Renata Mozrzymas

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 6–41 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 [30.39–41.65] vs. 32.90 [26.50–40.00] ng/mL, p = 0.034) and regular formula consumers (35.97 [30.03–42.28] vs. 30.20 [26.08–35.06] ng/mL, p = 0.002). Beta-carotene was elevated with regular intake (74.40 [56.70–98.45] vs. 53.20 [34.10–68.60] 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 < 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.

Background/Objectives: The impact of dietary adherence and regular formula intake on the vitamin levels in individuals with phenylketonuria (PKU) remains unclear. This study aimed to assess the influence of both adherence to dietary management and regular formula intake on the vitamin B12 and folate levels in individuals with PKU. Methods: This cross-sectional multicentre study included 63 patients with PKU aged 12–41 years. The participants were classified as adherent or non-adherent based on their mean plasma phenylalanine levels or as regular or irregular formula consumers. The participants’ vitamin B12 and folate levels were compared across these groups. In addition, a systematic search of PubMed, Web of Science, Scopus, and Cochrane Library identified 11,631 studies comparing vitamin B12 and folate levels between adherent vs. non-adherent patients and regular vs. irregular formula intake groups, of which eight met the inclusion criteria. Analyses were conducted using random-effects and fixed-effects models and effect sizes were expressed as standardised mean differences (SMDs). Results: This cross-sectional study showed significantly higher vitamin B12 and folate levels in adherent vs. non-adherent individuals (767.6 ± 264.5 vs. 524.7 ± 216.4 pg/mL; 13.44 ± 1.96 vs. 10.62 ± 3.36 ng/mL, both p < 0.001) and in regular vs. irregular formula consumers (746.7 ± 228.4 vs. 527.4 ± 281.9 pg/mL; 13.32 ± 2.25 vs. 10.48 ± 3.23 ng/mL, p < 0.0001 and p < 0.001 respectively). The meta-analysis found no significant differences between the adherent and non-adherent groups, which were defined based on their phenylalanine levels, but showed higher vitamin B12 levels (fixed-effects model, SMD: 1.080, 95% CI: 0.754, 1.405, p < 0.0001) and a near-significant trend toward higher folate levels (random-effects model, SMD: 0.729, 95% CI: −0.032, 1.490, p = 0.061) in regular formula consumers. Conclusions: Regular formula intake is a key determinant of vitamin B12 in patients with PKU. These findings highlight the importance of consistent formula use in dietary management and warrant further research.

This is the first study to evaluate vitamin K status in relation to dietary intake and phenylalanine dietary compliance in patients with phenylketonuria (PKU). The dietary and PKU formula intake of vitamin K was calculated in 34 PKU patients, with vitamin K status determined by the measurement of prothrombin induced by vitamin K absence (PIVKA-II). Blood phenylalanine concentrations in the preceding 12 months were considered. There were significantly more phenylalanine results exceeding 6 mg/dL in patients with normal PIVKA-II concentrations than in those with abnormal PIVKA-II levels (p = 0.035). Similarly, a higher total intake of vitamin K and dietary vitamin intake expressed as μg/day (p = 0.033 for both) and %RDA (p = 0.0002 and p = 0.003, respectively) was observed in patients with normal PIVKA-II levels. Abnormal PIVKA-II concentrations were associated with a lower OR (0.1607; 95%CI: 0.0273–0.9445, p = 0.043) of having a median phenylalanine concentration higher than 6 mg/dL. In conclusion, vitamin K deficiency is not uncommon in phenylketonuria and may also occur in patients with adequate vitamin K intake. PKU patients with better dietary compliance have a higher risk of vitamin K deficiency. The present findings highlight the need for further studies to re-evaluate dietary recommendations regarding vitamin K intake, both concerning formula-based and dietary consumption of natural products.

The aim of the study was to assess both patients’ and their parents’ knowledge of phenylketonuria (PKU) treatment and compliance with PKU diet. The study included 173 PKU patients aged 10–19 and 110 parents of PKU children who were enrolled in the study on the basis of questionnaire data. The study also included 45 patients aged ≥20. Our study demonstrated that only 45% (n = 74) of PKU patients knew daily Phe intake recommendations, 27% of patients (n = 41) knew the Phe content in a minimum of three out of four researched food products. Patients’ knowledge concerning Phe intake (p = 0.0181) and the knowledge of selected food products (p = 0.041819) improved with age. We did not establish such a correlation in the group of PKU children’s parents. Approximately 31% of patients and 22% of parents reported helplessness, which increased with the child’s age, associated with the necessity to adhere to the diet; 30% of patients reported feeling ashamed of the fact that they could not eat all food products. Regardless of age, children were more likely than parents to report helplessness (p = 0.032005). Among patients, 41.40% declared that they would wish to select products unassisted but their parents did not permit them to do so. The question of whether parents teach children self-reliance in meal preparation was answered affirmatively by 98% of parents and only 81% of children (p = 0.0001). Our data demonstrated that parents’ and children’s knowledge concerning treatment recommendations and food products does not have a direct impact on attitude to the PKU diet. Limiting children’s independence in meal selection, growing helplessness in the face of dietary adherence and shame resulting from the necessity to follow a different diet observed in PKU families are responsible for shaping and perpetuating a consistently negative attitude to the diet. The care of PKU paediatric patients requires consistent, long-term family and individual therapy which may counteract the effects of learned helplessness. In regard to the educational effort, a good parent-child relationship as well as the teaching of behaviours motivating patients to comply with the diet are of great importance.