Sulfated Vitamin D Metabolites Represent Prominent Roles in Serum and in Breastmilk of Lactating Women

Overview

Journal Clin Nutr

Publisher Elsevier

Date 2024 Jul 18

PMID 39024772

Authors

Carmen J Reynolds

Roy B Dyer

Sara S Oberhelman-Eaton

Brianna L Konwinski

Renee M Weatherly

Ravinder J Singh

Tom D Thacher

Affiliations

Soon will be listed here.

Abstract

Background: Concentrations of vitamin D (VitD) and 25-hydroxyvitamin D (25OHD) in breastmilk are low despite the essential role of VitD for normal infant bone development, yet additional metabolic forms of vitamin D may be present. This study evaluates the contribution of sulfated vitamin D metabolites, vitamin D-sulfate (VitD-S) and 25-hydroxyvitamin D-sulfate (25OHD-S) for lactating women and assesses the response to high-dose VitD supplementation.

Methods: Serum and breastmilk were measured before and after 28 days with 5000 IU/day VitD intake in 20 lactating women. Concentrations of VitD-S and 25OHD-S in milk, and 25OHD, 25OHD, 25OHD-S, VitD and VitD-S in serum were determined by mass spectrometry.

Results: Baseline vitamin D status was categorized as sufficient (mean ± SD serum 25OHD 69 ± 19 nmol/L), and both serum VitD and 25OHD increased following supplementation (p < 0.001). 25OHD-S was 91 ± 19 nmol/L in serum and 0.47 ± 0.09 nmol/L in breastmilk. VitD-S concentrations were 2.92 ± 0.70 nmol/L in serum and 6.4 ± 3.9 nmol/L in breastmilk. Neither sulfated metabolite significantly changed with supplementation in either serum or breastmilk.

Conclusions: Sulfated vitamin D metabolites have prominent roles for women during lactation with 25OHD-S highly abundant in serum and VitD-S distinctly abundant in breastmilk. These data support the notion that 25OHD-S and VitD-S may have physiological relevance during lactation and nutritional usage for nursing infants.

References

Kumar R, Londowski J, Murari M, Nagubandi S . Synthesis and biological activity of vitamin D2 3 beta-glucosiduronate and vitamin D2 3 beta-sulfate: role of vitamin D2 conjugates in calcium homeostasis. J Steroid Biochem. 1982; 17(5):495-502. DOI: 10.1016/0022-4731(82)90007-3. View

Greer F, Hollis B, Napoli J . High concentrations of vitamin D2 in human milk associated with pharmacologic doses of vitamin D2. J Pediatr. 1984; 105(1):61-4. DOI: 10.1016/s0022-3476(84)80361-3. View

Hoff N, Haddad J, Teitelbaum S, McAlister W, HILLMAN L . Serum concentrations of 25-hydroxyvitamin D in rickets of extremely premature infants. J Pediatr. 1979; 94(3):460-6. DOI: 10.1016/s0022-3476(79)80602-2. View

Ruangkit C, Suwannachat S, Wantanakorn P, Sethaphanich N, Assawawiroonhakarn S, Dumrongwongsiri O . Vitamin D status in full-term exclusively breastfed infants versus full-term breastfed infants receiving vitamin D supplementation in Thailand: a randomized controlled trial. BMC Pediatr. 2021; 21(1):378. PMC: 8408999. DOI: 10.1186/s12887-021-02849-z. View

Jan Mohamed H, Rowan A, Fong B, Loy S . Maternal serum and breast milk vitamin D levels: findings from the Universiti Sains Malaysia Pregnancy Cohort Study. PLoS One. 2014; 9(7):e100705. PMC: 4081124. DOI: 10.1371/journal.pone.0100705. View

Rios-Leyvraz M, Yao Q . Calcium, zinc, and vitamin D in breast milk: a systematic review and meta-analysis. Int Breastfeed J. 2023; 18(1):27. PMC: 10233556. DOI: 10.1186/s13006-023-00564-2. View

Basile L, Taylor S, Wagner C, Horst R, Hollis B . The effect of high-dose vitamin D supplementation on serum vitamin D levels and milk calcium concentration in lactating women and their infants. Breastfeed Med. 2007; 1(1):27-35. DOI: 10.1089/bfm.2006.1.27. View

Andrews L, Phlegar K, Baatz J, Ebeling M, Shary J, Gregoski M . Comparison of Infant Bone Mineral Content and Density After Infant Daily Oral Vit D 400 IU Supplementation Versus Nursing Mother Oral 6,400 IU Supplementation: A Randomized Controlled Lactation Study. Breastfeed Med. 2022; 17(6):493-500. PMC: 9234966. DOI: 10.1089/bfm.2021.0281. View

Zeghoud F, Vervel C, Guillozo H, Walrant-Debray O, Boutignon H, Garabedian M . Subclinical vitamin D deficiency in neonates: definition and response to vitamin D supplements. Am J Clin Nutr. 1997; 65(3):771-8. DOI: 10.1093/ajcn/65.3.771. View

10.

Thiele D, Ralph J, El-Masri M, Anderson C . Vitamin D3 Supplementation During Pregnancy and Lactation Improves Vitamin D Status of the Mother-Infant Dyad. J Obstet Gynecol Neonatal Nurs. 2016; 46(1):135-147. DOI: 10.1016/j.jogn.2016.02.016. View

11.

Tuckey R, Cheng C, Li L, Jiang Y . Analysis of the ability of vitamin D3-metabolizing cytochromes P450 to act on vitamin D3 sulfate and 25-hydroxyvitamin D3 3-sulfate. J Steroid Biochem Mol Biol. 2022; 227:106229. DOI: 10.1016/j.jsbmb.2022.106229. View

12.

Ziegler E, Hollis B, Nelson S, Jeter J . Vitamin D deficiency in breastfed infants in Iowa. Pediatrics. 2006; 118(2):603-10. DOI: 10.1542/peds.2006-0108. View

13.

Reynolds C, Koszewski N, Horst R, Beitz D, Goff J . Role of glucuronidated 25-hydroxyvitamin D on colon gene expression in mice. Am J Physiol Gastrointest Liver Physiol. 2020; 319(2):G253-G260. PMC: 7500262. DOI: 10.1152/ajpgi.00355.2019. View

14.

Dawodu A, Tsang R . Maternal vitamin D status: effect on milk vitamin D content and vitamin D status of breastfeeding infants. Adv Nutr. 2012; 3(3):353-61. PMC: 3649470. DOI: 10.3945/an.111.000950. View

15.

Oberson J, Benet S, Redeuil K, Campos-Gimenez E . Quantitative analysis of vitamin D and its main metabolites in human milk by supercritical fluid chromatography coupled to tandem mass spectrometry. Anal Bioanal Chem. 2019; 412(2):365-375. PMC: 6992569. DOI: 10.1007/s00216-019-02248-5. View

16.

Hollis B, Wagner C, Howard C, Ebeling M, Shary J, Smith P . Maternal Versus Infant Vitamin D Supplementation During Lactation: A Randomized Controlled Trial. Pediatrics. 2015; 136(4):625-34. PMC: 4586731. DOI: 10.1542/peds.2015-1669. View

17.

Stoutjesdijk E, Schaafsma A, Nhien N, Khor G, Kema I, Hollis B . Milk vitamin D in relation to the 'adequate intake' for 0-6-month-old infants: a study in lactating women with different cultural backgrounds, living at different latitudes. Br J Nutr. 2017; 118(10):804-812. DOI: 10.1017/S000711451700277X. View

18.

Oberhelman S, Meekins M, Fischer P, Lee B, Singh R, Cha S . Maternal vitamin D supplementation to improve the vitamin D status of breast-fed infants: a randomized controlled trial. Mayo Clin Proc. 2013; 88(12):1378-87. PMC: 3923377. DOI: 10.1016/j.mayocp.2013.09.012. View

19.

Wagner C, Greer F . Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics. 2008; 122(5):1142-52. DOI: 10.1542/peds.2008-1862. View

20.

Sahashi Y, Suzuki T, Higaki M, Asano T . Antirachitic potency of vitamin D sulfate in human milk. J Vitaminol (Kyoto). 1969; 15(1):78-82. DOI: 10.5925/jnsv1954.15.78. View