Fava beans and Parkinson’s disease: useful ‘natural supplement’ or useless risk?

In April 2008, a 54-year-old man of Ashkenazi Jewish/Polish descent developed an acute episode of malaise and severe jaundice. He was diagnosed with Parkinson s disease (PD) in May 2007 and was treated with rasagiline, 1 mg daily, and Co-Enzyme Q10, 1200 mg daily. His past medical history was significant for hepatitis B and Epstein-Barr virus, and Gilbert s disease. He had no family history of anemia or jaundice, although information was limited because most of his relatives perished in the Holocaust. In the fall of 2007, he began ingesting canned, frozen or pre-cooked fava beans as a form of natural L-dopa supplementation, with no adverse effects. In the spring of 2008, he switched to fresh, uncooked fava beans. Shortly thereafter, he experienced mild jaundice and fatigue. He stopped eating fava beans and his symptoms resolved the following week. Laboratory studies at that time were unremarkable. One week later, he again began eating uncooked fresh fava beans. Within 48 h, he developed severe fatigue, marked jaundice, and dark urine discoloration. Laboratory evaluation revealed creatine-phospho-kinase 250 U/l, total bilirubin 30 mg/dl, hematocrit 28%, and blood, not bilirubin, present on urinalysis. All other investigations, including hepatic transaminases and abdominal computerized tomography, were unremarkable. Enzymatic assay for glucose 6-phosphate dehydrogenase (G6PD) revealed very low activity of 0.25 IU/g Hgb (normal range, 4.25–8.25 IU/g Hgb). Genetic analysis determined that he was heterozygous for the C563T Mediterranean G6PD mutation, confirming that this was an episode of favism with hemolysis, and had Gilbert s disease. At 3 months follow-up after discontinuing the ingestion of fava beans, all clinical and laboratory abnormalities had normalized. Glucose 6-phosphate dehydrogenase deficiency is due to various mutations in the X-linked G6PD gene, affecting up to 400 million people of Mediterranean, African, Middle-Eastern and Asian descent, but is extremely rare amongst Ashkenazi Jews [1]. To our knowledge, there is only one other report of adult onset favism in an Ashkenazi Jews [2]. As the authors of that report suggest, reliance on ethnic origin in the diagnosis of inherited red blood cell defects can be misleading. There is no known biological reason to suggest that PD predisposes to favism nor is it likely that rasagiline or Co-Enzyme Q10 contributed to the hemolytic reaction. L-Dopa was first isolated in fava beans by Guggheneim in 1913 [3], long before its pharmacological role in PD was discovered [4]. Ingestion of fava beans as a source of natural L-dopa is popular amongst patients with PD, despite only anecdotal evidence of clinical efficacy [5] and the variable content of L-dopa measured in the beans. There is, however, limited public awareness that fava beans may trigger a severe hemolytic anemia, particularly amongst unsuspecting populations where G6PD deficiency is uncommon and fava beans are rarely eaten. It should be noted that the hemolytic reaction is not related to the L-dopa content of the beans. It is also important to notice that other serious complications have been reported in patients consuming fava beans, including a neuroleptic malignantlike syndrome that developed abruptly in a patient after the beans were discontinued [6]. Our case of favism, the second ever reported in an Ashkenazi Jew, serves as a powerful reminder that natural and seemingly innocuous food supplements can harbor significant health risks. Physicians should be ever mindful and vigilant of their risks and caution patients to avoid potentially catastrophic complications. As G6PD testing is widely available and relatively innocuous, it would seem prudent to screen patients with PD for G6PD deficiency prior to their consuming fava beans.