Understanding the Relationship between the Ketogenic Diet and the Heart: A Novel Therapeutic Potential for Cardiovascular Health

Priyanshi      Shah; Aanchal      Sawhney; FNU      Anamika; Sai   Gautham   Kanagala; Kinna      Parikh; Vaidehi      Mendpara; Nikita      Garg; Rohit      Jain

doi:10.2174/0118715257267341231031120105

Abstract

Obesity and cardiovascular diseases are major health problems worldwide, and weight loss is used as a treatment strategy to enhance various aspects. While there are many weight loss methods, one of the most effective is through a dietary approach. The ketogenic diet (KD), which is characterized by low carbohydrates and high levels of fat and/or protein, is used in obese patients as it is a promising treatment option for weight loss as well as for controlling the risk factors for cardiovascular diseases, as seen in its effects on cardio-metabolic outcomes, particularly in obesity, heart failure, and hypertension. In this review, we summarize the clinical evidence of the efficacy and safety of the KD in controlling risk factors for cardiovascular diseases and discuss the possible mechanisms of action based on recent evidence in understanding the influence of the KD at the cellular and molecular levels.

Keywords: Ketogenic diet, cardiovascular disease, low-density lipoprotein, beta-hydroxybutyrate, obesity, carbohydrates.

« Previous Next »

Graphical Abstract

[1]
Joseph, P.; Leong, D.; McKee, M.; Anand, S.S.; Schwalm, J.D.; Teo, K.; Mente, A.; Yusuf, S. Reducing the global burden of cardiovascular disease, Part 1. Circ. Res.,  2017, 121(6), 677-694.
 [http://dx.doi.org/10.1161/CIRCRESAHA.117.308903] [PMID:  28860318]

[2]
Singh, G.M.; Danaei, G.; Farzadfar, F. The age-specific quantitative effects of metabolic risk factors on cardiovascular diseases and diabetes: A pooled analysis. PLoS One,  2013, 8(7), e65174.
 [http://dx.doi.org/10.1371/journal.pone.0065174]

[3]
Boutari, C.; Mantzoros, C.S.A. 2022 update on the epidemiology of obesity and a call to action: as its twin COVID-19 pandemic appears to be receding, the obesity and dysmetabolism pandemic continues to rage on. Metabolism,  2022, 133, 155217.
 [http://dx.doi.org/10.1016/j.metabol.2022.155217] [PMID:  35584732]

[4]
 4. Investing in heart disease and stroke research - american heart association. Available from:
          https://www.heart.org/-/media/Files/About-Us/Policy-Research/Fa ct-Sheets/Public-Health-Advocacy-and-Research/Investing-in-Our-Hearts--NIH-Fact-Sheet.pdf

[5]
 Cardiovascular diseases (cvds). World Health Organization. Available from:
          https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)

[6]
Petersen, K.S.; Kris-Etherton, P.M. Diet quality assessment and the relationship between diet quality and cardiovascular disease risk. Nutrients,  2021, 13(12), 4305.
 [http://dx.doi.org/10.3390/nu13124305]

[7]
Migliaccio, S.; Brasacchio, C.; Pivari, F.; Salzano, C.; Barrea, L.; Muscogiuri, G.; Savastano, S.; Colao, A. What is the best diet for cardiovascular wellness? A comparison of different nutritional models. Int. J. Obes. Suppl.,  2020, 10(1), 50-61.
 [http://dx.doi.org/10.1038/s41367-020-0018-0] [PMID:  32714512]

[8]
 Ketogenic diet – where are we so far? Available from:
          https://www.jiacm.in/2021/Journal_78_Page_51_56.pdf

[9]
Batch, J.T.; Lamsal, S.P.; Adkins, M.; Sultan, S.; Ramirez, M.N. Advantages and disadvantages of the ketogenic diet: A review article. Cureus,  2020, 12(8), 9639.
 [http://dx.doi.org/10.7759/cureus.9639]

[10]
Nordmann, A.J.; Nordmann, A.; Briel, M.; Keller, U.; Yancy, W.S., Jr; Brehm, B.J.; Bucher, H.C. Effects of low-carbohydrate vs low-fat diets on weight loss and cardiovascular risk factors: A meta-analysis of randomized controlled trials. Arch. Intern. Med.,  2006, 166(3), 285-293.
 [http://dx.doi.org/10.1001/archinte.166.3.285] [PMID:  16476868]

[11]
O’Neill, B.; Raggi, P. The ketogenic diet: Pros and cons. Atherosclerosis,  2020, 292, 119-126.
 [http://dx.doi.org/10.1016/j.atherosclerosis.2019.11.021] [PMID:  31805451]

[12]
Schwingshackl, L.; Hoffmann, G. Comparison of effects of long-term low-fat vs high-fat diets on blood lipid levels in overweight or obese patients: A systematic review and meta-analysis. J. Acad. Nutr. Diet.,  2013, 113(12), 1640-1661.
 [http://dx.doi.org/10.1016/j.jand.2013.07.010] [PMID:  24139973]

[13]
Kirkpatrick, C.F.; Bolick, J.P.; Kris-Etherton, P.M.; Sikand, G.; Aspry, K.E.; Soffer, D.E.; Willard, K.E.; Maki, K.C. Review of current evidence and clinical recommendations on the effects of low-carbohydrate and very-low-carbohydrate (including ketogenic) diets for the management of body weight and other cardiometabolic risk factors: A scientific statement from the National Lipid Association Nutrition and Lifestyle Task Force. J. Clin. Lipidol.,  2019, 13(5), 689-711.e1.
 [http://dx.doi.org/10.1016/j.jacl.2019.08.003] [PMID:  31611148]

[14]
Masood, W.; Annamaraju, P.; Uppaluri, K.R. Ketogenic Diet; StatPearls Publishing: StatPearls Treasure Island, 2022. 

[15]
Cicero, A.F.G.; Benelli, M.; Brancaleoni, M.; Dainelli, G.; Merlini, D.; Negri, R. Middle and long-term impact of a very low-carbohydrate ketogenic diet on cardiometabolic factors: A multi-center, cross-sectional, clinical study. High Blood Press. Cardiovasc. Prev.,  2015, 22(4), 389-394.
 [http://dx.doi.org/10.1007/s40292-015-0096-1] [PMID:  25986079]

[16]
Yao, A.; Li, Z.; Lyu, J.; Yu, L.; Wei, S.; Xue, L.; Wang, H.; Chen, G.Q. On the nutritional and therapeutic effects of ketone body d-β-hydroxybutyrate. Appl. Microbiol. Biotechnol.,  2021, 105(16-17), 6229-6243.
 [http://dx.doi.org/10.1007/s00253-021-11482-w] [PMID:  34415393]

[17]
Kumar, A.A.; Kelly, D.P.; Chirinos, J.A. Mitochondrial dysfunction in heart failure with preserved ejection fraction. Circulation,  2019, 139(11), 1435-1450.
 [http://dx.doi.org/10.1161/CIRCULATIONAHA.118.036259] [PMID:  30856000]

[18]
Lopaschuk, G.D.; Ussher, J.R.; Folmes, C.D.L.; Jaswal, J.S.; Stanley, W.C. Myocardial fatty acid metabolism in health and disease. Physiol. Rev.,  2010, 90(1), 207-258.
 [http://dx.doi.org/10.1152/physrev.00015.2009] [PMID:  20086077]

[19]
Aubert, G.; Martin, O.J.; Horton, J.L.; Lai, L.; Vega, R.B.; Leone, T.C.; Koves, T.; Gardell, S.J.; Krüger, M.; Hoppel, C.L.; Lewandowski, E.D.; Crawford, P.A.; Muoio, D.M.; Kelly, D.P. The failing heart relies on ketone bodies as a fuel. Circulation,  2016, 133(8), 698-705.
 [http://dx.doi.org/10.1161/CIRCULATIONAHA.115.017355] [PMID:  26819376]

[20]
Ho, K.L.; Zhang, L.; Wagg, C.; Al Batran, R.; Gopal, K.; Levasseur, J.; Leone, T.; Dyck, J.R.B.; Ussher, J.R.; Muoio, D.M.; Kelly, D.P.; Lopaschuk, G.D. Increased ketone body oxidation provides additional energy for the failing heart without improving cardiac efficiency. Cardiovasc. Res.,  2019, 115(11), 1606-1616.
 [http://dx.doi.org/10.1093/cvr/cvz045] [PMID:  30778524]

[21]
Deng, Y.; Xie, M.; Li, Q.; Xu, X.; Ou, W.; Zhang, Y.; Xiao, H.; Yu, H.; Zheng, Y.; Liang, Y.; Jiang, C.; Chen, G.; Du, D.; Zheng, W.; Wang, S.; Gong, M.; Chen, Y.; Tian, R.; Li, T. Targeting mitochondria-inflammation circuit by β-hydroxybutyrate mitigates HFpEF. Circ. Res.,  2021, 128(2), 232-245.
 [http://dx.doi.org/10.1161/CIRCRESAHA.120.317933] [PMID:  33176578]

[22]
Zhang, Y.; Taufalele, P.V.; Cochran, J.D.; Robillard-Frayne, I.; Marx, J.M.; Soto, J.; Rauckhorst, A.J.; Tayyari, F.; Pewa, A.D.; Gray, L.R.; Teesch, L.M.; Puchalska, P.; Funari, T.R.; McGlauflin, R.; Zimmerman, K.; Kutschke, W.J.; Cassier, T.; Hitchcock, S.; Lin, K.; Kato, K.M.; Stueve, J.L.; Haff, L.; Weiss, R.M.; Cox, J.E.; Rutter, J.; Taylor, E.B.; Crawford, P.A.; Lewandowski, E.D.; Des Rosiers, C.; Abel, E.D. Mitochondrial pyruvate carriers are required for myocardial stress adaptation. Nat. Metab.,  2020, 2(11), 1248-1264.
 [http://dx.doi.org/10.1038/s42255-020-00288-1] [PMID:  33106689]

[23]
Zhang, W.; Guo, X.; Chen, L. Ketogenic diets and cardio-metabolic diseases. Front. Endocrinol.,  2021, 12, 753039.
 [http://dx.doi.org/10.3389/fendo.2021.753039]

[24]
Castellana, M.; Biacchi, E.; Procino, F.; Casanueva, F.F.; Trimboli, P. Very-low-calorie ketogenic diet for the management of obesity, overweight and related disorders. Minerva Endocrinol.,  2021, 46(2), 161-167.
 [http://dx.doi.org/10.23736/S2724-6507.20.03356-8] [PMID:  33213120]

[25]
Williams, L.; Rhodes, K.S.; Karmally, W.; Welstead, L.A.; Alexander, L.; Sutton, L. Familial chylomicronemia syndrome: Bringing to life dietary recommendations throughout the life span. J. Clin. Lipidol.,  2018, 12(4), 908-919.
 [http://dx.doi.org/10.1016/j.jacl.2018.04.010] [PMID:  29804909]

[26]
Pace, L.A.; Crowe, S.E. Complex relationships between food, diet, and the microbiome. Gastroenterol. Clin. North Am.,  2016, 45(2), 253-265.
 [http://dx.doi.org/10.1016/j.gtc.2016.02.004] [PMID:  27261897]

[27]
Masood, W.; Annamaraju, P.; Uppaluri, K.R. Ketogenic Diet. StatPearls; StatPearls Publishing: Treasure Island, FL, 2022. 

[28]
Bueno, N.B.; de Melo, I.S.V.; de Oliveira, S.L.; da Rocha Ataide, T. 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(7), 1178-1187.
 [http://dx.doi.org/10.1017/S0007114513000548] [PMID:  23651522]

[29]
Dhamija, R.; Eckert, S.; Wirrell, E. Ketogenic Diet. Can. J. Neurol. Sci.,  2013, 40(2), 158-167.
 [http://dx.doi.org/10.1017/S0317167100013676] [PMID:  23419562]

[30]
Paoli, A. Ketogenic diet for obesity: Friend or foe. Int. J. Environ. Res. Public Health,  2014, 11(2), 2092-2107.
 [http://dx.doi.org/10.3390/ijerph110202092]

[31]
Samaha, F.F.; Iqbal, N.; Seshadri, P.; Chicano, K.L.; Daily, D.A.; McGrory, J.; Williams, T.; Williams, M.; Gracely, E.J.; Stern, L. A low-carbohydrate as compared with a low-fat diet in severe obesity. N. Engl. J. Med.,  2003, 348(21), 2074-2081.
 [http://dx.doi.org/10.1056/NEJMoa022637] [PMID:  12761364]

[32]
Ludwig, D.S. The ketogenic diet: Evidence for optimism but high-quality research needed. J. Nutr.,  2020, 150(6), 1354-1359.
 [http://dx.doi.org/10.1093/jn/nxz308] [PMID:  31825066]

[33]
Polito, R.; Messina, G.; Valenzano, A. The role of very low calorie ketogenic diet in sympathetic activation through cortisol secretion in male obese population. J. Clin. Med.,  2021, 10(18), 4230.
 [http://dx.doi.org/10.3390/jcm10184230]

[34]
Yuan, X.; Wang, J.; Yang, S. Effect of the ketogenic diet on glycemic control, insulin resistance, and lipid metabolism in patients with T2DM: a systematic review and meta-analysis. Nutr. Diabetes,  2020, 10(1), 38.
 [http://dx.doi.org/10.1038/s41387-020-00142-z]

[35]
Castellana, M.; Conte, E.; Cignarelli, A.; Perrini, S.; Giustina, A.; Giovanella, L.; Giorgino, F.; Trimboli, P. Efficacy and safety of very low calorie ketogenic diet (VLCKD) in patients with overweight and obesity: A systematic review and meta-analysis. Rev. Endocr. Metab. Disord.,  2020, 21(1), 5-16.
 [http://dx.doi.org/10.1007/s11154-019-09514-y] [PMID:  31705259]

[36]
Volek, J.S.; Sharman, M.J.; Forsythe, C.E. Modification of lipoproteins by very low-carbohydrate diets. J. Nutr.,  2005, 135(6), 1339-1342.
 [http://dx.doi.org/10.1093/jn/135.6.1339] [PMID:  15930434]

[37]
Bergqvist, A.G.C. Long-term monitoring of the ketogenic diet. Do’s and Don’ts. Epilepsy Res.,  2012, 100(3), 261-266.
 [http://dx.doi.org/10.1016/j.eplepsyres.2011.05.020] [PMID:  21855296]

[38]
Caprio, M.; Infante, M.; Moriconi, E.; Armani, A.; Fabbri, A.; Mantovani, G.; Mariani, S.; Lubrano, C.; Poggiogalle, E.; Migliaccio, S.; Donini, L.M.; Basciani, S.; Cignarelli, A.; Conte, E.; Ceccarini, G.; Bogazzi, F.; Cimino, L.; Condorelli, R.A.; La Vignera, S.; Calogero, A.E.; Gambineri, A.; Vignozzi, L.; Prodam, F.; Aimaretti, G.; Linsalata, G.; Buralli, S.; Monzani, F.; Aversa, A.; Vettor, R.; Santini, F.; Vitti, P.; Gnessi, L.; Pagotto, U.; Giorgino, F.; Colao, A.; Lenzi, A.; Caprio, M.; Bogazzi, F.; Beccuti, G.; Biondi, B.; Cannavò, S.; Chiodini, I.; De Feudis, G.; Di Francesco, S.; Di Gregorio, A.; Fallo, F.; Foresta, C.; Giacchetti, G.; Granata, R.; Isidori, A.M.; Magni, P.; Maiellaro, P.; Caprino, M.P.; Pivonello, R.; Pofi, R.; Pontecorvi, A.; Simeoli, C. Very-low-calorie ketogenic diet (VLCKD) in the management of metabolic diseases: systematic review and consensus statement from the Italian Society of Endocrinology (SIE). J. Endocrinol. Invest.,  2019, 42(11), 1365-1386.
 [http://dx.doi.org/10.1007/s40618-019-01061-2] [PMID:  31111407]

[39]
Rusek, M.; Pluta, R.; Ułamek-Kozioł, M. Czuczwar, SJ Ketogenic Diet in Alzheimer’s Disease. Int. J. Mol. Sci.,  2019, 20(16), 3892.
 [http://dx.doi.org/10.3390/ijms20163892]

[40]
Crosby, L.; Davis, B.; Joshi, S. Ketogenic diets and chronic disease: Weighing the benefits against the risks. Front. Nutr.,  2021, 8, 702802.
 [http://dx.doi.org/10.3389/fnut.2021.702802]

[41]
McGaugh, E.; Barthel, B. A review of ketogenic diet and lifestyle. Mo. Med.,  2022, 119(1), 84-88.
 [PMID:  36033148]

[42]
Seidelmann, S.B.; Claggett, B.; Cheng, S.; Henglin, M.; Shah, A.; Steffen, L.M.; Folsom, A.R.; Rimm, E.B.; Willett, W.C.; Solomon, S.D. Dietary carbohydrate intake and mortality: A prospective cohort study and meta-analysis. Lancet Public Health,  2018, 3(9), e419-e428.
 [http://dx.doi.org/10.1016/S2468-2667(18)30135-X] [PMID:  30122560]

Rights & Permissions Print Cite

Article Metrics

18

1

Journal Information

For Authors

For Editors

For Reviewers

Explore Articles

Open Access

Open Access Articles

For Visitors

DOI https://dx.doi.org/10.2174/0118715257267341231031120105	Print ISSN 1871-5257
Publisher Name Bentham Science Publisher	Online ISSN 1875-6182

Cardiovascular & Hematological Agents in Medicinal Chemistry

Understanding the Relationship between the Ketogenic Diet and the Heart: A Novel Therapeutic Potential for Cardiovascular Health

Abstract

Graphical Abstract

Related Journals

Related Books

Related Articles