Advertisement

The Weight of Vitamin D on Obesity Outcomes: What Do We Know?

  • Shara R. Bialo
    Affiliations
    Division of Pediatric Endocrinology, Rhode Island Hospital/Hasbro Children's Hospital, Providence, Rhode Island
    Department of Pediatrics, Warren Alpert Medical School of Brown University, Providence, Rhode Island
    Search for articles by this author
  • Catherine M. Gordon
    Affiliations
    Divisions of Adolescent Medicine and Pediatric Endocrinology, Rhode Island Hospital/Hasbro Children's Hospital, Providence, Rhode Island
    Department of Pediatrics, Warren Alpert Medical School of Brown University, Providence, Rhode Island
    Search for articles by this author
      See Related Article p. 19
      Vitamin D remains an intensely debated and investigated topic; the roots of which are firmly planted in skeletal health and mineral metabolism. The role—or the question of the role—of vitamin D, however, is branching out widely to encompass many nonskeletal disorders. Observational studies provide support for an association between an individual's vitamin D status and immune function, cancer, pain, asthma, diabetes, and cardiovascular disease, leading many to suggest oral vitamin D supplementation for preventive and/or therapeutic benefit for these disorders [
      • Rosen C.J.
      • Adams J.S.
      • Bikle D.D.
      • et al.
      The nonskeletal effects of vitamin D: An Endocrine Society scientific statement.
      ,
      • Davis C.D.
      • Dwyer J.T.
      The “sunshine vitamin”: Benefits beyond bone?.
      ,
      • Codoner-Franch P.
      • Tavarez-Alonso S.
      • Simo-Jorda R.
      • et al.
      Vitamin D status is linked to biomarkers of oxidative stress, inflammation, and endothelial activation in obese children.
      ]. Nevertheless, the only firm conclusion drawn at this time is that there is a paucity of data from randomized, double-blind studies to define the relationship between vitamin D and nonskeletal ailments.
      Shah et al. [
      • Shah S.
      • Wilson D.M.
      • Bachrach L.K.
      Large doses of vitamin D fail to increase 25-OH vitamin D levels or to alter cardiovascular risk factors in obese adolescents: A pilot study.
      ] carried out a trial relevant to this important area of research in this issue of the Journal of Adolescent Health. Previous investigation has proposed insufficient serum 25-hydroxyvitamin D (25OHD) to be a contributor to vascular complications in obese children, with evidence provided by Codoñer-Franch et al. [
      • Codoner-Franch P.
      • Tavarez-Alonso S.
      • Simo-Jorda R.
      • et al.
      Vitamin D status is linked to biomarkers of oxidative stress, inflammation, and endothelial activation in obese children.
      ] including increased markers of oxidative stress, inflammation, and endothelial activation in that population. Shah et al. sought to elucidate whether insufficient serum 25OHD is the cause of or solely associated with inflammatory and cardiovascular markers in obese adolescents. Study participants were supplemented with large doses of ergocalciferol (150,000 international units [IU] at baseline and 12 weeks) in a clinical setting and outcome measurements including body mass index, serum 25OHD, inflammatory cytokines, adiponectin, C-reative protein, lipids, and hemoglobin A1c were measured at baseline, 12 and 24 weeks. Unfortunately, vitamin D supplementation did not significantly increase serum 25OHD concentrations, leaving the authors unable to answer the question as to whether there is a causal relationship between vitamin D insufficiency and metabolic risk factors among obese teenagers.
      Investigation into the etiology of medical complications among overweight and obese teenagers merits urgent attention given the current obesity epidemic. In the United States, the prevalence of obesity among children aged 2–18 years is almost 17% and has shown no sign of improvement over the previous decade [
      • Ogden C.L.
      • Carroll M.D.
      • Kit B.K.
      • Flegal K.M.
      Prevalence of childhood and adult obesity in the United States, 2011-2012.
      ]. These historic figures will haunt our medical establishment in the future as there is a large body of evidence demonstrating that overweight and obesity in childhood and adolescence increase the risk of cardiovascular and metabolic morbidity—including diabetes, hypertension, ischemic heart disease, and stroke—and premature mortality in adulthood [
      • Reilly J.J.
      • Kelly J.
      Long-term impact of overweight and obesity in childhood and adolescence on morbidity and premature mortality in adulthood: Systematic review.
      ,
      • von Bonsdorff M.B.
      • Tormakangas T.
      • Rantanen T.
      • et al.
      Early life body mass trajectories and mortality in older age: Findings from the Helsinki Birth Cohort Study.
      ].
      But, where does vitamin D fit into this grim picture? Vitamin D receptors are present in all cells implicated in atherosclerosis, and it is believed that vitamin D plays an immunomodulatory role through its various effects on inflammatory cells [
      • Kassi E.
      • Adamopoulos C.
      • Basdra E.K.
      • Papavassiliou A.G.
      Role of vitamin D in atherosclerosis.
      ]. It is widely accepted that obesity coexists with a low-grade inflammatory state, and insufficient serum vitamin D concentrations have long been associated with obesity. Specifically, among American youth aged 6–18 years, the prevalence of vitamin D deficiency is 29% in overweight and 34% in obese individuals and demonstrates a linear relationship with increasing body mass index [
      • Turer C.B.
      • Lin H.
      • Flores G.
      Prevalence of vitamin D deficiency among overweight and obese US children.
      ]. Several theories have been proposed to explain why obese individuals demonstrate lower circulating 25OHD concentrations than their healthy-weight counterparts, the most plausible being sequestration of fat-soluble vitamin D within excess adipose tissue [
      • Drincic A.T.
      • Armas L.A.
      • Van Diest E.E.
      • Heaney R.P.
      Volumetric dilution, rather than sequestration best explains the low vitamin D status of obesity.
      ]. Furthermore, overweight and obese youth are less likely to maintain nutrition-rich diets and are more likely to exhibit a sedentary lifestyle; thus, limiting sun exposure and decreasing cutaneous synthesis of vitamin D [
      • Wortsman J.
      • Matsuoka L.Y.
      • Chen T.C.
      • et al.
      Decreased bioavailability of vitamin D in obesity.
      ].
      Whether the inflammatory state that wreaks havoc on cardiovascular health is due to the direct effect of insufficient vitamin D or simply obesity with related vitamin D insufficiency remains to be determined. This question is an important one as vitamin D supplementation is a cost-effective therapy that could lessen the health and economic burden imposed by the long-term sequela of obesity and cardiovascular disease. The most effective method to achieve vitamin D repletion in obese patients, however, is another unanswered question. Shah et al. showed that they were unable to raise 25OHD levels significantly in obese study subjects using large, intermittent boluses of ergocalciferol despite an appropriately powered sample and study-supervised dosing; thus, eliminating the ubiquitous concern for nonadherence among adolescent research subjects. Such difficulty in the treatment of vitamin D deficiency has been documented, with overweight and obese youth often requiring two to three times higher doses of daily cholecalciferol supplementation to normalize deficient vitamin D levels compared with healthy weight control groups [
      • Holick M.F.
      • Binkley N.C.
      • Bischoff-Ferrari H.A.
      • et al.
      Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline.
      ,
      • Harel Z.
      • Flanagan P.
      • Forcier M.
      • Harel D.
      Low vitamin D status among obese adolescents: Prevalence and response to treatment.
      ]. This investigation also raises the question regarding the effectiveness of intermittent boluses versus daily supplementation of oral vitamin D, as well as whether there is a difference in the time to repletion between vitamin D2 and vitamin D3 formulations. Genetic differences affecting enzyme activity, as well as race and ethnic variability in 25OHD dose response to oral vitamin D, are also worth further study [
      • Wang T.J.
      • Zhang F.
      • Richards J.B.
      • et al.
      Common genetic determinants of vitamin D insufficiency: A genome-wide association study.
      ,
      • Drincic A.
      • Fuller E.
      • Heaney R.P.
      • Armas L.A.
      25-Hydroxyvitamin D response to graded vitamin D(3) supplementation among obese adults.
      ].
      With so many unknown parameters, it is clear that the best option for optimizing the well-being of adolescent patients is the prevention of obesity and vitamin D deficiency. Given that parental obesity more than doubles the risk of adult obesity among both obese and nonobese children [
      • Whitaker R.C.
      • Wright J.A.
      • Pepe M.S.
      • et al.
      Predicting obesity in young adulthood from childhood and parental obesity.
      ], pediatric and adolescent health providers must expand their attention to the family unit. There is universal support for a multidisciplinary approach to prevention and management of childhood obesity, including provider-initiated office, home, and school-based therapies [
      • Kelishadi R.
      • Azizi-Soleiman F.
      Controlling childhood obesity: A systematic review on strategies and challenges.
      ,
      • Ebbeling C.B.
      • Antonelli R.C.
      Primary care interventions for pediatric obesity: Need for an integrated approach.
      ,
      • Resnicow K.
      • McMaster F.
      • Bocian A.
      • et al.
      Motivational interviewing and dietary counseling for obesity in primary care: An RCT.
      ]. Vitamin D supplementation to prevent vitamin D deficiency (i.e., maintain serum 25OHD to >20 ng/mL) can be provided as an adjunct, with 1,000 IU per day for nonobese youth and up to 2,000–6,000 IU per day for obese youth [
      • Holick M.F.
      • Binkley N.C.
      • Bischoff-Ferrari H.A.
      • et al.
      Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline.
      ]. At this time, there are no safety data to prevent aiming for a 25OHD threshold of 30 ng/mL as the optimal target, with theoretical benefits to adolescents with obesity and other patient groups as endorsed by the Society for Adolescent Health and Medicine [
      Society for Adolescent Health and Medicine
      Recommended vitamin D intake and management of low vitamin D status in adolescents: A position statement of the society for adolescent health and medicine.
      ] and the Endocrine Society [
      • Holick M.F.
      • Binkley N.C.
      • Bischoff-Ferrari H.A.
      • et al.
      Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline.
      ], among other professional groups. However, this topic is presently one of hot debate. The intertwining branches of obesity and vitamin D insufficiency should continue to be fully examined, whereas bearing in mind that the best approach is to “nip the problem in the bud” by preventing the development of adolescent obesity altogether.

      References

        • Rosen C.J.
        • Adams J.S.
        • Bikle D.D.
        • et al.
        The nonskeletal effects of vitamin D: An Endocrine Society scientific statement.
        Endocr Rev. 2012; 33: 456-492
        • Davis C.D.
        • Dwyer J.T.
        The “sunshine vitamin”: Benefits beyond bone?.
        J Natl Cancer Inst. 2007; 99: 1563-1565
        • Codoner-Franch P.
        • Tavarez-Alonso S.
        • Simo-Jorda R.
        • et al.
        Vitamin D status is linked to biomarkers of oxidative stress, inflammation, and endothelial activation in obese children.
        J Pediatr. 2012; 161: 848-854
        • Shah S.
        • Wilson D.M.
        • Bachrach L.K.
        Large doses of vitamin D fail to increase 25-OH vitamin D levels or to alter cardiovascular risk factors in obese adolescents: A pilot study.
        J Adolesc Health. 2015; 57: 19-23
        • Ogden C.L.
        • Carroll M.D.
        • Kit B.K.
        • Flegal K.M.
        Prevalence of childhood and adult obesity in the United States, 2011-2012.
        JAMA. 2014; 311: 806-814
        • Reilly J.J.
        • Kelly J.
        Long-term impact of overweight and obesity in childhood and adolescence on morbidity and premature mortality in adulthood: Systematic review.
        Int J Obes. 2011; 35: 891-898
        • von Bonsdorff M.B.
        • Tormakangas T.
        • Rantanen T.
        • et al.
        Early life body mass trajectories and mortality in older age: Findings from the Helsinki Birth Cohort Study.
        Ann Med. 2015; 47: 34-39
        • Kassi E.
        • Adamopoulos C.
        • Basdra E.K.
        • Papavassiliou A.G.
        Role of vitamin D in atherosclerosis.
        Circulation. 2013; 128: 2517-2531
        • Turer C.B.
        • Lin H.
        • Flores G.
        Prevalence of vitamin D deficiency among overweight and obese US children.
        Pediatrics. 2013; 131: e152-e161
        • Drincic A.T.
        • Armas L.A.
        • Van Diest E.E.
        • Heaney R.P.
        Volumetric dilution, rather than sequestration best explains the low vitamin D status of obesity.
        Obesity. 2012; 20: 1444-1448
        • Wortsman J.
        • Matsuoka L.Y.
        • Chen T.C.
        • et al.
        Decreased bioavailability of vitamin D in obesity.
        Am J Clin Nutr. 2000; 72: 690-693
        • Holick M.F.
        • Binkley N.C.
        • Bischoff-Ferrari H.A.
        • et al.
        Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline.
        J Clin Endocrinol Metab. 2011; 96: 1911-1930
        • Harel Z.
        • Flanagan P.
        • Forcier M.
        • Harel D.
        Low vitamin D status among obese adolescents: Prevalence and response to treatment.
        J Adolesc Health. 2011; 48: 448-452
        • Wang T.J.
        • Zhang F.
        • Richards J.B.
        • et al.
        Common genetic determinants of vitamin D insufficiency: A genome-wide association study.
        Lancet. 2010; 376: 180-188
        • Drincic A.
        • Fuller E.
        • Heaney R.P.
        • Armas L.A.
        25-Hydroxyvitamin D response to graded vitamin D(3) supplementation among obese adults.
        J Clin Endocrinol Metab. 2013; 98: 4845-4851
        • Whitaker R.C.
        • Wright J.A.
        • Pepe M.S.
        • et al.
        Predicting obesity in young adulthood from childhood and parental obesity.
        N Engl J Med. 1997; 337: 869-873
        • Kelishadi R.
        • Azizi-Soleiman F.
        Controlling childhood obesity: A systematic review on strategies and challenges.
        J Res Med Sci. 2014; 19: 993-1008
        • Ebbeling C.B.
        • Antonelli R.C.
        Primary care interventions for pediatric obesity: Need for an integrated approach.
        Pediatrics. 2015; 135: 757-758
        • Resnicow K.
        • McMaster F.
        • Bocian A.
        • et al.
        Motivational interviewing and dietary counseling for obesity in primary care: An RCT.
        Pediatrics. 2015; 135: 649-657
        • Society for Adolescent Health and Medicine
        Recommended vitamin D intake and management of low vitamin D status in adolescents: A position statement of the society for adolescent health and medicine.
        J Adolesc Health. 2013; 52: 801-803

      Linked Article