In our study, the oral group had slightly higher baseline 25OHD levels than the IM group, but the IM group achieved a significantly higher increase in 25OHD levels than the oral group. For children aged 1 to 5 years, Shaikh et al. found that a single dose of 600,000 IU of cholecalciferol administered IM achieved a statistically significant higher range of serum 25OHD levels compared to oral administration of the same dose. In addition, this study suggests using the IM route for children suspected of having malabsorption (13). In a study conducted by Gupta et al., healthy adults were given either IM cholecalciferol (300,000 IU) or oral cholecalciferol (60,000 IU) weekly for five weeks, and the results showed that the IM group had significantly higher 25OHD levels than the oral group (14). Moreover, in older patients, Tellioglu et al. reported that older patients who received a single dose of 600,000 IU of cholecalciferol intramuscularly had a statistically significant increase in serum 25OHD levels compared to those who received the same dose orally (15). On the other hand, Cipriani et al. studied the bioavailability of oral or IM administration of a single dose of 600,000 IU of cholecalciferol in adults with vitamin D deficiency and found that both forms of vitamin D3 were effective in increasing serum 25OHD levels at day 90 of treatment (16). Cipriani et al. also reported that a single oral dose of 600,000 IU of cholecalciferol significantly increased 25OHD levels in healthy subjects (17). In 20 obese patients with vitamin D deficiency, Brar et al. showed that oral vitamin D (300,000 IU) therapy significantly increased 25OHD levels (18). Another study compared the effectiveness of oral administration of 2,000 IU cholecalciferol once daily for 12 weeks in obese and nonobese Caucasian adolescents and concluded that obese patients required higher cholecalciferol doses to treat vitamin D deficiency (19). At the first clinic visit, we advised our patients to consume vitamin D-rich foods and get regular sunlight exposure. The majority of them consumed these foods and were exposed to sunlight in order to increase their serum 25OHD levels. We assume that our patients’ dietary vitamin D intake has been increased, but we are unable to distinguish between vitamin D derived from food and that derived from sunlight’s effect on serum 25OHD levels. Although these foods and sunlight exposure have an impact on our results, it is impossible to avoid recommending them to patients in clinics.
One study investigated the pharmacokinetics of the 25OHD response to three different doses of oral cholecalciferol in obese adults and found that 2.5 IU/kg of oral cholecalciferol was required for each unit increase in 25OHD level (ng/ml) (20). Heaney et al. reported that the anticipated rate of increase in serum 25OHD level was 7 ng/ml for each 1,000 IU/day of cholecalciferol administered orally (21). After 12 weeks, we established that the anticipated rate of increase in serum 25OHD level was 0.38 ng/ml/kg for each 300,000 IU of cholecalciferol administered IM and 0.29 ng/ml/kg for each 300,000 IU of cholecalciferol administered orally. Additionally, we found that the anticipated daily rate of increase in serum 25OHD in the IM group was significantly higher than that in the oral group.
Although vitamin D deficiency was prevalent in obese children, the prevalence of rickets was low, implying that it was a relatively rare disease in obese children (1,22). If adequate Ca and vitamin D are consumed, the Ca concentrations remain within the normal range. If Ca or vitamin D consumption is decreased, Ca concentrations may decrease (22-24). Due to the feedback mechanism, decreased Ca concentrations result in increased PTH secretion, lowering serum PO4 levels by increasing PO4 excretion in the urine (22-25). Decreased PO4 levels cause rickets by inhibiting the apoptosis of hypertrophic chondrocytes (24,25). We found no evidence of rickets in 96 obese children with vitamin D deficiency due to their adequate Ca intake. These patients exhibited increased hunger or decreased satiation, suggesting that they may be at a lower risk of acquiring rickets. Moreover, our patients exhibited fewer musculoskeletal manifestations owing to adequate calcium intake. We expected obese children to have fewer musculoskeletal manifestations of vitamin D deficiency than nonobese children because they are more likely to get enough calcium from foods due to increased hunger or decreased satiation.
Vitamin D deficiency has been linked to a variety of disorders, including insulin resistance, type 2 diabetes, polycystic ovarian syndrome, and non-alcoholic fatty liver disease, as well as autoimmune and neoplastic diseases (3–5). Obese children are more likely to have these disorders as a result of their increased fat tissue. To avoid these disorders, serum 25OHD levels in obese children should be maintained above 20 ng/dl (2,26). Samaranayake et al. investigated the effects of vitamin D supplementation on obesity-related parameters, including anthropometric measures, body composition, and metabolic profiles in obese Sri Lankan children with vitamin D deficiency, and found that a high dose of vitamin D improved these parameters (26). Moreover, Aliashrafi et al. evaluated the efficacy of vitamin D supplementation on glucose homeostasis, insulin resistance, and matrix metalloproteinase levels in obese subjects with vitamin D deficiency and found that improving vitamin D status resulted in greater weight loss and a reduction of matrix metalloproteinase levels (27). Furthermore, Rajakumar et al. reported that optimizing the vitamin D status of obese children may improve their cardiovascular health (28). We found that supplementation with a single dose of 300,000 IU of cholecalciferol administered IM or orally normalized 25OHD levels in our obese patients. However, we were unable to follow these parameters in our patients. On their second clinic visits, the majority of children in our study felt well-being, and their guardians requested that the treatment be continued. Both routes for administering a 300,000 IU dose of cholecalciferol resulted in 25OHD levels within the normal range in our region.
Compliance is critical to achieve the 25OHD target level in children. For maximum efficacy, oral cholecalciferol supplementation should be regularly administered on a daily or weekly basis.
Single oral or IM doses of vitamin D may be a practical choice for treating children with vitamin D deficiency.
One of the strengths of our study was the pre-and post-comparison design, which eliminated confounding variables such as ethnicity, age, gender, or season. Another strength of our study was the inclusion of children with a broad range of BMI SDS values in the obese range, including those with extreme obesity, defined as a BMI SDS as high as 4.4 for age and gender. Prior to treatment, we also assessed nutritional Ca intake, sunlight exposure, and musculoskeletal findings.
Although our sample was relatively small for a post-comparison study in obese children, we revealed for the first time that supplementing with a single dose of 300,000 IU of cholecalciferol intramuscularly resulted in a greater increase in 25OHD levels than a single oral dose. This study would be interesting if we considered vitamin D intake during the observation period. Another limitation in our study is that the number of patients in the IM group was nearly double that of the oral group since most obese children with irritable bowel syndrome refused to receive oral vitamin D due to nausea and epigastric pain. Another limitation of our study was the inability to assess bone turnover markers and, consequently, the state of skeletal health. Our study was not designed to determine the pharmacokinetics of 25OHD response to treatments, which depend mainly on genetic factors, including 24-hydroxylase and 25-hydroxylase activity, as well as vitamin D-binding protein synthesis (29-32).
In conclusion, our findings show that the IM group had higher bioavailability than the oral group. Administration of a single dose of vitamin D (300,000 IU), either IM or orally, was found to normalize 25OHD levels in vitamin D deficient obese children.