By Chip J. Lavie, MD

Do Some Supplements Actually Help?

In one of his Straight Talk columns last year, one of my colleagues, Steve Nissen, MD, discussed “snake oils,” mostly in the context of dietary supplements that have not been shown to provide protection against cardiovascular disease (CVD) or to improve a patient’s overall health. Although I agree that this typically has been the case, there are several supplements that may provide some benefits to many of our CVD patients. In a prior Straight Talk column, I discussed lipid agents for triglycerides and HDL, including fibrates and nicotinic acid (the latter is also available in nonprescription form as a “supplement”), but others that may also help patients with CVD include: vitamin D, coenzyme Q10 (CoQ10), omega-3 fatty acids or fish oils, and red yeast rice. However, in the absence of truly definitive evidence, the jury is still out on all of these supplements.

There is substantial evidence that vitamin D has been associated with improving CVD risk factors, including metabolic syndrome/type II diabetes mellitus (T2DM), hypertension/left ventricular hypertrophy, dyslipidemia, inflammation, and depression (which I discussed in detail in a State-of-the-Art paper in JACC 2 years ago,¹ and in an upcoming review in Circulation²).

Numerous studies have demonstrated that low levels of 25 hydroxy (OH) D levels are associated with increased CVD risk factors and CVD events; some reports also suggest that patients with low 25 OH D levels who report myalgias on statins are able to tolerate these agents after vitamin D levels are replete. Certainly, there are non-CVD reasons to replete very low levels of vitamin D (especially levels <20 ng/mL), but considerable debate continues regarding whether raising vitamin D levels will reduce CVD, and determining the 25 OH D levels that lower CVD risks. These issues can only be answered with randomized controlled trials (RCTs), and hopefully ongoing ones will provide appropriate evidence.

At present, I believe that patients with 25 OH D levels <20 ng/mL should be supplemented, and consideration given to supplementing levels <30 ng/mL, especially when hypertension and/or T2DM is difficult to control or when patients have significant myalgias on statins.

CoQ10

Theoretically, coQ10 may have benefits in many CVD patients, including those with heart failure. Although this agent has potent antioxidant effects and may help skeletal and cardiac muscle function, the hype about coQ10 exceeds the evidence.

However, the largest current evidence is with statin-induced myalgias: studies suggest coQ10 reduces myalgias, whereas others have provided negative results. Richard Deichmann, MD, and I have recently published data from the Ochsner Health System showing mild benefits of coQ10 (200 mg/day) in exercise performance and muscle injury parameters in older athletes treated with statins.³ In real clinical practice, coQ10 may do even better than the clinical trials suggest, and may allow patients to tolerate much-needed statins. For once, the placebo effect may be working for us, and the supplement may also help replenish statin-induced reductions in coQ10 levels in muscle.

Omega-3 Fatty Acids and Fish Oils

Therapy with omega-3 fatty acids and fish oils continues to be controversial. Clearly, most of the recent trials have not been positive. Reductions in baseline risk due to statins and other aggressive treatments in acute myocardial infarction may explain these results. Additionally, because of the widespread publicity regarding the potential benefits of omega-3, many groups have increased their general consumption (which may be even higher in patients who volunteer for clinical trials). It has also been suggested that the use of olive oil as a placebo may e negating the omega-3 benefits, although I do not find this reason to be very plausible.

Nevertheless, several meta-analyses have suggested benefits from omega-3—even in the current era—but the reduction reaches about 10% range, as opposed to the 25–30% CVD event reductions reported a decade earlier. More recent evidence raises the issue that omega-3 may be relatively more effective in patients who are not taking statin medications. Patients and clinicians have been frightened by a highly publicized paper in a major cancer journal by Brasky et al.,⁴ suggesting that omega-3 was associated with increased risk of prostate cancer. Several of my colleagues and I, as well as others, have published evidence to the contrary.⁵ Currently, I believe that many patients will still benefit from fatty fish in their diets or from consuming omega-3 supplements.

Red Yeast Rice

Finally, there is evidence that red yeast rice may provide 25% reductions in LDL cholesterol, although at relatively high doses (e.g., 600 mg pills taken as 3 pills twice daily). Although issues regarding potential toxicity (renal, but especially hepatic), as well as the purity of various products has been raised, this therapy may still be considered for the relatively large number of patients who do not tolerate or refuse to take statin medications, despite high-risk profiles for CVD.⁶

Rest assured that I am not overpromoting any of these supplements, as none have stood the test of time or randomized clinical trials (except for maybe omega-3 fatty acids) compared to the evidence for statins, antiplatelet therapy, or other major therapies for the prevention and treatment of CVD. However, many patients have adverse effects and cannot or will not tolerate these agents, leaving room for additional help with dietary supplements. Although all of these supplements may help some of our patients with CVD or at high risk for CVD, at present they remain on life support and the jury is still out.

References

1. Lavie CJ, Lee JH, Milani RV. J Am Coll Cardiol. 2011;58:1547-56.
2. Lavie CJ, DiNicolantonio JJ, Milani RV, O’Keefe JH. Circulation. 2013, in press.
3. Deichmann RE, Lavie CJ, Dornelles AC. Phys Sportsmed. 2012;40:88-95.
4. Brasky TM, Darke AK, Song X, et al. J Natl Cancer Inst. 2013;105(15):1132-41.
5. DiNicolantonio JJ, McCarty MF, Lavie CJ, O’Keefe JH. Mol Med. 2013;110:293-5.
6. Shamim S, Al Badarin FJ, DiNicolantonio JJ, Lavie CJ, O’Keefe JH. Mol Med.
2013;110:349-54.

Chip J. Lavie, MD, is medical director of cardiac rehabilitation and director of exercise laboratories at the John Ochsner Heart and Valvular Institute at the University of Queensland School of Medicine in New Orleans. Dr. Lavie also works in the department of preventive medicine at the Pennington Biomedical research Laboratory in Baton Rouge.