Is Micronutrient supplementation next step for managing heart failure?

Netherlands: Supplementation with micronutrients -- particularly a combination of coenzyme Q10 (CoQ10), copper, zinc, iron, and selenium -- might be a potential therapeutic strategy in the treatment of heart failure patients by improving mitochondrial function, suggests a recent review. The study appears in the Journal of Internal Medicine. 

Heart failure is a devastating clinical syndrome, but current therapies are not able to abolish the disease burden. There is an urgent need for new strategies to treat or prevent heart failure. Over the past decade, a clear relationship is being established between poor cardiac performance and metabolic perturbations, including a reduction in mitochondrial oxidative phosphorylation, reduction in mitochondrial oxidative phosphorylation, and deficits in substrate uptake and utilization. These perturbations together result in the progressive depletion of cardiac adenosine triphosphate (ATP) and cardiac energy deprivation.

"Increasing the delivery of energy substrates (e.g. glucose, ketones, fatty acids) to the mitochondria will be of no use if the mitochondria are unable to convert these energy substrates into fuel, "Nils Bomer, Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands, and colleagues wrote in their study. "Micronutrients including zinc, copper, coenzyme Q10, and iron are required for the efficient conversion of macronutrients to ATP."

However, in about 50% of heart failure patients, there is a deficiency in one or more micronutrients in cross-sectional studies, they noted. They further suggested that "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." 

In particular, CoQ10, zinc, copper, selenium, and iron are required by the mitochondrial electron transport chain (mtETC) for efficient ATP production, the authors explain. Micronutrient deficiency in HF may contribute to defective mitochondrial function and reduced synthetic capacity for ATP.

Selenium's role in the ETC is the production of crucial antioxidant enzymes. Severe selenium deficiency may result in dilated cardiomyopathy, impaired exercise tolerance, reduced quality of life, and a higher mortality rate. Although there are no larger randomized controlled trials of selenium supplementation in HF patients, one trial in older people (including individuals with HF) found that it reduced cardiovascular mortality when combined with CoQ10.

Zinc's role in the ETC is as an antioxidant and zinc deficiency can result in an increased risk of cardiovascular and all-cause mortality, poorer New York Heart Association (NYHA) functional class, increased inflammation and myocardial damage, and impaired exercise capacity. There are no large randomized controlled trials of zinc in HF patients, but some evidence supports the role of a combination of zinc and selenium to improve left ventricular ejection fraction (LVEF), and multi-micronutrient supplements (including zinc) to increase LVEF and left ventricular end-diastolic volume.

Copper is involved in mitochondrial electron transport and free radical scavenging in the ETC, and copper deficiency is associated with connective tissue problems, muscle weakness, anemia, compromised cardiac mitochondrial respiration, and impaired ATP production. One trial evaluated the role of copper supplementation in people with ischemic heart disease, but results have not yet been published.

CoQ10 (ubiquinone) inhibits the peroxidation of lipids and lipoproteins. In the ETC, it facilitates ATP production as well as electron transfer. CoQ10 deficiency is associated with poorer NYHA functional class, lower LVEF, and increased N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, the authors note. Some research on CoQ10 supplementation in HF patients points to increases in symptom relief exercise capacity, duration, peak oxygen consumption, a better quality of life, and reduction in major adverse cardiac events

The sum up, failing myocardium might be "an engine out of fuel." However, increasing the delivery of energy substrates to the mitochondria cannot succeed if the mitochondria cannot turn these energy substrates into fuel (ATP) without wrecking the underperforming engine (increased ROS). Micronutrient deficiency changes the paradigm from "an engine out of fuel" to "a defective engine on a path to self-destruction."

Reference:

The study titled, "Micronutrient deficiencies in heart failure: Mitochondrial dysfunction as a common pathophysiological mechanism?" was published in the Journal of Internal Medicine.

DOI: https://doi.org/10.1111/joim.13455