skip to main content

Liprotide-encapsulated vitamin D3 modulates circulated PTH levels and improved bone microstructure

1Department of Nutrition Science, Faculty of Medicine, Universitas Diponegoro, Indonesia

2Department of Medical Biology and Biochemistry, Faculty of Medicine, Universitas Diponegoro, Indonesia

3Department of Pharmacology and Therapy, Faculty of Medicine, Universitas Diponegoro, Indonesia

4 Department of Nutrition, Faculty of Public Health, Universitas Ahmad Dahlan, Indonesia

View all affiliations
Received: 20 May 2023; Published: 28 Dec 2023.

Citation Format:

Background: vitamin D (25(OH)D) is a fat-soluble vitamin that is unstable in the gastrointestinal environment and has low bioavailability. A protein-lipid complex (liprotide) can be used as a shell to increase vitamin D stability and bioavailability. Liprotide can also serve as a delivery system for transporting vitamin D to its intended site. Little attention has been paid to utilizing liprotide as a delivery system for vitamin D and evaluating its functional activity.

Objective: to investigate the effect of liprotide-encapsulated vitamin D3 on PTH levels and bone microstructure in vitamin D and calcium (VD-Ca) deficient rats.

Materials and Methods: an overall of 24 Wistar rats had been divided into four groups, a normal control group (K), a VD-Ca group without treatment (K-), a VD-Ca group with 180 IU/200 gBW/day free vitamin D3 (FVD3), and a VD-Ca group with 180 IU/200 gBW/day liprotide-encapsulated vitamin D3 (LVD3). Before and after 28 days of vitamin D intervention, blood samples were taken and analysed for serum PTH levels. The microstructure of the bone was analyzed using the Scanning Electron Microscope (SEM).

Results: the VD-Ca rats supplemented with vitamin D3 (FVD3 and LVD3) had a significant decrease in serum PTH levels (p<0.001) and improved bone microstructure (p<0.05) compared to the (K-) group. The reduction of PTH in the LVD3 group was higher compared to the FVD3 group. The bone microstructure between the FVD3 and LVD3 groups is significantly different, as seen in the Ct.Wi parameter, with the LVD3 group having a higher Ct.Wi than the FVD3 group.

Conclusion: liprotide-encapsulated vitamin D3 improves the serum PTH level and bone microstructure in a rat model of vitamin D and calcium deficiency.

Note: This article has supplementary file(s).

Fulltext View|Download |  Research Instrument
Cover Letter
Type Research Instrument
  Download (20KB)    Indexing metadata
 Research Instrument
Ethical Clearance
Type Research Instrument
  Download (249KB)    Indexing metadata
Keywords: bone microstructure; encapsulation; liprotide; PTH; vitamin D3
Funding: Indonesian Ministry of Education, Culture, Research, and Technology under contract 187-13/UN7.6.1/PP/2022

Article Metrics:

  1. Palacios C, Gonzalez L. Is vitamin D deficiency a major global public health problem? J Steroid Biochem Mol Biol. 2014;144(PA):138-145. DOI: 10.1016/j.jsbmb.2013.11.003
  2. Raymond JL-, Morrow K. Krause and Mahan’s Food & The Nutrition Care Process. Fifteenth. Canada: Elsevier Inc.; 2021
  3. Chang S-W, Lee H-C. Vitamin D and health - The missing vitamin in humans. Pediatr Neonatol. 2019;60(3):237-244. DOI: 10.1016/j.pedneo.2019.04.007
  4. Glowka E, Stasiak J, Lulek J. Drug Delivery Systems for Vitamin D Supplementation and Therapy. Pharmaceutics. 2019;11(7):347-368. DOI: 10.3390/pharmaceutics11070347
  5. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011;96(7):1911-1930. DOI: 10.1210/jc.2011-0385
  6. Holick MF. The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord. 2017;18(2):153-165. DOI: 10.1007/s11154-017-9424-1
  7. Letavernier E, Verrier C, Goussard F, et al. Calcium and vitamin D have a synergistic role in a rat model of kidney stone disease. Kidney Int. 2016;90(4):809-817. DOI: 10.1016/j.kint.2016.05.027
  8. Reid IR, Bolland MJ, Grey A. Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis. Lancet. 2013;383(9912):146-155. DOI: 10.1016/S0140-6736(13)61647-5
  9. Alshahrani F, Aljohani N. Vitamin D: deficiency, sufficiency and toxicity. Nutrients. 2013;5(9):3605-3616. DOI: 10.3390/nu5093605
  10. Khammissa RAG, Fourie J, Motswaledi MH, Ballyram R, Lemmer J, Feller L. The Biological Activities of Vitamin D and Its Receptor in Relation to Calcium and Bone Homeostasis, Cancer, Immune and Cardiovascular Systems, Skin Biology, and Oral Health. Biomed Res Int. 2018;2018(9276380):1-9. DOI: 10.1155/2018/9276380
  11. Diarrassouba F, Garrait G, Remondetto G, Alvarez P, Beyssac E, Subirade M. Improved bioavailability of vitamin D3 using a β-lactoglobulin-based coagulum. Food Chem. 2015;172(1):361-367. DOI: 10.1016/j.foodchem.2014.09.054
  12. Pan K, Zhong Q. Organic Nanoparticles in Foods: Fabrication, Characterization, and Utilization. Annu Rev Food Sci Technol. 2016;7:245-266. DOI: 10.1146/annurev-food-041715-033215
  13. Pedersen JN, Frislev HS, Pedersen JS, Otzen DE. Using protein-fatty acid complexes to improve vitamin D stability. J Dairy Sci. 2016;99(10):7755-7767. DOI: 10.3168/jds.2016-11343
  14. Pedersen JN, Frederix PWJ., Pedersen JS, Marrink SJ, Otzen DE. Role of Charge and Hydrophobicity in Liprotide Formation: A Molecular Dynamics Study with Experimental Constraints. ChemBioChem. 2018;19(3):263-271. DOI: 10.1002/cbic.201700496
  15. Pedersen JN, Sørensen H V., Otzen DE. Stabilising vitamin D3 using the molten globule state of α-lactalbumin. J Dairy Sci. 2018;101(3):1817-1826. DOI: 10.3168/jds.2017-13818
  16. Liu Y, Qiao Z, Liu W, et al. Oleic acid as a protein ligand improving intestinal absorption and ocular benefit of fucoxanthin in water through protein-based encapsulation. Food Funct. 2019;10(7):4381-4395. DOI: 10.1039/c9fo00814d
  17. Reeves PG, Nielsen FH, Fahey GC. AIN-93 Purified Diets for Laboratory Rodents: Final Report of the American Institute of Nutrition Ad Hoc Writing Committee on the Reformulation of the AIN-76A Rodent Diet. J Nutr. 1993;123(11):1939-1951. DOI: 10.1093/jn/123.11.1939
  18. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2003;77:204-210. DOI: 10.1093/ajcn/77.1.204
  19. Rodriguez-Ortiz ME, Lopez I, Muñoz-Castañeda JR, et al. Calcium Deficiency Reduces Circulating Levels of FGF23. J Am Soc Nephrol. 2012;23(7):1190-1197. DOI: 10.1681/ASN.2011101006
  20. Hernández-Becerra E, Gutiérrez-Cortez E, Real A Del, et al. Bone Mineral Density, Mechanical, Microstructural Properties and Mineral Content of the Femur in Growing Rats Fed with Cactus Opuntia ficus indica (L.) Mill. (Cactaceae) Cladodes as Calcium Source in Diet. Nutrients. 2017;9(108):1-17. DOI: 10.3390/nu9020108
  21. Klintström E, Smedby Ö, Klintström B, Brismar TB, Moreno R. Trabecular bone histomorphometric measurements and contrast-to-noise ratio in cone-beam computed tomography. Dentomaxillofac Radiol. 2014;43(8):1-22. DOI: 10.1259/dmfr.20140196
  22. Miyamoto T, Katsuyama E, Kanagawa H, et al. Vitamin D Deficiency with High Intact PTH Levels is More Common in Younger than in Older Women: A Study of Women Aged 39–64 Years. Keio J Med. 2016;65(2):33-38. DOI: 10.2302/kjm.2015-0010-oa
  23. Aoun A, Maalouf J, Fahed M, Jabbour F El. When and How to Diagnose and Treat Vitamin D Deficiency in Adults: A Practical and Clinical Update. J Diet Suppl. 2020;17(3):336-354. DOI: 10.1080/19390211.2019.1577935
  24. Leko MB, Plei´c N, Gunjaˇca I, Zemunik T. Environmental Factors That Affect Parathyroid Hormone and Calcitonin Levels. Int J Mol Sci. 2022;23(44):1-26. DOI: 10.3390%2Fijms23010044
  25. Manoy P, Yuktanandana P, Tanavalee A, et al. Vitamin D Supplementation Improves Quality of Life and Physical Performance in Osteoarthritis Patients. Nutrients. 2017;9(8):799-812. DOI: 10.3390/nu9080799
  26. Sakchareonkeat P, Huang T-C, Suwannaporn P, Chiang YH, Hsu JL, Hong YH. Encapsulation efficiency of coenzyme Q10-liposomes in alginate. Nutr Food Sci. 2013;43(2):150-160. DOI: 10.1108/00346651311313463
  27. Šimoliūnas E, Rinkūnaitė I, Bukelskienė Ž, Bukelskienė V. Bioavailability of different vitamin D oral supplements in laboratory animal model. Med. 2019;55(6):265-271. DOI: 10.3390/medicina55060265
  28. Diarrassouba F, Garrait G, Remondetto G, Alvarez P, Beyssac E, Subirade M. Increased stability and protease resistance of the β-lactoglobulin/vitamin D3 complex. Food Chem. 2014;145:646-652. DOI: 10.1016/j.foodchem.2013.08.075
  29. Teng Z, Luo Y, Li Y, Wang Q. Cationic beta-lactoglobulin nanoparticles as a bioavailability enhancer: effect of surface properties and size on the transport and delivery in vitro. Food Chem. 2016;204(1):391-399. DOI: 10.1016/j.foodchem.2016.02.139
  30. Hernández-Becerra E, Jímenez-Mendoza D, Mutis-Gonzalez N, Pineda-Gomez P, Rojas-Molina I, Rodríguez-García ME. Calcium Deficiency in Diet Decreases the Magnesium Content in Bone and Affects Femur Physicochemical Properties in Growing Rats. Biol Trace Elem Res. 2020;197(1):224-232. DOI: 10.1007/s12011-019-01989-9
  31. Kim C, Park D. The effect of restriction of dietary calcium on trabecular and cortical bone mineral density in the rats. J Exerc Nutr Biochem. 2013;17(4):123-131. DOI: 10.5717/jenb.2013.17.4.123
  32. Cooper DML, Kawalilak CE, Harrison K, Johnston BD, Johnston JD. Cortical Bone Porosity: What Is It, Why Is It Important, and How Can We Detect It? Curr Osteoporos Rep. 2016;14(5):187-198. DOI: 10.1007/s11914-016-0319-y
  33. Best A, Holt B, Troy K, Hamill J. Trabecular bone in the calcaneus of runners. PLoS One. 2017;12(11):1-14. DOI: 10.1371/journal.pone.0188200
  34. Sims NA, Vrahnas C. Regulation of cortical and trabecular bone mass by communication 5 between osteoblasts, osteocytes and osteoclasts. Arch Biochem Biophys. 2014;561(1):22-28. DOI: 10.1016/
  35. Frislev HS, Nielsen J, Nylandsted J, Otzen D. Using Liprotides to Deliver Cholesterol to the Plasma Membrane. J Membr Biol. 2018;1(4):581-592. DOI: 10.1007/s00232-018-0034-y
  36. Wsoo MA, Razak SIA, Bohari SPM, et al. Vitamin D3-loaded electrospun cellulose acetate/polycaprolactone nanofibers: Characterisation, in-vitro drug release and cytotoxicity studies. Int J Biol Macromol. 2021;181(1):82-98. DOI: 10.1016/j.ijbiomac.2021.03.108
  37. Cipriani C, Romagnoli E, Pepe J, et al. Long-Term Bioavailability After a Single Oral or IntramuscularAdministration of 600,000 IU of Ergocalciferol or Cholecalciferol: Implications for Treatment and Prophylaxis. J Clin Endocrinol Metab. 2013;98(7):2709-2715. DOI: 10.1210/jc.2013-1586
  38. Diarrassouba F, Remondetto G, Liang L, Garrait G, Beyssac E, Subirade M. Effects of gastrointestinal pH conditions on the stability of the β-lactoglobulin/vitamin D3 complex and on the solubility of vitamin D3. Food Res Int. 2013;52(2):515-521. DOI: 10.1016/j.foodres.2013.02.026
  39. Alsaqr A, Rasoully M, Musteata FM. Investigating Transdermal Delivery of Vitamin D3. AAPS PharmSciTech. 2015;16(4):963-973. DOI: 10.1208/s12249-015-0291-3
  40. Kitay AM, Geibel JP. Stomach and Bone. Adv Exp Med Biol. 2017;1033(1):97-131. DOI: 10.1007/978-3-319-66653-2_6
  41. Khundmiri SJ, Murray RD, Lederer E. PTH and Vitamin D. Compr Physiol. 2016;6(2):561-601. DOI: 10.1002/cphy.c140071
  42. Biondi P, Pepe J, Biamonte F, et al. Oral calcidiol is a good form of vitamin D supplementation. Clin Cases Miner Bone Metab. 2017;14(2):207-208. DOI: 10.11138/ccmbm/2017.14.1.207
  43. Szymczak-Pajor I, Śliwińska A. Analysis of Association between Vitamin D Deficiency and Insulin Resistance. Nutrients. 2019;11(4):794-821. DOI: 10.3390/nu11040794
  44. Jeon S-M, Shin E-A. Exploring vitamin D metabolism andfunction in cancer. Exp Mol Med. 2018;50(4):1-14. DOI: 10.1038/s12276-018-0038-9
  45. Rehman R, Alam F, Baig M, Khan AH, Naseer A. Editorial: vitamin D deficiency and sufficiency in reproduction and bone metabolism. Front Endocrinol (Lausanne). 2021;12(740021):1-3. DOI: 10.3389/fendo.2021.740021
  46. Combs GF, McClung JP. The Vitamins: Fundamental Aspects in Nutrition and Health. Fifth. Amsterdam: Elsevier Science; 2016
  47. Goltzman D, Mannstadt M, Marcocci C. Physiology of the Calcium-Parathyroid Hormone-Vitamin D Axis. Front Horm Res. 2018;50:1-13. DOI: 10.1159/000486060
  48. Lips P. Interaction between Vitamin D and Calcium. Scand J Clin Lab Investig. 2012;72(243):60-64. DOI: 10.3109/00365513.2012.681960
  49. Rejnmark L, Ejlsmark-Svensson H. Effects of PTH and PTH Hypersecretion on Bone: a Clinical Perspective. Curr Osteoporos Rep. 2020;18(3):103-114. DOI: 10.1007/s11914-020-00574-7
  50. Alwan A, Rassy N Al, Berro A-J, et al. Vitamin D and Trabecular Bone Score in a Group of Young Lebanese Adults. J Clin Densitom. 2018;21(3):453-458. DOI: 10.1016/j.jocd.2018.02.002
  51. Won DJ, Seong KS, Jang CH, et al. Effects of vitamin D2-fortified shiitake mushroom on bioavailability and bone structure. Biosci Biotechnol Biochem. 2019;83(5):942-951. DOI: 10.1080/09168451.2019.1576497
  52. Mao L, Tamura Y, Kawao N, et al. Influence of diabetic state and vitamin D deficiency on bone repair in female mice. Bone. 2014;61(1):102-108. DOI: 10.1016/j.bone.2013.12.024
  53. Sengupta P. The Laboratory Rat: Relating Its Age with Human’s. Int J Prev Med. 2013;4(6):624-630
  54. Andreollo NA, Santos EF dos, Araújo MR, Lopes LR. Rat’s age versus human’s age: what is the relationship? ABCD Arq Bras Cir Dig. 2012;25(1):49-51. DOI: 10.1590/S0102-67202012000100011

Last update:

No citation recorded.

Last update: 2024-06-17 05:06:43

No citation recorded.