Zinc Deficiency and Heart Failure: A Systematic Review of the Current Literature

Zinc is an essential micronutrient found in 300 metalloenzymes, that affects the heart through modulation of oxidative stress in cardiomyocytes.

Zinc deficiency may be a relatively common occurrence in patients with heart failure, and may be observed as a result of impaired micronutrient consumption, upregulation of the neurohormonal axis, or hyperzincuria.

There are multiple potential pathophysiologic pathways through which zinc deficiency may contribute to the development or worsening of heart failure, including increased oxidative stress, derangements of the cardiomyocyte extracellular matrix, and loss of cardiomyocytes.

Epidemiologic studies suggest low serum zinc levels in heart failure particularly in studies of non-ischemic cardiomyopathy.

We found a small but growing body of evidence suggesting the role for zinc supplementation in the management of heart failure however further evaluation of the impact on outcomes is needed.

Zinc is an essential micronutrient that impacts the cardiovascular system through modulation of oxidative stress. It is unknown whether zinc levels are affected in heart failure (HF), and whether the association, if present, is causal. A systematic search for publications that report coexisting zinc deficiency in patients with HF was performed to provide an overview of the pathophysiological and epidemiological aspects of this association (last search April 2019). Review of the literature suggests multiple potential pathophysiologic causes for zinc deficiency in HF as a result of impaired micronutrient consumption, hyper-inflammatory state, upregulation of the renin-angiotensin-aldosterone axis, diminished absorption, and hyperzincuria from HF medications. In a longitudinal study of patients with HF in the setting of intestinal malabsorption, there was partial cardiomyocyte and left ventricular ejection fraction recovery with intravenous selenium and zinc supplementation. Two randomized double-blind control trials evaluating micronutrient and macronutrient supplementation including zinc in patients with HF found improvement in echocardiographic findings compared with placebo. Two recently completed studies evaluated the role for zinc supplementation in 2 different HF populations: a trial of zinc supplementation in patients with non-ischemic HF, and a trial of micronutrient supplementation (including B vitamins, vitamin D, and zinc) in veterans with systolic dysfunction; the results of which are still pending. Several pathobiological pathways to link zinc deficiency with the development and deterioration of HF are presented. Preliminary clinical data are supportive of such an association and future studies should further investigate the effects of zinc supplementation on outcomes in patients with HF.

Journal of Cardiac Failure
Volume 26, Issue 2, February 2020, Pages 180-189

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