Safety of Vitamin D Food Fortification and Supplementation: Evidence from Randomized Controlled Trials and Observational Studies.

Folasade A Adebayo,Christel Lamberg-Allardt,Kevin D Cashman,Taina Öhman,Mairead Kiely,Suvi T Itkonen

doi:10.3390/foods10123065

Folasade A Adebayo, Christel Lamberg-Allardt + Show 4 more

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https://doi.org/10.3390/foods10123065

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Abstract

The safety considerations of food-based solutions for vitamin D deficiency prevention, such as fortification and supplementation, are critical. On the basis of collective data from 20 randomized controlled trials (RCTs) and 20 national healthy surveys, as well as prospective cohort studies (PCSs) across the ODIN project (“Food-based solutions for optimal vitamin D nutrition and health through the life cycle”, FP7-613977), we analyzed the potential safety issues arising from vitamin D intakes and/or supplementation. These adverse consequences included high serum 25-hydroxyvitamin D (S-25(OH)D) concentrations (>125 nmol/L), high serum calcium concentrations, and vitamin D intakes in excess of the tolerable upper intake levels (ULs). In the RCTs (n = 3353, with vitamin D doses from 5–175 µg/day), there were no reported adverse effects. The prevalence of high S-25(OH)D was <10% when vitamin D supplements were administered, and <0.1% for fortified foods. Elevated serum calcium was observed among <0.5% in both administration types. No ODIN RCT participants exceeded the age-specific ULs. In observational studies (n = 61,082), the prevalence of high 25(OH)D among children/adolescents, adults, and older adults was <0.3%, with no evidence of adverse effects. In conclusion, high S-25(OH)D concentrations >125 nmol/L were rare in the RCTs and PCSs, and no associated adverse effects were observed.

Highlights

Vitamin D is important for musculoskeletal health, and its extraskeletal roles are played in the cellular, endocrine, immune, cardiovascular, and other systems [1,2]
The aim of this paper is to provide a summary of the key findings of the ODIN project as they relate to safety considerations in relation to increasing vitamin D intake and serum 25(OH)D concentrations
In one of the randomized controlled trials (RCTs), one subject receiving 143 μg/day of supplemental vitamin D had high serum calcium, while a higher prevalence of 2.9% was observed in the study with a daily dose of 163 μg/day vitamin D + 1000 mg calcium (Table 3)

Summary

Introduction

Vitamin D is important for musculoskeletal health, and its extraskeletal roles are played in the cellular, endocrine, immune, cardiovascular, and other systems [1,2]. Vitamin D food fortification has been the most suitable approach for enhancing vitamin D intake and status in the general population [4] This is important, especially for the people living in northern latitudes, where there is limited or no cutaneous vitamin D production for several months during wintertime because of the inadequate levels of UVB irradiation for the synthesis [5]. Besides vitamin D food fortification, which is the traditional way of adding vitamin D directly to food product, the vitamin D content of food can be increased through biofortification, without the direct exogenous addition [4] Examples of such biofortification include the increase in the vitamin D2 content of mushrooms by UVB-exposure that induces vitamin D production [6], and the increase in the vitamin D3 content of eggs through vitamin D-rich hen feed [7], among others [8]. Either from foods or supplements, vitamin D2 is generally considered less potent than vitamin D3 in raising and maintaining S-25(OH)D concentrations [12,13]

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