Comparison 1. PKU participants started on diet at diagnosis: Diet continuation versus discontinuation/relaxation later.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Blood phenylalanine level (micromol/l)	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
1.1 Blood phenylalanine level (0 to 3 months)	2	41	Mean Difference (IV, Fixed, 95% CI)	‐698.67 [‐869.44, ‐527.89]
1.2 Blood phenylalanine level (4 to 6 months)	1	10	Mean Difference (IV, Fixed, 95% CI)	‐871.20 [‐1261.53, ‐480.87]
1.3 Blood phenylalanine level (7 to 12 months)	1	10	Mean Difference (IV, Fixed, 95% CI)	‐913.5 [‐1370.42, ‐456.58]
1.4 Blood phenylalanine level (>12 months)	2	90	Mean Difference (IV, Fixed, 95% CI)	‐751.54 [‐883.41, ‐619.67]
2 Weight	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
2.1 Weight (0 to 3 month)	1	88	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐0.47, 0.07]
2.2 Weight (4 to 6 months)	1	88	Mean Difference (IV, Fixed, 95% CI)	‐0.20 [‐0.56, 0.16]
2.3 Weight (7 to 12 months)	1	88	Mean Difference (IV, Fixed, 95% CI)	‐0.10 [‐0.58, 0.38]
3 Intelligence Quotient (IQ)	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
3.1 IQ (> 12 months)	1	115	Mean Difference (IV, Fixed, 95% CI)	5.0 [0.40, 9.60]
4 Calorie intake (kcal/kg)	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
4.1 Calorie intake (0 to 3 months)	1	88	Mean Difference (IV, Fixed, 95% CI)	‐1.0 [‐11.06, 9.06]
4.2 Calorie intake (4 to 6 months)	1	88	Mean Difference (IV, Fixed, 95% CI)	‐3.0 [‐10.12, 4.12]
4.3 Calorie intake (7 to 12 months)	1	88	Mean Difference (IV, Fixed, 95% CI)	‐6.0 [‐12.51, 0.51]
5 Protein intake (g/kg)	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
5.1 Protein intake (0 to 3 months)	1	88	Mean Difference (IV, Fixed, 95% CI)	0.0 [‐0.40, 0.40]
5.2 Protein intake (4 to 6 months)	1	88	Mean Difference (IV, Fixed, 95% CI)	‐0.10 [‐0.33, 0.13]
5.3 Protein intake (7 to 12 months)	1	88	Mean Difference (IV, Fixed, 95% CI)	‐0.10 [‐0.31, 0.11]