Mitochondria and Cardiac Function

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Heart failure is a progressively debilitating disease that impacts 6.2 million US adults.1 Changes to cardiac energy metabolism may contribute to the severity of heart failure, as the failing heart experiences decreased mitochondrial oxidative capacity and increased ATP production from glycolysis. The fuel sources for ATP also change; ketone oxidation increases while glucose and amino acid oxidation decreases.2 Fatty acid oxidation may also increase in patients with comorbid obesity and type 2 diabetes. 2 Researchers suggest that these changes in energy metabolism combined may contribute to the heart becoming less efficient.2

Past treatment approaches have focused on symptom management, but researchers now say it is likely that the function of cardiomyocytes can be rescued from their ‘metabolically stunned’ state.3 Since the heart maintains specialized cellular processes that demand high but varying levels of energy, and because it stores only a small amount of energy substrate, the focus of current research is on developing treatment strategies for meeting those fluctuating workload demands.4,5

(Video Time: 1 minute) IFM Certified Practitioner Michael Stone, MD, discusses key nutrients to improve energy levels in heart failure patients.

Among the nutrients supported by the research is coenzyme Q10 (CoQ10), an essential compound of the human body that is synthesized in the mitochondrial inner membrane.6,7 A review of 14 randomized controlled trials on the efficacy of CoQ10 found that patients had a lower mortality rate and improved exercise capacity compared to study participants receiving a placebo.8 Supplementing with CoQ10 daily can improve a patient’s New York Heart Association Class (NYHA) rating.9,10 In 62 patients with reduced left ventricular ejection fraction (HFrEF) of mixed pathogenesis, four-month CoQ10 supplementation showed significant improvement of the NYHA rating.11 Moreover, Mortensen et al found significant results in long-term (two years) CoQ10 administration; improvement for at least one NYHA class grade from baseline had been reached in 86 heart failure patients compared to placebo.12,7 

In a 2018 review of the literature, Zozina et al suggest that, overall, there seems to be a beneficial role of CoQ10 co-administration as a supplemental therapy in different cardiac and metabolic conditions.6 CoQ10 may improve outcomes and quality of life and decrease morbidity and mortality; however, the authors point out that some findings in their review are based on preclinical or clinical studies with surrogate endpoints.6 Furthermore, the reported dosage of CoQ10 differs in a wide range from 100-300 mg for cardiovascular diseases.6 Future studies should be aimed at assessment of higher dosage of CoQ10 administration as well as evaluation of its pharmacokinetics and pharmacodynamics.6 

Another review found that heart failure patients may benefit from receiving nutraceuticals such as hawthorn, beet nitrates, L-carnitine, and vitamin D.13 However, despite several studies exploring the association of various supplements with cardiovascular risk, there is still a lack of consensus in the medical literature.13,14

Generally, patients with heart failure have decreased ATP production in cardiac myocytes as well as other abnormalities in cardiac metabolism, including cell death.5,15-16 Some innovative therapies consider this energy deficiency as both cause and effect at the level of gene expression.4 The electron transport chain and phosphorylation apparatus is now thought to be where the mitochondrial defects are found. Reduced ATP production is caused by progressively reduced mitochondrial respiratory pathway activity, which reduces pump function, stimulating soaring energy demand as functionality decreases.17

Preclinical models of therapies targeting the mitochondria have produced encouraging results, as have iron and exercise therapies that target mitochondrial biology.18 Mitochondrial biogenesis focuses on stimulating the production of new mitochondria through transcription of peroxisome proliferator–activated receptor gamma co-activator 1-alpha (PGC1?) in order to maintain the volume and flow of the mitochondrial network.3

Research into supporting mitochondrial health for cardiometabolic patients continues to evolve, including the development of new opportunities for safer and more effective early interventions to prevent and reverse cardiometabolic disease. Learn the latest interventions through IFM’s Cardiometabolic Advanced Practice Module:

Learn More About Cardiometabolic Function

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  1. Virani SS, Alonso A, Benjamin EJ, et al. Heart disease and stroke statistics—2020 update: a report from the American Heart Association. Circulation. 2020;141(9):e139-e596. doi:1161/CIR.0000000000000757
  2. Lopaschuk GD, Karwi QG, Tian R, Wende AR, Abel ED. Cardiac energy metabolism in heart failure. Circ Res. 2021;128(10):1487-1513. doi:1161/CIRCRESAHA.121.318241
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  10.  Madmani ME, Yusuf Solaiman A, Tamr Agha K, et al. Coenzyme Q10 for heart failure. Cochrane Database Syst Rev. 2014;(6):CD008684. doi:1002/14651858.CD008684.pub2
  11.  Pourmoghaddas M, Rabbani M, Shahabi J, Garakyaraghi M, Khanjani R, Hedayat P. Combination of atorvastatin/coenzyme Q10 as adjunctive treatment in congestive heart failure: a double-blind randomized placebo-controlled clinical trial. ARYA Atheroscler. 2014;10(1):1-5.
  12.  Mortensen AL, Rosenfeldt F, Filipiak KJ. Effect of coenzyme Q10 in Europeans with chronic heart failure: a sub-group analysis of the Q-SYMBIO randomized double-blind trial. Cardiol J. 2019;26(2):147-156. doi:5603/cj.a2019.0022
  13.  Cicero AFG, Colletti A. Nutraceuticals and dietary supplements to improve quality of life and outcomes in heart failure patients. Curr Pharm Des. 2017;23(8):1265-1272. doi:2174/1381612823666170124120518
  14.  Bronzato S, Durante A. Dietary supplements and cardiovascular diseases. Int J Prev Med. 2018;9:80. doi:4103/ijpvm.IJPVM_179_17
  15.  Davidson SM, Adameová A, Barile L, et al. Mitochondrial and mitochondrial-independent pathways of myocardial cell death during ischaemia and reperfusion injury. J Cell Mol Med. 2020;24(7):3795-3806. doi:1111/jcmm.15127
  16.  Doenst T, Nguyen TD, Abel ED. Cardiac metabolism in heart failure: implications beyond ATP production. Circ Res. 2013;113(6):709-724. doi:1161/CIRCRESAHA.113.300376
  17.  Rosca MG, Hoppel CL. Mitochondrial dysfunction in heart failure. Heart Fail Rev. 2013;18(5):607-622. doi:1007/s10741-012-9340-0
  18.  von Hardenberg A, Maack C. Mitochondrial therapies in heart failure. Handb Exp Pharmacol. 2017;243:491-514. doi:1007/164_2016_123

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