Malaria Is Associated with Diminished Levels of Ascorbic Acid: A Systematic Review and Meta-Analysis.

Background: It is still unclear how ascorbic acid levels relate to the pathogenesis of malaria. This systematic review synthesized different ascorbic acid levels in malaria patients with different severity levels of malaria and Plasmodium species. Methods: The systematic review protocol was registered in the PROSPERO database (CRD42023394849). A systematic search of PubMed, Embase, MEDLINE, Ovid, Scopus, and Google Scholar was conducted to identify studies that reported ascorbic acid and malaria. The pooled standardized mean difference (Cohen's d) with 95% confidence intervals (CIs) was calculated using the random-effects model. Results: A total of 1480 articles were obtained from the searches of the databases, and 30 studies were included for syntheses. The meta-analysis revealed that patients with malaria had lower levels of ascorbic acid than those without malaria or uninfected controls (p < 0.01, Cohen's d = -3.71, 95% CI = -4.44 to -2.98, I2 = 98.87%, 30 studies). Comparable levels of ascorbic acid were observed between patients with severe malaria and those with nonsevere malaria (p = 0.06, Cohen's d = -1.39, 95% CI = -2.85 to 0.07, I2 = 96.58%, 4 studies). Similarly, levels of ascorbic acid were comparable between patients with Plasmodium falciparum and Plasmodium vivax malaria (p = 0.34, Cohen's d = -1.06, 95% CI = -3.23 to 1.12, I2 = 97.30%, 3 studies). Conclusions: The meta-analysis reveals diminished levels of ascorbic acid in malaria cases. Manipulating the host's nutritional status, such as by supplementing it with ascorbic acid to restore reactive oxygen species balance, may alter the progression of malarial infection and prevention of disease severity. Antioxid. Redox Signal. 40, 460-469.

Effects of Daily Zinc Alone or in Combination with Other Nutrient Supplements on the Risk of Malaria Parasitaemia: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Zinc supplementation has been explored as a potential intervention to reduce the risk of malaria parasitaemia in randomised controlled trials (RCTs). However, inconsistent evidence has been obtained regarding the efficacy of zinc supplementation in the context of malaria prevention. This systematic review was implemented to survey the existing literature to determine the effects of the daily oral administration of zinc, either alone or in combination with other nutrient supplements, on the risk of malaria parasitaemia. The systematic review was prospectively registered in the PROSPERO database CRD42023424345 and followed PRISMA protocols. A comprehensive search was conducted across multiple databases, including Embase, MEDLINE, Ovid, PubMed, Scopus, ProQuest, and Google Scholar, from their inception until 6 May 2023. The risk of bias in RCTs was assessed using the Cochrane Risk of Bias Tool 2 (RoB 2). The effect sizes, represented as risk ratios (RRs) with 95% confidence intervals (CIs), were standardised by transforming them into log RRs and then pooling them using a fixed-effects or random-effects model depending on the heterogeneity across studies. Comparisons were made between individuals who received zinc alone or zinc in combination with other micronutrient supplements and those who did not receive zinc. A total of 1339 articles were identified through the database searches, and after the screening and selection process, 10 studies were included in the final synthesis. The meta-analysis revealed that zinc supplementation alone did not significantly affect the risk of malaria parasitaemia compared with placebo (p = 0.30, log RR = 0.05, 95% CI: -0.05-0.15, I2 = 0.00%, with 566 malaria cases in the zinc intake group and 521 malaria cases in the placebo group). However, the analysis demonstrated a borderline significant effect of zinc supplementation in combination with other micronutrients on the risk of malaria parasitaemia compared with placebo (p = 0.05, log RR = 1.31, 95% CI: 0.03-2.59, I2 = 99.22%, with 8904 malaria cases in the zinc intake group and 522 malaria cases in the placebo group). The findings of this systematic review indicate that zinc supplementation, either alone or combined with the supplementation of other micronutrients such as vitamin A, iron, or multiple nutrients, does not significantly alter the risk of malaria parasitaemia. Further research with larger sample sizes is warranted to explore the potential effects of multi-nutrient supplementation and to identify more specific micronutrients and additional factors associated with the risk of malaria, rather than just zinc alone, among individuals in different malaria-endemic areas.