Nutraceutical Benefits of Green Tea in Beta-Thalassemia with Iron Overload

*Pimpisid Koonyosying, Suthat Fucharoen and Somdet Srichairatanakool*

## **Abstract**

Secondary iron overload in patients with β-thalassemia is caused by multiple blood transfusions and increased iron absorption. Most of them die from cardiac arrest and infections while others from oxidative tissue damage and organ dysfunction. Under high saturation of transferrin with iron, redox-active iron such as nontransferrin-bound iron, labile plasma iron, and cellular labile iron pool is prone to the production of reactive oxygen species, oxidized biomolecules, oxidative tissue damages, and complications. Iron chelation therapy and antioxidant supplementation are a supportive treatment for patients' better quality of life and life expectancy. Green tea (*Camellia sinensis*) extract (GTE) is abundant with polyphenols, mainly epigallocatechin-3-gallate and nutraceuticals, which are beneficial for cell functions and health. Importantly, GTE possesses antioxidant, free radical scavenging, metal-chelating, anti-hemolysis properties in cell cultures, animals, and humans. This article has reported modes of actions and challenged such wonderful properties of green tea used to remove excessive iron, scavenge harmful radicals, restore malfunctions of vital organs, and treat patients with β-thalassemia with iron overload. Infeasibility and sustainability, the benefits of green tea can be applied for use in other diseases with iron toxicity and oxidative stress.

**Keywords:** *Camellia sinensis*, catechins, green tea, iron, oxidative stress, thalassemia

### **1. Introduction**

Erythrocytes or red blood cells (RBC) play a crucial role in oxygen carrying and transportation. The main component of RBC is hemoglobin (Hb) which consists of four subunits of globin chain with heme group at the center of each subunit. The types of Hb can be defined by different globin chain compositions. For instances, hemoglobin A (HbA) consists of two α-globin chains and two β-globin chains (α2β2), which is found in high levels of normal human blood. Hemoglobin A2 (HbA2) consists of two α-globin chains and two δ-globin chains (α2δ2), which is found in low levels of normal human blood and may be increased in the blood of patients with β-thalassemia. Fetal hemoglobin (HbF) consists of two α-globin chains and two γ-globin chains (α2γ2), which is present in high levels in fetal and newborn human blood. Likewise, embryonic hemoglobin such as hemoglobin Gower I (ζ2ε2) and Gower II (α2ε2) are produced in early life and switched to other Hb types during development.

Human β-thalassemia is characterized by mutations of β-globin gene, resulting in deficient production of the β-globin chains of Hb molecule (ineffective erythropoiesis) and chronic anemia. Over 200 mutations have been identified in this gene, and the type of mutations can influence the severity of the disease. Blood transfusions aim to maintain normal Hb levels to prevent tissue hypoxia, whereas repeated blood transfusions lead to the inevitable consequence of iron accumulation in the body. Iron deposition occurs considerably in almost all tissues but is primarily located in the spleen, liver, heart, and endocrine glands. Besides ferritin iron and hemosiderin, the uncommon forms of iron including labile or transient iron pools (LIP) in the tissues, nonheme iron in RBC membrane, and non-transferrin-bound iron (NTBI) and labile iron pool (LPI) in plasma appear to be redox-active and subsequently generate reactive oxygen species (ROS) via Haber-Weiss and Fenton reactions. The ROS can oxidize biomolecules, causing oxidative tissue damage, organ dysfunctions, complications, and death. Effective iron chelation needs giving to counteract the resulting iron overload and prevent oxidative tissue damage. So far, monotherapy or combined therapy with iron chelators such as desferrioxamine (DFO), deferiprone (DFP), and deferasirox (DFX) has been used for the treatment of patients with β-thalassemia with iron overload, but they present some side effects. Modified medical regimens such as adjunctive iron chelator and antioxidant and drug cocktail are purported to increase the chelation efficacy, minimize the side effects, and achieve additive chelation efficacy. Moreover, commercially available antioxidants such as vitamin C, vitamin E, and *N*-acetylcysteine (NAC) are usually given together with the chelators to relieve the oxidative stress in patients with thalassemia. Herein, an interesting natural product such as green tea extract from tea leaves (*Camellia sinensis*) has been documented in terms of bifunctional antioxidant and iron-chelating properties in iron-overloaded cells and mouse and human thalassemia, rather than its general biological and pharmacological properties.
