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. 2023 May 25;21(1):196.
doi: 10.1186/s12916-023-02874-y.

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

Chanthawat Patikorn  1   2 , Pantakarn Saidoung  1 , Tuan Pham  3 , Pochamana Phisalprapa  4 , Yeong Yeh Lee  5 , Krista A Varady  6 , Sajesh K Veettil  7 , Nathorn Chaiyakunapruk  8   9
Affiliations

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

Chanthawat Patikorn et al. BMC Med. .

Abstract

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 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.

Keywords: Ketegenic diet; Meta-analysis; Seizure; Systematic review; Umbrella review; Weight loss.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Study selection flow of meta-analyses. Abbreviation: CDSR, Cochrane database of systematic review
Fig. 2
Fig. 2
Associations of Types of Ketogenic Diet with Health Outcomes. Abbreviations: BMI, body mass index, DBP, diastolic blood pressure; GRADE, Grading of Recommendations, Assessment, Development, and Evaluations; HbA1c, hemoglobin A1c; HDL-C, high-density lipoprotein cholesterol; HOMA-IR, homeostatic model of insulin resistance; LDL-C, low-density lipoprotein cholesterol; SBP, systolic blood pressure; TEI, total energy intake
See this image and copyright information in PMC

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