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Cardiovascular Health

Mitochondria and Heart Failure

Reading Time: 4 minutes
Updated on: December 11, 2024

Heart failure is a progressively debilitating disease, and reports estimate that over 56.2 million people worldwide live with heart failure.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

(Video time: 2 minutes) In this video, IFM educator Michael Stone, MD, MS, IFMCP, discusses key nutrients to improve energy levels in heart failure patients. A leader in the functional medicine field, Dr. Stone is a board-certified family physician, practicing integrative and functional medicine. For over 35 years, his career has been as a nutrition-minded physician. Dr. Stone is actively involved in functional medicine research and continues to consult with residency programs across the United States, mentoring physicians.


CoQ10 & Other Supportive Nutrients

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.5,6 A 2017 meta-analysis 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.7 A 2021 systematic review also suggested that CoQ10 treatment may reduce the risk of all-cause mortality and reduce hospitalization related to heart failure.8 In addition, supplementing with CoQ10 daily may improve a patient’s New York Heart Association Class (NYHA) rating; however, further research to determine dosage and length of treatment is needed due to conflicting results from clinical trials.9,10

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.5 However, the reported dosage from these studies of CoQ10 differed in a wide range from 100-300 mg for cardiovascular diseases.5 Recent reviews also suggest that other nutraceuticals, specifically omega-3 supplementation, may also benefit patients with heart failure by improving heart function, reducing inflammation, and enhancing heart disease treatments.11,12

Heart Failure: Mitochondrial Mechanisms

Generally, patients with heart failure have decreased ATP production in cardiac myocytes as well as other abnormalities in cardiac metabolism, including cell death.4,13 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.14

Preclinical models of therapies targeting the mitochondria have produced encouraging results, as have iron and exercise therapies that target mitochondrial biology.15 A recent meta-analysis suggested that exercise improves mitochondrial biogenesis and associated moderate-intensity exercises with improved mitochondrial volume and density in patients with heart failure.16 Mitochondrial biogenesis focuses on stimulating the production of new mitochondria through transcription of peroxisome proliferator–activated receptor gamma co-activator 1-alpha (PGC1α) in order to maintain the volume and flow of the mitochondrial network.

Functional Medicine Considerations

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 diseases. The functional medicine model helps practitioners utilize a comprehensive, whole health approach to identify those factors that may be involved in a patient’s health condition such as chronic heart failure and the effective lifestyle-based approaches that may be appropriate for a personalized therapeutic intervention. Learn about the latest interventions and effective clinical tools for cardiometabolic conditions at IFM’s Cardiometabolic Functional Medicine Advanced Practice Module® (APM). 

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REFERENCES
  1. Martin SS, Aday AW, Almarzooq ZI, et al. 2024 Heart disease and stroke statistics: a report of US and global data from the American Heart Association [published correction appears in Circulation. 2024;149(19):e1164. doi:10.1161/CIR.0000000000001247]. Circulation. 2024;149(8):e347-e913. doi:10.1161/CIR.0000000000001209
  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:10.1161/CIRCRESAHA.121.318241
  3. Bayeva M, Gheorghiade M, Ardehali H. Mitochondria as a therapeutic target in heart failure. J Am Coll Cardiol. 2013;61(6):599-610. doi:10.1016/j.jacc.2012.08.1021
  4. Sabbah HN. Targeting the mitochondria in heart failure: a translational perspective. JACC Basic Transl Sci. 2020;5(1):88-106. doi:10.1016/j.jacbts.2019.07.009
  5. Zozina VI, Covantev S, Goroshko OA, Krasnykh LM, Kukes VG. Coenzyme Q10 in cardiovascular and metabolic diseases: current state of the problem. Curr Cardio Rev. 2018;14(3):164-174. doi:10.2174/1573403X14666180416115428
  6. Di Lorenzo A, Iannuzzo G, Parlato A, et al. Clinical evidence for Q10 coenzyme supplementation in heart failure: from energetics to functional improvement. J Clin Med. 2020;9(5):1266. doi:10.3390/jcm9051266 
  7. Lei L, Liu Y. Efficacy of coenzyme Q10 in patients with cardiac failure: a meta-analysis of clinical trials. BMC Cardiovasc Disord. 2017;17(1):196. doi:10.1186/s12872-017-0628-9
  8. Al Saadi T, Assaf Y, Farwati M, et al. Coenzyme Q10 for heart failure. Cochrane Database Syst Rev. 2021;(2)(2):CD008684. doi:10.1002/14651858.CD008684.pub3
  9. 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:10.5603/cj.a2019.0022
  10. Samuel TY, Hasin T, Gotsman I, et al. Coenzyme Q10 in the treatment of heart failure with preserved ejection fraction: a prospective, randomized, double-blind, placebo-controlled trial. Drugs R D. 2022;22(1):25-33. doi:10.1007/s40268-021-00372-1
  11. Prokopidis K, Therdyothin A, Giannos P, et al. Does omega-3 supplementation improve the inflammatory profile of patients with heart failure? A systematic review and meta-analysis. Heart Fail Rev. 2023;28(6):1417-1425. doi:10.1007/s10741-023-10327-0
  12. Nomali M, Heidari ME, Ayati A, et al. Omega-3 supplementation and outcomes of heart failure: a systematic review of clinical trials. Medicine (Baltimore). 2024;103(3):e36804. doi:10.1097/MD.0000000000036804
  13. 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:10.1111/jcmm.15127 
  14. Rosca MG, Hoppel CL. Mitochondrial dysfunction in heart failure. Heart Fail Rev. 2013;18(5):607-622. doi:10.1007/s10741-012-9340-0
  15. von Hardenberg A, Maack C. Mitochondrial therapies in heart failure. Handb Exp Pharmacol. 2017;243:491-514. doi:10.1007/164_2016_123
  16. Lim AY, Chen YC, Hsu CC, Fu TC, Wang JS. The effects of exercise training on mitochondrial function in cardiovascular diseases: a systematic review and meta-analysis. Int J Mol Sci. 2022;23(20):12559. doi:10.3390/ijms232012559