Inducing Heart Failure Through Excess Antioxidants

Several heart failure guidelines have stated that nutraceuticals offer no benefit to patients with heart failure with reduced ejection fraction (HFrEF).  Heart disease has been linked to oxidative stress.^1-2 Supplementing antioxidants, thereby modulating oxidative stress may protect the heart against oxidative stress.  Whether supplementing antioxidants is beneficial or harmful remains unknown.

A recent University of Alabama at Birmingham basic science study in transgenic mice shows that antioxidant-based approaches may not lead to beneficial anti-oxidant effects, but the more harmful pathological reductive stress.³  These mice developed cardiac remodeling identified as hypertrophic cardiomyopathy.  At 6 months, the mice developed diastolic ejection with a pathological increase in their left ventricular ejection fraction with 60% mortality at 18 months.  When this process was blocked, it prevented reductive stress without development of adverse cardiac remodeling. 

We always assess whether a new treatment is potentially beneficial or may cause harm before implementation.  This process should be the same as we counsel our patients about taking nutritional supplements.  Currently nutritional supplements are not recommended in patients with current or prior symptoms of HFrEF.⁴  Any supplement that claims to have antioxidant properties-real or imagined-should be avoided in patients with HFrEF.

Mark A. Munger, PharmD, FCCP, FACC, is a professor of pharmacotherapy and adjunct professor of internal medicine, at the University of Utah, where he also serves as the associate dean of Academic Affairs for the College of Pharmacy. 

References:

1. Hariharan N, Zhai P, Sadoshima J.  Oxidative stress stimulates autophagic flux during ischemia/reperfusion. Antioxid Redox Signal 2011;14:2179-90.
2. Santos CV, Raza S, Shah AM. Redox signaling in the cardiomyocyte: from physiology to failure. Int J Biochem Cell Biol 2016;74:145=51.
3. Shanmugam G. Want D, Gounder SS, et al. Reductive stress causes pathological cardiac remodeling and diastolic dysfunction. Antioxid Redox Signal 2020;32(18)1293-1311.
4. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.  J Am Coll Cardiol 2013;128:e240-e327.