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The effects of nutritional supplementation for children and adolescents with sickle cell disease: a systematic review and meta-analyses
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Advisor(s)
Abstract(s)
Background & aims: Sickle cell disease (SCD), a neglected chronic genetic blood disorder that severely impacts the pediatric population, often leading to premature death, is associated with compromised nutritional status. This study aimed to evaluate the effect of nutritional supplementation on SCD-related complications. Methods: A systematic review with searches in PubMed, Scopus, and Web of Science was performed. Randomized controlled trials (RCT) assessing diet or supplements as a complementary therapy for children and adolescents with SCD were included (PROSPERO: CRD42024532369). The data for outcomes of interest (efficacy, safety) were pooled using pairwise and network meta-analyses with ranking (p-score) analysis. The results were presented as odds ratio or mean differences with 95 % confidence intervals (NMAstudio2.0). Results: Twenty RCTs were included (2002–2023) (n = 2058), analyzing 9 dietary supplements on different regimens. All patients use hydroxyurea as an active treatment. Supplementation with fatty acids (n = 3 studies) and l-arginine (n = 4) presented higher efficacy and safety, significantly improving pain intensity, vaso-occlusive crises (VOC), and inflammation when compared to usual care/placebo (p < 0.05). Vitamin D3 (n = 6) at different dosages may reduce respiratory complications and length of hospital stay, yet further studies are needed to confirm its significant effects. Evidence is limited and of poor quality regarding the effects of add-on vitamin A (n = 2), magnesium sulfate (n = 2), and zinc (n = 4) for this population. Conclusions: The complementary use of certain supplements (fatty acids, l-arginine, vitamin D3) can enhance the management of VOC and improve patients' physiological functions. These supplements are often affordable and can contribute towards the reduction of opioid use and shorten patients' hospital stays - especially in low/middle-income countries where resources are scarce. Although further studies are needed to refine these findings (e.g., appropriate doses/regimens), practical guidelines and decision-makers may benefit from updated evidence.
Description
Keywords
Nutrition Sickle cell disease Dietary supplements Children Adolescents Systematic review Meta-analysis FCT_UIDB/05608/2020 FCT_UIDP/05608/2020
Citation
Orsi BC, Gorski D, Krul NE, Wiens A, Brito M, Tonin FS, et al. The effects of nutritional supplementation for children and adolescents with sickle cell disease: a systematic review and meta-analyses. Clin Nutr. 2025;47:157-68.
Publisher
Elsevier