Wheatgrass Extract (Mugineic Acid): An Inexpensive and Effective Iron Chelator in Patients with Myelodysyplastic Syndromes

Background: Patients with red blood cell (RBC) transfusion-dependent myelodysplastic syndromes (MDS) and congenital anemias are at risk of transfusional hemosiderosis and organ injury from reactive iron species. Available iron chelating drugs in the US are either inconvenient for administration (parenteral deferoxamine) or are costly (oral deferasirox or deferiprone - median cost for these drugs exceeds $13,000-$18,000/month, Master S et al Blood 2016; 128:4858). Additionally, available chelators frequently have adverse effects including gastrointestinal (GI) upset or renal insufficiency. Wheatgrass, a food supplement prepared from the cotyledons of the Triticum aestivum Common Wheat plant, is sold either as a freeze-dried powder or as a juice extracted from the fresh leaves of the plant. Recently wheatgrass was found to contain high concentrations of the hexedentate iron chelator mugineic acid, a phytosiderophore that has comparable efficacy to deferasirox (ICL670) in a murine model of iron overload, and which may be a clinically meaningful iron chelator (Das et al J Biochem 2016; 160:163, Mukhopadhyay S et al JCO 2009; 15S:7012).

Methods: Twelve patients with transfusion-dependent MDS (n=11) or congenital dyserythropoietic anemia (n=1) self-administered wheatgrass that they either grew themselves in potting soil or in an agricultural setting (n=3), procured from a juice bar (n=7), or obtained in powder form from a nutritional supplement store (n=2). Three patients also had known HFE variants. Seven patients had previously taken deferasirox and 2 patients had also received deferoxamine, but either did not tolerate these drugs or did not achieve adequate chelation. For patients using wheatgrass in the juice form, approximately 30 mL of juice was obtained from the leaves and stems of ~7 day-old wheatgrass. Serum ferritin was monitored over a period of at least 3 months. Serial hepatic T2* MRI was performed in 2 patients, one of whom also continued to take deferasirox.

Results: The serum ferritin of patients at baseline was 2370 ng/mL (range, 1553-6089 ng/mL). The median decrement in serum ferritin in patients taking wheatgrass was 834 ng/mL (range of reduction, 251 to 1774 ng/mL). 3 patients reported worsening in GI upset or diarrhea but only 1 patient discontinued wheatgrass due to these effects; other adverse events were not observed. Two patients who grew their own wheatgrass noted mold outbreaks in the culture and switched to wheatgrass obtained from a juice bar. 1 patient noted a reduction in transfusion needs (of uncertain connection to wheatgrass administration), and the hepatic iron concentration measured by MRI decreased in both patients who were assessed radiographically.

Conclusion: Mugineic acid in wheatgrass has iron chelating activity in patients with transfusion-associated iron overload. The annual cost of daily wheatgrass supplement from an urban juice bar (~$1500) is approximately 10% of the monthly cost of deferasirox or deferiprone in the US and less than 1% of the annual cost. Formal trials of wheatgrass or of purified mugineic acid in iron-overloaded patients with MDS or congenital anemias are indicated.