Transcription
A new vitamin D study has completely changed my view and the advice that I give to my patients. And because it took a novel approach, it uncovered something that we might have been missing up until this point.
So, not so long ago, researchers were alarmed about vitamin D. Specifically, they were worried that there was an epidemic of deficiency that could be contributing to a whole host of serious diseases. And the evidence for this came from early observational studies which uncovered concerning linkages everywhere. So, when we tested levels of vitamin D and compared those to health outcomes, it didn't look good. The result showed an association between low vitamin D and cancer, infectious diseases, autoimmune conditions, diabetes, and heart disease just to name a few.
So suddenly there was an explosion of interest in vitamin D and everyone was getting tested. The supplement use went through the roof and some influential guidelines published in 2012 by the endocrine society helped to fuel that trend.
But then came the big clinical trials like the vital trial. So 25,000 adults were given vitamin D or a placebo and they were followed up for a period of 5 years and the dramatic benefits that people had hoped for simply were not there. There was no clear reduction in heart attacks or strokes. Vitamin D didn't seem to help much with cancer either.
So the guidelines soon caught up to this new data and the latest endocrine society guidelines on vitamin D looked at all of these trials and brought things back down to earth. So for the general population, there was no clear evidence that supplementing with vitamin D improved health outcomes. So they concluded that we should just stick with the standard recommended daily allowance of 800 international units. There was no need for aggressive dosing. And since the studies hadn't given us a clear target for an optimal vitamin D blood level, they recommended against routine screening to check our levels. So in other words, they suggested to stop chasing the number if there wasn't a clear reason to be measuring it in the first place.
And as an evidence-based clinician, I took that advice seriously and I haven't ordered vitamin D blood tests on my otherwise healthy patients because instead if someone was older or housebound or clearly at high risk of deficiency, I simply recommended to them to take a moderate daily dose of vitamin D rather than send them for a blood test which they themselves would have to pay for. And up until that point, the test itself had not been shown to improve anything. But now I'm not sure.
So last week I was scrolling through the abstracts from a cardiology conference when a title caught my eye. It was for a randomized clinical trial called the target D trial and it involved vitamin D and serious heart-related health problems like heart attacks and strokes. It involved a very high-risk group of patients. So I clicked the abstract and I half expected to see another negative vitamin D trial to add to the long list. But instead I found something that threatened to upset the simple story.
So, take one of my patients for example who let me share his story and I've switched up his name. So, let's call him John. John is 62 and he hasn't paid much attention to his health so far. He ignored his chest discomfort for a day because work was busy and he didn't want to make a fuss. So, when he finally went to the hospital, his EKG was not subtle. He had had a serious heart attack and the cardiology team performed an angio and placed a stent in the blocked artery to open it up. Then he started the usual medications and after a few days he was stable enough to be discharged home. So of course he's grateful that he survived the ordeal, but he's a little shell-shocked and promising everyone that he was going to start eating better, he was going to exercise, he was going to take his tablets exactly as prescribed.
Now in the target D trial, people like John had one more additional decision to make before they left the hospital. So everyone in this trial received the usual standard of care, but half of them were also randomized to vitamin D management strategies. So they had their levels of vitamin D measured and most had what we would call low levels with an average of around 27 nanograms per milliliter. So in the vitamin D management group, the clinicians then used an algorithm to prescribe a vitamin D supplement and adjust the dose over time. Many of these patients had started with 5,000 international units per day and the goal was to get their blood level above 40 and keep it there. So the patients returned for repeat measurements and dose adjustments. The other half of the trial, the usual care group, they didn't have that structured protocol and they just received normal care for their circumstances. Researchers then followed up everyone for an average of just over four years. And they watched for serious cardiovascular events. So that included things like death, other heart attacks, hospitalization for heart failure or strokes. That combined outcome is what we call MACE, which stands for major adverse cardiovascular events.
So what happened to these people in the study? Well, on the surface, not a lot. When researchers looked at that combined MACE outcome, there was no statistically significant difference between the two groups, roughly 18 out of 100 people in the usual care group had one of those events during the follow-up. That compared with 16 out of 100 in the vitamin D management group. So the hazard ratio was 0.85, which indicates a 15% lower risk. But the confidence interval here was quite wide and it comfortably crossed one. So in plain language, the difference here might just be due to chance. And if this was the only information I saw, I would shrug it off and file the target D trial next to the vital study in the probably negative drawer.
But when we have a look at components of that composite outcome, something stands out. So the risk of having another heart attack was lower in the vitamin D group. So in the usual care group, about 18% of the patients had another heart attack during the study, but in the vitamin D group, it was closer to 4%. So that translates to an impressive risk reduction of 52%. So, put differently, for every 100 people, like my patient John, there were about four fewer heart attacks over that 4-year follow-up period in the vitamin D management group. Now, that's a relatively small absolute difference, but it's certainly not nothing.
And the researchers also did what's called a per protocol analysis. So, instead of counting everyone included in the study, they asked a different question. So, for those in the vitamin D arm who actually got their levels above 40 and kept them there, how did outcomes compare with those in the usual care arm? Well, in that analysis, the numbers look even more impressive, at least for the composite MACE outcome as well as deaths. And the risk reductions are greater here in the achieved target group.
And this is where it would be really easy to get carried away. There's a potential story here that feels compelling because there's something novel about the study design. It's the first time that we've really checked for the effects of vitamin D supplements by using custom dosing to raise people's levels above a target and follow them up over such a long period of time to see what happens to MACE. So, past studies have always just given the same supplement to everyone involved. And they've also included lots of people whose vitamin D levels were not particularly low. So maybe the reason that the clinical studies so far haven't found benefits is because we haven't been looking at what happens when we go from a low vitamin D level to an adequate one.
So here's how the plausible-sounding story goes. That we finally did the right study that we treated vitamin D properly to a target level rather than just with a random blanket dose and the heart attacks melted away. The skeptics were wrong and everyone after a heart attack should have their vitamin D level tested and treated aggressively. And I wouldn't be surprised if you see some health influencers saying this.
But we need to pause here for a moment because there are some big caveats. So the target D trial is a randomized clinical study, which is good. But it does not appear to have been blinded. So the patients and the clinicians, they knew who was in the vitamin D management group and who was not. And this means that there's a serious danger for bias in the results. So for one thing, there's the potential of a placebo effect with those taking vitamin D. So let me explain this one. So if a person knows that they're in the active protocol group, that might nudge them to be more engaged with their care. Doctors might be a bit more diligent with their other risk factor management and nurses might call them back a bit more promptly. Now, no one means to be acting in this way to skew the results, but it's just what happens in clinical studies like this and it's why we use blinding in studies. So, a more robust study design might have been to get both groups tested with regular blood tests and have a third party manage their vitamin D dosing. This way, the patients and the study nurses wouldn't know who's in which group, what the vitamin D levels are, or what the dose of vitamin D is being taken. That design would have significantly reduced potential bias.
And it's also worth noting that the primary outcome of this trial, again, the composite MACE metric did not show a statistically significant result. And when it comes to the per protocol analysis of heart attacks, so again, this is where we just look at the group that managed to reach their vitamin D target level. We need to be even more cautious. So even though there was a trend towards improvement in some areas as we saw, the results here do not reach statistical significance. So the treatment with vitamin D essentially failed the sensitivity analysis. So I know I'm getting a bit technical here, but this is really important. In other words, when researchers tried to narrow the analysis to just those cases where we would expect to see the strongest results if vitamin D was actually effective. The picture here was unclear.
We also have to notice some uncomfortable parts of this forest plot. So the hazard ratios for heart failure hospitalization as well as for strokes, they drift higher in the vitamin D group. And those findings, they're not statistically significant. And the confidence intervals are wide. So it may all well be noise. But it's another reminder that biology is messy and pushing people to higher levels of vitamin D of a hormone is not necessarily guaranteed to be free of trade-offs.
So what are the implications here? Well, the target D trial, it doesn't give us clean definitive answers that we might like. And there's nothing here that's likely going to overthrow the current recommendations from the endocrine society. But it does give us some tantalizing evidence that we could see some heart-related benefits in at least some populations by trying to reach certain vitamin D levels in the blood. But we need better designed studies that can address the limitations that we've looked at. And it would be interesting to do a trial of the general population rather than just high-risk individuals. But the trial results here, they do hint that reality might be a bit more complicated than the simple story from the current endocrine society guidelines about vitamin D that I explained earlier.
So here's how my approach is changing as a result of this new study. So let's go back to my patient John. So with the target D trial in mind, I'm going to have a slightly different conversation with him. So we'll talk about the normal stuff of course like lifestyle changes, statins, and other medications, but I'll also describe this new study results and say something like this. The vitamin D research is messy and there isn't a clear answer. The new target D study, it does give us some justification to go ahead with a vitamin D blood test. More research though is required and if it's a financial option for you and you're comfortable with the uncertainty of the research, then go ahead with that test. Equally, that test is not essential and we can stick with the Endocrine Society's current guidelines.
Now, before this new target D study, I wouldn't have brought that up before. And for my own health, I'm considering doing something that I haven't done up until now, which is test my own vitamin D levels. Again, this new study, it doesn't give us definitive evidence, but out of curiosity, I do want to see where my current levels stand. If it's clearly low, then I would consider boosting my vitamin D intake. So, I already take 1,000 international units as part of my multivitamin. And again, just because I take a supplement does not in any way mean that you should as well.
Now, this new study isn't the only one that's made headlines lately related to vitamin D. And some are interpreting another recent study as an indication that vitamin D slows aging. But what did that study actually find and what does it mean for longevity? Well, make sure to check out this next video here to find out.