Effects of ketogenic diet on health outcomes: an umbrella review of meta-analyses of randomized clinical trials.
Level 1 - systematic review of randomized trials
Umbrella review of meta-analyses of randomized controlled trials
PubMed 37231411 · doi:10.1186/s12916-023-02874-y
What was done
Umbrella review searching PubMed, EMBASE, Epistemonikos, and Cochrane database of systematic reviews up to February 15, 2023, to identify meta-analyses of randomized clinical trials (RCTs) evaluating ketogenic diets (KD), ketogenic low-carbohydrate high-fat diets (K-LCHF), and very low-calorie ketogenic diets (VLCKD). Meta-analyses were re-performed using a random-effects model, and evidence quality per association was rated using GRADE criteria.
What was found
Included 17 meta-analyses covering 68 RCTs (median sample size 42 [IQR 20–104] participants; median follow-up 13 [IQR 8–36] weeks) and 115 unique associations. Fifty-one associations (44%) were statistically significant. Four associations were supported by high-quality evidence: reduced triglycerides (n = 2), reduced seizure frequency (n = 1), and increased LDL-C (n = 1). Four associations were supported by moderate-quality evidence: decreased body weight, respiratory exchange ratio, and HbA1c, plus increased total cholesterol. The remaining associations had low (17) or very low (26) quality evidence. In overweight/obese adults, VLCKD improved anthropometric and cardiometabolic markers without worsening muscle mass, LDL-C, or total cholesterol; K-LCHF reduced body weight and body fat percentage but reduced muscle mass in healthy individuals.
Why it matters
This review grades aggregate evidence on ketogenic diets, confirming robust benefits for seizure reduction, weight loss, and glycemic control alongside clinically meaningful increases in LDL and total cholesterol.
Limits
Underlying RCTs had small sample sizes (median n = 42) and short follow-up periods (median 13 weeks). Most associations (60 of 115) had low or very low evidence quality. Hard clinical endpoints such as cardiovascular events and mortality were not assessed.
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