Optimal Vitamin D Supplementation Doses that Minimize the Risk for Both Low and High Serum 25-Hydroxyvitamin D Concentrations in the General Population

Abstract

The Recommended Dietary Allowance (RDA) is the nutrient intake considered to be sufficient to meet the requirements of 97.5% of the population. Recent reports revealed a statistical error in the calculation of the RDA for vitamin D opening the question of what the recommendation should be. We took a dual approach to answer this question: (1) we aggregated 108 published estimates on vitamin D supplementation and vitamin D status; and (2) we analyzed 13,987 observations of program participants. The aggregation of published data revealed that 2909 IU of vitamin D per day is needed to achieve serum 25-hydroxyvitamin D (25(OH)D) concentrations of 50 nmol/L or more in 97.5% of healthy individuals. For normal weight, overweight and obese program participants this was 3094, 4450 and 7248 IU respectively. These supplementation doses would also result in 2.5% of normal weight, overweight and obese participants having 25(OH)D concentrations above 210, 200 and 214 nmol/L respectively. As these concentrations are high, an approach that minimizes the risk for both low and high concentrations seems desirable. With this approach we estimated, for example, that doses of 1885, 2802 and 6235 IU per day are required for normal weight, overweight and obese individuals respectively to achieve natural 25(OH)D concentrations (defined as 58 to 171 nmol/L). In conclusion, the large extent of variability in 25(OH)D concentrations makes a RDA for vitamin D neither desirable nor feasible. We therefore propose recommendations be articulated in the form of an optimal intake that minimizes the risk for both low and high serum 25(OH)D concentrations. This contribution includes body weight specific recommendations for optimal intakes for various combinations of lower and upper 25(OH)D concentration targets.

Keywords: disease prevention; nutrition; optimal vitamin D intake; optimal vitamin D status; public health; recommended daily allowance; vitamin D; vitamin D deficiency; vitamin D supplementation.

Figure 1

The mean and 95% prediction interval (2.5th and 97.5th percentiles) of serum 25(OH)D concentrations by vitamin D supplementation derived from published study means and standard deviations. Note: The 2.5 percentile line depicts 25(OH)D concentrations for any given vitamin D supplementation dose with 2.5% of all expected 25(OH)D responses to have values below the line, and 97.5% to have values above the line. The 97.5 percentile line depicts 25(OH)D concentrations for any given vitamin D supplementation dose with 97.5% of all expected 25(OH)D responses to have values below the line, and 2.5% to have values above the line. The area between the 2.5 percentile line and the 97.5 percentile line depicts the 95% prediction interval of 25(OH)D concentrations for any given vitamin D supplementation dose. The equation for the mean response for reportedly healthy individuals is Y = 51.9 + 17.7 *(1 − e^−7.4*X) + 6.3 *X in which Y denotes serum 25(OH)D (in nmol/L) and X vitamin D supplementation (in 1000 IUs).

Figure 2

The median and 2.5th and 97.5th percentiles of serum 25(OH)D concentrations by vitamin D supplementation among 11,693 healthy participants of a preventive health program in Canada. Note: The 2.5 percentile line depicts 25(OH)D concentrations for any given vitamin D supplementation dose with 2.5% of all expected 25(OH)D responses to have values below the line, and 97.5% to have values above the line. The 97.5 percentile line depicts 25(OH)D concentrations for any given vitamin D supplementation dose with 97.5% of all expected 25(OH)D responses to have values below the line, and 2.5% to have values above the line. The area between the 2.5 percentile line and the 97.5 percentile line depicts the 95% prediction interval of 25(OH)D concentrations for any given vitamin D supplementation dose. The median, the 2.5th and 97.5th percentiles were estimated through quantile regression, a statistical approach that accommodates the clearly visible skewness in the distribution of 25(OH)D concentrations.

Figure 3

Proportion of participants with serum 25(OH)D concentrations above the lower natural limit, below the upper natural limit and within the natural range. Note: The purple line represents the proportion of individuals with serum 25(OH)D concentrations of 58 nmol/L or more by vitamin D supplementation level; the green line the proportion of participants with concentrations of 171 nmol/L or less; and the blue line the proportion of participants that have serum concentrations above 58 nmol/L and below 171 nmol/L. The blue line is curved and shows that the proportion above 58 nmol/L and below 171 nmol/L peaks at 87% at a supplementation dose of 2745 IU per day. At this optimal dose, 8% (100%–92%) will have serum 25(OH)D concentrations below 58 nmol/L and 5% (100%–95%) in excess of 171 nmol/L.

Figure 4

Proportion of participants with serum 25(OH)D concentrations above the lower natural limit, below the upper natural limit and within the natural range by body weight status. Note: The orange lines represent the proportion of individuals with serum 25(OH)D concentrations of 58 nmol/L or more by vitamin D supplementation level; the green lines the proportion of participants with concentrations of 171 nmol/L or less; and the blue lines the proportion of participants that have serum concentrations above 58 nmol/L and below 171 nmol/L.