Recent Advances in Formulation Strategies for Efficient Delivery of Vitamin D
AAPS PharmSciTech, January 2019, 20:11; https://doi.org/10.1208/s12249-018-1231-9
Rahul Gupta Chittaranjan Behera Gourav Paudwal Neha Rawat Ashish Baldi Prem N. Gupta
Review Article Theme: Lipid-Based Drug Delivery Strategies for Oral Drug Delivery
Forms of Vitamin D category listing has 113 items along with related searches
- Nanoemulsion Vitamin D is faster and better - many studies
- Vitamin D – food fortification around the world, types of microencapsulation – Feb 2020
- Liposomal Vitamin D cocktail targets some lung cancers – June 2018
- Nanoemulsion Vitamin D may be a substantially better form
- The lungs can activate vitamin D locally – a Vitamin D inhaler may help lungs – Aug 2016
- Nanoparticles could be used to increase vitamin D getting to the gut – Oct 2015
- Vitamin D Emulsions - nano 2X better than coarse – Dec 2017
Other Emulsified supplements are also good
Deficiency of vitamin D is a global concern affecting a huge number of human populations. This deficiency has a serious impact on human health not only affecting bone mineral density but also becoming the reason for cardiovascular disorders, infectious diseases, autoimmune diseases and cancers. Exposure to sunlight is the major source of vitamin D, but due to the present day-to-day lifestyle of working in a shade arouses the need for exogenous sources of vitamin D. Ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) are the two major forms of vitamin D, which are hydrophobic in nature and highly susceptible to environmental conditions, like temperature and light. Therefore, novel drug delivery systems could be explored for efficient delivery of vitamin D. In this review, a brief account of vitamin D is provided followed by a detailed description of recent advances in various delivery systems, including solid lipid nanoparticles, nanoemulsion, self-emulsifying drug delivery systems, polymeric nanoparticles and solid dispersion, for the efficient delivery of vitamin D.
References
1.
Hwalla N, Al-Dhaheri AS, Radwan H, Alfawaz HA, Fouda MA, Al-Daghri NM, et al. The prevalence of micronutrient deficiencies and inadequacies in the Middle East and approaches to interventions. Nutrients. 2017;9(3):228.
2.
Gupta R, Gupta A. Vitamin D deficiency in India: prevalence, causalities and interventions. Nutrients. 2014;6(2):729–75.
3.
Kennel KA, Drake MT, Hurley DL. Vitamin D deficiency in adults: when to test and how to treat. Mayo Clin Proc. 2010;85(8):752–8.
4.
Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc. Elsevier. 2017;86(1):50–60.
5.
Mostafa WZ, Hegazy RA. Vitamin D and the skin: focus on a complex relationship: a review. J Adv Res. 2015;6(6):793–804.
6.
FAO/WHO. Human vitamins and mineral requirements. In: Report of a joint FAO/WHO expert consultation in Bangkok, Thailand. FAO and Nutrition Division FAO Rome. 2001. http://www.fao.org/3/a-y2809e.pdf. Accessed 10 Dec 2017.
7.
Lavie CJ, Lee JH, Milani RV. Vitamin D and cardiovascular disease. J Am Coll Cardiol. 2011;58(15):1547–56.
8.
Joergensen C, Gall M-A, Schmedes A, Tarnow L, Parving H-H, Rossing P. Vitamin D levels and mortality in type 2 diabetes. Diabetes Care. 2010;33(10):2238 LP–2243.
9.
Schwalfenberg G. Vitamin D and diabetes: improvement of glycemic control with vitamin D3 repletion. Can Fam Physician. 2008;54(6):864–6.
10.
Tuohimaa P. Vitamin D, aging, and cancer. Nutr Rev. 2008;66(SUPPL.2):147–52.
11.
Garland CF, Gorham ED, Mohr SB, Garland FC. Vitamin D for cancer prevention: global perspective. Ann Epidemiol. 2009;19(7):468–83.
12.
Vitamin D: fact sheet for health professionals. NIH Office of Dietary Supplements, USA. 2018. https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/. Accessed 20 Dec 2017.
13.
Hollick M, Vitamin D. Treatment guidelines. In: Munjal YP, editor. Medicine update. India: The Association of Physicians of India; 2013. p. 619–25.
14.
Ross AC, Taylor CL, Yaktine AL, Valle HBD. Dietary reference intakes for calcium and vitamin D. US: National Academic Press; 2011.
15.
Mcneill AM, Wesner E. Sun protection and vitamin D. Skin Cancer Foundation J. 2016. https://www.skincancer.org/healthy-lifestyle/vitamin-d/damage. Accessed 25 Jan 2018.
16.
Clemens TL, Adams JS, Henderson SL, Holick MF. Increased skin pigment reduces the capacity of skin to synthesise vitamin D3. Lancet (London, England). 1982;1(8263):74–6.
17.
Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–81.
18.
Patients O, Lagunova Z, Porojnicu AC, Vieth R, F a L, Hexeberg S, et al. Serum 25-hydroxyvitamin D is a predictor of serum 1, 25-dihydroxyvitamin D in overweight and obese patients. J Nutr. 2011;141(1):112–7.
19.
Mazahery H, von Hurst PR. Factors affecting 25-hydroxyvitamin D concentration in response to vitamin D supplementation. Nutrients. 2015;7(7):5111–42.
20.
Grey A, Lucas J, Horne A, Gamble G, Davidson JS, Reid IR. Vitamin D repletion in patients with primary hyperparathyroidism and coexistent vitamin D insufficiency. J Clin Endocrinol Metab. 2005;90(4):2122–6.
21.
Adams JS, Hewison M. Hypercalcemia caused by granuloma forming disorders. In: Favus MJ, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism. Washington DC: American Society for Bone and Mineral Research; 2006. p. 200–2.
22.
Wagner CL, Greer FR. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics. 2008;122(5):1142–52.
23.
MacLaughlin J, Holick MF. Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest. 1985;76(4):1536–8.
24.
Mithal A, Wahl DA, Bonjour J-P, Burckhardt P, Dawson-Hughes B, Eisman JA, et al. Global vitamin D status and determinants of hypovitaminosis D. Osteoporos Int. 2009;20(11):1807–20.
25.
Bruyere O, Slomian J, Beaudart C, Buckinx F, Cavalier E, Gillain S, et al. Prevalence of vitamin D inadequacy in European women aged over 80 years. Arch Gerontol Geriatr. 2014;59(1):78–82.
26.
O’Keefe JH, Patil HR, Lavie CJ. Can vitamin D deficiency break your heart? Mayo Clin Proc. Elsevier Inc. 2012;87(4):412–3.
27.
O’Mahony L, Stepien M, Gibney MJ, Nugent AP, Brennan L. The potential role of vitamin D enhanced foods in improving vitamin D status. Nutrients. 2011;3(12):1023–41.
28.
Japelt RB, Jakobsen J. Vitamin D in plants: a review of occurrence, analysis, and biosynthesis. Front Plant Sci. 2013;4(136):1–20.
29.
National Center for Biotechnology Information. National library of medicine. USA: PubChem. https://pubchem.ncbi.nlm.nih.gov/. Accessed 11 Oct 2017
30.
DeLuca HF. The vitamin D story: a collaborative effort of basic science and clinical medicine. FASEB J Off Publ Fed Am Soc Exp Biol. 1988;2(3):224–36.
31.
Holick MF, Chen TC, Lu Z, Sauter E. Vitamin D and skin physiology: a D-lightful story. J Bone Miner Res. 2007;22(SUPPL. 2):V28–33.
32.
Hollis BW. Comparison of equilibrium and disequilibrium assay conditions for ergocalciferol, cholecalciferol and their major metabolites. J Steroid Biochem. 1984;21(1):81–6.
33.
Houghton LA, Vieth R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr. 2006;84(4):694–7.
34.
Cheng JB, Motola DL, Mangelsdorf DJ, Russell DW. De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase. J Biol Chem. 2003;278(39):38084–93.
35.
Cheng JB, Levine MA, Bell NH, Mangelsdorf DJ, Russell DW. Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc Natl Acad Sci. 2004;101(20):7711–5.
36.
Horst RL, Reinhardt TA, Ramberg CF, Koszewski NJ, Napoli JL. 24-Hydroxylation of 1,25-dihydroxyergocalciferol. An unambiguous deactivation process. J Biol Chem. 1986;261(20):9250–6.
PubMed37.
Heaney RP, Recker RR, Grote J, Horst RL, Armas LAG. Vitamin D(3) is more potent than vitamin D(2) in humans. J Clin Endocrinol Metab. 2011;96(3):E447–52.
38.
Romagnoli E, Mascia ML, Cipriani C, Fassino V, Mazzei F, D’Erasmo E, et al. Short and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly. J Clin Endocrinol Metab. 2008;93(8):3015–20.
39.
Armas LAG, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004;89(11):5387–91.
40.
Glendenning P, Chew GT, Seymour HM, Gillett MJ, Goldswain PR, Inderjeeth CA, et al. Serum 25-hydroxyvitamin D levels in vitamin D-insufficient hip fracture patients after supplementation with ergocalciferol and cholecalciferol. Bone. 2009;45(5):870–5.
41.
Leventis P, Kiely PDW. The tolerability and biochemical effects of high-dose bolus vitamin D2 and D3 supplementation in patients with vitamin D insufficiency. Scand J Rheumatol. 2009;38(2):149–53.
42.
Perry CL, Mcguire MT, Neumark-Sztainer D, Story M. Characteristics of vegetarian adolescents in a multiethnic urban population. J Adolesc Health. 2001;29(6):406–16.
43.
Key TJ, Appleby PN, Rosell MS. Health effects of vegetarian and vegan diets. Proc Nutr Soc. 2006;65(01):35–41.
44.
Wacker M, Holick MF. Sunlight and vitamin D: a global perspective for health. Dermatoendocrinol Landes Biosci. 2013;5(1):51–108.
45.
Zand L, Kumar R. The use of vitamin D metabolites and analogues in the treatment of chronic kidney disease. Endocrinol Metab Clin N Am. Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic. 2017;46(4):983–1007.
46.
Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA, et al. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int. 2007;71(1):31–8.
47.
DeLuca HF. Chemistry, metabolism, and circulation. In: Feldman D, Pike WJ, Adams J, editors. Vitamin D. San Diego: Academic Press; 2005. p. 3–11.
48.
Plum LA, DeLuca HF. The functional metabolism and molecular biology of vitamin D action. Clin Rev Bone Miner Metab. 2009;7(1):20–41.
49.
Cunningham J, Zehnder D. New vitamin D analogs and changing therapeutic paradigms. Kidney Int. Nature Publishing Group. 2011;79(7):702–7.
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Plum LA, DeLuca HF. Vitamin D, disease and therapeutic opportunities. Nat Rev Drug Discov. 2010;9(12):941–55.
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Patel MR, San Martin-Gonzalez MF. Characterization of ergocalciferol loaded solid lipid nanoparticles. J Food Sci. 2012;77(1):8–11.
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Demirbilek M, Lacin Turkoglu N, Akturk S, Akca C. VitD3-loaded solid lipid nanoparticles: stability, cytotoxicity and cytokine levels. J Microencapsul. 2017;34(5):454–62.
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Kumar M, Sharma G, Singla D, Singh S, Sahwney S, Chauhan AS, et al. Development of a validated UPLC method for simultaneous estimation of both free and entrapped (in solid lipid nanoparticles) all-trans retinoic acid and cholecalciferol (vitamin D3) and its pharmacokinetic applicability in rats. J Pharm Biomed Anal. 2014;91:73–80.
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Kohli K, Chopra S, Arora S, Khar RK, Pillai KK. Self-emulsifying drug delivery system for a curcuminoid based composition. United States patent, US 8835509B2. 2014. 16.
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Boardman D, Karki S, Leyes A, Ostovic D. Process for preparing stabilized vitamin D. United States patent, US 0019933A1. 2006. 26.
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Nguyen TLU, Tey SY, Pourgholami MH, Morris DL, Davis TP, Barner-Kowollik C, et al. Synthesis of semi-biodegradable crosslinked microspheres for the delivery of 1,25 dihydroxyvitamin D3 for the treatment of hepatocellular carcinoma. Eur Polym J. 2007;43(5):1754–67.
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Luo Y, Teng Z, Wang Q. Development of zein nanoparticles coated with carboxymethyl chitosan for encapsulation and controlled release of vitamin D3. J Agric Food Chem. 2012;60(3):836–43.
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Vora L, VG S, Vavia P. Zero order controlled release delivery of cholecalciferol from injectable biodegradable microsphere: in-vitro characterization and in-vivo pharmacokinetic studies. Eur J Pharm Sci. 2017;107:78–86.
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Huatan H. Vitamin D composition. European patent, EP 2680826B1. 2017. 23.
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Bothiraja C, Pawar A, Deshpande G. Ex-vivo absorption study of a nanoparticle based drug delivery system of vitamin D3 (Arachitol Nano™) using everted intestinal sac technique. J Pharm Investig. 2016;46(5):425–32.
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Sun P, Pan K, Wu Y. Dronedarone solid dispersion and preparation method thereof. United States patent, US 8921416B2. 2014. 30.
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Mahmoud MFAK, Ebeed MAMK. Homogeneous preparations containing vitamin D. European patent, EP 2468265A3. 2013. 2.
82.
Jin JN, Woo JS, Yi HG. Complex formulation for preventing or treating osteoporosis which comprises solid dispersion of vitamin D or its derivative and bisphosphonate. United States patent, US 0048511A1. 2010. 25.
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Gupta, R., Behera, C., Paudwal, G. et al. AAPS PharmSciTech (2019) 20: 11.
Advances in Vitamin D emulsions, nanoparticles, etc. – Jan 2019
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This page is in the following categories (# of items in each category)
- Nanoemulsion Vitamin D is faster and better - many studies
- Vitamin D – food fortification around the world, types of microencapsulation – Feb 2020
- Liposomal Vitamin D cocktail targets some lung cancers – June 2018
- Nanoemulsion Vitamin D may be a substantially better form
- The lungs can activate vitamin D locally – a Vitamin D inhaler may help lungs – Aug 2016
- Nanoparticles could be used to increase vitamin D getting to the gut – Oct 2015
- Vitamin D Emulsions - nano 2X better than coarse – Dec 2017
Other Emulsified supplements are also good
Deficiency of vitamin D is a global concern affecting a huge number of human populations. This deficiency has a serious impact on human health not only affecting bone mineral density but also becoming the reason for cardiovascular disorders, infectious diseases, autoimmune diseases and cancers. Exposure to sunlight is the major source of vitamin D, but due to the present day-to-day lifestyle of working in a shade arouses the need for exogenous sources of vitamin D. Ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) are the two major forms of vitamin D, which are hydrophobic in nature and highly susceptible to environmental conditions, like temperature and light. Therefore, novel drug delivery systems could be explored for efficient delivery of vitamin D. In this review, a brief account of vitamin D is provided followed by a detailed description of recent advances in various delivery systems, including solid lipid nanoparticles, nanoemulsion, self-emulsifying drug delivery systems, polymeric nanoparticles and solid dispersion, for the efficient delivery of vitamin D.
References
1.
Hwalla N, Al-Dhaheri AS, Radwan H, Alfawaz HA, Fouda MA, Al-Daghri NM, et al. The prevalence of micronutrient deficiencies and inadequacies in the Middle East and approaches to interventions. Nutrients. 2017;9(3):228.
2.
Gupta R, Gupta A. Vitamin D deficiency in India: prevalence, causalities and interventions. Nutrients. 2014;6(2):729–75.
3.
Kennel KA, Drake MT, Hurley DL. Vitamin D deficiency in adults: when to test and how to treat. Mayo Clin Proc. 2010;85(8):752–8.
4.
Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc. Elsevier. 2017;86(1):50–60.
5.
Mostafa WZ, Hegazy RA. Vitamin D and the skin: focus on a complex relationship: a review. J Adv Res. 2015;6(6):793–804.
6.
FAO/WHO. Human vitamins and mineral requirements. In: Report of a joint FAO/WHO expert consultation in Bangkok, Thailand. FAO and Nutrition Division FAO Rome. 2001. http://www.fao.org/3/a-y2809e.pdf. Accessed 10 Dec 2017.
7.
Lavie CJ, Lee JH, Milani RV. Vitamin D and cardiovascular disease. J Am Coll Cardiol. 2011;58(15):1547–56.
8.
Joergensen C, Gall M-A, Schmedes A, Tarnow L, Parving H-H, Rossing P. Vitamin D levels and mortality in type 2 diabetes. Diabetes Care. 2010;33(10):2238 LP–2243.
9.
Schwalfenberg G. Vitamin D and diabetes: improvement of glycemic control with vitamin D3 repletion. Can Fam Physician. 2008;54(6):864–6.
10.
Tuohimaa P. Vitamin D, aging, and cancer. Nutr Rev. 2008;66(SUPPL.2):147–52.
11.
Garland CF, Gorham ED, Mohr SB, Garland FC. Vitamin D for cancer prevention: global perspective. Ann Epidemiol. 2009;19(7):468–83.
12.
Vitamin D: fact sheet for health professionals. NIH Office of Dietary Supplements, USA. 2018. https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/. Accessed 20 Dec 2017.
13.
Hollick M, Vitamin D. Treatment guidelines. In: Munjal YP, editor. Medicine update. India: The Association of Physicians of India; 2013. p. 619–25.
14.
Ross AC, Taylor CL, Yaktine AL, Valle HBD. Dietary reference intakes for calcium and vitamin D. US: National Academic Press; 2011.
15.
Mcneill AM, Wesner E. Sun protection and vitamin D. Skin Cancer Foundation J. 2016. https://www.skincancer.org/healthy-lifestyle/vitamin-d/damage. Accessed 25 Jan 2018.
16.
Clemens TL, Adams JS, Henderson SL, Holick MF. Increased skin pigment reduces the capacity of skin to synthesise vitamin D3. Lancet (London, England). 1982;1(8263):74–6.
17.
Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–81.
18.
Patients O, Lagunova Z, Porojnicu AC, Vieth R, F a L, Hexeberg S, et al. Serum 25-hydroxyvitamin D is a predictor of serum 1, 25-dihydroxyvitamin D in overweight and obese patients. J Nutr. 2011;141(1):112–7.
19.
Mazahery H, von Hurst PR. Factors affecting 25-hydroxyvitamin D concentration in response to vitamin D supplementation. Nutrients. 2015;7(7):5111–42.
20.
Grey A, Lucas J, Horne A, Gamble G, Davidson JS, Reid IR. Vitamin D repletion in patients with primary hyperparathyroidism and coexistent vitamin D insufficiency. J Clin Endocrinol Metab. 2005;90(4):2122–6.
21.
Adams JS, Hewison M. Hypercalcemia caused by granuloma forming disorders. In: Favus MJ, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism. Washington DC: American Society for Bone and Mineral Research; 2006. p. 200–2.
22.
Wagner CL, Greer FR. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics. 2008;122(5):1142–52.
23.
MacLaughlin J, Holick MF. Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest. 1985;76(4):1536–8.
24.
Mithal A, Wahl DA, Bonjour J-P, Burckhardt P, Dawson-Hughes B, Eisman JA, et al. Global vitamin D status and determinants of hypovitaminosis D. Osteoporos Int. 2009;20(11):1807–20.
25.
Bruyere O, Slomian J, Beaudart C, Buckinx F, Cavalier E, Gillain S, et al. Prevalence of vitamin D inadequacy in European women aged over 80 years. Arch Gerontol Geriatr. 2014;59(1):78–82.
26.
O’Keefe JH, Patil HR, Lavie CJ. Can vitamin D deficiency break your heart? Mayo Clin Proc. Elsevier Inc. 2012;87(4):412–3.
27.
O’Mahony L, Stepien M, Gibney MJ, Nugent AP, Brennan L. The potential role of vitamin D enhanced foods in improving vitamin D status. Nutrients. 2011;3(12):1023–41.
28.
Japelt RB, Jakobsen J. Vitamin D in plants: a review of occurrence, analysis, and biosynthesis. Front Plant Sci. 2013;4(136):1–20.
29.
National Center for Biotechnology Information. National library of medicine. USA: PubChem. https://pubchem.ncbi.nlm.nih.gov/. Accessed 11 Oct 2017
30.
DeLuca HF. The vitamin D story: a collaborative effort of basic science and clinical medicine. FASEB J Off Publ Fed Am Soc Exp Biol. 1988;2(3):224–36.
31.
Holick MF, Chen TC, Lu Z, Sauter E. Vitamin D and skin physiology: a D-lightful story. J Bone Miner Res. 2007;22(SUPPL. 2):V28–33.
32.
Hollis BW. Comparison of equilibrium and disequilibrium assay conditions for ergocalciferol, cholecalciferol and their major metabolites. J Steroid Biochem. 1984;21(1):81–6.
33.
Houghton LA, Vieth R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr. 2006;84(4):694–7.
34.
Cheng JB, Motola DL, Mangelsdorf DJ, Russell DW. De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase. J Biol Chem. 2003;278(39):38084–93.
35.
Cheng JB, Levine MA, Bell NH, Mangelsdorf DJ, Russell DW. Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc Natl Acad Sci. 2004;101(20):7711–5.
36.
Horst RL, Reinhardt TA, Ramberg CF, Koszewski NJ, Napoli JL. 24-Hydroxylation of 1,25-dihydroxyergocalciferol. An unambiguous deactivation process. J Biol Chem. 1986;261(20):9250–6.
PubMed37.
Heaney RP, Recker RR, Grote J, Horst RL, Armas LAG. Vitamin D(3) is more potent than vitamin D(2) in humans. J Clin Endocrinol Metab. 2011;96(3):E447–52.
38.
Romagnoli E, Mascia ML, Cipriani C, Fassino V, Mazzei F, D’Erasmo E, et al. Short and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly. J Clin Endocrinol Metab. 2008;93(8):3015–20.
39.
Armas LAG, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004;89(11):5387–91.
40.
Glendenning P, Chew GT, Seymour HM, Gillett MJ, Goldswain PR, Inderjeeth CA, et al. Serum 25-hydroxyvitamin D levels in vitamin D-insufficient hip fracture patients after supplementation with ergocalciferol and cholecalciferol. Bone. 2009;45(5):870–5.
41.
Leventis P, Kiely PDW. The tolerability and biochemical effects of high-dose bolus vitamin D2 and D3 supplementation in patients with vitamin D insufficiency. Scand J Rheumatol. 2009;38(2):149–53.
42.
Perry CL, Mcguire MT, Neumark-Sztainer D, Story M. Characteristics of vegetarian adolescents in a multiethnic urban population. J Adolesc Health. 2001;29(6):406–16.
43.
Key TJ, Appleby PN, Rosell MS. Health effects of vegetarian and vegan diets. Proc Nutr Soc. 2006;65(01):35–41.
44.
Wacker M, Holick MF. Sunlight and vitamin D: a global perspective for health. Dermatoendocrinol Landes Biosci. 2013;5(1):51–108.
45.
Zand L, Kumar R. The use of vitamin D metabolites and analogues in the treatment of chronic kidney disease. Endocrinol Metab Clin N Am. Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic. 2017;46(4):983–1007.
46.
Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA, et al. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int. 2007;71(1):31–8.
47.
DeLuca HF. Chemistry, metabolism, and circulation. In: Feldman D, Pike WJ, Adams J, editors. Vitamin D. San Diego: Academic Press; 2005. p. 3–11.
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