The present study investigated nutritional status and body composition of patients suffering from transfusion-dependent β-thalassemia major. According to our results, the majority of patients (76.1%) were well-nourished, while 16.4% and 7.5% of patients were at moderate and high risk for malnutrition respectively. Although data regarding nutritional status of adult thalassemic patients are rather scarce, it is speculated that patients with thalassemia may be at increased risk for nutritional deficiencies due to elevated nutrient requirements and/or insufficient intake and absorption of nutrients. More specifically, Fung et al. demonstrated that typical dietary intake of patients with thalassemia was more frequently inadequate compared to control subjects [21]. Another study revealed that more than 30% of thalassemic subjects consumed inadequate levels of vitamin A, D, E, K, folate, calcium, and magnesium [10]. The exact reason behind inadequate intake of nutrients has yet to be determined, but it is supposed that comorbidities and treatments’ side effects contribute to insufficient nutrient intake [11].
Nonetheless, many individuals who reported adequate dietary intake had deficient levels of circulating nutrients, which in turn implies causes of nutrient excretion or loss, in addition to higher micronutrient requirements [11]. For example, due to iron’s molecular similarity to zinc and copper, it is likely that these nutrients may be chelated instead of, or along with, iron. Moreover, vitamin C and zinc levels also have a negative relationship with liver iron concentration. Iron overload increases hepatic metallothionein concentrations which bind zinc, leading to sequestration. In patients with thalassemia with hyperactive erythropoiesis, folate requirements are also increased and deficiencies are commonly reported [22].
On the other hand, 70.1% of our study sample fell into the normal weight category, according to BMI values. The prevalence of underweight was low (7.5%), whereas 22.4% of study patients were overweight and obese. Our results are in accordance with a previous study which assessed body composition in patients with thalassemia. The prevalence of underweight was 5.2% and the prevalence of overweight/obese was 26.5%. The latter was considered low when compared with median data from NHANES 1999–2000, suggesting that thalassemic patients are leaner than their healthy counterparts [23]. However, in another study in patients with thalassemia major, BMI was lower only in male patients, compared to healthy age-matched controls, whereas the female patient group exhibited non-statistically significant differences [7]. This inconsistency could be attributed to the fact that BMI is only a crude measure of nutritional and body composition status since it cannot distinguish patients with the same weight but different proportions of lean and fat body mass [24, 25]
For this reason, a more precise assessment of body composition is required, in order to detect patients with high levels of adiposity and/or low fat-free mass. In our study, we used the BIA method to assess body composition of thalassemic patients. Our analyses demonstrated that almost 87% of patients had low FFM index, whereas almost 75% of patients had high fat mass index. Moreover, a great number of patients (64.2%) were sarcopenic obese, i.e. they had high fat mass index in conjunction with low FFM index. Patients with thalassemia often present with low muscle mass which might be caused due to low physical activity levels commonly seen in these patients. It is assumed that thalassemic patients have decreased physical activity levels due to severe anemia and cardiomyopathies secondary to iron overload [26]. Sohn et al. assessed the cardiopulmonary function of 71, well-transfused thalassemic patients via graded treadmill exercise stress test. Their results showed that patients had limited exercise capacity, while patients with low hemoglobin levels had lower O2 pulse and Vo2max, regardless of gender. Moreover, iron toxicity caused by frequent blood transfusions may be related to vascular inflammation and direct modulation of heart rate response to exercise [27]. Given that physical activity levels are strongly related to body composition, especially lean body mass, it is expected that lack of exercise could lead to reduced muscle mass and increased adipose tissue mass in these patients [23].
Patients with thalassemia tend to have increased adiposity, as it is also reported in previous studies [23, 28]. These alterations in body composition are more frequently seen in thalassemic patients compared to the general population and are related to the high prevalence of sarcopenic obesity observed in our study. Sarcopenic obesity is considered to be a major risk factor for increased morbidity and impaired survival in many chronic diseases [29]. Nevertheless, the impact of sarcopenic obesity on thalassemic patients has yet to be determined. Since a considerable number of patients with thalassemia major are diagnosed with metabolic syndrome and other endocrine disorders [230,31] which could be aggravated by sarcopenic obesity, clinicians should focus on the thorough assessment of this group of patients that could benefit from proper dietary consultation and lifestyle changes.
As expected, medium and high-risk patients, according to MUST, had significantly lower BMI values, lower fat mass percentage, lower FFM index and lower FM index compared to low risk patients. However, an interesting finding was that a great percentage of low-risk patients (74.5%) were sarcopenic obese, whereas the prevalence of sarcopenic obesity was 31.2% in medium/high risk patients. This result highlights the urgent need of body composition analysis of these patients, since other methods of nutritional assessment are not very sensitive to capture alterations in lean and adipose tissue mass.
Body composition of especially low levels of lean mass have been also linked to vitamin D status [32]. In our study, 92.2% of patients were 25-OH-D deficient. Thalassemia is considered to be one of the chronic diseases associated with increased risk for vitamin D deficiency. The prevalence of vitamin D deficiency is particularly seen in β-thalassemia major patients on repeated blood transfusion. A previous study reported that only 18% of a sample of 361 patients with thalassemia residing in North America had sufficient levels of 25-OH vitamin D [33]. Similar levels of inadequacy have been also observed in other studies [34, 35]. Up to 80% of the vitamin D requirement is synthesized in the skin and only a small proportion is obtained from dietary sources. Interestingly, Goldberg et al. indicated that nearly 100% of subjects enrolled in their study consumed inadequate vitamin D, with over a third presenting with depressed circulating levels [11]. Defective synthesis of 25 OH vitamin D and/or hypoparathyroidism have been observed in these patients. Decreased outdoor activities in thalassemic patients can also compromise cutaneous synthesis of vitamin D [36, 37]. Timely high dose vitamin D supplementation of thalassemic patients could replenish vitamin D levels and potentially improve quality of life of these patients [38].
However, in this study there are some limitations that should be addressed. First, the number of patients was relatively small, thus statistical significance of some associations could have been lost. Second, it was a cross-sectional, single-center study that it is not able to determine cause-and-effect relationships between different variables. Moreover, in our study we did not include a control group in order to compare our findings with healthy individuals, especially in terms of body composition analysis. Last but not least, due to the variability between patients, our data may not be fully generalizable to all individuals with thalassemia.
To conclude, adult patients with β-thalassemia major in our group had altered body composition, presenting with increased adiposity and significantly low levels of lean body mass. The prevalence of sarcopenic obesity was also very high in this group of patients. In addition, vitamin D deficiency is very common in transfusion dependent thalassemic patients. Timely detection of patients at risk could lead to prioritization of patients that could benefit from nutritional interventions. Multicenter studies should be conducted in order to define the best dietary approach for these patients in order to attenuate negative effects of disease and treatments’ side effects.