Micronutrient deficiencies in heart failure: Mitochondrial dysfunction as a common pathophysiological mechanism?

Abstract

Heart failure is a devastating clinical syndrome, but current therapies are unable to abolish the disease burden. New strategies to treat or prevent heart failure are urgently needed. Over the past decades, a clear relationship has been established between poor cardiac performance and metabolic perturbations, including deficits in substrate uptake and utilization, reduction in mitochondrial oxidative phosphorylation and excessive reactive oxygen species production. Together, these perturbations result in progressive depletion of cardiac adenosine triphosphate (ATP) and cardiac energy deprivation. Increasing the delivery of energy substrates (e.g., fatty acids, glucose, ketones) to the mitochondria will be worthless if the mitochondria are unable to turn these energy substrates into fuel. Micronutrients (including coenzyme Q10, zinc, copper, selenium and iron) are required to efficiently convert macronutrients to ATP. However, up to 50% of patients with heart failure are deficient in one or more micronutrients in cross‐sectional studies. Micronutrient deficiency has a high impact on mitochondrial energy production and should be considered an additional factor in the heart failure equation, moving our view of the failing myocardium away from an “an engine out of fuel” to “a defective engine on a path to self‐destruction.” This summary of evidence suggests that supplementation with micronutrients—preferably as a package rather than singly—might be a potential therapeutic strategy in the treatment of heart failure patients.

Selenium, TGF-Beta and Infectious Endemic Cardiopathy: Lessons from Benchwork to Clinical Application in Chagas Disease

“…Considering the geographical differences in serum Se observed in our first study [23] in healthy persons (mean 72 mcg/L on Rio de Janeiro and 55 mcg/L in Belo Horizonte) and in severe CD patients (65 mcg/L in Rio de Janeiro and 35 mcg/L in Belo Horizonte), as well as the large differences observed in Se levels in diets from diverse Brazilian regions [55], that varied 100 times from one state to the other (e.g., beans in Ceará have 1.2 mcg of Se/g; in São Paulo, 0.016 mcg of Se/g), it is important to explore Se levels in CD patients at different geographical regions, both in Brazil and in other Latin American countries. However, it is difficult to associate low Se serum levels as a cause or a marker (effect) in CCC progression, since the high inflammatory and oxidative stress in severe CCC [35][36][37] would both require and consume selenoproteins [10,18,56].…”

Is the correction of micronutrient deficiencies the next step in heart failure management?

“…All things considered, an array of evidence, brilliantly reviewed by Bomer et al. [1], indicates that micronutrient supplementation could represent an effective treatment in HF, since the failing myocardium may be “an engine out of fuel” due to a micronutrient deficit. The next logical step, given this convincing supporting evidence, is to undertake large (likely publicly funded) trials that ascertain whether a clinical benefit is obtained when using multimicronutrient supplementation.…”

“…Micronutrients are key to the efficient use of macronutrients to produce ATP. These micronutrient deficits, present in up to 50% of patients, might actually promote the concept of "an engine out of fuel" in HF because of such deficits [1]. Among these five micronutrients (coenzyme Q10, zinc, copper, selenium, and iron), only iron is part of the routine daily practice of an HF physician.…”

“…In this context, the review published in this month's issue of the Journal of Internal Medicine by Bomer et al. [1] from the heart failure (HF) group at Groningen University will probably take most of us off guard. In this brilliant comprehensive review, the authors show convincing evidence building the case for micronutrients being an important component in HF.…”

“…Micronutrients are key to the efficient use of macronutrients to produce ATP. These micronutrient deficits, present in up to 50% of patients, might actually promote the concept of “an engine out of fuel” in HF because of such deficits [1].…”