The Effect of Fermented Papaya Preparation on Patients With Chronic Kidney Disease Under Dialysis Receiving Intravenous Iron

Background and rationale

Patients with chronic kidney disease (CKD) on hemodialysis often suffer from anemia. The anemia is primarily caused by insufficient production by the failing kidneys of the erythroid stimulating hormone - erythropoietin (Epo). Oxidative stress may be another reason for anemia. Oxidative stress in RBCs of these patients may be caused by:

1. Passage of the blood through the plastic tubing during the dialysis procedure. We have shown oxidative stress in RBCs following passage of blood through similar tubing during leukopheresis procedure (1). Other groups reported similar effects during hemodialysis.
2. Iron overload - In order to maximize the effect of Epo, the treatment is supplemented by IV injection of iron. This iron may accumulate and cause iron overload in some hemodialyzed patients. Under normal conditions, iron is transported in the blood and enters into cells following binding the plasma protein transferrin. However, when iron content in the plasma exceeds the binding capacity of transferrin, non-transferrin-bound iron (NTBI) appears. This iron enters cells via alternative pathways, and accumulates in the cytosol, where it participates in chemical reactions (Haber-Weiss, Fenton) that generate reactive oxygen species (ROS). Excess ROS overcomes the protective cellular anti-oxidant mechanisms and becomes cytotoxic. In the erythroid system, excess ROS causes accelerated apoptosis (programmed cell death) of precursor cells in the bone marrow and a short survival of mature RBCs in the circulation, resulting in chronic anemia. Excess iron and ROS may also damage other cells and lead to malfunctioning of vital organs, such as the heart and liver (2,3).

FPP has been reported to bind and neutralize (scavenge) ROS (4) as well as free iron (chelate) (5). Both activities ameliorate the oxidative stress.

Treatment with FPP of various diseases associated with oxidative stress, administered orally (3 gr. X 3 times a day), have been shown to significantly ameliorate the symptoms underlying these diseases (6-18). FPP has a long track-record of safe human consumption (19-20). It has been used for many years as a food-supplement by thousands of people around the world without any reported side effect.