ketogenic diet, ketomolecules, metabolic health


The clinical efficacy of ketoids has gradually gained great recognition. The purpose of this review article is to show that keto cells are considered not only as an alternative source of energy during starvation and low carbohydrate diets, but also as signaling molecules. It has been found that in species such as mice, rats, fish, flies, etc., low-calorie diets play an important role in the process of prolonging life and stopping age-related diseases. Ketomolecules formed on the background of the ketogenic diet are important regulators of metabolic health and prolongation of life of our body, which by many, still unknown, molecular mechanisms alleviate the aging process of phenotype, modulate the process of lipolysis, increase lipolysis, resilience, energy expenditure, affects the process of autophagy.


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Словарь иностранных слов. — М.: «Русский язык», 1989. — 624 с. ISBN 5-200-00408-8

Policy and Action for Cancer Prevention Food, Nutrition, and Physical Activity.

Thomas, L.K.; Ittmann, M.; Cooper, C. The role of leucine in ketogenesis in starved rats. Biochem. J. 1982, 204, 399–403

Soto-Mota, A.; Norwitz, N.G.; Clarke, K. Why a d-β-hydroxybutyrate monoester? Biochem. Soc. Trans. 2020, 48, 51–59. [CrossRef]

Cahill, G.F., Jr.; Herrera, M.G.; Morgan, A.P.; Soeldner, J.S.; Steinke, J.; Levy, P.L.; Reichard, G.A., Jr.; Kipnis, D.M. Hormone-fuel interrelationships during fasting. J. Clin. Investig. 1966, 45, 1751–1769

Reichard, G.A., Jr.; Owen, O.E.; Haff, A.C.; Paul, P.; Bortz, W.M. Ketone-body production and oxidation in fasting obese humans. J. Clin. Investig. 1974, 53, 508–515

Mary K. Campbell, Shawn O. Farrell. Biochemistry (неопр.). 5th. Cengage Learning 2006, 579. ISBN 0534405215

Березов Т. Т., Коровкин Б. Ф. Биологическая химия: УчебнПод. ред. акад. АМН СССР С. С. Дебова. 2-е изд., перераб. и доп. М.: Медицина, 1990, 528

Newman, J.C.; Verdin, E. β-hydroxybutyrate: Much more than a metabolite. Diabetes Res. Clin. Pr. 2014, 106, 173–181.Bock, H.; Fleischer, S. Preparation of a homogeneous soluble D-beta-10

Hydroxybutyrateapodehydrogenase from mitochondria. J. Biol. Chem. 1975, 250, 5774–5781.

Lehninger, A.L.; Sudduth, H.C.; Wise, J.B. D-beta-Hydroxybutyric dehydrogenase of muitochondria. J. Biol. Chem. 1960, 235, 2450–2455

Halestrap, A.P.; Wilson, M.C. The monocarboxylate transporter family–role and regulation. IUBMB Life 2012, 64, 109–119.

Halestrap, A.P. The SLC16 gene family-Structure, role and regulation in health and disease. Mol. Asp. Med. 2013, 34, 337–349.

Owen, O.E.; Morgan, A.P.; Kemp, H.G.; Sullivan, J.M.; Herrera, M.G.; Cahill, G.F., Jr. Brain metabolism during fasting. J. Clin. Investig. 1967, 46, 1589–1595

Abbasi, J. Ketone Body Supplementation-A Potential New Approach for Heart Disease. JAMA 2021, 326

Krebs, H. Biochemical aspects of ketosis. Proc. R. Soc. Med. 1960, 53, 71–80. [CrossRef] [PubMed]

Robinson, A.M.; Williamson, D.H. Physiological roles of ketone bodies as substrates and signals in mammalian tissues. Physiol. Rev. 1980, 60, 143–187. [CrossRef] [PubMed]

Laffel, L. Ketone bodies: A review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes Metab. Res. Rev. 1999, 15, 412–426

Gershuni, V.M.; Yan, S.L.; Medici, V. Nutritional ketosis for weight management and reversal of metabolic syndrome. Curr. Nutr. Rep. 2018, 7, 97–106. [CrossRef]

Cahill, G.F., Jr. Fuel metabolism in starvation. Annu. Rev. Nutr. 2006, 26, 1–22.

Balasse, E.O.; Féry, F. Ketone body production and disposal: Effects of fasting, diabetes, and exercise. Diabetes Metab. Rev. 1989, 5, 247–270

Rojas-Morales, P.; Tapia, E.; Pedraza-Chaverri, J. β-Hydroxybutyrate: A signaling metabolite in starvation response? Cell. Signal. 2016, 28, 917–923

Cotter, D.G.; Schugar, R.C.; Crawford, P.A. Ketone body metabolism and cardiovascular disease. Am. J. Physiol. Heart Circ. Physiol. 2013, 304, H1060–H1076

(D)-betaHydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. J. Biol. Chem. 2005, 280, 26649–26652

Offermanns, S. The nicotinic acid receptor GPR109A (HM74A or PUMA-G) as a new therapeutic target. Trends. Pharm. Sci. 2006, 27, 384–390

Tunaru, S.; Kero, J.; Schaub, A.; Wufka, C.; Blaukat, A.; Pfeffer, K.; Offermanns, S. PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nat. Med. 2003, 9, 352–355.

Lukasova, M.; Malaval, C.; Gille, A.; Kero, J.; Offermanns, S. Nicotinic acid inhibits progression of atherosclerosis in mice through its receptor GPR109A expressed by immune cells. J. Clin. Investig. 2011, 121, 1163–1173

Kashiwaya, Y.; Takeshima, T.; Mori, N.; Nakashima, K.; Clarke, K.; Veech, R.L. D-beta-hydroxybutyrate protects neurons in models of Alzheimer’s and Parkinson’s disease. Proc. Natl. Acad. Sci. USA 2000, 97

Shaafi, S.; Najmi, S.; Aliasgharpour, H.; Mahmoudi, J.; Sadigh-Etemad, S.; Farhoudi, M.; Baniasadi, N. The efficacy of the ketogenic diet on motor functions in Parkinson’s disease: A rat model. Iran. J. Neurol. 2016, 15, 63–69.

Tieu, K.; Perier, C.; Caspersen, C.; Teismann, P.; Wu, D.C.; Yan, S.D.; Naini, A.; Vila, M.; Jackson-Lewis, V.; Ramasamy, R.; et al. D-beta-hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease. J. Clin. Investig. 2003, 112, 892–901.

Newman, J.C.; Verdin, E. Ketone bodies as signaling metabolites. Trends Endocrinol. Metab. 2014, 25, 42–52.

Xu, D.; Lian, D.; Wu, J.; Liu, Y.; Zhu, M.; Sun, J.; He, D.; Li, L. Brain-derived neurotrophic factor reduces inflammation and hippocampal apoptosis in experimental Streptococcus pneumoniae meningitis. J. Neuroinflamm. 2017, 14, 156.

Makar, T.K.; Trisler, D.; Sura, K.T.; Sultana, S.; Patel, N.; Bever, C.T. Brain derived neurotrophic factor treatment reduces inflammation and apoptosis in experimental allergic encephalomyelitis. J. Neurol. Sci. 2008, 270, 70–76

Mattson, M.P.; Lovell, M.A.; Furukawa, K.; Markesbery, W.R. Neurotrophic factors attenuate glutamate-induced accumulation of peroxides, elevation of intracellular Ca2+ concentration, and neurotoxicity and increase antioxidant enzyme activities in hippocampal neurons. J. Neurochem. 1995, 65, 1740–1751.

Kirschner, P.B.; Jenkins, B.G.; Schulz, J.B.; Finkelstein, S.P.; Matthews, R.T.; Rosen, B.R.; Beal, M.F. NGF, BDNF and NT-5, but not NT-3 protect against MPP+ toxicity and oxidative stress in neonatal animals. Brain Res. 1996, 713, 178–185.

Witte, A.V.; Fobker, M.; Gellner, R.; Knecht, S.; Flöel, A. Caloric restriction improves memory in elderly humans. Proc. Natl. Acad. Sci. USA 2009, 106, 1255–1260.

Roberts, M.N.; Wallace, M.A.; Tomilov, A.A.; Zhou, Z.; Marcotte, G.R.; Tran, D.; Perez, G.; Gutierrez-Casado, E.; Koike, S.; Knotts, T.A.; et al. A ketogenic diet extends longevity and healthspan in adult mice. Cell Metab. 2017, 26, 539–546.

Veech, R.L.; Bradshaw, P.C.; Clarke, K.; Curtis, W.; Pawlosky, R.; King, M.T. Ketone bodies mimic the life span extending properties of caloric restriction. IUBMB Life 2017, 69, 305–314

Kumari, S.; Badana, A.K.; Malla, R. Reactive oxygen species: A key constituent in cancer survival. Biomark Insights 2018, 13, 1177271918755391

Klement, R.J.; Champ, C.E.; Otto, C.; Kämmerer, U. Anti-tumor effects of ketogenic diets in mice: A meta-analysis. PLoS ONE 2016, 11, e0155050

Allen, B.G.; Bhatia, S.K.; Anderson, C.M.; Eichenberger-Gilmore, J.M.; Sibenaller, Z.A.; Mapuskar, K.A.; Schoenfeld, J.D.; Buatti, J.M.; Spitz, D.R.; Fath, M.A. Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism. Redox Biol. 2014, 2, 963–970

Klement, R.J.; Sweeney, R.A. Impact of a ketogenic diet intervention during radiotherapy on body composition: I. Initial clinical experience with six prospectively studied patients. BMC Res. Notes 2016, 9, 143.

Schmidt, M.; Pfetzer, N.; Schwab, M.; Strauss, I.; Kämmerer, U. Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: A pilot trial. Nutr. Metab. 2011, 8, 54.

Fortier, M.; Castellano, C.A.; Croteau, E.; Langlois, F.; Bocti, C.; St-Pierre, V.; Vandenberghe, C.; Bernier, M.; Roy, M.; Descoteaux, M.; et al. A ketogenic drink improves brain energy and some measures of cognition in mild cognitive impairment. Alzheimers Dement. 2019, 15, 625–634.

Srivastava, S.; Baxa, U.; Niu, G.; Chen, X.; Veech, R.L. A ketogenic diet increases brown adipose tissue mitochondrial proteins and UCP1 levels in mice. IUBMB Life 2013, 65, 58–66

Xu, X.; Zhang, Q.; Tu, J.; Ren, Z. D-β-hydroxybutyrate inhibits microglial activation in a cell activation model in vitro. J. Med. Coll. PLA 2011, 26, 117–127.

Youm, Y.H.; Nguyen, K.Y.; Grant, R.W.; Goldberg, E.L.; Bodogai, M.; Kim, D.; D’Agostino, D.; Planavsky, N.; Lupfer, C.; Kanneganti, T.D.; et al. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nat. Med. 2015, 21, 263–269.

Han, Y.M.; Ramprasath, T.; Zou, M.H. β-hydroxybutyrate and its metabolic effects on age-associated pathology. Exp. Mol. Med. 2020, 52, 548–555

Stubbs, B.J.; Koutnik, A.P.; Volek, J.S.; Newman, J.C. From bedside to battlefield: Intersection of ketone body mechanisms in geroscience with military resilience. GeroScience 2021, 43, 1071–1081.

Koutnik, A.P.; D’Agostino, D.P.; Egan, B. Anticatabolic Effects of Ketone Bodies in Skeletal Muscle. Trends Endocrinol. Metab. 2019, 30, 227–229.9

Kwak, S.E.; Bae, J.H.; Lee, J.H.; Shin, H.E.; Zhang, D.; Cho, S.C.; Song, W. Effects of exercise-induced beta-hydroxybutyrate on muscle function and cognitive function. Physiol. Rep. 2021, 9, e14497.

Munroe, M.; Pincu, Y.; Merritt, J.; Cobert, A.; Brander, R.; Jensen, T.; Rhodes, J.; Boppart, M.D. Impact of β-hydroxy βmethylbutyrate (HMB) on age-related functional deficits in mice. Exp. Gerontol. 2017, 87, 57–66

Walsh, M.E.; Bhattacharya, A.; Sataranatarajan, K.; Qaisar, R.; Sloane, L.; Rahman, M.M.; Kinter, M.; Van Remmen, H. The histone deacetylase inhibitor butyrate improves metabolism and reduces muscle atrophy during aging. Aging Cell 2015, 14, 957–970

Angiolilli, C.; Baeten, D.L.; Radstake, T.R.; Reedquist, K.A. The acetyl code in rheumatoid arthritis and other rheumatic diseases. Epigenomics 2017, 9, 447–461

Praticò, D.; Trojanowski, J.Q. Inflammatory hypotheses: Novel mechanisms of Alzheimer’s neurodegeneration and new therapeutic targets? Neurobiol. Aging 2000, 21, 441–453

Puchalska, P.; Crawford, P.A. Multi-dimensional roles of ketone bodies in fuel metabolism, signaling, and therapeutics. Cell Metab. 2017, 25, 262–284

Camberos-Luna, L.; Massieu, L. Therapeutic strategies for ketosis induction and their potential efficacy for the treatment of acute brain injury and neurodegenerative diseases. Neurochem. Int. 2020, 133, 104614

Bueno NB, de Melo IS, de Oliveira SL, 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) 110:1178–87. doi: 10.1017/S0007114513000548

Boletnebud U. «The Keto Diet Harm And Benefits» // «Health without drugs» - Published on 2019 February 14

Stella Iacovides and Rebecca, M. Meiring «The effect of a ketogenic diet versus a high-carbohydrate, low-fat diet on sleep, cognition, thyroid function, and cardiovascular health independent of weight loss: study protocol for a randomized controlled trial» - Published on 2018 Jan 23

Hall, K. D. Energy expenditure and body composition changes after an isocaloric ketogenic diet in overweight and obese men. /K. D. Hall, K. Y. Chen, J. Guo … [et al.] // American journal of clinical nutrition. -2016. Vol. 104, no. 2 (August), 324−333.

Effect of the ketogenic diet on glycemic control, insulin resistance, and lipid metabolism in patients with T2DM: a systematic review and meta-analysis Nutrition & Diabetes (IF5.097), Pub Date: 2020-11-30.




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