Ketogenic Diet and Cardiac Substrate Metabolism
Abstract
:1. Introduction
2. Ketone Bodies
3. Ketone Bodies and the Heart
3.1. The Healthy Heart
3.2. Heart Failure
3.3. The Diabetic Heart Disease
4. The Ketogenic Diet and the Heart
5. Future Directions and Perspective
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Ye, F.; Li, X.J.; Jiang, W.L.; Sun, H.B.; Liu, J. Efficacy of and patient compliance with a ketogenic diet in adults with intractable epilepsy: A meta-analysis. J. Clin. Neurol. 2015, 11, 26–31. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Neves, G.S.; Lunardi, M.S.; Lin, K.; Rieger, D.K.; Ribeiro, L.C.; Moreira, J.D. Ketogenic diet, seizure control, and cardiometabolic risk in adult patients with pharmacoresistant epilepsy: A review. Nutr. Rev. 2021, 79, 931–944. [Google Scholar] [CrossRef] [PubMed]
- Dąbek, A.; Wojtala, M.; Pirola, L.; Balcerczyk, A. Modulation of Cellular Biochemistry, Epigenetics and Metabolomics by Ketone Bodies. Implications of the Ketogenic Diet in the Physiology of the Organism and Pathological States. Nutrients 2020, 12, 788. [Google Scholar] [CrossRef] [Green Version]
- Rusek, M.; Pluta, R.; Ułamek-Kozioł, M.; Czuczwar, S.J. Ketogenic Diet in Alzheimer’s Disease. Int. J. Mol. Sci. 2019, 20, 3892. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Weber, D.D.; Aminzadeh-Gohari, S.; Tulipan, J.; Catalano, L.; Feichtinger, R.G.; Kofler, B. Ketogenic diet in the treatment of cancer—Where do we stand? Mol. Metab. 2020, 33, 102–121. [Google Scholar] [CrossRef]
- Dowis, K.; Banga, S. The Potential Health Benefits of the Ketogenic Diet: A Narrative Review. Nutrients 2021, 13, 1654. [Google Scholar] [CrossRef]
- Kosinski, C.; Jornayvaz, F.R. Effects of Ketogenic Diets on Cardiovascular Risk Factors: Evidence from Animal and Human Studies. Nutrients 2017, 9, 517. [Google Scholar] [CrossRef]
- Zinman, B.; Wanner, C.; Lachin, J.M.; Fitchett, D.; Bluhmki, E.; Hantel, S.; Mattheus, M.; Devins, T.; Johansen, O.E.; Woerle, H.J.; et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N. Engl. J. Med. 2015, 373, 2117–2128. [Google Scholar] [CrossRef] [Green Version]
- Ferrannini, E.; Mark, M.; Mayoux, E. CV Protection in the EMPA-REG OUTCOME Trial: A “Thrifty Substrate” Hypothesis. Diabetes Care 2016, 39, 1108–1114. [Google Scholar] [CrossRef] [Green Version]
- Gormsen, L.C.; Svart, M.; Thomsen, H.H.; Sondergaard, E.; Vendelbo, M.H.; Christensen, N.; Tolbod, L.P.; Harms, H.J.; Nielsen, R.; Wiggers, H.; et al. Ketone Body Infusion With 3-Hydroxybutyrate Reduces Myocardial Glucose Uptake and Increases Blood Flow in Humans: A Positron Emission Tomography Study. J. Am. Heart Assoc. 2017, 6, e005066. [Google Scholar] [CrossRef]
- Nielsen, R.; Møller, N.; Gormsen, L.C.; Tolbod, L.P.; Hansson, N.H.; Sorensen, J.; Harms, H.J.; Frøkiær, J.; Eiskjaer, H.; Jespersen, N.R.; et al. Cardiovascular Effects of Treatment With the Ketone Body 3-Hydroxybutyrate in Chronic Heart Failure Patients. Circulation 2019, 139, 2129–2141. [Google Scholar] [CrossRef] [PubMed]
- Ferrannini, E.; Baldi, S.; Frascerra, S.; Astiarraga, B.; Heise, T.; Bizzotto, R.; Mari, A.; Pieber, T.R.; Muscelli, E. Shift to Fatty Substrate Utilization in Response to Sodium-Glucose Cotransporter 2 Inhibition in Subjects Without Diabetes and Patients With Type 2 Diabetes. Diabetes 2016, 65, 1190–1195. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Newman, J.C.; Verdin, E. β-Hydroxybutyrate: A Signaling Metabolite. Annu. Rev. Nutr. 2017, 37, 51–76. [Google Scholar] [CrossRef] [PubMed]
- Abdul Kadir, A.; Clarke, K.; Evans, R.D. Cardiac ketone body metabolism. Biochim. Biophys. Acta Mol. Basis. Dis. 2020, 1866, 165739. [Google Scholar] [CrossRef]
- Møller, N. Ketone Body, 3-Hydroxybutyrate: Minor Metabolite—Major Medical Manifestations. J. Clin. Endocrinol. Metab. 2020, 105, 2884–2892. [Google Scholar] [CrossRef]
- Puchalska, P.; Crawford, P.A. Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics. Cell Metab. 2017, 25, 262–284. [Google Scholar] [CrossRef] [Green Version]
- Cahill, G.F., Jr. Fuel metabolism in starvation. Annu. Rev. Nutr. 2006, 26, 1–22. [Google Scholar] [CrossRef] [Green Version]
- Cox, P.J.; Kirk, T.; Ashmore, T.; Willerton, K.; Evans, R.; Smith, A.; Murray, A.J.; Stubbs, B.; West, J.; McLure, S.W.; et al. Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes. Cell Metab. 2016, 24, 256–268. [Google Scholar] [CrossRef] [Green Version]
- van Bilsen, M.; van Nieuwenhoven, F.A.; van der Vusse, G.J. Metabolic remodelling of the failing heart: Beneficial or detrimental? Cardiovasc Res. 2009, 81, 420–428. [Google Scholar] [CrossRef]
- Murano, C.; Binda, A.; Palestini, P.; Baruscotti, M.; DiFrancesco, J.C.; Rivolta, I. Effect of the ketogenic diet in excitable tissues. Am. J. Physiol.-Cell Physiol. 2021, 320, C547–C553. [Google Scholar] [CrossRef]
- Kolwicz, S.C., Jr. Ketone Body Metabolism in the Ischemic Heart. Front. Cardiovasc Med. 2021, 8, 789458. [Google Scholar] [CrossRef] [PubMed]
- Murashige, D.; Jang, C.; Neinast, M.; Edwards, J.J.; Cowan, A.; Hyman, M.C.; Rabinowitz, J.D.; Frankel, D.S.; Arany, Z. Comprehensive quantification of fuel use by the failing and nonfailing human heart. Science 2020, 370, 364–368. [Google Scholar] [CrossRef] [PubMed]
- Karwi, Q.G.; Biswas, D.; Pulinilkunnil, T.; Lopaschuk, G.D. Myocardial Ketones Metabolism in Heart Failure. J. Card. Fail. 2020, 26, 998–1005. [Google Scholar] [CrossRef] [PubMed]
- Ferrannini, E.; Santoro, D.; Bonadonna, R.; Natali, A.; Parodi, O.; Camici, P.G. Metabolic and hemodynamic effects of insulin on human hearts. Am. J. Physiol. 1993, 264, E308–E315. [Google Scholar] [CrossRef]
- Svart, M.; Gormsen, L.C.; Hansen, J.; Zeidler, D.; Gejl, M.; Vang, K.; Aanerud, J.; Moeller, N. Regional cerebral effects of ketone body infusion with 3-hydroxybutyrate in humans: Reduced glucose uptake, unchanged oxygen consumption and increased blood flow by positron emission tomography. A randomized, controlled trial. PLoS ONE 2018, 13, e0190556. [Google Scholar] [CrossRef]
- Lauritsen, K.M.; Søndergaard, E.; Luong, T.V.; Møller, N.; Gormsen, L.C. Acute Hyperketonemia Does Not Affect Glucose or Palmitate Uptake in Abdominal Organs or Skeletal Muscle. J. Clin. Endocrinol. Metab. 2020, 105, 1785–1790. [Google Scholar] [CrossRef]
- Ingwall, J.S.; Weiss, R.G. Is the failing heart energy starved? On using chemical energy to support cardiac function. Circ. Res. 2004, 95, 135–145. [Google Scholar] [CrossRef]
- Neubauer, S. The failing heart–An engine out of fuel. N. Engl. J. Med. 2007, 356, 1140–1151. [Google Scholar] [CrossRef] [Green Version]
- Fillmore, N.; Mori, J.; Lopaschuk, G.D. Mitochondrial fatty acid oxidation alterations in heart failure, ischaemic heart disease and diabetic cardiomyopathy. Br. J. Pharmacol. 2014, 171, 2080–2090. [Google Scholar] [CrossRef] [Green Version]
- Voros, G.; Ector, J.; Garweg, C.; Droogne, W.; van Cleemput, J.; Peersman, N.; Vermeersch, P.; Janssens, S. Increased Cardiac Uptake of Ketone Bodies and Free Fatty Acids in Human Heart Failure and Hypertrophic Left Ventricular Remodeling. Circ. Heart Fail. 2018, 11, e004953. [Google Scholar] [CrossRef]
- Bedi, K.C., Jr.; Snyder, N.W.; Brandimarto, J.; Aziz, M.; Mesaros, C.; Worth, A.J.; Wang, L.L.; Javaheri, A.; Blair, I.A.; Margulies, K.B.; et al. Evidence for Intramyocardial Disruption of Lipid Metabolism and Increased Myocardial Ketone Utilization in Advanced Human Heart Failure. Circulation 2016, 133, 706–716. [Google Scholar] [CrossRef] [Green Version]
- Chen, L.; Song, J.; Hu, S. Metabolic remodeling of substrate utilization during heart failure progression. Heart Fail. Rev. 2019, 24, 143–154. [Google Scholar] [CrossRef]
- Sörensen, J.; Harms, H.J.; Aalen, J.M.; Baron, T.; Smiseth, O.A.; Flachskampf, F.A. Myocardial Efficiency: A Fundamental Physiological Concept on the Verge of Clinical Impact. JACC Cardiovasc. Imaging 2020, 13, 1564–1576. [Google Scholar] [CrossRef] [PubMed]
- Boudina, S.; Abel, E.D. Diabetic cardiomyopathy, causes and effects. Rev. Endocr. Metab. Disord. 2010, 11, 31–39. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rubler, S.; Dlugash, J.; Yuceoglu, Y.Z.; Kumral, T.; Branwood, A.W.; Grishman, A. New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am. J. Cardiol. 1972, 30, 595–602. [Google Scholar] [CrossRef]
- Kannel, W.B.; Hjortland, M.; Castelli, W.P. Role of diabetes in congestive heart failure: The Framingham study. Am. J. Cardiol. 1974, 34, 29–34. [Google Scholar] [CrossRef]
- Nichols, G.A.; Gullion, C.M.; Koro, C.E.; Ephross, S.A.; Brown, J.B. The incidence of congestive heart failure in type 2 diabetes: An update. Diabetes Care 2004, 27, 1879–1884. [Google Scholar] [CrossRef] [Green Version]
- Jia, G.; Whaley-Connell, A.; Sowers, J.R. Diabetic cardiomyopathy: A hyperglycaemia- and insulin-resistance-induced heart disease. Diabetologia 2018, 61, 21–28. [Google Scholar] [CrossRef]
- Søndergaard, E.; Jensen, M.D. Quantification of adipose tissue insulin sensitivity. J. Investig. Med. 2016, 64, 989–991. [Google Scholar] [CrossRef]
- Mizuno, Y.; Harada, E.; Nakagawa, H.; Morikawa, Y.; Shono, M.; Kugimiya, F.; Yoshimura, M.; Yasue, H. The diabetic heart utilizes ketone bodies as an energy source. Metabolism 2017, 77, 65–72. [Google Scholar] [CrossRef] [Green Version]
- Lauritsen, K.M.; Nielsen, B.R.R.; Tolbod, L.P.; Johannsen, M.; Hansen, J.; Hansen, T.K.; Wiggers, H.; Møller, N.; Gormsen, L.C.; Søndergaard, E. SGLT2 Inhibition Does Not Affect Myocardial Fatty Acid Oxidation or Uptake, but Reduces Myocardial Glucose Uptake and Blood Flow in Individuals With Type 2 Diabetes: A Randomized Double-Blind, Placebo-Controlled Crossover Trial. Diabetes 2021, 70, 800–808. [Google Scholar] [CrossRef]
- Di Raimondo, D.; Buscemi, S.; Musiari, G.; Rizzo, G.; Pirera, E.; Corleo, D.; Pinto, A.; Tuttolomondo, A. Ketogenic Diet, Physical Activity, and Hypertension-A Narrative Review. Nutrients 2021, 13, 2567. [Google Scholar] [CrossRef] [PubMed]
- Veech, R.L. The therapeutic implications of ketone bodies: The effects of ketone bodies in pathological conditions: Ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostaglandins Leukot. Essent. Fatty. Acids. 2004, 70, 309–319. [Google Scholar] [CrossRef] [PubMed]
- Zhang, W.; Guo, X.; Chen, L.; Chen, T.; Yu, J.; Wu, C.; Zheng, J. Ketogenic Diets and Cardio-Metabolic Diseases. Front. Endocrinol. 2021, 12, 753039. [Google Scholar] [CrossRef] [PubMed]
- Leone, A.; de Amicis, R.; Lessa, C.; Tagliabue, A.; Trentani, C.; Ferraris, C.; Battezzati, A.; Veggiotti, P.; Foppiani, A.; Ravella, S.; et al. Food and Food Products on the Italian Market for Ketogenic Dietary Treatment of Neurological Diseases. Nutrients 2019, 11, 1104. [Google Scholar] [CrossRef] [Green Version]
- Barzegar, M.; Afghan, M.; Tarmahi, V.; Behtari, M.; Khamaneh, S.R.; Raeisi, S. Ketogenic diet: Overview, types, and possible anti-seizure mechanisms. Nutr. Neurosci. 2021, 24, 307–316. [Google Scholar] [CrossRef]
- Kossoff, E.H.; Dorward, J.L. The modified Atkins diet. Epilepsia 2008, 49 (Suppl. S8), 37–41. [Google Scholar] [CrossRef]
- Floyd, J.C., Jr.; Fajans, S.S.; Conn, J.W.; Knopf, R.F.; Rull, J. Stimulation of insulin secretion by amino acids. J. Clin. Invest. 1966, 45, 1487–1502. [Google Scholar] [CrossRef]
- Courchesne-Loyer, A.; Croteau, E.; Castellano, C.A.; St-Pierre, V.; Hennebelle, M.; Cunnane, S.C. Inverse relationship between brain glucose and ketone metabolism in adults during short-term moderate dietary ketosis: A dual tracer quantitative positron emission tomography study. J. Cereb. Blood Flow Metab. 2017, 37, 2485–2493. [Google Scholar] [CrossRef] [Green Version]
- Freeman, J.M.; Vining, E.P.; Pillas, D.J.; Pyzik, P.L.; Casey, J.C.; Kelly, L.M. The efficacy of the ketogenic diet-1998: A prospective evaluation of intervention in 150 children. Pediatrics 1998, 102, 1358–1363. [Google Scholar] [CrossRef]
- Johnstone, A.M.; Horgan, G.W.; Murison, S.D.; Bremner, D.M.; Lobley, G.E. Effects of a high-protein ketogenic diet on hunger, appetite, and weight loss in obese men feeding ad libitum. Am. J. Clin. Nutr. 2008, 87, 44–55. [Google Scholar] [CrossRef] [Green Version]
- Bueno, N.B.; de Melo, I.S.; de Oliveira, S.L.; Ataide, T.d. Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: A meta-analysis of randomised controlled trials. Br. J. Nutr. 2013, 110, 1178–1187. [Google Scholar] [CrossRef] [Green Version]
- Westerterp-Plantenga, M.S.; Nieuwenhuizen, A.; Tomé, D.; Soenen, S.; Westerterp, K.R. Dietary protein, weight loss, and weight maintenance. Annu. Rev. Nutr. 2009, 29, 21–41. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sumithran, P.; Prendergast, L.A.; Delbridge, E.; Purcell, K.; Shulkes, A.; Kriketos, A.; Proietto, J. Ketosis and appetite-mediating nutrients and hormones after weight loss. Eur. J. Clin. Nutr. 2013, 67, 759–764. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dashti, H.M.; Al-Zaid, N.S.; Mathew, T.C.; Al-Mousawi, M.; Talib, H.; Asfar, S.K.; Behbahani, A.I. Long term effects of ketogenic diet in obese subjects with high cholesterol level. Mol. Cell Biochem. 2006, 286, 1–9. [Google Scholar] [CrossRef] [PubMed]
- Hussain, T.A.; Mathew, T.C.; Dashti, A.A.; Asfar, S.; Al-Zaid, N.; Dashti, H.M. Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes. Nutrition 2012, 28, 1016–1021. [Google Scholar] [CrossRef]
- Tay, J.; Luscombe-Marsh, N.D.; Thompson, C.H.; Noakes, M.; Buckley, J.D.; Wittert, G.A.; Yancy, W.S., Jr.; Brinkworth, G.D. A very low-carbohydrate, low-saturated fat diet for type 2 diabetes management: A randomized trial. Diabetes Care 2014, 37, 2909–2918. [Google Scholar] [CrossRef] [Green Version]
- Mayer, S.B.; Jeffreys, A.S.; Olsen, M.K.; McDuffie, J.R.; Feinglos, M.N.; Yancy, W.S., Jr. Two diets with different haemoglobin A1c and antiglycaemic medication effects despite similar weight loss in type 2 diabetes. Diabetes Obes. Metab. 2014, 16, 90–93. [Google Scholar] [CrossRef]
- Foster, G.D.; Wyatt, H.R.; Hill, J.O.; Makris, A.P.; Rosenbaum, D.L.; Brill, C.; Stein, R.I.; Mohammed, B.S.; Miller, B.; Rader, D.J.; et al. Weight and metabolic outcomes after 2 years on a low-carbohydrate versus low-fat diet: A randomized trial. Ann. Intern. Med. 2010, 153, 147–157. [Google Scholar] [CrossRef]
- Volek, J.S.; Sharman, M.J.; Forsythe, C.E. Modification of lipoproteins by very low-carbohydrate diets. J. Nutr. 2005, 135, 1339–1342. [Google Scholar] [CrossRef]
- Ference, B.A.; Ginsberg, H.N.; Graham, I.; Ray, K.K.; Packard, C.J.; Bruckert, E.; Hegele, R.A.; Krauss, R.M.; Raal, F.J.; Schunkert, H.; et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur. Heart J. 2017, 38, 2459–2472. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Buscemi, S.; Verga, S.; Tranchina, M.R.; Cottone, S.; Cerasola, G. Effects of hypocaloric very-low-carbohydrate diet vs. Mediterranean diet on endothelial function in obese women*. Eur. J. Clin. Invest. 2009, 39, 339–347. [Google Scholar] [CrossRef] [PubMed]
- Luong, T.V.; Pedersen, M.G.B.; Kjærulff, M.; Madsen, S.; Lauritsen, K.M.; Tolbod, L.P.; Søndergaard, E.; Gormsen, L.C. Ischemic heart failure mortality is not predicted by cardiac insulin resistance but by diabetes per se and coronary flow reserve: A retrospective dynamic cardiac (18)F-FDG PET study. Metabolism 2021, 123, 154862. [Google Scholar] [CrossRef]
- Hernández, M.A.G.; Canfora, E.E.; Jocken, J.W.E.; Blaak, E.E. The Short-Chain Fatty Acid Acetate in Body Weight Control and Insulin Sensitivity. Nutrients 2019, 11, 1943. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ferraris, C.; Meroni, E.; Casiraghi, M.C.; Tagliabue, A.; de Giorgis, V.; Erba, D. One Month of Classic Therapeutic Ketogenic Diet Decreases Short Chain Fatty Acids Production in Epileptic Patients. Front. Nutr. 2021, 8, 613100. [Google Scholar] [CrossRef]
- O′Neill, B.; Raggi, P. The ketogenic diet: Pros and cons. Atherosclerosis 2020, 292, 119–126. [Google Scholar] [CrossRef] [Green Version]
- Lagiou, P.; Sandin, S.; Weiderpass, E.; Lagiou, A.; Mucci, L.; Trichopoulos, D.; Adami, H.O. Low carbohydrate-high protein diet and mortality in a cohort of Swedish women. J. Intern. Med. 2007, 261, 366–374. [Google Scholar] [CrossRef]
- Trichopoulou, A.; Psaltopoulou, T.; Orfanos, P.; Hsieh, C.C.; Trichopoulos, D. Low-carbohydrate-high-protein diet and long-term survival in a general population cohort. Eur. J. Clin. Nutr. 2007, 61, 575–581. [Google Scholar] [CrossRef]
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Luong, T.V.; Abild, C.B.; Bangshaab, M.; Gormsen, L.C.; Søndergaard, E. Ketogenic Diet and Cardiac Substrate Metabolism. Nutrients 2022, 14, 1322. https://doi.org/10.3390/nu14071322
Luong TV, Abild CB, Bangshaab M, Gormsen LC, Søndergaard E. Ketogenic Diet and Cardiac Substrate Metabolism. Nutrients. 2022; 14(7):1322. https://doi.org/10.3390/nu14071322
Chicago/Turabian StyleLuong, Thien Vinh, Caroline Bruun Abild, Maj Bangshaab, Lars Christian Gormsen, and Esben Søndergaard. 2022. "Ketogenic Diet and Cardiac Substrate Metabolism" Nutrients 14, no. 7: 1322. https://doi.org/10.3390/nu14071322
APA StyleLuong, T. V., Abild, C. B., Bangshaab, M., Gormsen, L. C., & Søndergaard, E. (2022). Ketogenic Diet and Cardiac Substrate Metabolism. Nutrients, 14(7), 1322. https://doi.org/10.3390/nu14071322