McDonald 2018.

Study characteristics
Methods	Prospective, randomised controlled trial, single‐centre, comparing two MAD interventions: 1) MAD plus KetoCal during first month, followed by MAD alone in second month (intervention) to 2) MAD alone in the first month, followed by MAD plus KetoCal during second month (control) with MAD consisting of 20 g net carbohydrates per day. The intervention was conducted for two months, with a six‐month follow‐up period.
Participants	80 adult participants aged 18 years and over, four quantifiable seizures per month minimum, failed trial of two or more AEDs. Participants were recruited from Johns Hopkins Hospital, USA; Exclusion criteria included: unwillingness to restrict carbohydrate, BMI < 18.5kg/m2, pregnant, history of kidney disease, hypercholesterolaemia, milk allergy, metabolic or mitochondrial disorder in which KDs are contraindicated, prior use of MAD for two days or more, use of KetoCal at any time, use of classical KD in the past year.
Interventions	A comparison of two MAD interventions: 1. MAD plus KetoCal during first month, followed by MAD alone in second month (intervention) to 2. MAD alone in the first month, followed by MAD plus KetoCal during second month (control) with MAD consisting of 20 g net carbohydrates per day. The intervention was conducted for two months, with a six‐month follow‐up period.
Outcomes	Seizure reduction; Dietary adherence; Tolerability; Adverse effects.
Notes	From the treatment arm, 5 participants dropped out: 1 lost to follow‐up; and 4 discontinued the intervention. Four were excluded from the 1‐month analysis due to incomplete seizure logs or change in medication. In the control arm, 13 participants dropped out: 4 elected not to start the control diet; 4 lost to follow‐up; and 5 did not adhere to the intervention. Two were excluded from the 1‐month analysis due to lack of seizure log or changes to medication; Differences is baseline demographics were noted for mean weight (185.3 +/‐ 48.5 lbs in the control group and 162.3 +/‐ 49.7 lbs in the intervention group; P = 0.039) and mean BMI (30.3 lbs/in2 in control group; 25.9 lbs/in2 in intervention group; P = 0.007). carbohydrate, BMI <18.5kg/m2; This study was supported financially by Nutricia North America.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random number allocation.
Allocation concealment (selection bias)	Unclear risk	Not stated.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Blinding was not discussed in this paper, but considering the design of the study, blinding of participants and study personnel does not seem possible.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Blinding was not discussed in this paper, but considering the design of the study, blinding of outcome assessors does not seem possible.
Incomplete outcome data (attrition bias)	Unclear risk	Unclear if ITT used in study analysis.
Selective reporting (reporting bias)	Unclear risk	Protocol unavailable.
Other bias	High risk	Power calculation based on 85% retention rate (70% retention achieved in study). Significant differences in baseline weight and BMI.