Vitamin C is bad for malaria

The detrimental effect of Vitamin E on malaria infections is well known, the one of Vitamin C to a lesser extent. The malaria belt of the world (tropical regions) with rich sources of vitamin C constitutes malaria endemic zones. In these zones, where vitamin C rich food such as citrus fruits and green vegetables abound, a mutual relationship between the two appears to exist. A database of vitamin C contents in tropical vegetables and foods has been published. Moringa oleifera for example contains 7 times more vitamin C than oranges. M. Ogunlesi, W. Okiei, L. Azeez, V. Obakachi, M. Osunsanmi, G. Nkenchor. Vitamin C Contents of Tropical Vegetables and Foods Determined by Voltammetric and Titrimetric Methods and their Relevance to the Medicinal Uses of the Plants. Int J Electrochem Sci 2010, 5, 105-115. A strange feature of plants from the Artemisia family is that they do not contain ascorbic acid (vitamin C). Ascorbic acid affects malaria in several pathways. N Marwaha. Ascorbic acid co-administration with artemisinin based combination therapies in falciparum malaria Indian J Med Res. 2016 May; 143(5): 539–541. doi: 10.4103/0971-5916.187100 The enhancement of iron absorption by ascorbic acid is known since decades Hallberg L, Brune M, Rossander L.The role of vitamin C in iron absorption. Int J Vitam Nutr Res Suppl. 1989;30:103-8. Ascorbic acid is probably the most effective absorption enhancer of non-haem iron. This may be beneficial against anemia but is detrimental for malaria. ACTs are rendered less effective if taken with multivitamins that contain constituents such as Vitamin C. The presence of the antioxidant ascorbic acid strongly reduced DHA activity in the presence of normal hemoglobin (HbO) Silvia Parapini, Piero Olliaro, Visweswaran Navaratnam, Donatella Taramelli, Nicoletta Basilico. Stability of the Antimalarial Drug Dihydroartemisinin under. Physiologically Relevant Conditions: Implications for Clinical Treatment and Pharmacokinetic and In Vitro Assays. Antimicrob Agents Chemother April 2015) Ascorbic acid also reduces the antimalarial activity of ellagic acid and several ketones S. S. Mahajan, V. R. Kamath and S. S. Ghatpande. Synergistic antimalarial activity of ketones with rufigallol and vitamin C. Parasitology2005, 131, 459-466 doi.org/10.1017/S0031182005008267 A study from Nigeria involving 80 malaria infected adult patients (OC Adamanya et al., Int J Pure Appl Sci Technol, 2012, 10, 5157) shows that co-administration of orange juice, grapefruit juice or vitamin C concomitant with artesunate or amodiaquine severely diminishes the efficacy and potency of these widely used antimalarial drugs. In most of the patients under concomitant administration parasitemia was not cleared at the end of the treatment as it was for the controls where only artesunate or amodiaquine were administered. Adumanya OC, Uwakwe AA, Odeghe OB, Essien EB and Okere TO. Assessment of the potency of some selected anti-malaria drugs on the supplements of B2 and orange fruit juice (combination therapy) African Journal of Biochemistry Research 2012; 6 (14): 179-184. Nicholas F. Nwachukwu, Manish Mishra, Terrence Marcelle, Joshua B. Owolabi. Effects of Vitamins in Augmentation of Malaria Treatment: A review. Asian Pac. J. Health Sci., 2016; 3 (4):34-43 e-ISSN: 2349-0659, p-ISSN: 2350-0964 Ascorbic acid may increase parasitemia. The uptake of ascorbic acid into erythrocytes is increased as a result of malaria infection. Stocker R, Weidemann MJ, Hunt NH. Possible mechanisms responsible for the increased ascorbic acid content of Plasmodium vinckei-infected mouse erythrocytes. Biochim Biophys Acta. 1986 May 2;881(3):391-7. In an in vivo study the therapeutic potential of selected micronutients in Plasmodium berghei infected mice showed that vitamin A caused a 41 % suppression of parasitemia on day 4, vitamin E 35%, zinc 42 %, selenium 81 %, chloroquine 100% and Vitamin C none. OI Iribhogbe, EO Agbaje, IA Oreagba, OO Aina, AD Ota. Therapeutic potential of selected micronutrients in malaria: an in vivo study in Plasmodium berghei infected mice. Biology and Medicine, 4 (4): 193–201, 2012 In another in vivo trial Plasmodium yoelii infected mice received a supplement of vitamin C, but this did not reduce damages in both morphology and histology of liver and spleen. On days 7 to 11 parasitemia however increased by 30%. Rungruang, T., Kaewkongkwan, Y., 1Sukakul, T., Kettawan, A., Chompoopong, S. and Boonmars, The effect of vitamin C on morphology and histology of liver and spleen of Plasmodium - infected mice. Inter Food Res J, 2013, 20, 1639-1643. It appears that the Plasmodium parasite needs vitamin C. It has been noticed that in vitro cultures many parasite isolates see their population decline below 6 mg/L of ascorbic acid. Brockelman CR, Tan-ariya P, Menabandhu C. The influence of magnesium ion and ascorbic acid on the erythrocytic schizogony of Plasmodium vivax. Parasitol Res. 1987;73(2):107-12. Vitamin C may have additional detrimental effects in malaria. Results from an experimental study have shown that concurrent administration of artemether and ascorbic acid compromised the rates of parasite clearance in P. berghei malaria infection in mice. This effect was more pronounced at higher doses of ascorbic acid. Ganiyu KA, Akinleye MO, Fola T. A study of the effect of ascorbic acid on the antiplasmodial activity of artemether in Plasmodium berghei infected mice. J Appl Pharmaceut Sci. 2012;2:96–100 Vitamin C is the strongest hemolytic agent in comparison with other vitamins. IH Ibrahim, SM Mallam, H Omar, M Rizk. Oxidative hemolysis of erythrocytes induced by various vitamins. International J Biomed Sc 2006, 2-3, 295-299. Co-incubation of blood with vitamin C and artemether lumefantrine drug potentiates the haemolytic effects of the latter on reducing blood viscosity and elasticity in vitro. This may possibly have implications in relation to haemolysis in patients receiving vitamin C supplementation with artemether/lumefantrine during malaria therapy. McKoy MG, Kong-Quee Iii P, Pepple DJ. In vitro effects of co-incubation of blood with artemether/lumefantrine & vitamin C on the viscosity & elasticity of blood. Indian J Med Res. 2016 May;143(5):577-80. doi: 10.4103/0971-5916.187105. Ascorbic acid not only enhanced hemolysis, but also induced formation of thiobarbituric acid-reactive substances in the presence of hemin Li SD, Su YD, Li M, Zou CG. Hemin-mediated hemolysis in erythrocytes: effects of ascorbic acid and glutathione. Acta Biochim Biophys Sin (Shanghai). 2006 Jan;38(1):63-9. Artesunate in combination with ascorbic acid is spermatotoxic. PI Jewo, JA Shittu, MC Izegbu, OA Adesanya, LC Saalu, OA Ashiru. Modulatory Effects of Ascorbic Acid on Spermatoxicity of Artesunate in Rats. Nigerian Medical Practitioner Vol. 53 (4) 2008: pp. 62-65 There are very few medicinal plants which do not have a documented antiplasmodial effect. This is the case however for Curcuma longa, Moringa oleifera and Pomegranate juice. A study in Thailand confirmed that extracts of the Curcuma plant had no suppressive effect in Plasmodium yoelii infected mice. Pomegranate juice, curcuma and moringa powder have very all a very high antioxidant power. Pomegranate juice for example is 2-3 times stronger than red wine or tea. Curcuma longa 50 times higher than tomato or garlic. Moringa oleifera 3 times higher than spinach or peas. All these extracts are very rich in polyphenols and flavonoids. It was often assumed that a high polyphenol content and/or high antioxidant power were leading to good antimalarial properties. But this claim does not hold in light of a study from Thailand. Gil MI, Tomás-Barberán FA, Hess-Pierce B, Holcroft DM, Kader AA. Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. J Agric Food Chem. 2000 Oct;48(10):4581-9 Siriporn Tuntipopipat, Kunchit Judprasong, Christophe Zeder, Emorn Wasantwisut, Pattanee Winichagoon, Somsri Charoenkiatkul, Richard Hurrell, and Thomas Walczyk. Chili, but Not Turmeric, Inhibits Iron Absorption in Young Women from an Iron-FortifiedComposite Meal. The Journal of Nutrition, 2006, 136, 2970-2974. Despite the much higher amount of phenolics in Curcuma longa than in another plant, chili pepper Capsicum annuum has excellent antimalarial properties and the turmeric containing food none. The authors conclude that not only phenol quantity plays a role but also their quality, and particularly the iron binding capacity. Moringa oleifera and Curcuma longa are very rich in iron and ascorbic acid. Moringa for example contains 7 times more vitamin C than orange juice and 3 times more iron than roast beef. A deadly mix in case of malaria infection. For several of these reasons, ascorbic acid supplement will act as booster to malaria parasites in carriers. But it is difficult to find this warning in WHO documents or in prescription information about artemether, amodiaquine, mefloquine, lumefantrine. In a survey run in Nigeria in health centers, 200 questionnaires were returned showing that 173 (86.5%) of the medical staff were not aware that taking antioxidants such as vitamin C concurrently with ACTs caused an inhibition of the antimalarial effect. Who is to blame? Entering the keyword artemisinin on PubMed gives 5696 research papers. None of them refers to a possible antagonism with vitamin C ? Cui bono ? World production of synthesized vitamin C is currently estimated at 110,000 tonnes annually.