The Ketogenic Diet: Safety, Morbidity, and Mortality

Taufiqurrachman Nasihun*  -  [SCOPUS ID: 57195318576] Faculty of Medicine, Sultan Agung Islamic University, Indonesia

(*) Corresponding Author

In normal daily diet consisting of 52-55% carbohydrate, 32-34% fat, and 14-18% protein, a couple hours following meal and absorption there is abundant fuel supply particularly from glucose oxidation in most tissues (Kathleen M Botham and Mayes, 2015; USDA, 2015). Conversely, in ketosis condition, most tissues replace its energy requirement from glucose to ketone bodies resulting from hepatic ketogenesis (Cervenka and Kossoff, 2013; Mcdonald and Cervenka, 2017). In extra hepatic tissues, adenosine triphosphate (ATP) is synthesized through revert back of acetoacetate to acetoacetyl-CoA catalyzed by succinyl-CoA-acetoacetate CoA transferase. By this reaction acetoacetyl-CoA is split into two acetyl-CoA catalyzed by thiolase and then inserted into Kreb’s cycle to form ATP. Acetoacetate and b hydroxybutyrate are also able to traverse blood brain barrier and metabolized by cellular brain into ATP and used as energy also postulated as anticonvulsant (Freeman et al., 2007; J. L. Gamble et al., 1923). Moreover, when ketone bodies in circulation are increased, oxidation of ketone bodies also raised until saturation of the pathway is achieved at 12 mmol/L concentration (Kathleen M. Botham and Mayes, 2015). Concern to the energy synthesis, acetoacetate and 3-b hydroxybutyrate are the prominent ketone bodies which are readily oxidized in extra-hepatic tissues. Whilst acetone have not metabolic function and in large extent is volatilized through the lung marked by breathe odor (Kathleen M. Botham and Mayes, 2015; Paoli, 2014). Ketosis is also able to suppress hunger feeling and appetite, therefore potential to be a good regulator of the body’s calorie intake (Dashti et al., 2004).  However, ketosis which is induced by ketogenic diet (KD), in the long term, its safety, morbidity, and mortality remain inconclusive.

Keywords: The Ketogenic Diet; Safety; Morbidity; Mortality

  1. Botham, K.M., Mayes, P.A., 2015. Oxidation of Fatty acids: Ketogenesis. The McGraw-Hill Education, Rodwel VW, Bender DA, Botham KM, Kennelly PJ, Weil PA.
  2. Botham, K.M., Mayes, P.A., 2015. Biosynthesis of Fatty acids & eicosanoids, 30th ed. The McGraw-Hill Education, Rodwel VW, Bender DA, Botham KM, Kennelly PJ, Weil PA.
  3. Cervenka, M.C., Kossoff, E.H., 2013. Dietary Treatment of Intractable Epilepsy. Contin. (Minneap Minn) 19, 756–766. CON.0000431396.23852.56
  4. Dashti, H.M., Facs, F., Frcpath, T.C.M., Hussein, T., Chb, M.B., Dashti, H.M., Mathew, T.C., Hussein, T., 2004. Long-term effects of a ketogenic diet in obese patients. Exp. Clin. Cardiol. 9, 200–205.
  5. Freeman, J.M., Kossoff, E.H., Hartman, A.L., 2007. The Ketogenic Diet: One Decade Later. Pediatrics 119, 535–540.
  6. Ghosh, A., Gao, L., Thakur, A., Siu, P.M., Lai, C.W.K., 2017. Role of free fatty acids in endothelial dysfunction. J. Biomed. Sci. 24, 1–15.
  7. Hallberg, S.J., Mckenzie, A.L., Williams, P.T., Bhanpuri, N.H., Peters, A.L., Campbell, W.W., Hazbun, T.L., Volk, B.M., Mccarter, J.P., Phinney, S.D., Volek, J.S., 2018. Effectiveness and Safety of a Novel Care Model for the Management of Type 2 Diabetes at 1 Year: Diabetes Ther. 9, 583–612.
  8. Hemingway, C., Freeman, J.M., Pillas, D.J., Pyzik, P.L., 2001. The Ketogenic Diet: A 3- to 6-Year Follow-Up of 150 Children Enrolled Prospectively. Pediatrics 108, 898–905.
  9. Hernandez, T.L., Sutherland, J.P., Wolfe, P., Allian-sauer, M., Capell, W.H., Talley, N.D., Wyatt, H.R., Foster, G.D., Hill, J.O., Eckel, R.H., 2010. Lack of suppression of circulating free fatty acids and hypercholesterolemia during weight loss on a high-fat ,. Am J Clin Nutr. 578–585.
  10. J. L. Gamble, G. S. Ross, F. F. Tisdall, 1923. The metabolism of xed base during fasting. J Biol Chem. 57, 633– 695.
  11. Kinsman, Y.L., Vining, E.P.G., Quaskey, S.A., Mellits, D., Freeman, J.M., 1992. Efficacy of the Ketogenic Diet for Intractable Seizure Disorders: Review of 58 Cases. Epilepsia 33, 1132–1136.
  12. Lafountain, R.A., Miller, V.J., Barnhart, E.C., Hyde, P.N., Crabtree, C.D., Mcswiney, F.T., Beeler, M.K., Buga, A., Sapper, T.N., Short, J.A., Bowling, M.L., Kraemer, W.J., Simonetti, O.P., Maresh, C.M., Volek, J.S., 2019. Extended Ketogenic Diet and Physical Training Intervention in Military Personnel. Mil. Med. 0, 1–10.
  13. Levy, R.G., Cooper, P.N., Giri, P., Weston, J., 2015. Ketogenic diet and other dietary treatments for epilepsy ( Review ) Summary of Findings For The Main Comparison. John Wiley Sons.
  14. Manikam, N.R.M., Pantoro, N.I., Komala, K., Sari, A.D., 2018. Comparing the Efficacy of Ketogenic Diet with Low Fat Diet for Weight Loss in Obesity Patients: Evidence-Based Case Report. World Nutr. J. 7–14.
  15. Martin-McGill, K.J., Jackson, C.F., Bresnahan, R., Levy, R.G., Cooper, P.N., 2018. Cochrane Database of Systematic Reviews. Cochrane Libr.
  16. Mazidi, M., Katsiki, N., Mikhailidis, D.P., Sattar, N., 2019. Lower carbohydrate diets and all-cause and cause-specific mortality: a population-based cohort study and pooling of prospective studies 40, 2870–2879.
  17. Mcdonald, T.J.W., Cervenka, M.C., 2017. Ketogenic Diets for Adults With Highly Refractory Epilepsy. Epilepsy Curr. 17, 346–350.
  18. Paoli, A., 2014. Ketogenic Diet for Obesity: Friend or Foe? J. Environ. Res. Public Heal. 11, 2092–2107.
  19. Payne, N.E., Cross, J.H., Sander, J.W., Sisodiya, S.M., 2011. The ketogenic and related diets in adolescents and adults — A review. Epilepsia 52, 1941–1948.
  20. Seidelmann, S.B., Claggett, B., Cheng, S., Henglin, M., Shah, A., Steffen, L.M., Folsom, A.R., Rimm, E.B., Willett, W.C., 2018. Articles Dietary carbohydrate intake and mortality: a prospective cohort study and meta-analysis. Lancet Public Heal. 3, 419–428.
  21. USDA, 2015. Dietary Guidelines for Americans 2015–2020, 8th ed. Department of Agriculture.
  22. Volek, J.S., Luz, M., Feinman, R.D., Phinney, S.D., 2008. Dietary carbohydrate restriction induces a unique metabolic state positively affecting atherogenic dyslipidemia, fatty acid partitioning, and metabolic syndrome. Prog. Lipid Res. 47, 307–318.
  23. Volek, J.S., Phinney, S.D., Forsythe, C.E., Quann, E.E., Wood, R.J., Puglisi, M.J., Kraemer, W.J., Bibus, D.M., Fernandez, M.L., Feinman, R.D., 2009. Carbohydrate Restriction has a More Favorable Impact on the Metabolic Syndrome than a Low Fat Diet 297–309.
  24. Wheless, J.W., 2001. The Ketogenic Diet: An Effective Medical Therapy With Side Effects. J. Child Neurol. 16, 633–635.
  25. Wheless, J.W., 1995. The Ketogenic Diet: Fa(c)t or Fiction. J. Child Neurol. 10, 419 – 423.
  26. Wilder R. M., 1921. The effect of ketonemia on the course of epilepsy. Mayo Clin Bull 2, 30.
  27. Ye, F., Li, X., Jiang, W., Sun, H., Liu, J., 2015. Efficacy of and Patient Compliance with a Ketogenic Diet in Adults with Intractable Epilepsy: A Meta-Analysis. J Clin Neurol. 11, 26–31.

Open Access Copyright (c) 2020 Sains Medika: Jurnal Kedokteran dan Kesehatan
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Sains Medika: Jurnal Kedokteran dan Kesehatan

is published by Fakultas Kedokteran Universitas Islam Sultan Agung Semarang, Indonesia.
Jl. Raya Kaligawe Km.4, PO BOX 1054/SM Semarang 50112

ISSN: 2339-093X (Online) | 2085-1545 (Print)
DOI : 10.30659/sainsmed

This work is licensed under a Creative Commons Attribution 4.0 International License

Get a feed by atom here, RRS2 here and OAI Links here