UC San Diego Study Links Cholesterol-Lowering Statins To Fatigue

CAVANAUGH: This is KPBS Midday Edition. I'm Maureen Cavanaugh, it's Tuesday, June†12th. Our top story on Midday Edition, a new study from UC San Diego has found that the most popular drugs used to control cholesterol may make you too tired to exercise, which of course people with high cholesterol are supposed to do to help lower cholesterol. This catch 22 involves lower energy levels found in people who take statin drugs. Joining me to explain the findings are my guests, doctor Beatrice glum, associate professor of medicine at UC San Diego school of medicine. She is lead researcher in the study published in the current issue in archives of internal medicine. Welcome to the show. GOLOMB: Pleasure to be here. CAVANAUGH: Doctor Mimi Guarneri is also with us, cardiologist founder and medical director of the Scripps center for innovative medicine. Welcome to the program. GUARNERI: Thank you so much for having me. CAVANAUGH: Doctor Golomb when we talk about statins, what prescription drugs are we talking about? GOLOMB: I'll use the brand names here, Lipitor, Crestor, Zocor, Prevacol, also there are other ones like Mebacore, which is a statin, and Lescol, which is fluvostatin, and those are the major ones. CAVANAUGH: At least some of those I think most people have heard of. Who are they prescribed to? Are they people who have had heart attacks and strokes? Or people who want to prevent them? GOLOMB: They're prescribed to both. Of course since there are many more people that have not had heart attacks and strokes, they represent the bulk of the people to whom those drugs are given. CAVANAUGH: Okay. And before this particular study, other side effects were already associated with statins. What are they? GOLOMB: Well, a number of side effects have been associated with statins. They have been found to impair sleep, they do increase muscle enzymes on average, suggesting issues associated with muscle injury. One in the elderly found a significant increase in cancer, but that has not been the case in middle aged individuals. So there are a number of adverse effects. CAVANAUGH: I think there was a famous get-together amongst doctors talking about statins where somebody got up and proclaimed statins make women stupid because of the cognitive impairment that has been found in people who take this drug. GOLOMB: Right. In our observational study of statin adverse effects, cognitive problems are the second most frequently reported after muscle/fateen problems. That doesn't mean they're the second most common. But they're the second most reported. MAUREEN CAVANAUGH: Before we get to your newest study, doctor Guarneri, what has been your experience? GUARNERI: We have a lot of clinical experience. We take care of all those patients that other physicians give up on because they have side effects from statin, in their opinion. Our specialty is the use of nutraceuticals, and diet and and exercise and so on. What I commonly see, and I'm so glad this study came out, because it has been underreported up until this point, is fatigue is a major issue. Miopathy, muscle pain is a major issue. One thing that no one ever talks about is hair loss, is a major issue, particularly notable for women. We see lots of concerning things, including nutritional deficiencies that result from statin therapy. CAVANAUGH: Doctor Golomb, what made you want to test for connections between fatigue and statins? Is it what you were hearing from the clinicians? GOLOMB: It's what I was hearing from patients. My own patient, and also many patients who contacted us to report problems with these drugs. And fatigue coupled with the muscle problems on are the most commonly reported problems by patients. And randomized trials had not really reported an association. But none of them had really set out specifically to ask patients about energy or fatigue with exertion as an end point of the study. CAVANAUGH: What did this study find in terms of fatigue? What did you actually correlate between the use of statins and the way people felt during the day? GOLOMB: The two main questions we asked, and our feeling is what the patient experiences is the most important to the patient. So we asked them their level of energy at baseline, and also their level of fatigue with exertion, and we asked again on treatment whether it was much better, some better, about the same, somewhat worse or much worse. And they didn't know whether they had been randomized to statin or placebo. And when we looked at the results, we found that a substantial fraction of them reported diminutions in energy or fatigue with energy exertion or both. And particularly striking for women. CAVANAUGH: And did that increase as the dosage went up? Was that the kind of correlation that you found? GOLOMB: Right. There are other study types that showed that these problems are strongly dose-independent. We only used one dose of each of two cholesterol lowering drugs in the study. The most fat soluble, and the most water soluble to make sure the findings weren't just related to one. One turned out to be a little more potentent of the the Zocor was more poeten. They both contributed to the finding, but the more potent one did contribute more. And did you find a percentage? Were you able toicalulate a percentage people with fatigue after taking statins? GOLOMB: Because of the rating scale we used, the average finding in women on Zocor was a .4 defense, which would translate to 40% of women being somewhat worse than one of the two, or 20% being either much worse than one or somewhat worse in both, or 10% reporting both as much worse. O different subfractions of the population for which each of those statements were true. CAVANAUGH: You kind of lost me there. [ LAUGHTER ] GOLOMB: I know, I know. It doesn't really allow an exact percentage. But somewhere between 10-40% of women, closer to the 20-40% side that had these adverse effects discounting the fraction that would have developed this on placebo. CAVANAUGH: The way that statins go about lowering cholesterol, do we see any correlation there between the way these drugs operate and what might be causing this fatigue? GOLOMB: Absolutely. One of the path ways, that these substances prohibit is -- the main fat soluble antiox do not that the body uses. And the energy producing parts of cells are the parts that are most susceptible to the things that antioxidants react to. They also inhibit product of heme A, which is also involved in cell energy production, and on top of that, cholesterol itself transports fat soluble antioxidants, even vitamin D, is both a product of cholesterol and also travels in association with cholesterol in the blood. CAVANAUGH: So if someone were to take the supplement of zyme Q10 while they were taking Lipitor, do we have any reason to assume that that might off sufficient set some of that fatigue? GOLOMB: The answer appears to be both from be observational studies that it partially upsets. It's probably not the only mechanism. Some people report full resolution, and some report none, but it does improve the problem on average. CAVANAUGH: Doctor Guarneri, as you know, an estimated 1 in 4 Americans currently takes statins. Lipitor is the most popular prescription drug there is. Do you think doctors do a good enough job of weighing the risks and benefits of these drugs? GUARNERI: I absolutely don't think they do a good enough job. I just want to say that cholesterol in itself is not harmful. It's what happens to cholesterol, it becomes oxidized, glycolated, this is the result of things like inflammation, and we know the major mechanism or benefit from the statins is its antiinflammatory effects. You heard that there is one nutrient, the ubiquinol, but that's just the tip of the iceberg. The research shows that the membranes of the cells have a decrease in fatty acid, a decrease in vitamin E. Statins deplete the cells of Carnitine as well as coteen 10. So there are lots of issues with these medications. And I'm not against using medication, but I think you have to do exactly what you say. Weigh the risks and the benefits and quite frankly teach people how to eat, to lower their cholesterol. Because the majority of the cholesterol is still coming from the diets that people eat. And if you do choose to use a statin, then you should understand, a physician, what are the potential downstream effects of these medication, and do I need to support my patient with other right nutraceuticals, whether it's omega 3 or carnitine or coteen 10. CAVANAUGH: Learning to eat properly is so important for so many health concerns that people have. Is there an alternative however to taking statins that has also been proven to lower cholesterol? Suppose if someone has difficulty controlling their diet? GUARNERI: Absolutely. First and foremost, I always say food first. Cholesterol comes from animals. It you can eat as close as possible to a vegetarian diet, you're going to eliminate most of the cholesterol. If we go into the nutraceutical world, and just talk about LDL, the so called bad cholesterol, we can lower it with fiber, for example. Steel-cut oats or fiber in the form of supplements like glucomanin. Plant stanols, which we can get in our foods or in a supplement form, can lower LDL 10%. Citrus bergamot can lower LDL a good 10%. So we have lots of choices that go way beyond statin therapy. CAVANAUGH: Now, well Golomb, I know that you've been doing science here, this research not based on one therapy over another, but just basically trying to find out how these statins work, and what the side effect effects are. Based on what you've found out, who should not be taking statins? Do we know enough now to answer that question? GOLOMB: Well, I guess the way I approach medications in general, is that particularly for preventive medicines that are not this to reduce suffering but are there to benefit the patients, the index of whether a drug should be used is whether there's objective evidence that the drug benefits exceed the harms. And the available objective markers that equitably balance risk against benefit all cause mortality. And in older studies there was an index that by the old definition was a proxy for serious morbidity, things that cause life threatening disabilities. And they have not also led to any benefit to morbidity where both of these were looked at. By that index, looking at markers where the patient actually benefits, men under the age of 70-75 who have heart disease on average we see the benefit from these drugs. Women and people over age 70 who have heart disease have not shown benefit exceeding risk. In the trial of people over age 70, all-cause mortality was -- there was a statistically increase in new cancer. In younger individuals that don't have heart disease, people with as the doctor mentioned high markers of inflammation show benefit. The magnitude of that benefit is actually fairly small. So there still are risk benefit issues to be considered in that group. But even if high risk primary prevention who doesn't have high markers of inflammation, and smokes as well, the benefits have not been found to exceed the risks. CAVANAUGH: You go into -- as I woman, because it sounds as if women have a harder time getting benefits from these statins than men do. As a woman, you go into the doctor, he finds that you have high cholesterol, and says, you know, we got start you on one of those drugs. What kinds of questions do you need to ask at that point? GOLOMB: Oh, this is such a thorny question. Of course the current guidelines do have women treated as well as men, even though in my opinion, the evident doesn't really support that. But I think it would be worthwhile to ask the doctor do the benefits exceed the risks? This certainly shifts the cause of death from heart disease to other causes in women with heart disease. But there really is a request whether the patient wants to experience a shift in the cause of death and disability in turn for some risk of side effect or not, and I think the patient should be involved in that decision. There's a doctor in New Zealand who makes the case that patients who are in these categories like women and elderly who don't receive benefits from these drugs should sign a consent form. And I think there is an ethical argument to be made there. CAVANAUGH: And that same question, doctor, if you are placed in that position where the doctor is now telling you, you know, you better go on this stuff because your cholesterol is real high, what kind of questions and what kind of risk benefit analysis should you make yourself? GUARNERI: The first thing a woman needs to know is cholesterol is only a piece of the puzzle. A woman needs to know what is their blood pressure, what type of cholesterol do they have? For example, the HDL 2, which is -- 2B, what are they triglycerides? What are their inflammatory markers looking like? I take a look at my patients' arteries. I look at the arteries in the neck. Something very simple, simple ultrasound that allows me to calculate the thickness of the lining of the blood vessel. That's an easy way to look at someone's blood vessels. Look in the back of the eye. Do something called an ankle breakio index. They're all noninvasive tests that could predict risks. Endo thellial function, a machine tells us is this person at risk from a cardiovascular standpoint? Cholesterol as I said earlier if it's not oxidized is not harmful. CAVANAUGH: We've got to end it. I'm so sorry. This is fascinating but I'm simply out of time. I want to thank you both very much, it's very educational. Than you so much. GOLOMB: Thank you so much for having me. GUARNERI: Thank you so much.