There is an interesting article just published in Anticancer Research that comes to the conclusion that, “Universal intake of up to 40,000 IU vitamin D per day is unlikely to result in vitamin D toxicity.” However, one needs to interpret the content of this article — and this conclusion — with some care.
Garland et al. have initiated (but by no means completed) a community-based survey of the intake of vitamin D in a cohort of largely white men and women who self-selected to participate in the study after attendance at a seminar on vitamin D in 2008 or as a result of “extensive recruitment from internet invitations.” There were no exclusion criteria, so anyone could take part in this survey, regardless of their state of wellness or illness.The participants all paid a fee to take part in the study (inclusive of the costs of measuring their serum levels of 25-hydroxy vitamin D).
Every 6 months, the participants are being asked to self-administer a blood spot test. The blood spot sample is dried and mailed in to a centralized laboratory and each participant receives an e-mail telling them they can go to a web site to review their test result. Participants are also asked to complete an on-line health survey every 6 months. Any actions taken by the participants (i.e., to take, not take, increase or decrease supplementary vitamin D products) as a consequence of changes in their serum level of 25-hydroxy vitamin D over time is entirely a matter of personal choice.
We have been allowed to see a copy of the on-line survey that the participants are asked to complete. It is highly detailed and certainly appears to request sufficient information to allow estimation of: (a) the participants’ average daily exposure to dietary and environmental sources of vitamin D (excluding use of actual vitamin D supplements); (b) the participants’ use of actual vitamin D supplements; and (c) any toxic responses to excess levels of vitamin D. (It should be noted that a laboratory value of 25-hydroxy vitamin D ≥ 200 ng/ml in serum is normally considered to be a toxic level.)
Here are the results reported in the full text of the paper:
- The study has enrolled 3,667 participants (1,436 male; 2,231 female).
- The average (mean) age of the participants to date is 51.7 ± 13.3 years, and 92.8 percent are non-Hispanic whites.
- About 25 percent of the participants reported absolutely no intake of vitamin D supplements at enrollment in the study.
- 47 percent of participants reported taking vitamin D supplements of up to 2,000 IU/day.
- 1.8 percent of participants (n = 60) reported taking vitamin D supplements of > 10,000 IU/day.
- Based on Figure 2 in the paper, it appears that 20 individuals are self-medicating with > 20, 000 IU/day, and that 10 of those individuals are self-medicating with 50,000 IU/day.
- The participants’ serum 25-hydroxy vitamin D levels have risen as a function of self-reported vitamin D supplement ingestion. (This has been further confirmed in e-mail correspondence with the study managers based on data from those patients who have completed more than one 6-month cycle of follow-up blood spot testing and questionnaires.)
- Daily intakes of vitamin D of < 10,000 IU were not associated with serum 25-hydroxy vitamin D levels of ≥ 200 ng/ml.
The study report provides absolutely no clinical data for these patients (although relevant clinical data are being collected through the study questionnaires), nor does it provide data on the participants’ serum or urinary calcium levels.
The study report also offers no data on what percentage of the 3,667 study participants have completed (say) two or more serial blood spot tests or health surveys over time. All we know is that 3,667 people “participated” by providing some sort of data at least once. Based on these limited data, the authors state that “it is clear that there were no clinical evidences of toxicity” resulting from the use of vitamin D as of the time of the current report.
By carrying out a variety of mathematical calculations, the authors are able to reach some additional conclusions, as follows:
- They estimate that the “unsupplemented all-source input” of vitamin D was 3,300 IU/day. In other words, the average dietary and environmental vitamin D intake of the study participants if they took no vitamin D supplements was > 3,000 IU/day.
- They also estimate that a total daily intake of up to 40,000 IU “is unlikely to result in vitamin D toxicity” as previously mentioned.
What is important to understand about this study is that there is a distinction between the conclusions that can actually be drawn from the data collected as part of this study to date and the data that can be extrapolated through computations based on these data and data from prior studies.
This study is actually meant to be conducted over a period of 5 years in total. In other words, the study design allows for patients to provide a baseline serum sample and a completed survey at trial entry and then another nine serum samples and completed surveys over the next 5 years, during which they may choose to increase (or decrease) their daily intake of vitamin D through the use of vitamin D supplements. There is no information available on the type of vitamin D supplement that individual participants are using, so there may be some significant variation in product quality.
It is also important to note that, in communication with one of the study authors, it has been made very clear to us that he would not personally consider recommending a daily dose of 40,000 IU of vitamin D to anyone. The upper level of daily intake of vitamin D recommended for adults by the Institute of Medicine is 4,000 IU/day. So what the data provided in this study are suggesting is that up to 10 times that daily intake does not appear to be associated with vitamin D toxicity … but that also doesn’t necessarily make it a good idea.
The concept of a long-term, community-based, prospective study on the impact of vitamin D supplementation is an interesting one. If the study’s developers are able to keep nearly 4,000 people engaged in this trial over a 4-year period, we may well be able to learn a good deal more about the potential value of vitamin D supplementation. However, we don’t think that just because 40,000 IU/d seems to be a non-toxic dose of vitamin D (based on some careful statistical analysis of data from this and other trials), that the average prostate cancer patient should be dosing himself in that way without a very long conversation with his physician(s). And of course we have no idea whether any of the participants in the current study actually have — or are at any determinable level of risk for — prostate cancer.
In a media release issued by the University of California at San Diego last Wednesday, Dr. Garland, the study’s lead author, is quoted as follows: “Most scientists who are actively working with vitamin D now believe that 40 to 60 ng/ml is the appropriate target concentration of 25-[hydroxy] vitamin D in the blood for preventing the major vitamin D-deficiency related diseases, and have joined in a letter on this topic” (presumably to the Institute of Medicine). He goes on to state further that: “Now that the results of this study are in, it will become common for almost every adult to take 4000 IU/day.”
In our opinion Dr. Garland’s second statement is something of a stretch based on the results of the current study. Taking vitamin D supplements is unlikely to be a near-term priority for the large number of men and women in the US who are currently out of work and having difficulty paying for food, housing, and other rather more basic needs for themselves and their children.