Effects of Differing Levels of Carbohydrate Restriction on Mood Achievement of Nutritional Ketosis, and Symptoms of Carbohydrate Withdrawal in Healthy Adults: A Randomized Clinical Trial

Objectives: To our knowledge, minimal research exists on the effects of diets differing in carbohydrate restriction on symptoms of carbohydrate withdrawal and mood, and the achievement of nutritional ketosis (NK). The aim of this study was to compare ketonaemia, symptoms of carbohydrate withdrawal, and mood. We hypothesized that a moderate carbohydrate restriction would result in fewer symptoms and a reduced effect on mood. Methods: Seventy-seven healthy participants (25 men and 52 women; mean age: 39 y, range: 25–49; mean body mass index 27 kg/m2, range: 20–39) were randomized to receive either a very-low-carbohydrate ketogenic diet (VLCKD), low-carbohydrate diet (LCD), or moderately low-carbohydrate diet (MCD), containing 5%, 15%, and 25% total energy (TE) from carbohydrate, respectively, for 3 wk. Fasting blood ketone measures were recorded daily upon waking along with a data from symptom questionnaire and a 5-point mood-state scale. Using analysis of variance and a 5% two-sided α level to determine statistical significance, between-group outcomes were analyzed. Additional association and analyses were conducted by multiple linear regression. Results: In 75 of 77 initial participants included for analysis, mean serum levels of β-hydroxybutyrate (βOHB) were increased by 0.27 ± 0.32, 0.41 ± 0.38, and 0.62 ± 0.49 mmol/L for MCD, LCD, and VLCKD, respectively (P = 0.013). The achievement of NK was consistent for both VLCKD and LCD groups and sporadic for the MCD group. Only the VLCKD group exhibited 95% confidence interval levels that were consistently ≥0.5 mmol/L. The overall mean change in sum of symptoms scores (SOSS) from baseline was 0.81 ± 2.84 (P < 0.001). Changes in SOSS were highest in the VLCKD group (1.49 ± 2.47), followed by LCD (0.65 ± 2.70) and MCD (0.18 ± 3.3; P = 0.264). Small, statistically significant increases were seen for headache severity, constipation, diarrhea, halitosis, muscle cramps and muscle weakness, and light-headedness, whereas intestinal bloating and craving for sugar and starch improved from baseline. Only halitosis (P = 0.039) and muscle weakness (P = 0.005) differed significantly between the groups. Mood improved significantly from baseline overall, but there was no significant difference between groups (P = 0.181) Conclusions: Diets containing 5% TE from carbohydrates are ketogenic, but diets containing between 15% and 25% TE from carbohydrates can also result in mean βOHB ≥0.5 mmol/L. There was no meaningful difference in symptoms of carbohydrate withdrawal between diets that contain 5% to 25% TE from carbohydrate, and mood was improved overall, with no significant difference between interventions. Our conclusion, therefore, is that reduced carbohydrate diets should be prescribed by need rather than the desire to mitigate symptoms of carbohydrate withdrawal.