Study – To lower cholesterol, statins work, supplements don’t

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It is now well established that a high level of “bad” cholesterol (low density lipoprotein or LDL) increases the risk of heart disease. Additionally, LDL reduction is protective, reducing the risk of atherosclerotic vascular disease, with high-risk patients having more benefit. This is extremely convenient in terms of cardiac and vascular research, because we can now simply study whether a treatment is effective in lowering LDL. Tracking a blood marker is much easier than tracking health results, which have many confounding factors and take much longer.

People looking to improve their heart and vascular health by improving their cholesterol levels (reducing LDL and increasing good cholesterol – HDL) have many options. Regular exercise has been shown to improve cholesterol profiles and have many other health benefits. It is therefore a clear recommendation. The relationship between diet and cholesterol is more complex. Dietary cholesterol does not appear to have a significant effect on blood cholesterol for most people (some individuals, however, are genetically predisposed to react to cholesterol in their diet). Otherwise, the basic advice is to have an overall healthy diet, limiting saturated fats and consuming plenty of fruits and vegetables. Having a lean body mass is also helpful.

Diet, exercise and maintaining a healthy weight are enough for most people to maintain a healthy cholesterol profile and should always be part of any strategy to achieve this. However, not everyone can or maintains a healthy lifestyle. Also, many people are genetically predisposed to high cholesterol, and no healthy lifestyle will counteract their genetics. Therefore, for many people, adding a medication or supplement to help improve the cholesterol profile is a useful, if not necessary, strategy. This is the subject of a recent study published in the Journal of the American College of Cardiology.

The study includes 190 participants, which is modest in size.

This was a single-center, prospective, randomized, single-blind clinical trial in adults with no history of atherosclerotic cardiovascular disease (ASCVD), an LDL-C of 70 to 189 mg/dL, and an increased risk of ASCVD on 10 years. Participants were randomized to receive 5 mg per day of rosuvastatin, a placebo, fish oil, cinnamon, garlic, turmeric, plant sterols or red yeast rice.

The primary endpoint was change in LDL-C from baseline at 28 days. The rosuvastatin group confirmed the efficacy of this drug, with a 35.2% decrease in LDL-C from baseline. It is both clinically significant and statistically significant (

The main weakness of the study was its modest size. But that’s not really a significant issue, in my opinion, because the study was clearly large enough to detect a clinically meaningful effect. You could argue that the trial was too small to rule out a small beneficial effect from any of the supplements, which is true, but such a small effect probably isn’t worth it in all cases. The study was single-blinded, but since the only outcome measure was completely objective, a blood test result, that shouldn’t matter. Nevertheless, a larger, double-blind, multicenter trial would be welcome. I just doubt it would show anything different.

Negative results for all supplements except fish oil are to be expected. Previous evidence for these supplements has never been good. Turmeric, for example, suffers from insignificant bioavailability. Some versions of red yeast rice actually contain a small amount of lovastatin (a proven cholesterol-lowering drug), but not the brands available in the United States. Red yeast rice without lovastatin has no effect on cholesterol. Garlic has also been studied and found to be ineffective as a cholesterol-lowering agent. The evidence for cinnamon is also negative.

The story of plant sterols is a bit more complicated. The evidence shows a possible modest effect, around 9% LDL reduction. This effect may have been missed in the current study. But also, it requires having 2 grams of plant sterols twice a day, which many may find difficult. Additionally, there are lingering issues regarding the net clinical effects of these doses, so relying entirely on a marker such as blood LDL may not be everything. Margarines containing plant sterols may also contain trans fats, which can negate the benefits. It is therefore a delicate option, but which is perhaps not totally useless. Obviously, however, it does not replace a statin.

Fish oil is also a bit complicated. Although evidence shows that it does not lower total cholesterol and may even raise LDL a little, its main benefit may come from an increase in good HDL cholesterol. This is a situation where we need evidence from net clinical outcomes, but they are very difficult to document with modest interventions, as they would require thousands of subjects, or even tens of thousands, over years. to reach statistical significance. The bottom line with fish oil is that you can’t just sprinkle it on your steak. It does not replace a good diet or statin medication. But there may be benefits to helping increase HDL.

This one study, because it’s small, isn’t definitive on its own, but it adds to a growing body of evidence that pretty consistently shows the same thing. There are two proven strategies to significantly improve cholesterol profile and cardiovascular health: lifestyle factors and statins. Supplements are basically in the noise of the evidence and have either been found to be useless or at best have a modest effect that is hard to pinpoint. Supplements do not replace the first two strategies.

It also makes sense because supplements are drugs, they are just drugs that have been poorly purified and usually have poor pharmaceutical attributes (otherwise they would be marketed as drugs). What they have is effective (and deceptive) marketing.

  • Founder and current editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at Yale University School of Medicine. He is also the host and producer of the popular weekly science podcast, The Skeptics’ Guide to the Universe, and the author of NeuroLogicaBlog, a daily blog that covers news and issues in neuroscience, but also general science, scientific skepticism, philosophy of science, critical thinking and the intersection of science with media and society. Dr. Novella has also produced two courses with The Great Courses, and published a book on critical thinking – also called The skeptics guide to the universe.

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