Associations between insulin resistance and three B-vitamins in European adolescents: the HELENA study

Iris Iglesia, Marcela González-Gross, Inge Huybrechts, Pilar De Miguel-Etayo, Denes Molnar, Yannis Manios, Kurt Widhalm, Frédéric Gottrand, Anthony Kafatos, Asensión Marcos, Alejandro De la O Puerta, Catherine Leclercq, Stefaan De Henauw, Peter Stehle, Mathilde Kersting, Theodora Mouratidou, Luis Alberto Moreno


Objective: To assess whether adolescents with high body mass index (BMI), or fat mass index (FMI), in combination with insulin resistance (assessed with the Homeostatic Model Assessment [HOMA] index), had also lower blood vitamin B6, folate and vitamin B12 concentrations.

Methods and materials: Six hundred and fifteen adolescents from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study, with data on B-vitamins (both intakes and status), and BMI, FMI, HOMA, were selected. Intakes were assessed by two non-consecutive 24-h recalls. B-vitamins biomarkers were measured by chromatography and immunoassay. Analysis of covariance was applied to elucidate the differences in B-vitamins between combinations of groups defined according to the median of the z-scores of markers of body composition and insulin sensitivity.

Results: When considering energy intakes and education of the mother in the model, in females, vitamin B6 intakes were higher in the high BMI/high HOMA group than in the high BMI-low HOMA group. Similarly, vitamin B6 intakes were higher in the high FMI/high HOMA group than in the low FMI/low HOMA group. Plasma vitamin B12 was significantly lower in males in the high FMI/high HOMA group than in the low FMI/low HOMA group, keeping also significant their trends throughout the groups, a fact that can be observed also for females (p < 0.05).

Conclusion: Adolescents with combined higher adiposity and higher HOMA insulin sensitivity showed lower vitamin B12 plasma concentrations. These differences do not seem to be explained by dietary vitamin B12 intake.



Palabras clave

Vitamin B6. Folic acid. Vitamin B12. Adolescent. Body mass index. Insulin resistance.

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Lien N, Henriksen HB, Nymoen LL, Wind M, Klepp KI. Availability of data assessing the prevalence and trends of overweight and obesity among European adolescents. Public Health Nutr2010 Oct;13(10A):1680-7.

Global Health Risk. Mortality and burden disease attributable to selected major risks. Geneva, Switzerland: World Health Organization; 2009.

Division of Nutrition, Physical Activity, and Obesity, National Center for Chronic Disease Prevention and Health Promotion. [updated June 19, 20155/07/2016]; Available from:

Pinhas-Hamiel O, Doron-Panush N, Reichman B, Nitzan-Kaluski D, Shalitin S, Geva-Lerner L. Obese children and adolescents: A risk group for low vitamin b12 concentration. Archives of Pediatrics & Adolescent Medicine2006;160(9):933-6.

Pinhas-Hamiel O, Newfield RS, Koren I, Agmon A, Lilos P, Phillip M. Greater prevalence of iron deficiency in overweight and obese children and adolescents. Int J Obes Relat Metab Disord2003 Mar;27(3):416-8.

Frankenfield DC, Rowe WA, Cooney RN, Smith JS, Becker D. Limits of body mass index to detect obesity and predict body composition. Nutrition2001 Jan;17(1):26-30.

Tresaco B, Bueno G, Moreno LA, Garagorri JM, Bueno M. Insulin resistance and impaired glucose tolerance in obese children and adolescents. J Physiol Biochem2003 Sep;59(3):217-23.

Iglesia I, Mouratidou T, Gonzalez-Gross M, Huybrechts I, Breidenassel C, Santabarbara J, et al. Foods contributing to vitamin B6, folate, and vitamin B12 intakes and biomarkers status in European adolescents: The HELENA study. Eur J Nutr2016 May 25.

Institute of Medicine (1998) Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline, a report of the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline and Subcommittee on Upper Reference Levels of Nutrients. Food and Nutrition Board, Washington DC: National Academy Press

Clemens TL. Vitamin B12 deficiency and bone health. N Engl J Med2014 Sep 4;371(10):963-4.

Kerr MA, Livingstone B, Bates CJ, Bradbury I, Scott JM, Ward M, et al. Folate, related B vitamins, and homocysteine in childhood and adolescence: potential implications for disease risk in later life. Pediatrics2009 Feb;123(2):627-35.

Hunt A, Harrington D, Robinson S. Vitamin B12 deficiency. BMJ2014;349:g5226.

Ho M, Halim JH, Gow ML, El-Haddad N, Marzulli T, Baur LA, et al. Vitamin B12 in obese adolescents with clinical features of insulin resistance. Nutrients2014 Dec;6(12):5611-8.

Laing SP, Swerdlow AJ, Slater SD, Burden AC, Morris A, Waugh NR, et al. Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes. Diabetologia2003 Jun;46(6):760-5.

Reinstatler L, Qi YP, Williamson RS, Garn JV, Oakley GP, Jr. Association of biochemical B12 deficiency with metformin therapy and vitamin B12 supplements: the National Health and Nutrition Examination Survey, 1999-2006. Diabetes Care2012 Feb;35(2):327-33.

Gonzalez-Gross M, Benser J, Breidenassel C, Albers U, Huybrechts I, Valtuena J, et al. Gender and age influence blood folate, vitamin B(12), vitamin B(6), and homocysteine levels in European adolescents: the Helena Study. Nutr Res2012 Nov;32(11):817-26.

Healthy Lifestyle in Europe by Nutrition in Adolescence. [cited 2016 1/07/2016]; Available from:

Moreno LA, Gonzalez-Gross M, Kersting M, Molnar D, de Henauw S, Beghin L, et al. Assessing, understanding and modifying nutritional status, eating habits and physical activity in European adolescents: the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) Study. Public Health Nutr2008 Mar;11(3):288-99.

Moreno LA, De Henauw S, Gonzalez-Gross M, Kersting M, Molnar D, Gottrand F, et al. Design and implementation of the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study. Int J Obes (Lond)2008 Nov;32 Suppl 5:S4-11.

Beghin L, Castera M, Manios Y, Gilbert CC, Kersting M, De Henauw S, et al. Quality assurance of ethical issues and regulatory aspects relating to good clinical practices in the HELENA Cross-Sectional Study. Int J Obes (Lond)2008 Nov;32 Suppl 5:S12-8.

Vereecken CA, Covents M, Sichert-Hellert W, Alvira JM, Le Donne C, De Henauw S, et al. Development and evaluation of a self-administered computerized 24-h dietary recall method for adolescents in Europe. Int J Obes (Lond)2008 Nov;32 Suppl 5:S26-34.

Harttig U, Haubrock J, Knuppel S, Boeing H. The MSM program: web-based statistics package for estimating usual dietary intake using the Multiple Source Method. Eur J Clin Nutr2011 Jul;65 Suppl 1:S87-91.

Gonzalez-Gross M, Breidenassel C, Gomez-Martinez S, Ferrari M, Beghin L, Spinneker A, et al. Sampling and processing of fresh blood samples within a European multicenter nutritional study: evaluation of biomarker stability during transport and storage. Int J Obes (Lond)2008 Nov;32 Suppl 5:S66-75.

Kimura M, Kanehira K, Yokoi K. Highly sensitive and simple liquid chromatographic determination in plasma of B6 vitamers, especially pyridoxal 5'-phosphate. J Chromatogr A1996 Jan 26;722(1-2):295-301.

Ulleland M, Eilertsen I, Quadros EV, Rothenberg SP, Fedosov SN, Sundrehagen E, et al. Direct assay for cobalamin bound to transcobalamin (holo-transcobalamin) in serum. Clin Chem2002 Mar;48(3):526-32.

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia1985 Jul;28(7):412-9.

Iglesia I, Mouratidou T, Gonzalez-Gross M, Novakovic R, Breidenassel C, Jimenez-Pavon D, et al. Socioeconomic factors are associated with folate and vitamin B12 intakes and related biomarkers concentrations in European adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence study. Nutr Res2014 Mar;34(3):199-209.

Nagy E, Vicente-Rodriguez G, Manios Y, Beghin L, Iliescu C, Censi L, et al. Harmonization process and reliability assessment of anthropometric measurements in a multicenter study in adolescents. Int J Obes (Lond)2008 Nov;32 Suppl 5:S58-65.

Slaughter MH, Lohman TG, Boileau RA, Horswill CA, Stillman RJ, Van Loan MD, et al. Skinfold equations for estimation of body fatness in children and youth. Hum Biol1988 Oct;60(5):709-23.

Gonzalez-Gross M, Benser J, Breidenassel C, Albers U, Huybrechts I, Valtuena J, et al. Gender and age influence blood folate, vitamin B12, vitamin B6, and homocysteine levels in European adolescents: the Helena Study. Nutr Res2012 Nov;32(11):817-26.

MacFarlane AJ, Greene-Finestone LS, Shi Y. Vitamin B-12 and homocysteine status in a folate-replete population: results from the Canadian Health Measures Survey. Am J Clin Nutr2011 Oct;94(4):1079-87.

Beghin L, Huybrechts I, Vicente-Rodriguez G, De Henauw S, Gottrand F, Gonzales-Gross M, et al. Main characteristics and participation rate of European adolescents included in the HELENA study. Arch Public Health2012;70(1):14.

Kimmons JE, Blanck HM, Tohill BC, Zhang J, Khan LK. Associations between body mass index and the prevalence of low micronutrient levels among US adults. MedGenMed2006;8(4):59.

Damms-Machado A, Weser G, Bischoff SC. Micronutrient deficiency in obese subjects undergoing low calorie diet. Nutr J2012;11:34.

Huybrechts I. Dietary under-reporting by overweight and obese adolescents: results from the HELENA Study. Public Health Nutrition2012;15(Special Issue 8A):1555-.

Dick KJ, Nelson CP, Tsaprouni L, Sandling JK, Aissi D, Wahl S, et al. DNA methylation and body-mass index: a genome-wide analysis. Lancet2014 Jun 7;383(9933):1990-8.

Yajnik CS. Transmission of obesity-adiposity and related disorders from the mother to the baby. Ann Nutr Metab2014;64 Suppl 1:8-17.

Setola E, Monti LD, Galluccio E, Palloshi A, Fragasso G, Paroni R, et al. Insulin resistance and endothelial function are improved after folate and vitamin B12 therapy in patients with metabolic syndrome: relationship between homocysteine levels and hyperinsulinemia. Eur J Endocrinol2004 Oct;151(4):483-9.

Mazokopakis EE, Starakis IK. Recommendations for diagnosis and management of metformin-induced vitamin B12 (Cbl) deficiency. Diabetes Res Clin Pract2012 Sep;97(3):359-67.

Henriquez-Sanchez P, Sanchez-Villegas A, Doreste-Alonso J, Ortiz-Andrellucchi A, Pfrimer K, Serra-Majem L. Dietary assessment methods for micronutrient intake: a systematic review on vitamins. Br J Nutr2009 Dec;102 Suppl 1:S10-37.


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