{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T05:52:42Z","timestamp":1771307562079,"version":"3.50.1"},"reference-count":36,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T00:00:00Z","timestamp":1700611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia\/Minist\u00e9rio da Ci\u00eancia","award":["CINTESIS-UIDB\/04255\/2020 and UIDP\/04255\/2020"],"award-info":[{"award-number":["CINTESIS-UIDB\/04255\/2020 and UIDP\/04255\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>In PKU, the protein requirements are contentious. In 2018, we evaluated the protein intake in patients with PKU. Ninety-nine early treated patients aged 19.3 \u00b1 8.2 years (54% males) were studied. A total of 24 had hyperphenylalaninemia (HPA), 48 mild and 27 classical PKU. All had an annual nutritional status evaluation. A total of 83% were on diet therapy only, and 17% were on diet with tetrahydrobiopterin therapy. Anthropometry, metabolic control and nutritional intake [total protein (TP, g\/kg), natural protein (NP, g\/kg), protein equivalent from protein substitutes (PE, g\/kg)] were collected. TP adequacy (TPA) was calculated as a % of WHO (2007) safe levels of protein intake. Results were compared with the European PKU Guidelines (EPG). The median % contribution NP of TP intake was 53% [31\u2013100]. Most patients (78%) had a TP intake above the EPG recommendations. The median TPA was 171% [146\u2013203], with 79% [51\u2013165] from NP and 84% [0\u2013109] from PE. A TPA of 100\u2013140% was observed in 16 (16%) patients. Only n = 6 (6%) patients had a TPA &lt; 100%. These results emphasize the heterogeneity of PKU. More research is needed to understand the necessity of a single protein recommendation for all, as a \u2018one-size-fits-all\u2019 solution might not be appropriate.<\/jats:p>","DOI":"10.3390\/nu15234883","type":"journal-article","created":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T10:41:51Z","timestamp":1700649711000},"page":"4883","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Total Protein Intake in Patients with PKU: Adequacy Evaluation According to the European PKU Guidelines from 2017"],"prefix":"10.3390","volume":"15","author":[{"given":"Melanie","family":"Gomes","sequence":"first","affiliation":[{"name":"Nephrocare Portugal, Fresenius Medical Care Nutrition Departament, Rua Professor Salazar de Sousa, Lote 12, 1750-233 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1683-1314","authenticated-orcid":false,"given":"Manuela Ferreira","family":"Almeida","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica M\u00e9dica Jacinto Magalh\u00e3es, Centro Hospitalar Universit\u00e1rio de Santo Ant\u00f3nio, 4099-028 Porto, Portugal"},{"name":"Centro de Refer\u00eancia Para as Doen\u00e7as Heredit\u00e1rias do Metabolismo, Centro Hospitalar Universit\u00e1rio de Santo Ant\u00f3nio, 4099-028 Porto, Portugal"},{"name":"Unidade Multidisciplinar de Investiga\u00e7\u00e3o em Biomedicina, Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Catarina Sousa","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica M\u00e9dica Jacinto Magalh\u00e3es, Centro Hospitalar Universit\u00e1rio de Santo Ant\u00f3nio, 4099-028 Porto, Portugal"}]},{"given":"Maria In\u00eas","family":"Gama","sequence":"additional","affiliation":[{"name":"University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK"}]},{"given":"Maria","family":"Peres","sequence":"additional","affiliation":[{"name":"National Institute of Health Doutor Ricardo Jorge, Av. Padre Cruz, 1649-016 Lisboa, Portugal"}]},{"given":"\u00c9lia","family":"Pinto","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina, Universidade do Porto, FMUP, Alameda Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"given":"Anita","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Birmingham Children\u2019s Hospital, Birmingham B4 6NH, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4977-8345","authenticated-orcid":false,"given":"J\u00falio C\u00e9sar","family":"Rocha","sequence":"additional","affiliation":[{"name":"CINTESIS@RISE, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade Nova de Lisboa, Campo M\u00e1rtires da P\u00e1tria 130, 1169-056 Lisboa, Portugal"},{"name":"NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade Nova de Lisboa, Campo M\u00e1rtires da P\u00e1tria 130, 1169-056 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,22]]},"reference":[{"key":"ref_1","unstructured":"Stone, W.L., Basit, H., and Los, E. (2023). StatPearls, StatPearls Publishing."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1111\/bcp.13886","article-title":"Efficacy and safety of sapropterin dihydrochloride in patients with phenylketonuria: A meta-analysis of randomized controlled trials","volume":"85","author":"Qu","year":"2019","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.ymgmr.2015.07.002","article-title":"The challenge of long-term tetrahydrobiopterin (BH4) therapy in phenylketonuria: Effects on metabolic control, nutritional habits and nutrient supply","volume":"4","author":"Thiele","year":"2015","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ymgme.2018.03.006","article-title":"Pegvaliase for the treatment of phenylketonuria: Results of a long-term phase 3 clinical trial program (PRISM)","volume":"124","author":"Thomas","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1177392819857089","DOI":"10.1177\/1177392819857089","article-title":"A Comprehensive Review of Pegvaliase, an Enzyme Substitution Therapy for the Treatment of Phenylketonuria","volume":"13","author":"Hydery","year":"2019","journal-title":"Drug Target Insights"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s13023-017-0685-2","article-title":"The complete European guidelines on phenylketonuria: Diagnosis and treatment","volume":"12","author":"Macdonald","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_7","first-page":"58","article-title":"Nutritional Management of Phenylketonuria","volume":"68","author":"Macleod","year":"2010","journal-title":"Ann. Nestle Eng."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"155","DOI":"10.2147\/PHMT.S49329","article-title":"Dietary intervention in the management of phenylketonuria: Current perspectives","volume":"7","author":"Rocha","year":"2016","journal-title":"Pediatric. Health Med. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/gim.2013.157","article-title":"Phenylalanine hydroxylase deficiency: Diagnosis and management guideline","volume":"16","author":"Vockley","year":"2014","journal-title":"Genet. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"660","DOI":"10.2471\/BLT.07.043497","article-title":"Development of a WHO growth reference for school-aged children and adolescents","volume":"85","author":"Onis","year":"2007","journal-title":"Bull World Health Organ"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1017\/S0954422418000173","article-title":"Optimising amino acid absorption: Essential to improve nitrogen balance and metabolic control in phenylketonuria","volume":"32","author":"MacDonald","year":"2019","journal-title":"Nutr. Res. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.clnu.2020.11.003","article-title":"Dietary protein and protein substitute requirements in adults with phenylketonuria: A review of the clinical guidelines","volume":"40","author":"Firman","year":"2021","journal-title":"Clin. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"E340","DOI":"10.1152\/ajpendo.2001.280.2.E340","article-title":"The digestion rate of protein is an independent regulating factor of postprandial protein retention","volume":"280","author":"Dangin","year":"2001","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.ymgme.2017.07.007","article-title":"The relationship between dietary intake, growth and body composition in Phenylketonuria","volume":"122","author":"Evans","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/ejcn.2016.54","article-title":"Protein substitutes for phenylketonuria in Europe: Access and nutritional composition","volume":"70","author":"Pena","year":"2016","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"MacDonald, A., Ashmore, C., Daly, A., Pinto, A., and Evans, S. (2020). An Observational Study Evaluating the Introduction of a Prolonged-Release Protein Substitute to the Dietary Management of Children with Phenylketonuria. Nutrients, 12.","DOI":"10.3390\/nu12092686"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Daly, A., Pinto, A., Evans, S., and MacDonald, A. (2022). Glycomacropeptide in PKU-Does It Live Up to Its Potential?. Nutrients, 14.","DOI":"10.3390\/nu14040807"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.3945\/ajcn.2008.27280","article-title":"Improved nutritional management of phenylketonuria by using a diet containing glycomacropeptide compared with amino acids","volume":"89","author":"MacLeod","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_19","unstructured":"WHO (2007). Protein and amino acid requirements in human nutrition. World Health Organ. Tech. Rep. Ser., 935, 1\u2013265."},{"key":"ref_20","first-page":"44","article-title":"Consensus for the nutritional treatment of phenylketonuria","volume":"38","author":"Rocha","year":"2007","journal-title":"Acta Pedi\u00e1trica Port."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"WHO (2006). Child Growth Standards based on length\/height, weight and age. Acta Paediatr. Suppl., 450, 76\u201385.","DOI":"10.1111\/j.1651-2227.2006.tb02378.x"},{"key":"ref_22","unstructured":"WHO (1995). Physical status: The Use of and Interpretation of Anthropometry, Report of a WHO Expert Committee, World Health Organization."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/0377-8401(94)90036-1","article-title":"Protein quality of legume seeds for non-ruminant animals: A literature review","volume":"45","author":"Gatel","year":"1994","journal-title":"Anim. Feed. Sci. Technol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ilgaz, F., Marsaux, C., Pinto, A., Singh, R., Rohde, C., Karabulut, E., G\u00f6kmen-\u00d6zel, H., Kuhn, M., and MacDonald, A. (2021). Protein Substitute Requirements of Patients with Phenylketonuria on BH4 Treatment: A Systematic Review and Meta-Analysis. Nutrients, 13.","DOI":"10.3390\/nu13031040"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/j.ymgme.2011.08.023","article-title":"Nutrition in phenylketonuria","volume":"104","author":"MacDonald","year":"2011","journal-title":"Mol. Genet. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"211","DOI":"10.3945\/jn.116.240218","article-title":"The Indicator Amino Acid Oxidation Method with the Use of l-[1-13C]Leucine Suggests a Higher than Currently Recommended Protein Requirement in Children with Phenylketonuria","volume":"147","author":"Turki","year":"2017","journal-title":"J. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Daly, A., Evans, S., Pinto, A., Ashmore, C., and MacDonald, A. (2021). Protein substitutes in PKU; their historical evolution. Nutrients, 13.","DOI":"10.3390\/nu13020484"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s10545-010-9073-y","article-title":"The reality of dietary compliance in the management of phenylketonuria","volume":"33","author":"MacDonald","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s13023-021-01721-8","article-title":"Continuous use of glycomacropeptide in the nutritional management of patients with phenylketonuria: A clinical perspective","volume":"16","author":"Pena","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1038\/ejcn.2017.38","article-title":"Nutritional status in patients with phenylketonuria using glycomacropeptide as their major protein source","volume":"71","author":"Pinto","year":"2017","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1159\/000324924","article-title":"Adult patients with well-controlled phenylketonuria tolerate incidental additional intake of phenylalanine","volume":"58","author":"Hoeksma","year":"2011","journal-title":"Ann. Nutr. Metab."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Pinto, A., Almeida, M.F., Donald, M., Ramos, P.C., Rocha, S., Guimas, A., Ribeiro, R., Martins, E., Bandeira, A., and Jackson, R. (2019). Over restriction of dietary protein allowance: The importance of ongoing reassessment of natural protein tolerance in phenylketonuria. Nutrients, 11.","DOI":"10.3390\/nu11050995"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ymgme.2009.07.016","article-title":"Reassessment of phenylalanine tolerance in adults with phenylketonuria is needed as body mass changes","volume":"98","author":"MacLeod","year":"2009","journal-title":"Mol. Genet. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gama, M.I., Adam, S., Adams, S., Allen, H., Ashmore, C., Bailey, S., Cochrane, B., Dale, C., Daly, A., and De Sousa, G. (2022). Suitability and Allocation of Protein-Containing Foods According to Protein Tolerance in PKU: A 2022 UK National Consensus. Nutrients, 14.","DOI":"10.3390\/nu14234987"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1080\/21678707.2018.1536541","article-title":"Treatment options and dietary supplements for patients with phenylketonuria","volume":"6","author":"Rocha","year":"2018","journal-title":"Expert Opin. Orphan Drugs"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1136\/jmedgenet-2019-106278","article-title":"Predictability and inconsistencies of cognitive outcome in patients with phenylketonuria and personalised therapy: The challenge for the future guidelines","volume":"57","author":"Leuzzi","year":"2020","journal-title":"J. Med. Genet."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/23\/4883\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:27:40Z","timestamp":1760131660000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/23\/4883"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,22]]},"references-count":36,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["nu15234883"],"URL":"https:\/\/doi.org\/10.3390\/nu15234883","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,22]]}}}