Relationship between Ketones, Ghrelin, and, Appetite on Isocaloric Diets with Varying Carbohydrate Quality and Amount: Results from a Randomized Controlled Trial in People with Obesity (CARBFUNC).

The Journal of nutrition. 2023;153(2):459-469
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Diet induced fat loss can result in an increase in appetite, contributing to weight loss regression and reduced diet adherence after successful weight loss. Certain diets such as those very high in fat and low in carbohydrates, which switches the body’s main fuel source to fat instead of sugar, have been shown to suppress feelings of hunger after weight loss. When this occurs it is known as ketosis and these diets may suppress a hormone, which is responsible for feelings of hunger, known as ghrelin. Diets which focus on the quality of the carbohydrate being consumed have also been shown to affect appetite. This randomised control trial of 193 individuals aimed to determine the effect of ketosis and the quality of carbohydrates on ghrelin and feelings of hunger. The results showed that ketosis during a low carbohydrate high fat diet was insufficient to decrease levels of the hunger hormone ghrelin and increased feelings of hunger. Carbohydrate quality also failed to decrease feelings of hunger or the hunger hormone ghrelin. It was concluded that regardless of the diet, fat loss resulted in feelings of hunger, which could not be supressed by a high-quality carbohydrate diet or a low carbohydrate high fat diet. This study could be used by health care professionals to understand that weight loss may be hindered by an increase in appetite. If this occurs, strategies to limit the hunger hormone ghrelin may be successful in maintaining weight loss.

Abstract

BACKGROUND Low-carbohydrate high-fat (LCHF) diets may suppress the increase in appetite otherwise seen after diet-induced fat loss. However, studies of diets without severe energy restriction are lacking, and the effects of carbohydrate quality relative to quantity have not been directly compared. OBJECTIVES To evaluated short- (3 mo) and long-term (12 mo) changes in fasting plasma concentrations of total ghrelin, β-hydroxybutyrate (βHB), and subjective feelings of appetite on 3 isocaloric eating patterns within a moderate caloric range (2000-2500 kcal/d) and with varying carbohydrate quality or quantity. METHODS We performed a randomized controlled trial of 193 adults with obesity, comparing eating patterns based on "acellular" carbohydrate sources (e.g., flour-based whole-grain products; comparator arm), "cellular" carbohydrate sources (minimally processed foods with intact cellular structures), or LCHF principles. Outcomes were compared by an intention-to-treat analysis using constrained linear mixed modeling. This trial was registered at clinicaltrials.gov as NCT03401970. RESULTS Of the 193 adults, 118 (61%) and 57 (30%) completed 3 and 12 mo of follow-up. Throughout the intervention, intakes of protein and energy were similar with all 3 eating patterns, with comparable reductions in body weight (5%-7%) and visceral fat volume (12%-17%) after 12 mo. After 3 mo, ghrelin increased significantly with the acellular (mean: 46 pg/mL; 95% CI: 11, 81) and cellular (mean: 54 pg/mL; 95% CI: 21, 88) diets but not with the LCHF diet (mean: 11 pg/mL; 95% CI: -16, 38). Although βHB increased significantly more with the LCHF diet than with the acellular diet after 3 m (mean: 0.16 mmol/L; 95% CI: 0.09, 0.24), this did not correspond to a significant group difference in ghrelin (unless the 2 high-carbohydrate groups were combined [mean: -39.6 pg/mL; 95% CI: -76, -3.3]). No significant between-group differences were seen in feelings of hunger. CONCLUSIONS Modestly energy-restricted isocaloric diets differing in carbohydrate cellularity and amount showed no significant differences in fasting total ghrelin or subjective hunger feelings. An increase in ketones with the LCHF diet to 0.3-0.4 mmol/L was insufficient to substantially curb increases in fasting ghrelin during fat loss.

Lifestyle medicine

Fundamental Clinical Imbalances : Hormonal ; Immune and inflammation
Patient Centred Factors : Mediators/Obesity
Environmental Inputs : Diet ; Nutrients
Personal Lifestyle Factors : Nutrition
Functional Laboratory Testing : Blood

Methodological quality

Jadad score : 2
Allocation concealment : No

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