The upper limit (UL) for vitamin D, set by the 2011 Food and Nutrition Board, is 4,000 IU per day. This is defined as the highest level of daily consumption that causes no side effects in humans when used indefinitely without medical supervision.
The same board set the No Observed Adverse Effects Level (NOAEL) at 10,000 IU/day. The NOAEL is the dose at which there are no published studies showing any adverse effects of that dosage. As an aside, if there are any studies showing 20,000 IU/day is unsafe, I would like to see them.
Anyway, the Upper Limit is simply calculated from the NOAEL by dividing by a safety factor. In vitamin D’s case, they divided the NOAEL of 10,000 IU/day by 2.5 to get the Upper Limit of 4,000 IU/day.
At the Vitamin D Council, we recommend that patients exceed the Upper Limit, but not exceed the NOAEL of 10,000 IU/day, unless they are under medical supervision or know what they are doing. But why do we recommend more than the Food and Nutrition Board’s Upper Limit?
Because the question is, will 4,000 IU/day get 97.5% of the population above a certain 25(OH)D threshold, such as 30 ng/ml? Or are doses higher than 4,000 IU/day needed to achieve blood levels above 30 ng/ml, 30 ng/ml still being much lower than average 25(OH)D levels found in hunter gatherers living around the equator, which are about 46 ng/ml.
Doctor Etienne Cavalier and colleagues of the University of Liège in Belgium recently tried to find out if 4,000 IU/day is enough by giving large or stoss doses to a total of 140 subjects.
Cavalier E, Faché W, Souberbielle JC. A Randomised, Double-Blinded, Placebo-Controlled, Parallel Study of Vitamin D3 Supplementation with Different Schemes Based on Multiples of 25,000 IU Doses. Int J Endocrinol. 2013;2013:327265.
The study took place in Belgium between January and July of 2011 and included only healthy patients above the age of 50. In Belgium, the only vitamin D available to doctors is a 25,000 IU capsule of vitamin D3, so that is what they used. They used twice monthly dosing schedules, giving a dose in their office every two weeks to ensure 100% compliance. Here were their dosing groups:
- They gave the equivalent of about 4,200 IU/day to the first group of 40 patients whose initial 25(OH)D levels were below 10 ng/ml.
- They gave about 3,000 IU/day to a second group of 40 patients, whose initial levels were between 10 and 20 ng/ml.
- They gave about 2,000 IU/day to a third group whose initial levels were between 20 and 30 ng/ml.
- They gave about 1,600 IU/day to a fourth group whose initial levels were over 30 ng/ml
- They gave a placebo to a fifth group whose mean levels were 18 ng/ml.
Keep in mind the above doses are calculated from the “stoss” or large doses the patients were actually getting every two weeks. They tested 25(OH)D levels during the study including the final level which was drawn 30 days after the four groups completed their dosing schedules.
The first remarkable thing the authors found was that the placebo group’s levels did not rise in spite of the study ending in July. Apparently, older Belgium adults get little sunshine.
Next, they were surprised at how many of the subject still had final levels less than 30 ng/ml, despite what they considered large doses of vitamin D. The percentages of patients failing to achieve a final 25(OH)D of at least 30 ng/ml were 62% in group 1, 60% in group 2, 25% in group 3, 45% in group 4, and 86% in the placebo group. However, these final levels were drawn one month after the final dose of vitamin D, so they would have been higher if they were tested a week after the final dose.
Nevertheless, the authors wrote,
“Overall, this suggests that the doses of vitamin D3 administered in the present study were insufficient to achieve or maintain the 30 ng/mL target in a significant proportion of the included subjects. It must be underlined that the dose administered to the subjects with a baseline serum level ≤10 ng/mL was already very close (slightly above in fact) to the upper safety limit of 4,000 IU/day defined by the IOM. Thus, if a 25(OH)D level of 30 ng/mL or more is targeted in future studies, higher doses than the IOM Upper Limit should be used.”
I like it when academics contradict the Food and Nutrition Board’s recommendations. First, this study makes the Vitamin D Council’s recommendations (5,000 IU/day) seem reasonable, if not conservative. Second, it legitimizes what any practitioner who gives vitamin D and subsequently tests 25(OH)D levels will tell you; 4,000 IU/day is simply not enough for some people. In fact, 5,000 IU/day is not enough for some people. However, we recommend that anyone who exceeds 5,000 IU/day have a 25(OH)D test three months after taking such a dose to be sure that it achieves the desired effect, which is natural blood levels.