Advancements in food science for Phenylketonuria (PKU) management: a comprehensive review

Figures & data

Figure 1. Annual scientific production obtained from Scopus-Web of Science database on PKU-food related search.

Figure 2. Distribution of corresponding authors’ countries in PKU-related research, categorized by single country publications (SCP) and multiple country publications (MCP).

Figure 3. Database keywords co-occurrence network based on the search of PKU-food topic from Scopus and Web of Science database (a, left) and overlay visualization based on temporal dimension from 2000 to 2023 (b, right).

Figure 4. Principal component analysis of keywords from bibliometric database. Each point represents a keyword, color-coded by clusters that signify thematic concentrations in the research field. The axes intersect at zero, highlighting the mean-centered scaling of PCA dimensions.

Figure 5. Thematic map of PKU-related food science research trends using bibliometric data.

Table 1. PKU specified food supplements list obtained after web research.

Company – registered trademark	Product type	Product description	Phenylalanine content (mg/100g)	Main ingredients	Production area	Reference
Relief Therapeutics – PKU GOLIKE®	Bar	Medical food bar made with fruit and prolonged release amino acid mixture	25	Dehydrated pineapple 34.9%, amino-acid mixture 21.3%; dextrin, candied lemon 14.8%; dehydrated mango 3.9%, dehydrated papaya 3.7%, dehydrated apple 2.9 %	United States	www.pkugolike.com
	Granules	Phenylalanine-free medical food in the form of granules for oral use	0	Various Phe-free aminoacid mixture
Danone Nutricia –Lophlex®	Juice	Protein substitutes ready to drink	0	Orange juice concentrate, water, corn sirup solids	Europe	www.nutricia.co.uk
	Jam	Semi-solid (spoonable) protein substitute	0	Apple juice from concentrate, sugar, water, grape juice from concentrate, blackcurrant juice from concentrate
Danone Nutricia - PhenylAde®	GMP-Powder	Phenylalanine-free GMP powdered formula	0	Water, whey protein isolate (glycomacropeptide), sugar, refined vegetable oils (canola, high oleic sunflower)
Danone Nutricia - Easiphen®	Drink	Phenylalanine-free ready to eat drink for adults	0	Water, sugar, high oleic sunflower oil, canola oil, flavoring, dried glucose sirup, flavor enhancer (E330), stabilizers (E460(i), E412, E415), walnut oil, aminoacids mix
Danone Nutricia - GMPro® LQ	Drink	Low phenylalanine ready-to-drink liquid	7.2	Water, casein glycomacropeptide (GMP) isolate, sugar, refined vegetable oils, oil from Crypthecodinium cohnii, docosahexaenoic and eicosapentaenoic-rich oil from the microalgae Schizochytrium sp., aminoacids and vitamin mix
Vitaflo® - Vitabite™	Bar	Low phenylalanine energy bars	n.r.	Lactose, fractionated palm kernel oil, sucrose, flavorings, carob flour, soy lecithin	Europe	www.nestlehealthscience.it
Vitaflo® – Squeezie^TM	Drink	Apple and banana flavored ready-to-feed phenylalanine free protein substitute	0	Water, sucrose, maltodextrin, starch, dehydrated red apple, dehydrated banana, aminoacids mix, oil from Mortierella alpina, oil from Crypthecodinium cohnii, vegetable oil (high oleic sunflower oil), vitamin mix, antioxidants (E306, E304)
Vitaflo® – express plus™	Powder	Powdered Phenylalanine-free medical food	0	Aminoacids mix, corn starch, L-serine, corn sirup, refined tuna oil (fish), mineral salts mix, vitamins mix
Vitaflo® - PKU air®	Drink	Ready-to-drink phenylalanine-free protein substitute	0	Water, flavors, aminoacids mix, thickeners, soy lecithin, fish oil, acesulfame K, sucralose
Ajinomoto group - Glytactin®	Bar	Low phenylalanine chewy yoghurt bar	40.7	Coating (sugar, partially hydrogenated palm kernel oil, nonfat dry milk, soy lecithin, artificial flavoring), guava (natural cane sugar, citric acid), whey protein isolate (glycomacropeptide), corn sirup, coconut, palm fruit shortening, vitamin, mineral and aminoacids blend	United States	www.cambrooke.com
	GMP Powder	Glycomacropeptide (GMP) based powdered medical food complete with vitamins and minerals	0	Glycomacropeptide, maltodextrin, sugar, tapioca food starch, high oleic canola oil, tapioca sirup solids
	Drink	Ready to drink protein substitute	8	Water, sucrose, whey protein isolate (glycomacropeptide, glytactin), vitamin and mineral blend
MetaX - XPhe®	Bar	Low phenylalanine protein supplement	0	n.r	Europe	www.mamoxi.it
	Drink	Ready-to-drink protein supplement	0	n.r
Piam Farmaceutici – Afenil® 1/2/3/4	Drink	Ready to drink protein supplement	0	Mix of aminoacids, polyunsaturated fatty acids and minerals (not specified)	Europe	www.piamfarmaceutici.com
Piam Farmaceutici – Afenil GMP-up®	Bar	Low phenylalanine protein supplement based on GMP	21.03	n.r.

n.r. = not reported.

Figure 6. Schematic representation of a general 3-D food printer with its main components.

Table 2. Advantages and disadvantages of 3D food printing for PKU food production and formulations.

Advantages	Disadvantages
Customization and Precision: 3DFP allows for the exact control of ingredients, including the critical restriction of phenylalanine content in the diet of PKU patients. This precision ensures that each food item produced meets the specific nutritional requirements of the individual.	Accessibility and Cost: The high cost of 3DFP technology and its relative scarcity may limit access for many PKU patients, potentially making it an option only for those in more developed or affluent areas.
Nutritional Optimization: Beyond controlling phenylalanine, 3DFP can be used to fortify foods with vitamins and minerals that PKU patients may lack due to their restricted diets, ensuring a balanced and nutritious diet.	Technical Complexity: The need for specialized knowledge to operate 3D food printers and formulate suitable food matrices may pose a barrier to widespread adoption.
Increased Palatability and Variety: By creating foods that are more visually appealing and varied in texture and taste, 3DFP can make the PKU diet more enjoyable and easier to adhere to, especially for children.	Safety and Regulatory Concerns: Ensuring the safety and nutritional adequacy of 3D-printed foods requires strict regulatory oversight, which could slow down innovation and implementation.
Reduction in Preparation Time: 3DFP can produce ready-to-eat foods that require minimal preparation, offering convenience to PKU patients and their families.	Cultural Acceptance: Acceptance of 3D-printed food as a regular part of the diet may take time, as people may have reservations about consuming "printed" food, despite its nutritional adequacy.

Data availability statement

The data presented in this study are available on request from the corresponding author.