We read with interest the article by Marwaha, et al.(1) on the use of wheat grass juice (WGJ) to reduce transfusion requirements in patients with thalassemia major. We applaud the authors for their efforts in this innovative pilot study, and wish to speculate on possible mechanisms of action that may be considered in the event the authors or others wish to pursue this line of investigation.

Interval between transfusions (days)

22.4 (22.4, 17.5 - 27.5)

26.35 (28.7, 20.7 - 42.2)

0.001

Blood Transfusion (g/kg/year)

255 (242.6, 156 - 306)

188 (187.5, 91 - 291)

0.001

 (N = 16, * Median, Mean, Minimum - Maximum; § Wilcoxon signed-rank test).

First, likely recognizing that all statistically significant results may not be clinically significant, the authors chose a clinical albeit arbitrary endpoint to evaluate the success of the WGJ therapy to decrease transfusion requirements in the study patients. Using their definition of success (>25% reduction of blood transfused compared to the pre-WGJ period), they reasoned that 50% of the patients responded to the WGJ therapy. Using the data they provided in the table in the paper, we performed relevant statistical analyses on the entire cohort to evaluate the effects of WGJ on the total amount of blood transfused and the mean interval between transfusions. We found that WGJ therapy decreased the total volume of blood transfused and increased the intervals between blood transfusions of the entire study cohort (Table I). More importantly, the blood transfusion requirements and intervals between transfusions of the post-WGJ therapy period demonstrated negative and positive relation-ships respectively to the duration of WGJ therapy (Pearson’s correlation co-efficient of 0.560, P <0.05 and 0.627, P <0.01, respectively). These analyses suggest that not only is WGJ therapy effective, but also that the benefit is related to the duration of WGJ therapy. Second, as the authors chose not to speculate on the mechanism of the beneficial action of the WGJ therapy on their transfusion dependent patients, we would like to propose a testable hypothesis for consideration to facilitate future studies in this area. Historically, the beneficial effects of WGJ therapy have been attributed to its rich nutritional content that include antioxidant vitamins (C&E) and bio-flavenoids(2). We speculate that the effects of the WGJ therapy may be due to the action of natural antioxidants on red blood cell (RBC) antioxidant function, and corresponding effects on cellular enzyme function and membrane integrity. This thought is supported by studies that show decreased antioxidant capacities of RBCs of patients with thalassemia(3) as well as beneficial effects on RBC life-span by supplementation of antioxidants in vivo in other hemolytic disorders(4). Although, in this study, the authors did not measure RBC life-span, the greater interval between blood transfusions following institution of WGJ therapy suggests that RBC life-span was increased. Interestingly, the authors noted that the response to WGJ therapy took some months (the "neutral period"); this may suggest that the natural antioxidants contained in the WGJ are better able to prevent cellular injury than to repair RBC enzymes/membranes once damaged. Hence, RBCs, once damaged, would be cleared from the circulation by the reticulo-endothelial system as they would prior to the onset of the WGJ therapy, but newly formed RBCs would not be damaged and have a longer life-span. This antioxidant hypothesis can be easily tested by measuring indices of RBC antioxidant capacity previously noted to be abnormal in patients with thalassemia(3) in study subjects currently on WGJ therapy and matched control patients not consuming WGJ. Studies of RBC life-span may be attempted, but are more complex and are not likely to yield more information than the interval between blood transfusions already noted. Such an antioxidant mechanism of action of WGJ was also cited by Ben-Arye et al to explain the beneficial effects of WGJ therapy in patients with ulcerative colitis(2). While clinical trials are currently underway to find suitable blood substitutes for patients needing blood transfusions, they may not be readily available in developing countries nor would they be preferable to natural therapies aimed at preserving a patient’s own RBCs. Indeed, WGJ and other nutritional therapies may be considered as adjuvants to drug therapy. Using nutritional therapy to augment a patient’s antioxidant defenses in an effort to decrease morbidity and mortality has similarly been advocated in other more dreaded diseases such as cancer(5).

Caraciolo J. Fernandes,
Section of Neonatology,
Department of Pediatrics,
Texas Children Hospital,
Baylor College of Medicine,
Houston, Tx 77030,
E-mail: [email protected]
Donough J. O’Donovan,
Department of Pediatrics,
University College Hospital,
Galway, Ireland.

1. Marawaha RK, Bansal D, Kaur S, Trehan A. Wheat grass juice reduces transfusion requirement in patients with thalassemia major: a pilot study. Indian Pediatr 2004; 41: 716-720.

2. Ben-Arye E, Goldin E, Wengrower D, Stamper A, Kohn R, Berry E. Wheat grass juice in the treatment of active distal ulcerative colitis: a randomized double-blind placebo-controlled trial. Scand J Gastroenterol 2002; 37: 444-449.

3. Chan AC, Chow CK, Chiu D. Interaction of antioxidants and their implication in Genetic Anemia. Proc Soc Exp Biol Med 1999; 222: 274-282.

4. Hafez M, Amar ES, Zedan M, Hammad H, Sorour AH, el-Desouky ES, Gamil N. Improved erythrocyte survival with combined vitamin E and selenium therapy in children with glucose-6-phosphate dehydrogenase deficiency and mild chronic hemolysis. J Pediatr 1986; 108: 558-561.

5. Donaldson M. Nutrition and cancer: A review of the evidence for an anti-cancer diet. Nutrition Journal 2004; 3: 19.