Antioxidant supplementation for sickle cell disease

Abstract

Background Sickle cell disease (SCD) refers to a group of genetic disorders characterized by the presence of an abnormal haemoglobin molecule called haemoglobin S (HbS). When subjected to oxidative stress from low oxygen concentrations, HbS molecules form rigid polymers, giving the red cell the typical sickle shape. Antioxidants have been shown to reduce oxidative stress and improve outcomes in other diseases associated with oxidative stress. Therefore, it is important to review and synthesize the available evidence on the effect of antioxidants on the clinical outcomes of people with SCD. Objectives To assess the effectiveness and safety of antioxidant supplementation for improving health outcomes in people with SCD. Search methods We used standard, extensive Cochrane search methods. The latest search date was 15 August 2023. Selection criteria We included randomized and quasi‐randomized controlled trials comparing antioxidant supplementation to placebo, other antioxidants, or different doses of antioxidants, in people with SCD. Data collection and analysis Two authors independently extracted data, assessed the risk of bias and certainty of the evidence, and reported according to Cochrane methodological procedures. Main results The review included 1609 participants in 26 studies, with 17 comparisons. We rated 13 studies as having a high risk of bias overall, and 13 studies as having an unclear risk of bias overall due to study limitations. We used GRADE to rate the certainty of evidence. Only eight studies reported on our important outcomes at six months. Vitamin C (1400 mg) plus vitamin E (800 mg) versus placebo Based on evidence from one study in 83 participants, vitamin C (1400 mg) plus vitamin E (800 mg) may not be better than placebo at reducing the frequency of crisis (risk ratio (RR) 1.18, 95% confidence interval (CI) 0.64 to 2.18), the severity of pain (RR 1.33, 95% CI 0.40 to 4.37), or adverse effects (AE), of which the most common were headache, nausea, fatigue, diarrhoea, and epigastric pain (RR 0.56, 95% CI 0.31 to 1.00). Vitamin C plus vitamin E may increase the risk of SCD‐related complications (acute chest syndrome: RR 2.66, 95% CI 0.77 to 9.13; 1 study, 83 participants), and increase haemoglobin level (median (interquartile range) 90 (81 to 96) g/L versus 93.5 (84 to 105) g/L) (1 study, 83 participants) compared to placebo. However, the evidence for all the above effects is very uncertain. The study did not report on quality of life (QoL) of participants and their caregivers, nor on frequency of hospitalization. Zinc versus placebo Zinc may not be better than placebo at reducing the frequency of crisis at six months (rate ratio 0.62, 95% CI 0.17 to 2.29; 1 study, 36 participants; low‐certainty evidence). We are uncertain whether zinc is better than placebo at ...