A ketogenic diet, which induces a state of ketosis (raised concentrations of ketone bodies in the blood), is often used to help with weight loss. Supplementation with exogenous ketones, which also increases blood concentrations of ketone bodies, has been touted as a simple alternative to a ketogenic diet. However, is this approach an effective tool for weight loss?
Evidence from in vitro studies shows that beta-hydroxybutyrate, a ketone body, can regulate pathways involved in sympathetic nervous system (“fight or flight”) activation and energy expenditure.[1] Preclinical studies in rats have also found that infusing beta-hydroxybutyrate can stimulate leptin — a hormone that regulates food and energy intake — and decrease body weight.[2] Further studies in rodents have shown that short-term feeding with a ketone ester can decrease ad libitum food intake[3] and cause weight loss.[4][5][6] However, not all preclinical studies have found beneficial effects of exogenous ketones on total daily energy expenditure or body weight.[7]
Although preclinical studies show promise, the clinical effects of exogenous ketones on energy intake and weight loss are not well understood. A series of small randomized controlled trials has found that a single dose of exogenous ketones (either beta-hydroxybutyrate or a ketone ester) can slow the gastric emptying rate,[8] lower feelings of hunger and appetite,[9][10] increase feelings of satiety and fullness,[10] and decrease energy intake during ad libitum eating.[11]
However, some trials do not support the findings described above, showing no effects on hunger,[11] fullness,[11] or appetite.[8] Furthermore, there are mixed effects on the plasma concentrations of gut hormones that regulate appetite and satiety. For example, exogenous ketones do not affect glucose-dependent insulinotropic polypeptide [8][10] but can decrease ghrelin[10][9] and peptide YY.[9] Meanwhile, there was an increase in cholecystokinin in some[8] but not all[10] studies and a decrease in glucagon-like peptide 1 (GLP-1) in some[9] but not all[8][10] studies.
Additionally, the clinical effects on weight loss are also mixed. One randomized controlled crossover study found that 14 days of daily supplementation with beta-hydroxybutyrate led to an approximately 1 kg (2 lb) decrease in body weight in 15 people with obesity,[12] but another trial in 20 women did not find that beta-hydroxybutyrate influenced diet-induced weight-loss.[13]
In summary, while preclinical evidence is compelling, clinical evidence is sparse, and larger, high-quality randomized controlled trials are needed to make conclusions about the efficacy of exogenous ketones on weight loss and the regulation of energy intake.