Large, Single-Dose, Oral Vitamin D Supplementation in Adult Populations: A Systematic Review

doi:10.4158/EP13265.RA

Endocrine Practice

Volume 20, Issue 4, April 2014, Pages 341-351

https://doi.org/10.4158/EP13265.RA Get rights and content

ABSTRACT

Objective

Daily vitamin D supplementation is often inadequate in treating vitamin D deficiency due to poor compliance. A single, large dose of vitamin D given at timed intervals may be an alternative strategy.

Methods

We conducted a systematic literature review to investigate the efficacy of a single large bolus dose to treat vitamin D deficiency. We identified 2,243 articles in PubMed using the terms “high dose vitamin D,” “single dose vitamin D,” “bolus vitamin D,” or “annual dose vitamin D.” Review articles, cross-sectional studies, non-human studies, responses to other articles, and non-English articles were excluded. Manuscripts were also excluded if the study: (1) did not use oral cholecalciferol or ergocalciferol, (2) used vitamin D analogs, (3) enrolled participants under age 18 years, (4) administered doses < 100,000 international units (IU) (2.5 mg), or (5) administered > 1 dose per year. References of eligible manuscripts and the Cochrane databases were also searched. Two independent reviewers identified eligible manuscripts, and a third reviewer evaluated disagreements. Thirty manuscripts were selected using these criteria.

Results

Large, single doses of vitamin D consistently increased serum/plasma 25-hydroxyvitamin D (25[OH]D) concentrations in several vitamin D-sufficient and -deficient populations. Vitamin D₃ doses ≥ 300,000 IU provided optimal changes in serum/plasma 25(OH)D and parathyroid hormone (PTH) concentrations. Vitamin D supplementation also impacted bone health and extraskeletal endpoints.

Conclusion

This review recommends that vitamin D₃ be used for supplementation over vitamin D₂ and concludes that single vitamin D₃ doses ≥ 300,000 IU are most effective at improving vitamin D status and suppressing PTH concentrations for up to 3 months. Lower doses, however, may be sufficient in certain populations. Vitamin D doses

> 500,000 IU should be used judiciously in order to minimize adverse events. (Endocr Pract. 2014;20:341-351)

Section snippets

INTRODUCTION

Vitamin D insufficiency is linked not only to bone disease 1., 2. but also to several nonskeletal conditions, including type 2 diabetes mellitus (DM) (3), cardiovascular disease 4., 5., 6., 7., chronic lung disease 8., 9., 10., 11., tuberculosis (TB) 12., 13., 14., and upper respiratory infections 15., 16.. Vitamin D status is determined by serum 25-hydroxyvitamin D (25[OH]D), the major circulating form of vitamin D (17). Controversy exists as to what serum concentration of 25(OH)D is

METHODS

We searched the terms “high dose vitamin D,” “single dose vitamin D,” “bolus vitamin D,” or “annual dose vitamin D” in PubMed for articles published through September 1, 2012. Limits were preset to manuscripts published in the English language. Titles and abstracts were reviewed. Review articles, cross-sectional studies, non-human studies, and responses to other articles were excluded. Manuscripts were also excluded if the studies: (1) did not use oral cholecalciferol or ergocalciferol, (2)

Study Design

The 30 studies that met eligibility criteria of this paper were published after 1990 and evaluated adult populations receiving single, oral vitamin D doses > 100,000 IU. Elderly populations were sampled in 14 studies 26., 27., 29., 30., 31., 32., 33., 34., 35., 36., 37., 38., 39., 40., and vitamin D-deficient adults were observed in 2 studies 41., 42.. Five studies evaluated cardiovascular risk factors (DM, insulin resistance, peripheral artery disease [PAD], and stroke history) 3., 43., 44., 45.

DISCUSSION

This systematic review demonstrated the consistent efficacy and safety of single, large, oral doses of vitamin D in adults. All studies evaluated report a significant increase in serum/plasma 25(OH)D concentration relative to baseline, which tended to peak between days 7 and 30 (Fig. 2). Mean serum/plasma 25(OH)D concentration surpassed IOM guidelines for vitamin D sufficiency (25[OH]D concentration > 20 ng/mL) in all but 1 study (53). However, the formulation and dose of vitamin D appeared to

CONCLUSION

In conclusion, a single vitamin D₃ dose of ≥ 100,000 IU offers a consistently efficient means of improving shortterm vitamin D concentrations of > 20 ng/mL, although vitamin D₃ doses of ≥ 300,000 IU are necessary to achieve 25(OH)D concentrations > 30 ng/mL and lowering of plasma PTH concentrations. Although generally safe, bolus doses of > 500,000 IU of vitamin D₃ must be used with caution due to the potential for increased fracture risks, altered biochemical markers, and issues with tolerability,

DISCLOSURE

The authors have no multiplicity of interest to disclose.

ACKNOWLEDGMENT

Supported in part by the National Center for Advancing Translational Sciences of the National Institutes of Health, under Award Number UL1TR000454. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Vitamin D and ischemic stroke - Association, mechanisms, and therapeutics
2024, Ageing Research Reviews
Confronting the rising tide of ischemic stroke and its associated mortality and morbidity with ageing, prevention and acute management of ischemic stroke is of paramount importance. Mounting observational studies have established a non-linear association of vitamin D status with cardiovascular diseases, including ischemic stroke. Paradoxically, current clinical trials fail to demonstrate the cardiovascular benefits of vitamin D supplementation. We aim to update recent clinical and experimental findings on the role of vitamin D in the disease course of ischemic stroke, from its onset, progression, recovery, to recurrence, and the established and alternative possible pathophysiological mechanisms. This review justifies the necessities to address stroke etiological subtypes and focus on vitamin D-deficient subjects for investigating the potential of vitamin D supplementation as a preventive and therapeutic approach for ischemic stroke. Well-powered clinical trials are warranted to determine the efficacy, safety, timing, target individuals, optimal dosages, and target 25OHD concentrations of vitamin D supplementation in the prevention and treatment of ischemic stroke.
Vitamin D deficiency presenting as seizures
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Vitamin D deficiency is commonly seen in the general population, likely due to lack of adequate exposure to sunlight as well as lack of sufficient dietary intake. However, severe hypocalcemia secondary to vitamin D deficiency, manifesting as seizures is uncommon. We present a series of such cases encountered by us in the time frame of June 2020 to Dec 2021 (the first wave of the Covid-19 pandemic associated with a lockdown) during which patients of varying age groups presented with seizures. The only abnormality detected was severe hypocalcemia due to vitamin D deficiency and they all responded well to calcium and vitamin D replacement, without recurrence of seizures or hypocalcemia.
Efficacy and safety of single or consecutive double high-dose oral cholecalciferol supplementation in adult patients with vitamin D deficiency
2023, Steroids
Enhancing vitamin D levels as a crucial modifiable risk factor may provide a critical contribution to prevent susceptibility to various diseases, including musculoskeletal, autoimmune, and inflammatory rheumatic diseases as well as promoting overall health. However, adherence to daily vitamin D supplementation is generally poor, and there are some concerns regarding the high-dose vitamin D supplementation's safety. We aimed to investigate whether a single oral dose of 300,000 IU or consecutive two-day dosing of 300,000 IU each day of cholecalciferol could sufficiently and safely elevate vitamin D levels.
This cross-sectional study was conducted on 160 inpatients with vitamin D deficiency and various musculoskeletal diseases. Subjects with serum 25(OH)D levels between 10 and 20 ng/mL (mild to moderate deficiency) received a single oral dose of 300,000 IU cholecalciferol, while those with severe vitamin D deficiency (<10 ng/mL) were supplemented with consecutive two-day doses of 300,000 IU cholecalciferol (a total of 600,000 IU).
After one week of replacement therapy, the 25(OH)D levels increased from 6.3 (4.0–9.9) ng/mL to 53.3 (8.3–84.4) ng/mL and from 15.0 (10.1–19.6) ng/mL to 38.4 (16.3–67.7) in the group with severe and those with the mild-to-moderate vitamin D deficiency, respectively. Except for three patients, nearly all patients (98%) achieved levels above 20 ng/mL. No signs of toxicity were observed in any of the patients. During the 6-month follow-up, falls were observed in 3 patients (2.8%), but no fractures were reported.
A single dose of 300,000 IU of oral cholecalciferol or two consecutive doses with a total dose of 600,000 IU cholecalciferol can effectively and reliably increase the 25(OH)D serum levels within one week in nearly all patients. The results may contribute to optimizing treatment strategies for vitamin D deficiency and re-evaluating the potential negative impact of high-dose vitamin D supplementation.
Vitamin D and Zinc Supplementation to Improve Treatment Outcomes among COVID-19 Patients in India: Results from a Double-Blind Randomized Placebo-Controlled Trial
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There remains a need to identify low-cost interventions to improve coronavirus disease 2019 (COVID-19) outcomes. Vitamin D and zinc play a role in respiratory infections and could hold value as part of therapeutic regimens.
To determine the effect of vitamin D or zinc supplementation on recovery from COVID-19.
We conducted a double-blind, randomly assigned 2 x 2 factorial placebo-controlled trial with 1:1:1:1 allocation ratio, enrolling nonpregnant adults with COVID-19 from hospitals in Mumbai and Pune, India (NCT04641195). Participants (N = 181) were randomly assigned to vitamin D3 (180,000 IU bolus, then 2000 IU daily), zinc (40 mg daily), vitamin D3 and zinc, or placebo, for 8 wk. Participants were followed until 8 wk. The primary outcome was time to resolution of fever, cough, and shortness of breath. Secondary outcomes were duration of individual symptoms; need for assisted ventilation; duration of hospital stay; all-cause mortality; and blood biomarkers, including nutritional, inflammatory, and immunological markers.
We observed no effect of vitamin D or zinc supplementation on time to resolution of all 3 symptoms [vitamin D hazard ratio (HR): 0.92; 95% confidence interval (95% CI): 0.66, 1.30; P = 0.650; zinc HR: 0.94; 95% CI: 0.67, 1.33; P = 0.745)]. Neither vitamin D nor zinc supplementation was associated with secondary outcomes, except for increased endline serum vitamin D with vitamin D supplementation [median (interquartile range) difference between endline and baseline for vitamin D: 5.3 ng/mL (–2.3 to 13.7); for no vitamin D: –1.4 ng/mL (–5.6 to 3.9); P = 0.003]. We observed nonsignificant increases in serum zinc at endline following zinc supplementation. There was no evidence of interaction between vitamin D and zinc supplementation, no effect of either on hypercalcemia, and no adverse events.
Results suggest that neither vitamin D nor zinc supplementation improves COVID-19 treatment outcomes in this population. However, much larger-scale evidence, particularly from populations with vitamin D or zinc deficiency and severe infection, is required to corroborate our findings. This trial was registered at ClinicalTrials.gov and the Clinical Trials Registry of India as NCT04641195 and CTRI/2021/04/032593 respectively.
High-dose vitamin D supplementation in patients with COVID-19: A meta-analysis of randomized controlled trials
2024, Food Science and Nutrition
Vitamin D Reduces GABA-Positive Astrocytes in the 5xFAD Mouse Model of Alzheimer’s Disease
2024, Journal of Alzheimer's Disease

View all citing articles on Scopus

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Review ArticleLarge, Single-Dose, Oral Vitamin D Supplementation in Adult Populations: A Systematic Review

ABSTRACT

Objective

Methods

Results

Conclusion

Section snippets

INTRODUCTION

METHODS

Study Design

DISCUSSION

CONCLUSION

DISCLOSURE

ACKNOWLEDGMENT

Lancet.

Chest.

Am J Clin Nutr.

Mayo Clin Proc.

Lancet.

Am J Clin Nutr.

Contemp Clin Trials.

Am J Clin Nutr.

Maturitas.

Bone.

Am J Clin Nutr.

Nutr Metab Cardiovasc Dis.

Eur J Vasc Endovasc Surg.

Kidney Int.

Calcium and vitamin D in the prevention and treatment of osteoporosis - a clinical update

J Intern Med.

The effect of different doses of vitamin D(3) on markers of vascular health in patients with type 2 diabetes: a randomised controlled trial

Diabetologia.

Plasma 25-hydroxyvitamin D levels and risk of incident hypertension

Hypertension.

Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality

Arch Intern Med.

Vitamin D deficiency and risk of cardiovascular disease

Circulation.

25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study

Arch Intern Med.

Vitamin D deficiency is highly prevalent in COPD and correlates with variants in the vitamin D-binding gene

Thorax.

Vitamin D and bone health in adults with cystic fibrosis

Clin Endocrinol (Oxf).

Serum 25-hydroxy vitamin D and exercise capacity in COPD

Thorax.

Vitamin D status and acute lower respiratory infection in early childhood in Sylhet, Bangladesh

Acta Paediatr.

Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications

Endocr Rev.

Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline

J Clin Endocrinol Metab.

The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know

J Clin Endocrinol Metab.

Aloia JF. IOM committee members respond to Endocrine Society vitamin D guideline

J Clin Endocrinol Metab.

Review Article
Large, Single-Dose, Oral Vitamin D Supplementation in Adult Populations: A Systematic Review