Is Moringa bad for malaria ?

http://www.malariaworldIs Moringa bad for malaria ?
Moringa oleifera is called the „miracle tree“, and has a strong reputation for curing many diseases, but it is impossible to find any peer reviewed paper on PubMed which describes antimarial properties for this plant. This probably does not exclude the presence in the plant of a few molecules which could demonstrate antiplasmodial properties in vitro.
Dry leaves of the plant do not inhibit beta-hematin (G Mergeai, personal communication) in the assay which is often used to screen for antimalarials.
The plant is very rich in proteins, vitamins, polyphenols, minerals, but some recent studies (A Gychye et al., J of Toxicol. 2014, ID786979 ; A Odunlade et al., 5th World Congress on Biotechnology, june 25-27, 2’14) suggest to limit the daily consumption to 70 g because some deterioration in liver functions (increased ALT and AST) has frequently been noticed.
But this hardly explains why the plant has no or only insignificant antimalarial properties.
One of the reasons might be the high concentration of the amino acids methionine and glutamate in Moringa olifeira. The plant is much richer in aminoacids than in polyphenols.

Moringa contains 350 mg/100g methionine in dry leaves vs 50 in Artemisia annua . Methionine is an amino acid which increases the production of lecithin in the liver, it is a precursor of choline and phospholipids (V du Vigneaud et al., Nutrition Reviews 1974, 32, 144-46), the major constituants of lecithin. The latter definitely play a role in hemozoin crystallization on the inner membrane of the food vacuole (Nguyen t Huy et al., PlosOne, 2013, 8, e70025). Plasmodium uses specific carriers to import methionine and choline into the parasitized erythrocyte (ML Ancelin et al, BJ Letters, 1991, 283, 619-621 ; SA Cobbold et al., Int J Parasitol. 2011, 41, 125-35). There is even a bio-assay based on the beta-hematin formation promoted by lecithin for screening new antimalarial drugs (DT Trang et al., Anal Biochem 2006, 349, 292-296). There are not many plants rich in phospholipids and its precursor choline, except soya. Moringa contains 423 mg/100g of choline. A Malaysian study shows that Moringa oleifera oil contains 6.07% of phospholipids and soybean oil 7.15 %. Moringa leaf powder is used as replacement in soybean food for fishes.

Another molecule which boosts malaria is folate. The average folate in vegetables is 40 microg/100g but in Moringa oleifera it goes up to 540 microg/100g (K Witt Echo Research Note No 1, 2012). Several antifolate drugs, like pyrimethamine, are on the market since 50 years. Moringa is rich in glutamic acid – 5 times more than Artemisia- and para-aminobenzoic acid (PABA), two of the building blocks of folate (G Magnani et al., Biochem J, 2013455, 149-155). PABA is a major constituent in Moringa oleifera and soya (L Mbanga et al., Adv Biochem & Biotechnol., 2015, 1, 1-13). It was never detected in Artemisia annua. Plasmodium badly needs PABA and folate, and unlike humans, it can use PABA for de novo synthesis of folate. In fact humans do not need PABA. The parasite also eagerly salvages the glutamate provided in the plasma of the host. Parasitized erythrocytes activate a specific high-affinity glutamate transporter (M Winterberg et al., Blood, 2012 119, 3604-3612). This transporter is activated by sodium. Moringa is rich in sodium but the complete absence of sodium in Artemisia annua may contribute to the strong antimalarial properties of this plant. This transporter is also activated by glucose (Ping Wang et al., Mol Biochem Parasitol 2007, 154, 40-51).
The detrimental role of PABA on malaria has been described 60 years ago (F Hawking, British Medical Journal, 1954, Feb, 425-429). Rats fed on a milk diet were insusceptible to infection with Plasmodium berghei. Milk does not contain PABA or only traces. This insusceptibility was reversed by the addition of PABA or folic acid. The same experiences were repeated on monkeys and gave the same results.
It is likely that the relative immunity to malaria shown by infants in many parts of the Tropics may be due to a deficiency of PABA in their mother’s milk.
The excellent nutritional properties of Moringa could be related to folates, aminoacids, choline, lecithin and phospholipids. Which unfortunately promote hemozoin formation and help the parasite to thrive. And if the resistance of the antifolate drugs like sulfadoxine-pyrimethamine is increasing and already well documented (R Abdul-Ghani et al., Acta Tropica, 2013, 2, 163-190) the promotion of Moringa olifeira plantations might lead to a disaster.

Pierre Lutgen and Mutaz Akkawi
8 June 2015

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