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Rate of change of circulating 25-hydroxyvitamin D following sublingual and capsular vitamin D preparations

European Journal of Clinical Nutrition volume 73, pages 1630–1635 (2019)Cite this article

Subjects

Abstract

Background

Vitamin D is critical for skeletal health, and is increasingly associated with other pathologies encompassing gastrointestinal, immunological and psychological effects. A significant proportion of the population exhibits suboptimal levels of vitamin D, particularly in Northern latitudes in winter. Supplementation is advocated, but few data are available on achievable or typical rates of change. There has been considerable interest in the potential use of sublingual sprays for delivery of nutrient supplements, but data on efficacy remain sparse.

Methods

A randomised, placebo-controlled, three-arm parallel design study was conducted in healthy volunteers (n = 75) to compare the rate of change of vitamin D status in response to vitamin D3 (3000 IU/day) supplementation in capsule and sublingual spray preparations over a 6-week period between January and April 2017. Blood 25(OH)D concentrations were measured after day 0, 3, 7, 14, 21 and 42 days of supplementation with 3000 IU per diem.

Results

Baseline measurements show 25(OH)D deficiency (<30 nmol/l), insufficiency (31–46 nmol/l) and sufficiency (> 50 mmol/l) in 14.9, 44.6 and 40.5% of the participants, respectively. There was a significant elevation in blood concentrations of 25(OH)D in both of the treatment arms (capsule p = 0.003, spray p = 0.001) compared with control. The capsule and spray were equally efficacious. The rate of change ranged from 0.69 to 3.93 (capsule) and 0.64 to 3.34 (spray) nmol/L day with average change in blood 25(OH)D levels of 2 nmol/l/day. Rates followed a simple normal distribution in the study population (ks = 0.94 and 0.82 for capsule and spray, respectively). The data suggest that rates of change are higher in individuals with lower levels of 25(OH)D.

Conclusions

A sublingual vitamin D spray is an effective mode of delivery for supplementation in a healthy population. The data provide reference values and ranges for the rate of change of 25(OH)D for nutrikinetic analyses.

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References

  1. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 Report on dietary reference intakes for calcium and vitamin D from the institute of medicine: what clinicians need to know. Obstet Gynecol Gynecol Surv. 2011;66:356–7.

    Article  Google Scholar 

  2. Calvo MS, Whiting SJ, Barton CN. Vitamin D intake: a global perspective of current status. J Nutr. 2005;135:310–6.

    Article  CAS  Google Scholar 

  3. Holick MF. Vitamin D: physiology, molecular biology, and clinical applications, 2nd edn. Totowa: Humana; 2010.

  4. Institute of Medicine. Dietary reference intakes for calcium and vitamin D. Washington, DC: The National Academies Press; 2011.

  5. Holick M, Biancuzzo RM, Chen TC, Klein E, Young A, Bibuld D, et al. Vitamin D-2 is as effective as vitamin D-3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab. 2008;93:677–81.

    Article  CAS  Google Scholar 

  6. Palacios C, Gonzalez L. Is vitamin D deficiency a major global public health problem? J Steroid Biochem Mol Biol. 2014;144:138–45.

    Article  CAS  Google Scholar 

  7. SACN (Scientific Advisory Committee on Nutrition). Vitamin D and health report. London: TSO; 2016.

  8. Aloia JF, Patel M, Dimaano R, Li-Ng M, Talwar SA, Mikhail M, et al. Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration. Am J Clin Nutr. 2008;87:1952–8.

    Article  CAS  Google Scholar 

  9. Golzarand M, Hollis BW, Mirmiran P, Wagner CL, Shab-Bidar S. Vitamin D supplementation and body fat mass: a systematic review and meta- analysis. Eur J Clin Nutr. 2018;72:1345–57.

    Article  CAS  Google Scholar 

  10. Ng K, Scott J, Drake B, Chan A, Hollis B, Chandler P, et al. Dose response to vitamin D supplementation in African Americans: results of a 4-arm, randomized, placebo-controlled trial. Am J Clin Nutr. 2014;99:587–98.

    Article  CAS  Google Scholar 

  11. Gallagher J, Sai A, Templin T, Smith L. Dose response to vitamin D supplementation in postmenopausal women a randomized trial. Ann Intern Med. 2012;156:425–76.

    Article  Google Scholar 

  12. Lips P, Wiersinga A, van Ginkel FC, Jongen MJ, Netelenbos JC, Hackeng WH, et al. The effect of vitamin D supplementation on vitamin D status and parathyroid function in elderly subjects. J Clin Endocrinol Metab. 1988;67:644–50.

    Article  CAS  Google Scholar 

  13. Shea RL, Berg JD. Self-administration of vitamin D supplements in the general public may be associated with high 25-hydroxyvitamin D concentrations. Ann Clin Biochem. 2016;54:355–61.

    Article  Google Scholar 

  14. Tai S, Bedner M, Phinney K. Development of a candidate reference measurement procedure for the determination of 25-hydroxyvitamin D-3 and 25-hydroxyvitamin D-2 in human serum using isotope-dilution liquid chromatography-tandem mass spectrometry. Anal Chem. 2010;82:1942–8.

    Article  CAS  Google Scholar 

  15. Farrell C-JL, Martin S, McWhinney B, Straub I, Williams P, Herrmann M. State-of-the-art vitamin D assays: a comparison of automated immunoassays with liquid chromatography-tandem mass spectrometry methods. Clin Chem. 2012;58:531–42.

    Article  CAS  Google Scholar 

  16. Loveday SJ, Thompson JM, Mitchell EA. Bioelectrical impedance for measuring percentage body fat in young persons with Down syndrome: validation with dual‐ energy absorptiometry. Acta Paediatr. 2012;101:e491–5.

    Article  Google Scholar 

  17. Mo M, Wang S, Chen Z, Muyiduli X, Wang S, Shen Y, et al. A systematic review and meta- analysis of the response of serum 25-hydroxyvitamin D concentration to vitamin D supplementation from RCTs from around the globe. Eur J Clin Nutr. 2019;73:816–34.

    Article  CAS  Google Scholar 

  18. Lips P, Duong T, Oleksik A, Black D, Cummings S, Cox D, et al. A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the multiple outcomes of raloxifene evaluation clinical trial. J Clin Endocrinol Metab. 2001;86:1212–21.

    Article  CAS  Google Scholar 

  19. Dali MM, Moench PA, Mathias NR, Stetsko PI, Heran CL, Smith RL. A rabbit model for sublingual drug delivery: comparison with human pharmacokinetic studies of propranolol, verapamil and captopril. J Pharm Sci. 2006;95:37–44.

    Article  CAS  Google Scholar 

  20. Bialy LP, Wojcik C, Mlynarczuk-Bialy I. Mucosal delivery systems of antihypertensive drugs: a practical approach in general practice. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2018;162:71–8.

    Article  Google Scholar 

  21. Satia MC, Mukim AG, Tibrewala K, Bhavsar MS. A randomized two way cross over study for comparison of absorption of vitamin D3 buccal spray and soft gelatin capsule formulation in healthy subjects and in patients with intestinal malabsorption. Nutr J. 2015;14:1–9.

    Article  Google Scholar 

  22. Heaney RP, Armas LAG, Shary JR, Bell NH, Binkley N, Hollis BW. 25-Hydroxylation of vitamin D 3: relation to circulating vitamin D 3 under various input conditions. Am J Clin Nutr. 2008;87:1738–42.

    Article  CAS  Google Scholar 

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Funding

This work was jointly supported by BetterYou Ltd and The University of Sheffield.

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Authors and Affiliations

  1. Molecular Gastroenterology Research Group, Academic Unit of Surgical Oncology, Department of Oncology & Metabolism, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK

    Claire E. Williams & Bernard M. Corfe

  2. Department of Oncology & Metabolism, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK

    Elizabeth A. Williams

  3. Insigneo Institute for In Silico Medicine, The University of Sheffield, Sheffield, UK

    Bernard M. Corfe

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  1. Claire E. Williams
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Correspondence to Bernard M. Corfe.

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Conflict of interest

BetterYou co-funded this PhD and provided the supplements and placebos. This sponsor was not involved in the study design, delivery or interpretation of the data, which was undertaken entirely by The University of Sheffield. The authors declare that they have no conflict of interest.

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Williams, C.E., Williams, E.A. & Corfe, B.M. Rate of change of circulating 25-hydroxyvitamin D following sublingual and capsular vitamin D preparations. Eur J Clin Nutr 73, 1630–1635 (2019). https://doi.org/10.1038/s41430-019-0503-0

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