{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:18:51Z","timestamp":1791587931668,"version":"4.3.4"},"reference-count":95,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010438","name":"Poznan University of Medical Sciences","doi-asserted-by":"crossref","award":["146\/2024\/MGB"],"award-info":[{"award-number":["146\/2024\/MGB"]}],"id":[{"id":"10.13039\/501100010438","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: The impact of dietary adherence and formula intake regularity on fat-soluble vitamin status in phenylketonuria (PKU) is uncertain. This study assessed whether vitamin A, D, E, and beta-carotene levels differ by dietary adherence and regularity of Phe-free formula intake. Methods: A cross-sectional study included 98 individuals (age 6\u201341 years) with vitamin D measurements. In a subgroup of 68 patients, vitamin A, vitamin E, and beta-carotene levels were determined. Vitamin levels were compared between adherent and non-adherent groups and between participants with regular vs. irregular formula intake. A subsequent systematic review and meta-analysis of six studies (from PubMed, Scopus, Web of Science, and Cochrane; searched in August 2025) pooled standardised mean differences (SMDs) using fixed-effects and random-effects models. Results: The cross-sectional results showed higher vitamin D in adherent (35.60 [30.39\u201341.65] vs. 32.90 [26.50\u201340.00] ng\/mL, p = 0.034) and regular formula consumers (35.97 [30.03\u201342.28] vs. 30.20 [26.08\u201335.06] ng\/mL, p = 0.002). Beta-carotene was elevated with regular intake (74.40 [56.70\u201398.45] vs. 53.20 [34.10\u201368.60] ng\/mL, p = 0.003). Meta-analysis confirmed higher vitamin D in adherent individuals (fixed-effects model, SMD = 0.290, 95% CI: 0.004, 0.576, p = 0.047) and regular consumers (fixed-effects model, SMD = 0.750, 95% CI: 0.382, 1.118, p &lt; 0.0001). No differences were observed for vitamin E or beta-carotene. Conclusions: Adherence to diet and regular formula intake is associated with improved vitamin D status, underscoring the critical role of fortified formulas in PKU management. The very low certainty of evidence necessitates further research, especially for the other fat-soluble vitamins. Nonetheless, clinical practice should emphasise support for adherence and ongoing nutritional monitoring.<\/jats:p>","DOI":"10.3390\/nu17243932","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T15:41:12Z","timestamp":1765899672000},"page":"3932","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Vitamins D, A and E, and Beta-Carotene in Adherent and Non-Adherent Individuals with Phenylketonuria: Cross-Sectional Study, Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4115-8838","authenticated-orcid":false,"given":"Kamila","family":"Bokayeva","sequence":"first","affiliation":[{"name":"Poznan University of Medical Sciences, Department of Pediatric Gastroenterology and Metabolic Diseases, Szpitalna Str. 27\/33, 60-572 Pozna\u0144, Poland"},{"name":"Poznan University of Medical Sciences, Doctoral School, Bukowska Str. 70, 60-812 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0257-6180","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Jamka","sequence":"additional","affiliation":[{"name":"Poznan University of Medical Sciences, Department of Pediatric Gastroenterology and Metabolic Diseases, Szpitalna Str. 27\/33, 60-572 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0340-5914","authenticated-orcid":false,"given":"\u0141ukasz","family":"Ka\u0142u\u017cny","sequence":"additional","affiliation":[{"name":"Poznan University of Medical Sciences, Department of Pediatric Gastroenterology and Metabolic Diseases, Szpitalna Str. 27\/33, 60-572 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Du\u015b-\u017buchowska","sequence":"additional","affiliation":[{"name":"Poznan University of Medical Sciences, Department of Pediatric Gastroenterology and Metabolic Diseases, Szpitalna Str. 27\/33, 60-572 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Wich\u0142acz-Trojanowska","sequence":"additional","affiliation":[{"name":"Poznan University of Medical Sciences, Department of Pediatric Gastroenterology and Metabolic Diseases, Szpitalna Str. 27\/33, 60-572 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Mozrzymas","sequence":"additional","affiliation":[{"name":"Research and Development Center, Department of Pediatrics, Regional Specialist Hospital, Kamienskiego Str. 73a, 51-124 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Chrobot","sequence":"additional","affiliation":[{"name":"Metabolic Outpatient Clinic, Voievodship Children Hospital, Chodkiewicza Str. 44, 85-667 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8874-2401","authenticated-orcid":false,"given":"Dariusz","family":"Walkowiak","sequence":"additional","affiliation":[{"name":"Poznan University of Medical Sciences, Department of Organization and Management in Health Care, Marii Magdaleny Str. 14, 61-786 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2775-7607","authenticated-orcid":false,"given":"Olga","family":"\u013bubina","sequence":"additional","affiliation":[{"name":"Clinic of Medical Genetics and Prenatal Diagnostics, Children\u2019s Clinical University Hospital, Vien\u012bbas Gatve Str. 45, 1004 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilya","family":"Rabkevich","sequence":"additional","affiliation":[{"name":"Clinic of Medical Genetics and Prenatal Diagnostics, Children\u2019s Clinical University Hospital, Vien\u012bbas Gatve Str. 45, 1004 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1409-2933","authenticated-orcid":false,"given":"Szymon","family":"Kurek","sequence":"additional","affiliation":[{"name":"Poznan University of Medical Sciences, Department of Pediatric Gastroenterology and Metabolic Diseases, Szpitalna Str. 27\/33, 60-572 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5073-2435","authenticated-orcid":false,"given":"Anna","family":"Mi\u015bkiewicz-Chotnicka","sequence":"additional","affiliation":[{"name":"Poznan University of Medical Sciences, Department of Pediatric Gastroenterology and Metabolic Diseases, Szpitalna Str. 27\/33, 60-572 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulnara","family":"Sultanova","sequence":"additional","affiliation":[{"name":"School of Dentistry, Pharmacy, Nursing, Public Health and Preventive Medicine, West Kazakhstan Marat Ospanov Medical University, Maresyev Str. 68, Aktobe 030019, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4460-2604","authenticated-orcid":false,"given":"Karl-Heinz","family":"Herzig","sequence":"additional","affiliation":[{"name":"Poznan University of Medical Sciences, Department of Pediatric Gastroenterology and Metabolic Diseases, Szpitalna Str. 27\/33, 60-572 Pozna\u0144, Poland"},{"name":"Research Unit of Biomedicine and Internal Medicine, Faculty of Medicine, University of Oulu, Aapistie Str. 5, 90220 Oulu, Finland"},{"name":"Biocenter Oulu, University of Oulu, Aapistie Str. 5, 90220 Oulu, Finland"},{"name":"Medical Research Center, Oulu University Hospital, Aapistie Str. 5, 90220 Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9925-2376","authenticated-orcid":false,"given":"Madara","family":"Auzenbaha","sequence":"additional","affiliation":[{"name":"Clinic of Medical Genetics and Prenatal Diagnostics, Children\u2019s Clinical University Hospital, Vien\u012bbas Gatve Str. 45, 1004 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5813-5707","authenticated-orcid":false,"given":"Jaros\u0142aw","family":"Walkowiak","sequence":"additional","affiliation":[{"name":"Poznan University of Medical Sciences, Department of Pediatric Gastroenterology and Metabolic Diseases, Szpitalna Str. 27\/33, 60-572 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109125","DOI":"10.1016\/j.ymgme.2025.109125","article-title":"European Guidelines on Diagnosis and Treatment of Phenylketonuria: First Revision","volume":"145","author":"MacDonald","year":"2025","journal-title":"Mol. Genet. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/gim.2013.179","article-title":"Recommendations for the Nutrition Management of Phenylalanine Hydroxylase Deficiency","volume":"16","author":"Singh","year":"2014","journal-title":"Genet. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1111\/j.1365-277X.2008.00891.x","article-title":"Does Maternal Knowledge and Parent Education Affect Blood Phenylalanine Control in Phenylketonuria?","volume":"21","author":"Macdonald","year":"2008","journal-title":"J. Hum. Nutr. Diet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.ymgme.2017.01.001","article-title":"Adherence to Clinic Recommendations among Patients with Phenylketonuria in the United States","volume":"120","author":"Jurecki","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_5","unstructured":"Office of Dietary Supplements (2025, July 13). Vitamin A and Carotenoids, Available online: https:\/\/ods.od.nih.gov\/factsheets\/VitaminA-HealthProfessional\/."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12986-022-00696-y","article-title":"Fat-Soluble Vitamins: Updated Review of Their Role and Orchestration in Human Nutrition throughout Life Cycle with Sex Differences","volume":"19","author":"Youness","year":"2022","journal-title":"Nutr. Metab."},{"key":"ref_7","unstructured":"Marriott, B.P., Birt, D.F., Stallings, V.A., and Yates, A.A. (2020). Chapter 5\u2014Vitamin A and Provitamin A Carotenoids. Present Knowledge in Nutrition, Academic Press. [11th ed.]."},{"key":"ref_8","unstructured":"Ross, A.C., Caballero, B., Cousins, R.J., and Tucker, K.L. (2020). Modern Nutrition in Health and Disease, Jones & Bartlett Learning."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1194\/jlr.R037028","article-title":"Enzymology of Retinoic Acid Biosynthesis and Degradation","volume":"54","author":"Kedishvili","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"56","DOI":"10.5935\/0004-2749.20160018","article-title":"Vitamin A and the Eye: An Old Tale for Modern Times","volume":"79","author":"Faustino","year":"2016","journal-title":"Arq. Bras. Oftalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S0072-9752(08)02129-5","article-title":"Chapter 29\u2014Historical Aspects of the Major Neurological Vitamin Deficiency Disorders: Overview and Fat-Soluble Vitamin A","volume":"95","author":"Aminoff","year":"2009","journal-title":"Handbook of Clinical Neurology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.it.2016.12.006","article-title":"Retinoic Acid and Immune Homeostasis: A Balancing Act","volume":"38","author":"Erkelens","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"385","DOI":"10.3390\/nu3040385","article-title":"Vitamin A in Reproduction and Development","volume":"3","author":"Knutson","year":"2011","journal-title":"Nutrients"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1146\/annurev-immunol-041015-055427","article-title":"Retinoic Acid and Retinoic Acid Receptors as Pleiotropic Modulators of the Immune System","volume":"34","author":"Larange","year":"2016","journal-title":"Annu. Rev. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Miazek, K., Beton, K., \u015aliwi\u0144ska, A., and Bro\u017cek-P\u0142uska, B. (2022). The Effect of \u03b2-Carotene, Tocopherols and Ascorbic Acid as Anti-Oxidant Molecules on Human and Animal In Vitro\/In Vivo Studies: A Review of Research Design and Analytical Techniques Used. Biomolecules, 12.","DOI":"10.3390\/biom12081087"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.ymgme.2011.03.019","article-title":"Experimental Evidence That Phenylalanine Is Strongly Associated to Oxidative Stress in Adolescents and Adults with Phenylketonuria","volume":"103","author":"Sanayama","year":"2011","journal-title":"Mol. Genet. Metab."},{"key":"ref_17","unstructured":"Office of Dietary Supplements (2025, July 14). Vitamin E, Available online: https:\/\/ods.od.nih.gov\/factsheets\/VitaminE-HealthProfessional\/."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3711","DOI":"10.37358\/RC.19.10.7630","article-title":"The Therapeutic Relevance of Vitamin E","volume":"70","author":"Anghel","year":"2019","journal-title":"Rev. Chim."},{"key":"ref_19","unstructured":"USDA (2025, July 14). FoodData Central, Available online: https:\/\/fdc.nal.usda.gov\/."},{"key":"ref_20","first-page":"146","article-title":"The Role of Vitamins in the Diet of the Elderly II. Water-Soluble Vitamins","volume":"10","author":"Albert","year":"2017","journal-title":"Acta Univ. Sapientiae Aliment."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Niki, E., and Abe, K. (2019). Vitamin E: Structure, Properties and Functions. Food Chemistry, Function and Analysis, Royal Society of Chemistry.","DOI":"10.1039\/9781788016216-00001"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/ajcn\/77.1.185","article-title":"Lipophilic Antioxidants in Patients with Phenylketonuria123","volume":"77","author":"Artuch","year":"2003","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1037\/0894-4105.22.4.426","article-title":"Cognitive Functions and the Antioxidant System in Phenylketonuric Patients","volume":"22","author":"Artuch","year":"2008","journal-title":"Neuropsychology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.clinbiochem.2003.10.017","article-title":"A Longitudinal Study of Antioxidant Status in Phenylketonuric Patients","volume":"37","author":"Artuch","year":"2004","journal-title":"Clin. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1023\/A:1010500502275","article-title":"Plasma Phenylalanine Is Associated with Decreased Serum Ubiquinone-10 Concentrations in Phenylketonuria","volume":"24","author":"Artuch","year":"2001","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/s10571-011-9693-2","article-title":"Oxidative Stress in Phenylketonuria: What Is the Evidence?","volume":"31","author":"Ribas","year":"2011","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.clnu.2018.01.034","article-title":"Vitamin\/Mineral and Micronutrient Status in Patients with Classical Phenylketonuria","volume":"38","author":"Kose","year":"2019","journal-title":"Clin. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/sj.ejcn.1601529","article-title":"Effect of Diet on Plasma Total Antioxidant Status in Phenylketonuric Patients","volume":"57","author":"Schulpis","year":"2003","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1089\/ars.2011.4163","article-title":"Impact of Lipophilic Antioxidants and Level of Antibodies against Oxidized Low-Density Lipoprotein in Polish Children with Phenylketonuria","volume":"16","author":"Mikoluc","year":"2012","journal-title":"Antioxid. Redox Signal."},{"key":"ref_30","unstructured":"Office of Dietary Supplements (2025, July 14). Vitamin D, Available online: https:\/\/ods.od.nih.gov\/factsheets\/VitaminD-HealthProfessional\/."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ross, A.C., Taylor, C.L., Yaktine, A.L., and Del Valle, H.B. (2011). Dietary Reference Intakes for Vitamin D and Calcium. Dietary Reference Intakes for Calcium and Vitamin D, National Academies Press (US).","DOI":"10.1017\/S1368980011000565"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s00418-018-1648-y","article-title":"Functions of Vitamin D in Bone","volume":"149","author":"Goltzman","year":"2018","journal-title":"Histochem. Cell Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4400","DOI":"10.1096\/fj.12-210880","article-title":"Inhibition of Cytokine Secretion from Adipocytes by 1,25-Dihydroxyvitamin D3 via the NF-\u03baB Pathway","volume":"26","author":"Mutt","year":"2012","journal-title":"FASEB J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e1900728","DOI":"10.1002\/mnfr.201900728","article-title":"Vitamin D Deficiency Induces Insulin Resistance and Re-Supplementation Attenuates Hepatic Glucose Output via the PI3K-AKT-FOXO1 Mediated Pathway","volume":"64","author":"Mutt","year":"2020","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1080\/07315724.2018.1431160","article-title":"The Relationship Between Female Reproductive Functions and Vitamin D","volume":"37","author":"Arslan","year":"2018","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Medrano, M., Carrillo-Cruz, E., Montero, I., and Perez-Simon, J.A. (2018). Vitamin D: Effect on Haematopoiesis and Immune System and Clinical Applications. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092663"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Lumme, J., Morin-Papunen, L., Pesonen, P., Sebert, S., Hypp\u00f6nen, E., J\u00e4rvelin, M.-R., Herzig, K.-H., Ojaniemi, M., and Niinim\u00e4ki, M. (2023). Vitamin D Status in Women with a History of Infertility and Decreased Fecundability: A Population-Based Study. Nutrients, 15.","DOI":"10.3390\/nu15112522"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.kjms.2018.03.004","article-title":"Vitamin D: And Its Role in Breast Cancer","volume":"34","year":"2018","journal-title":"Kaohsiung J. Med. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"244","DOI":"10.4103\/aja.aja_14_18","article-title":"Vitamin D in Prostate Cancer","volume":"20","author":"Trump","year":"2018","journal-title":"Asian J. Androl."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1007\/s40263-019-00640-4","article-title":"Potential Role of Vitamin D for the Management of Depression and Anxiety","volume":"33","author":"Casseb","year":"2019","journal-title":"CNS Drugs"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e20210004","DOI":"10.1590\/2326-4594-jiems-2021-0004","article-title":"25 Hydroxy Vitamin D Level, Bone Health, Vitamin D and Calcium Intake in Chilean Patients with Phenylketonuria and Hyperphenylalaninemias","volume":"9","author":"Leiva","year":"2021","journal-title":"J. Inborn Errors Metab. Screen."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Bokayeva, K., Jamka, M., Walkowiak, D., Du\u015b-\u017buchowska, M., Herzig, K.-H., and Walkowiak, J. (2024). Vitamin Status in Patients with Phenylketonuria: A Systematic Review and Meta-Analysis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25105065"},{"key":"ref_43","unstructured":"Silva, M.F.S., Leal-Witt, M.J., Hamilton, V., Cornejo, V., Silva, M.F.S., Leal-Witt, M.J., Hamilton, V., and Cornejo, V. (2023). Vitamin D and Inborn Errors of Metabolism, IntechOpen."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Rojas-Agurto, E., Leal-Witt, M.J., Arias, C., Cabello, J.F., Bunout, D., and Cornejo, V. (2023). Muscle and Bone Health in Young Chilean Adults with Phenylketonuria and Different Degrees of Compliance with the Phenylalanine Restricted Diet. Nutrients, 15.","DOI":"10.3390\/nu15132939"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1159\/000479746","article-title":"Effects of Inadequate Amino Acid Mixture Intake on Nutrient Supply of Adult Patients with Phenylketonuria","volume":"71","author":"Hochuli","year":"2017","journal-title":"Ann. Nutr. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Anton-P\u0103duraru, D.-T., Trofin, F., Chis, A., Sur, L.M., Streang\u0103, V., M\u00eendru, D.E., Dorneanu, O.S., P\u0103duraru, D., Nastase, E.V., and Vulturar, R. (2025). Current Insights into Nutritional Management of Phenylketonuria: An Update for Children and Adolescents. Children, 12.","DOI":"10.3390\/children12020199"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mancilla, V.J., Mann, A.E., Zhang, Y., and Allen, M.S. (2021). The Adult Phenylketonuria (PKU) Gut Microbiome. Microorganisms, 9.","DOI":"10.3390\/microorganisms9030530"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Ostrowska, M., Nowosad, K., Mikoluc, B., Szczerba, H., and Komon-Janczara, E. (2024). Changes in the Gut and Oral Microbiome in Children with Phenylketonuria in the Context of Dietary Restrictions-A Preliminary Study. Nutrients, 16.","DOI":"10.3390\/nu16223915"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Pinheiro de Oliveira, F., Mendes, R.H., Dobbler, P.T., Mai, V., Pylro, V.S., Waugh, S.G., Vairo, F., Refosco, L.F., Roesch, L.F.W., and Schwartz, I.V.D. (2016). Phenylketonuria and Gut Microbiota: A Controlled Study Based on Next-Generation Sequencing. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157513"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Montanari, C., Ceccarani, C., Corsello, A., Zuvadelli, J., Ottaviano, E., Dei Cas, M., Banderali, G., Zuccotti, G., Borghi, E., and Verduci, E. (2022). Glycomacropeptide Safety and Its Effect on Gut Microbiota in Patients with Phenylketonuria: A Pilot Study. Nutrients, 14.","DOI":"10.3390\/nu14091883"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ramos Meyers, G., Samouda, H., and Bohn, T. (2022). Short Chain Fatty Acid Metabolism in Relation to Gut Microbiota and Genetic Variability. Nutrients, 14.","DOI":"10.3390\/nu14245361"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Di Profio, E., Magenes, V.C., Fiore, G., Agostinelli, M., La Mendola, A., Acunzo, M., Francavilla, R., Indrio, F., Bosetti, A., and D\u2019Auria, E. (2022). Special Diets in Infants and Children and Impact on Gut Microbioma. Nutrients, 14.","DOI":"10.3390\/nu14153198"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.jclinepi.2007.11.008","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for Reporting Observational Studies","volume":"61","author":"Altman","year":"2008","journal-title":"J. Clin. Epidemiol."},{"key":"ref_54","first-page":"e928","article-title":"Study Designs in Medical Research and Their Key Characteristics","volume":"92","author":"Nowak","year":"2023","journal-title":"J. Med. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"21","DOI":"10.7748\/nr.23.5.21.s5","article-title":"Fundamentals of Estimating Sample Size","volume":"23","author":"Malone","year":"2016","journal-title":"Nurse Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1111\/j.2047-6310.2012.00064.x","article-title":"Extended International (IOTF) Body Mass Index Cut-Offs for Thinness, Overweight and Obesity","volume":"7","author":"Cole","year":"2012","journal-title":"Pediatr. Obes."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.advms.2018.04.001","article-title":"Vitamin E Status and Its Determinants in Patients with Cystic Fibrosis","volume":"63","author":"Sapiejka","year":"2018","journal-title":"Adv. Med. Sci."},{"key":"ref_58","first-page":"345","article-title":"Vitamin A Status and Its Determinants in Patients with Cystic Fibrosis","volume":"16","author":"Sapiejka","year":"2017","journal-title":"Acta Sci. Pol. Technol. Aliment."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.clinbiochem.2014.03.025","article-title":"Pediatric Reference Value Distributions for Vitamins A and E in the CALIPER Cohort and Establishment of Age-Stratified Reference Intervals","volume":"47","author":"Raizman","year":"2014","journal-title":"Clin. Biochem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.cca.2009.03.058","article-title":"A Rapid HPLC Method Used to Establish Pediatric Reference Intervals for Vitamins A and E","volume":"405","author":"Moore","year":"2009","journal-title":"Clin. Chim. Acta"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Rusi\u0144ska, A., P\u0142udowski, P., Walczak, M., Borszewska-Kornacka, M.K., Bossowski, A., Chlebna-Sok\u00f3\u0142, D., Czech-Kowalska, J., Dobrza\u0144ska, A., Franek, E., and Helwich, E. (2018). Vitamin D Supplementation Guidelines for General Population and Groups at Risk of Vitamin D Deficiency in Poland\u2014Recommendations of the Polish Society of Pediatric Endocrinology and Diabetes and the Expert Panel with Participation of National Specialist Consultants and Representatives of Scientific Societies\u20142018 Update. Front. Endocrinol., 9.","DOI":"10.3389\/fendo.2018.00246"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"104747","DOI":"10.1016\/j.jstrokecerebrovasdis.2020.104747","article-title":"Cryptogenic Intracranial Hemorrhagic Strokes Associated with Hypervitaminosis E and Acutely Elevated \u03b1-Tocopherol Levels","volume":"29","author":"Le","year":"2020","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_63","unstructured":"(2025, September 24). 001529: Carotene, \u03b2. Available online: https:\/\/www.labcorp.com\/tests\/001529\/carotene-b."},{"key":"ref_64","unstructured":"(2025, September 24). FCATB\u2014Overview: Carotene, Beta. Available online: https:\/\/www.mayocliniclabs.com\/test-catalog\/overview\/75927#Clinical-and-Interpretive."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e700","DOI":"10.20883\/medical.e700","article-title":"Publication Ethics of Human Studies in the Light of the Declaration of Helsinki\u2014A Mini-Review","volume":"91","author":"Guzik","year":"2022","journal-title":"J. Med. Sci."},{"key":"ref_66","unstructured":"Posit Team (2024). RStudio: Integrated Development Environment for R, Posit Software, PBC."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_68","unstructured":"Higgins, J.P.T., Thomas, J., Chandler, J., Cumpston, M., Li, T., Page, M.J., and Welch, V.A. (2024, December 15). Cochrane Handbook for Systematic Reviews of Interventions Version 6.5 (Updated August 2024). Cochrane, 2024. Available online: https:\/\/www.cochrane.org\/authors\/handbooks-and-manuals\/handbook\/current."},{"key":"ref_69","unstructured":"Bokayeva, K., Jamka, M., Walkowiak, D., Herzig, K.-H., and Walkowiak, J. (2025, October 22). Fat-Soluble Vitamins Comparison in Adherent vs. Non-Adherent and Regular Formula Intake vs. Irregular Formula Intake Individuals with PKU: Systematic Review and Meta-Analysis. Available online: https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420251128538."},{"key":"ref_70","unstructured":"Wells, G.A., Shea, B., O\u2019Connell, D., Peterson, J., Welch, V., Losos, M., and Tugwell, P. (2025). The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Non-Randomized Studies in Meta-Analyses, Ottawa Hospital Research Institute. Available online: https:\/\/www.ohri.ca\/programs\/clinical_epidemiology\/oxford.asp."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Modesti, P.A., Reboldi, G., Cappuccio, F.P., Agyemang, C., Remuzzi, G., Rapi, S., Perruolo, E., and Parati, G. (2016). ESH Working Group on CV Risk in Low Resource Settings. Panethnic Differences in Blood Pressure in Europe: A Systematic Review and Meta-Analysis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147601"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"g5630","DOI":"10.1136\/bmj.g5630","article-title":"A GRADE Working Group Approach for Rating the Quality of Treatment Effect Estimates from Network Meta-Analysis","volume":"349","author":"Puhan","year":"2014","journal-title":"BMJ"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/j.dib.2015.07.026","article-title":"Micronutrient in Hyperphenylalaninemia","volume":"4","author":"Crujeiras","year":"2015","journal-title":"Data Brief"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"158","DOI":"10.30621\/jbachs.1539286","article-title":"Retrospective Evaluation of Diet Compliance on Plasma Amino Acid and Vitamin Levels in Patients with Phenylketonuria","volume":"9","author":"Kol","year":"2025","journal-title":"JBACHS"},{"key":"ref_75","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_76","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.jsbmb.2013.11.003","article-title":"Is Vitamin D Deficiency a Major Global Public Health Problem?","volume":"144","author":"Palacios","year":"2014","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"872","DOI":"10.2310\/JIM.0b013e318214ea2d","article-title":"Vitamin D: A D-Lightful Solution for Health","volume":"59","author":"Holick","year":"2011","journal-title":"J. Investig. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/jhn.12054","article-title":"Body Mass Index in Adult Patients with Diet-Treated Phenylketonuria","volume":"26","author":"Robertson","year":"2013","journal-title":"J. Hum. Nutr. Diet."},{"key":"ref_79","first-page":"483","article-title":"Overweight and Obesity in PKU: The Results from 8 Centres in Europe and Turkey","volume":"1","author":"Ahring","year":"2014","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1159\/000520047","article-title":"The Impact of Phenylketonuria on Body Composition in Adults","volume":"78","author":"Barta","year":"2021","journal-title":"Ann. Nutr. Metab."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13023-023-02636-2","article-title":"Overweight and Obesity in Adult Patients with Phenylketonuria: A Systematic Review","volume":"18","author":"Tankeu","year":"2023","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Pilz, S., M\u00e4rz, W., Cashman, K.D., Kiely, M.E., Whiting, S.J., Holick, M.F., Grant, W.B., Pludowski, P., Hiligsmann, M., and Trummer, C. (2018). Rationale and Plan for Vitamin D Food Fortification: A Review and Guidance Paper. Front. Endocrinol., 9.","DOI":"10.3389\/fendo.2018.00373"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"453","DOI":"10.3945\/an.113.003780","article-title":"Natural Vitamin D Content in Animal Products","volume":"4","author":"Schmid","year":"2013","journal-title":"Adv. Nutr."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1056\/NEJMra070553","article-title":"Vitamin D Deficiency","volume":"357","author":"Holick","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Venegas, E., Langeveld, S., Ahring, K., Benitez, R., Desloovere, A., Dios, E., G\u00f3mez, E., Hermida, A., Marsaux, C., and Verloo, P. (2024). Nutrient Status and Intakes of Adults with Phenylketonuria. Nutrients, 16.","DOI":"10.3390\/nu16162724"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.nutres.2015.11.007","article-title":"Normal Vitamin D Levels and Bone Mineral Density among Children with Inborn Errors of Metabolism Consuming Medical Food\u2013Based Diets","volume":"36","author":"Geiger","year":"2016","journal-title":"Nutr. Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"20373","DOI":"10.1038\/s41598-024-71145-4","article-title":"Evaluating a Novel Method for Vitamin A Analysis in an Observational Study of the UAE\u2019s Obese Population","volume":"14","author":"Hakeem","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_88","unstructured":"(2025, December 08). Vitamin A Toxicity\u2014Nutritional Disorders. Available online: https:\/\/www.msdmanuals.com\/professional\/nutritional-disorders\/vitamin-deficiency-dependency-and-toxicity\/vitamin-a-toxicity."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"100383","DOI":"10.1016\/j.phanu.2024.100383","article-title":"Structural, Functional, Nutritional and Clinical Aspects of Vitamin A: A Review","volume":"27","author":"Menezes","year":"2024","journal-title":"PharmaNutrition"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.freeradbiomed.2021.10.016","article-title":"Absorption, Transportation, and Distribution of Vitamin E Homologs","volume":"177","author":"Kiyose","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_91","unstructured":"(2025, August 13). Beta Carotene (Oral Route)\u2014Side Effects & Dosage. Available online: https:\/\/www.mayoclinic.org\/drugs-supplements\/beta-carotene-oral-route\/description\/drg-20066795."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1271\/bbb.130025","article-title":"Effects of Fats and Oils on the Bioaccessibility of Carotenoids and Vitamin E in Vegetables","volume":"77","author":"Nagao","year":"2013","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1203\/01.pdr.0000203091.45988.8d","article-title":"Phenylalanine Reduces Synaptic Density in Mixed Cortical Cultures from Mice","volume":"59","author":"Schwab","year":"2006","journal-title":"Pediatr. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.bbadis.2005.02.005","article-title":"Oxidative Stress in Patients with Phenylketonuria","volume":"1740","author":"Sirtori","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s10571-009-9455-6","article-title":"Experimental Evidence That Phenylalanine Provokes Oxidative Stress in Hippocampus and Cerebral Cortex of Developing Rats","volume":"30","author":"Fernandes","year":"2009","journal-title":"Cell. Mol. Neurobiol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/24\/3932\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T05:18:07Z","timestamp":1766121487000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/24\/3932"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,16]]},"references-count":95,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["nu17243932"],"URL":"https:\/\/doi.org\/10.3390\/nu17243932","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,16]]}}}