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Exogenous Ketone Salts Impact Blood Ketone Levels

BHB salts transiently increase in blood ketones in healthy adults

by Lewis Chang, PhD

A ketogenic diet is a dietary approach that promotes nutritional ketosis by restricting carbohydrates and increasing the intake of fat with adequate consumption of protein. According to systematic reviews and meta-analyses, ketogenic diets may prevent an increase in appetite on reduced calorie diets1 and help achieve long-term body weight reduction.2 Emerging studies have suggested that ketogenic diets may be beneficial in diabetes management and exercise performance.3,4

Compliance with ketogenic diets can be difficult because the amount of carbohydrate allowed is very low (usually <50 g/day), with 60-70% of total energy coming from dietary fat. Therefore, there has been a surge of commercially available products supplying exogenous ketones (such as beta-hydroxybutyrate [βHB] salts) to enhance compliance and facilitate the induction and maintenance of ketosis. However, there has been insufficient information in scientific literature on the oral response to exogenous ketone products in human subjects.

A new study recently published in the Journal of Nutritional Health & Food Engineering investigated the circulating βHB response in healthy volunteers following acute consumption of βHB salts.5 In a randomized, cross-over design, 10 men and women consumed placebo control or exogenous ketone salts, providing either 11.7 g (full dose) or 5.85 g (half dose) of βHB, with a wash-out period between intakes.5

The investigators found that:5

  • Consumption of 11.7 g βHB led to a significant increase in circulating βHB levels during the first hour, reaching ~1 mmol/L within 15 minutes compared with the placebo. The rise in βHB was comparable to that seen in physiological ketogenic situations, such as when following a ketogenic diet
  • Intake of the half dose of βHB led to increases in βHB levels between the full dose and the placebo
  • No severe gastrointestinal distress was observed during the study


These data are in line with another recently published human study in which circulating βHB levels reached 1.0 mmol/L during the first hour after 15 subjects consumed 12 g βHB.6 These studies provide evidence of acute-dose efficacy and safety of exogenous βHB salt supplements.5-6 However, long-term safety and efficacy of exogenous ketones in humans remain to be investigated.

Why is this Clinically Relevant?

  • Short-term consumption of exogenous ketones may help maintain circulating levels of ketone bodies within the range of nutritional ketosis
  • Exogenous ketone products may help support a ketogenic lifestyle by facilitating the keto-adaptation process
  • Long-term safety and efficacy of these exogenous ketones remain to be studied

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  1. Gibson AA, Seimon RV, Lee CM, et al. Do ketogenic diets really suppress appetite? A systematic review and meta-analysis. Obes Rev. 2015;16(1):64-76.
  2. 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(7):1178-1187.
  3. Feinman RD, Pogozelski WK, Astrup A, et al. Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base. Nutrition. 2015;31(1):1-13.
  4. Volek JS, Noakes T, Phinney SD. Rethinking fat as a fuel for endurance exercise. Eur J Sport Sci. 2015;15(1):13-20.
  5. O’Connor A, Chang J, Brownlow M, Contractor N. Acute oral intake of beta-hydroxybutyrate in a pilot study transiently increased its capillary levels in healthy volunteers. J Nutr Health Food Eng. 2018;8(4):324-328.
  6. Stubbs BJ, Cox PJ, Evans RD, et al. On the Metabolism of Exogenous Ketones in Humans. Frontiers in Physiology. 2017;8(848).

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