Evaluation of serum levels of 25-hydroxyvitamin D in overweight adolescents

Review Article

Vol. 16 nº 2 - Apr/Jun - 2019
Pages:102-
109

Evaluation of serum levels of 25-hydroxyvitamin D in overweight adolescents

Authors: ^¹, ^², ^³, ^⁴, ^⁵, ^⁶

¹PhD in Medicine and Surgery from the Universitat Autònoma de Barcelona (UAB – Spain). Professor at the Center for Health Sciences of the Regional University Foundation of Blumenau (FURB). Blumenau, SC, Brazil

²Master’s student in Public Health from the Regional University Foundation of Blumenau (FURB). Blumenau, SC, Brazil

³Resident in Pediatrics at Hospital Santo Antônio. Blumenau, SC, Brazil

⁴Undergraduate in Medicine from the School of Medicine of the Regional University Foundation of Blumenau (FURB). Blumenau, SC, Brazil

⁵PhD in Sciences from the School of Public Health of the University of Sao Paulo (USP). Professor at the Center for Health Sciences of the Regional University Foundation of Blumenau (FURB). Blumenau, SC, Brazil

⁶PhD in Neuroscience from the Federal University of Santa Catarina (UFSC). Professor at the Center for Health Sciences of the Regional University Foundation of Blumenau (FURB). Blumenau, SC, Brazil

Correspondence:

Deisi Maria Vargas
FURB – Campus 3, Room A-302
Sao Paulo Street, No. 2171. Itoupava Seca
Blumenau, SC, Brazil. Zip Code: 89030-001
( deisifurb@gmail.com )

Submitted on 16/09/2018
Approved on 02/09/2019

Keywords: Vitamin D; Adolescent; Obesity; Overweight.

Abstract

OBJECTIVE: To evaluate serum levels of 25-hydroxyvitamin D [25(OH)D] in overweight adolescents.
METHODS: Observational study with 86 overweight adolescents followed during secondary care service between August 2014 and August 2016. For the diagnosis of overweight, the criteria of the World Health Organization were considered. Serum levels of 25(OH)D were categorized as: sufficiency (≥ 30 ng/mL), insufficiency (between 20 and 29 ng/mL) and deficiency (< 20 ng/mL). The categories of vitamin D deficiency and insufficiency were grouped into the hypovitaminosis D category in some analyses.
RESULTS: Only 38.4% of adolescents had vitamin D levels above the recommended level, 23.2% had insufficient levels and 38.4% had deficient levels. There was a higher frequency of hypovitaminosis D (71.4% versus 52.3%; p = 0.03) and lower serum levels of 25(OH)D (23.9 ± 8.7 ng/mL versus 28.1 ± 10.6; p < 0.05) in obese adolescents compared to overweight adolescents. There was no difference in 25(OH)D levels between sex and age categories.
CONCLUSIONS: Hypovitaminosis D occurred in 61% of adolescents and was positively associated with obesity. An inverse relationship was observed between serum 25(OH)D levels and the degree of overweight.

INTRODUCTION Vitamin D deficiency is reaching epidemic proportions worldwide and in all age groups. Current evidence suggests a potential link between obesity and vitamin D deficiency in global populations ¹ . Vitamin D is a prohormone with two main forms: ergocalciferol and cholecalciferol. Both are metabolized by the liver to produce 25-hydroxyvitamin D, which is subsequently transformed by the kidney into 1,25-dihydroxy-vitamin D, its active form. The bioactive form of vitamin D has numerous functions in the body and is involved in the control of gene expression in various cell types and tissues, regulating cell proliferation, differentiation, and survival. Thus, the biological effects of vitamin D go beyond the regulation of mineral homeostasis and bone metabolism ¹ . In this context, interest in studying the association between serum vitamin D levels and metabolic diseases has gained prominence, especially those related to obesity ² . Hypovitaminosis D is common in several countries, regardless of nutritional status. In the pediatric age group, its magnitude appears to be greater in overweight children and adolescents and in those with chronic diseases ^3,4 . OBJECTIVES The scarcity of national articles addressing hypovitaminosis D in overweight adolescents ^5,6 motivated the performance of this study. Its objective is to evaluate vitamin D levels in overweight adolescents and their variations according to sex, age group and degree of excess weight. METHODS This observational study was conducted with 86 overweight Caucasian adolescents followed by the secondary health care service linked to the SUS, between August 2014 and August 2016. The following adolescents with the following characteristics were sequentially included in the study: overweight, normal height for age (Z-score> -2), neuropsychomotor development appropriate for age and without vitamin D supplementation. The study variables were sex, age, weight, height, BMI, degree of overweight and serum 25-hydroxy-vitamin D [(25OH)D]. The criteria recommended by the World Health Organization (WHO) were used to diagnose overweight, which considers overweight a BMI Z-score between +1 and < +2, obesity a Z-score between ≥ +2 and < +3 and severe obesity, ≥ +3 ⁷ . The following cutoff points were used to categorize serum 25(OH)D levels: sufficiency (values > 30 ng/mL); insufficiency (values between 20 and 29 ng/mL); and deficiency (values < 20 ng/mL) ⁸. Blood collection for biochemical analyses occurred between spring and summer. The classification of hypovitaminosis D comprised the categories of insufficiency and deficiency. The Kolmogorov-Smirnov test was applied in the statistical analysis to evaluate the distribution of numerical variables in relation to normality. BMI, 25(OH)D and age presented parametric distribution and were expressed as mean and standard deviation of the mean. To compare serum levels of vitamin D between categories of sex, age group and degree of overweight, the Student ‘s t-test was used . The chi-square test was used to study associations between the frequency of hypovitaminosis D and the degrees of overweight. The significance level adopted was p <0.05. The database was constructed in the EXCEL ^r program and the statistical analyses were performed in the StatPlus ^r program . The study was approved by the Human Ethics Committee of the Blumenau Hospital Foundation (opinion 2,090,278). RESULTS Between August 2014 and August 2016, 102 overweight adolescents were treated at the secondary health care service. Of these, 86 (47 males) met the inclusion criteria. The description of the numerical and categorical data is shown in Table 1. The mean age was 13.2 ± 2.1 years, with the majority of the adolescents studied being in the 10-14 age group and 51.2% being overweight. Six of the 42 adolescents in the obesity category were severely obese.

The 25(OH)D value ranged from 11.5 to 50.1 ng/mL, with a mean of 26.1 ± 9.7 ng/mL. Most adolescents (61.6%) had serum 25(OH)D levels below 30 ng/mL, and 38.4% were classified as deficient. There was no significant difference in 25(OH)D levels between males and females (25.6 ±9.9 versus 26.6 ±9.5 respectively; p = 0.820) or between age groups (10-14 year group 25.9 ±9.8 versus 15-19 year group 26.6 ±9.8; p = 0.770). However, a difference in mean 25(OH)D values was observed between the overweight categories, with lower 25(OH)D in obese adolescents (Figure 1).

Figure 1. Mean values and standard deviation of Vitamin D according to the degree of excess weight (* Student’s t-test ).

The distribution of vitamin D status according to the degree of excess weight is shown in Figure 2. Hypovitaminosis D was more frequent in obese adolescents (Figure 2 – Panel A). When analyzing vitamin D status considering the three categories (sufficiency, insufficiency and deficiency), no significant difference was observed. However, vitamin D deficiency affected almost 50% of obese adolescents and 30% of overweight adolescents (Figure 2 – Panel B).

Figure 2. Distribution of vitamin D status according to degree of excess weight (*chi-square test; number of participants identified in bars).

DISCUSSION The rates of occurrence of hypovitaminosis D in overweight adolescents described in the international and national literature vary widely ^4,5,9-14 . In the USA, the incidence of vitamin D deficiency is reported to be 29% ⁹ and 43% ^{10 and 79.8%}¹⁰ of hypovitaminosis D in obese adolescents. In Ethiopia ¹¹ , deficiency was found in 77.8% of overweight adolescents, while in Poland, the inclusion of only adolescents and the geographic region is common. Some of the risk factors for hypovitaminosis D described in the literature are: winter, little time for outdoor activities, dark skin, older age, more advanced pubertal stage, presence of obesity, low milk intake, low socioeconomic status and female gender ^13,15 . In this study, we found an association between obesity and hypovitaminosis D, but we did not find any association with female gender or older age group. Williams ¹⁰ and Vierucci ¹⁶ also did not observe any difference in vitamin D levels between the genders. However, a national study conducted in Joao Pessoa-PB showed a higher incidence of hypovitaminosis D in female adolescents ⁶ . Male adolescents tend to practice more outdoor activities with greater sun exposure and consequent greater synthesis of vitamin D. On the other hand, female adolescents have a higher body fat rate ¹⁷ and the frequency of sunscreen use by adolescents is generally higher in girls ¹⁶ . These are possible factors that would justify a lower 25(OH)D in females. We did not observe a difference in the occurrence of hypovitaminosis D between age groups. An American study demonstrated an inverse association between age group and hypovitaminosis D in obese adolescents, with occurrences of 64% and 42% in the age groups of 15 to 19 years and 10 to 14 years, respectively. Diet and lower sun exposure were considered possible factors related to this difference ¹⁰ . The Blumenau region has the third highest incidence of malignant melanoma in the world ¹⁸ , which constitutes a regional public health problem. The predisposing factors for the disease are: the majority of the Caucasian population composed of German and Italian descendants, and ultraviolet radiation considered very high by the WHO. Therefore, preventive actions are usually carried out frequently ¹⁸. This context could explain the lack of difference in 25(OH)D values according to sex and age group, since the habit of protecting oneself against skin cancer is present in most of the local population. Obese adolescents appear to be more predisposed to have lower 25(OH)D values. In this study, both hypovitaminosis D and vitamin D deficiency were more frequent in obese adolescents. This inverse association between the degree of excess weight and serum 25(OH)D values has been evidenced in other countries, although to different extents ^4,12 . In addition to behavioral factors, such as low precursor intake and reduced sun exposure ¹⁹ , hypovitaminosis D in overweight individuals may be related to intrinsic factors. Factors that may be involved in the pathophysiology of hypovitaminosis D related to excess weight are: the presence of receptors in adipose tissue with sequestration of vitamin D and reduction of its bioavailability to target tissues ²⁰ , as well as increased serum levels of leptin with inhibition of renal synthesis of the active form of vitamin D ²¹ . Vitamin D has numerous functions in the body. The most traditionally known is its action on the skeleton. It is an essential micronutrient for bone health, playing a relevant role in the acquisition and maintenance of bone mass throughout life cycles, and is one of the protective factors against osteoporosis ²² . However, due to its extra-skeletal effects, hypovitaminosis D appears to be related to other types of chronic diseases, such as diabetes, dyslipidemia and asthma ¹⁰ . Thus, hypovitaminosis D could have a synergistic effect on the genesis of comorbidities associated with excess weight, such as arterial hypertension, dyslipidemia, and diabetes mellitus , resulting in higher morbidity and mortality in this population ^23,24 . The global consensus for the pediatric age group defines serum 25(OH)D levels above 20 ng/mL as vitamin D sufficiency. This cutoff level was defined considering skeletal actions. However, there are recommendations for maintaining a serum vitamin D level ≥ 30 ng/mL for the occurrence of extraskeletal actions ⁸ . In terms of application in clinical practice, it is suggested to include the assessment of vitamin D status in overweight adolescents, especially those with obesity. Maintaining serum vitamin D above 30 ng/mL could be considered a treatment goal in this population group. Limiting factors of this study were the low number of adolescents with severe obesity, making it impossible to analyze vitamin D levels in this category in relation to other categories of excess weight; and the lack of information regarding conditions that may interfere with vitamin D synthesis, such as the use of sunscreen and the practice of outdoor activities. CONCLUSIONS Hypovitaminosis D affected a significant portion of the adolescents studied, with more than half of the adolescents with obesity having vitamin D levels below those recommended for extra-skeletal actions. There was no association between vitamin D levels and gender, or with age group. An association was observed between serum 25(OH)D and the degree of excess weight, with lower values in the group of adolescents with obesity.

References

1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266-81. 2. Cunha KA, Magalhaes EIS, Loureiro LMR, Sant’Ana LFR, Ribeiro AQ, Novaes JF. Calcium intake, serum vitamin D levels and childhood obesity: is there an association? Rev Paul Pediatr. 2015;33(2):222-9. 3. Lee JY, So TY, Thackray J. A Review on Vitamin D Deficiency Treatment in Pediatric Patients. J Pediatr Pharmacol Ther. 2013;18(4):277-91. 4. Turer CB, Lin H, Flores G. Prevalence of Vitamin D Deficiency Among Overweight and Obese US Children. Pediatrics. 2013;131;e152. 5. Oliveira RM, Novaes JF, Azeredo LM, Cândido AP, Leite IC. Association of vitamin D insufficiency with adiposity and metabolic disorders in Brazilian adolescents. Public Health Nutr. 2014;17(4):787-94. 6. Araújo EPS, Queiroz DJM, Neves JPR, Lacerda LM, Gonçalves MCR, Carvalho AT. Prevalence of hypovitaminosis D and association factors in adolescent students of a capital of northeastern Brazil. Nutr Hosp. 2017;34(6):1416-23. 7. BRAZIL. Protocols of the Food and Nutrition Surveillance System – SISVAN in health care. Secretariat of Primary Care. 2008; Brasília. Ministry of Health: 61. (WHO) 8. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jul;96(7):1911-30 9. Lenders CM, Feldman HA, von Scheven E, Merewood A, Sweeney C, Wilson DM et al. Relationship of body fat indices to vitamin D status and deficiency among obese adolescents. Am J Clin Nutr. 2009;90:459-67. 10. Williams R, Novick M, Lehman E. Prevalence of hypovitaminosis D and its association with comorbidities of childhood obesity. Perm J. 2014;18(4):32-9. 11. Wakayo T, Whiting SJ, Belachew T. Vitamin D Deficiency is Associated with Overweight and/or Obesity among School children in Central Ethiopia: A Cross-Sectional Study. Nutrients. 2016;8(4):190. doi: 10.3390/nu8040190. 12. Durá-Travé T, Gallinas-Victoriano F, Chueca-Guindulain MJ, Berrade-Zubiri S. Prevalence of hypovitaminosis D and associated factors in obese Spanish children. Nutrition & Diabetes. 2017;7,e248. doi:10.1038/nutd.2016.50. 13. Harel Z, Flanagan P, Forcier M, Harel D. Low vitamin D status among obese adolescents: prevalence and response to treatment. J Adolescent Health. 2011;48:448-52. 14. Wojcik M, Janus D, Kalicka-Kasperczyk A, Sztefko K, Starzyk JB. The potential impact of the hypovitaminosis D on metabolic complications in obese adolescents – preliminary results. Ann Agric Environ Med. 2017;24(4):636-9. 15. Tolppanen AM, Fraser A, Fraser WD, Lawlor DA. Risk factors for variation in 25-hydroxyvitamin D3 and D2 concentrations and vitamin D deficiency in children. J Clin Endocrinol Metab. 2012; 97(4):1202-10. 16. Vierucci F, Del Pistoia M, Fanos M, Gori M, Carlone G, Erba P et al. Vitamin D status and predictors of hypovitaminosis D in Italian children and adolescents: a cross-sectional study. Eur J Pediatr. 2013;172:1607-17. 17. Alvarez MM, Vieira AC, Sichieri R, Veiga GV. Association between central body anthropometric measures and metabolic syndrome components in a probabilistic sample of adolescents from public schools. Arq Bras Endocrinol Metab. 2008;52:649-57. 18. Nasser N. Cutaneous melanoma – 30-year epidemiological study in a city in southern Brazil, from 1980- 2009. An Bras Dermatol. 2011;86(5):932-41. 19. Kull M, Kallikorm R, Lember M. Body mass index determines sunbathing habits: implications on vitamin D levels. Intern Med J. 2009;39(4):256-8. 20. Worstman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr. 2000;72(3):690-3. 21. Tsuji K, Maeda T, Kawane T, Maysunuma A, Horiuchi N. Leptin stimulates fibroblast growth factor 23 expression in bone and suppresses renal 1 alpha,25 dihydroxyvitamin D3 synthesis in leptin-deficient mice. J Bone Miner Res 2010;25:1711-23. 22. Winzenberg T, Jones G. Vitamin D and bone health in childhood and adolescence. Calcif Tissue Int. 2013;92(2):140-50. 23. Daraghmeh AH, Bertoia ML, Al-Qadi MO, Abdulbaki AM, Roberts MB, Eaton CB. Evidence for the vitamin D hypothesis: The NHANES III extended mortality follow-up. Atherosclerosis. 2016; 255:96-101. 24. Challa AS, Makariou SE, Siomou EC. The relationship of vitamin D status with metabolic syndrome in childhood and adolescence: an update. J Pediatr Endocrinol Metab. 2015;28(11-12):1235-45.