Children with Cerebral Malaria

The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 6 No. 2 • April–May 2003

Low Plasma Arginine Concentrations and Decreased Nitric Oxide Production in Children with Cerebral Malaria

Malaria continues to be a very serious health problem in less developed countries where there are large populations of mosquitoes to spread the disease. (Early in the history of the United States, there was a serious problem with malaria, too, until swamps supporting the responsible mosquito populations were drained. We dread to think what will be happening in Florida when and if the restoration of the Everglades swamp system is undertaken. During the nineteenth century, malaria was found as far north as Chicago. As a child in Chicago, Durk read about and saw massive areas of swamps that had been drained and filled with soil to suppress the dangerous mosquito populations. It was a massive public health mega-engineering project, he says; one of the results of the work is that to this day the Chicago River runs backward.)

The most serious complication of malaria is cerebral malaria. A new study1 reports that in children with cerebral malaria, there is low plasma arginine concentration and decreased nitric oxide production. In fact, the same authors earlier showed plasma arginine and nitric oxide production inversely associated with the severity of malaria, with the lowest levels found in cerebral malaria. Low arginine plasma concentration was associated with death in individuals with cerebral malaria.

As the authors note, NO has antiparasitic effects. Apparently, arginine levels are depleted by the large amounts of NO made to fight the parasitic infection. When arginine levels are low, nitric oxide synthase (NOS) is “uncoupled” from the production of nitric oxide, producing superoxide radicals but little or no nitric oxide. Hence, low arginine levels can result in low nitric oxide production and greatly increased oxidative stress through the increase in superoxide and peroxynitrite (the reaction product of nitric oxide and superoxide).

The authors suggest, “Clinical trials are warranted to ascertain whether or not correction of L-arginine deficiency provides adjunctive prophylactic and therapeutic benefit in malaria.” We agree. Since NOS is activated by the neurotransmitter acetylcholine, we would also add choline and B5 to the arginine, as in the formulation we have been using for about 20 years.


  1. Lopansri et al. Low plasma arginine concentrations in children with cerebral malaria and decreased nitric oxide production. Lancet 361:676-8 (2003).

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