Review question
We reviewed the evidence that in people with PKU (who commenced the diet at diagnosis and either continued on the diet or relaxed the diet later in life) tyrosine supplementation alongside, or instead of low phenylalanine diet, improves: intelligence; neuropsychological performance; growth and nutritional status; mortality rate; and quality of life. This is an update of previously published versions of this review.
Background
Phenylketonuria is an inherited disease. People with phenylketonuria can either not process phenylalanine from their diet at all or only in part. High blood levels of phenylalanine can cause brain or nerve damage. A diet avoiding foods high in phenylalanine can be hard to follow. People with phenylketonuria can have low levels of the amino acid tyrosine in their blood.
Search date
The evidence is current to: 07 December 2020.
Study characteristics
The review included three trials with 56 people with phenylketonuria aged between six and 28 years of age. Trials compared adding tyrosine or placebo (a substance which contains no medication) to a phenylalanine-restricted diet and people were selected for one treatment or the other randomly. The length of the treatment and control arms were short in all three trials and some of the outcomes considered important in this review were not measured.
Key results
Although the amount of tyrosine measured in the blood of those taking the supplement was higher, there were no differences noted in any other outcome measures. There is no evidence to suggest that tyrosine should be routinely added to the diet of people with phenylketonuria. Further randomised controlled trials are needed to provide more evidence. However, given this is not an active area of research, we have no plans to update this review in the future.
Quality of the evidence
The three trials considered in this review were of a good quality, but only included a small number of participants.
From the available evidence no recommendations can be made about whether tyrosine supplementation should be introduced into routine clinical practice. Further randomised controlled studies are required to provide more evidence. However, given this is not an active area of research, we have no plans to update this review in the future.
Phenylketonuria is an inherited disease for which the main treatment is the dietary restriction of the amino acid phenylalanine. The diet has to be initiated in the neonatal period to prevent or reduce mental handicap. However, the diet is very restrictive and unpalatable and can be difficult to follow. A deficiency of the amino acid tyrosine has been suggested as a cause of some of the neuropsychological problems exhibited in phenylketonuria. Therefore, this review aims to assess the efficacy of tyrosine supplementation for phenylketonuria. This is an update of previously published versions of this review.
To assess the effects of tyrosine supplementation alongside or instead of a phenylalanine-restricted diet for people with phenylketonuria, who commenced on diet at diagnosis and either continued on the diet or relaxed the diet later in life. To assess the evidence that tyrosine supplementation alongside, or instead of a phenylalanine-restricted diet improves intelligence, neuropsychological performance, growth and nutritional status, mortality rate and quality of life.
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register which is comprised of references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Additional studies were identified from handsearches of the Journal of Inherited Metabolic Disease (from inception in 1978 to 1998). The manufacturers of prescribable dietary products used in the treatment of phenylketonuria were also contacted for further references.
Date of the most recent search of the Group's Inborn Errors of Metabolism Trials Register: 07 December 2020.
All randomised or quasi-randomised trials investigating the use of tyrosine supplementation versus placebo in people with phenylketonuria in addition to, or instead of, a phenylalanine-restricted diet. People treated for maternal phenylketonuria were excluded.
Two authors independently assessed the trial eligibility, methodological quality and extracted the data.
Six trials were found, of which three trials reporting the results of a total of 56 participants, were suitable for inclusion in the review. The blood tyrosine concentrations were significantly higher in the participants receiving tyrosine supplements than those in the placebo group, mean difference 23.46 (95% confidence interval 12.87 to 34.05). No significant differences were found between any of the other outcomes measured. The trials were assessed as having a low to moderate risk of bias across several domains.