Summary:
Sickle cell disease is a chronic inherited blood disorder in which red blood cells become rigid and sticky. These misshapen cells break down more quickly and can block blood vessels, leading to chronic anaemia, severe pain episodes, organ damage, and increased infection risk. The condition predominantly affects children and can cause significant illness and early mortality. Because nutrition may play a role in how the disease progresses, this research examined whether dietary supplements could help reduce symptoms or improve health outcomes. This paper is a systematic review of randomized controlled trials. Only studies that tested diet or nutritional supplements in children and adolescents with sickle cell disease were included, and a total of 2,058 participants met the criteria. Across the trials, nine different supplements were assessed. The strongest evidence came from studies testing fatty acids and L-arginine. These supplements consistently reduced pain, lowered inflammation, and decreased the frequency of vaso-occlusive crises compared with usual care or placebo. Vitamin D3, evaluated in six studies at varying doses, showed a possible benefit for reducing respiratory complications and shortening hospital stays, although more research is needed to confirm its effectiveness. Evidence for other supplements including vitamin A, magnesium sulfate, and zinc was limited and generally low in quality, making their effects uncertain. Overall, the findings suggest that certain nutritional supplements, particularly fatty acids, L-arginine, and possibly vitamin D3, may offer useful support alongside standard therapy for managing sickle cell disease in children. These options are relatively inexpensive and could help reduce reliance on opioids and shorten hospital stays, which is especially important in low-resource settings. Further research is needed to determine optimal dosing and treatment regimens.
Abstract:
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 in 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 complementary therapy for children and adolescents with SCD were included (PROSPERO:CRD42024532369). The data for outcomes of interest (efficacy, safety) were pooled by means of 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 were in use of hydroxyurea as 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.
Article Publication Date: 17/02/2025
DOI: 10.1016/j.clnu.2025.02.016
