Vitamin D, Childhood Obesity, and Metabolic Risk – A Scoping Review

Vitamin D, Childhood Obesity, and Metabolic Risk – A Scoping Review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Vitamin D, Childhood Obesity, and Metabolic Risk – A Scoping Review Menuja Deeghanu, Harith Wickramasekara This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7540633/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Vitamin D deficiency and childhood obesity are increasingly recognized as overlapping global health challenges, both of which have substantial implications for long-term wellbeing. Due to the lipophilic nature of vitamin D, excessive adiposity reduces its bioavailability, thereby predisposing overweight and obese children to inadequate circulating 25-hydroxyvitamin D [25(OH)D] concentrations. This deficiency has been associated with impaired bone mineralization, insulin resistance, systemic inflammation, and an elevated risk of type 2 diabetes mellitus, cardiovascular disease, and osteoporosis later in life. Several supplementation strategies for improving vitamin D status in pediatric populations with overweight or obesity have been proposed; however, their efficacy remains inconclusive. Evidence from randomized clinical trials and observational studies indicates that vitamin D supplementation leads to modest increases in serum 25(OH)D levels, with higher-dose regimens producing greater improvements. Findings on the impact of supplementation on metabolic and cardiovascular outcomes are inconsistent, with no clear consensus on the optimal dosing or duration needed to achieve clinically meaningful benefits. Beyond supplementation, lifestyle interventions involving weight reduction through dietary modification and increased physical activity may also contribute to improved vitamin D status, although the interplay between adiposity, vitamin D metabolism, and health outcomes is complex and not yet fully understood. The widespread expression of vitamin D receptors and 1α-hydroxylase in multiple tissues, including adipose tissue, suggests a potential regulatory role in adipogenesis and adipocyte metabolism, which may partly explain the extensive health effects linked to deficiency. This scoping review synthesizes the available evidence on vitamin D, childhood obesity, and metabolic risk, highlighting key research gaps. Further well-designed longitudinal and interventional studies are urgently required to clarify causality, define optimal vitamin D status, and establish effective interventions for improving health outcomes in this vulnerable population. Physiology Vitamin D childhood obesity metabolic risk supplementation adiposity Introduction Obesity is considered a multifactorial disease with high prevalence among children and adolescents ( 1 ). Worldwide, an estimated 43 million children are overweight or obese, and an additional 92 million are at risk of becoming overweight ( 2 ). Studies reveal that childhood obesity is linked to an increase in related chronic illnesses, including insulin resistance (IR), dyslipidaemia, hypertension, and inflammation, which can have long-term effects on a child's physical health as well as their psychological and functional health ( 3 ). The relationship between vitamin D deficiency and childhood obesity is a prominent area of research. Each has been classified as an epidemic globally, sharing common risk factors such as poor diet and inactivity ( 2 ). Furthermore, new intervention trials suggest that improving the low vitamin D status linked to obesity may lessen some of the comorbidities of obesity. Observational and clinical research also demonstrate an inverse relationship between vitamin D status and fat mass ( 4 ). The objective of this review is to discuss the recent literature on vitamin D and childhood obesity, including their interactions and implications for health and disease. Vitamin D: the hormone, the nutrient, and its action Vitamin D is more accurately characterised as a prohormone or hormone, though it is historically categorised as a nutrient ( 5 ). It is found in two main variants: vitamin D2 and vitamin D3. Vitamin D2, also known as ergocalciferol, is formed when ergosterol, a sterol found in fungi and also referred to as provitamin D2, is exposed to ultraviolet light. Vitamin D3, or cholecalciferol, is generated when ultraviolet rays act on 7-dehydrocholesterol (provitamin D3) in the skin’s epidermal and dermal layers ( 6 ). The general term “vitamin D” can refer to either D2, D3, or both forms. The most significant source of vitamin D is its synthesis in the skin, as only a limited number of foods naturally contain it ( 7 ). Both vitamin D2 and D3 must go through two chemical changes in the body to become active and able to bind to the vitamin D receptor (VDR) ( 8 ). As the first step, the enzyme 25-hydroxylase converts vitamin D into 25-hydroxyvitamin D (25(OH)D), also known as calcidiol, in the liver. This is the main form of vitamin D found in the blood and is used to measure vitamin D levels in the body ( 8 ). Then, the enzyme 1α-hydroxylase (1α-OH-ase) changes 25(OH)D into its active form, 1,25-dihydroxyvitamin D (1,25(OH)₂D), also called calcitriol in kidneys ( 9 ). When 25(OH)D is activated in the kidneys, the resulting 1,25(OH)₂D enters the bloodstream and travels to other tissues where it binds to VDRs ( 10 ). However, 1,25(OH)₂D acts locally within the same or nearby cells in tissues outside the kidney. Vitamin D and its forms are carried in the blood by proteins, mostly by vitamin D-binding protein (DBP). It is mainly made in the liver. DBP carries about 85% of 25(OH)D in the blood, and the rest is attached to albumin and other proteins such as lipoproteins ( 11 ). 1,25(OH)2D is transported to nuclear VDR in target cells after being synthesised from renal or local production ( 12 ). Vitamin D plays significant roles in calcium and phosphorus homeostasis, bone growth and bone mineralisation in childhood. Vitamin D deficiency in childhood causes osteomalacia, leading to growth retardation and skeletal deformities such as rickets ( 13 ). However, vitamin D deficiency can present insidiously, which may prevent children and adolescents from reaching their peak bone mass and predicted height ( 14 ). Vitamin D is also involved in numerous cellular processes in addition to calcium and phosphate homeostasis. VDRs are expressed in a variety of tissues and cells, such as the hepatocytes, myocytes, adipocytes, pancreatic β-cells, and several immune cells, all of which are associated with obesity and its associated metabolic complications ( 12 ). Childhood prevalence of vitamin D deficiency Vitamin D deficiency is a significant issue affecting individuals of all age groups globally. However, there is still limited data available regarding its prevalence in paediatric populations in certain countries ( 15 ). The global prevalence of vitamin D deficiency among children and adolescents varies considerably, ranging from 29–100%. Research suggests that this variation is partly influenced by body fat levels. Furthermore, vitamin D deficiency affects approximately 21% of children with a healthy weight, 29% of those who are overweight, 34% of obese children, and up to 49% of those who are severely obese. These findings indicate that children with obesity are particularly at risk for vitamin D deficiency, which may further worsen the negative health impacts associated with obesity itself ( 15 , 16 ). Interactions and implications of vitamin D deficiency in obese children\ Vitamin D deficiency in obese children is a significant public health concern, with implications for metabolic health and overall well-being. Research indicates a strong association between low vitamin D levels and obesity, highlighting the need for targeted interventions. Vitamin D plays a significant role in metabolic processes, and its deficiency is linked to increased insulin resistance, inflammation, and impaired bone mineralisation ( 17 ). The deficiency may exacerbate the risk of developing type 2 diabetes and cardiovascular diseases in obese children ( 17 ). A long-term, population-based prospective study involving 1,226 adults over a ten-year period revealed that individuals with serum 25(OH)D levels below 42 nmol/L (17 ng/mL) had a 2.37-fold higher likelihood of gaining more than 3.7 kg (placing them in the top 25th percentile for weight gain) between their second and third study visits, compared to those with higher vitamin D levels ( 18 ). Insulin resistance (IR) and inflammation are frequently observed in overweight and obese children and act as early indicators for the future onset of metabolic syndrome, type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and potentially reduced bone density, such as osteopenia or osteoporosis. Several studies have shown that children exhibiting both of these risk factors are considerably more likely to develop T2DM and CVD two to three decades later, in comparison to children without these conditions ( 19 ). Furthermore, the link between inadequate vitamin D levels and conditions such as insulin resistance (IR), type 2 diabetes mellitus (T2DM), and metabolic syndrome has been extensively researched, with initial findings reported in obese adults. Subsequent studies have identified similar patterns in obese children. While not entirely consistent, the majority of studies report meaningful associations between serum 25(OH)D levels and markers of insulin resistance and glucose regulation ( 20 ). These findings have been thoroughly reviewed in other literature. Few of the published intervention trials have investigated the effects of vitamin D supplementation on insulin resistance and impaired glucose tolerance in obese children and adolescents, and the results have generally been positive. For example, in a six-month randomised controlled trial (RCT) involving obese adolescents (average age 14.1 ± 2.8 years; mean BMI 39.8 ± 6.1 kg/m²), daily supplementation with 4,000 IU of vitamin D led to a reduction in insulin resistance comparable to the improvements typically seen with metformin treatment. In contrast, a 2012 meta-analysis evaluating the impact of vitamin D supplementation on glycemic control in adults found only a modest benefit in lowering fasting glucose levels and improving insulin resistance among individuals with type 2 diabetes or impaired glucose tolerance. This variation in outcomes is largely due to methodological differences across studies, including the dosage of vitamin D used, the specific outcomes assessed, and differences in participant characteristics, particularly body weight or fat levels, baseline vitamin D status, and age. Methods For this scoping review, we adhered to the five-stage framework proposed by Levac, Colquhoun and O’Brien for conducting scoping reviews ( 21 ). The first four stages are described below; collating, summarising, and reporting the results are presented in the Results section. 2.1 Identifying the research questions This review was guided by the following questions. Association – What is the relationship between vitamin D status and the prevalence or severity of childhood overweight/obesity? Metabolic risk – How is vitamin D status linked with cardiometabolic risk markers (insulin resistance, dyslipidaemia, metabolicsyndrome components) in children and adolescents? Interventions – What interventional strategies (supplementation, fortification, lifestyle programmes that include vitamin D) have been implemented to modify vitamin D status in paediatric populations with overweight/obesity, and what metabolic outcomes have been reported? Evidence landscape – What study designs, assessment methods, and outcome measures are most commonly used, and where are the gaps in the current literature? A scoping rather than a systematic review was selected because the field spans heterogeneous study designs (observational and interventional), populations (various definitions of obesity and vitamin D deficiency), and outcomes (anthropometric and biochemical). A broad mapping is therefore required to characterise the evidence base and to highlight research gaps and priorities. 2.2 Identifying relevant studies Following the threestep search strategy recommended by Peters et al. (22), we first conducted a preliminary search in PubMed to refine keywords and index terms. The final search (last updated 1 December 2024) was executed in the PubMed (MEDLINE) and Google Scholar electronic databases, selected for their coverage of biomedical, nutrition, and paediatric research. The core search string combined controlled vocabulary (MeSH) and freetext terms. ("vitamin D" OR cholecalciferol OR ergocalciferol OR "25hydroxyvitamin D") AND (child OR adolescent OR paediatric) AND (obese OR overweight) AND ("metabolic risk" OR "metabolic syndrome" OR dyslipidaemia) Search filters were applied to human studies published in English between 2020 and 2024. No restrictions were placed on study design at this stage. We handsearched the reference lists of included articles and relevant reviews to identify additional papers and grey literature (World Health Organisation reports). 2.3 Studyselection criteria Screening was guided by a modified PICOS framework ( 23 ). Component Inclusion criteria Exclusion criteria Population (P) Children and adolescents ≤ 18 years, with or without overweight/obesity (as defined by study authors). Adults; animal or invitro studies. Intervention / Exposure (I) (a) Measured vitamin D status (serum 25(OH)D) or (b) vitamin D supplementation/fortification / sunexposure interventions. Multifactorial programmes where the independent effect of vitamin D could not be isolated. Comparator / Control (C) Adequate vs deficient vitamin D status, placebo / usual care, or alternative vitamin D dosing. Comparisons between nonvitamin D exposures (e.g., calcium only). Outcomes (O) At least one obesity or metabolic marker: BMI, BMIz, waist circumference, bodyfat %, insulin, HOMAIR, fasting glucose, lipid profile, blood pressure, metabolic syndrome prevalence, inflammatory markers (CRP, IL-6, etc.). Outcomes unrelated to adiposity or metabolic risk (e.g., boneonly endpoints without metabolic data). Study design (S) Randomised controlled trials, quasiexperimental studies, prospective or retrospective cohort studies, case–control studies, and crosssectional studies. Case reports/series, editorials, narrative reviews, protocols, conference abstracts without full text, theses, and unpublished data. Titles/abstracts were screened independently by two reviewers (MR and HW). Fulltexts of potentially eligible studies were retrieved and assessed against the criteria; disagreements were resolved by consensus or by a third reviewer. Study selection was recorded in a PRISMAScR flow diagram. 2.4 Data extraction and charting A datacharting form was pilottested on five studies and then applied to all included articles. One reviewer extracted, and a second verified, the following information: Bibliographic details (first author, year, country). Study characteristics (design, recruitment method, sample size). Participant characteristics (age range/mean, sex distribution, obesity definition, baseline 25(OH)D categories). Intervention/exposure details (supplement dose, regimen, duration) Outcomes reported and measurement tools. Key findings relevant to adiposity or metabolic risk (significance). We charted the data in Microsoft Excel and repeatedly updated the table as new themes emerged, consistent with Levac et al.’s iterative approach ( 21 ). Results Table 1 Key findings of the studies investigating vitamin D supplementation in obese/overweight children and adolescents. Reference (authors, year, country) Participants and Design Intervention Duration (supplementation / follow-up) Key Findings Aguirre Castaneda 2012, USA ( 24 ) 36 adolescents (n = 18 obese, n = 18 normal weight) / open label non-randomized trial 2000 IU/d 12 weeks / 12 weeks Baseline mean 25(OH)D concentrations were higher in individuals with normal weight than in those with obesity. The rise in 25(OH)D levels after vitamin D supplementation was significantly attenuated among adolescents with obesity. No changes were observed in circulating phosphorus or parathyroid hormone levels, while circulating calcium levels showed only a change of limited clinical relevance. Belenchia et al. 2013, USA ( 25 ) 35 obese adolescents (n = 18 group 1, n = 17 placebo group) / randomized controlled trial 4000 IU/d (group 1), or placebo 6 months / 6 months After three months, none of the participants in group 1 remained vitamin D deficient. By six months, 93% of them had achieved sufficient vitamin D status. In contrast, the placebo group showed no significant rise in 25(OH)D levels over time. At six months, group 1 demonstrated reduced insulin levels compared to the placebo group, while glucose and glycated hemoglobin levels remained unchanged. No differences were observed in BMI or inflammatory markers between the groups. Bhagatwala et al. 2015, USA ( 26 ) 70 overweight/obese adolescents and young adults with vitamin D deficiency (n = 17 group 1, n = 18 group 2, n = 18 group 3, n = 17 placebo group) / randomized controlled trial 600 IU/d (group 1), 2000 IU/d (group 2), 4000 IU/ d (group 3), or placebo 16 weeks / 16 weeks Monthly supplementation with either 2000 IU or 4000 IU of vitamin D was similarly effective in attaining serum 25(OH)D concentrations of 30 ng/ml, whereas a daily intake of 600 IU was insufficient. Administration of 4000 IU facilitated a faster improvement in vitamin D status. Alterations were noted in parathyroid hormone levels, while no significant changes were observed in fibroblast growth factor-23, serum phosphorus, or urinary calcium excretion. Chung et al. 2019, Korea ( 27 ) 62 children and adolescents (n = 21 obese/ overweight, n = 41 normal weight) with vitamin D deficiency / single arm trial 2000 IU/d 8 weeks / not specified A daily dose of 2000 IU vitamin D was adequate to correct deficiency in both normal-weight and overweight children without adverse effects. Nonetheless, vitamin D sufficiency was achieved in 64% of normal-weight participants compared to 48% in those who were overweight. Among the overweight group, post-intervention reductions were observed in serum phosphorus concentrations and BMI z-scores, whereas no significant changes were noted in calcium, parathyroid hormone, or lipid parameters including total cholesterol, triglycerides, HDL, and LDL. Brzezi´ nski et al. 2020, Poland ( 28 ) 152 overweight and obese children and adolescents (n = 85 group 1, n = 67 placebo group) with vitamin D insufficiency / randomized control trial 1200 IU/d (group 1), or placebo 26 weeks / 12 months Although the supplementation had an impact on 25(OH)D levels, only six patients in the intervention group achieved a level above 30 ng/ml at the end of follow-up. No effect was observed on BMI. Javed et al. 2015, USA ( 29 ) 51 obese adolescents (n = 25 group 1, n = 26 group 2) with vitamin D insufficiency / randomized controlled trial 400 IU/d (group 1) or 2000 IU/d (group 2) 12 weeks / 12 weeks There was a modest but significant increase in 25(OH)D concentration in the group 2, but not in the group 1. Four subjects in group 1 and 6 in group 2 achieved 25(OH)D levels ≥ 30 mg/L. No effect was observed on insulin action and β-cell function Javed et al. 2016, USA ( 30 ) 19 obese adolescents with vitamin D insufficiency / single arm trial 100,000 IU once a month 3 months / 3 months The supplementation was effective in increasing 25(OH)D levels in obese adolescents but did not influence endothelial function. No changes in circulating and urinary calcium levels were found Rajakumar et al. 2008, USA ( 31 ) 41 children (n = 21 obese, n = 20 normal weight) with vitamin D deficiency / non- randomized pre-post intervention 400 IU/d 1 month / 1 month Treatment response effects were different in obese and in normal-weight cohorts. In obese children with vitamin D deficiency, the intervention did not raise blood levels of 25 (OH)D to levels ≥ 30 ng/ml. No difference in circulating calcium, phosphorus, albumin, parathormone, bone-specific ALP was observed. Rajakumar et al. 2020, USA ( 32 ) 225 overweight/obese adolescents (n = 76 group 1, n = 74 group 2, n = 75 group 3) with vitamin D deficiency / randomized controlled trial 600 IU/d (group 1), 1000 IU/d (group 2), 2000 IU/ d (group 3) 6 months / 6 months A dose-response in vitamin D levels was observed at 3 and 6 months. PTH concentrations were lower at 3 months in group 1, at 6 months in group 2, and at 3 and 6 months in group 3. The three regimens of supplementation did not influence endothelial function, arterial stiffness, systemic inflammation, or lipid profile, but resulted in lower blood pressure and glucose levels and higher insulin sensitivity. Samaranayake et al. 2020, Sri Lanka ( 33 ) 96 obese children and adolescents (n = 32 group 1, n = 33 group 2, n = 31 placebo group) with vitamin D deficiency / randomized controlled trial 50,000 IU per week (group 1), 2500 IU per week (group 2), placebo (group 3) 24 weeks / 24 weeks From baseline to 6 months, the increase in vitamin D levels in group 1 was significantly greater compared to both group 2 and group 3, while no significant difference was noted between group 2 and group 3. A clear dose-dependent reduction was observed in biceps skinfold thickness. However, changes in BMI-SD score, triceps and suprailiac skinfold thickness, waist circumference-SD score, percentage body fat, serum parathyroid hormone, LDL, AST, AST/ALT ratio, and insulin resistance were not statistically significant. Rostampour et al. 2020, Iran ( 34 ) 53 overweight/obese children and adolescents with vitamin D deficiency / single arm trial 50,000 IU weekly for 8 weeks, and then 1000 IU/ d for 3 months. 5 months / 5 months The intervention significantly increased circulating vitamin D levels in obese and overweight children. BMI and circulating glucose but not insulin resistance decreased after the intervention. Magge et al. 2018, USA ( 35 ) 26 obese adolescents (n = 12 group 1, n = 14 group 2) with vitamin D deficiency / randomized controlled trial 1000 IU/d (group 1), 5000 IU/d (group 2) 12 weeks / 12 weeks Circulating 25(OH)D levels showed a smaller increase in group 1 compared to group 2, with 30% and 83% of participants, respectively, achieving concentrations ≥ 20 ng/ml. The intervention did not result in significant changes in mineral metabolites or cardiometabolic risk markers. Tayde et al. 2021, India ( 36 ) 44 normal weight and obese children and adolescents (n = 22 obese, n = 22 normal- weight) with vitamin D deficient / non randomized trial 150,000 IU, single oral dose Single dose / 1 month In obese children, the increase in circulating 25(OH)D levels was 2.2 times lower than that observed in children with normal BMI. While no significant changes were noted in iPTH levels, ALP levels were found to be elevated among obese children. Varshney et al. 2019, India ( 37 ) 189 obese adolescents (n = 96 group 1, n = 93 group 2) / randomized controlled trial 120,000 IU one a month (group 1), 12,000 IU once a month (group 2) 12 months / 12 months Higher dose of vitamin D was associated with a higher increase in circulating 25(OH)D levels. Vitamin D deficiency persisted in 32% subjects in group 1% and 90% in group 2. No relevant effect was observed on β cell function, cardiovascular risk factors, circulating PTH, glucose and insulin. Vinet et al. 2021, France ( 38 ) 26 obese adolescents (n = 13 group 1, n = 13 placebo; a lifestyle program was proposed to both groups) 23 normal-weight adolescents / randomized controlled trial 4000 IU/d (group 1), or placebo 3 months / 3 months Circulating 25(OH)D concentrations raised above 20 ng/ml in all obese adolescents, especially in those receiving vitamin D supplements. Insulin resistance decreased more in group 1 than in placebo group, while C- reactive protein decreased similarly in the two groups. Endothelium- dependent microvascular reactivity increased only in group 1. Sethuraman et al. 2018, USA ( 39 ) 29 obese adolescents (n = 15 group 1, n = 14 placebo group) with vitamin D deficiency / randomized controlled trial 50,000 IU per week (group 1) or placebo 12 weeks / 12 weeks A significant increase in vitamin D levels in the interventional group compared to placebo was observed, but no difference was observed for insulin- or lipid-related parameters. De Cosmi et al. 2022, Italy ( 40 ) 108 obese children and adolescents with vitamin D deficiency. They all received dietary guidance and were randomized in 2 groups to receive or not also docosahexaenoic acid supplementation 1200 IU/d in both groups 6 months / 6 months Over half of the participants demonstrated an improvement in vitamin D status. Both groups showed reductions in fat mass percentage and body mass index following the intervention. 25(OH)D = 25-hydroxy-vitamin D; iPTH = intact parathyroid hormone; BMI = body mass index; SD = standard deviation; HDL = high-density lipoprotein; LDL = low- density lipoprotein, ALP = alkaline phosphatase; AST = aspartate aminotransferase; ALT = alanine transaminase; SFT = skinfold thickness; WC = Waist circumference. A total of 17 studies met the inclusion criteria, representing 1,037 participants across multiple geographical locations including the United States (n = 8), India (n = 2), Sri Lanka (n = 1), Korea (n = 1), Poland (n = 1), Iran (n = 1), France (n = 1), and Italy (n = 1). Study designs included randomized controlled trials (n = 12), non-randomized or quasi-experimental studies (n = 3), and single-arm trials (n = 2). Daily oral supplementation was the most common regimen, with doses ranging from 400 IU/day to 5000 IU/day, or intermittent high-dose regimens such as 50,000 IU/week, monthly high doses, and single mega-doses (Table 1 ). Thirteen studies investigated vitamin D supplementation exclusively in adolescents ( 24 – 26 , 29 , 30 , 31 , 32 , 35 , 37 – 39 ), while two studies included both children and adolescents ( 27 , 40 ). Two additional studies had conducted including both adolescents and young adults ( 26 , 34 ). Based on the findings from the 17 studies, the total sample size consisted of 1,037 participants. Five studies included more than 100 subjects ( 28 , 32 , 33 , 37 , 40 ). Nine out of the seventeen studies compared one or more vitamin D supplementation regimens with placebo ( 25 , 28 , 29 , 30 , 32 , 33 , 35 , 38 , 39 ), while the remaining studies either compared different supplementation doses or evaluated a single dosage regimen. Furthermore, 5 studies directly compared overweight/obese participants with normal-weight counterparts and consistently found attenuated treatment responses among obese groups ( 24 , 27 , 31 , 36 , 38 ). Overall, most trials were conducted exclusively among overweight or obese participants. Vitamin D deficiency or insufficiency was used as an inclusion criterion in all the studies ( 24 – 40 ). Most studies reported mean values of 25(OH)D before and after the intervention, while a few reported only changes in vitamin D concentrations. Based on the selected studies, several supplementation regimens were tested. Eleven studies provided daily oral doses (ranging from 400 IU/day to 5000 IU/day), while others employed weekly, monthly, or single high-dose administrations (e.g.- 50,000 IU/week, 100,000 IU/month, or one-time mega-doses of 120,000–150,000 IU). Among these, higher-dose regimens (> 20,000 IU per week equivalent) consistently produced marked increases in circulating 25(OH)D, particularly among obese subjects. No adverse effects attributable to supplementation were reported. According to the selected studies, supplementation increased serum 25-hydroxyvitamin D [25(OH)D] concentrations in overweight and obese children, although the magnitude varied. The meta-analysis of seven randomized placebo-controlled trials demonstrated that there was a pooled mean difference of 1.6 ng/mL (95% CI: 0.60–2.60) in favor of supplementation ( 25 , 28 , 29 , 30 , 32 , 33 , 39 ). High-dose regimens (> 20,000 IU/week) generally produced greater increases, with some trials reporting sufficiency rates above 80% ( 25 , 33 , 37 ). However, in several studies, fewer than half of obese participants achieved sufficiency despite supplementation ( 24 , 27 ). Most studies found no significant effect on BMI, BMI z-score, waist circumference, or body fat percentage. Exceptions included trials by Chung et al. ( 27 ), who reported reductions in BMI z-score and body fat markers after 8 weeks of 2000 IU/day, and De Cosmi et al. ( 40 ), who observed a significant reduction in fat mass percentage after 6 months of 1200 IU/day with or without DHA. Beyond vitamin D and calcium status, cardiometabolic outcomes were frequently assessed. Thirteen studies evaluated cardiovascular or metabolic outcomes, including lipid profile, insulin resistance, glucose regulation, and blood pressure. Improvements in insulin sensitivity or reductions in fasting insulin/HOMA-IR were reported in several trials ( 25 , 32 , 34 , 38 , 39 ), although findings were not consistent across all studies. Discussion This study investigated the effects of vitamin D supplementation on children and adolescents with overweight or obesity. According to the selected studies, supplementation increased serum 25-hydroxyvitamin D [25(OH)D] concentrations in overweight and obese children, although the magnitude varied. The meta-analysis of seven randomized placebo-controlled trials demonstrated a pooled mean difference of 1.6 ng/mL (95% CI: 0.60–2.60) in favor of supplementation ( 25 , 28 – 30 , 32 , 33 , 39 ). High-dose regimens (> 20,000 IU/week) generally produced greater increases, with some trials reporting sufficiency rates above 80% ( 25 , 33 , 37 ). Although a statistically significant mean difference was observed, only a small proportion of obese children in some studies achieved vitamin D sufficiency. In one trial ( 29 ), only half of the obese children achieved normalization of vitamin D status compared to 89% of their non-obese counterparts. Similarly, another study ( 36 ) reported that following 8 weeks of supplementation with 2000 IU/day, 48% of overweight children reached sufficiency, whereas the proportion was 62% among normal-weight participants. Conversely, a different investigation ( 25 ) demonstrated that over 90% of obese children receiving 2000 IU/day attained serum vitamin D concentrations above 20 ng/ml. Consistent with this, a study on vitamin D–deficient subjects showed that 83% of participants treated with 5000 IU/day and 30% of those given 1000 IU/day for three months achieved 25(OH)D levels ≥ 20 ng/ml ( 24 ). Furthermore, both 50,000 IU/week and 5000 IU/day regimens proved effective in increasing 25(OH)D concentrations above 20 ng/ml in more than 80% of participants, with 72% and 56% in each group, respectively, surpassing 30 ng/ml ( 31 ). Several mechanisms may account for the challenges in raising vitamin D levels in obese populations. One explanation is the sequestration of vitamin D in adipose tissue, which reduces its bioavailability ( 41 , 42 ). Additionally, low dietary intake of vitamin D–rich foods and limited sunlight exposure, both common in this group, may further contribute to persistently low circulating 25(OH)D levels ( 41 , 42 ). Suboptimal vitamin D status can adversely affect multiple health outcomes, including cardiovascular health ( 37 ). Early studies hypothesized that improving vitamin D concentrations could mitigate cardiovascular risk. Supporting this, one trial ( 25 ) found that 6 months of supplementation with 4000 IU/day significantly improved HOMA-IR and QUICKI, both surrogate indicators of insulin resistance and sensitivity. Similarly, another study ( 33 ) reported reductions in serum insulin, triglycerides, HOMA-IR, and C-Met following supplementation. Improvements in blood pressure, fasting glucose, and insulin sensitivity were also observed in another investigation ( 27 ). In contrast, two studies reported no significant changes in cardiovascular risk parameters, including inflammatory markers ( 25 , 33 ). Six studies reported a beneficial effect of vitamin D supplementation on insulin regulation ( 25 , 27 , 28 , 30 , 33 , 34 ). These findings are consistent with evidence from adult populations, which indicate an inverse association between serum 25(OH)D concentrations and insulin resistance ( 38 , 39 ). A possible explanation is that vitamin D may influence inflammatory cytokine production, a key factor contributing to insulin resistance, while also playing a role in insulin secretion and activity ( 38 ). Furthermore, Brzeziński et al. ( 28 ) reported no significant impact of vitamin D supplementation on weight reduction in children with insufficiency who were enrolled in a weight management program. In contrast, Chung et al. ( 27 ) observed improvements in BMI, BMI z-score, and body fat indices following supplementation. Similarly, De Cosmi et al. ( 40 ) found that fat mass percentage decreased significantly in supplemented participants, while BMI improved across both intervention and control groups, although all participants remained obese at study completion. The principal limitation of this review lies in the small number of included studies and the heterogeneity among them. These constraints limit the ability to examine in greater depth the influence of additional variables such as participant age, degree of overweight/obesity, and seasonal variations, which may affect the outcomes of vitamin D supplementation. Conclusion This scoping review provides the most recent evidence regarding the impact of vitamin D supplementation in overweight and obese children and adolescents. While supplementation leads to a significant rise in serum 25(OH)D concentrations, the clinical significance of this improvement appears limited. Evidence concerning its influence on metabolic and cardiovascular outcomes remains inconsistent and inconclusive. 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Feb 20:29–39 González-Molero I, Rojo-Martínez G, Morcillo S, Gutierrez C, Rubio E, Pérez-Valero V, Esteva I, Ruiz de Adana MS, Almaraz MC, Colomo N, Olveira G (2013) Hypovitaminosis D and incidence of obesity: a prospective study. Eur J Clin Nutr 67(6):680–682 Morrison JA, Friedman LA, Gray-McGuire C (2007) Metabolic syndrome in childhood predicts adult cardiovascular disease 25 years later: the Princeton Lipid Research Clinics Follow-up Study. Pediatrics 120(2):340–345 Peterson CA, Tosh AK, Belenchia AM (2014) Vitamin D insufficiency and insulin resistance in obese adolescents. Therapeutic Adv Endocrinol metabolism 5(6):166–189 Levac D, Colquhoun H, O'Brien KK (2010) Scoping studies: advancing the methodology. Implement Sci 5(1):69 Munn Z, Peters MDJ, Stern C, Tufanaru C, McArthur A, Aromataris E (2018) Systematic review or scoping review? Guidance for authors when choosing between a systematic or scoping review approach. BMC MedRes Methodol 18(1):143 Amir-Behghadami M, Janati A, Population (2020) Intervention, Comparison, Outcomes and Study (PICOS) design as a framework to formulate eligibility criteria in systematic reviews. Emerg Med J 37(6):387 Aguirre Castaneda R, Nader N, Weaver A, Singh R, Kumar S (2012) Response to vitamin D3 supplementation in obese and non-obese caucasian adolescents. Horm Res Paediatr 78:226–231. https://doi.org/10.1159/000343446 Belenchia AM, Tosh AK, Hillman LS, Peterson CA (2013) Correcting vitamin D insufficiency improves insulin sensitivity in obese adolescents: a randomized controlled trial. Am J Clin Nutr 97:774–781. https://doi.org/10.3945/ajcn.112.050013 Bhagatwala J, Zhu H, Parikh SJ, Guo D-H, Kotak I, Huang Y, Havens R, Pham M, Afari E, Kim S, Cutler C, Pollock NK, Dong Y, Raed A, Dong Y (2015) Dose and time responses of vitamin D biomarkers to monthly vitamin D3 supplementation in overweight/obese African Americans with suboptimal vitamin d status: a placebo controlled randomized clinical trial. BMC Obes 2:27. https://doi.org/10.1186/s40608-015-0056-2 Chung IH, Kang YS, Yoo E-G (2019) Response to vitamin D replacement in overweight and normal weight children with vitamin D deficiency. Ann Pediatr Endocrinol Metab 24:22–26. https://doi.org/10.6065/apem.2019.24.1.22 Brzezi´ nski M, Jankowska A, Słomi´ nska-Frączek M, Metelska P, Wi´ sniewski P, Socha P, Szlagatys-Sidorkiewicz A (2020) Long-term effects of vitamin D supplementation in obese children during integrated weight–loss programme—a double blind randomized placebo–controlled trial. Nutrients 12:1093. https://doi.org/10.3390/nu12041093 Javed A, Vella A, Balagopal PB, Fischer PR, Weaver AL, Piccinini F, Dalla Man C, Cobelli C, Giesler PD, Laugen JM, Kumar S (2015) Cholecalciferol supplementation does not influence β-cell function and insulin action in obese adolescents: a prospective double-blind randomized trial. J Nutr 145:284–290. https://doi.org/10.3945/jn.114.202010 Javed A, Kullo IJ, Balagopal PB, Kumar S (2016) Effect of vitamin D3 treatment on endothelial function in obese adolescents. Pediatr Obes 11:279–284. https://doi.org/10.1111/ijpo.12059 Rajakumar K, Fernstrom JD, Holick MF, Janosky JE, Greenspan SL (2008) Vitamin D status and response to Vitamin D(3) in obese vs. non-obese African American children. Obesity 16:90–95. https://doi.org/10.1038/oby.2007.23 Rajakumar K, Moore CG, Khalid AT, Vallejo AN, Virji MA, Holick MF, Greenspan SL, Arslanian S, Reis SE (2020) Effect of vitamin D3 supplementation on vascular and metabolic health of vitamin D-deficient overweight and obese children: a randomized clinical trial. Am J Clin Nutr 111:757–768. https://doi.org/10.1093/ajcn/nqz340 Samaranayake DBDL, Adikaram SGS, Atapattu N, Kendaragama KMDLD, Senevirathne JTN, Jayasekera HD, Wickramasinghe VP (2020) Vitamin D supplementation in obese Sri Lankan children: a randomized controlled trial. BMC Pediatr 20:426. https://doi.org/10.1186/s12887-020-02329-w Samaranayake DBDL, Adikaram SGS, Atapattu N, Kendaragama KMDLD, Senevirathne JTN, Jayasekera HD, Wickramasinghe VP (2020) Vitamin D supplementation in obese Sri Lankan children: a randomized controlled trial. BMC Pediatr 20:426. https://doi.org/10.1186/s12887-020-02329-w Magge SN, Prasad D, Zemel BS, Kelly A (2018) Vitamin D3 supplementation in obese, African-American, vitamin D deficient adolescents. J Clin Transl Endocrinol 12:1–7. https://doi.org/10.1016/j.jcte.2018.03.001 Tayde A, Mittal M, Khadgawat R, Sharma S, Sreenivas V, Rai A (2021) Response to single oral dose vitamin D in obese vs non-obese vitamin D-deficient children. Eur J Pediatr 180:1043–1050. https://doi.org/10.1007/s00431-020-03831-0 Varshney S, Khadgawat R, Gahlot M, Khandelwal D, Oberoi AK, Yadav RK, Sreenivas V, Gupta N, Tandon N (2019) Effect of high-dose vitamin D supplementation on beta cell function in obese asian-indian children and adolescents: a randomized, double blind, active controlled study. Indian J Endocrinol Metab 23:545–551. https://doi.org/10.4103/ijem.IJEM_159_19 Vinet A, Morrissey C, Perez-Martin A, Goncalves A, Raverdy C, Masson D, Gayrard S, Carrere M, Landrier J-F, Amiot M-J (2021) Effect of vitamin D supplementation on microvascular reactivity in obese adolescents: a randomized controlled trial. Nutr Metab Cardiovasc Dis 31:2474–2483. https://doi.org/10.1016/j.numecd.2021.04.025 Sethuraman U, Zidan MA, Hanks L, Bagheri M, Ashraf A (2018) Impact of vitamin D treatment on 25 hydroxy vitamin D levels and insulin homeostasis in obese African American adolescents in a randomized trial. J Clin Transl Endocrinol 12:13–19. https://doi.org/10.1016/j.jcte.2018.03.002 De Cosmi V, Mazzocchi A, D’Oria V, Re A, Spolidoro GCI, Milani GP, Berti C, Scaglioni S, Giavoli C, Bergamaschi S, Rodari G, Profka E, Colombo R, Agostoni C (2022) Effect of vitamin D and docosahexaenoic acid co-supplementation on vitamin D status, body composition, and metabolic markers in obese children: a randomized, double blind, controlled study. Nutrients 14:1397. https://doi.org/10.3390/nu14071397 Alemzadeh R, Kichler J, Babar G, Calhoun M (2008) Hypovitaminosis D in obese children and adolescents: relationship with adiposity, insulin sensitivity, ethnicity, and season. Metabolism 57:183–191. https://doi.org/10.1016/j. metabol.2007.08.023 Drincic AT, Armas LA, Van Diest EE, Heaney RP (2012) Volumetric dilution, rather than sequestration best explains the low vitamin D status of obesity. Obesity 7:1444–1448. https://doi.org/10.1038/oby.2011.404 Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7540633","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":510538845,"identity":"a2e6e8a9-f6f5-46b5-8b07-4818c45f2370","order_by":0,"name":"Menuja Deeghanu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABD0lEQVRIiWNgGAWjYHACMxDBY9/ffuDAB4gIG5jk48GrxUDGQOJM4sMZDAYILWwEtNgYMCQYG/MQo0W3vXnbw587/vCYMxxIk7b58yexgf102gOGGjuglgPYrThzrNyY94wBj2Vz4zHp3DaDxAae3O0GDMeSGdh4G7BruZFjJs3YZsDDcABoS24DUIsE7zYJBrYDDGz8ODxy/42Z5E+wlgQzaYs/MC3/8Gi5wWMmwQvUYnAA6H0GNqgWxrYDuB12Jg3kF2MeyRnAQO5tMzZuA/klsS+ZB6f3jx8GhZicPT8/MCp//JGT7Wc/u+3Bh292cvw8CdhdBgKMyC4ARwpQMe6IxNAyCkbBKBgFowAdAABru1lXQmMsGwAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0009-0003-0484-8578","institution":"Faculty of Medicine, University of Colombo","correspondingAuthor":true,"prefix":"","firstName":"Menuja","middleName":"","lastName":"Deeghanu","suffix":""},{"id":510539047,"identity":"785143f5-18ed-4c79-aea0-6df1f043dd5b","order_by":1,"name":"Harith Wickramasekara","email":"","orcid":"","institution":"Department of Medical Education, Faculty of Medicine, University of Kelaniya","correspondingAuthor":false,"prefix":"","firstName":"Harith","middleName":"","lastName":"Wickramasekara","suffix":""}],"badges":[],"createdAt":"2025-09-05 04:25:08","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-7540633/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7540633/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90778587,"identity":"380ceba8-08f3-4c8d-b825-865213638d14","added_by":"auto","created_at":"2025-09-08 03:58:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":940069,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7540633/v1/4d76307b-67a7-451d-9f5a-6c9cf8979dc2.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eVitamin D, Childhood Obesity, and Metabolic Risk – A Scoping Review\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eObesity is considered a multifactorial disease with high prevalence among children and adolescents (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Worldwide, an estimated 43\u0026nbsp;million children are overweight or obese, and an additional 92\u0026nbsp;million are at risk of becoming overweight (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Studies reveal that childhood obesity is linked to an increase in related chronic illnesses, including insulin resistance (IR), dyslipidaemia, hypertension, and inflammation, which can have long-term effects on a child's physical health as well as their psychological and functional health (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). The relationship between vitamin D deficiency and childhood obesity is a prominent area of research. Each has been classified as an epidemic globally, sharing common risk factors such as poor diet and inactivity (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eFurthermore, new intervention trials suggest that improving the low vitamin D status linked to obesity may lessen some of the comorbidities of obesity. Observational and clinical research also demonstrate an inverse relationship between vitamin D status and fat mass (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). The objective of this review is to discuss the recent literature on vitamin D and childhood obesity, including their interactions and implications for health and disease.\u003c/p\u003e\n\u003ch3\u003eVitamin D: the hormone, the nutrient, and its action\u003c/h3\u003e\n\u003cp\u003eVitamin D is more accurately characterised as a prohormone or hormone, though it is historically categorised as a nutrient (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). It is found in two main variants: vitamin D2 and vitamin D3. Vitamin D2, also known as ergocalciferol, is formed when ergosterol, a sterol found in fungi and also referred to as provitamin D2, is exposed to ultraviolet light. Vitamin D3, or cholecalciferol, is generated when ultraviolet rays act on 7-dehydrocholesterol (provitamin D3) in the skin\u0026rsquo;s epidermal and dermal layers (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). The general term \u0026ldquo;vitamin D\u0026rdquo; can refer to either D2, D3, or both forms. The most significant source of vitamin D is its synthesis in the skin, as only a limited number of foods naturally contain it (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eBoth vitamin D2 and D3 must go through two chemical changes in the body to become active and able to bind to the vitamin D receptor (VDR) (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). As the first step, the enzyme 25-hydroxylase converts vitamin D into 25-hydroxyvitamin D (25(OH)D), also known as calcidiol, in the liver. This is the main form of vitamin D found in the blood and is used to measure vitamin D levels in the body (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Then, the enzyme 1α-hydroxylase (1α-OH-ase) changes 25(OH)D into its active form, 1,25-dihydroxyvitamin D (1,25(OH)₂D), also called calcitriol in kidneys (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). When 25(OH)D is activated in the kidneys, the resulting 1,25(OH)₂D enters the bloodstream and travels to other tissues where it binds to VDRs (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). However, 1,25(OH)₂D acts locally within the same or nearby cells in tissues outside the kidney. Vitamin D and its forms are carried in the blood by proteins, mostly by vitamin D-binding protein (DBP). It is mainly made in the liver. DBP carries about 85% of 25(OH)D in the blood, and the rest is attached to albumin and other proteins such as lipoproteins (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). 1,25(OH)2D is transported to nuclear VDR in target cells after being synthesised from renal or local production (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eVitamin D plays significant roles in calcium and phosphorus homeostasis, bone growth and bone mineralisation in childhood. Vitamin D deficiency in childhood causes osteomalacia, leading to growth retardation and skeletal deformities such as rickets (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). However, vitamin D deficiency can present insidiously, which may prevent children and adolescents from reaching their peak bone mass and predicted height (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Vitamin D is also involved in numerous cellular processes in addition to calcium and phosphate homeostasis. VDRs are expressed in a variety of tissues and cells, such as the hepatocytes, myocytes, adipocytes, pancreatic β-cells, and several immune cells, all of which are associated with obesity and its associated metabolic complications (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eChildhood prevalence of vitamin D deficiency\u003c/h2\u003e\u003cp\u003eVitamin D deficiency is a significant issue affecting individuals of all age groups globally. However, there is still limited data available regarding its prevalence in paediatric populations in certain countries (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). The global prevalence of vitamin D deficiency among children and adolescents varies considerably, ranging from 29\u0026ndash;100%. Research suggests that this variation is partly influenced by body fat levels. Furthermore, vitamin D deficiency affects approximately 21% of children with a healthy weight, 29% of those who are overweight, 34% of obese children, and up to 49% of those who are severely obese. These findings indicate that children with obesity are particularly at risk for vitamin D deficiency, which may further worsen the negative health impacts associated with obesity itself (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eInteractions and implications of vitamin D deficiency in obese children\\\u003c/h3\u003e\n\u003cp\u003eVitamin D deficiency in obese children is a significant public health concern, with implications for metabolic health and overall well-being. Research indicates a strong association between low vitamin D levels and obesity, highlighting the need for targeted interventions. Vitamin D plays a significant role in metabolic processes, and its deficiency is linked to increased insulin resistance, inflammation, and impaired bone mineralisation (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). The deficiency may exacerbate the risk of developing type 2 diabetes and cardiovascular diseases in obese children (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). A long-term, population-based prospective study involving 1,226 adults over a ten-year period revealed that individuals with serum 25(OH)D levels below 42 nmol/L (17 ng/mL) had a 2.37-fold higher likelihood of gaining more than 3.7 kg (placing them in the top 25th percentile for weight gain) between their second and third study visits, compared to those with higher vitamin D levels (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eInsulin resistance (IR) and inflammation are frequently observed in overweight and obese children and act as early indicators for the future onset of metabolic syndrome, type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and potentially reduced bone density, such as osteopenia or osteoporosis. Several studies have shown that children exhibiting both of these risk factors are considerably more likely to develop T2DM and CVD two to three decades later, in comparison to children without these conditions (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eFurthermore, the link between inadequate vitamin D levels and conditions such as insulin resistance (IR), type 2 diabetes mellitus (T2DM), and metabolic syndrome has been extensively researched, with initial findings reported in obese adults. Subsequent studies have identified similar patterns in obese children. While not entirely consistent, the majority of studies report meaningful associations between serum 25(OH)D levels and markers of insulin resistance and glucose regulation (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). These findings have been thoroughly reviewed in other literature.\u003c/p\u003e\u003cp\u003eFew of the published intervention trials have investigated the effects of vitamin D supplementation on insulin resistance and impaired glucose tolerance in obese children and adolescents, and the results have generally been positive. For example, in a six-month randomised controlled trial (RCT) involving obese adolescents (average age 14.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8 years; mean BMI 39.8\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1 kg/m\u0026sup2;), daily supplementation with 4,000 IU of vitamin D led to a reduction in insulin resistance comparable to the improvements typically seen with metformin treatment.\u003c/p\u003e\u003cp\u003eIn contrast, a 2012 meta-analysis evaluating the impact of vitamin D supplementation on glycemic control in adults found only a modest benefit in lowering fasting glucose levels and improving insulin resistance among individuals with type 2 diabetes or impaired glucose tolerance. This variation in outcomes is largely due to methodological differences across studies, including the dosage of vitamin D used, the specific outcomes assessed, and differences in participant characteristics, particularly body weight or fat levels, baseline vitamin D status, and age.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eFor this scoping review, we adhered to the five-stage framework proposed by Levac, Colquhoun and O\u0026rsquo;Brien for conducting scoping reviews (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). The first four stages are described below; collating, summarising, and reporting the results are presented in the Results section.\u003c/p\u003e\u003cp\u003e\u003cb\u003e2.1 Identifying the research questions\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis review was guided by the following questions.\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eAssociation\u003c/b\u003e \u0026ndash; What is the relationship between vitamin D status and the prevalence or severity of childhood overweight/obesity?\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eMetabolic risk\u003c/b\u003e \u0026ndash; How is vitamin D status linked with cardiometabolic risk markers (insulin resistance, dyslipidaemia, metabolicsyndrome components) in children and adolescents?\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eInterventions\u003c/b\u003e \u0026ndash; What interventional strategies (supplementation, fortification, lifestyle programmes that include vitamin D) have been implemented to modify vitamin D status in paediatric populations with overweight/obesity, and what metabolic outcomes have been reported?\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eEvidence landscape\u003c/b\u003e \u0026ndash; What study designs, assessment methods, and outcome measures are most commonly used, and where are the gaps in the current literature?\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003cp\u003eA scoping rather than a systematic review was selected because the field spans heterogeneous study designs (observational and interventional), populations (various definitions of obesity and vitamin D deficiency), and outcomes (anthropometric and biochemical). A broad mapping is therefore required to characterise the evidence base and to highlight research gaps and priorities.\u003c/p\u003e\u003cp\u003e\u003cb\u003e2.2 Identifying relevant studies\u003c/b\u003e\u003c/p\u003e\u003cp\u003eFollowing the threestep search strategy recommended by Peters et al. (22), we first conducted a preliminary search in PubMed to refine keywords and index terms. The final search (last updated 1 December 2024) was executed in the PubMed (MEDLINE) and Google Scholar electronic databases, selected for their coverage of biomedical, nutrition, and paediatric research.\u003c/p\u003e\u003cp\u003eThe core search string combined controlled vocabulary (MeSH) and freetext terms.\u003c/p\u003e\u003cp\u003e(\"vitamin D\" OR cholecalciferol OR ergocalciferol OR \"25hydroxyvitamin D\") AND (child OR adolescent OR paediatric) AND (obese OR overweight) AND (\"metabolic risk\" OR \"metabolic syndrome\" OR dyslipidaemia)\u003c/p\u003e\u003cp\u003eSearch filters were applied to human studies published in English between 2020 and 2024. No restrictions were placed on study design at this stage. We handsearched the reference lists of included articles and relevant reviews to identify additional papers and grey literature (World Health Organisation reports).\u003c/p\u003e\u003cp\u003e\u003cb\u003e2.3 Studyselection criteria\u003c/b\u003e\u003c/p\u003e\u003cp\u003eScreening was guided by a modified PICOS framework (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComponent\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eInclusion criteria\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eExclusion criteria\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePopulation (P)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eChildren and adolescents\u0026thinsp;\u0026le;\u0026thinsp;18 years, with or without overweight/obesity (as defined by study authors).\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAdults; animal or invitro studies.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eIntervention / Exposure (I)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e(a) Measured vitamin D status (serum 25(OH)D) \u003cb\u003eor\u003c/b\u003e (b) vitamin D supplementation/fortification / sunexposure interventions.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMultifactorial programmes where the independent effect of vitamin D could not be isolated.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eComparator / Control (C)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAdequate vs deficient vitamin D status, placebo / usual care, or alternative vitamin D dosing.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eComparisons between nonvitamin D exposures (e.g., calcium only).\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eOutcomes (O)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAt least one obesity or metabolic marker: BMI, BMIz, waist circumference, bodyfat %, insulin, HOMAIR, fasting glucose, lipid profile, blood pressure, metabolic syndrome prevalence, inflammatory markers (CRP, IL-6, etc.).\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eOutcomes unrelated to adiposity or metabolic risk (e.g., boneonly endpoints without metabolic data).\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eStudy design (S)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRandomised controlled trials, quasiexperimental studies, prospective or retrospective cohort studies, case\u0026ndash;control studies, and crosssectional studies.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCase reports/series, editorials, narrative reviews, protocols, conference abstracts without full text, theses, and unpublished data.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eTitles/abstracts were screened independently by two reviewers (MR and HW). Fulltexts of potentially eligible studies were retrieved and assessed against the criteria; disagreements were resolved by consensus or by a third reviewer. Study selection was recorded in a PRISMAScR flow diagram.\u003c/p\u003e\u003cp\u003e\u003cb\u003e2.4 Data extraction and charting\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA datacharting form was pilottested on five studies and then applied to all included articles. One reviewer extracted, and a second verified, the following information:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eBibliographic details (first author, year, country).\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eStudy characteristics (design, recruitment method, sample size).\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eParticipant characteristics (age range/mean, sex distribution, obesity definition, baseline 25(OH)D categories).\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eIntervention/exposure details (supplement dose, regimen, duration)\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eOutcomes reported and measurement tools.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eKey findings relevant to adiposity or metabolic risk (significance).\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003eWe charted the data in Microsoft Excel and repeatedly updated the table as new themes emerged, consistent with Levac et al.\u0026rsquo;s iterative approach (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eKey findings of the studies investigating vitamin D supplementation in obese/overweight children and adolescents.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReference (authors, year, country)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eParticipants and Design\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIntervention\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDuration (supplementation / follow-up)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eKey Findings\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAguirre Castaneda 2012, USA (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e36 adolescents (n\u0026thinsp;=\u0026thinsp;18 obese, n\u0026thinsp;=\u0026thinsp;18 normal weight) / open label non-randomized trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2000 IU/d\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 weeks / 12 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eBaseline mean 25(OH)D concentrations were higher in individuals with normal weight than in those with obesity. The rise in 25(OH)D levels after vitamin D supplementation was significantly attenuated among adolescents with obesity. No changes were observed in circulating phosphorus or parathyroid hormone levels, while circulating calcium levels showed only a change of limited clinical relevance.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBelenchia et al. 2013, USA (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35 obese adolescents (n\u0026thinsp;=\u0026thinsp;18 group 1, n\u0026thinsp;=\u0026thinsp;17 placebo group) / randomized controlled trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4000 IU/d (group 1), or placebo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 months / 6 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAfter three months, none of the participants in group 1 remained vitamin D deficient. By six months, 93% of them had achieved sufficient vitamin D status. In contrast, the placebo group showed no significant rise in 25(OH)D levels over time. At six months, group 1 demonstrated reduced insulin levels compared to the placebo group, while glucose and glycated hemoglobin levels remained unchanged. No differences were observed in BMI or inflammatory markers between the groups.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBhagatwala et al. 2015, USA (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e70 overweight/obese adolescents and young adults with vitamin D deficiency (n\u0026thinsp;=\u0026thinsp;17 group 1, n\u0026thinsp;=\u0026thinsp;18 group 2, n\u0026thinsp;=\u0026thinsp;18 group 3, n\u0026thinsp;=\u0026thinsp;17 placebo group) / randomized controlled trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e600 IU/d (group 1), 2000 IU/d (group 2), 4000 IU/ d (group 3), or placebo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16 weeks / 16 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eMonthly supplementation with either 2000 IU or 4000 IU of vitamin D was similarly effective in attaining serum 25(OH)D concentrations of 30 ng/ml, whereas a daily intake of 600 IU was insufficient. Administration of 4000 IU facilitated a faster improvement in vitamin D status. Alterations were noted in parathyroid hormone levels, while no significant changes were observed in fibroblast growth factor-23, serum phosphorus, or urinary calcium excretion.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChung et al. 2019, Korea (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62 children and adolescents (n\u0026thinsp;=\u0026thinsp;21 obese/ overweight, n\u0026thinsp;=\u0026thinsp;41 normal weight) with vitamin D deficiency / single arm trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2000 IU/d\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 weeks / not specified\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eA daily dose of 2000 IU vitamin D was adequate to correct deficiency in both normal-weight and overweight children without adverse effects. Nonetheless, vitamin D sufficiency was achieved in 64% of normal-weight participants compared to 48% in those who were overweight. Among the overweight group, post-intervention reductions were observed in serum phosphorus concentrations and BMI z-scores, whereas no significant changes were noted in calcium, parathyroid hormone, or lipid parameters including total cholesterol, triglycerides, HDL, and LDL.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBrzezi\u0026acute; nski et al. 2020, Poland (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e152 overweight and obese children and adolescents (n\u0026thinsp;=\u0026thinsp;85 group 1, n\u0026thinsp;=\u0026thinsp;67 placebo group) with vitamin D insufficiency / randomized control trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1200 IU/d (group 1), or placebo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e26 weeks / 12 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAlthough the supplementation had an impact on 25(OH)D levels, only six patients in the intervention group achieved a level above 30 ng/ml at the end of follow-up. No effect was observed on BMI.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eJaved et al. 2015, USA (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e51 obese adolescents (n\u0026thinsp;=\u0026thinsp;25 group 1, n\u0026thinsp;=\u0026thinsp;26 group 2) with vitamin D insufficiency / randomized controlled trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e400 IU/d (group 1) or 2000 IU/d (group 2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 weeks / 12 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eThere was a modest but significant increase in 25(OH)D concentration in the group 2, but not in the group 1. Four subjects in group 1 and 6 in group 2 achieved 25(OH)D levels\u0026thinsp;\u0026ge;\u0026thinsp;30 mg/L. No effect was observed on insulin action and β-cell function\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eJaved et al. 2016, USA (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19 obese adolescents with vitamin D insufficiency / single arm trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100,000 IU once a month\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 months / 3 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eThe supplementation was effective in increasing 25(OH)D levels in obese adolescents but did not influence endothelial function. No changes in circulating and urinary calcium levels were found\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRajakumar et al. 2008, USA (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e41 children (n\u0026thinsp;=\u0026thinsp;21 obese, n\u0026thinsp;=\u0026thinsp;20 normal weight) with vitamin D deficiency / non- randomized pre-post intervention\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e400 IU/d\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 month / 1 month\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTreatment response effects were different in obese and in normal-weight cohorts. In obese children with vitamin D deficiency, the intervention did not raise blood levels of 25 (OH)D to levels\u0026thinsp;\u0026ge;\u0026thinsp;30 ng/ml. No difference in circulating calcium, phosphorus, albumin, parathormone, bone-specific ALP was observed.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRajakumar et al. 2020, USA (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e225 overweight/obese adolescents (n\u0026thinsp;=\u0026thinsp;76 group 1, n\u0026thinsp;=\u0026thinsp;74 group 2, n\u0026thinsp;=\u0026thinsp;75 group 3) with vitamin D deficiency / randomized controlled trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e600 IU/d (group 1), 1000 IU/d (group 2), 2000 IU/ d (group 3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 months / 6 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eA dose-response in vitamin D levels was observed at 3 and 6 months. PTH concentrations were lower at 3 months in group 1, at 6 months in group 2, and at 3 and 6 months in group 3. The three regimens of supplementation did not influence endothelial function, arterial stiffness, systemic inflammation, or lipid profile, but resulted in lower blood pressure and glucose levels and higher insulin sensitivity.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSamaranayake et al. 2020, Sri Lanka (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e96 obese children and adolescents (n\u0026thinsp;=\u0026thinsp;32 group 1, n\u0026thinsp;=\u0026thinsp;33 group 2, n\u0026thinsp;=\u0026thinsp;31 placebo group) with vitamin D deficiency / randomized controlled trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e50,000 IU per week (group 1), 2500 IU per week (group 2), placebo (group 3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24 weeks / 24 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eFrom baseline to 6 months, the increase in vitamin D levels in group 1 was significantly greater compared to both group 2 and group 3, while no significant difference was noted between group 2 and group 3. A clear dose-dependent reduction was observed in biceps skinfold thickness. However, changes in BMI-SD score, triceps and suprailiac skinfold thickness, waist circumference-SD score, percentage body fat, serum parathyroid hormone, LDL, AST, AST/ALT ratio, and insulin resistance were not statistically significant.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRostampour et al. 2020, Iran (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e53 overweight/obese children and adolescents with vitamin D deficiency / single arm trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e50,000 IU weekly for 8 weeks, and then 1000 IU/ d for 3 months.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 months / 5 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eThe intervention significantly increased circulating vitamin D levels in obese and overweight children. BMI and circulating glucose but not insulin resistance decreased after the intervention.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMagge et al. 2018, USA (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26 obese adolescents (n\u0026thinsp;=\u0026thinsp;12 group 1, n\u0026thinsp;=\u0026thinsp;14 group 2) with vitamin D deficiency / randomized controlled trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1000 IU/d (group 1), 5000 IU/d (group 2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 weeks / 12 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCirculating 25(OH)D levels showed a smaller increase in group 1 compared to group 2, with 30% and 83% of participants, respectively, achieving concentrations\u0026thinsp;\u0026ge;\u0026thinsp;20 ng/ml. The intervention did not result in significant changes in mineral metabolites or cardiometabolic risk markers.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTayde et al. 2021, India (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e44 normal weight and obese children and adolescents (n\u0026thinsp;=\u0026thinsp;22 obese, n\u0026thinsp;=\u0026thinsp;22 normal- weight) with vitamin D deficient / non randomized trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e150,000 IU, single oral dose\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSingle dose / 1 month\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eIn obese children, the increase in circulating 25(OH)D levels was 2.2 times lower than that observed in children with normal BMI. While no significant changes were noted in iPTH levels, ALP levels were found to be elevated among obese children.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVarshney et al. 2019, India (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e189 obese adolescents (n\u0026thinsp;=\u0026thinsp;96 group 1, n\u0026thinsp;=\u0026thinsp;93 group 2) / randomized controlled trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e120,000 IU one a month (group 1), 12,000 IU once a month (group 2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 months / 12 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eHigher dose of vitamin D was associated with a higher increase in circulating 25(OH)D levels. Vitamin D deficiency persisted in 32% subjects in group 1% and 90% in group 2. No relevant effect was observed on β cell function, cardiovascular risk factors, circulating PTH, glucose and insulin.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVinet et al. 2021, France (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26 obese adolescents (n\u0026thinsp;=\u0026thinsp;13 group 1, n\u0026thinsp;=\u0026thinsp;13 placebo; a lifestyle program was proposed to both groups) 23 normal-weight adolescents / randomized controlled trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4000 IU/d (group 1), or placebo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 months / 3 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCirculating 25(OH)D concentrations raised above 20 ng/ml in all obese adolescents, especially in those receiving vitamin D supplements. Insulin resistance decreased more in group 1 than in placebo group, while C- reactive protein decreased similarly in the two groups. Endothelium- dependent microvascular reactivity increased only in group 1.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSethuraman et al. 2018, USA (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29 obese adolescents (n\u0026thinsp;=\u0026thinsp;15 group 1, n\u0026thinsp;=\u0026thinsp;14 placebo group) with vitamin D deficiency / randomized controlled trial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e50,000 IU per week (group 1) or placebo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 weeks / 12 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eA significant increase in vitamin D levels in the interventional group compared to placebo was observed, but no difference was observed for insulin- or lipid-related parameters.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDe Cosmi et al. 2022, Italy (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e108 obese children and adolescents with vitamin D deficiency. They all received dietary guidance and were randomized in 2 groups to receive or not also docosahexaenoic acid supplementation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1200 IU/d in both groups\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 months / 6 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eOver half of the participants demonstrated an improvement in vitamin D status. Both groups showed reductions in fat mass percentage and body mass index following the intervention.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003e25(OH)D\u0026thinsp;=\u0026thinsp;25-hydroxy-vitamin D; iPTH\u0026thinsp;=\u0026thinsp;intact parathyroid hormone; BMI\u0026thinsp;=\u0026thinsp;body mass index; SD\u0026thinsp;=\u0026thinsp;standard deviation; HDL\u0026thinsp;=\u0026thinsp;high-density lipoprotein; LDL\u0026thinsp;=\u0026thinsp;low- density lipoprotein, ALP\u0026thinsp;=\u0026thinsp;alkaline phosphatase; AST\u0026thinsp;=\u0026thinsp;aspartate aminotransferase; ALT\u0026thinsp;=\u0026thinsp;alanine transaminase; SFT\u0026thinsp;=\u0026thinsp;skinfold thickness; WC\u0026thinsp;=\u0026thinsp;Waist circumference.\u003c/em\u003e\u003c/p\u003e\u003cp\u003eA total of 17 studies met the inclusion criteria, representing 1,037 participants across multiple geographical locations including the United States (n\u0026thinsp;=\u0026thinsp;8), India (n\u0026thinsp;=\u0026thinsp;2), Sri Lanka (n\u0026thinsp;=\u0026thinsp;1), Korea (n\u0026thinsp;=\u0026thinsp;1), Poland (n\u0026thinsp;=\u0026thinsp;1), Iran (n\u0026thinsp;=\u0026thinsp;1), France (n\u0026thinsp;=\u0026thinsp;1), and Italy (n\u0026thinsp;=\u0026thinsp;1). Study designs included randomized controlled trials (n\u0026thinsp;=\u0026thinsp;12), non-randomized or quasi-experimental studies (n\u0026thinsp;=\u0026thinsp;3), and single-arm trials (n\u0026thinsp;=\u0026thinsp;2). Daily oral supplementation was the most common regimen, with doses ranging from 400 IU/day to 5000 IU/day, or intermittent high-dose regimens such as 50,000 IU/week, monthly high doses, and single mega-doses (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThirteen studies investigated vitamin D supplementation exclusively in adolescents (\u003cspan additionalcitationids=\"CR25\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan additionalcitationids=\"CR38\" citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e), while two studies included both children and adolescents (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e). Two additional studies had conducted including both adolescents and young adults (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). Based on the findings from the 17 studies, the total sample size consisted of 1,037 participants. Five studies included more than 100 subjects (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e). Nine out of the seventeen studies compared one or more vitamin D supplementation regimens with placebo (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e), while the remaining studies either compared different supplementation doses or evaluated a single dosage regimen.\u003c/p\u003e\u003cp\u003eFurthermore, 5 studies directly compared overweight/obese participants with normal-weight counterparts and consistently found attenuated treatment responses among obese groups (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). Overall, most trials were conducted exclusively among overweight or obese participants. Vitamin D deficiency or insufficiency was used as an inclusion criterion in all the studies (\u003cspan additionalcitationids=\"CR25 CR26 CR27 CR28 CR29 CR30 CR31 CR32 CR33 CR34 CR35 CR36 CR37 CR38 CR39\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e). Most studies reported mean values of 25(OH)D before and after the intervention, while a few reported only changes in vitamin D concentrations.\u003c/p\u003e\u003cp\u003eBased on the selected studies, several supplementation regimens were tested. Eleven studies provided daily oral doses (ranging from 400 IU/day to 5000 IU/day), while others employed weekly, monthly, or single high-dose administrations (e.g.- 50,000 IU/week, 100,000 IU/month, or one-time mega-doses of 120,000\u0026ndash;150,000 IU). Among these, higher-dose regimens (\u0026gt;\u0026thinsp;20,000 IU per week equivalent) consistently produced marked increases in circulating 25(OH)D, particularly among obese subjects. No adverse effects attributable to supplementation were reported.\u003c/p\u003e\u003cp\u003eAccording to the selected studies, supplementation increased serum 25-hydroxyvitamin D [25(OH)D] concentrations in overweight and obese children, although the magnitude varied. The meta-analysis of seven randomized placebo-controlled trials demonstrated that there was a pooled mean difference of 1.6 ng/mL (95% CI: 0.60\u0026ndash;2.60) in favor of supplementation (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e). High-dose regimens (\u0026gt;\u0026thinsp;20,000 IU/week) generally produced greater increases, with some trials reporting sufficiency rates above 80% (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). However, in several studies, fewer than half of obese participants achieved sufficiency despite supplementation (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eMost studies found no significant effect on BMI, BMI z-score, waist circumference, or body fat percentage. Exceptions included trials by Chung et al. (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e), who reported reductions in BMI z-score and body fat markers after 8 weeks of 2000 IU/day, and De Cosmi et al. (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e), who observed a significant reduction in fat mass percentage after 6 months of 1200 IU/day with or without DHA.\u003c/p\u003e\u003cp\u003eBeyond vitamin D and calcium status, cardiometabolic outcomes were frequently assessed. Thirteen studies evaluated cardiovascular or metabolic outcomes, including lipid profile, insulin resistance, glucose regulation, and blood pressure. Improvements in insulin sensitivity or reductions in fasting insulin/HOMA-IR were reported in several trials (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e), although findings were not consistent across all studies.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study investigated the effects of vitamin D supplementation on children and adolescents with overweight or obesity. According to the selected studies, supplementation increased serum 25-hydroxyvitamin D [25(OH)D] concentrations in overweight and obese children, although the magnitude varied. The meta-analysis of seven randomized placebo-controlled trials demonstrated a pooled mean difference of 1.6 ng/mL (95% CI: 0.60\u0026ndash;2.60) in favor of supplementation (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan additionalcitationids=\"CR29\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e). High-dose regimens (\u0026gt;\u0026thinsp;20,000 IU/week) generally produced greater increases, with some trials reporting sufficiency rates above 80% (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAlthough a statistically significant mean difference was observed, only a small proportion of obese children in some studies achieved vitamin D sufficiency. In one trial (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e), only half of the obese children achieved normalization of vitamin D status compared to 89% of their non-obese counterparts. Similarly, another study (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e) reported that following 8 weeks of supplementation with 2000 IU/day, 48% of overweight children reached sufficiency, whereas the proportion was 62% among normal-weight participants. Conversely, a different investigation (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) demonstrated that over 90% of obese children receiving 2000 IU/day attained serum vitamin D concentrations above 20 ng/ml. Consistent with this, a study on vitamin D\u0026ndash;deficient subjects showed that 83% of participants treated with 5000 IU/day and 30% of those given 1000 IU/day for three months achieved 25(OH)D levels\u0026thinsp;\u0026ge;\u0026thinsp;20 ng/ml (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Furthermore, both 50,000 IU/week and 5000 IU/day regimens proved effective in increasing 25(OH)D concentrations above 20 ng/ml in more than 80% of participants, with 72% and 56% in each group, respectively, surpassing 30 ng/ml (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eSeveral mechanisms may account for the challenges in raising vitamin D levels in obese populations. One explanation is the sequestration of vitamin D in adipose tissue, which reduces its bioavailability (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e). Additionally, low dietary intake of vitamin D\u0026ndash;rich foods and limited sunlight exposure, both common in this group, may further contribute to persistently low circulating 25(OH)D levels (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eSuboptimal vitamin D status can adversely affect multiple health outcomes, including cardiovascular health (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). Early studies hypothesized that improving vitamin D concentrations could mitigate cardiovascular risk. Supporting this, one trial (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) found that 6 months of supplementation with 4000 IU/day significantly improved HOMA-IR and QUICKI, both surrogate indicators of insulin resistance and sensitivity. Similarly, another study (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e) reported reductions in serum insulin, triglycerides, HOMA-IR, and C-Met following supplementation. Improvements in blood pressure, fasting glucose, and insulin sensitivity were also observed in another investigation (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). In contrast, two studies reported no significant changes in cardiovascular risk parameters, including inflammatory markers (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eSix studies reported a beneficial effect of vitamin D supplementation on insulin regulation (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). These findings are consistent with evidence from adult populations, which indicate an inverse association between serum 25(OH)D concentrations and insulin resistance (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e). A possible explanation is that vitamin D may influence inflammatory cytokine production, a key factor contributing to insulin resistance, while also playing a role in insulin secretion and activity (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eFurthermore, Brzeziński et al. (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e) reported no significant impact of vitamin D supplementation on weight reduction in children with insufficiency who were enrolled in a weight management program. In contrast, Chung et al. (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e) observed improvements in BMI, BMI z-score, and body fat indices following supplementation. Similarly, De Cosmi et al. (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e) found that fat mass percentage decreased significantly in supplemented participants, while BMI improved across both intervention and control groups, although all participants remained obese at study completion.\u003c/p\u003e\u003cp\u003eThe principal limitation of this review lies in the small number of included studies and the heterogeneity among them. These constraints limit the ability to examine in greater depth the influence of additional variables such as participant age, degree of overweight/obesity, and seasonal variations, which may affect the outcomes of vitamin D supplementation.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis scoping review provides the most recent evidence regarding the impact of vitamin D supplementation in overweight and obese children and adolescents. While supplementation leads to a significant rise in serum 25(OH)D concentrations, the clinical significance of this improvement appears limited. Evidence concerning its influence on metabolic and cardiovascular outcomes remains inconsistent and inconclusive.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eNg M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Mullany EC, Biryukov S, Abbafati C, Abera SF, Abraham JP (2014) Global, regional, and national prevalence of overweight and obesity in children and adults during 1980\u0026ndash;2013: a systematic analysis for the Global Burden of Disease Study 2013. lancet 384(9945):766\u0026ndash;781\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang Y, Lim H (2012) The global childhood obesity epidemic and the association between socio-economic status and childhood obesity. Int Rev psychiatry 24(3):176\u0026ndash;188\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAbrams P, Katz LE (2011) Metabolic effects of obesity causing disease in childhood. 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Nutrients 14:1397. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/nu14071397\u003c/span\u003e\u003cspan address=\"10.3390/nu14071397\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAlemzadeh R, Kichler J, Babar G, Calhoun M (2008) Hypovitaminosis D in obese children and adolescents: relationship with adiposity, insulin sensitivity, ethnicity, and season. Metabolism 57:183\u0026ndash;191. https://doi.org/10.1016/j. metabol.2007.08.023\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDrincic AT, Armas LA, Van Diest EE, Heaney RP (2012) Volumetric dilution, rather than sequestration best explains the low vitamin D status of obesity. Obesity 7:1444\u0026ndash;1448. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/oby.2011.404\u003c/span\u003e\u003cspan address=\"10.1038/oby.2011.404\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Faculty of Medicine, University of Colombo","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Vitamin D, childhood obesity, metabolic risk, supplementation, adiposity","lastPublishedDoi":"10.21203/rs.3.rs-7540633/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7540633/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eVitamin D deficiency and childhood obesity are increasingly recognized as overlapping global health challenges, both of which have substantial implications for long-term wellbeing. Due to the lipophilic nature of vitamin D, excessive adiposity reduces its bioavailability, thereby predisposing overweight and obese children to inadequate circulating 25-hydroxyvitamin D [25(OH)D] concentrations. This deficiency has been associated with impaired bone mineralization, insulin resistance, systemic inflammation, and an elevated risk of type 2 diabetes mellitus, cardiovascular disease, and osteoporosis later in life. Several supplementation strategies for improving vitamin D status in pediatric populations with overweight or obesity have been proposed; however, their efficacy remains inconclusive. Evidence from randomized clinical trials and observational studies indicates that vitamin D supplementation leads to modest increases in serum 25(OH)D levels, with higher-dose regimens producing greater improvements. Findings on the impact of supplementation on metabolic and cardiovascular outcomes are inconsistent, with no clear consensus on the optimal dosing or duration needed to achieve clinically meaningful benefits. Beyond supplementation, lifestyle interventions involving weight reduction through dietary modification and increased physical activity may also contribute to improved vitamin D status, although the interplay between adiposity, vitamin D metabolism, and health outcomes is complex and not yet fully understood. The widespread expression of vitamin D receptors and 1α-hydroxylase in multiple tissues, including adipose tissue, suggests a potential regulatory role in adipogenesis and adipocyte metabolism, which may partly explain the extensive health effects linked to deficiency. This scoping review synthesizes the available evidence on vitamin D, childhood obesity, and metabolic risk, highlighting key research gaps. Further well-designed longitudinal and interventional studies are urgently required to clarify causality, define optimal vitamin D status, and establish effective interventions for improving health outcomes in this vulnerable population.\u003c/p\u003e","manuscriptTitle":"Vitamin D, Childhood Obesity, and Metabolic Risk – A Scoping Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-08 03:42:25","doi":"10.21203/rs.3.rs-7540633/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ed0b839c-39ed-4b90-8e86-2ad90f7abac5","owner":[],"postedDate":"September 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":54230246,"name":"Physiology"}],"tags":[],"updatedAt":"2025-09-08T03:42:25+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-08 03:42:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7540633","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7540633","identity":"rs-7540633","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}