Background
Obesity is associated with an array of metabolic disorders, such as insulin resistance, hiperinsulinemia, impaired glucose tolerance, abnormal fasting glycaemia, symptomatic diabetes mellitus, dyslipidaemia and cardiovascular disorders, namely arterial hypertension. Moreover, overweight or obese subjects are at increased risk of joint and skeletal disorders, respiratory problems, kidney diseases and alimentary dysfunction, especially non-alcoholic fatty liver disease. High risk of complications associated with childhood obesity justifies early implementation of intervention programmes. Many previous studies demonstrated that the most effective form of intervention are integrated multidisciplinary weight-loss programmes, involving not only children but also their family members [
1‐
3]. Reduction of fat mass is associated with normalization of metabolic parameters, such as inflammatory markers, lipid profile, insulin resistance and arterial blood pressure [
3‐
6]. Thus, early effective intervention increases the likelihood of staying healthy at older age.
Role of vitamin D in energetic metabolism has been emphasized quite recently. Many obese children present with low blood concentrations of vitamin D [
7‐
9], probably due to its insufficient dietary intake and too small amount of outdoor physical activity [
10,
11]. Also greater fat mass seems to be associated with lower blood concentration of vitamin D, which may, at least partially, result from sequestration of this vitamin in adipose tissue [
12]. Animal experiments with labelled vitamin D demonstrated that it is accumulated in adipose tissue and slowly released to circulation [
13].
Another important issue is contribution of vitamin D to the etiopathogenesis of metabolic syndrome. Previous studies documented inverse relationships between blood concentration of vitamin D, waist circumference, systolic blood pressure, insulin resistance, fasting glycaemia, total cholesterol, triglyceride and LDL cholesterol levels in paediatric subjects, as well as positive associations between concentrations of vitamin D and HDL cholesterol [
7,
14,
15]. Vitamin D seems to interfere with insulin secretion both directly, binding to its receptors (VDR) on pancreatic β cells, and indirectly, modulating extracellular concentration of calcium [
16].
Importantly, a positive association has been found between concentration of vitamin D and sensitivity to insulin in obese children; furthermore, the level of this vitamin correlated inversely with concentration of glycated haemoglobin (HbA1c) [
17]. Moreover, obese children with low concentrations of vitamin D presented with elevated levels of inflammatory mediators, such as cathepsin S, chemerin and soluble vascular cell adhesion molecule (sVCAM); this may imply indirectly that vitamin D acts as an immunomodulator [
14]. Although supplementation of vitamin D contributed to a decrease in insulin resistance in obese adolescents, their levels of inflammatory markers (CRP, TNF-α, IL-6) remained unchanged [
18].
These findings imply that vitamin D deficient obese children may be at increased risk of many metabolic disorders, such as insulin resistance, hiperinsulinemia, impaired glucose tolerance, abnormal fasting glycaemia, symptomatic diabetes mellitus, dyslipidaemia and arterial hypertension. Indeed, a number of observational studies documented a substantial role of vitamin D deficiency in etiopathogenesis of metabolic syndrome and other obesity-related complications. However, we still lack evidence from interventional studies confirming causal character of these relationships.
Metabolic effects of obesity on bone growth and maturation are still not fully understood. Moreover, the results of previous studies analysing bone mass and bone density in obese individuals are highly inconclusive. While according to some authors, bone mass decreases with body weight [
19], others did not document a significant effect of body weight on bone mineral density [
20,
21] or even demonstrated that obese children, adolescents and adults presented with relatively higher bone mass and dimensions [
22,
23]. An increase in bone mass and bone density in obese subjects is postulated to result from greater mechanical load, direct effect of leptin or enhanced enzymatic activity of aromatase [
23‐
26]. Nevertheless, obesity was also shown to be associated with a marked increase in bone fracture risk in paediatric population [
23].
Vitamin D plays an important biological role in the process of bone maturation and mineralization. Previous studies documented an inverse relationship between blood concentration of vitamin D and bone mineral density [
27,
28]. In a recently published meta-analysis, supplementation of vitamin D was shown to improve both bone mineral density and total bone mass in subjects deficient with this vitamin [
29]. The effects of the supplementation seem to be particularly favourable in premenarcheal girls with normal body weight, in whom administration of vitamin D was shown to result in an increase in both bone mass and fat-free mass [
30].
Surprisingly, the results of previous studies analysing a relationship between obesity, vitamin D and bone metabolism are sparse and highly inconclusive. An analysis of 58 morbidly obese teenagers demonstrated that individuals with physiological blood concentrations of parathyroid hormone (PTH) presented with normal bone mineral density, irrespectively of their vitamin D levels [
31].
In contrast, a recently published study including a small group of adolescents with obesity (
n = 24) or normal body weight (
n = 25) showed that the former presented with higher bone mineral density than their normal-weight peers; this relationship turned out to be independent of blood concentration of vitamin D, physical activity level and fat-free mass content. However, in the same study, bone mineral density correlated with blood concentrations of leptin and insulin [
25].
The abovementioned data suggest that further research on the role of vitamin D in bone metabolism of obese individuals may be of vital importance.
Aside from many unquestioned favourable health effects, weight loss may also contribute to enhanced bone turnover and cause a decrease in bone mineral density. The results of a recently published systemic review imply that a decrease in bone mass may be a consequence of a calorie-restricting diet, rather than a result of an exercise-induced weight-loss [
32]. However, this evidence originates mostly from studies conducted among adults [
33‐
35] and to the best of our knowledge, the issue in question was a subject of only one study including adolescents after bariatric surgeries [
36]. Furthermore, the results of intervention studies suggest that a low-calorie albeit high-protein (ca. 30%) diet, with high amounts of dairy products, may prevent bone mass loss and protect against a decrease in bone mineralization [
37].
Available data on the efficacy of vitamin D supplementation in adults subjected to a weight-loss intervention are inconclusive and limited. Although in one study, administration of vitamin D turned out to be associated with more evident decrease in fat mass content in persons being on a slimming diet [
38], in another experiment, similar intervention did not exert any effect on total body weight [
39,
40]. However, the abovementioned findings are not necessarily contradictory, as the loss of fat mass is not an equivalent of a decrease in total body weight.
Most of the previous studies dealing with the problem in question were observational and centred around an association between vitamin D status and bone mineral density.
Owing a paucity of data on the biological role of vitamin D supplementation during weight-loss intervention in children, we decided to verify this association during a double-blind placebo-controlled randomized trial. The aim of the currently ongoing study is to verify if supplementation of vitamin D to obese children deficient with this vitamin exerts an effect on an outcome of an integrated weight-loss intervention.
Discussion
The study is currently ongoing and the data are still collected. No partial results have been published thus far. Obesity, defined as an excessive accumulation of adipose tissue with resultant impairment of body functioning, is associated with an increase in morbidity and mortality risk. A dramatic increase in the prevalence of overweight and obesity among children has been documented during recent 30 years. A study conducted at the Institute of Food and Nutrition within the framework of the National Programme for Obesity Prevention showed that about 12–14% of Polish children are obese [
45], and in another study performed by Kułaga et al. in 2007–2009, the prevalence of overweight and obesity among boys and girls was estimated at 18.7% and 14.1%, respectively [
46,
47]. Also our own data obtained within the framework of the “6–10-14 for Health” programme imply that the problem of excess body weight refers to 15.6% of paediatric population in Gdansk.
Many authors emphasized the importance of a complex approach to children with obesity. Also involvement of family members, friends and acquaintances is considered to be an important determinant of a successful weight-loss intervention [
1‐
3].
Our preliminary findings imply that 12-month intervention is sufficient for a significant decrease in absolute BMI value, BMI percentile and fat mass content (p = 0.0001).
The hereby presented study is conducted within the framework of a well-established programme, and we benefit from our previous 5-year experiences with this project.
The study protocol will enable us to estimate the prevalence of vitamin D deficiency in obese children from Gdansk and to compare this figure with available epidemiological data for other populations [
7‐
9]. Aside from a decrease in physical activity level, overt inflammatory response and hormonal dysregulation, excess body weight likely affects also bone metabolism and bone mineral density. However, available data in this matter are still inconclusive [
19‐
26]. Importantly, a link between obesity and bone mass/bone density has not been confirmed in any large population-based study. The discrepancies between the results of previous studies may reflect methodological differences (e.g. measurement of bone density in various segments of the skeleton) or individual variability in bone maturation rate. Further, available evidence regarding the effect of weight loss on bone mineral density is generally sparse, inconclusive and limited mostly to adults [
32‐
35].
Still little is known about the effects of vitamin D supplementation on the outcome of a weight-loss intervention in obese subjects. All published studies dealing with the problem in question included exclusively adults [
38,
40] and centred around BMI and fat mass only [
38,
39]. One recent study analysed weight loss-related changes in bone mineral density of 50–75-year-old subjects [
40]; to the best of our knowledge, this is the only report documenting potential beneficial effects of vitamin D supplementation in prevention of bone mass loss during body weight reduction. The hereby presented project seems to be justified in view of a metabolic diversity typical for the puberty; in our opinion, this study may provide an important insight into biological effects of vitamin D supplementation in obese children being enrolled to an integrated multidisciplinary program for body weight reduction.
It is noteworthy that the results of this study will likely find an application in everyday clinical practice. Providing adequate evidence from this project, monitoring of vitamin D level and its supplementation in deficient subjects may become an imperative in paediatric patients with excess body weight.
Patient flow chart depicts the process of qualifying participants of the “6–10-14 for Health” programme to the study. As all children participating in the programme are overweight/obese, blood concentrations of 25(OH) D3 will be determined, and only the subjects with vitamin D3 levels below 30 ng/ml will be enrolled, providing consent from their parents/legal guardians. Then, all the subjects will be managed in line with the “6–10-14 for Health” programme protocol.
The flow chart depicts the procedure and scheme of qualification, randomization, duration of the study and included interventions.
The table provides detailed information about the procedures (medical examination, laboratory tests) included at consecutive stages of the study.
Acknowledgements
The authors express their gratitude to all participants, their parents and members of the “6-10-14 for Health” team for their input into the study. The authors would also like to thank the University Clinical Centre administrative staff for their help in conducting the study, special thanks to the Clinical Trials Office staff at the University Clinical Centre for all the assistance in developing and running the study.