History of Ketone Supplementation

Research on ketone supplementation dates back to the early 1940s when scientists showed that beta-hydroxybutyrate (BHB) and acetoacetate (AcAc), two of the three types of ketone bodies, improved oxygen efficiency and sperm motility in animals. The 1950s and ‘60s saw an explosion of research investigating the effects of ketone infusions on blood glucose and insulin in animals and humans.[1] Currently, there are multiple, pilot and full-scale studies being conducted on exogenous ketones, and the numerous benefits produced by elevating ketone bodies via supplementation.

Here is a summary of the key scientific facts:

  1. Ketones are the most energy-efficient fuel, yielding more ATP than glycolysis. For instance, pyruvate (end-glycolytic substrate) produces 10 ATP while BHB yields 13 ATP. In other words, ketones yield 30% more cellular energy with less oxidative stress.[2,3]
  2. Ketones, as the most energy-efficient fuel, may be beneficial for the brain and muscles in times of stress, such as during exercise.[4,5]
  3. Elevation of ketone bodies increases the redox span between complex I and complex II of the mitochondrial electron transport chain (by reducing the mitochondrial NAD couple and oxidizing the coenzyme Q couple).[6]
  4. Supplemental ketones may mimic the benefits experienced with elevated levels of endogenous ketones produced with reduced carbohydrate intake (i.e., ketogenic dieting) or prolonged fasting by:
    • Increasing satiety, thus to improve body composition.
    • Increasing brown adipose tissue (BAT), which increases energy expenditure and may provide a “metabolic advantage”.
    • Improving cognitive performance (e.g., better clarity, focus, energy).

How Does BHB Work in Your Body?

Under physiological conditions in which ample carbohydrate is available, or after an overnight fast, circulating ketone body concentrations are relatively low (0.1–0.5 mmol/L).[10] However, limiting carbohydrate intake (such as prolonged fasting, carbohydrate restriction, or prolonged exercise) forces the body to burn fat for fuel. A portion of the acetyl-CoA derived from fatty acids is converted to ketone bodies via hepatic mitochondria (up to 150 g/day).[11]

The brain is an extremely active organ and demands a large amount of energy. The blood brain barrier prevents the brain and CNS from deriving energy from fat directly, but ketones can be used as an “alternate fuel source”. These are created in the liver from fats via the process of ketogenesis and translocated through the blood for conversion back to acetyl-CoA, which is used as an alternative source of energy by the tricarboxylic acid (TCA) cycle.[12] Ketones fuel the brain, as well as skeletal and cardiac muscles.

Supplementing with BHB expedites the process of achieving ketosis, provides the benefits of elevated blood ketone levels, and accelerates keto-adaptation with or without following a ketogenic diet. Let's take a closer look at the documented and researched benefits of taking a clinically dosed BHB Supplement like Ketond:

1. Improves Focus

BHB improves energy metabolism in the hypoxia, anoxia and global cerebral ischemia. [13] Elevated ketone bodies replace glucose as the major energy substrate for the brain and thus may be neuroprotective, helping preserve cognitive function.[14]

In a recent study, our team investigated the ability of BHB to improve focus.

Methods: Eight college-aged males and females were randomly assigned either ketones (BHBSalts) or placebo. The subjective feelings (including: Mood (M), Energy (E), Hunger (H), Gastrointestinal distress (GI), and Focus (F)) of participants were collected to determine differences between the two groups.

Results: There was a significant group by time interaction in which perceived focus was significantly greater in the ketone supplemented group at 60 and 120 minutes when compared to placebo (6AU-3.8AU).

Conclusion: Ketone supplementation is effective at acutely enhancing focus.

2. Increases Energy

BHB, an alternative energy substrate, has been widely reported to improve metabolic efficiency (i.e., energetic performance) in animal models, primarily through mechanisms involving alternations in glycolytic intermediates and enhanced mitochondrial energetics.[15,16]

In data provided by Burgess, BHB produces relatively more energy than glucose. It yields more ATP (13 ATP/C2) than glucose (12.67 ATP/C2) and increases the free energy released from ATP hydrolysis.[17]

3. Enhances Athletic Performance

Oral exogenous ketones increase plasma BHB levels and fat oxidation, while reducing glycolysis and plasma lactate. This alters the bodies’ fuel preference, increases glycogen synthesis and ultimately enhances endurance in athletes.[18-20]

In 2016, Cox et al.[18] showed the metabolic benefit of ketone metabolism through the administration of an exogenous ketone drink to athletes.

Methods: Athletes ingested of a drink containing exogenous ketone + carbohydrate or carbohydrate alone according to their body weights. Following an overnight fast, study participants completed bicycle exercise trials consisting of 1 hr steady-state followed by a 30 min time trial for maximum distance.

Results: Athletes cycled on average 411±162 m further over 30 min on ketone + carbohydrate versus carbohydrate equating to a mean performance improvement of 2%.

Conclusion: The physiological alterations achieved by acute nutritional ketosis may improve performance in athletes.

4. Increases Satiety

Exogenous BHB salt increases satiety through a mechanism related to the oxidation of BHB to AcAc.[21] BHB salt exhibited increased satiety in both human and animal studies.[22-23] Exogenous ketone supplementation improves blood BHB level and reduces the desire to eat.

In 2017, Stubbs et al.[23], investigated the effects of an exogenous ketone on increased satiety.

Methods: Following an overnight fast, subjects with normal body weight consumed 1.9 kcal/kg of exogenous ketone, or isocaloric dextrose, in similar drinks. A three-measure visual analogue scale was used to measure hunger, fullness, and desire to eat.

Results: Subjects reported increased fullness (satiety) while hunger and desire to eat were significantly suppressed 1.5 hours after consumption of exogenous ketone, compared with consumption of isocaloric dextrose.

Conclusion: Exogenous ketone drinks reduced hunger and desire to eat, accompanied by decreased levels of the hunger hormone, ghrelin, compared with dextrose drinks.

5. Accelerated State of Ketosis

Oral BHB salts increase plasma ketone levels. [24,25] They help consumers effectively and efficiently achieve ketosis. Compared to various ketosis strategies, oral BHB salts provide a safe and effective regimen to maximize the benefits of low carb/ketogenic diets.

Recently, Stubbs et al., [24] studied the metabolism of drinks containing ketone salts

Methods: In the trial, investigators researched the blood BHB concentrations of 15 healthy participants following ingestion of 3.2 mmol/kg of BHB ketone salts

Results: The ketone salt drink elevated blood BHB concentrations and returned to baseline within 3–4 h.

Conclusion: Exogenous ketone drinks are a practical, efficacious way to achieve ketosis.

Summary

The ketogenic movement is rapidly growing across the globe as more of our population seek better health and quality of life. The use of BHB supplementation has grown in tandem with this trend, opening up a new market for supplement innovation. Ketond is the market leader and consumers brand of choice when it comes to premium and clinically proven supplements that support all dietary lifestyles.

Ketond® supplements that contain BHB provide a wide array of consumers with key benefits including increased energy, performance, focus and improved body composition. Supported by an ever expanding pool of scientific data, the number of people using BHBs continues to grow and the number of people using Ketond grows even faster.

Ketond® uses the purest, safest form of BHB that safely provides solid benefits to all individuals following ketogenic diets, exercise regimens and those requiring more energy or mentality clarity.

References

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[2]. M. D. Laird, P. Clerc, B. M. Polster, et al., Augmentation of normal and glutamate-impaired neuronal respiratory capacity by exogenous alternative biofuels. Translational Stroke Research, 2013, 4(6):643.
[3]. T. Shimazu, M. D. Hirschey, J. Newman, et al. Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science, 2013, 339(6116):211-214.
[4]. C. L. Robertson, S. Scafidi, M. C. McKenna, et al., Mitochondrial mechanisms of cell death and neuroprotection in pediatric ischemic and traumatic brain injury. Exp Neurol. 2009, 218(2):371–80.
[5]. K. Sato, Y. Kashiwaya, C. A. Keon, et al. Insulin, ketone bodies, and mitochondrial energy transduction. FASEB J. 1995;9(8):651–8.
[6]. M. Maalouf, P. G. Sullivan, L. Davis, et al., Ketones inhibit mitochondrial production of reactive oxygen species production following glutamate excitotoxicity by increasing NADH oxidation. Neuroscience, 2007, 145:256–264.
[7]. J. C. Newman, E. Verdin, Ketone bodies as signaling metabolites. Trends Endocrinol Metab. 2014, 25(1):42–52.
[8]. M. Robinson, D. H. Williamson. Physiological roles of ketone bodies as substrates and signals in mammalian tissues. Physiol. Rev., 1980;60(1):143–87.
[9]. R. L. Veech, B. Chance, Y. Kashiwaya, et al., Ketone bodies, potential therapeutic uses. IUBMB Life. 2001;51(4):241–7.
[10]. A. K. P. Taggart, J. Kero, X. D. Gan, et al., D-beta-hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMAG. Journal of Biological Chemistry, 2005, 280:26649–26652.
[11]. G. A. Reichard, O. E. Owen, A. C. Haff, et al., Ketone-body production and oxidation in fasting obese humans, J. Clin. Invest. 1974, 53 (2):508–515.
[12]. J. S. Volek, T. Noakes, S. D. Phinney, Rethinking fat as a fuel for endurance exercise. European journal of sport science, 2015, 15(1):13.
[13]. M. Suzuki, M. Suzuki, K. Sato, et al. Effect of beta-hydroxybutyrate, a cerebral function improving agent, on cerebral hypoxia, anoxia and ischemia in mice and rats. Japanese Journal of Pharmacology, 2001, 87(2):143.
[14]. A. J. Murray, N. S. Knight, M. A. Cole, et al., Novel ketone diet enhances physical and cognitive performance, FASEB J. 2016, 30, 4021–4032.
[15]. R. L. Veech, 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(3):309–19.
[16]. K. Sato, Y. Kashiwaya, C. A. Keon, et al. Insulin, ketone bodies, and mitochondrial energy transduction. FASEB J. 1995;9(8):651–8.
[17]. S. C. Burgess, K. Iizuka, N. H. Jeoung, et al. Carbohydrate-response element-binding protein deletion alters substrate utilization producing an energy-deficient liver. Journal of Biological Chemistry, 2008, 283(3):1670.
[18]. P. J. Cox, T. Kirk, T. Ashmore, et al., Nutritional ketosis alters fuel preference and thereby endurance performance in athletes, Cell Metabolism 2016, 24, 256–268.
[19]. M. Evans, K. E. Cogan and B. Egan, Metabolism of ketone bodies during exercise and training: physiological basis for exogenous supplementation. J Physiol., 2017, 595(9):2857.
[20]. D. A. Holdsworth, P. J. Cox, T. Kirk, et al., A ketone ester drink increases postexercise muscle glycogen synthesis in humans. Medicine & Science in Sports & Exercise, 2017, 49(9):1789.
[21]. W. Langhans, F. Wiesenreiter, E. Scharrer, Different effects of subcutaneous D, L-3-hydroxybutyrate and acetoacetate injections on food intake in rats. Physiology & Behavior, 1983, 31(4):483-486.
[22]. R. Rossi, S. Dörig, P. E. Del, et al., Suppression of Feed Intake after Parenteral Administration of D-beta- Hydroxybutyrate in Pygmy Goats. J Vet. Med. A Physiol. Pathol. Clin. Med., 2000, 47(1):9.
[23]. B. J. Stubbs, P. J. Cox, R.D. Evans, et al., A Ketone Ester Drink Lowers Human Ghrelin and Appetite. Obesity, 2017, 0.
[24]. B.J. Stubbs, P. J. Cox, et al., Acute nutritional ketosis: implications for exercise performance and metabolism. Frontiers in Physiology, 2017, 8.
[25]. B. Plecko, S. Stoeckler-Ipsiroglu, E. Schober, et al., Oral β-Hydroxybutyrate Supplementation in Two Patients with Hyperinsulinemic Hypoglycemia: Monitoring of β-Hydroxybutyrate Levels in Blood and Cerebrospinal Fluid, and in the Brain by In Vivo Magnetic Resonance Spectroscopy. Pediatric Research, 2002, 52(2):301.

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