at the side effects of statin use and lowering cholesterol, some of which are quite significant. Diabetes, an increase in arterial plaque deposits, muscle weakness, loss of sexual function, neurological problems, and total global amnesia are a few side effects experienced by statin users.

Regarding an increase in arterial plaque deposits, Dr. Campbell said, “Two recent studies that have come out ... in Atherosclerosis 6,673 patients showed that statins had a 52-percent increase in the prevalence and extent of calcified coronary plaques compared to non-users. Then there was another study in Diabetes Care showing that type-2 diabetics with advanced atherosclerosis who used statins have significantly higher amounts of carotid artery calcifications compared to those who use it less or don’t use it at all.”

Yunsheng Ma and Annie Culver published another study that followed 153,840 menopausal women from 50-79 years old. In a multi-year follow up, they found that statin use was associated with a 71 percent greater risk of developing diabetes.

Perlmutter, widely regarded as an expert in the neurological field, says that cognitive issues with statins “are rampant.”

Dr. Golomb went on to tell the story of a lawyer she saw in her practice “who said that his cognitive function had deteriorated to the point that if clients asked him a question he would ask them, ‘what do you think?’ because he really couldn’t reason for himself anymore. He wrote a letter to his esteemed academic cardiologist about this issue and they said ‘We followed the cognitive issue and, despite the FDA warning, we think that all those people who get cognitive problems have other reasons for having cognitive problems and you need to stay on the drug.’ Here’s a person who has plausibly had an incredibly serious, career-threatening event that may very well be an adverse effect of his drug, and his cardiologist is telling him he needs to stay on them.”

Perhaps the most egregious side effect of statins is that they keep the body from making coenzyme Q10 (CoQ10). As mentioned earlier, statins block the enzyme called HMG-CoA reductase, which in turn prevents the liver from synthesizing cholesterol. The problem is, blocking that enzyme also inhibits the production of CoQ10. This is problematic as CoQ10 is needed in every cell of the body. It is needed for cell growth and maintenance, it is a potent antioxidant, it helps enzymes do the work of digesting food and performing other processes, it helps the heart in many ways, and guards against cancer. Depleting CoQ10 leads to more free radical production, which (in Perlmutter’s opinion) essentially cancels out any antioxidant benefits statins may have.

So where do all these side effects come from? Simply put, the body needs cholesterol for a great many things. Cholesterol is essential for cell structure and function. It’s a raw material we need to synthesize steroid hormones like testosterone and estrogen, bile acids, and corticosteroids that regulate sugar, fat, protein metabolism, and the immune system.

“This demonization of cholesterol that has happened since the early Framingham work is so off base,” Dr. Perlmutter says. “Twenty-five percent of the body’s cholesterol is in the brain where it is performing desperately important tasks of antioxidation. The brain actually manufactures vitamin D from cholesterol … This idea of lowering cholesterol because cholesterol is bad, that is just not sitting well with current science … Why would your liver, that evolved in terms of its metabolic processes—at least over the past 2.6 million years—be making suddenly such a terrible mistake and creating a chemical that is bad for your body? Does that make any sense at all?”

If not statins, then what?

Whether or not cholesterol is the villain, heart disease still comes from somewhere and it’s still far and away the leading cause of death in America in any given year. (Heart disease kills as many people as all forms of cancer and all traffic fatalities combined.) Plaque still builds up in arteries, people suffer from hypertension, and heart attacks are still killers.

Dr. Sinatra summed up the feelings of our panelists when he said, “So our plea … is instead of focusing on cholesterol, let’s focus on other factors that cause inflammation and oxidative stress in the body that leads to illness whether it’s cardiovascular disease, neurological, or even cancer.”

Inflammation and oxidative stress

If cholesterol is out as Public Enemy Number One, those two are in. (To read further on inflammation and oxidative stress, check out our “Cholesterol: Who Needs It?” feature in the February 2013 issue of our sister publication, Alternative Medicine, as well as Jonny Bowden’s “The Great Cholesterol Myth” cover story in this issue.)

In short if you were looking to cut down on inflammation and oxidative stress, you would cut out smoking and excessive alcohol consumption, address obesity if need be, get regular cardiovascular exercise, and avoid trans fats and refined carbs, instead adding antioxidant-rich fresh fruits and vegetables.

The statin industry

Now that statins have been part of mainstream medical culture for a few decades, it will take time to turn the ship. As Dr. Perlmutter said, “…there is a huge, powerful lobby involved in perpetrating the myth of the demon of cholesterol … and that we’ve got to lower it to levels that are almost immeasurable with the use of these potentially toxic medications. That needs to change.”

In the meantime, however, well-informed readers can research and come to their own conclusions.


Krill Oil: An Omega-3 Powerhouse

Omega-3 fatty acids are known to decrease triglyceride levels and blood pressure, reduce inflammatory markers, improve endothelial function, and prevent blood from clotting too easily. Fish oil has been the standard bearer for some time, but krill oil has recently become available and it merits serious consideration as it has a few advantages over fish oil. First, krill oil is much more easily digestible (or “bioavailable”) as it is water soluble to a greater degree than standard fish oil. Secondly, krill oil has a phospholipid outer layer. This is important because to do any good in your body, the omega-3s must be able to get inside the cells: the cell wall is made of phospholipids, so the krill oil is already in the proper form to gain admittance with no conversion required. Thirdly, the astaxanthin in krill oil (responsible for the natural red color) protects the omega-3s from oxidation. Michael Eades, MD, writes, “The antioxidant potency of krill oil is such that when compared to fish oil in terms of ORAC (oxygen radical absorbance capacity) values, it was found to be 48 times more potent than fish oil.”

A study published in Alternative Medicine Review showed that, in their test subjects, a 3.0 gram/day dose of krill oil over a 90-day period reduced total cholesterol by 18 percent, reduced LDL by 39 percent, increased HDL by 60 percent, and lowered triglycerides by 27 percent.

The icing on the cake, as it were, is that krill oil is very ecologically responsible: the biomass of krill is estimated to be five times greater than the collective biomass of all the fish species commercially harvested today.