Pick Your Poison: Overweight or High Cholesterol

Overweight and have high cholesterol? You may have to pick one to work on at a time, according to data from the lab of John Thyfault, an associate professor of nutrition and exercise physiology at University of Missouri.

Statins work really well at lowering bad LDL cholesterol, but they can cause muscle ache in some patients. Thyfault and colleagues decided to see if cholesterol-lowering drugs would affect benefits from exercise in obese and overweight patients.

The study, published in the Journal of the American College of Cardiology, used Merck's (NYSE: MRK  ) Zocor, but it seems safe to assume that other statins -- Pfizer's (NYSE: PFE  ) Lipitor and AstraZeneca's (NYSE: AZN  ) Crestor -- would give similar results given that statins work in the same way.

Taking Zocor didn't affect adherence to the exercise program -- both the group taking Zocor and those prescribed exercise alone went to 95% of exercise sessions over 12 weeks -- but there were dramatic effects on the outcomes of the exercise.

Cardiovascular fitness, defined by the amount of oxygen consumed normalized to body weight, increased by 10% in patients prescribed exercise alone, but only by 1.5% in those who also took a statin. The researchers also found that a marker for activity of mitochondria, which turn oxygen and sugar into energy, decreased by 4.5% in the patients who took Zocor, but increased, as it should, by 13% in the group that wasn't given the drug.

The increased fitness translated into weight loss. Over the 12 weeks, the exercise-only group lost 1.7% of their body weight on average, but the weight of the group that took Zocor increased slightly.

The study was small -- just 37 subjects between the two groups -- but the results were dramatic enough that they were statistically significant, meaning it was unlikely to have happened by chance alone.

Alternatives
The obvious solution is to lose the weight first and then start taking a statin. Changing diet and exercise should have a positive effect on cholesterol anyway.

Bristol-Myers Squibb's (NYSE: BMY  ) Pravachol, an older statin, has been show to have less of a negative effect on mitochondrial content than other statins. Doctors could also prescribe lower doses. In the study, a 40 mg dose was given, but Zocor's label suggests that doctors can start as low as 10 mg.

Merck has another cholesterol-lowering drug Zetia, which works in a different way as statins and could be used as an alternative. Of course, Zetia doesn't lower cholesterol all that much by itself and is mostly used as an add-on therapy to statins. It's even co-formulated with Zocor as Vytorin and with Lipitor as Liptruzet. Beyond Zetia and statins, there are a few other cholesterol-lowering drugs, including PCSK9 inhibitors, which aren't on the market yet.

I doubt these data will have a dramatic effect on sales of any of the drugs -- and Lipitor, Zocor, and Pravachol are available as generics, so their sales are already toast -- but it may spur a larger study to drive home the message that losing weight is made even harder by taking a statin.

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  • Report this Comment On May 19, 2013, at 2:05 PM, Uthatruth wrote:

    Instead of touting Zetia you might have mentioned that it is one of the most discredited drugs ever. Yes, it lowers cholesterol. But in large scale trials it showed little or no ability to lower stroke and heart attack risk. And it has lots of side effects, besides being expensive.

    By now almost everyone whomis paying attention knows that low doses of statins, especially the earliest ones on the market, now available as generics, DO lower heart attack and stroke risks, by a mechanism that is still not fully understood. The lowering of your cholesterol number is just a marker for -- probably not a cause of -- those lowered risks.

    Zetia survives on ignorance -- the too-facile and probably incorrect idea that "high cholesterol CAUSES heart attacks and strokes".

  • Report this Comment On May 19, 2013, at 2:21 PM, mrudrums wrote:

    You can work on both at the same time. Exercise AND diet can help with both ailments. But instead the healthcare and drug industry would rather give you a pill for cholesterol and then another pill for weight loss. I would take good nutrition over a pill with scary side effects any day.

  • Report this Comment On May 19, 2013, at 2:32 PM, luckyagain wrote:

    Take niacin instead. Your HDL will go up, your LDL will go down.

  • Report this Comment On May 19, 2013, at 6:35 PM, endodoc1985 wrote:

    Ultratruth doesn't know the data.

    The effect, if any, of Zetia on cardiovascular disease endpoints (e.g., MI) are being assessed in the IMPROVE-IT trial, in over 18,000 subjects, with data expected this June (the trial is event-driven, so will stop after about 5280 MIs have occurred).

    The ENHANCE trial that came out in 2008 was a much smaller (n = 700) shorter (2 year) surrogate trial assessing the additive effect of Zetia on top of simvastatin on cIMT (carotid intimal medial thickness) in patients with familial hypercholesterolemia who had aalready been treated with statins for at least a decade. They all had normal, thin cIMT at baseline. Despite a greater reduction in LDL-chol with Vytorin (Zetia+Sim) vs. Sim alone, there was no significant difference on the progression in cIMT.

    There were several problems with this trial design, however. 1st, treaatment with statins "delipidates" atherosclerotoc plaque, leaving behind the built up connective tissue/fibrosis that is not effected by lipid-lowering or statin therapy. So in retrospect, no impact on cIMT should have been expected with wither treatment (which is exactly what was observed). 2nd, the CV of the cIMT measurement was substantially greater than the change in either group, or certainly than the difference between the two groups; thus, the study was grossly under-poweered. 3rd, almost all trials that correlated change in cIMT to cardiovascular events have looked at the common carotid artery, omitting the carotid bulb and the internal carotid. The ENHANCE study pooled all 3; of note, when the bulb was removed, Vytorin showed a trend of improvement in cIMT vs. simvastatin alone.

    To state that an underpowered surrogate endpoint tiral in healthy subjects proves that the additional LDL lowering by adding Zetia to statin provides no difference in MI in high risk subjects is absurd. Don't get me wrong - it may turn out that adding Zetia on top of effective statin therapy doesn't provide meaningful additional benefit. But that will be determined in a few months from the IMPROVE-IT trial; it has not yet been addressed (and certainly not by the ENHANCE trial).

    Learn to understand data before you post....

  • Report this Comment On May 20, 2013, at 5:16 PM, Uthatruth wrote:

    In the meantime, we should be paying $60 a month for Zetia, whose side effects ARE known but, as you admit, whose benefits remain entirely theoretical? WHY is a drug with no proven benefits actually on sale to the general public?

  • Report this Comment On May 20, 2013, at 5:22 PM, Uthatruth wrote:

    Or IS there some group (perhaps those who cannot tolerate a statin) in which Zetia HAS been shown to lower heart attack and stroke risk? If so, tell us. I've looked hard and all I see, endlessly repeated in Zetia ads and media comments, the undeniable fact that Zetia lowers cholesterol.

    What we wanted, I thought, in exchange for all our money and side effects risks, was a reduction in clinically significant events. Give me health, please, not cholesterol bragging rights.

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