foodsystFood systemsПищевые системы2618-97712618-7272Федеральный научный центр пищевых систем им. В.М. Горбатова РАН10.21323/2618-9771-2023-6-3-279-282foodsyst-295Research ArticleСтатьиNutritional contents of low phenylalanine diets: A mini reviewПищевая ценность диет с низким содержанием фенилаланина: мини-обзорhttps://orcid.org/0000-0002-9919-8760АммарА. С. М.AmmarA. S. M.

Аммар Абдалла С. M., профессор, кафедра науки о питании и технологии, Сельскохозяйственный факультет

12613, Гиза, ул. Гамаа

Тел.: +2–0101–997–17–99

Abdalla S. M. Ammar, Professor, Food Science and Technology Department

Gamaa Street, Giza, 12613

Tel.: +2–0101–997–17–99

Faculty of Agriculture

abdallaammar@agr.cu.edu.egКаирский УниверситетЕгипетCairo UniversityEgypt20231210202363279282Copyright © Ammar A., 20232023Аммар А.Ammar A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.fsjour.com/jour/article/view/295

Increased interest in the utilization of nutrition management of patients with phenylketonuria is clear. Applications include a small measured amount of phenylalanine given in the form of exchange food, phenylalanine-free protein substitute and low phenylalanine foods. In this article, the essential nutritional contents of low phenylalanine diets and the latest techniques and procedures used for creating several types of low phenylalanine diets from different food sources for persons with phenylketonuria are reviewed. The principles of these methods are described. Most of the techniques and procedures employed to remove Phe from the protein hydrolysate are based on the liberation of the amino acid using enzymatic hydrolysis. Free Phe is then removed via adsorption. Therefore, knowing the phenylalanine (Phe) content of foods as well as principles of procedures and techniques used for creating low Phe diets is very important for managing the diet of patients with phenylketonuria. Allowed foods and foods that should be avoided by persons with phenylketonuria are mentioned. Low Phe cereal based foods (i. e. toast bread, pasta, shamy bread, pan bread and rice) and dairy based foods are also considered. The US FDA regulation of aspartame labeling is also stated.

Повышенный интерес к применению управления питанием пациентов с фенилкетонурией очевиден. Примеры использования включают небольшие определенные количества фенилаланина, поступающего в виде «обменных» пищевых продуктов, не содержащую фенилаланин белковую замену и пищевые продукты с низким содержанием фенилаланина. В данной статье сделан обзор содержания важных компонентов диет с низким содержанием фенилаланина и самых современных методов и процедур, используемых для создания нескольких видов диет с низким содержанием фенилаланина из различных пищевых источников для лиц с фенилкетонурией. Описаны принципы этих методов. Большинство методов и процедур, применяемых для удаления Phe из белкового гидролизата, основано на высвобождении аминокислоты, используя ферментативный гидролиз. Свободный Phe затем удаляется путем адсорбции. Таким образом, знание содержания фенилаланина в пищевых продуктах, а также принципов методов и процедур, применяемых для создания диет с низким содержанием фенилаланина, очень важно для управления диетой для пациентов с фенилкетонурией. Перечислены разрешенные пищевые продукты и продукты, употребления которых следует избегать пациентам с фенилкетонурией. Также рассмотрены пищевые продукты на основе зерновых (т. е. хлеб для тостов, макаронные изделия, пита, формовой хлеб и рис) и молочные продукты. Также сообщается о регулировании US FDA маркировки аспартама.

фенилкетонурияфенилаланинпациентыаспартамдиетаphenylketonuriaphenylalaninepatientsaspartamedietReferencesHendriksz, C.J., Walter, J.H. (2004). Update on phenylketonuria. Current Paediatrics, 14(5), 400–406. https://doi.org/10.1016/j.cupe.2004.05.003Hendriksz, C.J., Walter, J.H. (2004). Update on phenylketonuria. Current Paediatrics, 14(5), 400–406. https://doi.org/10.1016/j.cupe.2004.05.003Sirtori, L.R., Dutra-Filho, C.S., Fitarelli, D., Sitta, A., Haeser, A., A G Barschak, A.G. et al. (2005). Oxidative stress in patients with phenylketonuria. Biochimica et Biophysica Acta (BBA) — Molecular Basis of Disease, 1740(1), 68–73. https://doi.org/10.1016/j.bbadis.2005.02.005Sirtori, L.R., Dutra-Filho, C.S., Fitarelli, D., Sitta, A., Haeser, A., A G Barschak, A.G. et al. (2005). Oxidative stress in patients with phenylketonuria. Biochimica et Biophysica Acta (BBA) — Molecular Basis of Disease, 1740(1), 68–73. https://doi.org/10.1016/j.bbadis.2005.02.005Flydal, M. I., Martinez, A. (2013). Phenylalanine hydroxylase: function, structure, and regulation. IUBMB Life, 65(4), 341–349. https://doi.org/10.1002/iub.1150Flydal, M. I., Martinez, A. (2013). Phenylalanine hydroxylase: function, structure, and regulation. IUBMB Life, 65(4), 341–349. https://doi.org/10.1002/iub.1150Okano, Y., Hase, Y., Lee, D.-H., Furuyama, J.-I., Shintaku, H., Oura, T. et al. (1992). Frequency and distribution of phenylketonuric mutations in Orientals. Human Mutation, 1(3), 216–220. https://doi.org/10.1002/humu.1380010307Okano, Y., Hase, Y., Lee, D.-H., Furuyama, J.-I., Shintaku, H., Oura, T. et al. (1992). Frequency and distribution of phenylketonuric mutations in Orientals. Human Mutation, 1(3), 216–220. https://doi.org/10.1002/humu.1380010307Shawky, R.M., Elhawary, N.A., Elsayed, S.M., Abdel-Hamid, H., Elsedfy, H.H. (2006). Updated listing of mutation map at the human phenylalanine locus among Egyptian population. The Egyptian Journal of Medical Human Genetics, 7, 15–22.Shawky, R.M., Elhawary, N.A., Elsayed, S.M., Abdel-Hamid, H., Elsedfy, H.H. (2006). Updated listing of mutation map at the human phenylalanine locus among Egyptian population. The Egyptian Journal of Medical Human Genetics, 7, 15–22.Effat, L.K., Essawi, M.L., Abd El Hamid, M.S., Hawary, N., Gad, Y.Z. (2008). Screening for six Mediterranean mutation in 90 Egyptians patients with phenylketonuria. Bratislava Medical Journal — Bratislavske Lekarske Listy, 109(1), 17–19.Effat, L.K., Essawi, M.L., Abd El Hamid, M.S., Hawary, N., Gad, Y.Z. (2008). Screening for six Mediterranean mutation in 90 Egyptians patients with phenylketonuria. Bratislava Medical Journal — Bratislavske Lekarske Listy, 109(1), 17–19.Silao, C.L.T., Canson, D.M., Hernandez, K.N., Chiong, M.A.D., Capistrano-Estrada, S., David-Padilla, C. (2009). Mutations of the phenylalanine hydroxylase (PAH) gene in Filipino patients with phenylketonuria. Acta Medica Philippino, 43(2), 36–39. https://doi.org/10.47895/amp.v43i2.2515Silao, C.L.T., Canson, D.M., Hernandez, K.N., Chiong, M.A.D., Capistrano-Estrada, S., David-Padilla, C. (2009). Mutations of the phenylalanine hydroxylase (PAH) gene in Filipino patients with phenylketonuria. Acta Medica Philippino, 43(2), 36–39. https://doi.org/10.47895/amp.v43i2.2515Sutivijit, Y., Banpavichit, A., Wiwanitkit, V. (2011). Prevalence of neonatal hypothyroidism and phenylketonuria in Southern Thailand: A 10-year report. Indian Journal of Endocrinology and Metabolism, 15(2), 115–117. https://doi.org/10.4103/2230–8210.81941Sutivijit, Y., Banpavichit, A., Wiwanitkit, V. (2011). Prevalence of neonatal hypothyroidism and phenylketonuria in Southern Thailand: A 10-year report. Indian Journal of Endocrinology and Metabolism, 15(2), 115–117. https://doi.org/10.4103/2230–8210.81941Lim, J.S., Tan, E.S., John, C.M., Poh, S., Yeo, S.J., Ang, J.S.M. et al. (2014). Inborn error of metabolism (IEM) screening in Singapore by electrospray ionizationtandem mass spectrometry (ESI/MS/MS): An 8 year journey from pilot to current program. Molecular Genetics and Metabolism, 113(1–2), 53–61. https://doi.org/10.1016/j.ymgme.2014.07.018Lim, J.S., Tan, E.S., John, C.M., Poh, S., Yeo, S.J., Ang, J.S.M. et al. (2014). Inborn error of metabolism (IEM) screening in Singapore by electrospray ionizationtandem mass spectrometry (ESI/MS/MS): An 8 year journey from pilot to current program. Molecular Genetics and Metabolism, 113(1–2), 53–61. https://doi.org/10.1016/j.ymgme.2014.07.018Xiang, L., Tao, J., Deng, K., Li, X., Li, Q., Yuan, X. et al. (2019). Phenylketonuria incidence in China between 2013 and 2017 based on data from the Chinese newborn screening information system: A descriptive study. BMJ Open, 9(8), Article e031474. https://doi.org/10.1136/bmjopen-2019–031474Xiang, L., Tao, J., Deng, K., Li, X., Li, Q., Yuan, X. et al. (2019). Phenylketonuria incidence in China between 2013 and 2017 based on data from the Chinese newborn screening information system: A descriptive study. BMJ Open, 9(8), Article e031474. https://doi.org/10.1136/bmjopen-2019–031474Mohsen, S.M., Yaseen, A.A., Shouk, A.A., Ammar, A.M., Mohammad, A.A. (2021). Quality characteristics improvement of low phenylalanine pasta. Egyptian Journal of Food Science, 49(2), 287–296. https://doi.org/10.21608/ejfs.2021.76597.1105Mohsen, S.M., Yaseen, A.A., Shouk, A.A., Ammar, A.M., Mohammad, A.A. (2021). Quality characteristics improvement of low phenylalanine pasta. Egyptian Journal of Food Science, 49(2), 287–296. https://doi.org/10.21608/ejfs.2021.76597.1105van Calcar, S.C., Ney, D.M. (2012). Food products made with glycomacropeptide, a low-phenylalanine whey protein, provide a new alternative to amino acid–based medical foods for nutrition management of phenylketonuria. Journal of the Academy of Nutrition and Dietetics, 112(8), 1201–1210. https://doi.org/10.1016/j.jand.2012.05.004van Calcar, S.C., Ney, D.M. (2012). Food products made with glycomacropeptide, a low-phenylalanine whey protein, provide a new alternative to amino acid–based medical foods for nutrition management of phenylketonuria. Journal of the Academy of Nutrition and Dietetics, 112(8), 1201–1210. https://doi.org/10.1016/j.jand.2012.05.004van Wegberg, A.M.G., MacDonald, A., Ahring, K., Bélanger-Quintana, A., Blau N., Bosch, A.M. et al. (2017). The complete European guidelines on phenylketonuria: diagnosis and treatment. Orphanet Journal of Rare Diseases, 12, Article 162. https://doi.org/10.1186/s13023–017–0685–2van Wegberg, A.M.G., MacDonald, A., Ahring, K., Bélanger-Quintana, A., Blau N., Bosch, A.M. et al. (2017). The complete European guidelines on phenylketonuria: diagnosis and treatment. Orphanet Journal of Rare Diseases, 12, Article 162. https://doi.org/10.1186/s13023–017–0685–2Zaky, M.S., Effat, L.K., Hassan, S.S. (2016). Evaluation of physical growth and weight patterns of Egyptian Children with phenylketonuria under a phenylalanine-restricted diet. Anatomy & Physiology: Current Research, 6(1), Article 1000187. https://doi.org/10.4172/2161–0940.1000187Zaky, M.S., Effat, L.K., Hassan, S.S. (2016). Evaluation of physical growth and weight patterns of Egyptian Children with phenylketonuria under a phenylalanine-restricted diet. Anatomy & Physiology: Current Research, 6(1), Article 1000187. https://doi.org/10.4172/2161–0940.1000187Kamel, A.S., Ahmed, E.E.G., Hassan, F.S., Masoud, M., Mohamed, W. S. (2021). Relationship between time at diagnosis and clinical manifestations of phenylketonuria in a sample of Egyptian children. Alexandria Journal of Pediatrics, 34(2), 76–182. https://doi.org/10.4103/ajop.ajop_20_21Kamel, A.S., Ahmed, E.E.G., Hassan, F.S., Masoud, M., Mohamed, W. S. (2021). Relationship between time at diagnosis and clinical manifestations of phenylketonuria in a sample of Egyptian children. Alexandria Journal of Pediatrics, 34(2), 76–182. https://doi.org/10.4103/ajop.ajop_20_21Silva, V.D.M., de Marco, L.M., Afonso, W.O., Lopes, D.C.F., Januario, J.N., Aguiar, M.J.B. et al. (2007). Preparation of low-phenylalanine whey hydrolysates, using papain and pancreatin immobilized on activated carbon and alumina. American Journal of Food Technology, 2(5), 327–341. https://doi.org/10.3923/ajft.2007.327.341Silva, V.D.M., de Marco, L.M., Afonso, W.O., Lopes, D.C.F., Januario, J.N., Aguiar, M.J.B. et al. (2007). Preparation of low-phenylalanine whey hydrolysates, using papain and pancreatin immobilized on activated carbon and alumina. American Journal of Food Technology, 2(5), 327–341. https://doi.org/10.3923/ajft.2007.327.341Pencharz, B., Hsu, J. W.-C., Ball, R. O., (2007). Aromatic amino acid requirements in healthy human subjects. The Journal of Nutrition, 137(6 Suppl 1), S1576 — S1578. https://doi.org/10.1093/jn/137.6.1576SPencharz, B., Hsu, J. W.-C., Ball, R. O., (2007). Aromatic amino acid requirements in healthy human subjects. The Journal of Nutrition, 137(6 Suppl 1), S1576 — S1578. https://doi.org/10.1093/jn/137.6.1576SYaseen A. A., Shouk A. A. (2011). Low phenylalanine Egyptian shamy bread. Polish Journal of Food and Nutrition Sciences, 61(4), 257–262. https://doi.org/10.2478/v10222–011–0029–1Yaseen A. A., Shouk A. A. (2011). Low phenylalanine Egyptian shamy bread. Polish Journal of Food and Nutrition Sciences, 61(4), 257–262. https://doi.org/10.2478/v10222–011–0029–1MacDonald, A., Rylance, G., Davies, P., Asplin, D., Hall, S.K., Booth, I.W. (2003). Free use of fruits and vegetables in phenylketonuria. Journal of Inherited Metabolic Disease, 26(4), 327–338. https://doi.org/10.1023/a:1025150901439MacDonald, A., Rylance, G., Davies, P., Asplin, D., Hall, S.K., Booth, I.W. (2003). Free use of fruits and vegetables in phenylketonuria. Journal of Inherited Metabolic Disease, 26(4), 327–338. https://doi.org/10.1023/a:1025150901439Guimarães, C.P., Lanfer-Marquez, U.M. (2005). Estimation of phenylalanine (Phe) contents in dehydrated soups: Significance of non-protein nitrogen. Brazilian Journal of Pharmaceutical Sciences, 41(3), 365–376. https://doi.org/10.1590/S1516–93322005000300010 (In Portuguese)Guimarães, C.P., Lanfer-Marquez, U.M. (2005). Estimation of phenylalanine (Phe) contents in dehydrated soups: Significance of non-protein nitrogen. Brazilian Journal of Pharmaceutical Sciences, 41(3), 365–376. https://doi.org/10.1590/S1516–93322005000300010 (In Portuguese)Ozboy, O. (2002). Development of corn starch-gum bread for phenylketonuria patients. Food/Nahrung, 46(2), 87–91. https://doi.org/10.1002/1521-3803(20020301)46:2%3C87::AID-FOOD87%3E3.0.CO;2-YOzboy, O. (2002). Development of corn starch-gum bread for phenylketonuria patients. Food/Nahrung, 46(2), 87–91. https://doi.org/10.1002/1521-3803(20020301)46:2%3C87::AID-FOOD87%3E3.0.CO;2-YDalei, S.K., Adlakha, N. (2022). Food regime for phenylketonuria: Presenting complications and possible solutions. Journal of Multidisciplinary Healthcare, 15, 125–136. https://doi.org/10.2147/JMDH.S330845Dalei, S.K., Adlakha, N. (2022). Food regime for phenylketonuria: Presenting complications and possible solutions. Journal of Multidisciplinary Healthcare, 15, 125–136. https://doi.org/10.2147/JMDH.S330845Mohsen, S.M., Yaseen, A.A., Ammar, A.M., Mohammad, A.A. (2010). Quality characteristics improvement of low-phenylalanine toast bread. International Journal of Food Science and Technology, 45(10), 2042–2051. https://doi.org/10.1111/j.1365–2621.2010.02365.xMohsen, S.M., Yaseen, A.A., Ammar, A.M., Mohammad, A.A. (2010). Quality characteristics improvement of low-phenylalanine toast bread. International Journal of Food Science and Technology, 45(10), 2042–2051. https://doi.org/10.1111/j.1365–2621.2010.02365.xYaseen, A.A., Shouk, A.A., El-Hamzy, E.M.A., Ashour, M.M.S. (2012). Production and evaluation of low phenylalanine pan bread. Journal of Applied Sciences Research, 8(12), 5799–5805.Yaseen, A.A., Shouk, A.A., El-Hamzy, E.M.A., Ashour, M.M.S. (2012). Production and evaluation of low phenylalanine pan bread. Journal of Applied Sciences Research, 8(12), 5799–5805.Yaseen, A. A., Shouk, A. A. (2011). Low phenylalanine pasta. International Journal of Nutrition and Metabolism, 3(10), 128–135.Yaseen, A. A., Shouk, A. A. (2011). Low phenylalanine pasta. International Journal of Nutrition and Metabolism, 3(10), 128–135.Silvestre, M.P.C., Vieira, C.R., Silva, M.R., Carreira, R.L., Silva, V.D.M., Morais, H.A. (2009). Protein extraction and preparation of protein hydrolysates from rice with low phenylalanine content. Asian Journal of Scientific Research, 2(3), 146–154. https://doi.org/10.3923/ajsr.2009.146.154Silvestre, M.P.C., Vieira, C.R., Silva, M.R., Carreira, R.L., Silva, V.D.M., Morais, H.A. (2009). Protein extraction and preparation of protein hydrolysates from rice with low phenylalanine content. Asian Journal of Scientific Research, 2(3), 146–154. https://doi.org/10.3923/ajsr.2009.146.154Hassanpour, S., Khosravi-Darani, K., Ramezan, Y., Hashempour-Baltork, F. (2023). Evaluation of producing low phenylalanine milk by formulation procedure for phenylketonuria patients. Letters in Applied NanoBioScience, 12(4), Article 142. https://doi.org/10.33263/LIANBS124.142Hassanpour, S., Khosravi-Darani, K., Ramezan, Y., Hashempour-Baltork, F. (2023). Evaluation of producing low phenylalanine milk by formulation procedure for phenylketonuria patients. Letters in Applied NanoBioScience, 12(4), Article 142. https://doi.org/10.33263/LIANBS124.142Bu, T., Zhou, M., Zheng, J., Yang, P., Song, H., Li, S. et al. (2020). Preparation and characterization of a low-phenylalanine whey hydrolysate using two-step enzymatic hydrolysis and macroporous resin adsorption. LWT, 132, Article 109753. https://doi.org/10.1016/j.lwt.2020.109753Bu, T., Zhou, M., Zheng, J., Yang, P., Song, H., Li, S. et al. (2020). Preparation and characterization of a low-phenylalanine whey hydrolysate using two-step enzymatic hydrolysis and macroporous resin adsorption. LWT, 132, Article 109753. https://doi.org/10.1016/j.lwt.2020.109753Solverson, P., Murali, S.G., Brinkman, A.S., Nelson, D.W., Clayton, M.K., Yen, C.-L.E. et al. (2012). Glycomacropeptide, a low-phenylalanine protein isolated from cheese whey, supports growth and attenuates metabolic stress in the murine model of phenylketonuria. American Journal of Physiology-Endocrinology and Metabolism, 302(7), E885–E895. https://doi.org/10.1152/ajpendo.00647.2011Solverson, P., Murali, S.G., Brinkman, A.S., Nelson, D.W., Clayton, M.K., Yen, C.-L.E. et al. (2012). Glycomacropeptide, a low-phenylalanine protein isolated from cheese whey, supports growth and attenuates metabolic stress in the murine model of phenylketonuria. American Journal of Physiology-Endocrinology and Metabolism, 302(7), E885–E895. https://doi.org/10.1152/ajpendo.00647.2011Soares, R.D.L., Biasutti, E.A.R., Capobiango, M., Vieira, C.R., Silva, V.D.M., Morais, H.A. et al. (2006). Preparation of enzymatic skim milk hydrolysates with low phenylalanine content. Acta Farmaceutica Bonaerense, 25(3), 325–332.Soares, R.D.L., Biasutti, E.A.R., Capobiango, M., Vieira, C.R., Silva, V.D.M., Morais, H.A. et al. (2006). Preparation of enzymatic skim milk hydrolysates with low phenylalanine content. Acta Farmaceutica Bonaerense, 25(3), 325–332.Silvestre, M.P.C., Lopes, C.O., Silva, M.R., Silva, V.D.M., Aguiar, M.J.B., Amorin, L.L. (2011). Study of Brazilian beans: Protein extraction and hydrolysis followed by phenylalanine removal. American Journal of Food Technology, 6(10), 893–903. https://doi.org/10.3923/ajft.2011.893.903Silvestre, M.P.C., Lopes, C.O., Silva, M.R., Silva, V.D.M., Aguiar, M.J.B., Amorin, L.L. (2011). Study of Brazilian beans: Protein extraction and hydrolysis followed by phenylalanine removal. American Journal of Food Technology, 6(10), 893–903. https://doi.org/10.3923/ajft.2011.893.903van Spronsen, F.J., van Wegberg, A.M.J., Ahring, K., Bélanger-Quintana, A., Blau, N., Bosch, A.M. et al. (2017). Key European guidelines for the diagnosis and management of patients with phenylketonuria. The Lancet Diabetes and Endocrinology, 5(9), 743–756. http://doi.org/10.1016/S2213–8587(16)30320–5van Spronsen, F.J., van Wegberg, A.M.J., Ahring, K., Bélanger-Quintana, A., Blau, N., Bosch, A.M. et al. (2017). Key European guidelines for the diagnosis and management of patients with phenylketonuria. The Lancet Diabetes and Endocrinology, 5(9), 743–756. http://doi.org/10.1016/S2213–8587(16)30320–5FDA (2023). CFR — Code of Federal Regulations Title. Title 21—Food and Drugs, Chapter1 — Food and Drugs Administration Department of Health and Human Services, Subchapter C- Drugs general, Part 201- Labelling, Subpart A- General Labelling Provision. Retrieved from https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=201.21 Accessed April 16, 2023FDA (2023). CFR — Code of Federal Regulations Title. Title 21—Food and Drugs, Chapter1 — Food and Drugs Administration Department of Health and Human Services, Subchapter C- Drugs general, Part 201- Labelling, Subpart A- General Labelling Provision. Retrieved from https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=201.21 Accessed April 16, 2023

The authors declare that there are no conflicts of interest present.