**Michał Brzezi ´nski 1,2,\*, Agnieszka Jankowska 1, Magdalena Słomi ´nska-Fr ˛aczek 3, Paulina Metelska 2,4, Piotr Wi´sniewski 5, Piotr Socha <sup>6</sup> and Agnieszka Szlagatys-Sidorkiewicz <sup>1</sup>**


Received: 24 March 2020; Accepted: 13 April 2020; Published: 15 April 2020

**Abstract:** Background: Vitamin D was studied in regards to its possible impact on body mass reduction and metabolic changes in adults and children with obesity yet there were no studies assessing the impact of vitamin D supplementation during a weight management program in children and adolescence. The aim of our study was to assess the influence of 26 weeks of vitamin D supplementation in overweight and obese children undergoing an integrated 12–months' long weight loss program on body mass reduction, body composition and bone mineral density. Methods: A double–blind randomized placebo–controlled trial. Vitamin D deficient patients (<30 ng/ml level of vitamin D) aged 6–14, participating in multidisciplinary weight management program were randomly allocated to receiving vitamin D (1200 IU) or placebo for the first 26 weeks of the intervention. Results: Out of the 152 qualified patients, 109 (72%) completed a full cycle of four visits scheduled in the program. There were no difference in the level of BMI (body mass index) change – both raw BMI and BMI centiles. Although the reduction of BMI centiles was greater in the vitamin D vs. placebo group (−4.28 ± 8.43 vs. −2.53 ± 6.10) the difference was not statistically significant (*p* = 0.319). Similarly the reduction in fat mass—assessed both using bioimpedance and DEXa was achieved, yet the differences between the groups were not statistically significant. Conclusions: Our study ads substantial results to support the thesis on no effect of vitamin D supplementation on body weight reduction in children and adolescents with vitamin D insufficiency undergoing a weight management program.

**Keywords:** vitamin D; obesity; weight–loss; body composition

#### **1. Introduction**

Worldwide prevalence of overweight and obesity is increasing both in adults and children [1,2]. It is observed on all continents, with the highest burden in those from lower socioeconomic and educational groups [1,3]. Obesity among others is associated with a wide range of metabolic disorders, such as

insulin resistance, hyperinsulinemia, and impaired tolerance of glucose, abnormal fasting plasma glucose, symptomatic diabetes mellitus, lipid disorders and cardiovascular disorders, namely arterial hypertension [4–6]. Obesity alone is responsible for a significant increase in the risk of mortality in general population with [7]. In view of high risk of complications resulting from childhood obesity, early implementation of intervention programs seems to be vitally important, as in children and adolescents it is the first–choice intervention, although with limited effectiveness [8]. Several previous studies showed that integrated multidisciplinary weight–loss programs, which include the child's family as well, are the most effective [9–11]. Reduction of fat mass is associated with normalization of metabolic parameters, such as inflammatory markers, lipid profile, insulin resistance and arterial blood pressure [12–14]. Therefore, early and efficient intervention increases likelihood of staying healthy in the future. As pharmacological and surgical interventions in children are limited [15–17], trials looking for substances supporting lifestyle interventions were run, looking at several different dietary supplements, hers (green tea, yerba mate), DHA (docosahexaenoic acid) among others [18–22]. Vitamin D was also studied in regards to its possible impact on body mass reduction and metabolic changes in adults and children with obesity [23,24].

The role of vitamin D in energetic metabolism has been emphasized recently. Obese children frequently present with low blood concentrations of vitamin D [25–27]. This probably results from lower dietary intake of this vitamin by obese individuals on the one hand, and less outdoor physical activity on the other [28–30]. Moreover, a higher percentage of fat mass is associated with a lower blood concentration of vitamin D, which may, at least partially, result from its sequestration in adipose tissue [31]. Animal experiments with labelled vitamin D showed that this vitamin is accumulated in adipose tissue and slowly released to blood [32].

Consequently, a vitamin D deficiency in obese children seems to be associated with a significant increase of risk of many metabolic disorders associated with obesity, such as insulin resistance, hyperinsulinemia, impaired tolerance of glucose, abnormal fasting plasma glucose, symptomatic diabetes mellitus, lipid disorders and cardiovascular morbidity, namely arterial hypertension [5,6]. There is a number of observational studies which demonstrate the substantial role of vitamin D deficiency in developing metabolic syndrome and other complications of obesity [33–35]. However, we lack interventional studies to link these observations to demonstrate a causal relationship.

In this study we wanted to assess the influence of 26 weeks of vitamin D supplementation in overweight and obese children undergoing an integrated 12–months' long weight loss program on body mass reduction, body composition and bone mineral density [36].

#### **2. Materials and Methods**

Detailed information about the study protocol, participants and design of the interventional program has been previously published [36]. All study participants were recruited from "6–10–14 for Health" program run by University Clinical Center in Gdansk, Poland. The program is a multidisciplinary, interventional program dedicated to children aged 6–15 and their parents. All school children in Gdansk aged 6–15 are screened in a 3–4–year–interval by dedicated teams (pediatrician and or nurses). All children with BMI centile above 85th centile are invited to the "6–10–14 for Health" program. All participants of the "6–10–14 for Health" program and their family members (parents/caregivers) were offered 12–month integrated intervention, including individual medical (pediatric), dietetic, physical activity and psychological counselling, during one meeting (4 x 20–25min). This intervention was offered to all the participants in a 0–3–6–12 month scheme.

#### *2.1. Trial Design*

A double–blind placebo–controlled trial. Vitamin D deficient patients (<30 ng/ml level of vitamin D) participating in multidisciplinary weight program were randomized to two arms (1:1 ratio): receiving vitamin D (1200 IU) or placebo for the first 26 weeks of the intervention.

We hypothesized that the supplementation with vitamin D in obese children showing low serum 25(OH)D3 during weight–loss program could positively influence body mass index (BMI), muscle mass, bone mass and mineral density and biochemical markers of metabolic complications related to obesity compared to placebo.

The study was conducted at the Department of Paediatrics, Paediatric Gastroenterology, Allergology and Children Nutrition, the Medical University of Gdansk and within the framework of "6–10–14 for Health" Interventional Programme, University Clinical Centre in Gdansk.

#### *2.2. Participants*

Eligible participants were children aged 6, 9–11 and 14, according to the "6–10–14 for Health" program protocol:

**Inclusion criteria:** overweight (BMI ≥ 85th < 95th percentile) or obesity (BMI ≥ 95th percentile), identified on the basis of anthropometric parameters using Polish reference centile charts—OLAF project [37]; blood concentration of 25(OH)D3 < 30 ng/ml; written informed consent of legal caregivers.

**Exclusion criteria:** Chronic conditions (asthma or allergies, inflammatory diseases of connective tissue, gastrointestinal disorders, diseases of kidneys and liver, disorders of bone metabolism); contraindications to administration of vitamin D; administration of any preparation containing vitamin D, calcium, or steroid hormones during three months preceding the study.

#### *2.3. Ethics Approval and Consent to Participate*

The study is approved by Independent Bioethics Committee for Scientific Research at Medical University of Gdansk, Poland, [NKBBN/130–206/2015] dated 25.05.2015. The parents/caregivers gave their written consent before the start of any study procedure. The study protocol was peer reviewed by financial supporter (Fundacja Nutricia) independent commission, during the grant application process. Trial registration no: NCT 02828228; trial registration date: 8 June 2016 registered in: ClinicalTrials.gov.

#### *2.4. Study Procedure*

The study period covered four appointments within the "6–10–14 for Health" obesity management program at the 0, 3, 6 and 12 month mark. All visits included individual meetings with a pediatrician, dietician, physical activity specialist and psychologist. All child/parent dyads had individual meetings with all 4 specialists—one directly after other. Detailed information about the program can be found in previous publications [36]. During the first appointment, the caregivers of all children were asked to provide written consent to the child taking part in the trial. Refusal to participate in the trial did not influence participation in the interventional obesity management program. Children with low blood concentration of 25(OH)D3 (<30 ng/ml) were referred for DXA (dual–energy x–ray absorptiometry) within two weeks from the starting visit.

The enrolled subjects were randomly assigned to one of the two groups using computer generated randomization tables. Then participants were randomly assigned to one of the two trial groups:


Study time line chart is shown in Figure 1.

**Figure 1.** Patients' time line in the study.
