It is now well-established that having high levels of “bad” cholesterol (low density lipoprotein, or LDL) increases the risk of heart disease. Further, lowering LDL is protective, reducing the risk of atherosclerotic vascular disease, with higher risk patients having more of a benefit. This is extremely convenient in terms of cardiac and vascular research because now we can study simply if a treatment effectively lowers LDL. Following a marker in the blood is a lot easier than tracking health outcomes, which have a lot of confounding factors and takes a much longer time.

People looking to improve their cardiac and vascular health by improving their cholesterol numbers (lowering LDL and increasing good cholesterol – HDL) have lots of options. Regular exercise has been shown to improve peoples’ cholesterol profile, and has lots of other health benefits, and so it is a clear recommendation. The relationship between diet and cholesterol is more complex. Dietary cholesterol does not seem to have a significant effect on blood cholesterol for most people (some individuals, however, are genetically predisposed to respond to cholesterol in their diet). Otherwise the basic advice is to have an overall healthy diet, limiting saturated fats and having plenty of fruits and vegetables. Having a lean body mass is also helpful.

Diet, exercise, and maintaining a healthy weight is enough for most people to maintain a healthy cholesterol profile, and should always be part of any strategy to do so. However, not everyone can or does maintain a healthy lifestyle. Also, many people are genetically predisposed to high cholesterol, and no amount of healthy lifestyle will counteract their genetics. For many people, therefore, adding either a drug or a supplement to help improve cholesterol profile is a helpful or even necessary strategy. That is the focus of a recent study published in the Journal of the American College of Cardiology.

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

It was a single-center, prospective, randomized, single-blind clinical trial among adults with no history of atherosclerotic cardiovascular disease (ASCVD), an LDL-C of 70-189 mg/dL and an increased 10-year risk of ASCVD. Participants were randomized to 5 mg daily of rosuvastatin, 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 that this medication is effective, with a 35.2% decrease in LDL-C from baseline. That is both clinically significant and statistically significant (<0.001). None of the six supplements showed any significant reduction in LDL-C.

The primary weakness of the study was its modest size. But this is not really a significant issue, in my opinion, because the study was clearly large enough to detect a clinically significant effect. One might 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 is likely not worthwhile in any case. The study was single-blinded, but because the only outcome measure was completely objective, a blood test result, this should not matter. Still, a larger, double-blinded, and multi-center trial would be welcome. I just doubt it would show anything different.

The negative results for all the supplements save fish oil is to be expected. The previous evidence for these supplements was never 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 US. Red yeast rice without lovastatin has no effect on cholesterol. Garlic has also been studied, and shown 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 does show a possible modest effect, about a 9% lowering of LDL. This effect may have been missed in the current study. But also, this requires having 2 grams of plant sterols twice a day, which many may find difficult. Further, there are lingering issues of the net clinical effects of these doses, so relying entirely on a marker such as blood LDL may not be the whole story. Margarines with plant sterols may also contain trans fats, which can wipe out the benefits. So this is a tricky option, but may not be entirely useless. Clearly, however, it is no substitute for a statin drug.

Fish oil is also a bit complicated. While the evidence shows it does not lower total cholesterol, and may even increase LDL a bit, its primary benefit may come from increased 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 because they would requires thousands of subjects, or tens of thousands, over years to get to statistical significance. The bottom line with fish oil is – you can’t just sprinkle it on your steak. It is no substitute for a good diet, or a statin drug. But there may be some benefit in helping to increase HDL.

This one study, because it is modest, is not definitive unto itself, but it does add to a growing body of evidence that is fairly consistently showing the same thing. There are two strategies proven to significantly improve cholesterol profile and cardiovascular health – lifestyle factors, and statin drugs. Supplements are basically drown in the noise of the evidence, and have either been shown to be useless or at best have a modest effect that is difficult to pin down. Supplements are not a substitute for the first two strategies.

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

Author

  • Founder and currently Executive Editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at the 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 the 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 the media and society. Dr. Novella also has produced two courses with The Great Courses, and published a book on critical thinking - also called The Skeptics Guide to the Universe.

Posted by Steven Novella

Founder and currently Executive Editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at the 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 the 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 the media and society. Dr. Novella also has produced two courses with The Great Courses, and published a book on critical thinking - also called The Skeptics Guide to the Universe.