Effect of Ketosis on Appetite Hormones

One of the most remarkable clinical observations in people embarking on severely calorie-restricted ketogenic diets, is the almost complete lack of hunger that occurs within a few days of dieting.

Although clinically well described, the biological basis for this “appetite suppressant” effect of ketosis is less well understood.

Now, Priya Sumithran and colleagues from Melbourne University, Australia, in a paper published in the European Journal of Clinical Nutrition, describe the hormonal alterations associated with weight loss induced by a ketogenic diet.

Their study included 39 non-diabetic overweight or obese subjects who completed an 8-week ketogenic very-low-energy diet (VLED), followed by 2 weeks of reintroduction of foods.

During the ketogenic VLED, subjects lost 13% of initial weight and fasting ketones (β-hydroxybutyrate) increased significantly as expected.

This increase in ketones was accompanied with a suppression of the increase in ghrelin normally seen with weight loss. weight-reduced subjects also had significantly lower leptin, peptide YY, amylin and pancreatic polypeptide levels, compared with week 10 values. In contrast, Fasting GIP, glucagon-like peptide 1 and CCK were not different in weight-reduced subjects between weeks 8 and 10. In addition subjective ratings of appetite were lower at week 8 than after refeeding.

The authors describe their significant findings regarding the effect of ketosis on ghrelin as follows:

“In mildly ketotic participants, the increase in the circulating concentration of ghrelin, a potent stimulator of appetite, which otherwise occurs as a result of diet-induced weight loss, was suppressed. The present findings are in keeping with a recent report of a 12-week carbohydrate-restricted diet, during which 28 overweight subjects lost ~6.5% of their starting weight without a significant change in fasting plasma ghrelin. In our study, postprandial ghrelin concentrations were also measured, and found to remain unchanged following weight loss as long as subjects were ketotic. After refeeding, fasting and postprandial ghrelin concentrations rose significantly.”

No doubt, these findings provide a plausible biological basis for the clinical observation of suppressed hunger and appetite in individuals on ketogenic diets and may well explain the better long-term adherence to such diets in clinical practice.

The observed increase in ghrelin on “refeeding” is also in line with the often observed immediate onset of “cravings” and discontinuation of the diet the minute patients come off their strictly ketogenic regimen. Thus, for example, patients paradoxically often find the highly caloric restrictive phase of total liquid formula diets (e.g. Optifast) far easier to comply with that the loosening of this regimen with the introduction of “real” food.

In conclusion, this study clearly demonstrates that circulating concentrations of several hormones and nutrients which influence appetite are significantly altered after weight loss induced by a ketogenic diet, compared with after refeeding.

Clearly, a better understanding of these mechanisms could one day lead to interventions that may help improve the long-term adherence to dietary caloric restriction.

AMS
Edmonton, AB

Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, & Proietto J (2013). Ketosis and appetite-mediating nutrients and hormones after weight loss. European journal of clinical nutrition PMID: 23632752