Malaria, Fava Beans and Favism

[Additional material by Valentina Caracuta, Laboratory of Archaeobotany and Palaeoecology, University of Salento, Italy]

Malaria is a debilitating disease and humans have been adapting and mutating constantly to overcome the disease or mitigating its effects. Today there are three known mutations[1]. The first are (multiple) sickle-cell anemias[2], the second is thalassaemia[3] and the third is glucose-6-phosfate-dehydrogenase deficiency (or G6PD deficiency)[4].

The fava bean (Vivia faba) is a broad flat bean that is a dietary staple in malaria-endemic areas along the Mediterranean coasts. Glucose-6-phosfate-dehydrogenase (or G6PD) is an enzyme that serves to reduce one specific sugar, glucose-6-phosfate, to another sugar. During the process it releases an energy-rich molecule.

Several forms of glucose-6-phosfate-dehydrogenase deficiency exist in human populations. The pattern of deficiency has been thought to correspond to the distribution of malaria caused by the malaria parasite(Plasmodium falciparum) Although this hypothesis is still in dispute, many scientists support it.

The malaria parasite lives in the red blood cells and 'feeds' off energy-rich molecules. Individuals with a mutation in the G6PD-gene, the so-called glucose-6-phosfate-dehydrogenase deficiency, produce energy via an alternative pathway that doesn't involve this specific enzyme. The malaria parasite cannot use this alternative molecule. Furthermore, G6PD deficient blood cells seem to turn over more quickly, thus allowing less time for the parasite to grow and multiply.

With G6PD deficiency, fava bean consumption leads to a hemolytic crisis ('breaking of red blood cells') and a series of chemical reactions that release free radicals and hydrogen peroxide into the blood stream. This condition is known as favism. Favism is characterized most often by four signs and symptoms: weakness or fatigue, pallor, jaundice and haemoglobinuria.

The question is therefore: is glucose-6-phosfate-dehydrogenase deficiency really a survival mechanism to mitigate the effects of malaria or are they simply two problems occurring in the same geological area? While one rogue study supported the assertion that patients with G6PD-deficient red blood cells had no protection against a Plasmodium falciparum infection[5], most studies do prove that G6PD deficiency is protective against malaria [6],[7],[8],[9].

[1] Choremies et al: Three inherited red-cell abnormalities in a district of Greece. Thalassaemia, sickling, and glucose-6-phosphate-dehydrogenase deficiency in Lancet – 1963
[2] Luzzatto: Sickle Cell Anaemia and Malaria in Mediterranean Journal of Hematology and Infectious Diseases - 2012
[3] Wambua et al: The Effect of α+-Thalassaemia on the Incidence of Malaria and Other Diseases in Children Living on the Coast of Kenya in Plos Med – 2006
[4] Hendrick: Population genetics of malaria resistance in humans in Heredity - 2011
[5] Kotepui et al: Prevalence and hematological indicators of G6PD deficiency in malaria-infected patients in Infectious Diseases of Poverty - 2016
[6] Bienzle et al: Glucose-6-phosfate dehydrogenase and malaria: Greater resistance of females heterzygous for enzyme deficiency and of males with non-deficient variant in Lancet - 1972 
[7] Ruwende et al: Natural selection of hemi and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria in Letters to Nature - 1995 
[8] Guindo et al: X-Linked G6PD Deficiency Protects Hemizygous Males but Not Heterozygous Females against Severe Malaria in PLoS Medicine - 2007
[9] Lesly et al: The Impact of Phenotypic and Genotypic G6PD Deficiency on Risk of Plasmodium vivax Infection: A Case-Control Study amongst Afghan Refugees in Pakistan in PLoS Medicine - 2010