OBJECTIVES: Sickle Cell Disease (SCD) is a neglected chronic hereditary blood disorder associated with a wide range of health-related complications, including painful vaso-occlusive crises (VOC), acute chest syndrome, delayed growth, and premature death. Our study aims to assess the impact of nutritional supplementation on children and adolescents with SCD as a complementary strategy to improve patients’ clinical conditions and quality of life.

METHODS: A systematic review with searches in PubMed, Scopus, Web of Science was performed to retrieve randomized controlled trials related to the study goals (PROSPERO-CRD42024532369). For each outcome of interest (e.g., efficacy, safety) data were pooled by means of pairwise and network meta-analyses with p-score analysis. The results were presented as risk ratio or mean differences with 95% credibility intervals (NMAstudio-2.0). RoB 2 tool was used to assess trials' risk of bias.

RESULTS: Nineteen studies (2002-2023) (n=1,732), analyzing 9 different interventions (different regimens of dietary supplements) were included. All patients were in use of hydroxyurea as active treatment. Supplementation with fatty acids (n=4) and L-arginine (n=6) presented higher efficacy by significantly improving pain intensity and reducing VOC and inflammation when compared to usual care/placebo (p<0.05). Vitamin D3 (n=7) at different dosages presented additional benefits in reducing respiratory complications (p<0.05). Zinc (n=4) was associated with improvements on children's growth. Although citrulline (n=2) (p<0.005), vitamin A (n=2) (p<0.001), and lime juice (n=1) (p<0.001) may improve some SCD-related complications, evidence is still limited and of poor quality.

CONCLUSIONS: The complementary use of certain supplements (fatty acids, L-arginine, vitamin D3) can enhance the management of VOC and improve patients’ vascular and pulmonary functions. These supplements, often affordable, can additionally help reducing opioid use and shorten 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.