Abstract
Growing evidence support the role of vitamin D in brain function and behavior. This study investigated the relationship between 25-hydroxyvitamin D3 [25(OH)D3] levels, biochemical profile and symptoms of depression and anxiety in healthy individuals. Symptoms of depression were assessed by the Beck Depression Inventory (BDI) and anxiety was evaluated with the State-Trait Anxiety Inventory (STAI). Our sample included 36 individuals, mostly women 27(75%), 36.39 ± 9.72 years old, non-smokers 31(86.1%), body mass index of 26.57 ± 3.92 kg/m2, 27.95 ± 7.50% body fat. Participants were divided into those with 25(OH)D3 levels lower than 40 ng/mL (mean 28.16 ± 7.07) and equal or higher than 40 ng/mL (mean 53.19 ± 6.32). Those with lower 25(OH)D3 had higher levels of triacylglycerol, triacylglycerol/high density lipoprotein (HDL) ratio, high glucose and homeostatic model assessment of insulin resistance (HOMA-IR) index. No changes were observed in sociodemographic variables, body composition, inflammatory parameters and cortisol. Additionally, in the groups with low and high 25(OH)D3 levels, STAI state, STAI trait and BDI scores were not statistically different. Levels of 25(OH)D3 were inversely and independently associated with glucose and HOMA-IR, but not associated with triacylglycerol, depression and anxiety scores. Lower levels of 25(OH)D3 were associated with dysfunction in glucose metabolism but not with depression and anxiety in healthy individuals.
Similar content being viewed by others
Abbreviations
- [25(OH)D3]:
-
25-hydroxyvitamin D3
- [1,25(OH)2D3]:
-
1,25-dihydroxyvitamin D3
- BDI:
-
Beck Depression Inventory
- BMI:
-
body mass index
- CNS:
-
central nervous system
- CRP:
-
C-reactive protein
- ELISA:
-
Enzyme-Linked Immunosorbent Assay
- HOMA-B:
-
homeostatic model assessment of beta cells function
- HOMA-IR:
-
homeostatic model assessment of insulin resistance
- HDL:
-
high density lipoprotein
- LDL:
-
low density lipoprotein
- S.D.:
-
standard deviation
- STAI:
-
State-Trait Anxiety Inventory
- SPSS:
-
Statistical Program for Social Sciences
References
Afzal S, Nordestgaard BG, Bojesen SE (2013) Plasma 25-hydroxyvitamin D and risk of non-melanoma and melanoma skin cancer: a prospective cohort study. J Invest Dermatol 133:629–636. https://doi.org/10.1038/jid.2012.395
Afzal S, Bojesen SE, Nordestgaard BG (2014) Reduced 25-hydroxyvitamin D and risk of Alzheimer's disease and vascular dementia. Alzheimers Dement 10:296–302. https://doi.org/10.1016/j.jalz.2013.05.1765
Altay H, Zorlu A, Kocum HT, Demircan S, Yilmaz N, Yilmaz MB (2012) Relationship between parathyroid hormone and depression in heart failure. Arq Bras Cardiol 99:915–923. https://doi.org/10.1590/S0066-782X2012005000088
Alvarez JA, Ashraf A (2010) Role of vitamin D in insulin secretion and insulin sensitivity for glucose homeostasis. Int J Endocrinol 2010:351385. https://doi.org/10.1155/2010/351385
Beck AT, Steer RA, Garbin MG (1988) Psychometric properties of the Beck depression inventory: 25 years of evaluation. Clin Psychol Rev 8:77–100. https://doi.org/10.1016/0272-7358(88)90050-5
Bertone-Johnson ER (2009) Vitamin D and the occurrence of depression: causal association or circumstantial evidence? Nutr Ver 67:481–492. https://doi.org/10.1111/j.1753-4887.2009.00220.x
Biaggio AM, Natalício L, Spielberger CD (1977) Desenvolvimento da forma experimental em português do Inventário de Ansiedade Traço-Estado (IDATE) de Spielberger. Arq Bras Psic Apl 29:31–41
Bikle DD (2014) Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol 21:319–329. https://doi.org/10.1016/j.chembiol.2013.12.016
Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF et al (2008) Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev 29:726–776. https://doi.org/10.1210/er.2008-0004
Caprio M, Infante M, Calanchini M, Mammi C, Fabbri A (2017) Vitamin D: not just the bone. Evidence for beneficial pleiotropic extraskeletal effects. Eat Weight Disord 22:27–41. https://doi.org/10.1007/s40519-016-0312-6
Chabas JF, Stephan D, Marqueste T, Garcia S, Lavaut MN, Nguyen C, Legre R, Khrestchatisky M, Decherchi P, Feron F (2013) Cholecalciferol (vitamin D3) improves myelination and recovery after nerve injury. PLoS One 8:65034. https://doi.org/10.1371/journal.pone.0065034
Chaowen W, Wenwei R, Jianhua C et al (2016) Association between serum levels of vitamin D and the risk of post-stroke anxiety. Medicine 95:1–5. https://doi.org/10.1097/MD.0000000000003566
Christakos S, Dhawan P, Benn B et al (2007) Vitamin D: molecular mechanism of action. Ann N Y Acad Sci 1116:340–348. https://doi.org/10.1196/annals.1402.070
Dicou E (2009) Neurotrophins and neuronal migration in the developing rodent brain. Brain Res Rev 60:408–417. https://doi.org/10.1016/j.brainresrev.2009.03.001
Eelen G, Verlinden L, Van Camp M et al (2004) The effects of 1alpha, 25-dihydroxyvitamin D3 on the expression of DNA replication genes. J Bone Miner Res 19:133–146. https://doi.org/10.1359/JBMR.0301204
Endler NS, Kocovski NL (2001) State and trait anxiety revisited. J Anxiety Disord 15:231–245. https://doi.org/10.1016/S0887-6185(01)00060-3
Fedotova J, Pivina S, Sushko A (2017) Effects of chronic vitamin D3 hormone administration on anxiety-like behavior in adult female rats after long-term Ovariectomy. Nutrients 9:28. https://doi.org/10.3390/nu9010028
Féron F, Burne TH, Brown J et al (2005) Developmental vitamin D3 deficiency alters the adult rat brain. Brain Res Bull 65:141–148. https://doi.org/10.1016/j.brainresbull.2004.12.007
Gorenstein C, Andrade L (1996) Validation of a Portuguese version of the Beck depression inventory and the StateTrait anxiety inventory in Brazilian subjects. Braz J Med Biol Res 29:453–457. https://doi.org/10.1590/S0100-879X2005000300011
Han B, Zhu FX, Yu HF, Liu S, Zhou JL (2018) Low serum levels of vitamin D are associated with anxiety in children and adolescents with dialysis. Sci Rep 8:5956. https://doi.org/10.1038/s41598-018-24451-7
Hayes CE, Nashold FE, Spach KM, Pedersen LB (2003) The immunological functions of the vitamin D endocrine system. Cell Mol Biol 49:277–300
Hoogendijk WJ, Lips P, Dik MG, Deeg DJ, Beekman AT, Penninx BW (2008) Depression is associated with decreased 25-hydroxyvitamin D and increased parathyroid hormone levels in older adults. Arch Gen Psychiatry 65:508–512. https://doi.org/10.1001/archpsyc.65.5.508
Hua F, Reiss JI, Tang H, Wang J, Fowler X, Sayeed I, Stein DG (2012) Progesterone and low-dose vitamin D hormone treatment enhances sparing of memory following traumatic brain injury. Horm Behav 61:642–651
Jean-Louis G, Zizi F, Luther TC, Brown CD, McFarlane SI (2008) Obstructive sleep apnea and cardiovascular disease: role of the metabolic syndrome and its components. J Clin Sleep Med 4:261–272
Jia F, Shan L, Wang B, Li H, Feng J, Xu Z, Saad K (2018) Fluctuations in clinical symptoms with changes in serum 25(OH) vitamin D levels in autistic children: three cases report. Nutr Neurosci 8:1–4. https://doi.org/10.1080/1028415X.2018.1458421
Jiang P, Zhang WY, Li HD, Cai HL, Xue Y (2013) Repeated haloperidol administration has no effect on vitamin D signaling but increase retinoid X receptors and Nur77 expression in rat prefrontal cortex. Cell Mol Neurobiol 33:309–312. https://doi.org/10.1007/s10571-012-9902-7
Jorde R, Grimnes G (2011) Vitamin D and metabolic health with special reference to the effect of vitamin D on serum lipids. Prog Lipid Res 50:303–312. https://doi.org/10.1016/j.plipres.2011.05.001
Jorde R, Waterloo K, Saleh FN, Haug E, Svartberg J (2006) Neuropsychological function in relation to serum parathyroid hormone and serum 25-hydroxyvitamin D levels - the Tromso study. J Neurol 253:464–470. https://doi.org/10.1007/s00415-005-0027-5
Jorde R, Sneve M, Figenschau Y, Svartberg J, Waterloo K (2008) Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial. J Intern Med 264:599–609. https://doi.org/10.1111/j.1365-2796.2008.02008.x
Kalueff AV, Lou YR, Ilkka L et al (2004) Increased anxiety in mice lacking vitamin D receptor gene. NeuroReport 15:1271–1274. https://doi.org/10.1097/01.wnr.0000129370.04248.92
Kampmann U, Mosekilde L, Juhl C, Moller N, Christensen B, Rejnmark L, Wamberg L, Orskov L (2014) Effects of 12 weeks high dose vitamin D3 treatment on insulin sensitivity, beta cell function and metabolic markers in patients with type 2 diabetes and vitamin D insufficiencya double-blind, randomized, placebo-controlled trial. Metabolism 63:1115–1124. https://doi.org/10.1016/j.metabol.2014.06.008
Kayaniyil S, Vieth R, Retnakaran R, Knight JA, Qi Y, Gerstein HC, Perkins BA, Harris SB, Zinman B, Hanley AJ (2010) Association of vitamin D with insulin resistance and beta-cell dysfunction in subjects at risk for type 2 diabetes. Diabetes Care 33:1379–1381. https://doi.org/10.2337/dc09-2321
Khoraminya N, Tehrani-Doost M, Jazayeri HA, Djazayery A (2012) Australian & therapeutic effects of vitamin D as adjunctive therapy to fluoxetine in patients with major depressive disorder. N Z J Psychiatry 47:271–275. https://doi.org/10.1177/0004867412465022
Kimball SM, Mirhosseini N, Rucklidge J (2018) Database analysis of depression and anxiety in a community sample - response to a micronutrient intervention. Nutrients 10:1–17. https://doi.org/10.3390/nu10020152
Maddaloni E, Cavallari I, Napoli N, Conte C (2018) Vitamin D and diabetes mellitus. Front Horm Res 50:161–176. https://doi.org/10.1159/000486083
Maestro B, Molero S, Bajo S, Davila N, Calle C (2002) Transcriptional activation of the human insulin receptor gene by 1, 25-dihydroxyvitamin D3. Cell Biochem Funct 20:227–232. https://doi.org/10.1002/cbf.951
Maki KC, Fulgoni VL, Keast DR, Rains TM (2012) Vitamin D intake and status are associated with lower prevalence of metabolic syndrome in U.S. adults: National Health and nutrition examination surveys 2003–2006. Metab Syndr Relat Disord 10:363–372. https://doi.org/10.1089/met.2012.0020
Manchanda P, Bid H (2012) Vitamin D receptor and type 2 diabetes mellitus: growing therapeutic opportunities. Indian J Hum Genet 18:274–275. https://doi.org/10.4103/0971-6866.107975
Martinez AP, de Azevedo GR (2012) The Bristol stool form scale: its translation to Portuguese, cultural adaptation and validation. Rev Lat Am Enfermagem 20:583–589. https://doi.org/10.1590/S0104-11692012000300021
Masuyama R (2014) Role of local vitamin D signaling and cellular calcium transport system in bone homeostasis. J Bone Miner Metab 32:1–9. https://doi.org/10.1007/s00774-013-0508-z
Milaneschi Y, Hoogendijk W, Lips P, Heijboer AC, Schoevers R, van Hemert AM, Beekman ATF, Smit JH, Penninx BWJH (2014) The association between low vitamin D and depressive disorders. Mol Psychiatry 19:444–451. https://doi.org/10.1038/mp.2013.36
Minasyan A, Keisala T, Lou YR, Kalueff AV, Tuohimaa P (2007) Neophobia, sensory and cognitive functions, and hedonic responses in vitamin D receptor mutant mice. J Steroid Biochem Mol Biol 104:274–280. https://doi.org/10.1016/j.jsbmb.2007.03.032
Moritz B, Schwarzbold ML, Guarnieri R, Diaz AP, Rodrigues ALS, Dafre AL (2017) Effects of ascorbic acid on anxiety state and affect in a non-clinical sample. Acta Neurobiol Exp 77:362–372
Nair R, Maseeh A (2012) Vitamin D: the “sunshine” vitamin. J Pharmacol Pharmacother 3:118–126. https://doi.org/10.4103/0976-500X.95506
Nikooyeh B, Neyestani TR, Farvid M, Alavi-Majd H, Houshiarrad A, Kalayi A, Shariatzadeh N, Gharavi A’, Heravifard S, Tayebinejad N, Salekzamani S, Zahedirad M (2011) Daily consumption of vitamin D- or vitamin D+ calcium fortified yogurt drink improved glycemic control in patients with type 2 diabetes: a randomized clinical trial. Am J Clin Nutr 93:764–771. https://doi.org/10.3945/ajcn.110.007336
Patrick PA, Visintainer PF, Shi Q, Weiss IA, Brand DA (2012) Vitamin D and retinopathy in adults with diabetes mellitus. Arch Ophthalmol 130:756–760. https://doi.org/10.1001/archophthalmol.2011.2749
Pittas AG, Stark PC, Harris SS, Dawson-Hughes B (2007) The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults. Diabetes Care 30:980–986. https://doi.org/10.2337/dc06-1994
Reid IR (2004) Effects of calcium supplementation on circulating lipids. Drugs Aging 21:7–17
Reiss S (1997) Trait anxiety: It's not what you think it is. J Anxiety Disord 11:201–214. https://doi.org/10.1016/S0887-6185(97)00006-6
Ross AC, Manson JE, Abrams SA et al (2011) The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 96:53–58. https://doi.org/10.1210/jc.2010-2704
Schöttker B, Haug U, Schomburg L, Köhrle J, Perna L, Müller H, Holleczek B, Brenner H (2013) Strong associations of 25-hydroxyvitamin D concentrations with all-cause, cardiovascular, cancer, and respiratory disease mortality in a large cohort study. Am J Clin Nutr 97:782–793. https://doi.org/10.3945/ajcn.112.047712
Sergeev IN, Rhoten WB (1995) 1,25-Dihydroxyvitamin D3 evokes oscillations of intracellular calcium in a pancreatic beta-cell line. Endocrinology 136:2852–2861. https://doi.org/10.1210/endo.136.7.7789310
Shaffer JA, Edmondson D, Wasson LT, Falzon L, Homma K, Ezeokoli N, Li P, Davidson KW (2014) Vitamin D supplementation for depressive symptoms: a systematic review and meta-analysis of randomized controlled trials. Psychosom Med 76:190–196. https://doi.org/10.1097/PSY.0000000000000044
Sheline YI, Barch DM, Garcia K (2006) Cognitive function in late life depression: relationships to depression severity, cerebrovascular risk factors and processing speed. Biol Psychiatry 60:58–65. https://doi.org/10.1016/j.biopsych.2005.09.019
Song Y, Wang L, Pittas AG, del Gobbo LC, Zhang C, Manson JE, Hu FB (2013) Blood 25-hydroxy vitamin D levels and incident type 2 diabetes: a meta-analysis of prospective studies. Diabetes Care 36:1422–1428. https://doi.org/10.2337/dc12-0962
Spielberger CD, Gorsuch RL, Lushene RE (1970) Manual for the state-trait anxiety inventory. Consulting Psychologists Press, Palo Alto
Sung CC, Liao MT, Lu KC, Wu CC (2012) Role of vitamin D in insulin resistance. J Biomed Biotechnol 2012:634195–634111. https://doi.org/10.1155/2012/634195
Tang H, Hua F, Wang J, Sayeed I, Wang X, Chen Z, Yousuf S, Atif F, Stein DG (2013) Progesterone and vitamin D: improvement after traumatic brain injury in middle-aged rats. Horm Behav 64:527–538. https://doi.org/10.1016/j.yhbeh.2013.06.009
Tang H, Hua F, Wang J, Yousuf S, Atif F, Sayeed I, Stein DG (2015) Progesterone and vitamin D combination therapy modulates inflammatory response after traumatic brain injury. Brain Inj 17:1–10. https://doi.org/10.3109/02699052.2015.1035330
Tsur A, Feldman BS, Feldhammer I, Hoshen MB, Leibowitz G, Balicer RD (2013) Decreased serum concentrations of 25-hydroxycholecalciferol are associated with increased risk of progression to impaired fasting glucose and diabetes. Diabetes Care 36(5):1361-7. https://doi.org/10.2337/dc12-1050.
Upadhyay RK (2014) Transendothelial transport and its role in therapeutics. Int Sch Res Notices 27:1–39. https://doi.org/10.1155/2014/309404
Vacek JL, Vanga SR, Good M, Lai SM, Lakkireddy D, Howard PA (2012) Vitamin D deficiency and supplementation and relation to cardiovascular health. Am J Cardiol 109:359–363. https://doi.org/10.1016/j.amjcard.2011.09.020
Van Belle TL, Gysemans C, Mathieu C (2013) Vitamin D and diabetes: the odd couple. Trends Endocrinol Metab 24(11):561–568. https://doi.org/10.1016/j.tem.2013.07.002
Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, Benjamin EJ, D’Agostino RB, Wolf M, Vasan RS (2008) Vitamin D deficiency and Risc of cardiovascular disease. Circulation 117, 503-511-controlled trial. Metabolism 63:1115–1124. https://doi.org/10.1161/CIRCULATIONAHA.107.706127
Wang H, Xia NY, Peng DQ (2012) Influence of vitamin D supplementation on plasma lipid profiles: a meta-analysis of randomized controlled trials. Lipids Health Dis 11:42. https://doi.org/10.1186/1476-511X-11-42
Williams JA, Romero VC, Clinton CM, Vazquez DM, Marcus SM, Chilimigras JL, Hamilton SE, Allbaugh LJ, Vahratian AM, Schrader RM, Mozurkewich EL (2016) Vitamin D levels and perinatal depressive symptoms in women at risk: a secondary analysis of the mothers, omega-3, and mental health study. BMC Pregnancy Childbirth 16:203. https://doi.org/10.1186/s12884-016-0988-7
Wong KE, Szeto F, Zhang W et al (2009) Involvement of the vitamin D receptor in energy metabolism: regulation of uncoupling proteins. Am J Physiol Endocrinol Metab 296:820–828. https://doi.org/10.1152/ajpendo.90763.200
Acknowledgements
This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES). MPK and ALSR are CNPq Research Fellows.
Author information
Authors and Affiliations
Contributions
M.P.K and A.L.R. were involved in the conception and design of the study and drafting of the manuscript; G.A. and G.A.S.C. were responsible for acquisition and analysis of data and drafting the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Casseb, G.A.S., Ambrósio, G., Rodrigues, A.L.S. et al. Levels of 25-hydroxyvitamin D3, biochemical parameters and symptoms of depression and anxiety in healthy individuals. Metab Brain Dis 34, 527–535 (2019). https://doi.org/10.1007/s11011-018-0371-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11011-018-0371-7