February 2015 Question 2
Vitamin D toxicity can occur when an individual takes 40,000 IU of D-3 for 1 month. Why do you think this study used such a high level of Vitamin D? Do you agree with their methods?
posted by Unknown @ 1:12 PM
30 comments
30 Comments:
The methods to prove a toxicity seem unethical. If there was a physician or health professional monitoring the dosage and correcting the side effects it would still be risky. I'm not sure how else to claim a supplement's toxicity level in a safe way. Perhaps they used the highest level they thought would be safe enough to treat. The subjects in the study hopefully were well enough informed on the methods being used.
Since this study was conducted over one day, I think these levels of Vitamin D were safe to use in the participants. If the study were to be extended over a longer period of time, they may want to consider changing the dose of the supplementation. I think they used such a high level in this study because they wanted to see if a one-time dose of the vitamin would increase serum levels dramatically. They were also looking at how well it is absorbed with the consumption of fat, so I think they wanted a large enough supplementation to be able to see differences between the 3 groups in this study. I would not be too concerned about the methods of this study, but I think it is important that they screen all of their participants prior to their enrollment to make sure none of them are taking doses of vitamin D that could exceed safe levels over a long period of time.
I don't have a problem with their methodology. Giving the participants 50,000 IU of the supplement only once doesn't sound too risky. I agree with Susan that if they would extend the study over a longer period of time that they would need to lower the dosage so as to reduce the risk of a toxicity.
I also think that the study authors used such a large dose so that they could tell if the groups actually had a significant difference in levels of serum vitamin D. If they hadn't used a megadose, there maybe wouldn't have been a significant increase in serum levels of the vitamin in any of the groups, which would pretty much prove nothing and the results of the study would have been a moot point.
As the questions stated, a toxicity level would be 40,000 IU of D3 for 1 month. This study was only for 1 day, which is probably why the researchers believed a higher dose is appropriate. I think they want to make sure the D3 is going to absorb, and we all know that not 100% of the supplement gets absorbed, which is why most supplements are way over their RDA.
I agree with Susan that a screening process may be beneficial to make sure that the participants won't be harmed in the study by taking a large dose. A longer study seems to be the better option for the original research, but then I would be more concerned about toxicity if they're continually using a high dose.
Basically, I don't think a 1 time dose as in their method is a big deal but more than that and I'd have some concerns.
Like others have been mentioned, the researchers probably wanted a high enough dosage to measure a difference, knowing that it wasn't all going to be absorbed.
Susan, I think you bring up a good point about screening participants beforehand because vitamin D supplements are pretty popular and you never know how many IUs people are taking on their own.
I agree with what most people are saying about the high level of Vitamin D supplementation being acceptable in this one day trial. For such a short-term study, a high dose was surely necessary to generate valid results that showed a significant difference from the control. With a toxicity taking almost a month to develop, even with the high level of dosage, I view the methods ethical for the purpose of the study.
I would be curious to see, however, the effects of the supplementation for even a week. The study participants saw a significant increase in Vitamin D levels 10-14 hours after supplementation, but it is long-term, sustainable levels of Vitamin D that we are most interested in as nutrition professionals.
Tina, you also bring up a valid point that not all of the supplement would be absorbed. Vitamin D was studied in great detail in our Advanced Metabolism course and we learned that Vitamin D from oral sources is less than 50% absorbed. Exposure to the sun to allow optimal photoconversion of Vitamin D to its active form would result in approximately 10,000 IU alone.
A one-time dosage would most likely not be harmful. If they were dosing the participants this much each day, that would create a problem, however, I don't believe the ethical review board would allow it. They most likely used this high of a dosage to obtain maximum absorption/effects. It has not been established, to my knowledge, that a higher dosage leads to greater absorption. Most nutrients can only be absorbed in certain amounts and the rest is waste. This criteria would have been good to test if they were seeking to establish the maximum amount able to be absorbed at one time.
I agree with Susan that since this study only lasted one day, harmful effects are unlikely. I also agree that the researchers wanted to make it easy to determine if a difference was present. Arthur makes a great point about whether a smaller amount would have produced a significant difference. I am comfortable with their methods.
I believe that this study used a higher amount of Vitamin D in order to see some differences in the results because the study was only done over one day. Both the original and supplemental article used over 50,000 IUD of Vitamin D in their methods section, meaning that this amount has been approved and used before in other research studies besides the one in the original article. It may actually be the standard of what is suppose to be used. While the dosage of this may not be harmful over one day, it could over time. Therefore, if this research study was held over several weeks, the dosage of the supplement taken would need to be adjusted to prevent any negative consequences. As mentioned in the comments above, the idea to screen patients for other vitamins and supplements they are taking is a good idea to prevent any type of overdose or toxicity.
Like many have previously mentioned, I think this study used such a high level of Vitamin D because the study only lasted one day. The researchers needed a high level of Vitamin D to make noticeable changes in the participants’ blood lab values. Smaller amounts of Vitamin D supplementation may make small changes in blood lab values over time, but the researchers had a limited timeframe. I think the researchers’ methods were logical since the study only lasted one day. If the study was conducted over a long period of time and they still used the 50,000 IU dose, then I would be concerned that the participants may develop Vitamin D toxicity.
Susan made a great point that it is important for participants to go through a screening process before participating in almost any study. I believe this study's screening process was well-designed, because it stated that, "Inclusion criteria included use of not more than 400 IU vitamin D or 1,000 mg calcium per day…" Therefore, the researchers protected the participants' safety by ensuring none of them were currently taking high doses of supplements. This also prevents certain extraneous variables from affecting the results.
I do not disagree (sorry, the double negative felt more appropriate than "I agree") with Tuft's supplementation of 55,905 IU D-3 because participants were only subjected to this high level for one day. I believe the researchers chose this dose, as Jessica said, to enhance the likelihood of detecting a change in participants, and a difference between the three groups, during the course of the trial.
I agree with Jenn that it would be interesting and important to the field of dietetics to find the long-term effects of the study methods and whether they are sustainable. If Tufts were to repeat the study for a longer duration, hopefully he would choose a lower dosage and it would provide a more realistic picture of what these findings would mean for the general public.
I agree with Caroline that the screening process was well-designed. The researchers wanted to make sure that their participants weren't using megadoses on their own prior to the study, which is commendable.
I also like what Charity brought up about the ethical review board, and what they would/wouldn't allow. IRB approval is considerably difficult to achieve, especially when testing on human subjects. To achieve full IRB approval, the authors probably had to provide background research regarding tolerable upper limits of Vitamin D megadoses for use in research studies.
Janelle also pointed out that there was precedent involved. The supplemental article also used a 50,000 IU dose, and did so without consequence to any of the participants. Also like Janelle said, perhaps 50,000 IU is considered the gold standard of Vitamin D doses for single-day studies. The authors would not knowingly try to cause a toxicity in their participants, nor would they submit a potentially hazardous proposition to the IRB.
I do agree with everyone that if they would modify this study over a longer period of time, the dose would have to be lowered to maintain safety, and also to achieve IRB approval.
As many others have said, I believe the researchers chose to use such a high amount of D3 in the supplement to be able to more clearly identify any changes in the participants' lab values. I do not think that a one-time high dosage of D3 is to be of concern, however all participants should be informed of the possible risks of consuming high levels of VItamin D.
I agree with Tina's point that not all of the 50,000 IU vitamin D3 will be fully absorbed. Additionally, Susan's idea of screening all participants to ensure none of them are taking additional supplements that may cause harm in addition to the D3 that will be consumed during the study.
I understand the supplements were tested, but with what he have been learning about supplements lately, one could assume that not every single supplement was tested. To play devil's advocate, can we account for supplements that were not the actual dosage that was thought to be given? How then would the outcome differ in terms of statistical significance? Would this even be a factor for a presumed dosage that high?
Considering the study used 50,000 IU of D-3 and the toxicity level is 40,000 IU, the study sounds a little unethical. However, when you consider that the toxicity would occur if a person were exceeding that level over a one month period, then I do not think the researchers were putting the participants at risk since the study was a one day dose. They probably needed that high of a dose to truly see the absorption in the serum.
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I also believe that for the purpose of this study based on the short duration the high dosage of Vitamin D is ok and was necessary in order to be able to determine if there were significant changes in absorption. However, if this study was to be duplicated and carried out for a longer duration the dosage would have to be further looked at to determine that Vitamin D at this level for an extended period of time would not cause the development of Vitamin D toxicity. Lastly, I think its crucial that the researchers know what other supplements the participants are taking prior to the study to ensure that the other supplements being taking are not influencing the absorption or the lack of absorption of the Vitamin D.
I do not think they would have conducted the study if that large dose would have been harmful to the participants. For study purposes, I think it was important to give them such a high dose of vitamin D. It would be interesting to see the result if this same study was conducted with a lower dosage. I would predict the results would not be as dramatic with a lower dose and they would have to have more than a one-time dose to see any differences.
I agree with what Tina, Jenn and Steph said about all of the dosage not being absorbed. That is probably part of the reason it was considered safe and why the researcher decided on using a higher dose for the study.
I do not think the high dosage is dangerous considering the experiment was conducted for one day. It is likely that the researchers decided to use such a high amount to ensure that there would be a measurable amount absorbed into the serum. I do not disagree with their methods, although I cannot agree without knowing their reasoning for choosing the specified amount of vitamin D in addition to the fact the researchers informed the participants of the possible risks of toxicity. But again, I do not think it is dangerous unless the trial was extended.
I believe the study used such a high dose to try to allow for maximum absorption. If I were a researcher in this study I would have given the subjects 40,000 IUs. I believe that is still a large amount and would have shown the same results. While I don't think toxicity would have been problematic in this situation, from what I understand toxicity from Vitamin D results from several months of ingestion of 50,000 IUs, if the toxicity level is suggested to be more than 40,000 the participants should not have been given more than 40,000 IUs.
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The large dose was likely used to ensure absorption was not limited by quantity of available dietary vitamin D, allowing them to better isolate the effects of the MUFA:PUFA ratio. This was also likely the reason for the short study duration of a single day. Considering 40,000IU of vitamin D would need to be taken for a whole month before toxicity occurs this study does not seem unethical at its present duration. If the study were repeated to examine the effects of proportional differences in the MUFA:PUFA ratio on absorption longitudinally, the dosage would certainly need to be adjusted to remain ethically acceptable. Close monitoring for toxicity would also need to be included in the methodology. Another thought to consider with such high, pharmacologic doses of vitamin D is if a difference in absorption is found with varying ratios of MUFA:PUFA, will it be found at a level that is significant and meaningful to the general population.
I feel that perhaps one reason as to why the researchers chose to use a very high amount Vitamin D supplement dosage was due to the age of their sample population. As individuals age, they tend to lose some of their absorptive capabilities for many nutrients. The researchers may have felt the need to up the dietary supplement amount in order to obtain more measurable results. The fact that the research study was performed during the winter months when the synthesis of Vitamin D from the skin is nearly non-existent in certain regions could have played a factor as well. There would be a much lower concentration of plasma D-3 present in the body prior to supplementation and this would therefore potentially decrease the risks for toxicity.
It does however seem very absurd that they would include such high amounts of Vitamin D-3, considering the well-known toxicity limits. One thing that I would like to add to this is the fact that it would be completely impossible to try and replicate the amount of Vitamin-D3 that was supplemented to the individuals through whole-natural foods. Therefore it simply does not make sense to me as to why the researchers would try to claim this influence of MUFA:PUFA over vitamin-D3 absorption when they are using completely unrealistic amounts of supplementation. Would there have been any significant relationships found at all had they used a more realistic amount of supplemented Vitamin D?
The screening process as noted by many other respondents does act as a safe guard. However, much of the research nutrition is turning to variations in genetics. Our genetics can play a significant role in how effectively our bodies absorb and utilize nutrients. Nutrigenetics is an exciting area of study with much potential for creating truly individualized nutrition recommendations and safe guards.
Charity brings up a great point with the ethical board committee. Completing an IRB form and going through the process to verify and validate an ethical and safe research study is long and tedious. If a high supplementation amount were truly unsafe, the ethical board committee would not approve for the study to occur if it could potentially and negatively harm participants.
John has a great point regarding realistic amounts of vitamin D. We obviously wouldn't encourage our clients to take 50,000 IU of vitamin D daily, even during the winter months. So would the results be similar if the researchers had a use a realistic level that the public can consume daily long term without negative effects? For example, would supplementing 600-800 IU to the participants produce the same results of fat increasing serum levels?
I think that researchers used such a high concentration of Vitamin D to exaggerate any increases in serum levels so that immediate inferences about MUFA:PUFA could be made. In terms of participant safety, I don't have a problem with their use of extreme supplementation because the risk of the subjects actually experiencing negative health effects caused by the supplementation is highly unlikely (and I'm sure the IRB made the researchers check.....check....and double check one more time... that such high levels of Vitamin D supplementation was clinically proven to not be harmful). In terms of validity (of generalizations made) however, I am a bit skeptical. I would want to know why they decided that ultra high supplementation of Vit D on one day can suggest that MUFA:PUFA ratio has no effect.
Viv said that she thinks "It is likely that the researchers decided to use such a high amount to ensure that there would be a measurable amount absorbed into the serum.", I totally agree and think that was their aim for using such high amounts. I am wondering if doing a one day, high level supplementation is truly reflective of the actual Vitamin D metabolism in the body.
Also, Janelle makes a really good point about screening participants for other vitamin and mineral supplements they may be taking. I hadn't thought of that. If the study was for a longer period of time I think that analyzing each participant's diet may also reveal some interesting correlations (but maybe not?).
I'm glad Vivian pointed out that while she doesn't disagree with the researchers decision she doesn't agree with it either. It is important to be critical of research and look at the explanations for decisions before supporting the study. Hopefully they did inform the subjects about the toxicity risk.
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