Booster Ketones: Battling Hunger – Hunger Hormones and Exogenous Ketones
Ketogenic diets (KDs) consist of very low carbohydrate intake with a variable amount of fat. During a KD, the insufficient supply of carbohydrate for metabolic needs (20 g/d or 5% of total daily energy intake) forces the body to use fat primarily as a fuel source. Although the original KD had a 4:1 lipid/nonlipid ratio, with a very high percentage of daily energy intake from fat (≅ 80%) 1, many different schemes have been used to lower the lipid/nonlipid ratio, such as no restrictions in daily energy intake, with ad libitum fat and a relatively high amount of protein (up to 1.8 g/kg of body weight per day). KDs have become popular in recent decades (mainly after Atkins’ book was published 2) as effective tools for weight loss 3.
Even though there is no universal agreement, a recent meta‐analysis suggests that KDs are effective as weight loss therapy, at least in the short to medium term 4. Unfortunately, the precise mechanism of action promoting weight loss is still a subject of debate.
Four main possible reasons have been suggested 3 for the KD’s effectiveness on weight loss (listed in order of the strength of evidence): 1 appetite reduction (strong evidence), 2 reduced lipogenesis and increased fat oxidation (strong evidence), 3 a thermic effect of proteins (strong/medium evidence), and 4 increased resting energy expenditure (weak evidence).
Regarding the first point, some authors have proposed that there is a direct appetite‐suppressant action of ketone bodies, especially by D‐β‐hydroxybutyrate (BHB), which may act as an energy/satiety signal. There is some evidence suggesting that a KD could reduce the so‐called yo‐yo effect (weight cycling) 5, mainly through a reduction of orexigenic hormones 6.
For this reason, the new study by Stubbs and colleagues 7 published in this issue of Obesity is of particular interest. The authors directly investigated the effect of a new ketone ester (KE) on circulating levels of glucose, insulin, ghrelin, glucagon‐like peptide 1 (GLP‐1), and peptide tyrosine tyrosine (PYY), as well as on psychological parameters such as hunger, fullness, and the desire to eat 7. Moreover, with the administration of exogenous ketone, they separated the effects of low blood glucose from those of high blood ketone concentrations. Previous studies from the same group have elucidated the physiology of this molecule, (R)‐3‐hydroxybutyl (R)‐3‐hydroxybutyrate KE, showing its safety and effectiveness to elevate blood ketone levels 8. In the present study, Stubbs and colleagues 7demonstrated that after consumption of this KE drink, plasma insulin, ghrelin, GLP‐1, and PYY levels were significantly lower compared with those following a dextrose drink. Reported hunger and the desire to eat were also lower, whereas fullness was higher after the KE drink.
Highly interesting, in this author’s opinion, is the good correlation between blood BHB and subjective hunger data. These results suggest that the level of blood BHB may be a pillar in appetite control during a diet protocol. Less promising appears to be the down regulation of the anorexigenic hormones GLP‐1 and PYY, prompting some caution in the use of KE as a weight loss strategy (Figure 1). Future studies that compare blood BHB levels and reported hunger during a standard KD and after KE administration can hopefully be designed to examine the reciprocal influences of high blood BHB and normal/low levels of blood glucose.