February 11, 2009
There's nothing like hearing the results of studies directly from those who actually conducted the research. In this interview, you'll meet one of these impressive HIV researchers and read her explanation of a study she presented at the 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009).
My name is Kate Childs. I've just recently been doing a master's at Mt. Sinai School of Medicine, although I am a clinician looking after patients with HIV.
This study is looking at the effect of varying doses of vitamin D supplementation on serum vitamin D level in a group of HIV-infected men from New York.1 We took a group of 72 men and we measured their vitamin D levels at baseline. A level of less than 30 ng/mL [nanograms per milliliter] is defined as a suboptimal level of vitamin D.
What percentage of the men had suboptimal levels?
Seventy four percent. In fact, 53% had a level of less than 20, which would be deficiency. The men who had a suboptimal level were advised to start taking vitamin D3 in calcium citrate supplements. The dose that we recommended was based on their baseline value. The men who were severely deficient with a level of less than 10 were asked to take a total of 2,800 IUs [international units] of vitamin D3 plus one gram of solid calcium citrate.
Those with a level of 10 to 20 were advised to take 1,800 units and the men with a level of between 20 and 30 were recommended to take 800 IUs of vitamin D3. As I said, [every group was asked] to take one gram of calcium citrate as well.
Why was the calcium necessary?
Vitamin D and calcium are completely synergistic in their actions. Many people do not have enough calcium in their diets, so you're not going to see any type of benefit of vitamin D if you don't get calcium as well.
The ones with a level in the optimal range were not advised to take any supplements because obviously we thought they were already in the optimal range.
We also stratified according to adherence. We asked men if they took the supplements: never, sometimes, or always, so you can see that unsurprisingly the ones who always took the supplements had a significantly greater increase in their vitamin D level.
How did you arrive at the recommended doses?
It was just based on literature review. There's actually no data on this at all in HIV-positive patients. I believe a paper's been published in the interim, so it was based on the recommendations of experts such as Michael Hollick who's written extensively on vitamin D, and also on the observation that in fact many of our patients had already been taking doses of 400 IUs at baseline as part of a multivitamin supplement.
Obviously that did nothing at all to help them avoid being vitamin D deficient. So, in the subjects who reported complete adherence, we saw quite an increase. We saw an increase of 14.4 ng/mL. But it's important to say that even though they all had an increase, only 40 percent of them managed to get into the optimal range, so still, a lot of them did not.
You can see that over here [in the poster], so these are the individual patients. Once they crossed that line, they're in the optimal range, but most of them still didn't manage to.
Why do you think that they didn't manage to make it into the optimal range?
We don't know. It's fairly surprisingly.Obviously there still could be adherence issues even though, they said that they had to take it all the time, but perhaps we needed higher doses, perhaps we needed longer duration of followup. The median duration of followup was 18 weeks.
Were the men asked to take the supplements once-a-day and did they have to take it at any specific time?
They could take it at any time and it was a once-a-day dose. The other thing that was quite interesting that we saw is vitamin D is made in the skin by the action of sunlight. So there's a well-observed increase in vitamin D levels in the summer, when obviously the sun is shining more.
What we actually found is that patients that weren't advised to take supplements -- so the ones who started off in that optimal range actually experienced a decrease from winter to summer, so this chart [on the poster] shows men who were advised to take vitamin D supplements and the ones who were not advised. This is the change in vitamin D.
Everyone who was advised to take supplements had an increase. But in fact, all the ones who weren't advised to take supplements had a decrease. That's quite an important point, so we feel strongly that clinicians should not be reassured.
When they measure someone's vitamin D level in the winter and they say, "OK it's a bit low, but in the summer it'll be fine." Our data doesn't support that. We think clinicians need to be quite vigilant.
In conclusion, we were giving high doses -- doses that were many times greater than their adequate intake, but they were safe and they did not lead to hypercalcemia.
Is hypercalcemia the only risk of high dose of vitamin D?
So you check that along the way?
Yes, we monitored everyone's serum calcium levels. We found basically that it was safe, that it increased serum vitamin D levels, but that possibly either higher vitamin D doses or a longer duration of followup are needed because a majority still do not make it into the optimal range.
Also, importantly, that clinicians should not assume that patients' levels will increase in the summer because we actually saw very minimal seasonal variation.
Can you tell me some of the benefits that are seen in optimal vitamin D in someone who's HIV positive in particular.
Most of the literature is in patients who are not HIV positive. I have to say there's a phenomenal wealth of data, mostly on a cross-sectional basis showing association of low vitamin D levels with more diabetes, more hypertension, more cardiovascular risk, more systemic inflammation, depression, fatigue, autoimmune diseases, cancers, many cancers being associated with low levels of vitamin D.
In terms of HIV, there aren't many studies as yet showing that in HIV, but obviously all those outcomes I just described are extremely relevant and important in the context of HIV, so we think that patients with HIV infection probably have even more to gain than your average man on the street from having an optimal level of vitamin D. It's an easily modifiable parameter that could have a real health benefit.
Inflammation is a big problem for HIV-infected people and if you have low vitamin D levels, that could be a problem as well, right?
Precisely, I mean inflammation's obviously one of the most important things that is being looked at in the context of HIV infection at the moment. Certainly low vitamin D levels have been associated with increased systemic inflammation. So yes, we think vitamin D is probably very important for patients with HIV.
Are you going to be continuing looking at this? Is this going ...
We are. We're hoping to do further followup measurements one year after they were initially invited to be given supplements, which obviously will remove the effect of seasonal variation to see if we managed to attain optimal vitamin D levels.
We'll also be looking at other parameters, such as their PTH [parathyroid hormone] level and their calcium levels. So we're going to carry on looking at this group of men.
Will you also be looking at a better way to maybe deliver the supplements becauseif it didn't work for some people, that's kind of an issue.
It's difficult. It's very difficult. I think we have to make sure that we've optimized the study in terms of adherence and in terms of duration of followup because we don't want to just be throwing bigger and bigger doses of vitamin D at people and then risk developing hypercalcemia in a small number.
I certainly think that vitamin D3 supplementation, which is what we used is the actual supplement shown to be the most potent and also the one that's least likely to cause hypercalcemia because other forms of vitamin D can cause hypercalcemia more readily than this.
What vitamin D supplement brand did you recommend to patients?
We had to recommend it and they just went out and purchased it, which is unfortunately a constraint. We would have loved to be able to prescribe it.
So it could be varying doses. Because not all vitamins have what they are supposed to have. It's an unregulated business.
That's absolutely true. We recommended that they take the certain dose of calcium citrate and a certain dose of vitamin D, but you're right. You're right. That's a limitation.
Okay, thank you very much.
This transcript has been edited for clarity.