devaboone

I think doing an update would be great, when I have time. Just a note: the article you cited was not a randomized controlled trial. It is a meta-analysis that included only 2 small RCTs and a ton of observational studies.

The image from my post that you are referring to is looking only at RCTs. In RCTs, Vitamin D supplementation rarely shows a positive effect. This does not mean that Vitamin D supplementation is useless.

Even in my post from 2020, I mention that respiratory illness is one area that has shown a benefit of Vitamin D. Here is what I wrote:

"The areas in which meta-analyses have identified benefits from Vitamin D:

Fracture prevention in elderly nursing home residents (when also given with calcium): This is not surprising. We know that Vitamin D and calcium can prevent bone loss in severe Vitamin D deficiency. Elderly adults who are not getting outside are more likely to be severely deficient in Vitamin D, and supplements likely help.

Asthma and respiratory infection: Vitamin D seems to reduce asthma attacks in adults with mild to moderate disease, and daily or weekly Vitamin D seems to prevent acute respiratory infection in those with Vitamin D less than 10 ng/ml (25 nmol/l). There is considerable excitement around Vitamin D's potential role in Covid treatment, though we do not yet have enough evidence to make a definitive conclusion.

Cancer mortality: Vitamin D does not appear to prevent cancer, but may reduce death rates from cancer overall (when all cancers are combined) when Vitamin D is taken for several years. It is not known whether Vitamin D itself fights cancer. It could also be that individuals with cancer are more prone to developing severe Vitamin D deficiency, which leads to bone loss, fragility, and fractures, which increase mortality.

Atopic dermatitis (eczema): Vitamin D supplementation may prevent exacerbation of eczema. There are only a small number of trials, with small numbers of patients, so this requires more research."

We do have more information on Covid and Vitamin D now, and I would agree that Vitamin D was likely beneficial for some people. I would also add that I had a bunch of patients come in with high calcium because they started high-dose Vitamin D during Covid and never decreased the dose.

I’m the author. In reading the comments here, there are some common questions and misunderstandings that I would like to address.

First, about the patient being an outlier:

I wrote the article because I see cases like hers pretty frequently, and it’s frustrating. She is an outlier in the severity of her symptoms, but not an outlier in getting Vitamin D toxicity from 5,000 units daily. I get at least one patient a week contacting me about their high calcium levels - and when I get into their medical history it is clear that Vitamin D is the cause of the high calcium. In most cases, they are on 5,000 units daily. Stopping the Vitamin D allows the calcium to drop back to normal, though it usually takes a few months.

Regarding those of you on high doses who are doing just fine:

I believe you. This actually doesn’t change the point of my article. I even state in there that some people can take high doses and not develop any problems. And some people need higher doses of Vitamin D because they have problems with Vitamin D metabolism. In addition, there are people on higher doses because they are treating other medical conditions like psoriasis. The point of my article is that you need to monitor your calcium and Vitamin D levels if you are going to take these higher doses. And you need to know the risks of taking high-dose Vitamin D over a long period of time. There are risks to any medication; treat Vitamin D like the medication that it is.

About the multiple studies posted here with statements that high-dose Vitamin D is safe and toxicity is rare:

It's really important to follow the sources. I cannot say this enough. Most of the articles cited are review articles that are simply repeating things from other review articles. You have to keep following the citations back to find the actual studies in which humans consumed Vitamin D.

When you do that, you find very few human studies on high doses. The larger studies on Vitamin D will typically use more moderate doses, such as 2,000 units daily. Most of the articles on high doses are case reports in which someone took outrageous amounts of Vitamin D and eventually got really sick from it. These case reports don’t tell us where the safe level is, only that some people can tolerate outrageous doses for a short period of time.

But isn’t there an actual study showing that high doses are safe? One controlled study that many of the review articles refer back to is a small study done in men in high latitudes in winter, when skin production of Vitamin D is decreased. It consisted of a small number of patients who were randomized to receive different amounts of Vitamin D, from none to 10,000 units daily. Only a small number actually got 10,000 units a day, the highest dose. And this was over a period of just 5 months, in the winter, in high latitude, when it is difficult to get skin production of Vitamin D. You can read the article here: https://pubmed.ncbi.nlm.nih.gov/12499343/ Also note that in this study, they found that adequate Vitamin D levels were maintained with doses well under 10,000 units daily.

A few of the review articles lead back to Michael Holick, controversial figure. He is well-known for pushing high doses of Vitamin D. Please read this NY Times article for a great summary of the issues here: https://www.nytimes.com/2018/08/18/business/vitamin-d-michae...

Regarding skin production of Vitamin D and why you don’t overdose on the sun:

Others mentioned this in their responses, but just to reiterate: you can’t get toxic levels of Vitamin D from being in the sun, because of the complex interactions that occur with UVB exposure. For those who want a very detailed explanation, read this article: https://www.tandfonline.com/doi/full/10.4161/derm.24494. TL;DR version: after a certain amount of previtamin D and Vitamin D3 is made as a result of UVB radiation, excess exposure then causes breakdown of these into products that are inactive, so you get to an equilibrium where you can’t make more Vitamin D even with more sun exposure.

And for those who think I am somehow anti-Vitamin D:

I take Vitamin D, and recommend it to patients all the time (unless they have high calcium). I recommend moderate amounts, since for most people a dose of 1,000 to 2,000 units daily is more than enough. I do have patients who need to take much higher doses, and I have some patients on 5,000 units daily who are doing just fine. There are even rare patients who need more than that. The key here is that I’m monitoring their calcium and Vitamin D levels, and I only recommend 5,000 units daily if there is some evidence that they require it.

About selling high doses in pharmacies:

I really don’t like that in the US you can pretty easily buy 10,000 unit Vitamin D pills over the counter at common pharmacies (example: https://www.walgreens.com/store/c/nature's-bounty-d3-10,000-.... I would prefer that pharmacies sold Vitamin D in doses of 1,000 or 2,000 units, rather than 5,000 units, since the lower doses are almost always safe, but the higher doses may not be. Someone mentioned that Tylenol and ibuprofen are also dangerous, but available over the counter. This is not exactly the same thing, since those bottles are generally very conservative in how much they recommend taking, with strict warnings about not taking too much. This is not the case with most Vitamin D bottles.

If you want more info on Vitamin D, I wrote a couple other posts that cover some important background information and then the evidence for Vitamin D: Part 1, Basics of Vitamin D: https://www.devaboone.com/post/vitamin-d-part-1-back-to-basi... Part 3, Evidence for supplementation: https://www.devaboone.com/post/vitamin-d-part-3-the-evidence

Note that I wrote these several years ago in 2020. There have been more trials published since then, but the results are similar.

I wrote the article because I see cases like hers pretty frequently. She is an outlier in the severity of her symptoms, but not an outlier in getting Vitamin D toxicity from 5,000 units daily. I get at least one patient a week contacting me about their high calcium levels - and when I get into their medical history it is clear that Vitamin D is the cause of the high calcium. In most cases, they are on 5,000 units daily.

Some people need higher doses of Vitamin D because they have problems with Vitamin D metabolism. Those people are outliers as well.

And there are people who can take 5,000 units of Vitamin D over a prolonged period and still have normal calcium levels. The key here is that they are checking calcium and Vitamin D levels.

For most people who need Vitamin D, a dose of 1,000 to 2,000 units daily is more than enough. None of your articles contradict that, and actually that is the dose they are recommending.

Also, Michael Holick is a controversial figure. A lot of the articles pushing high doses of Vitamin D lead back to him. Please read this NY Times article for a great summary of his issues: https://www.nytimes.com/2018/08/18/business/vitamin-d-michae...

This is one case report. Yes, this person took an insane amount of Vitamin D and ended up very sick from it. But we can't really conclude that amounts under her dose are safe.

It's really important to follow the sources when you see something like this quoted. The article you link to is not an actual study in which people were given Vitamin D. It is a review article, and the specific sentence you quote references an article by Michael Holick, who then references two other articles. One of those articles is just a review, not citing new evidence.

The one piece of evidence that these are all referring back to is a small study done in men in high latitudes in winter, when skin production of Vitamin D is decreased. It consisted of a small number of patients who were randomized to receive different amounts of Vitamin D, so only a small number actually got 10,000 units a day, the highest dose. And this was over a period of just 5 months. You can read the article here: https://pubmed.ncbi.nlm.nih.gov/12499343/

Note that the highest dose in this study was 10,000 units a day, which I would agree can be safe for some people over a short period of time. But it was not necessary in this study to attain goal Vitamin D levels, and over time that dose can definitely cause problems.

Also, where is the 50,000 to 100,000 unit evidence coming from? I'm not sure actually, since there are no human studies looking at that dose. This may be a "theoretical" dose based on studies in other animals, or a false extrapolation based on human studies.

There is a big difference between Canada and the US in how Vitamin D is treated.

In the US, you can go into any major pharmacy chain like CVS or Walgreens and purchase Vitamin D over the counter in 5,000 unit pills, with the bottle instructions saying to take once daily. I periodically check the Vitamin D supplements available and will find them with 10,000 units per pill, again with instructions to take once daily.

Many of the patients from the US who come to me are taking Vitamin D - and 5,000 units a day is a common dose. Most of them are told to take this by their physician, and others are on the dose because they just went to the pharmacy and picked up a bottle, which happened to contain 5,000 units.

Just a quick google search produced these 10,000 unit pills available at Walgreens, made by a common vitamin company. Note that the instructions are to take once daily, and there is no mention of watching calcium levels: https://www.walgreens.com/store/c/nature's-bounty-d3-10,000-...

Hey there! I'm here now and will try to respond to everything brought up. Some of the confusion stems from the complexity of the issue. There has been a lot of research on the clinical role of Vitamin D, much of it of questionable quality. On the basic science of it, there is a lot of great research, but these articles are often hard to read unless you have a PhD in biochemistry.

I am a physician (specialty surgeon) in the US, so can comment from that perspective.

Clinical documentation is often the bane of my existence, so there is definitely a need for innovation. But entering this market (in the US, anyway) may be challenging. I do not know anything about the German market, but in the US, there are a few things to note. First, this market is already pretty saturated. There are some big players (like Epic) that dominate the hospitals, as well as many smaller companies that cater to specialized markets, such as solo practitioners or mental health providers. If your clinical documentation system is not outrageously better than these (and even if it is), it may be hard to break into this market.

Another challenge in the US is around regulations and CMS requirements. Clinical documentation is the way providers ensure that they can get paid. CMS has a lot of requirements in what needs to be in your software. I don't know this area as well, so can't comment too much. But if you want to come to the US, you will need to know it really well.

As a physician, I find it hard to believe that you could cut the cost of clinical procedures by 20% with just documentation software. How are you calculating that? I'm also skeptical about such large profit margins.

For example, the comment from Paul Gambill, the CEO of Nori who is quoted extensively in the article. He wrote in to clarify that he does not agree with the title and that he does in fact think that afforestation is necessary.

For those interested in Vitamin D and Covid, here is a summary of the research so far: https://www.devaboone.com/post/vitamin-d-and-covid

I see Vitamin D toxicity at MUCH lower doses than in this case report. Here is my description of one patient: https://www.devaboone.com/post/vitamin-d-part-2-shannon-s-st...

Most of the patients I see with vitamin D toxicity are on 5000 units daily or more. And it can take a while (years) for toxicity to occur. Vitamin D builds up during that time since it is fat-soluble. If you want to take Vitamin D over a long period of time, at least check your levels.

The headlines on Vitamin D and Covid far surpass the actual data. Here is my summary on the latest research: https://www.devaboone.com/post/vitamin-d-and-covid

Which fields put names in alphabetical order? In medicine, at least, deciding who goes in the first and last name spots is a really big deal, and fights over this sometimes ruin professional relationships.

The chart is only regarding RCTs. In the best individual trials that we have, it does not show a benefit for respiratory infections. But we do see some suggestion of benefit in meta-analyses. In general, if the meta-analysis shows something that is not seen in RCTs, then we probably need more evidence. But it does seem to be a real effect.

I don't think it is all due to sampling error. In my article I mention that one of the areas in which Vitamin D shows promise is with respiratory illness. I think there likely is an effect, just not as dramatic as the headlines are making it.

I wrote the article. It was very hard to write a concise article about all of Vitamin D research, and so I didn't have space to address it, though I really appreciate the feedback. Race and Vitamin D is an interesting area. The VITAL trial, which is the largest study on Vitamin D that we have, with 25,000 participants, tried to enroll more Blacks, and in the end 20% of the participants were Black. They showed the same results, but interestingly it did seem like there might be a trend toward fewer cancers for Blacks who received Vitamin D, but this was not definitive. More research on this is needed.

The other reason I didn't get into race and Vitamin D is that we then start getting into the blood levels, and what really constitutes deficiency. I think we are a little too liberal with our diagnosis of deficiency right now.

I wrote the blog post. Unfortunately I was not able to include every study on Vitamin D, and had to pare it back to the largest and/or most significant studies. Most of the studies you mention are small and published in obscure journals.

As for my argument, I would never claim that Vitamin D is "a pretty useless vitamin". It is extremely useful, and is lifesaving for people with hypoparathyroidism. But that doesn't mean we should all be taking it. Note that the studies you mention are looking at treating something, not preventing something. Many of the people supplementing are doing it because they believe it will keep them healthy - and this does not appear to be the case. That is more the point of my article. The articles you cite are interesting and hopefully will produce larger trials.

Here is what the article states: "Therefore, a multivariate logistic regression analysis was performed to adjust the model by possible confounding variables such as hypertension and type 2 diabetes mellitus for the probability of the admission to the Intensive Care Unit in patients with Calcifediol treatment vs Without Calcifediol treatment (odds ratio: 0.03 (95%CI: 0.003-0.25) (Table 3). The dependent variable considered was the need to be treated or not in ICU (dichotomous variable).) CI:-0.30 - 0.03 p:0.08." The statement is worded in a confusing way, but that is a non-significant p value. Of course we should not put too much into "statistical significance" but it is interesting to note.

I tried really really hard to put in all of the most significant studies on Vitamin D. Small, low-quality studies didn't make it in, but the major trials did.

I didn't watch the whole video but I read the study. There is a lot of excitement about this study, but the details in it matter. It was randomized - but when you look at the two groups (treatment vs. control), they had some key differences. The control group (who didn't receive Vitamin D) had more men (69% vs 54%), more people with hypertension (57% vs 24%) and diabetes (19% vs 6%). These are all areas that increase the risk of severe disease. So the groups were not the same. If you just compare the numbers of those who went into the ICU vs. not, then the results look amazing. But once you correct for hypertension and diabetes, it was not so impressive - it was not statistically significant in the study. This does not mean that I think Vitamin D has no effect. There is some evidence for Vitamin D in respiratory illnesses. But the effect is not as dramatic as some of the headlines for this study would imply.

There is a lot of excitement about this study, but the details in it matter. It was randomized - but when you look at the two groups (treatment vs. control), they had some key differences. The control group (who didn't receive Vitamin D) had more men (69% vs 54%), more people with hypertension (57% vs 24%) and diabetes (19% vs 6%). So the groups were not the same. If you just compare the numbers of those who went into the ICU vs. not, then the results look amazing. But once you correct for hypertension and diabetes, it was not so impressive - it was not statistically significant in the study. (It is in the study but most people breeze right over that.)

That is a reasonable hypothesis. Also, people who are very ill are less likely to get outside and get enough sun, so they will develop low Vitamin D. Vitamin D is likely a marker of poor health. (Once the Vitamin D gets low enough, we do see direct harmful effects from it (think rickets in children), and this may contribute to poor health at that point.)

Thanks for the feedback. I will edit the article to specify that she was NOT taking any calcium throughout all of this. This is not uncommon - Vitamin D seems to be more effective at raising calcium levels than calcium itself. I do take issue with your claim that the majority of people with Vitamin D levels of 80 are fine. We actually do not know this. I can't say whether they are fine or not. But I can say that I see enough of them with high calcium levels, who are clearly not fine. They may be in the minority. Still, we do need to treat Vitamin D like a medication. Like any medication, some people will do just fine on high doses. Others will not. That's ok; we just need to be aware of that and watch out for harmful effects.

This is exactly it. I was able to see it because I deal with this every day. I am not more holistic than other doctors; I just know how to look at calcium and Vitamin D levels.

This is a correlation. There are lots of conditions that are associated with low Vitamin D. Mortality overall is associated with low Vitamin D. But it doesn't mean that the low Vitamin D caused any of these problems. Having overall poor health leads to Vitamin D deficiency. The increase in mortality is more likely related to your overall health status, not your Vit D status.

I really like the Cochrane reviews, and love that they periodically update areas when there is more recent research. And you are correct, their articles on Vitamin D have become less enthusiastic with time. This makes sense I think, since the initial publications on a topic will all be "positive" - they have to find something new to get published (creating a publication bias). And they do try to account for publication bias, but really the best way to fix it is to have more studies. With Vitamin D getting so much attention, you can get published whether you find a correlation or not, so you have a wider range of studies to look at. I wanted to give a summary of the Cochrane reviews and the largest human trials of Vitamin D in the next blog post.

Thanks! Yes, I am very new to this. Hoping that by continuing to write, I'll get better. The comments on here are great for helping me understand how things are interpreted.

The problem is that a lot of people taking Vitamin D may not need it. The percentage of the population with vitamin D deficiency depends on your definition of deficiency - and that changes. From large trials in humans, there is very little benefit to most adults in taking Vitamin D. If you are deficient and you are an elderly woman in a nursing home, then yes, we have good evidence that vit D supplementation will help you. If you are a younger healthy male, probably not.

Thanks. It's hard to balance the strictly scientific with enough of the "softer" stuff to make it interesting for a wide audience.