Adverse events from large dose vitamin D supplementation taken for one year or longer

Malihi, Zarintaj; Wu, Zhenqiang; Lawes, Carlene M.M.; Scragg, Robert

doi:10.1016/j.jsbmb.2018.12.002

Cited by 49 publications

(50 citation statements)

References 68 publications

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“…These implants are a last option to prevent death in people with end-stage heart failure and their increased use was linked to vitamin D-induced hypercalcemia (254). Indeed, long-term (≥12 months) treatment with "high" dose vitamin D (≥2,800 IU/day) may increase risk of hypercalcemia (255). Further controversy lies in the frequency of dosing (e.g., daily vs. bolus monthly), although for acute respiratory infections, metaanalyses point toward increased efficacy of daily dosing with 400-1,000 IU vitamin D (240).…”

Section: Vitamin D Dose Considerationsmentioning

confidence: 99%

Investigating the Potential for Ultraviolet Light to Modulate Morbidity and Mortality From COVID-19: A Narrative Review and Update

Gorman

Weller

2020

Front. Cardiovasc. Med.

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During the COVID-19 (coronavirus disease of 2019) pandemic, researchers have been seeking low-cost and accessible means of providing protection from its harms, particularly for at-risk individuals such as those with cardiovascular disease, diabetes and obesity. One possible way is via safe sun exposure, and/or dietary supplementation with induced beneficial mediators (e.g., vitamin D). In this narrative review, we provide rationale and updated evidence on the potential benefits and harms of sun exposure and ultraviolet (UV) light that may impact COVID-19. We review recent studies that provide new evidence for any benefits (or otherwise) of UV light, sun exposure, and the induced mediators, vitamin D and nitric oxide, and their potential to modulate morbidity and mortality induced by infection with SARS-CoV-2 (severe acute respiratory disease coronavirus-2). We identified substantial interest in this research area, with many commentaries and reviews already published; however, most of these have focused on vitamin D, with less consideration of UV light (or sun exposure) or other mediators such as nitric oxide. Data collected to-date suggest that ambient levels of both UVA and UVB may be beneficial for reducing severity or mortality due to COVID-19, with some inconsistent findings. Currently unresolved are the nature of the associations between blood 25-hydroxyvitamin D and COVID-19 measures, with more prospective data needed that better consider lifestyle factors, such as physical activity and personal sun exposure levels. Another short-coming has been a lack of measurement of sun exposure, and its potential to influence COVID-19 outcomes. We also discuss possible mechanisms by which sun exposure, UV light and induced mediators could affect COVID-19 morbidity and mortality, by focusing on likely effects on viral pathogenesis, immunity and inflammation, and potential cardiometabolic protective mechanisms. Finally, we explore potential issues including the impacts of exposure to high dose UV radiation on COVID-19 and vaccination, and effective and safe doses for vitamin D supplementation.

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Section: Vitamin D Dose Considerationsmentioning

confidence: 99%

Investigating the Potential for Ultraviolet Light to Modulate Morbidity and Mortality From COVID-19: A Narrative Review and Update

Gorman

Weller

2020

Front. Cardiovasc. Med.

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“…Vitamin D and its metabolites regulate the secretion of hormones and have complex functions in calcium and phosphorus homeostasis, as for instance regulation of intestinal calcium and phosphate absorption, calcium mobilization from bones and reabsorption of calcium in the kidneys (54). Hypercalcemia may occur in humans supplemented with high doses of vitamin D (55,56), especially when combined with calcium intake (57)(58)(59). In addition, hypercalcemia was also reported in the treatment of chronic obstructive pulmonary disease (49) and type 2 diabetes mellitus (47) upon high-dose vitamin D. In cardiovascular disease (CVD) the incidence of hypercalcemia tended to be higher upon moderately high vitamin D supplementation (53).…”

Section: Secondary Hypercalcemia As a Risk Of Vitamin D High-dose Supmentioning

confidence: 99%

High-Dose Vitamin D-Mediated Hypercalcemia as a Potential Risk Factor in Central Nervous System Demyelinating Disease

2020

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The exact cause of multiple sclerosis (MS) is unknown; however, it is considered to be an inflammatory disease of the central nervous system (CNS) triggered by a combination of both environmental and genetic factors. Vitamin D deficiency is also discussed as a possible disease-promoting factor in MS, as low vitamin D status is associated with increased formation of CNS lesions, elevated number of relapses and accelerated disease progression. However, it remains unclear whether this association is causal and related and most importantly, whether vitamin D supplementation in MS is of direct therapeutic benefit. Recently, we could show that in a murine model of MS, administration of a moderate vitamin D dose was of clinical benefit, while excessive vitamin D supplementation had a negative effect on disease severity. Of note, disease exacerbation was associated with high-dose vitamin D caused secondary hypercalcemia. Mechanistically dissecting this outcome, we found that hypercalcemia independent of vitamin D similarly triggered activation of disease-perpetuating T cells. These findings caution that vitamin D should be supplemented in a controlled and moderate manner in patients with MS and concomitantly highlight calcium as a novel potential MS risk factor by itself. In this review, we will summarize the current evidence from animal and clinical studies aiming to assess whether vitamin D may be of benefit in patients with MS. Furthermore, we will discuss any possible secondary effects of vitamin D with a particular focus on the role of calcium on immune cells and in the pathogenesis of CNS demyelinating disease.

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“…They also did not observe a higher risk, even among those participants with higher intakes of calcium [91]. In a recent systematic review analysis (15 studies, 3150 participants, ≥2800 IU per day vitamin D 2 or D 3 supplementation), Malihi et al demonstrated that one year or longer supplementation with a daily, weekly or monthly dose of vitamin D 2 /D 3 did not significantly increase the risk of total adverse events or kidney stones, although there was a trend towards increased hypercalcemia, and possibly for hypercalciuria [92].…”

Section: How Can a Healthy Vitamin D Status Be Achieved And Maintamentioning

confidence: 99%

A Critical Appraisal of Strategies to Optimize Vitamin D Status in Germany, a Population with a Western Diet

2019

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During the last decade, our scientific knowledge of the pleiotropic biological effects of vitamin D metabolites and their relevance to human health has expanded widely. Beyond the well-known key role of vitamin D in calcium homeostasis and bone health, it has been shown that vitamin D deficiency is associated with a broad variety of independent diseases, including several types of cancer, and with increased overall mortality. Moreover, recent findings have demonstrated biological effects of the vitamin D endocrine system that are not mediated via activation of the classical nuclear vitamin D receptor (VDR) by binding with high affinity to its corresponding ligand, the biologically active vitamin D metabolite 1,25-dihydroxyvitamin D (1,25(OH)2D). In contrast, many of these new biological effects of vitamin D compounds, including regulation of the circadian clock and many metabolic functions, are mediated by other vitamin D metabolites, including 20-hydroxyvitamin D and 20,23-dihydroxyvitamin D, and involve their binding to the aryl hydrocarbon receptor (AhR) and retinoid-orphan receptor (ROR). In most populations, including the German population, UVB-induced cutaneous vitamin D production is the main source for fulfilling the human body’s requirements of vitamin D. However, this causes a dilemma because solar or artificial UVR exposure is associated with skin cancer risk. In addition to UVB-induced vitamin D production in skin, in humans, there are two other possible sources of vitamin D: from diet and supplements. However, only a few natural foods contain substantial amounts of vitamin D, and in most populations, the dietary source of vitamin D cannot fulfill the body´s requirements. Because an increasing body of evidence has convincingly demonstrated that vitamin D deficiency is very common worldwide, it is the aim of this paper to (i) give an update of the vitamin D status in a population with a western diet, namely, the German population, and to (ii) develop strategies to optimize the vitamin D supply that consider both the advantages as well as the disadvantages/risks of different approaches, including increasing vitamin D status by dietary intake, by supplements, or by UVB-induced cutaneous synthesis of vitamin D.

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Adverse events from large dose vitamin D supplementation taken for one year or longer

Cited by 49 publications

References 68 publications

Investigating the Potential for Ultraviolet Light to Modulate Morbidity and Mortality From COVID-19: A Narrative Review and Update

Investigating the Potential for Ultraviolet Light to Modulate Morbidity and Mortality From COVID-19: A Narrative Review and Update

High-Dose Vitamin D-Mediated Hypercalcemia as a Potential Risk Factor in Central Nervous System Demyelinating Disease

A Critical Appraisal of Strategies to Optimize Vitamin D Status in Germany, a Population with a Western Diet

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