Transcript
Speaker: You are listening to the What's the Proof podcast, where we seek to help doctors and other clinicians incorporate the best available evidence into their everyday clinical decision making. The content of this podcast is meant for educational purposes only and should not be construed as personalized medical advice. The views and opinions expressed are those of the host and guest, and no content on this podcast has been approved or sanctioned by Atrium Health.
Speaker: Vitamin D, a supplement so commonly recommended yet so widely misunderstood. For years, the question of its role in disease prevention has been tough to answer. But now, new guidelines shed light on this controversial topic. On today's episode of What's the Proof, we'll break down these practice -changing recommendations so you can confidently address your patient's questions about checking vitamin D levels or starting a supplement.
Speaker: Hi everyone. Welcome to What's the Proof, the family medicine podcast that seeks to help doctors and other clinicians incorporate the best available evidence into their everyday decision -making. I'm Bobby Scott and with me are Sandy Robertson and Dawn Kavanas. Dawn, how are you doing today?
Speaker: I'm doing great. I got up. I'm still feeling feeling very motivated by our last podcast. I got up and did my workout, then went for my little walk around the pond. good about that i yeah I have to do that in the mornings now because we put up new fencing and I have this goat that keeps putting its head through the fence.
Speaker: And he doesn't realize how big its head is, or how big its horn so he gets stuck. So he'll just be down there, bang, because he had his head stuck. So it was by turn to check the fence. Is it a baby goat? It is not. It is an adult goat that should know better. But that's my life. I love the empathy, Dawn. They don't seem to be that smart to me. I don't know. Are they intelligent animals?
Speaker: They're tricky, like they can, you know, put their head through and not remember how big their head is and can't figure out how to get it out of the fence. And then also are like Houdini's and can find the one little crack in the fence and be able to get out and you cannot figure out how they got out of the fence. So it's, you never know. They keep you guessing. bad well i'm I'm glad for your sake that the weather's gotten a little bit warmer here. So maybe you don't have that 10 degree cold walk in the morning, right? Yes, I have a heated vest though.
Speaker: oh wow advanced how about you guys how how have y 'all been doing with the with the exercise
Speaker: i was I'm gonna give my myself, I don't know, seven out of 10. The winter's been rougher for me with some viral illnesses and lack of motivation and the abundance of comfort food post -holidays, but i'm I'm back at it. This past week has been, past seven days have been really good for me, so I'm hoping that it can just keep going in that direction.
Speaker: How about you, Bobby? Yeah, it's a cold and flu season. I'm recovering from a cold right now, so that's why I might sound a little froggy today, but yeah, it's ah it's been okay. I think it's still getting out there and rucking even when it's real cold. I usually try to go around you know late afternoon when the sun's at its peak. and that i mean I usually can warm up enough. is The first 10 to 15 minutes are pretty pretty rough, but by the time I get my heart rate going, I'm i'm usually good for a little bit.
Speaker: I still just struggle with getting the weightlifting in every week. yeah okay Do I need to start challenging you? I can do that. I need some kind of better system to do it. ok but yeah we We could talk about that. i think Yeah, I'll think about that. In all fairness, I was not going to miss this morning's workout because I thought Sandy might ask me. so That is a motivator. Me too. really are count about it yeah do Me too. proud I'm proud of both of you. You're doing great.
Speaker: Well, thank you. Thank you. let Let's, let's, uh, go ahead and get started with today's discussion. Okay. I'm excited. i to Yes, me too.
Speaker: We know that vitamin D plays an essential role in our bodies, particularly when it comes to bone health. Hundreds of studies have investigated the role of vitamin D in humans. Like many other topics, early studies were epidemiologic, and they showed associations of low vitamin D status with a myriad of conditions such as metabolic, cardiovascular, and immune dysfunctions, as well as certain malignancies and infectious diseases.
Speaker: epidemiologic studies, like these are really meant to stimulate further research, but instead supplementation with vitamin D and testing vitamin D levels have really become widespread in medicine. So the randomized controlled trials that examine causation would come much later, but by then, as Don would say, the horse was already out of the barn.
Speaker: this mismatch between early adoption. the goat stuck in the fence. Yeah, that's got to be some new new idiom there. But and yeah, so this mismatch between early adoption of a standard of care that is testing vitamin D levels and supplementing accordingly, and the later arrival of patient -oriented evidence has created controversy as it suggests a necessary reversal of the standard.
Speaker: Fortunately though, we have some new guidelines and they provide a whole lot of clarity that I think should make this transition easier. So let's unpack these latest findings on vitamin D and explore their implications for clinical practice and see why it's essential to interpret this evidence thoughtfully.
Speaker: Yes, so let's take a look at the 2024 Endocrine Society Practice Guidelines. and They focus on vitamin D supplementation and testing for the general population without known vitamin D deficiency or specific indications for testing. That's super important. So this is general population without known vitamin D deficiency or specific indications for testing. ah These recommendations were developed by a multidisciplinary panel of experts using evidence -based criteria. Importantly,
Speaker: the guideline, they, you know, they plan to review this annually to incorporate new evidence as it emerges. We will discuss each of their key recommendations and the rationale behind them. So first, who should receive vitamin D supplementation?
Speaker: This is empiric supplementation, meaning the use of vitamin D, ah vitamin D3 or D2 in amounts that, one, exceed the dietary reference intakes established by the Institute of Medicine and are implemented without testing for vitamin D levels.
Speaker: So supplementation could come in the form of fortified foods, vitamin formulations containing vitamin D, or daily intake of a supplement pill or drops. Remember, in populations without established medical indications for vitamin D treatment, such as rickets or osteomalacia. So according to the guidelines, supplementation is suggested for the following. So children aged 1 through 18 years, pregnant individuals,
Speaker: adults age 75 and older and adults with prediabetes. Conversely, supplementation is not recommended for non -pregnant adults age 19 and 74. So basically everybody else. So the system the systematic reviews underpinning these recommendations help us understand why the Endocrine Society made these recommendations. So Sandy, would you break this down by population for us?
Speaker: I would be happy to. And I'm gonna let everybody kind of digest that because it's really hard to to focus on these groups and and understand that there's a large group now that we're not recommending supplementation to. So I wanna start out before I go into these four categories, just to say that this guideline was very clear and very transparent that the optimal dose for any of these um categories is unclear. So when I go through... It's clear that it's not clear. That's right. That's right. and And a lot of research has gone into this, okay? And i I will review for you what these doses that they're recommending they're suggesting are, but just understand that we don't have just a set dose
Speaker: um that we know that we've tested in a randomized control fashion um with all of these studies. so But in general, I just want you to know that the guidelines favor lower daily doses rather than weekly or monthly doses. So that's what you're going to hear me say um throughout this. So first, let's start with the kiddos.
Speaker: So children age 1 to 18. The primary reason for this is for the prevention of rickets, although there are no randomized controlled trials to prove this, which is very interesting. This is a universally accepted method for preventing rickets rickets and has become the standard of care prior to the development of modern methodologies.
Speaker: There are some non -randomized controlled trial data to support this in infants, and guideline makers thought it would be prudent to extrapolate this to all children with open growth plates. I think all of us will probably say, that's fine. Now, in addition to that, right, everybody agrees, right? We're just gonna let that go.
Speaker: In addition to that, the review included 12 randomized control trials on respiratory infections worldwide. Now, the benefits were small, if any, so the guideline gave this a low certainty conditional recommendation. And just so for your reference, the doses in these 12 randomized control trials ranged from 300 to 2 ,000 IUs daily, okay? So low certainty conditional recommendation for the prevention of respiratory infections in children.
Speaker: but it is recommended. Okay, category two, pregnancy. Boy, all right, analyzing pregnancy outcomes is challenging due to all the diverse trial designs. ah The systematic review suggests potential benefits, including reduced risk of preeclampsia,
Speaker: IUGR and neonatal complications. Because they assess that empiric supplementation is inexpensive and may be cost effective and is probably acceptable to key stakeholders, the panel also gave this a low certainty conditional recommendation. And overall, the dose that they recommend, even though they know it's a little bit unclear, is 600 IUs a day, okay?
Speaker: The third category, and this is um very interesting to me, adults age 75 and older. So we have data from 25 trials. This is 49 ,000 participants that are over the age of 75 and older that showed a slight reduction in all -cause mortality. And what that equated to was six fewer deaths per 1 ,000 people.
Speaker: Now, importantly, these results didn't vary significantly based on vitamin D levels. So whether you had levels below 20 nanograms per mL or greater, um there were benefits seen, okay, in both categories. This, unlike the other two categories, um is a moderate certainty conditional recommendation. So a little bit stronger in the recommendation. And the dose that they kind of landed on here was 800 IU's a day.
Speaker: Lastly, and I will admit to my listeners and to my colleagues that I didn't see this in the data, um is adults with prediabetes.
Speaker: So among 11 trials, these are all randomized controlled trials, three were specifically designed to test the risk of progression to diabetes with either vitamin D or placebo. So in these trials, there were about 4 ,100 participants, and it showed a 15 % relative risk reduction in disease in diabetes progression with vitamin D supplementation. and The median dose in these trials was 2 ,600 IUs a day.
Speaker: To give you some absolute numbers, this equates to 24 fewer progressions from prediabetes to diabetes per 1 ,000 people after three years of use. Now, in these trials, the benefits appear to be greater in older adults, so those over the age of 62, those with a baseline vitamin D level of less than 12, so very, very low, and individuals with a BMI less than 30.
Speaker: So there you go. Excellent. Well, let's now shift gears into and talk about who should not supplement according to the guidelines. And the quick, easy answer is it's basically everybody else. So adults aged 19 to 49, there's the data here are sparse. There are a few trials that are small looking at respiratory infections and fatigue, and they really did not show any consistent benefits.
Speaker: There's some limited evidence on bone mass density and and that those also failed to show improvement. So and ages 19 to 49, not much evidence for benefit there. and um Adults age 50 to 74. Now this group had the most data.
Speaker: It included some very large, newer trials like the vital study and the dehealth study. The vital study had 25 ,000 participants. The dehealth study had 21 ,000, and they reviewed a lot of different outcomes like cardiovascular disease, cancer, all -cause mortality, fractures, basically all these outcomes that the epidemiologic studies suggested an association with, they tested them. right And these were two very large, well -designed RCTs, and they showed that there is little to no benefit to routine supplementation for the prevention of cardiovascular disease, cancer, all -cause mortality, and even fractures. So let me say that again, because there appears to be little to no benefit for routine vitamin D supplementation in this population.
Speaker: for any of the outcomes that were previously suggested by the observational data, and that's pretty big deal. That's you that's that's a big, um probably going to be a big change for a lot of people. right um Now, the guideline gave this a moderate certainty recommendation, which I felt personally was a bit of a waffle.
Speaker: I thought it should be considered high certainty based on the evidence that they ah included. and But they explained that this was because the trials had a large number of patients who would have been considered vitamin D replete at baseline. So they didn't feel comfortable giving it a high certainty recommendation. But either way, the recommendation still stands. This is not recommended for this group.
Speaker: And as a side note, I also disagreed with their rationale for recommending routine supplementation in pregnancy. I mean, if you look at the studies included, they all demonstrated a risk reduction. However, the confidence intervals for each outcome crossed one, indicating that it's possible that vitamin D is not helpful or may even be harmful for these outcomes.
Speaker: And their rationale, they cited another meta -analysis that also had similar results and felt that the point estimates trended towards benefit, so they gave it a conditional recommendation. And now, I mean, that's just me, I guess. I tend to be more of a purist, and I don't like recommending something unless we have more confidence of benefit. But you know since most prenatal vitamins have vitamin D in them anyway, it's probably just me being nitpicky and crotchety.
Speaker: You're so nitpicking and crotchety. That's the word that ascribed Dr. Scott Webb. Right, right. So we've identified the groups from whom supplementation may be beneficial and for whom it's not recommended. This naturally raises the next question. Should we monitor vitamin D levels in those taking supplements?
Speaker: Man, I get asked this all the time in clinic. like Almost every day I get a question surrounding this. so this is This is really great for me to review. so Surprisingly, the answer is no. The guideline is explicit in that there is no evidence to support routine vitamin D testing for screening or dose adjustments in any of these populations. This represents a significant reversal from previous guidelines published in 2011.
Speaker: So to reiterate, the new Endocrine Society guideline advises against routine vitamin D screening in the absence of well -established indications such as osteomalacia. This applies even to some special population groups like adults and children with obesity, adults and children with dark complexion, pregnant individuals.
Speaker: So, notably, the you know United States Prevention Services Task Force, the USPSTF, reached a similar conclusion in 2014 and reaffirmed it in 2021, stating that there was insufficient evidence for screening vitamin D in community -dwelling, asymptomatic, non -pregnant adults.
Speaker: Now some might be asking, you know, what's the harm? So vitamin D in itself is honestly a low risk supplement and low cost, but there is considerable system costs related to taking levels and screening. Inappropriate testing is estimated to cost, to get this, 2 .5 million annually with excess Medicare costs exceeding 800 million.
Speaker: Yes, those those numbers add up for that low risk test, right? We just, sometimes the patient wants it. We just will do it, but it really adds up. So here's my question, Dawn and Bobby. If we're not testing, how do we define vitamin D deficiency?
Speaker: Right? Isn't that a thing? Like, so do I put that like in the chart? So, okay. All right, so this is another area where the guidelines have shifted. Clinically, deficiency is defined as having signs or symptoms of rickets or osteomalacia. However, in practice, deficiency has become commonly defined by circulating blood levels of vitamin D, the 25 hydroxy vitamin D that we always measure.
Speaker: I mean, we're numbers people, right? So we love to see numbers. We love to see them go up and go down. and All right, there is no universally endorsed lab threshold definition of vitamin D deficiency.
Speaker: That's even hard to read um because for decades I would have answered that differently. So to cut to the chase, the panel found no evidence for specific vitamin D thresholds tied to meaningful health outcome benefits. As such, the previously recommended target of 30 nanograms per mL from the 2011 guidelines is no longer endorsed. Similarly, the Endocrine Society no longer endorses any specific level to define vitamin D sufficiency, insufficiency, and deficiency.
Speaker: The lack of an optimal level for improving outcomes was evident in subgroup analyses from the major trials like the vital trial and the dehealth trial. These showed no consistent differences in results for participants with vitamin D levels above or below 20, which is what most of us kind of accepted as a vitamin D deficient level. in prior to today, right? So the bottom line here is there is no evidence to support checking vitamin D levels for screening, achieving treatment targets, or for making dosage adjustments in those who are being supplemented. This is a very significant change and clinicians and patients may take some time to adjust to this change in mindset.
Speaker: Yes. is Gosh, it is so much simpler. i mean It is. I love it. After so after years of you highly opinionated and cloudy practice surrounding vitamin D, yeah we now have you know the best evidence we now have says that empirically, you should take a supplement if you're in one of these groups.
Speaker: But if you're on it, you don't need to worry about your levels. And this is really such a relief to me, and I think it will be much easier for the patients than we fear. yeah Actually, I shared this with a patient in clinic last week, and she was actually so grateful that she did not have to think about her levels because they were really a source of worry for her.
Speaker: She was happy to know that she could just take her supplement and she didn't have to worry. and yeah She was pre -diabetic, so she did have a reason to take it. She wasn't one of these groups. and I can see it being more challenging to suggest patients who aren't in one of these groups to stop taking their supplement when somebody has already told them that they were deficient in the past. yeah I think that'll probably take the time and more conversations. But I think this is a good place to remember that yeah vitamin D is a cheap low risk supplement. So if patients want to take it and they're not in one of those groups, it's probably not a big deal. But if we can stop monitoring their levels all the time, that's a big win. All right. Don, what do you think?
Speaker: Yeah, I have a lot of thoughts. um ah One, I think it's so great when guidelines agree, right? So we have interchronologists agreeing with family doctors, and and we have guidelines to show that. So I really appreciate the 2024 Interkin Society guidelines that have landed up now with the USPS, TF 2014, 2021, they all kind of agree.
Speaker: And I think that makes it easier for me as a clinician, you know, there's not like that doubt, like, well, maybe they, this, this, you know, I guess, I hate to admit this as a family doctor, but there's still sometimes if your specialist is telling you something different, it still makes you question, you know, what your guidelines, even if you feel comfortable with the data.
Speaker: so I think, um full disclosure, like when the USPS TF guidelines came out, Dr. Slauson kind of led the charge for us family doctors in the system to reduce our testing. And he sent out little letters to those clinicians who were testing too much vitamin D. And I was a winner of one of those letters because I was high performer here.
Speaker: And um in not the best way. So that really got my, one, it was embarrassing. And then two, it really made me look at the guidelines and I really reduced my testing. Did I stop all testing? I did not vi because I had patients come in and say, but I'm vitamin D deficient and then I'm really worried. And so like, I would let those folks pass through, even though I knew the guidelines just because it made them happy. And I just, it was too hard of a conversation. It's just nice looking at all this together today to be able to say, no, actually, I think I might be able to have a better conversation, even with those more difficult cases, um, with these current guidelines. And it's just really helpful. So yeah, I think this will change my practice and help me further reduce. So I can make Dr. Slauson who's now retired, but I still want to make him happy. So I hope he's listening to this so you can know that you've redeemed yourself. You've come full circle. I'm trying so hard.
Speaker: Yeah, I agree, Dawn. I mean, this this was really, this is one of those situations where I read the abstract, I had to put it away, like, oh, this is going to be tough. I know there's going to be so many family medicine residents and attendings that are going to look at me like I've lost my mind when I start suggesting this. And then I took a deep dive and this, I mean, listen, it's not an It's not a quick read. I think it's 47 pages, 286 references, but it is really well thought out. And when you really take the time to go through and read it, it's really hard to argue against it, even when your gut reaction says, this doesn't feel right to me. And this is just another example of we have to be flexible enough
Speaker: in our training to to realize that sometimes we have to change practice. And I know that's hard. You know, this route this kind of reminds me of when I had to tell a physician that writing albuterol only for asthma was no longer a thing. Remember that? Like I dreaded that. I dreaded that conversation. And ah now it's become standard practice, you know, that we don't do that for for most of our patients. So, Bobby, what what's your take -home message on this?
Speaker: yeah i think it's Yeah, I think that's a great point. I really agree with that. I think vitamin D is this area where we've seen the evidence evolve significantly over time.
Speaker: yeah it's ah It's a really great example of how you know we in medicine, we tend to get really excited about observational data and then we adopt that practice widely before we really even have the causational data from the RCTs to back that up. So just to remember, ah observational studies really are, they should suggest interventions to test with RCTs. They're not meant to be used for drawing conclusions about their effectiveness.
Speaker: It's taken us many years now for us to pump the brakes on vitamin D, but I think we're finally getting there. and yeah This is really why we do this podcast because we believe that it's important that physicians are equipped to understand these concepts and that's really what evidence informed decision making is all about. so I agree. Good job.
Speaker: right we may not We may not be very popular though. You have to be prepared for that, right? Just smile. Just smile. I think there's an angry mob lining outside lighting up outside right now. it's ok torture I I think I'm used to it now. It's all right. yeah Well, before we end, I do want to take the opportunity to explain why we think clinicians should follow this guideline, because I think that's an important takeaway from this too. you know As highly complex as modern medicine is today, physicians increasingly rely on clinical guidelines, and therefore we need we need to have the ability to discern which guidelines are relevant and trustworthy.
Speaker: Now, the guideline trustworthiness relevance and utility scoring tool tool, which is more simply described as G trust, is a tool that helps us do just that.
Speaker: And we'll put a link to it in the show notes, but it is a series of questions to determine whether a guideline is useful and trustworthy. So let's walk through them together for this guideline. So the question's about relevance and utility. So do the recommendations focus on improving patient -oriented outcomes, explicitly comparing benefits versus harms?
Speaker: Yes, this guideline does that, and it does it really well. Yes, it does. If the guideline does not do this, then it's a stop point there. It's not worth reading. You can go ahead and put it down. Are the recommendations clear and actionable? Absolutely. There's another strength to this guideline. Is the patient population and condition relevant to my clinical setting? Well, definitely. This is bread and butter family medicine.
Speaker: For the questions on trustworthiness, are the guidelines based on a systema systematic review of the research data? Yes. This guideline conducted a very transparent systematic review and meta -analysis based on standard protocols. and This is another one where if the answer is no, you should just stop reading the guideline. Are the important recommendations based on graded evidence, and do they include a description of the quality of the evidence?
Speaker: Yes, this guideline, I thought was really cool. It has a very nice interactive website that not only goes into all that in detail, but it outlines precisely their rationale for each recommendation. And so this is another one of those stop checkpoints. So if the answer is no on this, you stop reading the guideline.
Speaker: Next question is, did the guideline development team include a research analyst such as a statistician or epidemiologist? Yeah. Yes. This panel had two, so it was yeah very good. and And I think they needed both of them to calculate all of this this data. Yes, yes. It's very robust, yep. And then they have questions on interpretation. So are the chair of the panel and a majority of the rest of the committee free from declared financial conflicts of interest?
Speaker: and the funding for the guideline did not come from industry. And this panel had 14 members and only one member, so that's 7 % of the panel, had a relevant conflict of interest and it was not the chair. um And they did not receive any funding from any industry source. So this was all very clearly outlined in the guideline.
Speaker: And then finally, did the guideline group include members from the most relevant specialties and include other key stakeholders such as patients, payers, and public health entities? And yes, this patient this panel included endocrinologists, both adult and pediatric, internists, an OBGYN, an epidemiologist, an epidemiologist, I can't pronounce that, and a patient representative. and There was no family physician, sadly, but yeah we'll we we'll overlook that one. so So to reiterate, if any of the stop items I mentioned are true, then the guideline is not useful. And if you have zero or one, no answers, it's probably a useful guideline. If there are two, it may not be useful, so kind of take it with a grain of salt. And if there are three or more, then it's not considered a useful guideline. And so these guidelines are excellent. They mean yes for every single criteria ah criterion on this sheet. so
Speaker: We read a decent number of guidelines for this podcast and for our jobs, and I think it's safe to say that we were very impressed by these. I personally think they are a model of how guidelines should be written. and I agree. yeah yeah and we'll and we'll link ah We'll include a link to the GTRUS tool in the show notes, so hopefully you'll find it helpful for assessing whether a particular guideline is credible and relatable or reliable for your clinical practice in the future.
Speaker: Anyway, that's all the time we have for this episode. Thanks again. As always, Dawn and Sandy is always such a great time recording with you both. Absolutely. It's a pleasure.
Speaker: Thank you, Bobby, and thank you to all of our listeners. If you found this episode valuable, please help us spread the word by sharing with your colleagues, friends, or anyone interested in evidence -based practice. Also, we'd love to hear from you. Share your thoughts, experiences, and questions with us by emailing whatstheproofpodcastatgmail .com or reaching out on X at The Proof Podcast. Until next time, thanks for tuning in to What's The Proof.
