Vieth R, Chan PR & MacFarlane GD: Efficacy and safety of vitamin D3 intake exceeding the lowest observed effect level. Am. J. Clin. Nutr. 73, 288-294

Mount Sinai Hospital, Toronto, Ontario, Canada.
American Journal of Clinical Nutrition (Impact Factor: 6.77). 03/2001; 73(2):288-94.
Source: PubMed


The Food and Nutrition Board of the National Academy of Sciences states that 95 microg vitamin D/d is the lowest observed adverse effect level (LOAEL).
Our objective was to assess the efficacy and safety of prolonged vitamin D3 intakes of 25 and 100 microg (1000 and 4000 IU)/d. Efficacy was based on the lowest serum 25-hydroxyvitamin D [25(OH)D] concentration achieved by subjects taking vitamin D3; potential toxicity was monitored by measuring serum calcium concentrations and by calculating urinary calcium-creatinine ratios.
Healthy men and women (n = 61) aged 41 +/- 9 y (mean +/- SD) were randomly assigned to receive either 25 or 100 microg vitamin D3/d for 2-5 mo, starting between January and February. Serum 25(OH)D was measured by radioimmunoassay.
Baseline serum 25(OH)D was 40.7 +/- 15.4 nmol/L (mean +/- SD). From 3 mo on, serum 25(OH)D plateaued at 68.7 +/- 16.9 nmol/L in the 25-microg/d group and at 96.4 +/- 14.6 nmol/L in the 100-microg/d group. Summertime serum 25(OH)D concentrations in 25 comparable subjects not taking vitamin D3 were 46.7 +/- 17.8 nmol/L. The minimum and maximum plateau serum 25(OH)D concentrations in subjects taking 25 and 100 microg vitamin D3/d were 40 and 100 nmol/L and 69 and 125 nmol/L, respectively. Serum calcium and urinary calcium excretion did not change significantly at either dosage during the study.
The 100-microg/d dosage of vitamin D3 effectively increased 25(OH)D to high-normal concentrations in practically all adults and serum 25(OH)D remained within the physiologic range; therefore, we consider 100 microg vitamin D3/d to be a safe intake.

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Available from: Gordon Macfarlane, May 28, 2014
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    • "Supplemental vitamin D at 4000 IU/d does not modulate plasma calcium [34] but significantly decreases plasma PTH [35] in adults with initially low serum 25(OH)D concentrations (i.e., < 20 ng/mL). In this study consisting of subjects with mostly sufficient serum 25(OH)D concentrations prior to supplementation, supplemental vitamin D did not significantly influence plasma calcium or PTH concentrations. "
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    ABSTRACT: Serum 25-hydroxyvitamin D (25(OH)D) concentrations associate with skeletal muscle weakness (i.e., deficit in skeletal muscle strength) after muscular injury or damage. Although supplemental vitamin D increases serum 25(OH)D concentrations, it is unknown if supplemental vitamin D enhances strength recovery after a damaging event. Reportedly healthy and modestly active (30 minute of continuous physical activity at least 3 time/week) adult males were randomly assigned to a placebo (n = 13, age, 31(5) y; BMI, 26.9(4.2) kg/m2; serum 25(OH)D, 31.0(8.2) ng/mL) or vitamin D (cholecalciferol, 4000 IU; n = 15; age, 30(6) y; BMI, 27.6(6.0) kg/m2; serum 25(OH)D, 30.5(9.4) ng/mL) supplement. Supplements were taken daily for 35-d. After 28-d of supplementation, one randomly selected leg performed an exercise protocol (10 sets of 10 repetitive eccentric-concentric jumps on a custom horizontal plyo-press at 75% of body mass with a 20 second rest between sets) intended to induce muscle damage. During the exercise protocol, subjects were allowed to perform presses if they were unable to complete two successive jumps. Circulating chemistries (25(OH)D and alanine (ALT) and aspartate (AST) aminotransferases), single-leg peak isometric force, and muscle soreness were measured before supplementation. Circulating chemistries, single-leg peak isometric force, and muscle soreness were also measured before (immediately) and after (immediately, 1-h [blood draw only], 24-h, 48-h, 72-h, and 168-h) the damaging event. Supplemental vitamin D increased serum 25(OH)D concentrations (P < 0.05; [almost equal to]70%) and enhanced the recovery in peak isometric force after the damaging event (P < 0.05; [almost equal to]8% at 24-h). Supplemental vitamin D attenuated (P < 0.05) the immediate and delayed (48-h, 72-h, or 168-h) increase in circulating biomarkers representative of muscle damage (ALT or AST) without ameliorating muscle soreness (P > 0.05). We conclude that supplemental vitamin D may serve as an attractive complementary approach to enhance the recovery of skeletal muscle strength following intense exercise in reportedly active adults with a sufficient vitamin D status prior to supplementation.
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    • "The results of our fortification model (see example calculation in chapter “results”), stating that an average individual needs approximately 23.7 μg a day to reach a concentration of 75 nmol/L, are in line with other observations [7,11,24,39-44]. Other publications are of similar statements, proposing 25 μg to obtain an adequate serum 25(OH)D in the absence of UVB irradiance [45] or to raise the level by up to 25 nmol/L [46], which is comparable to our results. "
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    • "In an Indian randomised controlled trial, supplementation in men with three doses of 120,000 IU of vitamin D at fortnightly intervals was not associated with any adverse events in general or specifically relating to hypercalcaemia [36]. In a Canadian trial, 4000 IU of vitamin D3 daily for 2–5 months in healthy adults did not result in any adverse effects [46]. Two clinical studies of 10,000 IU/day have demonstrated an elevation of serum 25(OH)D concentrations to the high end of normal concentrations without inducing toxicity in healthy volunteers [44,45]. "
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    ABSTRACT: The global prevalence of type 2 diabetes is increasing. Effective strategies to address this public health challenge are currently lacking. A number of epidemiological studies have reported associations between low concentrations of 25-hydroxy vitamin D and the incidence of diabetes, but a causal link has not been established. We investigate the effect of vitamin D supplementation on the metabolic status of individuals at increased risk of developing type 2 diabetes.Methods/design: In a randomised double-blind placebo-controlled trial individuals identified as having a high risk of type 2 diabetes (non-diabetic hyperglycaemia or positive diabetes risk score) are randomised into one of three groups and given 4 doses of either placebo, or 100,000 IU Vitamin D2 (ergocalciferol) or 100,000 IU Vitaming D3 (cholecalciferol) at monthly intervals. The primary outcome measure is the change in glycated haemoglobin level between baseline and 4 months. Secondary outcome measures include blood pressure, lipid and apolipoprotein levels, PTH and safety of supplementation and C-reactive protein. The trial is being conducted at two sites (London and Cambridge, U.K.) and a total of 342 participants are being recruited. Trial data examining whether supplementation of vitamin D improves glycaemic status and other metabolic parameters in people at risk of developing type 2 diabetes are sparse. This trial will evaluate the causal role of vitamin D in hyperglycaemia and risk of type 2 diabetes. Specific features of this trial include recruitment of participants from different ethnic groups, investigation of the relative effectiveness and safety of vitamin D2 and D3 and an evidence based approach to determination of the dose of supplementation.Trial registration: EudraCT2009-011264-11; ISRCTN86515510.
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