Ketogenic Diet and Multiple Health Outcomes: An Umbrella Review of Meta-Analysis

Abstract

Numerous studies have examined the effects of ketogenic diets (KD) on health-related outcomes through meta-analyses. However, the presence of biases may compromise the reliability of conclusions. Therefore, we conducted an umbrella review to collate and appraise the strength of evidence on the efficacy of KD interventions. We conducted a comprehensive search on PubMed, EMBASE, and the Cochrane Database until April 2023 to identify meta-analyses that investigated the treatment effects of KD for multiple health conditions, which yielded 23 meta-analyses for quantitative analyses. The evidence suggests that KD could increase the levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), the respiratory exchange rate (RER), and could decrease total testosterone and testosterone levels (all p-random effects: <0.05). The combination of KD and physical activity can significantly reduce body weight and increase the levels of LDL-C and cortisol. In addition, KD was associated with seizure reduction in children, which can be explained by the ketosis state as induced by the diet. Furthermore, KD demonstrated a better alleviation effect in refractory childhood epilepsy, in terms of median effective rates for seizure reduction of ≥50%, ≥90%, and seizure freedom. However, the strength of evidence supporting the aforementioned associations was generally weak, thereby challenging their credibility. Consequently, future studies should prioritize stringent research protocols to ascertain whether KD interventions with longer intervention periods hold promise as a viable treatment option for various diseases.

Keywords: cancer; ketogenic diets; meta-analysis; obesity; overweight; seizure reduction; umbrella review.

Figure 1

Study selection profile.

Figure 2

Quantitative synthesis and evidence grading for meta-analyses of diet intervention for clinical and non-clinical health problems. SMD, standardized mean difference [5,9,24,57,58,59,64,65,66,69,70,71,72]. BMI, body mass index; DBP, diastolic blood pressure; FFM, fat-free mass; FM, fat mass; HDL, high density lipoprotein; HOMA-IR, homeostatic model assessment index of insulin resistance; HbA1c, glycated hemoglobin; HRmax, maximal heart rate during exercise; LBM, lean body mass; LDL, low density lipoprotein; RER, respiratory exchange rate; RPE, perceived exertion; SBP, systolic blood pressure; TTE, time to exhaustion; TC, total cholesterol; TG, triglycerides; VAT, visceral adipose tissue; VO2max, maximum oxygen uptake; WC, waist circumference; KD, ketogenic diet; VLCKD, very-low-carbohydrate ketogenic diets; K-LCHF, ketogenic low-carbohydrate, high-fat; MAD, modified Atkins diet; HP, high-protein; MP, moderate-protein; MD, mean difference; O, observed number of studies with positive finding; ref, reference; SMD, standardized mean difference; WMD, weighted mean difference; OR, odds ratio; RR, relative risk.

Figure 3

Quantitative synthesis and evidence grading for meta-analyses of diet intervention for clinical and non-clinical health problems OR, odds ratio [56,60,67,68,73,74]. KD, ketogenic diet; VLCKD, very-low-carbohydrate ketogenic diets; MAD, modified Atkins diet; OR, odds ratio.

Figure 4

Quantitative synthesis and evidence grading for meta-analyses of the combination of diet and physical activity interventions for clinical and non-clinical health problems. SMD, standardized mean difference [18,61,62,63]. BFP, body fat percentage; BMI, body mass index; FFM, fat-free mass; FM, fat mass; HDL, high density lipoprotein; LDL, low density lipoprotein; TC, total cholesterol; TG, triglycerides; WC, waist circumference; KD, ketogenic diet; HP, high-protein; MP, moderate-protein; MD, mean difference; O, observed number of studies with positive finding; ref, reference; SMD, standardized mean difference; WMD, weighted mean difference.