Patients with thalassemia are frequently deficient in key micronutrients. Attempts to correct these inadequacies through nutritional supplementation have been met with some success, although disparities between intake and circulating levels continue to be observed. This study employed a convenience sample of 41 well-nourished transfusion dependent patients with thalassemia to identify possible mechanisms behind nutritional deficiencies. Each subject completed a Block 2005© Food Frequency Questionnaire (FFQ), through which macro and micronutrient intake was quantified. Fasting blood was drawn to assess vitamins A, C, D, E, copper, selenium, zinc and hematologic parameters. Dietary intake was found to be inadequate compared to Institute of Medicine (IOM) recommendations for many of the fat-soluble vitamins, as well as calcium and zinc. Circulating deficiencies of vitamins C, D, copper, zinc and γ tocopherol were also present in over 20% of patients. Many individuals who consumed an adequate dietary intake had deficient levels of circulating nutrients, which suggest alternative etiologies of nutrient excretion or loss, in addition to higher micronutrient requirements. Liver iron concentration displayed a significant negative relationship with vitamins C (r=−0.62, p<0.001), E (r=−0.37, p=0.03), and zinc (r=−0.35, p=0.037), indicating that in iron-overloaded patients, these nutrients are either endogenously consumed at higher rates or sequestered within the liver, resulting in a functional nutrient deficiency. While this study identified hepatic iron overload to be a significant cause of nutritional deficits commonly observed in patients with thalassemia, multiple etiologies are simultaneously responsible. In response to these findings, nutritional status should be monitored regularly in at-risk patients with thalassemia, and prophylactically addressed with supplementation or aggressive chelation to avoid associated co-morbidities.

Many patients with beta-thalassemia major have depressed circulating levels of essential micronutrients. These nutritional deficiencies may be caused by an elevated requirement for these nutrients, increased excretion and/or because of inadequate dietary intake. However, the relationship between dietary intake and circulating levels of key nutrients has not been explored. Therefore, the aim of this prospective, cross-sectional study was to quantitate intake using gold standard dietary assessment techniques, as well as to assess circulating levels of key micronutrients in the fasted state in a contemporary sample of subjects with transfusion-dependent thalassemia (age >5 years). Dietary intake was determined with the Block©2005 3-day semi-quantitative food frequency questionnaire (NutritionQuest, Berkeley, CA) completed within 3 months of a pre-transfusion blood sample. Dietary intake (mg/day) was calculated relative to the Institute of Medicine recommendations for age and gender. Intake was then compared to circulating levels of vitamin C, 25-OH vitamin D, alpha & gamma-tocopherol, zinc, copper and selenium. The usage of nutritional supplements was documented. All results were analyzed using STATA (v 9.3, College Station, TX). Forty-one patients (20 male, mean age 28.3 ± 10.7 years) with an average BMI of 22.1 ± 5.2 kg/cm2 and pre-transfusion hemoglobin of 10.9 ± 1.5 g/dL were enrolled. The mean liver iron concentration (LIC) measured by Ferritometer was 13.5 ± 11.3 mg/g dry liver-weight. As has been observed previously, 14 to 30% of patients had low circulating levels of Zn, Cu, 25-OHD, vitamin C and alpha-tocopherol. No deficiencies were observed for selenium. Patients consumed on average 1555 ± 835 kcal/d (80% of estimated energy requirement) and 1.3 ± 0.9 g/kg protein. Average dietary intake was inadequate (less than estimated average requirement) for Ca, Zn, Cu, and vitamins C, D, and E. Among patients with low circulating micronutrient levels, 86% of those with low serum zinc also had low dietary zinc intake; similarly, 88% of those with low circulating copper also had low copper intake. Significant inverse correlations were observed between LIC and blood concentrations of the antioxidants vitamin C (r = -0.62), alpha-tocopherol (r = -0.37) and zinc (r = -0.35). The relationship between iron overload and vitamin C was further explored in a retrospective sample of 49 patients where simultaneous values of both measures were available (228 samples). Vitamin C level progressively decreased with increasing iron burden. The mean vitamin C level was 0.57 ± 0.47 mg/dL with LIC >15 mg/g compared with 1.06 ± 0.45 mg/dL when LIC was <7 mg/g (P <0.001). Serum ferritin levels were not associated with vitamin C deficiency (plasma concentration <0.4 mg/dL) at mild to moderate degrees of liver iron overload. However, with extreme iron overload (LIC >25 mg/g), ferritin levels were significantly greater in the presence of vitamin C deficiency (6545 ± 2597 ng/mL versus 4720 ± 1915 ng/mL, p=0.045). These data suggest that iron overload negatively influences blood levels of several micronutrients. Moreover, dietary intake is insufficient to support circulating levels of nutrients in optimally transfused thalassemia patients. Nutritional adequacy is essential for optimal health, and vitamin C status can impact chelation efficiency. Future research should consider nutritional supplementation and health outcomes in patients with transfusion-dependent thalassemia. Disclosures No relevant conflicts of interest to declare.