Journal Article

Effects of ketogenic diet on health outcomes: an umbrella review of meta-analyses of randomized clinical trials

Phisalprapa, Pochamana, Veettil, Sajesh K., Patikorn, Chanthawat, Varady, Krista A., Lee, Yeong Yeh, Saidoung, Pantakarn, Chaiyakunapruk, Nathorn, Pham, Tuan

2023

Overview

Background Systematic reviews and meta-analyses of randomized clinical trials (RCTs) have reported the benefits of ketogenic diets (KD) in various participants such as patients with epilepsy and adults with overweight or obesity . Nevertheless, there has been little synthesis of the strength and quality of this evidence in aggregate. 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 A 1c , 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adult / Adults / Bias / Biomedicine / Blood pressure / Body fat / Body mass index / Body Weight / Carbohydrates / Cardiovascular Diseases / Cholesterol / Cholesterol, LDL / Clinical trials / Convulsions & seizures / Diet / Diet, Ketogenic / Epilepsy / Heart rate / Hemoglobin / High carbohydrate diet / High density lipoprotein / High fat diet / Humans / Ketegenic diet / Ketogenesis / Ketogenic diet / Low carbohydrate diet / Low density lipoprotein / Low fat diet / Medical research / Medicine / Medicine & Public Health / Medicine, Experimental / Meta-analysis / Meta-Analysis as Topic / Muscles / Nutrient deficiency / Obesity / Overweight / Patient outcomes / Randomized Controlled Trials as Topic / Research Article / Seizure / Seizures / Statistical analysis / Systematic review / Triglycerides / Umbrella review / Weight control / Weight loss / Weight reduction