Rebuttal To T-Nation’s Avoid This Ketogenic Ripoff Article

The ‘article’ “avoid this ketogenic ripoff” published by Mike Sheridan contains a great deal of misinformation, which mistakenly suggest that you should avoid exogenous ketone supplementation. I would like to respond by summarizing the most important results based on research studies on both animals and humans and clinical information. It is important to note that no studies to date have been done to assess body composition alterations after ketone supplementation administration, an important consideration of the bodybuilding and fitness community that the article targets. The research on exogenous ketone is mainly focused on applications which may not be of interest to the target audience, including CNSO2 toxicity, seizures, genetic disorders and cancer.

  1. To be clear, ketones are not ‘a byproduct of ketosis’. This would suggest that ketones are an unintended consequence. Ketone bodies, such as β-hydroxybutyrate (βHB or β-OHB), acetone and acetoacetate (AcAc) are synthetized by liver cells from fatty acids, which process leads to ketosis when blood levels rise above 0.5 mmol/L (to about 5-7 mmmol/L) (Veech, 2013).
  2. The body makes ketone bodies and uses them when it’s both in a calorie or carb-restricted state, and‘without the presence of glucose in the blood. Under normal physiological conditions, ketone bodies are synthetized in liver mitochondria mainly from fatty acids derived from human milk and adipose tissues, which provide energy for certain tissues/organs such as skeletal and heart muscle, renal cortex and brain (Künnecke et al., 1993; Dedkova and Blatter, 2014). βHB is also synthesized in astrocytes, which serve as fuel for brain cells (Edmond et al., 1987; Achanta and Rae, 2017). Moreover, under normal conditions, ketone bodies are major metabolic fuels for the brain of the suckling rats and human newborn (Hawkins et al., 1971b; Cahill, 2006) and later, when glucose is the main source of energy in the brain, ketone bodies are synthetized and used as fuel for certain tissues/organs such as the brain (Künnecke et al., 1993; Dedkova and Blatter, 2014).
  3. Consumption of ketone ester and βHB salt may have beneficial effects in the treatment of obesity: ketone ester and βHB salt enhanced the level of anorexinogenic malonyl CoA in the brain (Kashiwaya et al., 2010), and reduced visceral adipocyte volume (Caminhotto et al., 2017), respectively.
  4. Absorption of ketone bodies is rapid, thus, desired level of ketone bodies can be achieved by ketone ester consumption without potential side effects, which may be evoked by consuming the ketogenic diet (such as elevation of blood cholesterol and triglyceride levels) (Kwiterovich et al., 2003; Veech, 2013).
  5. Under fasting conditions, ketone bodies provide about 75% of energy for brain tissue. In different circumstances, when the level of ketone bodies increase in the body, the use of other substrates (e.g., glucose and lactate) as fuel, even if at a lower level, but is continued (Cahill, 2006). Thus, after consuming ketone supplements, the use of other energy substrates as fuel will not stop.
  6. The effect of ketone body administration on insulin levels may depend on the way of administration and the type of ketone bodies. However, increase in insulin level after ketone body administration has not been observed under any conditions in human, rats and dogs after βHB/βHB salt infusion, in contrast the insulin levels were rather decreased (Balasse et al., 1967; Balasse an Ooms, 1968; Devecerski et al., 1968; Hawkins et al., 1971a). Moreover, results from animal and human studies suggest that ketone ester and ketone salt (βHB salt) supplemented diet may decrease both blood glucose and insulin levels and increase insulin sensitivity in the brain and heart (Amiel et al., 1991; Sato et al., 1995; Kashiwaya et al., 2010; Kesl et al., 2016).
  7. Beneficial effects, which may be attributable to ketone bodies/exogenous ketone supplementation (partly theoretically), for example: 1) consuming ketone esters decreased brain amyloid-β and phosphorylated tau and improved cognitive functions in a genetic mouse model of Alzheimer’s disease (Kashiwaya et al., 2013); (2) ketones prevented free radical damage and βHB increased the destruction of free radicals; βHB suppressed oxidative stress by inhibition of histone deacetylase (Shimazu et al., 2013; Veech, 2013); 3) ketone salt Na-βHB dissolved in resuscitation fluids can prevent apoptosis in lung that occurs after severe hemorrhage in a rodent model (Alam et al., 2001); 4) βHB may extend the lifespan for example via inhibition of histone deacetylase by AMP kinase (AMPK) and sirtuin Sir2-dependent mechanisms, and reduction of apoptosis (Xiao et al., 2007; Edwards et al., 2014; Newman and Verdin, 2014); 5) ketone bodies increased mitochondrial efficiency and biogenesis (Bough et al., 2006; Kashiwaya et al., 2010); 6) βHB has a homeostatic function, which allow us to survive prolonged starvation (Taggart et al., 2005); 7) βHB may improve reaction time and exercise performance (Cox et al., 2016; Egan and D’Agostino, 2016);8) ketone bodies serve as alternative energy source for the brain, heart, and skeletal muscle (Yudkoff et al., 2007; Branco et al., 2016); 9) ketosis/βHB may improve the symptoms of certain diseases such as Alzheimer’s disease, Parkinson’s disease, schizophrenia, amyotrophic lateral sclerosis (ALS), glucose transporter 1 (GLUT1)-deficiency syndrome, anxiety, depression, autism, cancer, and epilepsy (Veech, 2004; Stafstrom and Rho, 2012; D’Agostino et al., 2013; Hashim and VanItallie, 2014; Poff et al., 2015; Ari et al., 2016; Branco et al., 2016; Achanta and Rae, 2017; Bostock et al., 2017; Kovács et al., 2017; Tefera et al., 2017); and 10) βHB may have other different physiological role in different species (Hawkins and Biebuyck, 1979; Achanta and Rae, 2017). Most recently there has been an intense interest in the potential for ketones to increase longevity, since exogenous ketones target many of the signaling pathways associated with calorie-restriction induced extension of life span in several model systems.

In summary, exogenous ketones provide an alternative form of energy that has many applications and metabolic advantages over glucose. Ketones also have a profound effect on gene expression and suppression of inflammatory pathways tightly linked to several pathologies and age-related chronic illnesses. Like creatine, it may take several years for the studies to validate the optimal dose, formulation and performance application of exogenous ketones. The emerging data on this new energy source suggests a broad range of therapeutic and performance applications. The main advantage associated with exogenous ketones may be linked to preserving CNS function under environmental extremes, which was the original application of funded DARPA and DoD-funded studies on these compounds.  Exogenous ketones may also be effective for mitigating pathologies associated with limited glucose availability or impaired glucose transport, which could describe a broad range of pathologies.


Achanta LB, Rae CD. β-Hydroxybutyrate in the brain: One molecule, multiple mechanisms. Neurochem Res. 2017 Jan;42(1):35-49. doi: 10.1007/s11064-016-2099-2.

Alam HB, Austin B, Koustova E, Rhee P. Resuscitation-induced pulmonary apoptosis and intracellular adhesion molecule-1 expression in rats are attenuated by the use of Ketone Ringer’s solution. J Am Coll Surg. 2001 Sep;193(3):255-63.

Amiel SA, Archibald HR, Chusney G, Williams AJ, Gale EA. Ketone infusion lowers hormonal responses to hypoglycaemia: evidence for acute cerebral utilization of a non-glucose fuel. Clin Sci (Lond). 1991 Aug;81(2):189-94.

Ari C, Kovács Z, Juhasz G, Murdun C, Goldhagen CR, Koutnik AP, Poff AM, Kesl SL, D’Agostino DP. Exogenous Ketone Supplements Reduce Anxiety-Related Behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk Rats. Front Mol Neurosci. 2016 Dec 6;9:137. doi: 10.3389/fnmol.2016.00137. eCollection 2016.

Balasse E, Couturier E, Franckson JR. Influence of sodium beta-hydroxybutyrate on glucose and free fatty acid metabolism in normal dogs. Diabetologia. 1967 Dec;3(6):488-93.

Balasse E, Ooms HA. Changes in the concentrations of glucose, free fatty acids, insulin and ketone bodies in the blood during sodium beta-hydroxybutyrate infusions in man. Diabetologia. 1968 Jun;4(3):133-5.

Bostock EC, Kirkby KC, Taylor BV. The current status of the ketogenic diet in psychiatry. Front Psychiatry. 2017 Mar 20;8:43. doi: 10.3389/fpsyt.2017.00043. eCollection 2017.

Bough KJ, Wetherington J, Hassel B, Pare JF, Gawryluk JW, Greene JG, Shaw R, Smith Y, Geiger JD, Dingledine RJ. Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet. Ann Neurol. 2006 Aug;60(2):223-35.

Branco AF, Ferreira A, Simões RF, Magalhães-Novais S, Zehowski C, Cope E, Silva AM, Pereira D, Sardão VA, Cunha-Oliveira T. Ketogenic diets: from cancer to mitochondrial diseases and beyond. Eur J Clin Invest. 2016 Mar;46(3):285-98. doi: 10.1111/eci.12591.

Cahill GF Jr. Fuel metabolism in starvation. Annu Rev Nutr. 2006;26:1-22.

Caminhotto RO, Komino ACM, de Fatima Silva F, Andreotti S, Sertié RAL, Boltes Reis G, Lima FB. Oral β-hydroxybutyrate increases ketonemia, decreases visceral adipocyte volume and improves serum lipid profile in Wistar rats. Nutr Metab (Lond). 2017 Apr 24;14:31. doi: 10.1186/s12986-017-0184-4. eCollection 2017.

Cox PJ, Kirk T, Ashmore T, Willerton K, Evans R, Smith A, Murray AJ, Stubbs B, West J, McLure SW, King MT, Dodd MS, Holloway C, Neubauer S, Drawer S, Veech RL, Griffin JL, Clarke K. Nutritional ketosis alters fuel preference and thereby endurance performance in athletes. Cell Metab. 2016 Aug 9;24(2):256-68. doi: 10.1016/j.cmet.2016.07.010.

D’Agostino DP, Pilla R, Held HE, Landon CS, Puchowicz M, Brunengraber H, Ari C, Arnold P, Dean JB. Therapeutic ketosis with ketone ester delays central nervous system oxygen toxicity seizures in rats. Am J Physiol Regul Integr Comp Physiol. 2013 May 15;304(10):R829-36. doi: 10.1152/ajpregu.00506.2012. Epub 2013 Apr 3.

Dedkova EN, Blatter LA. Role of β-hydroxybutyrate, its polymer poly-β-hydroxybutyrate and inorganic polyphosphate in mammalian health and disease. Front Physiol. 2014 Jul 17;5:260. doi: 10.3389/fphys.2014.00260. eCollection 2014.

Devecerski M, Pierce CE, Frawley TF. Effect of ketone acids on glucose and fat metabolism in adipose tissue of the rat. Metabolism. 1968 Oct;17(10):877-84.

Edmond J, Robbins RA, Bergstrom JD, Cole RA, de Vellis J. Capacity for substrate utilization in oxidative metabolism by neurons, astrocytes, and oligodendrocytes from developing brain in primary culture. J Neurosci Res. 1987;18(4):551-61.

Edwards C, Canfield J, Copes N, Rehan M, Lipps D, Bradshaw PC. D-beta-hydroxybutyrate extends lifespan in C. elegans. Aging (Albany NY). 2014 Aug;6(8):621-44.

Egan B, D’Agostino DP. Fueling performance: ketones enter the mix. Cell Metab. 2016 Sep 13;24(3):373-5. doi: 10.1016/j.cmet.2016.08.021.

Hashim SA, VanItallie TB. Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester. J Lipid Res. 2014 Sep;55(9):1818-26. doi: 10.1194/jlr.R046599.

Hawkins RA, Alberti KG, Houghton CR, Williamson DH, Krebs HA. The effect of acetoacetate on plasma insulin concentration. Biochem J. 1971a Nov;125(2):541-4.

Hawkins RA, Williamson DH, Krebs HA. Ketone-body utilization by adult and suckling rat brain in vivo. Biochem J. 1971b Mar;122(1):13-8.

Hawkins RA, Biebuyck JF. Ketone bodies are selectively used by individual brain regions. Science. 1979 Jul 20;205(4403):325-7.

Kashiwaya Y, Pawlosky R, Markis W, King MT, Bergman C, Srivastava S, Murray A, Clarke K, Veech RL. A ketone ester diet increases brain malonyl-CoA and Uncoupling proteins 4 and 5 while decreasing food intake in the normal Wistar Rat. J Biol Chem. 2010 Aug 20;285(34):25950-6. doi: 10.1074/jbc.M110.138198.

Kashiwaya Y, Bergman C, Lee JH, Wan R, King MT, Mughal MR, Okun E, Clarke K, Mattson MP, Veech RL. A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer’s disease. Neurobiol Aging. 2013 Jun;34(6):1530-9. doi: 10.1016/j.neurobiolaging.2012.11.023.

Kesl SL, Poff AM, Ward NP, Fiorelli TN, Ari C, Van Putten AJ, Sherwood JW, Arnold P, D’Agostino DP. Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague-Dawley rats. Nutr Metab (Lond). 2016 Feb 4;13:9. doi: 10.1186/s12986-016-0069-y. eCollection 2016.

Kovács Z, D’Agostino DP, Dobolyi A, Ari C. Adenosine A1 receptor antagonism abolished the anti-seizure effects of exogenous ketone supplementation in Wistar Albino Glaxo Rijswijk rats. Front Mol Neurosci., 2017 July;

Künnecke B, Cerdan S, Seelig J. Cerebral metabolism of [1,2-13C2]glucose and [U-13C4]3-hydroxybutyrate in rat brain as detected by 13C NMR spectroscopy. NMR Biomed. 1993 Jul-Aug;6(4):264-77.

Kwiterovich PO Jr, Vining EP, Pyzik P, Skolasky R Jr, Freeman JM. Effect of a high-fat ketogenic diet on plasma levels of lipids, lipoproteins, and apolipoproteins in children. JAMA. 2003 Aug 20;290(7):912-20.

Newman JC, Verdin E. Ketone bodies as signaling metabolites. Trends Endocrinol Metab. 2014 Jan;25(1):42-52. doi: 10.1016/j.tem.2013.09.002.

Poff AM, Ward N, Seyfried TN, Arnold P, D’Agostino DP. Non-Toxic Metabolic Management of Metastatic Cancer in VM Mice: Novel Combination of Ketogenic Diet, Ketone Supplementation, and Hyperbaric Oxygen Therapy. PLoS One. 2015 Jun 10;10(6):e0127407. doi: 10.1371/journal.pone.0127407. eCollection 2015.

Sato K, Kashiwaya Y, Keon CA, Tsuchiya N, King MT, Radda GK, Chance B, Clarke K, Veech RL. Insulin, ketone bodies, and mitochondrial energy transduction. FASEB J. 1995 May;9(8):651-8.

Shimazu T, Hirschey MD, Newman J, He W, Shirakawa K, Le Moan N, Grueter CA, Lim H, Saunders LR, Stevens RD, Newgard CB, Farese RV Jr, de Cabo R, Ulrich S, Akassoglou K, Verdin E. Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science. 2013 Jan 11;339(6116):211-4. doi: 10.1126/science.1227166.

Stafstrom CE, Rho JM. The ketogenic diet as a treatment paradigm for diverse neurological disorders. Front Pharmacol. 2012 Apr 9;3:59. doi: 10.3389/fphar.2012.00059. eCollection 2012.

Taggart AK, Kero J, Gan X, Cai TQ, Cheng K, Ippolito M, Ren N, Kaplan R, Wu K, Wu TJ, Jin L, Liaw C, Chen R, Richman J, Connolly D, Offermanns S, Wright SD, Waters MG. (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. J Biol Chem. 2005 Jul 22;280(29):26649-52.

Tefera TW, Tan KN, McDonald TS, Borges K. Alternative fuels in epilepsy and amyotrophic lateral sclerosis. Neurochem Res. 2017 Jun;42(6):1610-1620. doi: 10.1007/s11064-016-2106-7.

Veech RL. 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 Mar;70(3):309-19.

Veech RL. Ketone esters increase brown fat in mice and overcome insulin resistance in other tissues in the rat. Ann N Y Acad Sci. 2013 Oct;1302:42-8. doi: 10.1111/nyas.12222.

Veech RL, Bradshaw PC, Clarke K, Curtis W, Pawlosky R, King MT. Ketone bodies

mimic the life span extending properties of caloric restriction. IUBMB Life. 2017

May;69(5):305-314. doi: 10.1002/iub.1627. Epub 2017 Apr 3. Review. PubMed PMID:


Xiao XQ, Zhao Y, Chen GQ. The effect of 3-hydroxybutyrate and its derivatives on the growth of glial cells. Biomaterials. 2007 Sep;28(25):3608-16.

Yudkoff M, Daikhin Y, Melø TM, Nissim I, Sonnewald U, Nissim I. The ketogenic diet and brain metabolism of amino acids: relationship to the anticonvulsant effect. Annu Rev Nutr. 2007;27:415-30.



Instagram did not return a 200.

Follow Us!