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

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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.


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.


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.


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

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Correspondence to Bernard M. Corfe.

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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 (2019) doi:10.1038/s41430-019-0503-0

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