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Background: Phenylketonuria (PKU) is a rare genetic metabolic disorder in which especially high phenylalanine (Phe) concentrations cause brain dysfunction. If untreated, this brain dysfunction results in severe microcephaly, intellectual disability, and behavioral problems. Dietary restriction of Phe is the mainstay of PKU treatment, with long-term successful outcomes. Aspartame, an artificial sweetener sometimes added into medications, is metabolized in the gut into Phe. Then, patients suffering from PKU on a Phe-restricted diet should avoid consumption of aspartame. The aim of our study was to evaluate the number of drugs containing aspartame and/or Phe as an excipient, and to quantify their corresponding Phe intake. Methods: The list of drugs marketed in France containing aspartame and/or Phe was established using a national medication database called "Theriaque". For each drug, the corresponding daily Phe intake was calculated according to age and weight and was distributed into 3 categories: high (> 40 mg/d), medium (10 to 40 mg/d) and low (< 10 mg/d) Phe intake. Results: The number of drugs containing Phe or its precursor aspartame remained very limited (n = 401). Among the aspartame containing drugs, Phe intakes were significant (medium or high) for only half of them whereas there were negligible for the others. Furthermore, these medications with a significant Phe intake were limited to few pharmaceutical classes (mainly antiinfectives agents, analgesics, and drugs for nervous system), and within these classes the drugs were limited to a small number of molecules, including principally amoxicillin, amoxicillin + clavulanic acid and paracetamol/ acetaminophen. Discussion: In situations requiring the use of these molecules, we propose as an alternative, the use of an aspartame-free form of these molecules or a form with a low Phe intake. If it is not possible, we propose as second-line the use of another antibiotics or analgesics. Finally, we have to remember the benefits-risk balance to use medications containing significant Phe intake in PKU patients. Indeed, it may be better to use a Phe containing medication in the absence of an aspartame-free form of this drug rather than to leave a person with PKU without treatment. [ABSTRACT FROM AUTHOR]

This study aimed to estimate the exposure to seven additives (benzoates, parabens, nitrites, nitrates, BHA, BHT and aspartame) in children aged less than 3 years old in France. A conservative approach, combining individual consumption data with maximum permitted levels, was carried out for all the additives. More refined estimates using occurrence data obtained from products’ labels (collected by the French Observatory of Food Quality) were conducted for those additives that exceeded the acceptable daily intake (ADI). Information on additives’ occurrence was obtained from the food labels. When the ADI was still exceeded, the exposure estimate was further refined using measured concentration data, if available. When using the maximum permitted level (MPL), the ADI was exceeded for benzoates (1.94 mg kg–1bw day–1), nitrites (0.09 mg kg–1bw day–1) and BHA (0.39 mg kg–1bw day–1) in 25%, 54% and 20% of the entire study population respectively. The main food contributors identified with this approach were current foods as these additives are not authorised in specific infant food: vegetable soups and broths for both benzoates and BHA, delicatessen and meat for nitrites. The exposure estimate was significantly reduced when using occurrence data, but in the upper-bound scenario the ADI was still exceeded significantly by the age group 13–36 months for benzoates (2%) and BHA (1%), and by the age group 7–12 months (16%) and 13–36 months (58%) for nitrites. Measured concentration data were available exclusively for nitrites and the results obtained using these data showed that the nitrites’ intake was below the ADI for all the population considered in this study. These results suggest that refinement of exposure, based on the assessment of food levels, is needed to estimate the exposure of children to BHA and benzoates for which the risk of exceeding the ADI cannot be excluded when using occurrence data. [ABSTRACT FROM PUBLISHER]