Vitamin B12 and Folate in Adherent and Non-Adherent Individuals with Phenylketonuria: A Cross-Sectional Study, Systematic Review, and Meta-Analysis
Bokayeva, Kamila; Jamka, Małgorzata; Walkowiak, Dariusz; Duś-Żuchowska, Monika; Kałużny, Łukasz; Wichłacz-Trojanowska, Natalia; Chrobot, Agnieszka; Mozrzymas, Renata; Sultanova, Gulnara; Herzig, Karl-Heinz; Walkowiak, Jarosław (2025-07-01)
MDPI
01.07.2025
Bokayeva, K., Jamka, M., Walkowiak, D., Duś-Żuchowska, M., Kałużny, Ł., Wichłacz-Trojanowska, N., Chrobot, A., Mozrzymas, R., Sultanova, G., Herzig, K.-H., & Walkowiak, J. (2025). Vitamin B12 and Folate in Adherent and Non-Adherent Individuals with Phenylketonuria: A Cross-Sectional Study, Systematic Review, and Meta-Analysis. Metabolites, 15(7), 438. https://doi.org/10.3390/metabo15070438
https://creativecommons.org/licenses/by/4.0/
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
https://creativecommons.org/licenses/by/4.0/
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
https://creativecommons.org/licenses/by/4.0/
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202508195426
https://urn.fi/URN:NBN:fi:oulu-202508195426
Tiivistelmä
Abstract
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.
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.
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