METHODS: Healthy subjects were screened not to have conditions that exerts abnormal EtCO2 nor contraindicated for KD. Subjects underwent seven days of KD while the EtCO2 and blood ketone (beta-hydroxybutyrate; β-OHB) parameters were sampled at day zero (t0) and seven (t7) of ketosis respectively. Statistically, the t-test and Pearson's coefficient were conducted to determine the changes and correlation of both parameters.
RESULTS: 12 subjects completed the study. The mean score ± standard deviation (SD) for EtCO2 were 35.08 ± 3.53 and 35.67 ± 3.31 mm Hg for t0 and t7 respectively. The mean score ±SD for β-OHB were 0.07 ± 0.08 and 0.87 ± 0.84 mmol/L for t0 and t7 respectively. There was no significant difference of EtCO2 between the period of study (p > 0.05) but the β-OHB increased during t7 (p
METHODS: To grade the evidence from published meta-analyses of RCTs that assessed the association of KD, ketogenic low-carbohydrate high-fat diet (K-LCHF), and very low-calorie KD (VLCKD) with health outcomes, PubMed, EMBASE, Epistemonikos, and Cochrane database of systematic reviews were searched up to February 15, 2023. Meta-analyses of RCTs of KD were included. Meta-analyses were re-performed using a random-effects model. The quality of evidence per association provided in meta-analyses was rated by the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) criteria as high, moderate, low, and very low.
RESULTS: We included 17 meta-analyses comprising 68 RCTs (median [interquartile range, IQR] sample size of 42 [20-104] participants and follow-up period of 13 [8-36] weeks) and 115 unique associations. There were 51 statistically significant associations (44%) of which four associations were supported by high-quality evidence (reduced triglyceride (n = 2), seizure frequency (n = 1) and increased low-density lipoprotein cholesterol (LDL-C) (n = 1)) and four associations supported by moderate-quality evidence (decrease in body weight, respiratory exchange ratio (RER), hemoglobin A1c, and increased total cholesterol). The remaining associations were supported by very low (26 associations) to low (17 associations) quality evidence. In overweight or obese adults, VLCKD was significantly associated with improvement in anthropometric and cardiometabolic outcomes without worsening muscle mass, LDL-C, and total cholesterol. K-LCHF was associated with reduced body weight and body fat percentage, but also reduced muscle mass in healthy participants.
CONCLUSIONS: This umbrella review found beneficial associations of KD supported by moderate to high-quality evidence on seizure and several cardiometabolic parameters. However, KD was associated with a clinically meaningful increase in LDL-C. Clinical trials with long-term follow-up are warranted to investigate whether the short-term effects of KD will translate to beneficial effects on clinical outcomes such as cardiovascular events and mortality.