{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T12:07:16Z","timestamp":1777896436740,"version":"3.51.4"},"reference-count":53,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Although there is a general assumption that a phenylalanine (Phe)-restricted diet promotes overweight in patients with phenylketonuria (PKU), it is unclear if this presumption is supported by scientific evidence. This systematic review aimed to determine if patients with PKU are at a higher risk of overweight compared to healthy individuals. A literature search was carried out on PubMed, Cochrane Library, and Embase databases. Risk of bias of individual studies was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies, and the quality of the evidence for each outcome was assessed using the NutriGrade scoring system. From 829 articles identified, 15 were included in the systematic review and 12 in the meta-analysis. Body mass index (BMI) was similar between patients with PKU and healthy controls, providing no evidence to support the idea that a Phe-restricted diet is a risk factor for the development of overweight. However, a subgroup of patients with classical PKU had a significantly higher BMI than healthy controls. Given the increasing prevalence of overweight in the general population, patients with PKU require lifelong follow-up, receiving personalised nutritional counselling, with methodical nutritional status monitoring from a multidisciplinary team in inherited metabolic disorders.<\/jats:p>","DOI":"10.3390\/nu13103443","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T21:38:09Z","timestamp":1632865089000},"page":"3443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Is the Phenylalanine-Restricted Diet a Risk Factor for Overweight or Obesity in Patients with Phenylketonuria (PKU)? A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4685-3562","authenticated-orcid":false,"given":"Catarina","family":"Rodrigues","sequence":"first","affiliation":[{"name":"Nutrition and Metabolism, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal"},{"name":"Comprehensive Health Research Centre, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal"}]},{"given":"Alex","family":"Pinto","sequence":"additional","affiliation":[{"name":"Dietetic Department, Birmingham Children\u2019s Hospital, Steelhouse Lane, Birmingham B4 6NH, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5165-9513","authenticated-orcid":false,"given":"Ana","family":"Faria","sequence":"additional","affiliation":[{"name":"Nutrition and Metabolism, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal"},{"name":"Comprehensive Health Research Centre, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal"},{"name":"CINTESIS\u2014Center for Health Technology and Services Research, NOVA Medical School, Campo dos M\u00e1rtires da P\u00e1tria 130, 1169-056 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2162-1450","authenticated-orcid":false,"given":"Diana","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Nutrition and Metabolism, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal"},{"name":"Comprehensive Health Research Centre, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal"},{"name":"CINTESIS\u2014Center for Health Technology and Services Research, NOVA Medical School, Campo dos M\u00e1rtires da P\u00e1tria 130, 1169-056 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9402-4833","authenticated-orcid":false,"given":"Annemiek M. J.","family":"van Wegberg","sequence":"additional","affiliation":[{"name":"Division of Metabolic Diseases, Beatrix Children\u2019s Hospital, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands"}]},{"given":"Kirsten","family":"Ahring","sequence":"additional","affiliation":[{"name":"Department of PKU, Copenhagen University Hospital, DK-2600 Glostrup, Denmark"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8717-469X","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Feillet","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Reference Center for Inborn Errors of Metabolism, H\u00f4pital d\u2019Enfants Brabois, CHU Nancy, 54500 Vandoeuvre les Nancy, France"}]},{"given":"Concei\u00e7\u00e3o","family":"Calhau","sequence":"additional","affiliation":[{"name":"Nutrition and Metabolism, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal"},{"name":"CINTESIS\u2014Center for Health Technology and Services Research, NOVA Medical School, Campo dos M\u00e1rtires da P\u00e1tria 130, 1169-056 Lisboa, Portugal"}]},{"given":"Anita","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Dietetic Department, Birmingham Children\u2019s Hospital, Steelhouse Lane, Birmingham B4 6NH, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0320-1839","authenticated-orcid":false,"given":"Andr\u00e9","family":"Moreira-Ros\u00e1rio","sequence":"additional","affiliation":[{"name":"Nutrition and Metabolism, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal"},{"name":"CINTESIS\u2014Center for Health Technology and Services Research, NOVA Medical School, Campo dos M\u00e1rtires da P\u00e1tria 130, 1169-056 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4977-8345","authenticated-orcid":false,"given":"J\u00falio C\u00e9sar","family":"Rocha","sequence":"additional","affiliation":[{"name":"Nutrition and Metabolism, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal"},{"name":"CINTESIS\u2014Center for Health Technology and Services Research, NOVA Medical School, Campo dos M\u00e1rtires da P\u00e1tria 130, 1169-056 Lisboa, Portugal"},{"name":"Reference Centre of Inherited Metabolic Diseases, Centro Hospitalar Universit\u00e1rio de Lisboa Central, 1169-045 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ymgme.2012.07.006","article-title":"High prevalence of overweight and obesity in females with phenylketonuria","volume":"107","author":"Burrage","year":"2012","journal-title":"Mol. 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