***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Aim : To evaluate the effects of phenylalanine (Phe)‐free essential amino acid ( AA ) tablets enriched in tyrosine and tryptophan on the performance of intellectually disabled adult patients with untreated phenylketonuria ( PKU ) . Methods : Phe‐free AA tablets and placebo tablets were administered to 19 untreated PKU subjects on a normal diet for 6 mo in a prospect i ve double‐blinded crossover study . The adaptive behaviour of the patients was tested prior to the study and at 6 and 12 mo after the start , using a simplified version of the Vinel and Adaptive Behaviour Scale . For each sub‐domain , the patients were rated either “ 0 ” ( for poor performance ) or “ 1 ” ( for good performance ) . Neurological signs and symptoms and specific behavioural characteristics were recorded monthly by caretakers . Every 6 mo , neurological examination of the patients was performed , and the caretakers were interviewed . The statistical significance of the results was tested by means of the Fisher 's exact and Wilcoxon tests . Results : The most significant changes were an improved concentration and the development of a meaningful smile , which were observed in 44 % and 43 % of the patients on AA tablet treatment , respectively , but not patients on placebo . Other important but less significant changes included increased awareness of external stimuli ( 63 % ) and less self‐injury ( 43 % ) , and 40 % were smiling and laughing occasionally . The mean overall rating increased from an initial value of 6.3 to 10.1 in patients when on AA tablet treatment ( p=0.002 ) , and to 7.0 in patients when on placebo ( p=0.068 ) . The difference between active AA treatment and placebo was statistically significant ( p=0.027 ) Uneven administration of an L-amino acid protein substitute is an important contributing factor in variability in plasma phenylalanine concentrations over the 24-hour period in patients with phenylketonuria under treatment . The aim of this study was to determine whether manipulating the timing of protein substitution would reduce variability in plasma phenylalanine over 24 h. Sixteen children ( aged 1 - 11 years ) with well-controlled phenylketonuria were entered into a r and omized crossover study in which four protocol s of the same daily dose of protein substitute administration were compared . In protocol A , three equal , divided doses were given with meals over 10 h ; in protocol B , three equal doses over 14 h ; in protocol C , four equal doses over 14 h ; and in protocol D , six equal doses over 24 h ( 3 subjects only ) . Four-hourly skin puncture blood specimens were collected for 48 h in each study protocol . In protocol s A , B and C , but not in protocol D , there was wide variability in 24 h plasma phenylalanine . The median daily differences ( μmol/L ) between highest and lowest phenylalanine concentrations were : for protocol A , 140 ; for protocol B , 100 ; for protocol C , 120 ; and for protocol D , 40 . In protocol D , 97 % of all phenylalanine concentrations were below 120 μmol/L and no concentration fell below 40νmol/L. Administration of protein substitute overnight as well as during daytime produces stable and lower plasma phenylalanine concentrations and may lead to improved dietary phenylalanine tolerance BACKGROUND As part of a study on the effects of a fat-supplemented phenylalanine (phe)-free protein substitute on the fatty acid status of children with phenylketonuria ( PKU ) , the adequacy of the diets of children aged 1 - 10 years for fat and essential fatty acids ( EFA ) was assessed . METHODS Subjects r and omized in a 1 : 1 ratio to a phe-free protein substitute supplemented with EFA ( test-treatment group ) or a phe-free , fat-free protein substitute ( control group ) for 20 weeks . 3-day semi-weighed records of food intakes collected at the end of the study period . RESULTS Total fat and alpha-linolenic acid ( alpha-LA ) intakes were found to be poor in the control group ( n = 19 ) . Those in the test-treatment group ( n = 24 ) had higher fat and EFA intakes ( P < 0.05 ) , bringing intakes closer to population norms . The youngest children ( < 5 years of age ) in the control group appeared to be especially vulnerable to poor fat intakes because of the restricted diversity of their diets and , regardless of age , alpha-LA intakes by this group were poor compared with the non-PKU population . CONCLUSIONS The quantity and quality of fat in the diets of children with PKU , in particular young children , should be given careful consideration in trying to optimize the ratio of linoleic acid : alpha-LA in their diets and in satisfying the requirements of this group for fat and alpha-LA Growth and metabolic status of 25 infants with PKU were evaluated based on protain intake . Food A‐fed infants received a medical food containing 3.12 g protein equivalent per 100 kcal and Food B‐fed infants received a medical food containing 2.74 g protein equivalent per 100 kcal . Growth percentiles of infants in the Food A group were significantly greater than those for infants in the Food B group at 6 months of age ( Food A percentiles : crown‐heel length 55 , head circumference 60 , weight 73 . Food B percentiles : crown‐heel length 28 ; head circumference 29 , weight 39 ) . At study entrance , only crown‐heel length of the two groups differed ; Food B infants had a significantly greater mean crown‐heel length percentile ( p < 0.05 ) . Mean phenylalanine ( PHE ) intake was 38 % greater by Food A‐fed infants than by Food B‐fed infants . Plasma PHE concentrations and mean energy intakes of the two groups did not differ . Mean protein intake of Food A‐fed infants was greater during the first three months of life and significantly greater ( p < 0.05 ) during the second three months of life than by Food B‐fed infants . Mean protein intake 24 % greater than Recommended Dietary Allowances ( RDA ) was associated with better PHE tolerance and growth than was found when mean protein intake was 9 % greater than RDA A new amino acid formulation and a variety of treatment products incorporating it were evaluated for long-term safety , efficacy , and acceptance in 25 subjects with phenylketonuria over a period of 5 years . Palatability of the treatment was improved by reducing the required intake of amino acids , reformulating the mixture to have better taste , and providing vitamins and minerals as tablets . The hypotheses were that these strategies would improve compliance and metabolic control and maintain nutritional status in subjects . Compliance with treatment was determined from mean reported intakes ( 4-day diet records ) and from mean ‘ received ’ intakes using receipts of treatment products actually shipped to individuals upon request . Mean amino acid intakes prescribed were significantly reduced from study entry to end , from 1.2 g/kg to 0.7 g/kg ( p < 0.001 ) . Reported intakes were similarly reduced from 1.3 g/kg to 0.7 g/kg ( p < 0.001 ) . While actually ‘ received ’ intakes of  amino acid formula  were also significantly reduced ( p < 0.001 ) , intakes by this measure were much lower than either prescribed or reported , 0.9 g/kg at entry and 0.4 g/kg at the end of the study , suggesting that acceptance of the treatment ( usage of products ) , even when made more palatable , is below clinical expectations . In spite of these findings , mean serum proteins and minerals , height and weight were not significantly reduced during the study , supporting the safety of lowered intakes of amino acids and of nutritionally incomplete products . While the increase in mean serum phenylalanine concentration from 0.38 to 0.48 mmol/L was significant ( p < 0.03 ) , this mean rise of 0.1 mmol/L during a corresponding mean age increase of 4.2 years ( from 6.9 to 11.1 years ) is lower than in other recent reports from longitudinal studies of outcomes during this age range in subjects treated with traditional products . These data support the safety and efficacy of a more palatable and flexible approach to treatment Background : A phenylalanine-free amino acid based protein substitute is necessary to provide the major source of protein in phenylketonuria ( PKU ) . Protein substitutes in PKU are usually given as drinks . These are unpalatable and compliance is often poor . Tablets containing a suitable mixture of phenylalanine-free amino acids ( Aminogran Food Supplement , UCB ) are now available . Aims : To compare the effectiveness and acceptability of these tablets with conventional protein substitute drinks . Methods : Twenty one subjects with PKU , aged 8–25 years , participated in a r and omised crossover study . During one phase , subjects received at least 40 % of their protein substitute requirements from the amino acid tablets and the rest from their usual protein substitute tablets . During the other phase , they received their usual protein substitute . Each period lasted 12 weeks . Blood phenylalanine concentrations were measured at least once every two weeks and other plasma amino acids were measured at the beginning , at crossover , and at the end of the study . The subjects kept a diary of all protein substitute taken . Results : Compliance appeared to be better with the new tablets than with patients ’ usual protein substitutes . Ninety per cent ( 18/20 ) recorded that they took the tablets as prescribed , compared with 65 % ( 13/20 ) fully compliant with their usual protein substitute . Moreover , plasma phenyalanine was lower on the amino acid tablets , and the median difference in blood concentrations between the two groups was 46 μmol/l ( 95 % CI 14.8 to 89.0 , p = 0.02 ) . Tyrosine increased by a median of 16 μmol/l daily on the amino acid tablets ( 95 % CI 7.1 to 40.5 , p = 0.01 ) . Most subjects ( 70 % ) preferred incorporating the new tablets into their usual protein substitute regimen . Conclusions : Amino acid tablets are an effective and relatively popular protein substitute in older children , teenagers , and adults with PKU 
    Output:
    
No conclusions could be made about the short- or long-term use of protein substitute  in phenylketonuria due to the lack of adequate trial data .