Introduction

The substance widely referred to as vitamin C is an equilibrium mixture containing L-ascorbic acid, semidehydroascorbic acid and L-dehydroascorbic acid with over 80 percent of the vitamin C activity accounted for by L-ascorbic acid at equilibrium ₁. These three forms comprise a reversible redox system making the vitamin an effective quencher of free radicals such as the singlet O₂ ^- species ₂. Evidence abounds on the role of this vitamin in disease and maintenance of health ₃,₄,₅. Vitamin C has been reported to be markedly decreased in patients at risk of developing multiple organ failure ₆. In a study on the effect of vitamin C on plasma lipids, Howard and Meyers ₇ were able to show some evidence of an inverse relationship between vitamin C intake and the development of atherosclerosis. The mediatory role of vitamin C in this instance may not only be due to its antioxidant activity, but also through a plasma lipid-modifying effect. The oxidative modification of low density lipoproteins (LDL) has been postulated to be one of the early steps in atherogenesis. In this respect ascorbate has been shown to reduce LDL oxidative susceptibility, even though it is not lipophilic ₈. Vitamin C has also been shown to have a positive therapeutic effect in the treatment and control of autoimmune disorders, including diabetes mellitus and acquired Immune Deficiency Syndrome (AIDS), whose immunological background data are in favour of the participation of an autoimmune mechanism in the genesis of the disease ₉.

Endothelium-dependent vasodilatation is an also known to be impaired in humans with diabetes mellitus via inactivation of endothelium-derived nitric oxide by oxygen-derived free radicals. Vitamin C has been reported to improve this condition, thus further supporting the hypothesis that nitric oxide inactivation by oxygen-derived free radicals contributes to abnormal vascular reactivity in diabetes ₁₀. Paolisso et al. ₁₁ have also been able to show that chronic vitamin C administration improves whole body glucose disposal and non-oxidative glucose metabolism in aged non-insulin dependent (type II) diabetic patients. Similarly, a high vitamin C intake has been documented to reduce the risk of cartilage loss and progression in people with osteoarthritis ₁₂. Thus the specific objective of this work was to assess the serum concentration of L-ascorbic acid in patients presenting with acute, uncomplicated falciparum malaria infection with the aim of establishing its adequacy and availability for reactive oxygen species scavenging or need for supplementation during the disease.

Patients And Methods

Study Locale

Patients and Study Design

Serum Sample Collection and Preparation

Assay for serum L-ascorbic acid

Statistical Analysis

Ethics

Results

Results obtained showed a significantly higher serum L-ascorbic acid concentration in all categories of falciparum malaria patients as shown in tables 1 and 2.

Figure 1

Table 1: Serum L-ascorbic acid concentration in adult malaria patients and control.

Figure 2

Table 2: Serum L-ascorbic acid concentration in infected children and control.

Mean serum L-ascorbic acid in both adult male and female patients was over twice the control serum L-ascorbic acid concentration of 0.53 ± 0.03 mg/dl, p < 0.05, table 1. A similar pattern was obtained among children presenting with acute, uncomplicated falciparum malaria infection, with values being twice above the control serum L-ascorbic acid concentration of 0.55 ± 0.03 mg/dl, p < 0.05, table 2. Among the patients, no difference was found to exist in the mean serum L-ascorbic acid concentration although the value was higher among females (both adults and children) relative to their male counterparts.

Discussion

Potentially damaging free radicals or reactive oxygen species are produced in cells under normal conditions through either homolytic cleavage of a covalent bond, univalent oxidation or reduction ₁₅. Such free radicals, particularly reactive oxygen species have been implicated in the pathogenesis of various diseases, including atherosclerosis, diabetes mellitus, cancer and Parkinson's disease ₁₆,₁₇,₁₈,₁₉. In particular, lipid peroxidation induced by free radicals is believed to be one of the major causes of cell membrane damage, leading to cell lysis and dysfunction ₂₀. Free radical defenses in the body comprise of a complex antioxidant system including vitamins A, E and C, glutathione and enzymatic antioxidants such as glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase ₁₅, ₂₁,₂₂. Biologically, free radicals are known to exert some physiological functions in the body such as biosynthesis, detoxification and microorganism clearance ₂₃,₂₄. Therefore it is the duty of the antioxidant defenses to maintain normal homeostatic balance between free radical production and clearance. During acute falciparum malaria infection the host immune system is activated, leading to the release of reactive oxygen species. Specifically, macrophage-generated oxygen species are known to function as non-specific effector molecules in their defense arsenal ₂₅. In performing their protective role of destroying parasitized red blood cells, macrophage-generated reactive oxygen species also affect non-parasitized cells leading to the accumulation of organic peroxides and oxidation of membrane lipids ₂₆ and cellular destruction. This state of oxidant-induced stress has been known to occur in malaria patients as evidenced by the increased serum levels of malondialdehyde (MDH) in this disease ₂₇. Equally striking is the failure of some key antioxidant defenses such as vitamin E, serum iron glutathione peroxidase and superoxide dismutase in maintaining reactive oxygen species homeostasis during malaria infection ₂₅. The observed increase in serum L-ascorbic acid can arise as a result of the mobilization of the available stores of this vitamin from the patient's leukocytes whose population and activity is known to increase in response to acute falciparum malaria infection. This leukocyte L-ascorbate mobilization can serve as a compensatory mechanism by the host to mitigate the effect of the potentially hazardous failure of the antioxidant defenses earlier mentioned. Because L-ascorbate is now primarily channeled to providing first protection against antioxidant damage, it is not available to carryout its other role of regenerating the metabolically active form of vitamin E ₁₅as evidenced by the reported decrease in serum vitamin E concentration in malaria infection ₂₇. Although some studies exist which report decreased serum L-ascorbate in falciparum malaria infection ₂₈. The low serum ascorbate is a reflection of the severity of the infection which has progressed to severe or complicated malaria with multiple organ involvement and a complex scenario of pathogenic determinants each uniquely capable of significantly contributing to the body reactive oxygen species pool ₂₉,₃₀,₃₁,₃₂. The increase in L-ascorbate concentration observed in this study should not be seen as adequate considering the failure of the other antioxidant defenses. L-ascorbate supplementation is suggested to augment existing serum levels taking into cognizance the potentially vital role of this vitamin in the scavenging of reactive oxygen species produced in acute, uncomplicated falciparum malaria infection.