Vitamin D: Bolus Is Bogus—A Narrative Review

Abstract

In this review we summarize the impact of bolus versus daily dosing of vitamin D on 25(OH)D and 1,25(OH) 2 D levels, as well as on key countervailing factors that block vitamin D functions at the cellular level. Further, we discuss the role of bolus versus daily dosing of vitamin D for several health outcomes, including respiratory infections and coronavirus disease 2019 (COVID-19), rickets, falls and fractures, any cancer, and cancer-related mortality. This discussion appears timely because bolus doses continue to be tested for various disease outcomes despite a growing amount of evidence suggesting lack of efficacy or even detrimental effects of bolus dosing of vitamin D for outcomes where daily dosing at modest levels was effective in the vitamin D deficient. As a result, these discordant results may bias health recommendations for vitamin D if the recommendations are based on meta-analyses combining both daily and bolus dosing trials.

The Interaction of Vitamin D and Corticosteroids: A Mortality Analysis of 26,508 Veterans Who Tested Positive for SARS-CoV-2

“…Given the recent results of the randomized placebo-controlled trial of a one-time bolus of high-dose Vit D, which showed no improvement in hospital length of stay in COVID-19 patients [ 36 ], it is noteworthy that Vit D use by patients in our study was generally low-dose daily administration from days to weeks post-COVID-19 diagnosis. There is ample evidence that chronic, daily Vit D dosing is superior to bolus high-dose administration for many reasons, several of which have been summarized in recent publications [ 122 , 123 , 124 ]. For example, a single high dose of Vit D, versus daily administration, has been reported to activate the 24-hydroxylase enzyme (CYP24A1), leading to increased production of the inactive form of Vit D (i.e., 24,25(OH) 2 D 3 ) [ 125 ].…”

Clinical Practice in the Prevention, Diagnosis and Treatment of Vitamin D Deficiency: A Central and Eastern European Expert Consensus Statement

“…Daily, weekly, or monthly vitamin D supplementation, at equivalent doses, lead to similar increases in 25(OH)D serum concentrations, when measured after 2 to 3 months [ 65 , 66 , 67 ]. Adherence may be better with intermittent vitamin D dosing, but there are also concerns that high intermittent vitamin D doses may be less beneficial or might even be harmful in certain settings [ 67 , 68 , 69 ].…”

“…Daily, weekly, or monthly vitamin D supplementation, at equivalent doses, lead to similar increases in 25(OH)D serum concentrations, when measured after 2 to 3 months [ 65 , 66 , 67 ]. Adherence may be better with intermittent vitamin D dosing, but there are also concerns that high intermittent vitamin D doses may be less beneficial or might even be harmful in certain settings [ 67 , 68 , 69 ]. In view of the available evidence from clinical vitamin D trials and some pathophysiological considerations (e.g., altered vitamin D metabolism with high intermittent vitamin D doses), a daily vitamin D dosing schedule should rather be preferred, but when exceedingly high intermittent vitamin D doses are avoided, a weekly or monthly dosing schedule can also be applied [ 66 , 67 ].…”

“…Adherence may be better with intermittent vitamin D dosing, but there are also concerns that high intermittent vitamin D doses may be less beneficial or might even be harmful in certain settings [ 67 , 68 , 69 ]. In view of the available evidence from clinical vitamin D trials and some pathophysiological considerations (e.g., altered vitamin D metabolism with high intermittent vitamin D doses), a daily vitamin D dosing schedule should rather be preferred, but when exceedingly high intermittent vitamin D doses are avoided, a weekly or monthly dosing schedule can also be applied [ 66 , 67 ]. The panel members could not reach a clear consensus on a clear cut-off for exceedingly high vitamin D doses, but single doses above about 50,000 IU of vitamin D should rather be avoided.…”

Bone Fragility in Chronic Kidney Disease Stage 3 to 5: The Use of Vitamin D Supplementation

“…A large meta-analysis reported no beneficial effect of vitamin D versus placebo or vitamin D + calcium versus calcium [ 64 ]. However, this meta-analysis included studies that recruited a relatively low number of participants or used either very low daily doses (400 UI/day) or very high intermittent (300,000–500,000 IU/year) doses, two actions known to have either no effect (very low doses) or even detrimental effects (very high intermittent doses) on the risk of falls and fractures by mechanisms not yet understood [ 65 ]. When the analysis was restricted to RCTs that used daily vitamin D doses of 800–1000 IU (8 RCTs), the conclusion was that vitamin D reduced the risk of fracture by 14% (RR 0.86, 95% CI 0.75–0.98) compared to placebo [ 66 ].…”