Evaluation of the efficacy of two doses of vitamin D supplementation on glycemic, lipidemic and oxidative stress biomarkers during pregnancy: a randomized clinical trial

Soudabe Motamed, Bahareh Nikooyeh, Maryam Kashanian, Maryam Chamani, Bruce W Hollis, Tirang R Neyestani, Soudabe Motamed, Bahareh Nikooyeh, Maryam Kashanian, Maryam Chamani, Bruce W Hollis, Tirang R Neyestani

Abstract

Background: Vitamin D deficiency during pregnancy is common and is likely to be associated with metabolic complications in the mother. The aim of this study was to assess the efficacy of two doses of vitamin D supplementation during pregnancy on maternal and cord blood vitamin D status and metabolic and oxidative stress biomarkers.

Methods: The eligible pregnant women (n = 84) invited to participate in the study and randomly allocated to one of the two supplementation groups (1000 IU/d vitamin D and 2000 IU/d). Biochemical assessments of mothers including serum concentrations of 25(OH)D, calcium, phosphate, iPTH, fasting serum sugar (FBS), insulin, triglyceride, total cholesterol, LDL-C, HDL-C, malondialdehyde (MDA) and total antioxidant capacity (TAC) were done at the beginning and 34 weeks of gestation. Cord blood serum concentrations of 25(OH)D, iPTH, MDA and TAC were assessed at delivery as well. To determine the effects of vitamin D supplementation on metabolic markers 1-factor repeated-measures analysis of variance (ANOVA) was used. Between groups comparisons was done by using Independent-samples Student's t-test or Mann-Whitney test. P < 0.05 was considered as significant.

Results: Supplementation with 1000 IU/d and 2000 IU/d vitamin D resulted in significant changes in vitamin D status over pregnancy (24.01 ± 21.7, P < 0.001 in 1000 IU/d group and 46.7 ± 30.6 nmol/L, P < 0.001 in 2000 IU/d group). Daily intake of 2000 compared with 1000 IU/d tended to increase the serum concentration of HDL-C (10 ± 8.37, P < 0.001 in 1000 IU/d group and 9.52 ± 11.39 mg/dL, P < 0.001 in 2000 IU/d group). A significant decrement in serum concentration of iPTH observed in both groups (- 4.18 ± 7.5, P = 0.002 in 1000 IU/d group and - 8.36 ± 14.17, P = 0.002 in 2000 IU/d group).

Conclusions: Supplementation with 2000 IU/d vitamin D as compared with 1000 IU/d, is more effective in promoting vitamin D status and HDL-C serum concentration and in decreasing iPTH over pregnancy.

Trial registration: This trial is registered at clinicaltrials.gov ( NCT03308487 ). Registered 12 October 2017 'retrospectively registered'.

Keywords: Glycemic status; lipid profile; Pregnancy; Vitamin D supplementation.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow diagram of the study

References

    1. Sorenson RL, Brelje TC. Adaptation of islets of Langerhans to pregnancy: beta-cell growth, enhanced insulin secretion and the role of lactogenic hormones. Horm Metab Res. 1997;29(6):301–307. doi: 10.1055/s-2007-979040.
    1. Pusukuru R, Shenoi AS, Kumar Kyada P, Ghodke B, Mehta V, Bhuta K, et al. Evaluation of lipid profile in second and third trimester of pregnancy. J Clin Diagn Res. 2016;10(3):QC12–QQC6.
    1. Mankuta D, Elami-Suzin M, Elhayani A, Vinker S. Lipid profile in consecutive pregnancies. Lipids Health Dis. 2010;9:58. doi: 10.1186/1476-511X-9-58.
    1. Palacios C, Kostiuk LK, Peña-Rosas JP. Vitamin D supplementation for women during pregnancy. Cochrane Database Syst Rev. 2019;7(7):CD008873. 10.1002/14651858.CD008873.pub4.
    1. Dovnik A, Mujezinović F. The association of vitamin D levels with common pregnancy complications. Nutrients. 2018;10(7):867. doi: 10.3390/nu10070867.
    1. Al-Ajlan A, Al-Musharaf S, Fouda MA, Krishnaswamy S, Wani K, Aljohani NJ, et al. Lower vitamin D levels in Saudi pregnant women are associated with higher risk of developing GDM. BMC Pregnancy Childbirth. 2018;18(1):86. doi: 10.1186/s12884-018-1723-3.
    1. Naseh A, Ashrafzadeh S, Rassi S. Prevalence of vitamin D deficiency in pregnant mothers in Tehran and investigating its association with serum glucose and insulin. J Matern Fetal Neonatal Med. 2018;31(17):2312–2318. doi: 10.1080/14767058.2017.1342796.
    1. O'Brien E, O'Sullivan E, Kilbane M, Geraghty A, McKenna M, McAuliffe F. Season and vitamin D status are independently associated with glucose homeostasis in pregnancy. BJOG Int J Obstet Gynaecol. 2017;124:95. doi: 10.1111/1471-0528.14193.
    1. Soytac Inancli I, Yayci E, Atacag T, Uncu M. Is maternal Vitamin D associated with gestational diabetes mellitus in pregnant women in Cyprus? Clin Exp Obstet Gynecol. 2016;43(6):840–843.
    1. Jamilian M, Karamali M, Taghizadeh M, Sharifi N, Jafari Z, Memarzadeh MR, et al. Vitamin D and evening primrose oil administration improve glycemia and lipid profiles in women with gestational diabetes. Lipids. 2016;51(3):349–356. doi: 10.1007/s11745-016-4123-3.
    1. Al-Ajlan A, Krishnaswamy S, Alokail MS, Aljohani NJ, Al-Serehi A, Sheshah E, et al. Vitamin D deficiency and dyslipidemia in early pregnancy. BMC Pregnancy Childbirth. 2015;15:314. 10.1186/s12884-015-0751-5.
    1. Wang L, Song Y, Manson JE, Pilz S, Marz W, Michaelsson K, et al. Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies. Circ Cardiovasc Qual Outcomes. 2012;5(6):819–829. doi: 10.1161/CIRCOUTCOMES.112.967604.
    1. Swart KM, Lips P, Brouwer IA, Jorde R, Heymans MW, Grimnes G, et al. Effects of vitamin D supplementation on markers for cardiovascular disease and type 2 diabetes: an individual participant data meta-analysis of randomized controlled trials. Am J Clin Nutr. 2018;107(6):1043–1053. doi: 10.1093/ajcn/nqy078.
    1. Demer LL, Hsu JJ, Tintut Y. Steroid hormone Vitamin D: implications for cardiovascular disease. Circ Res. 2018;122(11):1576–1585. doi: 10.1161/CIRCRESAHA.118.311585.
    1. Sears C. The relationship between 25-hydroxy Vitamin D, parathyroid hormone and Glycemia during pregnancy and postpartum. Can J Diabetes. 2016;40(3):196–197. doi: 10.1016/j.jcjd.2016.04.001.
    1. Hemmingway A, O'Callaghan KM, Hennessy A, Hull GLJ, Cashman KD, Kiely ME. Interactions between Vitamin D status, Calcium Intake and Parathyroid Hormone Concentrations in Healthy White-Skinned Pregnant Women at Northern Latitude. Nutrients. 2018;10(7):916. 10.3390/nu10070916.
    1. Mannaerts D, Faes E, Cos P, Briede JJ, Gyselaers W, Cornette J, et al. Oxidative stress in healthy pregnancy and preeclampsia is linked to chronic inflammation, iron status and vascular function. PLoS One. 2018;13(9):e0202919. doi: 10.1371/journal.pone.0202919.
    1. Chiarello DI, Abad C, Rojas D, Toledo F, Vázquez CM, Mate A, et al. Oxidative stress: normal pregnancy versus preeclampsia. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2018.
    1. Jauniaux E, Burton GJ. The role of oxidative stress in placental-related diseases of pregnancy. J Gynecol Obstet Biol Reprod (Paris) 2016;45(8):775–785. doi: 10.1016/j.jgyn.2016.02.012.
    1. Chiarello DI, Abad C, Rojas D, Toledo F, Vazquez CM, Mate A, et al. Oxidative stress: Normal pregnancy versus preeclampsia. Biochim Biophys Acta Mol basis Dis. 2018;24 PubMed PMID: 30590104. Epub 2018/12/28. eng.
    1. Uberti F, Morsanuto V, Molinari C. Vitamin D in oxidative stress and diseases. A Critical Evaluation of Vitamin D-Basic Overview. 2017.
    1. Wimalawansa SJ. Vitamin d deficiency: effects on oxidative stress, epigenetics, gene regulation, and aging. Biology. 2019;8(2):30. doi: 10.3390/biology8020030.
    1. Sepidarkish M, Farsi F, Akbari-Fakhrabadi M, Namazi N, Almasi-Hashiani A, Maleki A, et al. The effect of vitamin D supplementation on oxidative stress parameters: a systematic review and meta-analysis of clinical trials. Pharmacol Res. 2018.
    1. Nikooyeh B, Anari R, Neyestani TR. Vitamin D, oxidative stress, and diabetes: crossroads for new therapeutic approaches. In: Diabetes, oxidative stress and dietary antioxidants. London: Academic Press; 2020. p. 385–395.
    1. Palacios C, Gonzalez L. Is vitamin D deficiency a major global public health problem? J Steroid Biochem Mol Biol. 2014;144 Pt A:138–145. doi: 10.1016/j.jsbmb.2013.11.003.
    1. Saraf R, Morton SM, Camargo CA, Jr, Grant CC. Global summary of maternal and newborn vitamin D status - a systematic review. Matern Child Nutr. 2016;12(4):647–668. doi: 10.1111/mcn.12210.
    1. Pirdehghan A, Vakili M, Dehghan R, Zare F. High prevalence of Vitamin D deficiency and adverse pregnancy outcomes in Yazd, a central province of Iran. J Reprod Infertil. 2016;17(1):34–38.
    1. Abbasian M, Chaman R, Amiri M, Ajami ME, Jafari-Koshki T, Rohani H, et al. Vitamin D Deficiency in Pregnant Women and Their Neonates. Global J Health Sci. 2016;8(9):54008. doi: 10.5539/gjhs.v8n9p83.
    1. Motamed S, Nikooyeh B, Kashanian M, Hollis BW, Neyestani TR. Efficacy of two different doses of oral vitamin D supplementation on inflammatory biomarkers and maternal and neonatal outcomes. Matern Child Nutr. 2019;15(4):e12867. doi: 10.1111/mcn.12867.
    1. Motamed S, Nikooyeh B, Kashanian M, Neyestani T. Evaluation of the efficacy of 1000 and 2000 IU/d vitamin D supplementation during pregnancy on maternal and newborn vitamin D status, metabolic, inflammatory and oxidative stress biomarkers, and maternal and neonatal outcomes: a study protocol. J Nutr Food Sci Res. 2018;5(3):3–10.
    1. Yesiltepe Mutlu G, Ozsu E, Kalaca S, Yuksel A, Pehlevan Y, Cizmecioglu F, et al. Evaluation of vitamin D supplementation doses during pregnancy in a population at high risk for deficiency. Horm Res Paediatr. 2014;81(6):402–408. doi: 10.1159/000358833.
    1. Brustad M, Alsaker E, Engelsen O, Aksnes L, Lund E. Vitamin D status of middle-aged women at 65-71 degrees N in relation to dietary intake and exposure to ultraviolet radiation. Public Health Nutr. 2004;7(2):327–335. doi: 10.1079/PHN2003536.
    1. Vasheghani-Farahani A, Tahmasbi M, Asheri H, Ashraf H, Nedjat S, Kordi R. The Persian, last 7-day, long form of the international physical activity questionnaire: translation and validation study. Asian J Sports Med. 2011;2(2):106–116. doi: 10.5812/asjsm.34781.
    1. 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. Diabetologia. 1985;28(7):412–419. doi: 10.1007/BF00280883.
    1. Neyestani TR, Fereydouni Z, Hejazi S, Salehi-Nasab F, Nateghifard F, Maddah M, et al. Vitamin C status in Iranian children with acute lymphoblastic leukemia: evidence for increased utilization. J Pediatr Gastroenterol Nutr. 2007;45(1):141–144. doi: 10.1097/MPG.0b013e31804c5047.
    1. Kominiarek MA, Rajan P. Nutrition recommendations in pregnancy and lactation. Med Clin North Am. 2016;100(6):1199–1215. doi: 10.1016/j.mcna.2016.06.004.
    1. Cooper C, Harvey NC, Bishop NJ, Kennedy S, Papageorghiou AT, Schoenmakers I, et al. Maternal gestational vitamin D supplementation and off spring bone health (MAVIDOS): a multicentre, double-blind, randomised placebo-controlled trial. Lancet Diabetes Endocrinol. 2016;4(5):393–402. doi: 10.1016/S2213-8587(16)00044-9.
    1. Zerofsky M, Jacoby B, Pedersen TL, Stephensen CB. Effects of a Randomized, Controlled Trial of Daily Vitamin D3 Supplementation During Pregnancy on Regulatory Immunity and Inflammation. FASEB J. 2016; PubMed PMID: WOS:000406444700515.
    1. Hollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. J Bone Miner Res. 2011;26(10):2341–2357. doi: 10.1002/jbmr.463.
    1. Rodda CP, Benson JE, Vincent AJ, Whitehead CL, Polykov A, Vollenhoven B. Maternal Vitamin D supplementation during pregnancy prevents Vitamin D deficiency in the newborn: an open-label randomized controlled trial. Clin Endocrinol. 2015;83(3):363–368. doi: 10.1111/cen.12762.
    1. Zhang Q, Cheng Y, He M, Li T, Ma Z, Cheng H. Effect of various doses of vitamin D supplementation on pregnant women with gestational diabetes mellitus: a randomized controlled trial. Exp Ther Med. 2016;12(3):1889–1895. doi: 10.3892/etm.2016.3515.
    1. Casey C, McGinty A, Holmes VA, Hill AJ, Patterson CC, Young IS, et al. Maternal vitamin D and markers of glycaemia during pregnancy in the Belfast Centre of the Hyperglycaemia and adverse pregnancy outcome study. Diabet Med. 2018;35(7):972–979. doi: 10.1111/dme.13632.
    1. Bal M, Ersoy GS, Demirtas O, Kurt S, Tasyurt A. Vitamin D deficiency in pregnancy is not associated with diabetes mellitus development in pregnant women at low risk for gestational diabetes. Turk J Obstet Gynecol. 2016;13(1):23–26. doi: 10.4274/tjod.10170.
    1. Asemi Z, Foroozanfard F, Hashemi T, Bahmani F, Jamilian M, Esmaillzadeh A. Calcium plus vitamin D supplementation affects glucose metabolism and lipid concentrations in overweight and obese vitamin D deficient women with polycystic ovary syndrome. Clin Nutr. 2015;34(4):586–592. doi: 10.1016/j.clnu.2014.09.015.
    1. Sergeev IN, Rhoten WB. 1,25-Dihydroxyvitamin D3 evokes oscillations of intracellular calcium in a pancreatic beta-cell line. Endocrinology. 1995;136(7):2852–2861. doi: 10.1210/endo.136.7.7789310.
    1. Grimes SB, Wild R, et al. Effect of pregnancy on lipid metabolism and lipoprotein levels. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, et al., editors. Endotext. South Dartmouth: , Inc.; 2000.
    1. Ghodke B, Pusukuru R, Mehta V. Association of Lipid Profile in pregnancy with preeclampsia, gestational diabetes mellitus, and preterm delivery. Cureus. 2017;9(7):e1420.
    1. Alvarez JJ, Montelongo A, Iglesias A, Lasuncion MA, Herrera E. Longitudinal study on lipoprotein profile, high density lipoprotein subclass, and postheparin lipases during gestation in women. J Lipid Res. 1996;37(2):299–308.
    1. Feingold KR, Wiley T, Moser AH, Lear SR, Wiley MH. De novo cholesterogenesis in pregnancy. J Lab Clin Med. 1983;101(2):256–263.
    1. Belo L, Caslake M, Gaffney D, Santos-Silva A, Pereira-Leite L, Quintanilha A, et al. Changes in LDL size and HDL concentration in normal and preeclamptic pregnancies. Atherosclerosis. 2002;162(2):425–432. doi: 10.1016/S0021-9150(01)00734-1.
    1. Desoye G, Schweditsch MO, Pfeiffer KP, Zechner R, Kostner GM. Correlation of hormones with lipid and lipoprotein levels during normal pregnancy and postpartum. J Clin Endocrinol Metab. 1987;64(4):704–712. doi: 10.1210/jcem-64-4-704.
    1. Larsson A, Palm M, Hansson LO, Axelsson O. Reference values for clinical chemistry tests during normal pregnancy. BJOG. 2008;115(7):874–881. doi: 10.1111/j.1471-0528.2008.01709.x.
    1. Lepsch J, Eshriqui I, Farias DR, Vaz JS, Cunha Figueiredo AC, Adegboye AR, et al. Association between early pregnancy vitamin D status and changes in serum lipid profiles throughout pregnancy. Metabolism. 2017;70:85–97. doi: 10.1016/j.metabol.2017.02.004.
    1. Jin D, Yao MN, Yin WJ, Zhu P. The association of Vitamin D levels with lipid metabolism during pregnancy. Zhonghua Yu Fang Yi Xue Za Zhi. 2019;53(6):628–632.
    1. Asemi Z, Hashemi T, Karamali M, Samimi M, Esmaillzadeh A. Effects of vitamin D supplementation on glucose metabolism, lipid concentrations, inflammation, and oxidative stress in gestational diabetes: a double-blind randomized controlled clinical trial. Am J Clin Nutr. 2013;98(6):1425–1432. doi: 10.3945/ajcn.113.072785.
    1. Yazdchi R, Gargari BP, Asghari-Jafarabadi M, Sahhaf F. Effects of vitamin D supplementation on metabolic indices and hs-CRP levels in gestational diabetes mellitus patients: a randomized, double-blinded, placebo-controlled clinical trial. Nutr Res Pract. 2016;10(3):328–335. doi: 10.4162/nrp.2016.10.3.328.
    1. Karamali M, Beihaghi E, Mohammadi AA, Asemi Z. Effects of high-dose Vitamin D supplementation on metabolic status and pregnancy outcomes in pregnant women at risk for pre-eclampsia. Horm Metab Res. 2015;47(12):867–872. doi: 10.1055/s-0035-1548835.
    1. Wang Y, Si S, Liu J, Wang Z, Jia H, Feng K, et al. The associations of serum lipids with Vitamin D status. PLoS One. 2016;11(10):e0165157. doi: 10.1371/journal.pone.0165157.
    1. Hollis BW, Wagner CL. Vitamin D requirements and supplementation during pregnancy. Curr Opin Endocrinol Diabetes Obes. 2011;18(6):371–375. doi: 10.1097/MED.0b013e32834b0040.
    1. Okonofua F, Menon RK, Houlder S, Thomas M, Robinson D, O'Brien S, et al. Calcium, vitamin D and parathyroid hormone relationships in pregnant Caucasian and Asian women and their neonates. Ann Clin Biochem. 1987;24(1):22–28. doi: 10.1177/000456328702400103.
    1. Bowyer L, Catling-Paull C, Diamond T, Homer C, Davis G, Craig ME. Vitamin D, PTH and calcium levels in pregnant women and their neonates. Clin Endocrinol. 2009;70(3):372–377. doi: 10.1111/j.1365-2265.2008.03316.x.
    1. Dror DK, King JC, Fung EB, van Loan MD, Gertz ER, Allen LH. Evidence of associations between feto-maternal vitamin D status, cord parathyroid hormone and bone-specific alkaline phosphatase, and newborn whole body bone mineral content. Nutrients. 2012;4(2):68–77. doi: 10.3390/nu4020068.
    1. Hirota Y, Anai T, Miyakawa I. Parathyroid hormone-related protein levels in maternal and cord blood. Am J Obstet Gynecol. 1997;177(3):702–706. doi: 10.1016/S0002-9378(97)70167-4.
    1. Bond H, Dilworth MR, Baker B, Cowley E, Requena Jimenez A, Boyd RD, et al. Increased maternofetal calcium flux in parathyroid hormone-related protein-null mice. J Physiol. 2008;586(7):2015–2025. doi: 10.1113/jphysiol.2007.149104.
    1. Gargari BP, Tabrizi FPF, Sadien B, Jafarabadi MA, Farzadi L. Vitamin D Status Is Related to Oxidative Stress But Not High-Sensitive C-Reactive Protein in Women with Pre-Eclampsia. Gynecol Obstet Investig. 2016;81(4):308–314. doi: 10.1159/000441781.
    1. Nakai K, Fujii H, Kono K, Goto S, Kitazawa R, Kitazawa S, et al. Vitamin D activates the Nrf2-Keap1 antioxidant pathway and ameliorates nephropathy in diabetic rats. Am J Hypertens. 2014;27(4):586–595. doi: 10.1093/ajh/hpt160.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa