Can multivitamins extend your lifespan or are they just giving you "expensive urine"? Join Josh and Adam in this Dr Journal Club podcast episode as they dive into a revealing JAMA Network Open study, exploring the true impact of multivitamin use on mortality risk. With 30% of the population regularly consuming these supplements, understanding their real benefits and potential harms is crucial.
In this episode, we break down the study's analysis of data from three prospective US cohorts to answer whether multivitamins truly prevent all-cause mortality, cancer, and cardiovascular disease.
Tune in for a critical evaluation of this popular health practice and see if multivitamins are truly worth the hype.
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2820369
Learn more and become a member at www.DrJournalClub.com
Check out our complete offerings of NANCEAC-approved Continuing Education Courses.
Can multivitamins extend your lifespan or are they just giving you "expensive urine"? Join Josh and Adam in this Dr Journal Club podcast episode as they dive into a revealing JAMA Network Open study, exploring the true impact of multivitamin use on mortality risk. With 30% of the population regularly consuming these supplements, understanding their real benefits and potential harms is crucial.
In this episode, we break down the study's analysis of data from three prospective US cohorts to answer whether multivitamins truly prevent all-cause mortality, cancer, and cardiovascular disease.
Tune in for a critical evaluation of this popular health practice and see if multivitamins are truly worth the hype.
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2820369
Learn more and become a member at www.DrJournalClub.com
Check out our complete offerings of NANCEAC-approved Continuing Education Courses.
Welcome to the Dr Journal Club podcast, the show that goes under the hood of evidence-based integrative medicine. We review recent research articles, interview evidence-based medicine thought leaders and discuss the challenges and opportunities of integrating evidence-based and integrative medicine. Continue your learning after the show at www. d rjournalclub. com.
Dr. Joshua Goldenberg:Please bear in mind that this is for educational and entertainment purposes only. Talk to your doctor before making any medical decisions, changes, etc. Everything we're talking about that's to teach you guys stuff and have fun. We are not your doctors. Also, we would love to answer your specific questions on drjournalclub. com. You can post questions and comments for specific videos, but go ahead and email us directly at josh at drjournalclub. com. That's josh at drjournalclub. com. Send us your listener questions and we will discuss it on our pod.
Dr. Joshua Goldenberg:Hello and welcome to another Dr Journal Club podcast with your host, josh and Adam, your heroes and sidekicks for evidence-based review and critical evaluation of the medical literature, of the medical literature. And what's the? You have? Adam's got this like hoodie on and what is the character in Beavis and Butthead that always has their like like? I am Gornolio, that's like the impression that I'm getting, but we are competent leaders in the integrative, evidence-based medicine field, ladies and gentlemen, so do not worry about our side banter.
Dr. Joshua Goldenberg:Okay, today we are going to be talking about an article out of JAMA Network, the open sister journal or child journal from JAMA on multivitamin use. You always know it's important when I get independent emails from both my parents saying you should talk about this on Dr Journal Club. And then we got a few emails as well from other providers. I think this must have hit the media waves pretty, pretty hard. How about you? And then I think you independently sent it to me also. So it's kind of all over the news.
Dr. Adam Sadowski:Yeah, I have email subscriptions to like new england journal of medicine and jama, and then I think within jama I also subscribe to not only the open, because the open the reason why it's called open is open access, so you don't need institutional there's. They're all anyone can read them for free, which is awesome, um, and there's some interesting articles in there and they kind of cover a variety of topics. But then there there's JAMA proper, jama internal medicine and JAMA cardiology. Those are the other three within JAMA that I look at. Sometimes I have free articles in there that I have access to.
Dr. Adam Sadowski:Other times I don't have much luck getting access to full, full articles, usually the um, like the main headliner articles like the big um, the big what's the term? Um landmark trials are typically free um, which is good. Yeah, those are the ones that I I care more about. A lot of the other side stuff are like super, super, super niche stuff, um, that aren't really clinically relevant to me but would be interesting from a research standpoint, usually require institutional access. That I don't have. So that's usually how I'm staying up to date on stuff is I just constantly get these like email things and whenever I go for a walk in the morning, it's usually what I'm doing is going through like email, social media, listening to podcasts, that kind of stuff, and then, when I'm looking through my email, stuff will come through. I'll look at it, and then I usually spam your phone with like 400 different articles that we need to read. Yes, and that's how this one came up, actually, yeah, that works pretty well.
Dr. Joshua Goldenberg:I mean, it's kind of like a little anecdote around dissemination and science. Like when you write grants, you always have to have a dissemination section and there should really be one in journal articles too, and I mean this is how this information gets disseminated, right, it's like you've got podcasts and subscriptions. I'm hearing stuff from my mom Like this is how this information gets out there and changes practice, right, because now we're talking about it and it's an important part of science. I think there's a couple areas in science that are finally getting appropriate recognition. One is patient and public involvement. It's like now a required section.
Dr. Joshua Goldenberg:Like if you just submit to BMJ, for example, or any of their sister articles, journals, you have to say how the public or patients were involved. Our grant going in next week has a whole section on how we're involving the public and people with lived experience. And then the other is dissemination. It's like, okay, you can do the science, but you don't just like submit your article and walk away. Like there's some responsibility here in you getting the word out and changing practice, which I think in general is a good thing.
Dr. Adam Sadowski:Yeah, I'd agree, I'd agree.
Dr. Joshua Goldenberg:Okay, cool. So, uh, with multiple attacks on this one, we've heard from everybody, so we're going to do it. Um, so this is the multivitamin use and mortality risk in three prospective US cohorts, and Michelle will get you the link for that. Um, this was a sort of combination cohort study across three different cohorts. Do you want to walk us through the methods, or how should we parse this one?
Dr. Adam Sadowski:Yeah, so just for like background. Basically everybody knows about multivitamins at this point, going all the way back to the Flintstone times, when people had a Flintstone gummies which were absolutely disgusting.
Dr. Joshua Goldenberg:I remember those times.
Dr. Adam Sadowski:To now evolving into these, like really gummies these delectable gummies Addicting, yeah, that are basically just candy with some vitamin C in it. Yeah, but it's important because a lot of people take multivitamins for whatever reason. I'm sure that really it's kind of pertinent to everybody. It seems like everybody, whenever they visit the doctor, will say, oh, I'm not taking anything, but I do take a multi, and great or whatever. And about 30% of the population is using some sort of regular multivitamin or using a multivitamin on a regular basis.
Dr. Joshua Goldenberg:Yeah, that's a lot. That's one in regular basis.
Dr. Adam Sadowski:Yeah, that's a lot, that's one, one in three people, yeah, and some of the the issues with regards to the data looking uh at, you know, are multivitamins beneficial or not? Um, is the issue of confounding where, uh, a lot of people who are using multivitamins are already healthy to begin with, so it's kind of hard to determine whether or not they're even getting benefit to their use outside of, you know, not being in a deficient state, so otherwise generally healthy, well-rounded diet, you know, non-smokers, et cetera, et cetera. Typically, the people who are using multivitamins are typically healthy, and so there's this idea of the healthy user effect. And then, conversely, you have people who are not in good health, who suddenly have a coming to Jesus moment perhaps, and then we'll start taking multivitamins, sort of like as an entrance to wanting to live a healthier lifestyle and view a multivitamin as this healthy thing to do, and so we'll start supplementing with a multivitamin.
Dr. Adam Sadowski:And so we don't really know, or it's not that we don't know, it's just that the evidence is pretty mixed. The United States Preventive Services Task Force has pretty much made the recommendation that if you're otherwise a healthy individual, there's really no need for a multivitamin supplementation for the purposes of preventing death, because in the United States, everything is basically fortified, and so, even if you don't have the best diet, having a true nutritional deficiency not to be confused with insufficiency is pretty rare. There's not many people in the United States who are walking around with, let's say, rickets or scurvy.
Dr. Joshua Goldenberg:Not anymore.
Dr. Adam Sadowski:Whereas, yeah, not anymore. And so you know, when it comes to using a multivitamin in getting physiologic excess to what you're already getting on a daily basis, is there any sort of actual benefit to that in people who are otherwise healthy? Um, and just using a multivitamin in preventing uh all cause mortality, cancer, cardiovascular disease.
Dr. Joshua Goldenberg:Right.
Dr. Adam Sadowski:And that's that's what the paper is looking at.
Dr. Joshua Goldenberg:Yeah, exactly, and I think the so there's a couple, a couple things. So, yeah, I love that healthy user, sick user effect discussion, just methodologically. Sometimes that sick user effect you know we might call that like reverse causation, bias, right? So remember, so observational studies, which is what this is. You know, association does not equal causation. That's why we love randomized, controlled trials. But when you have an association, instead of thinking that A is driving B so like the multivitamin is driving the disease outcome, like you're not dying as much, it may actually be that B is driving A and that's why they're associated.
Dr. Joshua Goldenberg:So the sick user effect is, essentially they have a and that's driving their use of vitamins because they have this belief that it's healthy and it will help them. So you'll see that association, but it's because of the reverse causation. So, anyway, so just neat methodological stuff. I would also say that. So this is looking at mortality and people usually take it, as I've heard people say, like quote unquote insurance to make sure they're getting everything that they need, and the argument would be well, okay, like we should be seeing some health benefits here, and so this question is really on a mortality level. Are we seeing a difference with long follow up?
Dr. Adam Sadowski:They also did look at heart disease and cerebral vascular accidents.
Dr. Joshua Goldenberg:Did they look at those as separate outcomes or death because of?
Dr. Adam Sadowski:That is a good question. I think they did death because of, and they also looked at all-cause mortality, so they did separate it out.
Dr. Joshua Goldenberg:Yeah, but they're not looking at MIs or other diseases short of death. So I guess, just trying to foreshadow counter arguments, one might be, you know, okay, well, maybe it's not leading to a change in death but maybe it has other benefits or wellness outcomes or things like that. But we'll well, that's foreshadowing, so we'll get to that. So I think you set that up really really well. Some of the oh so, what are the issues? So the big issues with this is you need large cohorts of people to be able to see these sorts of outcomes with statistical significance. You need long follow-up, because the argument is like, okay, you take a multivitamin for six months, like you know, if you'd have a randomized control trial or something like that, like yes, that's ideal, but you're not going to study them for 30 years and that's the type of follow-up you might need to see these types of outcomes. So you need these large observational studies. So one issue is lag time effect and so you need large cohorts with multi-decade follow-up, which is what the study is trying to do. And the other is this you know, like you said, the healthy user and sick data to be able to stratify by other markers of health and separate that out as a variable or do multivariate adjustments? Do we still see this effect? So when you have these large cohorts, you could do that type of statistical magic or voodoo, depending on who you're talking to.
Dr. Joshua Goldenberg:Depending on who you're talking to and then from a sick user effect, they also did this clever thing where they excluded everyone at the beginning at their baseline levels, who had cancer, diabetes, any of these major diseases, because of the fear of the sick user effect.
Dr. Joshua Goldenberg:So really they limited their cohorts to people that were going in, like you said, healthy, and then looking at their self reportreport of multivitamin use and the development of death. And then the last thing is well, what if people change over time? You know their multivitamin use, or if they develop diabetes in the middle there, and then that's what's driving their multivitamin use. So they did have some sequential time data from these cohorts about people's multivitamin use over time, not very nuanced and detailed, I think it was like every few years or five years or decades or something like that, but they had something time-linked where they can kind of update that as well. So the neat thing is that there's big questions about multivitamins, studying multivitamins, and so they thought, hey, with this approach. With these techniques, we might be able to address some of these issues.
Dr. Adam Sadowski:Yeah, and I think we also have to remember that, when it comes to these kind of studies, something that we have to take into account is the fact that a lot of it is self-reported, and so you know you're relying on people saying yes, I take a multivitamin every day, or I only take it every three days, and so the accuracy or the precision within that is pretty poor, so we do have to take that into account as a limitation.
Dr. Joshua Goldenberg:And it doesn't speak to the quality of the multivitamin either. Right, it's just asking someone if they take a multivitamin every day or not.
Dr. Adam Sadowski:Yeah, you know, if you were to take someone randomly off the street and just say how many times a week do you eat burritos?
Dr. Joshua Goldenberg:I don't think the answer is going to be very accurate. Right, and you don't know if they had whole foods, made that at home burritos versus going to Taco Bell three times a day. Right, and so it's somewhat analogous here is that there's no quality metric here.
Dr. Adam Sadowski:But, but does that matter? Remember when we talked about that before?
Dr. Joshua Goldenberg:Well, so that's the question, right? So we're just sort of saying so you know. So, dr, I am going to tell you that it doesn't matter. It's all expensive urine, and this proves it. And I'm just playing devil's advocate and saying that this is not measuring quality, right? So this is just asking people if they have a multivitamin and then trying to associate that answer with death. Yeah, yeah, okay, we're cool with that.
Dr. Adam Sadowski:We'll just move along so we'll move along.
Dr. Joshua Goldenberg:Okay, we're not cool with that, but it's a detente. Okay, go ahead yeah.
Dr. Adam Sadowski:So in this study they had three cohorts for a total of just shy of 400,000 participants, so they had about 34,000 deaths for a total of just under 8 million person-year follow-ups. So one way to look at that is if I had 8 million people in a study and followed them for one year, or if I had one person who I followed for 8 million years.
Dr. Joshua Goldenberg:You're now just falling apart here.
Dr. Adam Sadowski:Yeah, yeah, it's a lot, it's a a lot, it's a lot of data basically we have we have a lot of follow-up data that you can't get from a randomized control, trial or other study types. So this is this is sort of the benefit of doing these large prospective cohort studies although there's a lot of limitations from them, you can get a lot of good data from them. And then if get a lot of good data from them, and then if you look at the confidence intervals, because of the high number of participants and the long follow-up, the confidence intervals tend to be a lot, much more narrow, which is usually reassuring.
Dr. Joshua Goldenberg:No, so that's the point. It's like we talked about. For this sort of research question, you really are going to need multi-decade follow-up, and that's where these cohorts come in with all limitations. So did we say so? These are three cohorts, so it's the NIH, aarp Diet and Health Study Cohort, the PLCO Cancer Screening Trial Cohort and the Agricultural Health Study Cohort, I believe, the latter of which is like a cohort of pesticide applicators. So I had a big question about applicability and external validity with these cohorts, but it's something that we need to kind of consider. They did look at the differences between cohorts to see if there were any obvious differences and didn't seem to see it. But these are the people in this, this study.
Dr. Adam Sadowski:Yeah, and the PLCO was the prostate, lung, colon, ovarian cancer screening trial cohort and that goes back to. All of these go back to the early to mid nineties. So the NIH AARP health study cohort goes back to 1995. The PLCO cohort goes back to 1993. And then the AHS, the Agricultural Health Survey, goes back to 1993. Why they didn't include, like the nurse's health study or you know, some of these other large well-known cohort studies kind of remains elusive. I'm sure the data there has got to exist.
Dr. Joshua Goldenberg:You'd think so.
Dr. Adam Sadowski:I would be hard-pressed if it doesn't.
Dr. Joshua Goldenberg:It did seem like a random selection of cohorts. I mean, I've seen the NIH AARP all the time in lots of studies. I've never seen a study on this agricultural health cohort or the secondary analysis of PLCO cancer screening cohort either.
Dr. Adam Sadowski:I'm wondering if that agricultural health study was trying to tap into like a more rural patient population base.
Dr. Joshua Goldenberg:Maybe it would be nice to have had some justification. Maybe that's what we're struggling with here is why were they not? Why are they not the author's not justifying the selection? Is this just pragmatic, like this is what they had buddies in that could get access to, or was this chosen for specific reasons? Because I'm left scratching my head as to why these cards were chosen and if they were appropriate and if it's applicable to the larger US population, and I wouldn't have these questions if they had a good rationale for their selection, which they don't seem to explain.
Dr. Adam Sadowski:Yeah, because if we look at the NIH AARP cohort, those individuals were 50 to 71 years of age.
Dr. Joshua Goldenberg:Right.
Dr. Adam Sadowski:Yep, they lived in one to two metro areas or in six different states, but they didn't specify which states. They were excluded from data collection in this study if they provided answers through a proxy. So let's say you know, you ask the individual, do you use a multivitamin? And then their brother answers for them. If they died before receiving this questionnaire, which is pretty obvious exclusionary criteria If they had cancer, some sort of major adverse cardiovascular event, diabetes or end-stage renal disease at baseline, or if they had cancer, some sort of major adverse cardiovascular event, diabetes or end stage renal disease at baseline, or if they had basically implausible caloric intake not necessarily implausible, but just excess.
Dr. Adam Sadowski:And I mean that's important because if you're, one could assume that if you're eating caloric excess then you're going to be sort of physiologically overachieving on nutrients that would be available in a multivitamin. Theoretically, now, you could be eating just like caloric excess from like lots and lots and lots of soda. But they did apply that exclusionary criteria to, I think to all of the studies anyway. And then any of the cohorts that had missing covariates that they were interested in were also excluded. The PLCO was done at 10 different centers. The ages there at baseline were 54 to 74. They excluded data from there If participants died at baseline collection for this particular study, if they had missing outcomes on at least eight different responses for the questionnaires that they were interested in and then for the AHS. These were individuals who were at least 18 years of age that were pesticide applicators, living in Iowa and Northern Carolina.
Dr. Joshua Goldenberg:Yeah, interesting. Again, would have loved to see a rationale for the selection of these cohorts. For the most part the censoring I was okay with. Again, they censored the people with these major conditions on purpose to avoid I believe again it's not explained to avoid this sick user effect. And I and the caloric, like the extreme caloric intake we've seen stuff like that before, sort of these, and you kind of tried to explain it mythologically and I think also it's sometimes used as a quality metric, like they're just not reporting things properly if it's this extreme, but they don't really define what extreme means, which is, again, maybe that's in a supplement somewhere, but I don't see it here. So, yeah, so I mean, for the most part I'm okay, but just a lot of questions about the selection of the population here that I think a couple sentences explanation would have put my mind at ease. Otherwise I'm okay with it.
Dr. Joshua Goldenberg:Look, the thing is we don't do this for money. This is pro bono and, quite honestly, the mothership kind of ekes it out every month or so, right? So we do this because we care about this, we think it's important, we think that integrating evidence-based medicine and integrative medicine is essential and there just aren't other resources out there. The moment we find something that does it better, we'll probably drop it. We're busy folks, but right now this is what's out there. Unfortunately, that's it, and so we're going to keep on fighting that good fight.
Dr. Joshua Goldenberg:And if you believe in that, if you believe in intellectual honesty in the profession and integrative medicine and being an integrative provider and bringing that into the integrative space, please help us, and you can help us by becoming a member on Dr Journal Club. If you're in need of continuing education credits, take our NANSEAC approved courses. We have ethics courses, pharmacy courses, general courses. Interact with us on social media, listen to the podcast, rate our podcast, tell your friends. These are all ways that you can sort of help support the cause. Okay, so with those caveats, shall we jump into the next section exposure assessment.
Dr. Adam Sadowski:Yeah, so basically they looked at people who were non-users of multivitamins versus daily users and which kind of I kind of like it makes the data a little bit cleaner because you're you're more likely if someone's like an actual daily user, they're more likely to be a daily user than someone who's like infrequently using. Then you're trying to quantify okay, well, how, how often are you taking it?
Dr. Adam Sadowski:right and then they also defined, like you said earlier, that it was all, it was all cause mortality, but the death from specifically, cancer, heart disease and strokes. And then they looked at the covariates of age, sex, race, ethnicity, education, smoking status, bmi, marital status, physical activity, alcohol, coffee, healthy eating index, family history of cancer and use of other supplements.
Dr. Joshua Goldenberg:Yeah, and this is important for the healthy user effect. So we've been dealing with the sick user effect by censoring people with disease at baseline and by looking at these surrogates for healthy users, like healthy eating index we've talked about that before alcohol intake, physical activity, bmi. In theory, they're going to be using this to try to control for those potential confounders, so that's why that is particularly interesting. And then, of course, they have three different cohorts, so they're somewhat measured in different ways and so, again, it has to be harmonized across these cohorts before they can do their analysis.
Dr. Adam Sadowski:Yep, yep, yep, yep.
Dr. Joshua Goldenberg:Cool.
Dr. Adam Sadowski:And then, when they looked at their analysis, they did both individual analyses and pooled analyses, where the pooled analyses was the main outcome of interest.
Dr. Joshua Goldenberg:Pooled across all three cohorts Yep.
Dr. Adam Sadowski:Exactly. So they individualized them across each individual cohort. So you have three different cohorts. So they did one analysis was let's just look at each cohort individually. We had three different cohorts. So they did one analysis was let's just look at each cohort individually. And then they also said OK, well, now let's do what we really care about, which is pooling all the data together and analyzing that. So we combined all three cohorts.
Dr. Joshua Goldenberg:Yes, this is. There's some interesting stuff here and it's complicated stats even for us. But there's a few things that I did want to touch on. So one is so they have three different cohorts, right I did want to touch on. So one is so they have three different cohorts, right, and they claim that they did individual analysis on each individual cohort and that it was similar enough that they then pooled them. But they don't show unless I missed it, they don't show any evidence of that or say what similar means. They also say there's low between-study heterogeneity. Again, I don't see any high square statistic or rationale and that is their rationale for pooling them. And when they say pooling them, they actually mean a meta-analysis, which is rare.
Dr. Joshua Goldenberg:Normally we're used to seeing meta-analyses after attached to a systematic review. This is a meta-analysis attached to three cohorts. It isn't unprecedented, it happens and it can be kosher. But they also they did a fixed effects meta-analysis, which is very rarely done.
Dr. Joshua Goldenberg:Usually you do random effects. Fixed effects assumes that the intervention and everything else is exactly the same and the only difference that you're dealing with in the meta-analysis is the size of the samples, is the size of the studies. There's basically no statistical or mathematical input from the heterogeneity component, whereas random effects assumes you're getting an average of different populations and different types of interventions and doses and therefore is more conservative, has wider confidence intervals, not less impressive p-values, because it makes these assumptions and it incorporates the assumed reasonable heterogeneity in a population like that. So you have to be careful. Fixed effects are going to like over-argue p-values and stuff like that and be overly precise.
Dr. Joshua Goldenberg:And I don't see how they get away with saying that you've got three different cohorts across very different populations, people just saying they take a multivitamin you have no idea what type of multivitamin, what the dose of the multivitamins were and getting away with doing a fixed effects meta-analysis on that. So maybe I am missing something and if you're a statistician please call in and correct me. But that was a little. I'm not saying it's a red flag, I'm just saying sort of like the cohort selection. I was left scratching my head and would have liked some explanation as to the rationale for that, because that did not seem like how I would look at that. Anyway right.
Dr. Adam Sadowski:Yeah, no, it was.
Dr. Joshua Goldenberg:It was a little confusing yeah, okay, so they, so they. But for let's say, let's, let's assume, for the sake of argument, playing devil's advocate, it was okay to pull these cohorts and that it was okay to use fixed effects, and so now we're going to talk about the results that they found when they did that. Yeah, yeah, brought my attention is that we're talking about I think I said three decades earlier, but really we're talking about a median follow-up of, you know, 23, 21, almost 24 years across all the cohorts. We're talking about 23 and a half years median follow-up, so it is still a lot of follow-up time and anything else from baseline, besides what we've talked about before, about describing those cohorts that you wanted to touch on.
Dr. Adam Sadowski:I mean the average age basically was 62. And, excuse me, the median age was 62.
Dr. Joshua Goldenberg:At baseline, right? So I think that's relevant too. This is an older, these are older folks, and you know, it's not too surprising that the AARP cohort in there as well, right? So you have to be what? 50 to even be a member of the AARP. So, yeah, so this is.
Dr. Adam Sadowski:this is a population that's skewing older already with a with a interquartile range of 57 to 66. So I mean, it's still like middle of the road patient population, that these are the majority of patients who are going to be being seen from like a primary care status. And you know, you kind of want the data, I would feel like on on people who are at higher risk for, for you know, death anyway because, um, if you have a younger cohort and you're and you're following them, then even harder, yeah.
Dr. Adam Sadowski:Yeah, it would be harder to track the data that you're trying to evaluate, and so this would actually help if there was an effect with use of multivitamins to show you know again, if we think about, like our absolute risk, those who are at higher risk for things. If there's a higher risk, you would expect the intervention to provide more benefit than someone who's at you know a primordial risk or primary prevention risk standpoint.
Dr. Joshua Goldenberg:Yeah, and then that's so. That's true and fair and I don't have a huge issue, just to note that it's an older cohort. And then the other thing I wanted to point out is the HEI score. I know we kind of ragged on HEI before as like it's an imperfect measure of healthy eating, but it's sort of what we have and commonly used. So it's a scale of zero to 100. And in here in these cohorts the average and this seemed mostly consistent across the different cohorts it looks like the AHS which went with the AHS that was the agricultural one has a little bit of a lower healthy eating index but for the most part they're scoring in the 60s and I believe 100 score is considered the best and reflects sort of that 100% alignment with major you know, common dietary recommendations in the United States. So they're in that 60 to 70 range on average as far as healthy eating.
Dr. Adam Sadowski:And we also are kind of seeing a healthy user effect where, compared to those who are not using multivitamin, they're more likely. Individuals who are using multivitamins are more likely to use other supplements in general, have a lower BMI, better diet quality, less use of tobacco products, etc. Etc.
Dr. Joshua Goldenberg:Yeah, so that's exactly the point, right? I think now that they have this level data on people's diet and their BMI and their physical activity and supplement use, in theory they can try to control for that and just look for residual effects of multivitamins. And we we had a analogous issue. What was one of the papers we did I forget what it was studying which looked at the oh, it was ultra processed foods and tried to separate that out from the HEI and we, argued, had a pretty hard time doing that. But this is their attempt of basically saying you know, let's make sure that it's not just the fact that people that eat healthy are taking multivitamins and we're seeing the effect because they're eating healthy. Right, right, right, right, okay cool.
Dr. Adam Sadowski:So let's get into the sort of the meat and potatoes of it and I think right, right, okay, cool.
Dr. Adam Sadowski:So let's get into the sort of the meat and potatoes of it and I think, yeah, let's do the fun stuff. I think the best way to kind of present this is talk about the well they split it up as to what's called fp1 and fp2, so follow-up period one and follow-up period two, where follow-up period one was years of follow-up between years one through 12, and then follow-up period two was beyond 12 years, and I feel like beyond 12 years is a little bit more of the data that we should kind of focus in on because it's more long-term from that standpoint. But we will discuss both.
Dr. Joshua Goldenberg:Okay, yep Gotcha. Alrighty, okay, okay, yep, gotcha.
Dr. Adam Sadowski:Alrighty, okay. So when it comes to mortality, there was a 4% increased risk in individuals using daily multivitamins compared to non-users, and that hazard ratio was 1.04 with a confidence interval of 1.02 to 1.07. So a 4% increased risk ranging anywhere from 2% to 7%, but that was limited to years 1 through 12. Once we extended out beyond 12 years, that was no longer statistically significant and although the point estimate didn't change at 4%, the confidence interval was much wider and ranged from 0.99, so a 1% benefit in reducing the risk to 1.08, so across that threshold of 1. And so it was anywhere from 1% protective to 8%, increasing the risk of mortality, and that was all-cause mortality. When we look at heart disease, cancer and stroke across neither, across none of the FP2 time points was there. Basically everything was consistent, right For FP2, there was no statistically significant differences between the two for heart disease, cardiovascular disease or cancer.
Dr. Joshua Goldenberg:From death, from those things. Right, right, yeah, correct.
Dr. Adam Sadowski:But when? And then, when we look at heart disease, there was a 6% increase risk which ranged from 1% to 11%, isolated to the first follow-up period for the first 12 years, which is consistent with the mortality data.
Dr. Joshua Goldenberg:So I wonder if, if this was done as a random effects meta-analysis, that confidence interval would have been wider, and even that statistically significant increased risk would also not be statistically significant. So I'm curious about that, but I think the take-home is. What is clear, though, is there's definitely is no signal for benefit. The question is, you know, is there actually a signal for harm or not? I'm not sure, but certainly there does not seem to be a signal for benefit. Would you? How would you take that?
Dr. Adam Sadowski:Yeah.
Dr. Joshua Goldenberg:Okay.
Dr. Adam Sadowski:Yeah, I'd agree, and again, that that signal for harm is only in the, in the short term, and it's really really small.
Dr. Joshua Goldenberg:Right, exactly, and really close to losing significance if those confidence intervals got a bit wider. So I'm a little suspicious. But yeah, okay, cool, and they don't have a good argument. I mean, I guess you could come up with some mechanism as much as you love, mechanism of how it could cause harm, but certainly we're not seeing a signal for benefit there. Okay, excellent, I think that's the main take home. Is there anything else that you wanted to talk about as far as the overall results, or should we jump into sort of that discussion piece?
Dr. Adam Sadowski:No, I was going to jump into the discussion piece and just say that you know, this is yet again some more evidence that's consistent with prior evidence showing no benefit of, you know, multivitamin supplementation or super physiologic doses of various nutrients for otherwise healthy individuals. It's consistent with the USPSTF recommendation. It's consistent with a prior randomized control trial.
Dr. Joshua Goldenberg:Looking at this and so yeah, I mean the data is the data looking at this and so, yeah, I mean I, the data is the data.
Dr. Joshua Goldenberg:Yeah, the data is the data.
Dr. Joshua Goldenberg:I think that I would agree with the few caveats I think I said before, which is, you know, this is sort of interesting cohort selection.
Dr. Joshua Goldenberg:I'm not sure what to make of it, I'm not sure what to make of the choice of meta analysis type, and but I certainly don't see a signal of benefit. But then again, I would say there's no metric here for the quality or dose in the multivitamins, simply looking for an association between people saying they take a multivitamin every day and then dying over the next few decades. So I think that is a fair criticism. That being said, it's going to be a very challenging study and probably impossible to answer that question, because you would need 30-year cohorts with data on the quality and type of multivitamin and then some statement about what actually is considered a high quality that everyone agrees on and all of those things, and then you'd have even more of an issue of a healthy user effect for people that are seeking out specific high quality multivitamins as opposed to grabbing something off the shelf. So I don't know how you would do that study, but I think it is fair to argue that however that question is still open, based on this study.
Dr. Adam Sadowski:I don't know if I agree because and again it goes back to the idea of priors. So you know, we already have quite a bit of evidence showing that there's a lack of benefit, you know. So we have consistency in that standpoint. We can only work with through, or we can only work with what we have, and what we have for the most part, is pointing towards no benefit. And then to say, to rationalize, saying, oh well, I'm using a high quality supplement and you know, these cohorts don't pertain to my person, my patient. Therefore, this is actually, you know, a reason to recommend, you know, iv nutrients or this fancy multivitamin. I don't think you can make that argument, and it goes back to that idea of priors that we've talked about before, where you really need to have a really good case and strong evidence to suggest why you're making that recommendation over what has already been established in the literature.
Dr. Joshua Goldenberg:Yeah, and to bolster your side of this, thank you To steel man, you a bit here. It would be one thing for me to say, well, you can't really answer this specific question, but what's the harm? And as long as you do, inform consent.
Dr. Adam Sadowski:Well, we also have evidence of harm right Well exactly.
Dr. Joshua Goldenberg:So that's my point is that even though we've been saying maybe we have some questions about that harm signal, there is a harm signal now, right, like that is out there in the literature and it's it's, you know, it's, it's, it's there and so and it's about death. It's not about like belly aches, right. So I think that balance argument changes to where it's say okay, well, maybe you can hand wave and say it's not a perfect study and dah, dah, dah, dah and whatever is. And you have, you have good arguments about that, whatever is argument. And when you just say no, basta, we're done.
Dr. Joshua Goldenberg:You commonly bring up with vitamin D, for example, but even that shifts if you've got a signal of harm, if you've got questions about the signal of harm. So I don't know, man, Actually, on retrospect, maybe I'm leaning into your camp a little bit and just saying not only am I not going to start recommending Maltese, maybe we even ask people to stop. I don't know, it's not medical advice, we're just talking about research and implications, but I think the argument about shifting that onus is a good one.
Dr. Adam Sadowski:Yep, and so far from what we've looked at on this podcast, it looks like the Shilajit so far has been the only thing that has panned out.
Dr. Joshua Goldenberg:Shilajit is the clear winner.
Dr. Adam Sadowski:Knee osteoarthritis.
Dr. Joshua Goldenberg:No curcumin. For what was it? Curcumin for functional dyspepsia? But then a new study came out basically showing a harm signal with curcumin in liver disease. We're going to have to look at that. Liver failure we're going to have to look at that study next week I think. But yeah, interesting, interesting stuff.
Dr. Joshua Goldenberg:But there are very few things in our rarefied list, the Dr Journal Club list, of large magnitude, high quality evidence that things work. And so what's our running list? Probiotics for necrotizing, necrotizing colitis. We've got maybe semaglutide we don't actually know if that's true and apparently without looking it up, we've got Vi semaglutide we don't actually know if that's true and and apparently without looking it up, we've got um viagra, according to you. And then what was the other one we did last time? Oh yeah, e-cigs. E-cigs seems to have super high evidence with a large magnitude of effect as well. So what's the world coming to me? But don't do the multivitamins. What it's like this? This is the strangest final conclusion. You, we should be doing e-cigs and Viagra and jump on the semaglutide bad wagon, but don't do the multivitamin. Is this really where we want to leave our listeners after today?
Dr. Adam Sadowski:we're here for a fun time, not a long time we should leave it at that, alright.
Dr. Joshua Goldenberg:Dear listeners, thank you for putting up with us and we will see you next week. If you enjoy this podcast, chances are that one of your listeners. Thank you for putting up with us and we will see you next week.
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Dr. Joshua Goldenberg:Hey y'all y'all. This is. Josh. Dr
Dr. Joshua Goldenberg:You know we talked about some really interesting stuff today. I think one of the things we're going to do that's relevant. There is a course we have on Dr Journal Club called the EBM Boot Camp. That's really meant for clinicians to sort of help them understand how to critically evaluate the literature, etc. Etc. Some of the things that we've been talking about today. Go ahead and check out the show notes link. We're going to link to it directly. I think it might be of interest. Don't forget to follow us on social and interact with us on social media at DrJournalClub. Drjournalclub on Twitter, we're on Facebook, we're on LinkedIn, etc. Etc. So please reach out to us. We always love to talk to our fans and our listeners. If you have any specific questions you'd like to ask us about research, evidence, being a clinician, etc. Don't hesitate to ask. And then, of course, if you have any topics that you'd like us to cover on the pod, please let us know as well.
Introducer:Thank you for listening to the Doctor Journal Club podcast, the show that goes under the hood of evidence-based integrative medicine. We review recent research articles, interview evidence-based medicine thought leaders and discuss the challenges and opportunities of integrating evidence-based and integrative medicine. Be sure to visit www. drjournalclub. com to learn more.