Fava beans: a boon or a bane?

In the Mediterranean “bean-dom” one ruler conquered for centuries until  America was discovered and trading gave rise to cultivation of foreign beans in the region.  Fava beans are native to Middle Eastern and Mediterranean countries predominating Egyptian culture for centuries.   Its historical significance is seen in the English fairy tale, “Jack and the beanstalk,” where is it disputed that the magical beans were, in fact, fava beans.  Nevertheless there have been accounts of strong aversion towards these beans with the most famous example of Pythagoreans.

Centuries following the demise of Pythagoras, several theories have spun around his strong dislike towards fava beans.  Great minds that pride in logical reasoning have put forth untested theories  that sound nothing short of rainbows and unicorns.  However in the recent years, empirical studies and sound scientific methods have established a strong hypothesis that fits the bill.

A condition called favism, develops in individuals that have a deficiency of an enzyme called glucose-6-phosphate dehydrogenase (G6PD deficiency).  Most G6PD-deficient individuals remain asymptomatic as long as they are not exposed to certain environmental conditions that could trigger its clinical manifestations, which include jaundice, blood in urine, kidney failure followed by a fatal “fava” death. However these beans are not the only ones to be blamed.  In some cases, certain kinds of pollen can also trigger favism.  This led to a popular belief in the twentieth century that it could be a simple case of allergy!  We do, however, have evidence to believe otherwise.

Glucose-6-phosphate is a crucial enzyme in the pentose phosphate pathway, an alternative to the glycolytic pathway.  The pathway creates a reducing environment in cells that have to face the wrath of highly unstable oxidants and superoxide radicals inevitably existing as by-products of metabolic processes.  The first step of the pathway involves the oxidation of glucose-6-phosphate to 6-phosphogluconate.  The electrons lost in the oxidation are taken up by NADP+ to form NADPH.  What role does NADPH play in the bigger picture?

On examining the microenvironments within a cell, the harsh reality of toxic radicals comes to light.  Glutathione peroxidase, a polypeptide with cysteine residues, comes to the rescue fighting off hydrogen peroxide and converting it into water.  This, however comes with a price.   Glutathione peroxidase sacrifices electrons  and in its oxidised form, it is an injured soldier that needs help.  This is where NADPH steps in, giving up its own electrons to revive and restore reduced glutathione peroxidase.  NADP+ is formed in the process and without the cell’s obsessive need to maintain homeostasis, its concentration would continue rising with catastrophic consequences.   In G6PD-deficient individuals the cell cannot replace the NADPH lost because of the inability to enter the Pentose Phosphate pathway.  Therefore,  any oxidant can trigger the symptoms of favism.  Divicine in fava beans is the substance that gives rise to free radicals in the cell.

Although fava beans seem unpopular according to this theory, there is an irony in this tale.   Geographically, G6PD deficiency occurs in high frequencies in tropical areas, including the Mediterranean region.  A logical fallacy would be one in which a curse was cast upon the region to bear flourishing fava beans that could ultimately lead to the fatal death of majority of the population.   The question remains as to how G6PD-deficient genotype remained prevalent in such a case?

In-vitro studies show Plasmodium species causing Malaria are highly sensitive to even slight changes in the oxidative environment that cells can normally tolerate, selectively killing the parasite without harming the host cell.    Therefore the same biochemical mechanism that is fatal in G6PD -deficient individuals can be protective in normal individuals against Malaria. This means fava beans are a natural drug against Malaria, serving as a disguised cure for centuries in the tropical regions.  It is unfortunate that Pythagoreans only saw one side of the coin, or in this case, one side of the pod.