Summary of findings 1. Ketogenic diet (KD) compared to usual care for children with drug‐resistant epilepsy.

Ketogenic diet (KD) compared to usual care for children with drug‐resistant epilepsy
Patient or population: children (aged 1 to 18 years) with drug‐resistant epilepsy Setting: outpatients Intervention: KD (including: classic KD (4:1), classic KD and MCT KD combined, MAD, MCT KD, and sMAD) Comparison: control intervention (usual care)
Outcomes	Anticipated absolute effects* (95% CI)		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with usual care	Risk with KD
Seizure freedom (100% reduction in seizure frequency) Follow‐up: 3 months to 4 months	Study population		RR 3.16 (1.20 to 8.35)	385 (4 RCTs)	⊕⊝⊝⊝ Very lowa,c
	21 per 1000	66 per 1000 (25 to 174)
50% or greater reduction in seizure frequency Follow‐up: 3 months to 4 months	Studypopulation		RR5.80 (3.48 to 9.65)	385 (4 RCTs)	⊕⊕⊝⊝ Lowa,b
	78 per 1000	453 per 1000 (272 to 754)
Adverse effects Follow‐up: 3 months to 4 months	The most frequent adverse effects reported by participants in dietary intervention groups were: vomiting, constipation and diarrhoea. These adverse effects were also commonly reported by participants in the usual care groups. Other less common adverse effects reported included: dysphagia, lethargy, lower respiratory tract infection, hyperammonaemic encephalopathy, weight loss, nausea, infections (pneumonia, sepsis), acute pancreatitis, decrease in bone matrix density, gallstones, fatty liver, nephrocalcinosis, hypercholesterolaemia, status epilepticus, acidosis, dehydration, tachycardia, hypoglycaemia, hunger, abdominal pain, clinically relevant reduction in height, hypercalcinaemia and renal stones.			425 (5 RCTs)	⊕⊕⊝⊝ Lowa,d
Cognition and behaviour Follow‐up: 4 months	Children randomised to KD were more active (P = 0.005), more productive (P = 0.039) and less anxious (P = 0.049) after four months, than children randomised to the usual care group.			57 (1 RCT)	⊕⊝⊝⊝ Very lowa,c,d
Quality of life Follow‐up: 4 months	There were no significant differences in QALYs between KD and usual care treatment groups at four or 16 months.			57 (1 RCT)	⊕⊝⊝⊝ Very lowa,c,d
Treatment withdrawal Follow‐up: 3 months to 6 months	Studypopulation		RR 1.08 (0.74 to 1.57)	425 (5 RCTs)	⊕⊕⊝⊝ Lowa,b
	184 per 1000	198 per 1000 (136 to 288)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; KD: ketogenic diet; MAD: modified Atkins diet; MCT: medium‐chain triglyceride; QALY: quality of life‐adjusted year; RCT: randomised controlled trial RR: risk ratio; sMAD: simplified modified Atkins diet
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

^aDowngraded once due to risk of bias: some included studies were not blinded, had missing data or unclear methodological details reported.
^bDowngraded once due to imprecision: low overall sample size, plus low number of events (< 200). Confidence in results from small number of participants is low.
^cDowngraded twice due to imprecision: low overall sample size, plus low number of events (< 50). Confidence in results from small number of participants is low.
^dDowngraded once due to imprecision: a narrative synthesis was used for this outcome.