Cardiac Heart Rate Dependence on Mitochondrial Deuterium 2H Content
Main Article Content
Abstract
Mitochondrial cardiac ATP production efficiency in beef hearts has been known to decrease with increasing systemic deuterium 2H levels since the 1980’s. Recently ketogenic diets which are known to decrease deuterium levels in humans were found to decrease both the resting and exercise heart rates in a volunteer. Furthermore, resting heart rates were found to systematically vary with the deuterium content from the previous meal consumed by six volunteers. A cardiac model is proposed showing extreme sensitivity of heart rate on the deuterium loading of the ATP synthase nanomotors. A predicted increase in heart rate by 28% is expected with a 5% decrease in ATP production. This finding strongly suggests that high deuterium levels in the fatty acids contribute to the diastolic dysfunction in heart failure not already attributed to direct structural damage, i.e., heart failure with preserved ejection fraction.
Keywords:
ATP, ATPase nanomotor, cardiac, deuterium, deuterium-depletion, deuterium-depleted water, heart failure with preserved ejection fraction
Article Details
How to Cite
JONES, Edwin C; PHELPS, James E; JARDET, Cortney L.
Cardiac Heart Rate Dependence on Mitochondrial Deuterium 2H Content.
Medical Research Archives, [S.l.], v. 10, n. 5, june 2022.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2833>. Date accessed: 23 apr. 2024.
doi: https://doi.org/10.18103/mra.v10i5.2833.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. L.J. Dorgan and S.M.Schuster, “The Effect of Nitration and D2O on the Kinetics of Beef Heart Mitochondrial Adenosine Triphosphatase,” J. Biol. Chem. Vol. 256(8): 3910-3916, 1981.
2. J.L. Urbauer, L.J. Dorgan, and S.M. Schuster, “Effects of deuterium on the kinetics of beef heart mitochondrial ATPase,” Arch. Biochem. and Biophysics, vol. 231(2): 498-502, 1984. https://doi.org/10.1016/0003-9861(84)90413-2.
3. L.J. Dorgan, J.L. Urbauer, and S.M. Schuster, “Metal Dependence and Thermodynamic Characteristics of the Beef Heart Mitochondria Adenosine Triphosphatase,” J. Biol. Chem. Vol. 259(5): 2816-2821, 1984. https://pubmed.ncbi.nlm.nih.gov/6230351/
4. E. Chirieri, I. Aricescu, C. Ganea and V. Vasilescu, “The Effect of Deuteration on the Frog Retina Bioelectrogenesis,” Naturwissenschaften 64(3): 149-150, 1977. https://doi.org/10.1007/BF00450581
5. The Nobel Prize in Chemistry 1997. NobelPrize.org. https://www.nobelprize.org/prizes/chemistry/1997/summary/
6. A. Olgun, “Biological effects of deuteronation: ATP synthase as an example,” Theor. Biol. Med. Model. 2007 Feb 22;4:9. PMID: 17316427; PMCID: PMC1808445. https://doi.org/10.1186/1742-4682-4-9.
7. D. Hao, M.O. Sarfaraz, F. Farshidfar, D.G. Bebb, C.Y. Lee, C.M. Card, M. David, and A.M. Weljie, “Temporal characterization of serum metabolite signatures in lung cancer patients undergoing treatment,” Metabolomics (2016) 12:58 https://doi.org/10.1007/s11306-016-0961-5.
8. S.J. Gros, S.G. Holland-Cunz, C.T. Supuran and O. Braissant, “Personalized Treatment Response Assessment for Rare Childhood Tumors Using Microcalorimetry-Exemplified by Use of Carbonic Anhydrase IX and Aquaporin 1 Inhibitors,” Int. J. Mol. Sci. 2019, 20, 4984. https://doi.org/10.3390/ijms20204984.
9. N. Pandey, V. Lanke and P.K. Vinod, “Network-based metabolic characterization of renal cell carcinoma,” Scientific Reports 2020, 10:5955. https://doi.org/10.1038/s41598-020-62853-8.
10. K. Arima, M.C. Lau, M. Zhao et al., “Metabolic Profiling of Formalin-Fixed Paraffin-Embedded Tissues Discriminates Normal Colon from Colorectal Cancer, Mol. Cancer Res. 2020; 18: 883-90. https://doi.org/10.1158/1541-7786.MCR-19-1091.
11. G. Somlyai, I. Somlyai, I. Fórizs, G. Czuppon, A. Papp and M. Molnár, “Effect of Systemic Subnormal Deuterium Level on Metabolic Syndrome Related and other Blood Parameters in Humans: A Preliminary Study,” Molecules vol. 25(6), 1376, 2020. https://doi.org/10.3390/molecules25061376.
12. E.C. Jones and C.L. Jardet, “Functional Improvement in b-Islet Cells and Hepatocytes with Decreasing Deuterium from Low Carbohydrate Intake in a Type-II Diabetic,” Medical Research Archives, vol. 9, issue 6, 19 pages, 16-Jun-2021. https://doi.org/10.18103/mra.v9i6.2475
13. L.M. Rossow, D.H. Fukuda, C.A. Fahs, J.P. Loenneke, and J.R. Stout, “Natural Bodybuilding Competition Preparation and Recovery: A 12-Month Case Study,” Int J Sports Physiol Perform 2013 Sep;8(5):582-92. https://doi.org/10.1123/ijspp.8.5.582
14. M.T. Jensen, “Resting heart rate and relation to disease and longevity: past, present and future, “ Scand J Clin Lab Invest, 79(1-2): 108-116, 2019. https://doi.org/10.1080/00365513.2019.1566567
15. L. Boros, “Biological Nanomechanics: ATP Synthesis and Deuterium Depletion,” 2016 presentation. https://youtu.be/6P8gqB4zLGQ
16. E.C. Jones, J.C. Rylands, and C.L. Jardet, “Regeneration of Pancreatic β-Islet Cells in a Type-II Diabetic,” Case Reports in Endocrinology, vol. 2018, Article ID 6147349, 6 pages, 2018. https://doi.org/10.1155/2018/6147349.
17. S. Martínez, A. García, E. Luzardo, M. Chávez-Castillo, L.C. Olivar, J. Salazar, M. Velasco, J.J.R. Quintero and V. Bermúdez, “Energetic metabolism in cardiomyocytes: molecular basis of heart ischemia and arrhythmogenesis,” Vessel Plus 2017; 1:230-41. https://doi.org/10.20517/2574-1209.2017.34
18. H. Okura, Y. Takada, A. Yamabe, T. Kubo, K. Asawa, T. Ozaki, H. Yamagishi, I. Toda, M. Yoshiyama, J. Yoshikawa, and K. Yoshida, “Age- and Gender-Specific Changes in the Left Ventricular Relaxation,” Circulation: Cardiovascular Imaging 2:1, 41-46, 2009. https://doi.org/10.1161/CIRCIMAGING.108.809087
19. UKEssays. (November 2018). “Calcium In Contraction Of The Heart.” Retrieved from https://www.ukessays.com/essays/biology/roles-of-calcium-in-contraction-of-the-heart-biology-essay.php?vref=1
20. S.D. Solomon, J. Wu, L. Gillam and B. Bulwer, “Echocardiography” in Thoracic Key. https://thoracickey.com/echocardiography/#s0065
21. L. Boros and G. Somlyai (private communication). These data are summarized at https://www.osmiowater.co.uk/osmioblog/deuterium-content-in-different-foods-and-deuterium-depletion.html
22. T.A. Hussain, T.C. Mathew, A.A. Dashti, S. Asfar, N. Al-Zaid and H.M. Dashti, “Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes,” Nutrition, vol. 28(10): 1016-1021, 2012. https://doi.org/10.1016/j.nut.2012.01.016.
23. G. M.C. Rosano, C. Vitale and H. Spoletini, “Metabolic approach to heart failure: The role of metabolic modulators,” The Egyptian Heart Journal 67: 177-181 (2015). https://doi.org/10.1016/j.ehj.2015.03.004
24. P. Meagher, M. Adam, R. Civitarese, A. Bugyei-Twum and K.A. Connelly, “Heart Failure With Preserved Ejection Fraction in Diabetes: Mechanisms and Management,” Can J of Cardiol. 34: 632-643 (2018). https://doi.org/10.1016/j.cjca.2018.02.026
25. B. Zhou and R. Tian, “Mitochondrial dysfunction in pathophysiology of heart failure,” J Clin Invest. 128(9): 3716-3726 (2018). https://doi.org/10.1172/JCI120849
26. A. Kumar, D.P. Kelly and J. Chirinos, “Mitochondrial Dysfunction in Heart Failure with Preserved Ejection Fraction,” Circulation 139(11): 1435-1450 (2019). https://doi.org/10.1161/CIRCULATIONAHA.118.036259
27. S. Bose and A. Le, “Glucose Metabolism in Cancer,” Adv Exp Med Biol. 2018; 1063: 3-12. https://doi.org/10.1007/978-3-319-77736-8_1
28. W. Bild, I. Stefanescu, I. Haulica, C. Lupusoru, G. Titescu, R. Iliescu and V. Nastasa, “Research concerning the radioprotective and immunostimulating effects of deuterium-depleted water,” Rom J Physiol. 1999 Jul-Dec; 36(3-4): 205-18. PMID: 11797936
29. E. Anyanwu, F. Klinke and C. Konermann, “Morphological hazards of deuterium oxide as a cardioplegic agent,” Thorac. Cardiovasc. Surg. 32(1): 27-34 (1984). https://doi.org/10.1055/s-2007-1023340
30. J.C. Lech, S.I. Dorfsman, Z. Répás, T.P.J. Krüger, I.M. Gyalai and L.G. Boros, “What to feed or what not to feed-that is still the question,” Metabolomics 17: 102 (2021). https://doi.org/10.1007/s11306-021-01855-7
31. J. Schleucher, P. Vanderveer, J.L. Markley and T.D. Sharkey, “Intramolecular deuterium distributions reveal disequilibrium of chloroplast phosphoglucose isomerase,” Plant Cell Environ. 22: 525-533 (1999). https://doi.org/10.1046/j.1365-3040.1999.00440.x
32. H. E. LeWine, "Increase in resting heart rate is a signal worth watching," Harvard Health Publishing, 29-Aug-2020. https://www.health.harvard.edu/blog/increase-in-resting-heart-rate-is-a-signal-worth-watching-201112214013
33. B.J. Schoenfeld , A. Alto, J. Grgic, G. Tinsley, C.T. Haun, B.I. Campbell, G. Escalante, G.T. Sonmez, G. Cote, A. Francis, E.T. Trexler, “Alterations in Body Composition, Resting Metabolic Rate, Muscular Strength, and Eating Behavior in Response to Natural Bodybuilding Competition Preparation: A Case Study,” J Strength Cond Res 2020 Nov;34(11):3124-3138. https://doi.org/10.1519/JSC.0000000000003816
34. R.U. Cofresí, B.D. Bartholow, K. Fromme, "Female drinkers are more sensitive than male drinkers to alcohol-induced heart rate increase," Exp Clin Psychopharmacol. 2020 Oct;28(5):540-552. http://doi.org/10.1037/pha0000338
35. Z. Zhou, C. Shen, Z. Lu, Z. Ao, L. Song and F. Cong, "Effects of deuterium-depleted Chinese liquor on glucose metabolism and islet cells and their function of diabetic rats," J. Shanghai Jiaotong Univ. 30 (10): 1204-1207. https://doi.org/10.3969/j.issn.1674-8115.2010.10.005
2. J.L. Urbauer, L.J. Dorgan, and S.M. Schuster, “Effects of deuterium on the kinetics of beef heart mitochondrial ATPase,” Arch. Biochem. and Biophysics, vol. 231(2): 498-502, 1984. https://doi.org/10.1016/0003-9861(84)90413-2.
3. L.J. Dorgan, J.L. Urbauer, and S.M. Schuster, “Metal Dependence and Thermodynamic Characteristics of the Beef Heart Mitochondria Adenosine Triphosphatase,” J. Biol. Chem. Vol. 259(5): 2816-2821, 1984. https://pubmed.ncbi.nlm.nih.gov/6230351/
4. E. Chirieri, I. Aricescu, C. Ganea and V. Vasilescu, “The Effect of Deuteration on the Frog Retina Bioelectrogenesis,” Naturwissenschaften 64(3): 149-150, 1977. https://doi.org/10.1007/BF00450581
5. The Nobel Prize in Chemistry 1997. NobelPrize.org. https://www.nobelprize.org/prizes/chemistry/1997/summary/
6. A. Olgun, “Biological effects of deuteronation: ATP synthase as an example,” Theor. Biol. Med. Model. 2007 Feb 22;4:9. PMID: 17316427; PMCID: PMC1808445. https://doi.org/10.1186/1742-4682-4-9.
7. D. Hao, M.O. Sarfaraz, F. Farshidfar, D.G. Bebb, C.Y. Lee, C.M. Card, M. David, and A.M. Weljie, “Temporal characterization of serum metabolite signatures in lung cancer patients undergoing treatment,” Metabolomics (2016) 12:58 https://doi.org/10.1007/s11306-016-0961-5.
8. S.J. Gros, S.G. Holland-Cunz, C.T. Supuran and O. Braissant, “Personalized Treatment Response Assessment for Rare Childhood Tumors Using Microcalorimetry-Exemplified by Use of Carbonic Anhydrase IX and Aquaporin 1 Inhibitors,” Int. J. Mol. Sci. 2019, 20, 4984. https://doi.org/10.3390/ijms20204984.
9. N. Pandey, V. Lanke and P.K. Vinod, “Network-based metabolic characterization of renal cell carcinoma,” Scientific Reports 2020, 10:5955. https://doi.org/10.1038/s41598-020-62853-8.
10. K. Arima, M.C. Lau, M. Zhao et al., “Metabolic Profiling of Formalin-Fixed Paraffin-Embedded Tissues Discriminates Normal Colon from Colorectal Cancer, Mol. Cancer Res. 2020; 18: 883-90. https://doi.org/10.1158/1541-7786.MCR-19-1091.
11. G. Somlyai, I. Somlyai, I. Fórizs, G. Czuppon, A. Papp and M. Molnár, “Effect of Systemic Subnormal Deuterium Level on Metabolic Syndrome Related and other Blood Parameters in Humans: A Preliminary Study,” Molecules vol. 25(6), 1376, 2020. https://doi.org/10.3390/molecules25061376.
12. E.C. Jones and C.L. Jardet, “Functional Improvement in b-Islet Cells and Hepatocytes with Decreasing Deuterium from Low Carbohydrate Intake in a Type-II Diabetic,” Medical Research Archives, vol. 9, issue 6, 19 pages, 16-Jun-2021. https://doi.org/10.18103/mra.v9i6.2475
13. L.M. Rossow, D.H. Fukuda, C.A. Fahs, J.P. Loenneke, and J.R. Stout, “Natural Bodybuilding Competition Preparation and Recovery: A 12-Month Case Study,” Int J Sports Physiol Perform 2013 Sep;8(5):582-92. https://doi.org/10.1123/ijspp.8.5.582
14. M.T. Jensen, “Resting heart rate and relation to disease and longevity: past, present and future, “ Scand J Clin Lab Invest, 79(1-2): 108-116, 2019. https://doi.org/10.1080/00365513.2019.1566567
15. L. Boros, “Biological Nanomechanics: ATP Synthesis and Deuterium Depletion,” 2016 presentation. https://youtu.be/6P8gqB4zLGQ
16. E.C. Jones, J.C. Rylands, and C.L. Jardet, “Regeneration of Pancreatic β-Islet Cells in a Type-II Diabetic,” Case Reports in Endocrinology, vol. 2018, Article ID 6147349, 6 pages, 2018. https://doi.org/10.1155/2018/6147349.
17. S. Martínez, A. García, E. Luzardo, M. Chávez-Castillo, L.C. Olivar, J. Salazar, M. Velasco, J.J.R. Quintero and V. Bermúdez, “Energetic metabolism in cardiomyocytes: molecular basis of heart ischemia and arrhythmogenesis,” Vessel Plus 2017; 1:230-41. https://doi.org/10.20517/2574-1209.2017.34
18. H. Okura, Y. Takada, A. Yamabe, T. Kubo, K. Asawa, T. Ozaki, H. Yamagishi, I. Toda, M. Yoshiyama, J. Yoshikawa, and K. Yoshida, “Age- and Gender-Specific Changes in the Left Ventricular Relaxation,” Circulation: Cardiovascular Imaging 2:1, 41-46, 2009. https://doi.org/10.1161/CIRCIMAGING.108.809087
19. UKEssays. (November 2018). “Calcium In Contraction Of The Heart.” Retrieved from https://www.ukessays.com/essays/biology/roles-of-calcium-in-contraction-of-the-heart-biology-essay.php?vref=1
20. S.D. Solomon, J. Wu, L. Gillam and B. Bulwer, “Echocardiography” in Thoracic Key. https://thoracickey.com/echocardiography/#s0065
21. L. Boros and G. Somlyai (private communication). These data are summarized at https://www.osmiowater.co.uk/osmioblog/deuterium-content-in-different-foods-and-deuterium-depletion.html
22. T.A. Hussain, T.C. Mathew, A.A. Dashti, S. Asfar, N. Al-Zaid and H.M. Dashti, “Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes,” Nutrition, vol. 28(10): 1016-1021, 2012. https://doi.org/10.1016/j.nut.2012.01.016.
23. G. M.C. Rosano, C. Vitale and H. Spoletini, “Metabolic approach to heart failure: The role of metabolic modulators,” The Egyptian Heart Journal 67: 177-181 (2015). https://doi.org/10.1016/j.ehj.2015.03.004
24. P. Meagher, M. Adam, R. Civitarese, A. Bugyei-Twum and K.A. Connelly, “Heart Failure With Preserved Ejection Fraction in Diabetes: Mechanisms and Management,” Can J of Cardiol. 34: 632-643 (2018). https://doi.org/10.1016/j.cjca.2018.02.026
25. B. Zhou and R. Tian, “Mitochondrial dysfunction in pathophysiology of heart failure,” J Clin Invest. 128(9): 3716-3726 (2018). https://doi.org/10.1172/JCI120849
26. A. Kumar, D.P. Kelly and J. Chirinos, “Mitochondrial Dysfunction in Heart Failure with Preserved Ejection Fraction,” Circulation 139(11): 1435-1450 (2019). https://doi.org/10.1161/CIRCULATIONAHA.118.036259
27. S. Bose and A. Le, “Glucose Metabolism in Cancer,” Adv Exp Med Biol. 2018; 1063: 3-12. https://doi.org/10.1007/978-3-319-77736-8_1
28. W. Bild, I. Stefanescu, I. Haulica, C. Lupusoru, G. Titescu, R. Iliescu and V. Nastasa, “Research concerning the radioprotective and immunostimulating effects of deuterium-depleted water,” Rom J Physiol. 1999 Jul-Dec; 36(3-4): 205-18. PMID: 11797936
29. E. Anyanwu, F. Klinke and C. Konermann, “Morphological hazards of deuterium oxide as a cardioplegic agent,” Thorac. Cardiovasc. Surg. 32(1): 27-34 (1984). https://doi.org/10.1055/s-2007-1023340
30. J.C. Lech, S.I. Dorfsman, Z. Répás, T.P.J. Krüger, I.M. Gyalai and L.G. Boros, “What to feed or what not to feed-that is still the question,” Metabolomics 17: 102 (2021). https://doi.org/10.1007/s11306-021-01855-7
31. J. Schleucher, P. Vanderveer, J.L. Markley and T.D. Sharkey, “Intramolecular deuterium distributions reveal disequilibrium of chloroplast phosphoglucose isomerase,” Plant Cell Environ. 22: 525-533 (1999). https://doi.org/10.1046/j.1365-3040.1999.00440.x
32. H. E. LeWine, "Increase in resting heart rate is a signal worth watching," Harvard Health Publishing, 29-Aug-2020. https://www.health.harvard.edu/blog/increase-in-resting-heart-rate-is-a-signal-worth-watching-201112214013
33. B.J. Schoenfeld , A. Alto, J. Grgic, G. Tinsley, C.T. Haun, B.I. Campbell, G. Escalante, G.T. Sonmez, G. Cote, A. Francis, E.T. Trexler, “Alterations in Body Composition, Resting Metabolic Rate, Muscular Strength, and Eating Behavior in Response to Natural Bodybuilding Competition Preparation: A Case Study,” J Strength Cond Res 2020 Nov;34(11):3124-3138. https://doi.org/10.1519/JSC.0000000000003816
34. R.U. Cofresí, B.D. Bartholow, K. Fromme, "Female drinkers are more sensitive than male drinkers to alcohol-induced heart rate increase," Exp Clin Psychopharmacol. 2020 Oct;28(5):540-552. http://doi.org/10.1037/pha0000338
35. Z. Zhou, C. Shen, Z. Lu, Z. Ao, L. Song and F. Cong, "Effects of deuterium-depleted Chinese liquor on glucose metabolism and islet cells and their function of diabetic rats," J. Shanghai Jiaotong Univ. 30 (10): 1204-1207. https://doi.org/10.3969/j.issn.1674-8115.2010.10.005