Author	Reviewer
Milan Gupta, MD, FRCPC, FCCS, CPC(HC) Assistant Professor, Department of Medicine, University of Toronto Medical Director, Canadian Collaborative Research Network Brampton, ON	Paul M. Ridker, MD, MPH Director, Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital Eugene Braunwald Professor of Medicine, Harvard School of Medicine Boston, MA

Watch this video summary with blog author Dr. Milan Gupta

Many of your patients are taking dietary or health supplements, whether you realize it or not. Marketed as natural health products, vitamins or minerals, these agents are often thought of by the public as important for heart health or for cholesterol lowering. Roughly 50% of Canadians, and up to 80% of Americans, regularly use dietary supplements, usually without physician advice or knowledge. The annual market for such supplements in USA approaches $50 billion per year. Although regulated in Canada by the Natural and Non-Prescription Products Health Directorate, natural health products can make only very limited health claims and do not have to provide much safety information on their labels. They are also not required to confirm efficacy through clinical trials. In some cases, as with fish oil supplements, the medical community has conducted multiple rigorous clinical trials, showing absolutely no cardiovascular or cancer benefit. Canadian lipid guidelines actually have a strong recommendation against the use of fish oil supplements for CV protection. Similarly, past clinical trials have failed to show health benefits of vitamin E or folic acid supplementation. These trials, however, have rarely diminished enthusiasm for supplements and our patients are often on the receiving end of misleading advertising campaigns that infer health benefits that simply do not exist. Most supplements and herbal remedies have not been evaluated at all.

Many dietary supplements are consumed by Canadians who believe they lower cholesterol levels and are thus ‘heart healthy’. Regrettably, many patients abandon their prescribed statins for natural health products, believing they are just as efficacious as statins, yet safer. Given the increasing prevalence of cardiovascular disease and the benefits of cholesterol lowering in preventing CV events, it is important that we understand the role, if any, of natural health products as an adjunct to, or replacement for, effective statin therapy.

What do I tell my patients who claim they can’t take statins due to muscle symptoms?

Patients starting statins often also start to exercise for the first time in years. As a consequence, many feel the aches and pains of exercise yet blame it on the statin. So as a first rule of thumb, don’t prescribe exercise at the same visit that you initiate statin therapy.

Placebo-controlled clinical trials suggest that muscle aches truly related to statin therapy occur in less than 5-10% of patients. A recent meta-analysis of 19 large statin trials showed that only one in fifteen patient reports of muscle symptoms were actually due to the statin, and the majority of those were mild in severity. The SAMSON study took a novel approach to assessing statin muscle effects. They randomized ‘statin-intolerant’ patients to taking 4 months of atorvastatin 20 mg tablets daily, 4 months of matching placebo tablets, and four months of no tablets whatsoever, and asked them to daily rate their muscle pain. The symptom score was significantly higher in statin months than in no-tablet months but was also higher in placebo months. In fact, there was no statistically significant difference in symptom score between the statin months and the placebo months. While there seemed to be clear intolerance to statin tablets, there was equally clear intolerance to placebo tablets. In other words, the source of the intolerance was the act of taking a tablet, not the statin itself, otherwise known as the nocebo effect.

In daily practice, many of us will prescribe every other day statins to patients who have complained of muscle aches. This simple strategy is often highly effective and can be cost saving as well.

Do dietary supplements lower LDL-cholesterol levels?

A variety of natural health products are purported to reduce cholesterol levels and are thought of as safer than statins. Many of my patients have told me they take various supplements for this very purpose. I suspect some, if not many of them, aren’t taking their prescribed statin at all. The Supplements, Placebo, or Rosuvastatin (SPORT) Study finally answered the question about dietary supplements and cholesterol lowering.

The SPORT investigators enrolled patients between 40 and 79 years of age, at intermediate CV risk (without manifest ASCVD), who had LDL-cholesterol levels above 1.8 mmol/L in the absence of any lipid-lowering therapy. Patients were randomized to one of eight blinded arms: rosuvastatin 5 mg, placebo, fish oil, cinnamon, garlic, turmeric, plant sterols, or red yeast rice. After four weeks of treatment, rosuvastatin 5 mg daily resulted in a mean percent decrease in LDL-C of 37.9%, which was highly statistically significant. By contrast, when compared to placebo, none of the dietary supplements significantly lowered LDL-C at all, and garlic actually significantly increased LDL-C. Furthermore, adverse events were similar between the rosuvastatin group and all of the supplement groups, with no difference in muscle symptoms between groups. SPORT clearly demonstrates that many of the “cholesterol substitutes” that our patients are taking simply do not work, important information you need to discuss with your patients.

What does this mean for my patients?

A recent meta-analysis of clinical trials and prospective cohort studies including over 2 million subjects showed that vitamin/mineral supplements had no appreciable effect on improving CV mortality in the general population.

While select guidelines in the past have endorsed plant sterols or red yeast rice for cholesterol lowering, the SPORT study seems to provide guidance that neither of these supplements or the others tested lower LDL-C, and none are ‘safer’ than the lowest marketed dose of rosuvastatin.

Therefore, our patients need to be reminded that no dietary supplements that claim to improve heart health or cholesterol levels have proven to do so, at least not through rigorous clinical trials, the gold standard in medicine. The safety of statins across their dose range has been proven time and time again, as has the cardiovascular event reduction associated with statin use.

It takes time and patience to counsel people regarding the health benefits of statins, and to counter their perceptions of statin intolerance or adverse effects. Armed with strong scientific data, such as those from SAMSON, SPORT, meta-analyses and guidelines, it is worth the effort to advise our patients to stick with their statins, and to stop wasting their money on ineffective dietary supplements.

The development of this blog was overseen by the Canadian Collaborative Research Network

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References:

Research GV. North America dietary supplements market report, 2021-2028 2022

[Available from: https://www.grandviewresearch.com/industry-analysis/north-america-dietary-supplements-market.

Pearson GJ et al. 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults. Can J Cardiol. 2021;37(8):1129-1150.

Kim J et al. Association of Multivitamin and Mineral Supplementation and Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis. Circ Cardiovasc Qual Outcomes. 2018;11(7):e004224.

Howard JP et al. Side Effect Patterns in a Crossover Trial of Statin, Placebo, and No Treatment. J Am Coll Cardiol. 2021 Sep 21;78(12):1210-1222.

Laffin LJ et al. Comparative Effects of Low-Dose Rosuvastatin, Placebo and Dietary Supplements on Lipids and Inflammatory Biomarkers. J Am Coll Cardiol. 2022 (in press)

Cholesterol Treatment Trialists’ Collaboration. Effect of Statin Therapy on Muscle Symptoms: An Individual Participant Data Meta-Analysis of Large-Scale, Randomised, Double-Blind Trials. Lancet. 2022 Sep 10;400(10355):832-845.