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).
Level 2 - randomized trial
Individual randomized controlled trial.
PubMed 36894239 · doi:10.1016/j.tjnut.2022.12.030
What was done
The randomized controlled trial (CARBFUNC) evaluated 193 adults with obesity assigned to one of three isocaloric, moderately energy-restricted diets (2000–2500 kcal/day) differing in carbohydrate quality or quantity: acellular carbohydrates (flour-based whole-grain products; comparator), cellular carbohydrates (minimally processed foods with intact cellular structure), or a low-carbohydrate high-fat (LCHF) diet. Intention-to-treat analysis using constrained linear mixed modeling evaluated short-term (3 months) and long-term (12 months) changes in fasting plasma concentrations of total ghrelin, beta-hydroxybutyrate (βHB), and subjective appetite ratings.
What was found
At 12 months, all 3 eating patterns showed similar reductions in body weight (5%–7%) and visceral fat volume (12%–17%) alongside similar protein and energy intakes. After 3 months, fasting 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 LCHF than the acellular diet at 3 months (mean: 0.16 mmol/L; 95% CI: 0.09, 0.24; achieving 0.3–0.4 mmol/L), this did not produce a statistically significant group difference in ghrelin unless the two high-carbohydrate groups were pooled (mean: -39.6 pg/mL; 95% CI: -76, -3.3). No significant between-group differences were observed in feelings of hunger.
Why it matters
This trial directly compares the appetite and hormonal effects of carbohydrate cellularity against carbohydrate restriction under non-severe energy restriction. The modest ketosis achieved on a moderate-calorie LCHF diet was insufficient to meaningfully prevent the rise in fasting ghrelin or curb subjective hunger during fat loss relative to cellular or acellular carbohydrate sources.
Limits
Attrition was substantial, with only 118 of 193 participants (61%) completing 3 months and 57 (30%) completing 12 months. The study evaluated fasting appetite markers rather than postprandial responses, and the degree of ketosis achieved was mild.
Cited by
- supports Individuals on high-carbohydrate diets almost never have blood beta-hydroxybutyrate levels above 0.3 millimolar.