Episode #381: How a Supplement Sent a Soldier to the Hospital- A Medical Mystery

0:00 [SPEAKER_01]: The patient is 23 years old. [SPEAKER_01]: He's active duty military, stationed at a base where physical readiness isn't just a requirement. [SPEAKER_01]: It's part of the culture. [SPEAKER_01]: He's muscular, he's conditioned, and by all outward appearances, he's a physical specimen. [SPEAKER_01]: But for two weeks, something's been deeply wrong.

0:14 [SPEAKER_01]: It started with nausea, then the vomiting, then a persistent agonizing pain in his jaw that felt like his teeth were being pulled out. [SPEAKER_01]: He assumes it's a bug. [SPEAKER_01]: He'd been swimming in a freshwater river recently, so maybe he caught a parasite. [SPEAKER_01]: And he tries to work through it on his own.

0:27 [SPEAKER_01]: He takes nearly a dozen aspirin a day just to keep the job pain quiet enough to function. [SPEAKER_01]: When he finally walks into a civilian urgent care, the nurse takes his blood pressure. [SPEAKER_01]: It's 180 over 110. [SPEAKER_01]: Way too high. [SPEAKER_01]: Then they run a quick chemistry panel and they find out his creatine's 3.5.

0:41 [SPEAKER_01]: His kidneys are shutting down basically. [SPEAKER_01]: This 23-year-old soldier is rushed to a hospital. [SPEAKER_01]: The doctors are looking for infections, they're looking for rare diseases from the river, and they're looking for kidney stones. [SPEAKER_01]: But the answer wasn't in the water.

0:53 [SPEAKER_01]: It was in a conversation he had with a guy at the gym about six months ago. [SPEAKER_01]: Welcome back to the Barbell Medicine podcast where we bring modern medicine to strength conditioning and strength conditioning, modern medicine on your host Dr. Jordan Faganbaum. [SPEAKER_01]: And today, I'm joined as always by the second most handsome doctor in North America, Dr. Austin Baraki.

1:19 [SPEAKER_01]: Now Austin, we're ending the year with something a little different. [SPEAKER_01]: We've been hitting a science hard on peptides, injuries, and sarcopenia. [SPEAKER_01]: But today, I'm bringing you a mystery case. [SPEAKER_01]: I've got the history and physical. [SPEAKER_01]: I've got the labs.

1:33 [SPEAKER_01]: I've got the imaging and I have a [SPEAKER_01]: should have been at the peak of his health and you're going to be the attending on this one. [SPEAKER_01]: So I'm going to give you the data as it arrived at the bedside and we're going to see if you can figure out why a healthy young soldier's body started failing.

1:47 [SPEAKER_01]: Now my prediction, as I said you all fair, I think you're probably going to get this one. [SPEAKER_01]: I have confidence also I feel like this is something you may have seen before. [SPEAKER_01]: So the question you is, are you ready? [SPEAKER_01]: has ready as I think I'm going to be let's say he says he says nervously.

2:03 [SPEAKER_01]: Okay. [SPEAKER_01]: Well, let's set the stage. [SPEAKER_01]: Our patient arrives at the hospital. [SPEAKER_01]: He is a well-appearing soldier 23 years of age and again, he looks well, which is the first weird thing because you'd expect someone who's been throwing up for two weeks to look sick, but he doesn't.

2:19 [SPEAKER_01]: In fact, his biggest complaint [SPEAKER_01]: Now he tells you that two weeks ago he went swimming in a fresh water river shortly after that the GI issues started. [SPEAKER_01]: So he had nausea, vomiting, diarrhea, and then about a week ago he started having severe unrelenting jaw pain, which is what prompted him to seek care.

2:40 [SPEAKER_01]: He's actually been using about eight tabs of aspirin and ibuprofen 400 milligrams a time for about one week before the presentation, but he continues to have pain. [SPEAKER_01]: Now, he previously had gone to the urgent care center earlier this day because he was unable to keep anything down and his job pain went to 10 out of 10.

2:59 [SPEAKER_01]: Then they found that he had a creatine of 3.5 and a systolic blood pressure was in the 180s, so they subsequently curved him to your hospital. [SPEAKER_01]: Now, naturally, the first thought in the ER was that he was hypervillemic. [SPEAKER_01]: They thought he was dehydrated from acute colitis or some other waterborne pathogen.

3:14 [SPEAKER_01]: He picked up in the river. [SPEAKER_01]: But here's the first data point that kind of breaks that theory. [SPEAKER_01]: He tells you he's been drinking six liters of water per day and he's peeing a lot of clear urine, which was confirmed in the emergency department, so they called you. [SPEAKER_01]: So Austin, we have this young soldier with what looks like a cute renal failure and massive hypertension.

3:35 [SPEAKER_01]: Now, the initial history points to a riverborne infection or dehydration, but he's apparently euvalemic and producing tons of dilute urine. [SPEAKER_01]: So when you see a young fit guy with a blood pressure of 180 over 110, and his kidneys are apparently tanking, all in the context of severe jaw pain.

3:52 [SPEAKER_01]: How do you go about building your differential? [SPEAKER_01]: Are you looking at the river or is your mind going somewhere else? [SPEAKER_00]: Yeah, this is super interesting. [SPEAKER_00]: I was not expecting actually most of what you laid out there. [SPEAKER_00]: There's a lot of different directions you could go because you're right that the initial exposure of the vomiting for two weeks after going swimming, that does suggest some sort of pathogen type exposure, but somebody who is severely dehydrated from vomiting for two weeks generally isn't going to be coming in with a blood pressure in the 180s.

4:18 [SPEAKER_00]: So for me, that was an immediate [SPEAKER_00]: kind of contrary data point. [SPEAKER_00]: The creatine of 3.5 could be explained by all of the insets that he's using, the aspirin and the ibuprofen and things like that. [SPEAKER_00]: But I'm not going to lock in 100% on that because there are also infectious things that can be acquired that can lead to kidney failure, depending on what part of the world you're in, certain tropical exotic infections, things like lip dispiroses and other things can cause a GI syndrome, water borne exposure, things like that and lead to kidney failure among other things.

4:50 [SPEAKER_00]: So, you know, it is a little bit challenging how to focus on the vomiting because so many things can lead to vomiting. [SPEAKER_00]: The kidney failure could be related to the NSAIDs, but could be related to something else, so I'm gonna actually continue to interrogate that a little bit.

5:03 [SPEAKER_00]: The blood pressure is actually maybe surprising to you the least of my concerns right now. [SPEAKER_00]: I tend to get much more concerned when people's blood pressure is way too low, or if it is so high that it is the direct cause of the patient's problems. [SPEAKER_00]: So for example, if somebody has such high blood pressure that it's contributing to an aortic dissection or something like that, this level of blood, I mean, sometimes even when patients are actively wretched against a blood pressure cuff, it can make the blood pressure readings falsely high and ER blood pressure readings are, you know, not going to be the most accurate for just, you know, what, what somebody's resting blood pressure is outside of these emergency situations.

5:37 [SPEAKER_00]: So I'm actually putting the blood pressure [SPEAKER_00]: For now to the side, I'm tracking the creatine, but not putting a massive amount of focus on it. [SPEAKER_00]: I think I know where that's coming from. [SPEAKER_00]: The vomiting is too non-specific for me to really have a clear sense of what to make of it because it can come from so many different things.

5:55 [SPEAKER_00]: And so that leads me with the jaw pain, which seems to be super localizing and it's almost the most severe symptom that the person is reporting. [SPEAKER_00]: And so I'm just gonna listen to what he's telling me. [SPEAKER_00]: And then like, he's telling me, I have 10 out of 10 jaw pain, this is the thing.

6:08 [SPEAKER_00]: that made me go to urgent care today, not the fact that I've been vomiting for a few weeks. [SPEAKER_00]: He certainly doesn't feel his creatine. [SPEAKER_00]: He doesn't feel his blood pressure, but the more localizing of a symptom that I have, the more specificity it might give me. [SPEAKER_00]: And so I definitely want to interrogate.

6:22 [SPEAKER_00]: this job pain a little bit further that in most situations is going to involve some degree of imaging. [SPEAKER_00]: But if I had to start to generate some sort of hypothesis about what could be going on there, I'm breaking it down and to be something inflammatory, for example, could there be some kind of infection or inflammatory focus in that area, some kind of an abscess in the head neck jaw mouth-type area.

6:45 [SPEAKER_00]: Is there a fracture for some odd reason that I would have to then explain? [SPEAKER_00]: other sorts of things like that. [SPEAKER_00]: So that's kind of how I'm, I say, distributing my attention at the moment. [SPEAKER_00]: First on the jaw and then secondarily on the other things. [SPEAKER_00]: The last thing I guess I'll comment on is it is very odd that he reports to be drinking six liters of water per day.

7:06 [SPEAKER_00]: That is a lot and then putting out a lot of dilute urine. [SPEAKER_00]: My first question would be like how confident am I in that history that he is in fact drinking sick leaders They do I believe that I would then do some basic blood and you're in testing to get a sense But that raises concerns about could this patient have diabetes and there are different types of diabetes There's diabetes Melidus, which is what most people under know about the diabetes related into blood sugar problems that can lead to Pying a lot and then you drink a lot as a result and then there's also something called diabetes and cipidus that I [SPEAKER_00]: won't get into details of right now, but we'll bring it back if it becomes relevant where people are just spontaneously peeing out too much dilute urine and then having to drink to keep up with it.

7:46 [SPEAKER_00]: So that's also something I'm tracking, but I'm really focused on the jaw right now because I'm thinking that given the severity and how focal that is there that that might give me the best lead point to to make some progress in the case. [SPEAKER_01]: All right, well, the team runs the work up.

8:01 [SPEAKER_01]: They do the urinalysis, a urine microscopy, infectious titers on autoimmune panel. [SPEAKER_01]: They do imaging of the jaw. [SPEAKER_01]: They repeat his blood chemistry. [SPEAKER_01]: They even do a renal ultrasound to look for obstruction or renal artery stenosis because of the blood pressure.

8:16 [SPEAKER_01]: Almost everything comes back normal. [SPEAKER_01]: He's got no cast, no crystals, no dismorphic cells in the urine. [SPEAKER_01]: His renal artery ultrasound is clean, is all dosturone to reenin ratio is normal, which rules out most of the obvious secondary causes or is hypertension, but is creatinine is still elevated at 3.5.

8:33 [SPEAKER_01]: Now, again, the patient's focus is on his... [SPEAKER_01]: jaw. [SPEAKER_01]: It's not on his creatinine. [SPEAKER_01]: It's not on his nausea. [SPEAKER_01]: He's an agony. [SPEAKER_01]: His main complaint is his jaw. [SPEAKER_01]: And it's so bad that he's no longer controlled with ibuprofen or what they were giving him in the ED.

8:48 [SPEAKER_01]: He requests opioids just to sit still. [SPEAKER_01]: And here's where the case gets a little stranger. [SPEAKER_01]: He's got, again, no fracture seen on imaging of the jaw. [SPEAKER_01]: And he's got no evidence of infection, no evidence of any other like autoimmune disease or something like that.

9:02 [SPEAKER_01]: His kidneys look [SPEAKER_01]: But, and his morning labs after he was admitted, his calcium started to climb. [SPEAKER_01]: They actually did a trial of fluid restriction, but his calcium was 13.7 in the morning. [SPEAKER_01]: Now, Austin, why does this young soldier have a calcium of nearly 14?

9:20 [SPEAKER_01]: And how in the world could this tie back to his severe opioid requiring jaw pain? [SPEAKER_01]: What's your next move for this patient? [SPEAKER_00]: And you have done a great job finding a case that captures many aspects of my interest here, I feel like yeah so hypercalcemia this this high blood calcium level you know among all cumbers my first question when I see that type of level is just a how high is it sometimes I'll see very mildly elevated levels and that I can be seen as something as simple as some dehydration which was of course an initial concern based on this patients reported history of vomiting but proved to not be the case upon further evaluation.

9:57 [SPEAKER_00]: And so then, basically, the higher the calcium goes, the more it kind of changes the differential diagnosis or how we tend to think about things. [SPEAKER_00]: But fundamentally, I want to get a sense of, is there a problem with this patient's parathyroid hormone, which is a hormone that regulates our blood calcium levels, meaning, is he.

10:14 [SPEAKER_00]: inappropriately producing too much parathyroid hormone, and that's making his calcium levels go up. [SPEAKER_00]: Or is this calcium high despite having normal parathyroid kind of function? [SPEAKER_00]: And so getting a PTH level is the next step here to break that down. [SPEAKER_00]: My guess is that his PTH level is going to be appropriately suppressed.

10:32 [SPEAKER_00]: It's not going to be very high in this situation. [SPEAKER_00]: I'm sure you'll let me know here in a little bit. [SPEAKER_00]: And so then other causes, if it is in fact what what will [SPEAKER_00]: Then other questions would start to arise. [SPEAKER_00]: For example, does this patient have vitamin D problems, like vitamin D toxicity?

10:50 [SPEAKER_00]: See taking too much vitamin D supplementation or does he have medical conditions that can lead to excessive activation of vitamin D? [SPEAKER_00]: There's a whole bunch of those that again, I could nerd out on, but I will only bring up if they become relevant in a little bit. [SPEAKER_00]: And then lastly, is he taking some form of calcium supplementation?

11:06 [SPEAKER_00]: So for example, was this patient taking a whole bunch of insects, gave himself a septumic ulcer and had bad esophageitis and reflux and then started taking boatloads of tombs to try to relieve those types of symptoms and tombs are calcium carbonate and you can certainly make yourself hyper calciumic from that.

11:23 [SPEAKER_00]: And then what happens when you have high blood calcium levels is something called, it can lead to essentially diabetes insipidus and what's called nephrocalcinosis. [SPEAKER_00]: So you can [SPEAKER_00]: peeing out tons and tons and tons of dilute urine because the high calcium impairs your kidneys ability to concentrate urine.

11:40 [SPEAKER_00]: And so then he has to drink a bunch of water to keep up. [SPEAKER_00]: So that's one way that I could kind of like craft a narrative that fits how we ended up in this situation with the [SPEAKER_00]: Kidney failure, commonly seen in hypercalcemia, the polyuret, commonly seen in hypercalcemia.

11:55 [SPEAKER_00]: The jaw pain though is still what's interesting to me and how I tie that in. [SPEAKER_00]: Because a lot of times when people have a high blood calcium levels related to some problem of the bones, like bony disease, then you can end up with things like pathologic fractures and things like that.

12:11 [SPEAKER_00]: But you already told me, there was no fracture on his imaging. [SPEAKER_00]: You didn't really tell me what was seen if there was anything seen on the imaging of his jaw. [SPEAKER_00]: a little bit intrigued by that, but yeah, so to summarize now, this high blood calcium level explains certain aspects, his kidney situation, his bland urine testing, the peeing a lot, the drinking a lot, I'm still unsure of what to make of the, of the jaw pain.

12:33 [SPEAKER_00]: And so next steps will be checking PTH status, checking vitamin D status, asking him about, hey, have you been taking a bunch of calcium supplementation of any kind, terms, [SPEAKER_00]: things like that or or other calcium containing substances. [SPEAKER_00]: There are also some other drugs that can cause this, but again, I'll like I think like vitamin A and so and a few other things that I'll leave aside for now.

12:52 [SPEAKER_00]: But so yeah, tell me what we got next. [SPEAKER_01]: All right. [SPEAKER_01]: Yeah. [SPEAKER_01]: So just to review for the listeners, we've got this young soldier with apparently some acute kidney injury going on. [SPEAKER_01]: He's got some hypertension and he's got a high calcium level.

13:06 [SPEAKER_01]: We've looked at the obvious stuff again, the renal ultrasound's clean, the infectious work up is all negative and so yeah, doesn't look like he picked up anything in the river, but then they check his parathyroid hormone as you. [SPEAKER_01]: discussed. [SPEAKER_01]: Again, when calcium is high, these glands usually should be turned off, appropriately suppressed, is the what the term you use.

13:29 [SPEAKER_01]: And so in this patient, his PTH level was just five, which is appropriately suppressed. [SPEAKER_01]: So the glands are doing exactly what they were supposed to do. [SPEAKER_01]: They're shutting down because they detected that there was already way too much calcium in the blood. [SPEAKER_01]: So this kind of rules out, maybe there's something growing on that gland that causes it to go rogue and pump out too much hormone and increase calcium through [SPEAKER_01]: So then they ordered a chest X ray.

13:50 [SPEAKER_01]: They wanted to look at the lungs and the lymph nodes to see if there was any enlarged nodes, which we call high-lar adenopathy, which might have pointed towards something like sarcoidosis. [SPEAKER_01]: So if you've ever watched house, they just have to loop this or sarcoidosis always comes up.

14:03 [SPEAKER_01]: And that can ramp up vitamin D levels. [SPEAKER_01]: But the X ray was completely clear. [SPEAKER_01]: No masses, no swelling. [SPEAKER_01]: Vitamin D levels are currently pending. [SPEAKER_01]: So, at this point in the story, the doctors were actually considering performing a kidney biopsy, which basically involves taking a needle, takes small pieces of the kidney for testing, because the patient's high blood pressure and kidney issues just weren't making sense.

14:24 [SPEAKER_01]: But before they went through that procedure, they actually sent a medical student back into the room to do a medical reconciliation, which is basically just a look. [SPEAKER_01]: What meds are you taking? [SPEAKER_01]: What supplements are you taking? [SPEAKER_01]: It's also another opportunity to do like a little interview with the patient.

14:39 [SPEAKER_01]: Now, the patient had already told the doctors he wasn't taking any steroids or gym supplements. [SPEAKER_01]: However, the student changed the framing of the question. [SPEAKER_01]: Instead of just asking about drugs or supplements, he asked if they were taking anything natural or healthy over the counter.

14:53 [SPEAKER_01]: This is a huge distinction. [SPEAKER_01]: For many people, I'm sure you run into this, even especially as a med student, you get kind of embarrassed. [SPEAKER_01]: You're like, oh, I didn't ask about that directly. [SPEAKER_01]: It's like, they left out history. [SPEAKER_01]: So, yeah, many patients don't use things labeled natural as medicine, so they often don't mention it.

15:08 [SPEAKER_01]: Now, the soldier says, look, I'm just bulking right now, I'm taking a multivitamin, I'm taking vitamin B12, and this one specific supplement I heard about in the gym. [SPEAKER_01]: I've been taking it every morning for six months, because I was told it's the only way to maximize natural testosterone production.

15:24 [SPEAKER_01]: So, Austin, this is your final clue. [SPEAKER_01]: The patient is taking an over-the-counter supplement in high doses because of a gym myth he heard about testosterone. [SPEAKER_01]: Now, combined with a suppressed PTH, a sky-high calcium level and agonizing jaw pain. [SPEAKER_01]: What's your final diagnosis for this soldier?

15:42 [SPEAKER_00]: Yeah, this is interesting. [SPEAKER_00]: So going back to some of the things that we're mentioned, yeah, I mean, sarcoidosis is an example of one of those conditions that I mentioned called granulomatis diseases that can lead to overactivation of vitamin D. And so if his vitamin D levels had been sky-high, depending on what type 25 hydroxy, 125 hydroxy vitamin D, et cetera, that can help us start to make some progress on those types of conditions like sarcoidosis or certain lymphomas, certain infections that can lead to that kind of thing.

16:08 [SPEAKER_00]: The fact that they were considering kidney biopsies a little bit interesting to me, I don't think I would have been in that space mainly because you told me that his urinalysis was totally benign. [SPEAKER_00]: And so it did not really point to a primary kidney disease as the cause here.

16:22 [SPEAKER_00]: So I would not have been in that space. [SPEAKER_00]: I would have, as I mentioned in the last kind of step, doing exactly what was done here. [SPEAKER_00]: Going back and talking, grilling him about everything that he was potentially taking. [SPEAKER_00]: Now, if I think through what types of drug supplements things like that that can lead to increases in blood calcium level, there are a handful of commonly used drugs that we know that can lead to hypercalcemia.

16:44 [SPEAKER_00]: I mentioned a few of them things like certain types of blood pressure medicines like die sides. [SPEAKER_00]: I think lithium can play a role, again, vitamin A. I think has some [SPEAKER_00]: relationship there, there are a few others. [SPEAKER_00]: I would be actually probably doing some searching of my own looking through what sorts of supplements do people take regularly to boost testosterone that can contribute to that.

17:02 [SPEAKER_00]: I think, you know, you hear so many things in the fitness guru and like testosterone optimization space that people take. [SPEAKER_00]: I've heard of things like like a fourth zinc. [SPEAKER_00]: I've heard of people, of course, taking vitamin D to increase their testosterone. [SPEAKER_00]: I've heard of people using like boron to increase their vitamin D levels.

17:20 [SPEAKER_00]: I've heard of [SPEAKER_00]: you know, many other ones. [SPEAKER_00]: And so narrowing that exactly down and tying that into the job pain, this is actually a point where I would be having a little bit of trouble predicting it outside of doing some searching or just like obviously the patient tell me what he's taking and then like cross referencing that on the internet with potential contributions to hypercalcemia like this.

17:43 [SPEAKER_01]: Okay, well, I'm going to give you one final clue. [SPEAKER_01]: I know I said that was the final clue, but this is the actual final clue, final final clue, the final boss. [SPEAKER_01]: So the lab finally calls the floor. [SPEAKER_01]: They had to dilute the sample multiple times because the levels were off the charts.

17:58 [SPEAKER_01]: The serum, 25 hydroxy vitamin D level, is unquantifiable. [SPEAKER_01]: Listed as greater than 200 nanograms per milliliter. [SPEAKER_01]: Does that help you with your diagnosis? [SPEAKER_01]: Yeah, dude, it's taking potloads of vitamin D. In fact, the diagnosis is severe hypervitaminosis D. A patient reveals that he's been taking at least 10,000 IUs or international units of vitamin D every single day for the last half of a year.

18:24 [SPEAKER_01]: I wasn't trying to hurt himself. [SPEAKER_01]: He was following the advice from a friend at the gym who cited a popular, but often misunderstood studies suggesting that vitamin D supplementation could skyrocket testosterone levels. [SPEAKER_01]: my gosh, this is so dumb. [SPEAKER_01]: Team immediately started him on aggressive fluid resuscitation.

18:42 [SPEAKER_01]: His calcium peak at 13.7, but slowly began to drift down as they flushed out his system. [SPEAKER_01]: He was discharged for outpatient monitoring and he agreed to stop taking supplemental vitamin D. They never actually did measure his testosterone levels just to see life. [SPEAKER_00]: Yeah, quick.

18:57 [SPEAKER_00]: Yeah, I would have measured his testosterone level either in the hospital setting. [SPEAKER_00]: This is both not not smart, so would not advise people. [SPEAKER_00]: I'd be curious, you know, if they measured a phosphate level, did you have a phosphate level in the labs that you were able to report?

19:11 [SPEAKER_00]: Because that would be also like, I would have gotten this actually far earlier if you had given me that his both has calcium and his phosphate levels were high, because that can be a giveaway and then because PTH tends to make phosphate go down and vitamin D tends to make it go up. [SPEAKER_00]: Now, the scary thing is, because vitamin D is one of these fat soluble vitamins, it can accumulate quite a bit.

19:35 [SPEAKER_00]: And so this is something that can last a long time before it gets better. [SPEAKER_00]: Sometimes these patients have to get put on glucocorticoids like prednisone, actually, to try to [SPEAKER_00]: reduce the associated risk of hypercalcemia from vitamin D toxicity. [SPEAKER_00]: And that can last for months after people have this kind of thing.

19:54 [SPEAKER_00]: And so if this guy was hoping to take a bunch of vitamin D to make his testosterone go up so that he could train in the gym and get jacked. [SPEAKER_00]: And instead gave himself vitamin D toxicity leading the hypercalcemia. [SPEAKER_00]: And if he let's say required prednisone, really shot himself in the foot there because he's going to end up on a catabolic steroid until he can get through this period.

20:11 [SPEAKER_00]: And obviously get his calcium levels down and his kidney function back to normal. [SPEAKER_00]: So pretty, pretty unfortunate, and I think a good cautionary tale against kind of taking excess vitamin D very casually like this. [SPEAKER_01]: Yeah, pretty interesting course afterwards, also.

20:25 [SPEAKER_01]: So a month later, his creatinine level is still 2.09, which is high. [SPEAKER_01]: The kidneys were still struggling. [SPEAKER_01]: And in this case, it seems like the kidneys were essentially caught in a perfect storm. [SPEAKER_01]: Now, the primary issue was a massive overload of vitamin D, which pushed blood calcium levels [SPEAKER_01]: The high calcium is already kind of hard on the kidneys, but the situation was made worse by the use of aspirin and the NSAIDs.

20:50 [SPEAKER_01]: These medications further restricted blood flow to the kidney and can cause direct damage to the filtering tubes. [SPEAKER_01]: A condition we call acute tubular necrosis. [SPEAKER_01]: So yeah, as you mentioned, it's a powerful reminder that even common supplements that are over the counter can become toxic when the underlying physiology is pushed out of balance.

21:09 [SPEAKER_00]: Yeah. [SPEAKER_00]: 100%. [SPEAKER_00]: It's not super clear to me that he actually had a ton of direct kidney injury related to the NSA. [SPEAKER_00]: If his total of his urine testing was completely bland, benign. [SPEAKER_00]: But as I said, you know, the Nefro calciumosis that you can end up with from chronic exposure to high blood calcium levels can be problematic like this.

21:29 [SPEAKER_00]: And so he had a bunch of different potential mechanisms of [SPEAKER_00]: of kidney injury. [SPEAKER_00]: So, yeah, hopefully, backs off of many of those supplements and takes better advice in the future. [SPEAKER_00]: But scary case. [SPEAKER_01]: Yeah, three months later, his creatine was down to a healthy baseline of one.

21:45 [SPEAKER_01]: His calcium had been normalized. [SPEAKER_01]: Six months later, his vitamin D was still at 80, which is on the high end, showing just how long this fat soluble vitamin stays in the system. [SPEAKER_01]: But here's the really interesting, at least to me, part of the case. [SPEAKER_01]: It was also unfortunate.

22:00 [SPEAKER_01]: Even after his kidneys recovered, he remained hyper-tensive. [SPEAKER_01]: The damage to his vascular system from that period of high calcium appeared to be lasting. [SPEAKER_01]: So I did some digging like how could this happen. [SPEAKER_01]: It seems like this high calcium level, especially like six months of taking 10,000 I use of vitamin D per day.

22:18 [SPEAKER_01]: It seems like it can act as a slow-moving toxin for the blood vessels. [SPEAKER_01]: So like when calcium is that high for that long, it can deposit into the walls of the arteries themselves. [SPEAKER_01]: Calcium phosphate salts actually deposit in the middle layer, the tunicomedia of the arterial walls, which is known as metastatic calcification.

22:38 [SPEAKER_01]: which tends to increase this pulse wave velocity and systemic bascular resistance which can lead to kind of this structural hypertension if you want to call it that. [SPEAKER_01]: Like normally the arteries are like these high-quality rubber hoses, they're flexible and they bounce back with every heartbeat which helps keep your blood pressure in a healthy range.

22:56 [SPEAKER_01]: But because of the period of high calcium, the vessels had effectively been turned into something more like lead pipes that had lost their stretch. [SPEAKER_01]: And now because the pipes are more rigid, the heart has to pump much harder to move blood through them, which keeps the blood pressure high.

23:10 [SPEAKER_01]: So the kidneys are doing their job again on the hormones are, quote, balanced, but the physical structure of the vascular system has been permanently changed. [SPEAKER_01]: So no longer treating this temporary imbalance, but he might have to be on some anti-hypertensives. [SPEAKER_01]: to Austin, our soldier recovered from his kidney function, but he stayed hyper-tensive from a medicine perspective, once this crisis initially is over, he's discharged.

23:35 [SPEAKER_01]: What does the cleanup look like for a patient over the next 12 months or so? [SPEAKER_00]: Yeah, this is interesting. [SPEAKER_00]: I mean, you're hypothesis about the blood pressure. [SPEAKER_00]: I would call it a hypothesis that's a little bit challenging to prove, of course, I'd be curious what his blood pressure was like before all this happened.

23:56 [SPEAKER_00]: All along, having diffuse kind of systemic calcification of your arteries at age 23, even with a few months of this, I'm still not 100% sure is entirely case. [SPEAKER_00]: I do see that happen though, I see it much more often, unfortunately in patients with more either advanced vasco disease in general or patients with bad kidney disease, especially dialysis patients.

24:17 [SPEAKER_00]: I've seen a pretty horrible condition called calcifal axis where they get that calcification of their blood vessels and it leads to [SPEAKER_00]: kind of developing all over the place from this calcium phosphate deposition. [SPEAKER_00]: So that's a, that's a, that's a maybe for me. [SPEAKER_00]: I do think that there are a lot of ways that we have to control his blood pressure.

24:35 [SPEAKER_00]: And so, you know, the, the, the strategy for that would be fairly actually routine to get his blood pressure down once you've ruled out secondary causes, which they did, you know, a pretty reasonable initial evaluation for that kind of thing. [SPEAKER_00]: As I mentioned, if his, [SPEAKER_00]: calcium level is persistently very high.

24:53 [SPEAKER_00]: There's other medical things that are sometimes done like I mentioned. [SPEAKER_00]: Sometimes people get put on glucocorticoids, printed on things like that. [SPEAKER_00]: But really it's going to be, you know, time and letting his body kind of do its job getting off of these things, getting control of his blood pressure usually with medications, or if there's a secondary cause treating it.

25:09 [SPEAKER_00]: And then not really, fortunately at tunnel, it's 23 year olds can be pretty robust and resilient even after going through something as dramatic as this. [SPEAKER_00]: He seems to have mostly recovered based on the trajectory that you told me so far. [SPEAKER_01]: Yeah. [SPEAKER_01]: All right.

25:20 [SPEAKER_01]: Well, let's talk about this job pain for a second because I was wondering about it and sure you're wondering about the audience, like wondering why to me, this is fascinating. [SPEAKER_01]: So to tell me what you think about this potential mechanism. [SPEAKER_01]: So we know that excess vitamin D doesn't just increase calcium absorption from the gut.

25:37 [SPEAKER_01]: It can actually drive some level of bone resorption. [SPEAKER_01]: We usually think of vitamin D as a good thing, but in extreme amounts, it can cause the body to aggressively pull calcium out of the bones and into the bloodstream. [SPEAKER_01]: So this could explain the jaw pain, not like a dental problem, but rather the physical sensation of his body stealing calcium from his own skeleton, including his jaw, to dump it into the blood.

25:58 [SPEAKER_01]: So I looked into this a little bit regarding the jaw specifically, but bone resorption is systemic, but the jaw is a side of very high bone turnover sort of normally. [SPEAKER_01]: So in cases of extreme bone resorption, which we see in hyperparathyroidism or severe vitamin detoxicity like this patient, people can develop what are called brown tumors or focal areas of bone loss.

26:21 [SPEAKER_01]: And so it's possible that this agonizing pain he felt was his own bone structure being chemically dismantled from the inside out. [SPEAKER_01]: Potentially causing micro fractures that were missed on routine hygiene and changes in the local bone marrow environment from the rapid bone [SPEAKER_01]: So I went into like a radiology rabbit hole and like how often does standard like x-rays miss this and Oh, it's a pleasure.

26:44 [SPEAKER_01]: It's been going on for a long time and it's very severe. [SPEAKER_01]: So it would have been interesting if he got some either advanced imaging or some sort of like radio labeled imaging to assess this out, but I don't know. [SPEAKER_01]: What do you think about that mechanism? [SPEAKER_00]: Yeah, so your right that the jaw seems to be an area of more aggressive turnover and that's why, for example, when patients are put on certain treatments for osteoporosis like this phosphonates, we often tend to be a little bit cautious, especially if they have dental work pending things like that, there's phenomenon called osteonacrosis of the jaw that can happen in those patients where there's some bone that actually dies in the jaw related to the use of those medicines.

27:17 [SPEAKER_00]: So we tend to be pretty cautious around that. [SPEAKER_00]: I haven't heard of this happening from vitamin D toxicity, but if it is accelerating bone turnover, I find that a plausible mechanism. [SPEAKER_00]: I also am completely unsurprised that just like routine x-rays of the jaw, especially these are just like routine ER x-rays, and this is not shade at the ER, but rather that those types of x-rays are done pretty quickly, sometimes even like a lot of ER x-rays are done portable at the bedside and being read, looking for major emergencies by emergency radiologists, and so the really detailed nuances I wouldn't be surprised if those don't always get caught, or if you need some more.

27:54 [SPEAKER_00]: uh... type bone scan or some sort of like uh... you know imaging that uh... looks for uh... cell activity in the area some sort of nuclear medicine uh... you know this is outside getting outside my uh... air of expertise in practice i frequently just get on the phone with the radiologist and i'm like hey [SPEAKER_00]: Here's what I'm thinking.

28:10 [SPEAKER_00]: Here's what I'm worried about. [SPEAKER_00]: What's the best scan for me to, you know, to look for this particular issue? [SPEAKER_00]: And that's what I would be have been doing in this situation to try to figure it out if the plane x-rays were unrevealing, which is again, not at all surprising to me.

28:22 [SPEAKER_00]: So I find that to be plausible, interesting. [SPEAKER_00]: We know the jaw is a, is a hotbed of bone activity and relates a lot of these conditions. [SPEAKER_01]: Yeah. [SPEAKER_01]: All right. [SPEAKER_01]: Well, let's talk about a little bit of the brosides that ultimately doomed our shit here.

28:36 [SPEAKER_01]: One study that gets a lot of airtime has been cited of bunch is this Pills study from 2011. [SPEAKER_01]: I've seen it actually cited a few times online in the Biohacker and sort of natural testosterone optimization circles. [SPEAKER_01]: It's suggested a link between vitamin D supplementation and testosterone now.

28:53 [SPEAKER_01]: In the study, a group taking about 3,300 I use a vitamin D per day for a year, increased their testosterone levels from an average of 300 nanograms per deceler, to 380 nanograms per deceler, whereas those taking up placebo didn't see any changes. [SPEAKER_01]: So you look at that and you're like, hmm, that's a bump.

29:12 [SPEAKER_01]: I want a bump, more testosterone, more gains. [SPEAKER_01]: There are a few problems with this study. [SPEAKER_01]: So one, it was not actually designed to test testosterone levels. [SPEAKER_01]: It was actually a secondary post-hoc analysis of a weight loss study. [SPEAKER_01]: The researchers didn't recruit men to see a vitamin D built muscle or increased testosterone.

29:30 [SPEAKER_01]: They just looked back at a small group of 54 dudes who happened to have their testosterone levels measured. [SPEAKER_01]: Now, in the world of science, when you dig through enough data after a study is already over, you can typically find a correlation with something by sheer coincidence if you look at enough variables.

29:45 [SPEAKER_01]: No shade intended, but this is a classic case of data mining being presented as a primary discovery. [SPEAKER_01]: It happens all the time, unfortunately. [SPEAKER_01]: The second problem with the study, again, we're talking about 54 people. [SPEAKER_01]: In a study that small, one or two outliers can completely skew the average, the difference was modest, 300 to 380 nanograms per deceler, so not crazy.

30:06 [SPEAKER_01]: So tiny sample size, the statistical signal can be incredibly noisy there. [SPEAKER_01]: This is why larger, better control trials and meta-analysis. [SPEAKER_01]: with hundreds of thousands of patients can be better at showing the real relationship. [SPEAKER_01]: The other problem here is that they used an immunocase to measure testosterone levels, which is an older type of test that is notoriously unreliable, especially at lower testosterone levels, compared to the new test we use, which are LCMS.

30:34 [SPEAKER_01]: And then finally, even if we take the study at face value, the increase they found is almost certainly not clinically significant. [SPEAKER_01]: This slight bump in numbers, which are they're well within the test error bars. [SPEAKER_01]: And the study did not measure like muscle proteins synthesis.

30:48 [SPEAKER_01]: It didn't measure one rep max strength or muscular hypertrophy body composition. [SPEAKER_01]: or even symptoms of testosterone deficiency so like a slightly higher number on a lab report to me doesn't matter if it doesn't actually change the person's life. [SPEAKER_01]: We see this all the time.

31:03 [SPEAKER_01]: People will take this tiny shift in a surrogate marker and then especially with a supplement and they'll just run with it, market it to the hills. [SPEAKER_01]: Now, three recent meta-analysis essentially closed the door on this. [SPEAKER_01]: They looked at the totality of the evidence and found that Vitamin D is pretty much a total wash for testosterone levels, regardless if someone has low or normal testosterone levels or low or normal Vitamin D levels.

31:27 [SPEAKER_01]: So the analogy I think about here is like, [SPEAKER_01]: If you take vitamin D to boost testosterone, it's kind of like trying to fix a car that won't start by adding more gas to the tank. [SPEAKER_01]: If the engine is the problem, it doesn't matter if your gas tank was bone dry or already half full, adding more fuel is not gonna make the car run.

31:46 [SPEAKER_01]: You can keep pumping more and more gas. [SPEAKER_01]: That's the vitamin D, but you're not fixing the motor. [SPEAKER_01]: That's the source of the testosterone efficiency. [SPEAKER_01]: You're just creating potentially a massive spill that could become a fire hazard or in our patient's case.

31:58 [SPEAKER_01]: Metastatic, calcimed deposition. [SPEAKER_01]: So Austin, we have this massive industry built on the idea that more is better and that vitamins are typically benign. [SPEAKER_01]: Walk us through why vitamin D is different from water soluble vitamins like vitamin C or vitamin B12. [SPEAKER_01]: And why do you think that natural testosterone marketing that that machine cleans to stuff like this?

32:21 [SPEAKER_00]: Yeah, lots of reasons, it's certainly a hot topic these days, even though we've been talking about testosterone for many, many years at this point. [SPEAKER_00]: So to the first question, the concept of fat soluble vitamins is, you know, it has to do with the type of solution that they dissolve best into, whether it's fat or our water-based bloodstream.

32:40 [SPEAKER_00]: And water soluble vitamins tend to last, [SPEAKER_00]: or a shorter period of time in the body and can get readily excreted in the urine as a water-based kind of medium. [SPEAKER_00]: The fat soluble vitamins tend to get sequestered in our adipose and our body fat, and they can sit there for a long time.

32:56 [SPEAKER_00]: They're not easily excreted in the urine because we are excreting water and not kind of a fatty. [SPEAKER_00]: We don't pee out oil as a way to excrete that. [SPEAKER_00]: That would be a problem. [SPEAKER_00]: And so that the trade offs there are that, you know, if if somebody is completely deficient in, say their diet is completely deficient in water soluble vitamins, they are more readily going to become deficient in that on a shorter timeframe because the intake and output happens on a shorter basis.

33:25 [SPEAKER_00]: Whereas the fat soluble vitamins that tend to can accumulate and get sequestered, you're going to be a little bit more resistant to developing deficiencies if you have some stores kind of built up in your body fat. [SPEAKER_00]: The trade-off there is that if you get toxic, if you have too much of it, then it can kind of accumulate and you can have prolonged toxicity.

33:43 [SPEAKER_00]: instead of if somebody overdoses on thiamine, I'm not concerned at all. [SPEAKER_00]: In fact, I probably intentionally overdose people on thiamine in the hospital all the time because the risks of being deficient in thiamine are so great, whereas the risks of me giving them way too much are essentially zero.

33:59 [SPEAKER_00]: And so I err on the side of treating people very aggressively with thiamine when they're at risk for deficiency if they have, you know, alcohol use issues, things like that. [SPEAKER_00]: But I don't at all do that with vitamin D. There's no situation where I'm [SPEAKER_00]: aggressively giving somebody vitamins A or D or E or K being the predominant kind of fat soluble vitamins outside of very, very, very rare types of situations.

34:22 [SPEAKER_00]: And so that's the fundamental difference in one that played out in this patient's case. [SPEAKER_00]: I totally get, you know, when people perceive a problem, or if, in fact, they do have a problem like testosterone deficiency trying to seek out what basic measures be at lifestyle, what on quote natural or otherwise, can I do to try to improve this?

34:39 [SPEAKER_00]: And I don't even fault people who might say, look, I understand what you're saying that 80, you know, nanograms is not a clinically significant difference, but [SPEAKER_00]: Maybe if I do this to get 80, and I stack it with sleeping better, and that gets me 50, and I lose a little bit of weight, and that gets me 100.

34:53 [SPEAKER_00]: Maybe that takes me from 300 to 500 or 600, and, you know, the accumulating effect of multiple small interventions or something like that. [SPEAKER_00]: Like, okay, I mean, it sounds like we're pursuing a generally, we're aiming to pursue a generally healthy lifestyle pattern, trying to, you know, tinker with a lot of small variables and hoping that that adds up to, you know, a generalized improved downstream state of health.

35:13 [SPEAKER_00]: I think that that's not a crazy idea, but of course this is also being done like as seen in this case, without a good understanding of what are the potential downsides of things like dosage and monitoring and how I'm actually going about this process, right? [SPEAKER_00]: And so to those meta analyses, I'm not surprised that it end up coming out in the wash.

35:31 [SPEAKER_00]: There's also some questions of how much does it matter kind of how you got there, type picture, right? [SPEAKER_00]: So. [SPEAKER_00]: If somebody had a vitamin D level of zero, I wouldn't be surprised if maybe having some vitamin D replacement leads to improvements in various other things, but of course, at the same time, my question is like, what led to their vitamin D level being zero, are they just frankly completely now nourished for some reason?

35:53 [SPEAKER_00]: Do they have some undiagnosed, you know, GI, pancreatic intestinal disease that leads them to be unable to absorb? [SPEAKER_00]: Certain nutrients all together, and it's not as simple as just, oh, just give them to the vitamin D and then it'll fix their testosterone, but maybe a whole bunch of systems can be made to function better if we identify the underlying issue here, right, and the same as somebody's testosterone level is, you know, zero.

36:14 [SPEAKER_00]: That's actually the lowest I've ever seen is the testosterone level is [SPEAKER_00]: Yeah, okay, it's not going to be like take vitamin D and get your level from zero to 80 and that's like, why did it get there? [SPEAKER_00]: So that's part of why when we talk about testosterone deficiency, we talk a lot about the importance of accurate diagnosis, a proper medical assessment to think through what sorts of things could be contributing, what sort of levers can we pull and how hard should we pull those things?

36:40 [SPEAKER_00]: Is there a scenario where I might tell somebody? [SPEAKER_00]: Yeah, we should probably put you on some vitamin D. Yeah, I can see that happening, but that is not really very common for me to say, oh, your testosterone is like mildly low. [SPEAKER_00]: Let's just get you on some vitamin D and it should fix your testosterone levels.

36:53 [SPEAKER_00]: This is more like [SPEAKER_00]: severe deficiency to help address a lot of issues while I try to get to the bottom of like why did any of this happen, right? [SPEAKER_00]: So it's it's really interesting hearing myself say this because I recognize how often out there there is this view of yet doctors just treat symptoms.

37:10 [SPEAKER_00]: They don't look for quote unquote root causes. [SPEAKER_00]: Meanwhile, here I am, you know, saying, hey, I'm curious why we ended up in this state of testosterone deficiency of severe vitamin D deficiency, [SPEAKER_00]: And I'd rather figure that out and address those things where there's a lot of folks in this kind of biohacker optimization space, though, like not really terribly curious about how those things happen, but they rather just like take the zinc and the boron and the vitamin D and the, and the, you know, the, the ser, the sarms or whatever, whatever, the kind of stuff to make the numbers look prettier.

37:42 [SPEAKER_00]: It's almost like a total inversion of that same perspective when applied in other contexts. [SPEAKER_01]: Yeah. [SPEAKER_01]: Yeah. [SPEAKER_01]: That's a good summary. [SPEAKER_01]: And we know that like lifestyle and general health status plays a significant role in both vitamin D levels and testosterone levels.

37:57 [SPEAKER_01]: So it's no surprise to me that there's a correlation between the two being low. [SPEAKER_01]: For example, an individual with excess body fat, not sleeping well, maybe their dietary pattern is not as good as we want it to be. [SPEAKER_01]: It's no [SPEAKER_01]: Surprised to me that these things trend together and that if you improve somebody's health, that both things will trend back the other way.

38:17 [SPEAKER_01]: The real question that we're getting at here is does independent of all of that, adding a vitamin D supplement actually help. [SPEAKER_01]: I know it'll make the number, the vitamin D number look better, but I have a low pre-test probability that that doing it will independently raise testosterone levels unless other stuff changes.

38:37 [SPEAKER_00]: Totally and yeah and certainly like to what we would deem a clinically significant degree. [SPEAKER_00]: It's not taking it's very unlikely Absent a whole bunch of other lifestyle changes and things like that to say oh, it's going to take your level from 200 to 500 Like I would deem that to be yeah, that's legit.

38:51 [SPEAKER_00]: That's clinically significant, but you know the idea that I'm going to start taking a thousand IU or 5,000 IU or 10,000 IU Please don't take a lot more than that on a daily basis or even up to 10,000 IU a day is generally not a great idea for a lot of people [SPEAKER_00]: But that alone absent any other changes is going to lead to that level of change in real life is very unlikely.

39:13 [SPEAKER_01]: Yeah. [SPEAKER_01]: All right. [SPEAKER_01]: Well, let's wrap this case up. [SPEAKER_01]: I want to pivot to what this means for a person listening to this who's also currently looking at a bottle of vitamin D on their kitchen counter. [SPEAKER_01]: We've seen the extreme on one side, this young soldier with potential kidney failure and some hypertension, but the subclinical version of this happens more often than people realize.

39:33 [SPEAKER_01]: So, here are my takeaways from this. [SPEAKER_01]: One, [SPEAKER_01]: is the testosterone myth, which I think we kind of beat into submission. [SPEAKER_01]: The engine behind this entire case was the belief that vitamin D is like a pro hormone for testosterone. [SPEAKER_01]: As we mentioned, multiple recent meta-analysis have shown that vitamin D supplementation has no significant effect on testosterone levels in men, regardless of their initial testosterone or vitamin D levels.

39:56 [SPEAKER_01]: Whether you're vitamin D deficient or not, taking 10,000 IUs a day isn't going to turn you into a pro bodybuilder. [SPEAKER_01]: mostly it's going to turn your blood in a calcium soup. [SPEAKER_01]: The second parole here is this is uh, there's some dosine confusion that's happening in the public.

40:10 [SPEAKER_01]: One of the most dangerous things to me that's happened in the supplement aisle is the labeling for vitamin D. So in 2020 the FDA began requiring manufacturers to list vitamin D in both micrograms and international units and so people are often conflating the touch. [SPEAKER_00]: Usually it's like 10, 25, or 50 mic pills is pretty common dose breakdown.

40:33 [SPEAKER_00]: So I'm not too often that I see much higher than that, but if somebody's taking 50 mic pills and then taking enough to get 5,000 a day like that would be, yeah, you get overdosed pretty quick on something like that. [SPEAKER_01]: Yeah, the math on this is one microgram equals 40 IUs. [SPEAKER_01]: So if a patient sees a bottle, it says 125 micrograms or whatever, and they think it's a small number, they may not realize that they're actually taking 5,000 IUs per serving.

40:55 [SPEAKER_01]: So if they double up because they feel tired or they've read something online or social media influencer says something, suddenly they're taking 10,000 IUs a day, which can lead to some toxicity. [SPEAKER_01]: Now, Austin, as a physician, seen patients in the hospital, [SPEAKER_01]: How often are you seeing them, when they come in, they're technically overdosing on a medication simply because they're either a misunderstanding the direction or they're taking a supplement incorrectly because the label is confusing.

41:21 [SPEAKER_00]: Yeah, unfortunately, it happens super often. [SPEAKER_00]: I think there's this is an era of what we'll call polypharmacy. [SPEAKER_00]: A lot of people are on a lot of medicines. [SPEAKER_00]: And statistically, as soon as you're over three medicines, then your odds of having drug drug interactions goes way up.

41:36 [SPEAKER_00]: And the complexity of dosing ends up getting to be a bigger problem, especially for people who tend to take more medicines as they get older. [SPEAKER_00]: So if you have a medicine that this one's twice a day, this one's three times a day, this one's in the morning, [SPEAKER_00]: You know, don't mix these up and then you and then people start having side effects and maybe somebody puts them on a medicine to treat that side effect and then you're even making it more complex and more interactions.

41:59 [SPEAKER_00]: This gets messy really fast and unfortunately, you know, sometimes I'll spend a week working on the words in the hospital and I'll just take stock of you know how many people have I admitted because of a complication of a medicine that they're taking and it is unfortunately. [SPEAKER_00]: high proportion of the time where people might come in for dizziness or falls or vomiting or kidney issues or you know liver issues or something like that related to something that they're taking which may have been you know most of the time is being prescribed we obviously with good intent not nefarious intent but sometimes with insufficient caution or insufficient monitoring or insufficient explanation or instruction or things like that and so yeah to some extent it's on us of course to some extent it's on the

42:40 [SPEAKER_00]: You know, adhere to these things, but oftentimes it comes down to inadequate explanation, education, and like shared plan formation of how are we going to go about this and people can suffer, you know, problems as a result. [SPEAKER_00]: So, especially when there are supplements that are not reported or asked about that also get thrown in the next, then you can augment that risk as well.

42:57 [SPEAKER_00]: So it's a complex world and and something that unfortunately I see actually pretty often. [SPEAKER_01]: Yep. [SPEAKER_01]: Yep. [SPEAKER_01]: All right. [SPEAKER_01]: The next Pearl is some of who kind of talked about already the fat soluble trap. [SPEAKER_01]: So as Dr. Brocky said, unlike vitamin C or B vitamins, where you essentially just pee out the excess, vitamin D's fat soluble.

43:16 [SPEAKER_01]: It stores in your ad opposed tissue and has a long half-life. [SPEAKER_01]: Now our soldier in this case had elevated levels six months after he stopped taking the supplement. [SPEAKER_01]: So if you overdo it, you can't just detox it out in a weekend, you're stuck with those levels for a pretty long slow recovery.

43:32 [SPEAKER_01]: Now in a recent review by bullion, they kind of explain the molecular why behind this soldier's crisis. [SPEAKER_01]: So when we talk about vitamin D, we're usually just looking [SPEAKER_01]: But this particular review highlighted free vitamin D hypothesis. [SPEAKER_01]: Most of our vitamin D is carried around by a specific transport protein called vitamin D binding protein.

43:55 [SPEAKER_01]: You can think of this as like a taxi service for the hormone. [SPEAKER_01]: As long as vitamin D is on the taxi, in the taxi, it's mostly sequestered and safe. [SPEAKER_01]: But our patient was taking 10,000 I use a day for six months. [SPEAKER_01]: He essentially saturated every single taxi in the bloodstream.

44:11 [SPEAKER_01]: So Austin, you can weigh in on this. [SPEAKER_01]: We spend so much time talking about the left side of the curve, the deficiency side, but our patient was on the right side. [SPEAKER_01]: access. [SPEAKER_01]: When we look at this from a molecular level, why is it so dangerous to overwhelm these binding proteins and have a bunch of free vitamin D just floating around?

44:29 [SPEAKER_01]: How does this change how we should interpret a standard vitamin D lab test? [SPEAKER_00]: Yeah, there's a difference, not only in this kind of free bound idea, but also like inactive and active forms of the vitamin. [SPEAKER_00]: So I mentioned, for example, 25 hydroxy vitamin D as a kind of prototypical quote unquote storage form that's not physiologically active.

44:49 [SPEAKER_00]: And our body has a lot of complex regulated ways by which it activates vitamin D to 125 or calcetriol. [SPEAKER_00]: And so there are in fact situations in practice where I might put somebody on calcetriol, straight up on that active form of vitamin D. [SPEAKER_00]: Somebody who might listen to this, they might say, oh, why don't I just skip the, you know, over the counter stuff.

45:09 [SPEAKER_00]: I want to go straight to the active form. [SPEAKER_00]: I want to get the the real deal stuff. [SPEAKER_00]: And it's like, yeah, that's an even faster route to getting toxic because our body is very good at deciding how much do I need to activate, how much do I need bound free, et cetera, things like that.

45:22 [SPEAKER_00]: The reasons why I might use it is if somebody is physiologically unable to activate their vitamin D, like if they have, you know, a complete kidney failure in their dialysis patients and things like that. [SPEAKER_00]: And so trying to override these homeostatic mechanisms is often a foolish endeavor and so that's you're just going to be in a situation where you're at higher risk of toxicity and unintended side effects if you try to override the system, especially in an unmonitored way.

45:48 [SPEAKER_00]: So that would be among many reasons why, and in this context, especially because of as you alluded to how long acting these things are anything that is very, very long acting, there are, you know, even greater concerns about potential toxicity, there are some medicines out there that we use just to deviate a little bit from the vitamin D topic, but medicines that have half lives of a couple months and so somebody develops toxicity, for example, from a drug like amy at a run.

46:14 [SPEAKER_00]: like that's an anti-aurethmic drug that's used in cardiovascular medicine. [SPEAKER_00]: I use it relatively often, but I'm also very, very aware that it's like if I induce toxicity in this, it is going to take months for this to ends up getting out of this patient system. [SPEAKER_00]: There are also to shout out to one of my favorite podcasts, the poison lab in toxicology.

46:31 [SPEAKER_00]: There have been [SPEAKER_00]: toxic exposures and poisonings that have happened with essentially derivatives of like rodent killer type things that are often based in comorant comorant so like blood thinning type medicines and so those are so long acting lasting for months on end that people are having to take like massive doses of vitamin K to out counteracted because they're elevated bleeding risk for months on end and at any given time if they [SPEAKER_00]: were, you know, unable to keep up with that, that they would essentially bleed out to death.

47:02 [SPEAKER_00]: There have been some outbreaks and poisonings reported. [SPEAKER_00]: So long, those are a few examples of how very long acting things have unique risks that can be exceptionally challenging to manage. [SPEAKER_00]: I've heard of and seen cases of severe vitamin D toxicity that as we saw in this case take months, drugs that I use that take months and other poisonings that also take months and months and months to fully resolve.

47:25 [SPEAKER_01]: Yeah, this paper, I mentioned that they hypothesize that when you saturate all of these vitamin D transport proteins, the binding proteins, that you can get some spillover of free vitamin D, and it does tend to be somewhat active, it's unbound, and it can enter these cells like unregulated, so the like the taxis aren't dropping off the vitamin D appropriately, it's just kind of going places, and that potentially triggered this patient's this patient's case.

47:53 [SPEAKER_01]: It is a hypothesis. [SPEAKER_01]: We don't know that exactly yet, but I thought I found that interesting. [SPEAKER_01]: To close this out, I think we should look at the updated clinical practice guidelines from the endocrine society, which marked a significant change in how many approach vitamin D. For many years, many in the fitness and medical communities have operated under the assumption that we should be testing everyone.

48:15 [SPEAKER_01]: and aiming for a specific number for vitamin D levels, usually like 30 nanograms per milliliter. [SPEAKER_01]: These new guidelines move us away from that treat-to-target model and towards a more nuanced evidence-based approach. [SPEAKER_01]: So here's the breakdown of what is now recommended in these clinical practice guidelines.

48:33 [SPEAKER_01]: First, for children and adolescents age 11-18, they do recommend vitamin D supplementation. [SPEAKER_01]: Primarily, to prevent rickets, there's some evidence and also may lower the risk of respiratory tract infections in this population. [SPEAKER_01]: For pregnant individuals, they also recommend supplementation, potentially lowers the risk of preeclampsia, preterm birth, and neonatal mortality.

48:56 [SPEAKER_01]: Third, four adults and with high risk, like pre-diabetes or diabetes, the guidelines suggest supplementation in addition to lifestyle modification to reduce the progression of type 2 diabetes and the trials reviewed the average dose was around 3,500 units internationally units per day. [SPEAKER_01]: And in fourth, for adults age 75 and older, they also recommend supplementation of vitamin D, just due to the potential mortality benefit identified in a number of meta-analysis.

49:26 [SPEAKER_01]: However, for the people that are listening to this podcast, most of them anyway. [SPEAKER_01]: those between the ages of 1974, they suggest against routine supplementation beyond the current dietary reference and takes, which are about 600 to 800 I use per day. [SPEAKER_01]: Perhaps the most significant change and people may be surprised to know this.

49:46 [SPEAKER_01]: They recommend against routine vitamin D testing. [SPEAKER_01]: They suggest the inscraining in a general population, including those with obesity or with the various complexions. [SPEAKER_01]: If they are otherwise healthy and do not have established medical indications like hypocalcemia or malabsorption diseases, [SPEAKER_01]: Importantly, they no longer endorse a universal target of at least 30 nanograms per milliliter for sufficiency.

50:12 [SPEAKER_01]: They've acknowledged that the evidence does not support a single threshold for all people and all conditions and the costs and risks of widespread testing often outweigh the benefits in this population. [SPEAKER_01]: So also in the endocrine society, just flip the script on this 30 nanogram per milliliter target, you know, why did the medical community move away from this target?

50:33 [SPEAKER_01]: Are they moving away from this target? [SPEAKER_01]: Because this is relatively new. [SPEAKER_01]: I think this paper was published in 2024. [SPEAKER_01]: And how would you talk to a patient who is worried because their lab results says 28? [SPEAKER_00]: Yeah, this is a pretty murky area, I would say.

50:46 [SPEAKER_00]: I think that there's been a lot of views around how we set diagnostic cut-offs, how we set lab cut-offs, are we setting something that correlates with over efficiency versus what's enough for a large enough swath of the population's efficiency. [SPEAKER_00]: There's a spectrum of kind of nutrient status.

51:02 [SPEAKER_00]: And then there's also the murkyness of like, how much is our blood vitamin D levels actually a marker of nutrient status? [SPEAKER_00]: They tend to correlate with general health in a lot of ways. [SPEAKER_00]: As people get unhealthier, in general, they tend to go down and as health tends to improve.

51:19 [SPEAKER_00]: They tend to also improve for varying reasons, not just related to, for example, how much you get in your diet. [SPEAKER_00]: There's obviously a lot of other factors that can impact vitamin D levels. [SPEAKER_00]: There's been ideas, for example, that instead of treating to a particular target vitamin D level that we should maybe treat to the level that leads to the most suppression of parathyroid hormone.

51:37 [SPEAKER_00]: That maybe that means that as parathyroid hormone goes up, [SPEAKER_00]: maybe it's going up because you are relatively vitamin D deficient leading to none of calcium in your blood and PTH has to make up the difference. [SPEAKER_00]: That's another hypothesis and it's like I would want to have some sort of prospective cohort or prospective evidence saying that, oh, if I treat people to maximally suppress their PTH, that some real outcome that a patient might care about is better.

52:01 [SPEAKER_00]: Maybe they have [SPEAKER_00]: You know, some better quality of life or longevity or lower osteoporosis fracture risk something like that to hang my hat on short of that. [SPEAKER_00]: It's just biochemical evidence that it's like that could make sense maybe you know and and I don't feel super strongly and almost any direction here like if somebody wants to do that [SPEAKER_00]: Okay, I just don't have a strong sense of confidence that they're going to benefit, but if again, if it's being monitored, then I don't have a great sense that it's going to be harmed.

52:28 [SPEAKER_00]: And so then it comes down to like, what are the costs and who's paying. [SPEAKER_00]: And if they're like, I want to do this, I'm going to pay money. [SPEAKER_00]: I'm going to monitor them like you know, but but as far as generating guidelines for public health and saying we need ensures to pay for all of this and it's like, no, we definitely need stronger evidence to say.

52:44 [SPEAKER_00]: This is going to be worth the time in the effort and the expense to do if we're going to have public payers or third party payers actually addressing this kind of thing. [SPEAKER_00]: For somebody who gets the levels checked in, as you said, 28, for example, and they're very concerned. [SPEAKER_00]: I would elicit those concerns, tell me what you're most worried about.

53:01 [SPEAKER_00]: Also, be curious why it was checked in the first place was that one of those kind of what we call phishing expeditions of I was just curious, so I got it done to see. [SPEAKER_00]: or was there some clear compelling clinical indication? [SPEAKER_00]: And then the last part would be, do they have any other medical conditions, like the ones where you mentioned where there's actually maybe evidence that they should be, for example, do they have multiple sclerosis?

53:19 [SPEAKER_00]: Yeah, that's a situation where no doubt I would actually have them supplementing, because there's actually a little bit better evidence in the context of MS. [SPEAKER_00]: compared with many other conditions. [SPEAKER_00]: If they said, I'm doing it because I just want to get that extra boost on my testosterone.

53:32 [SPEAKER_00]: It's like, well, we got some conversations to have and probably, you know, I bet you probably get better results from just like maybe sleeping in extra 30 minutes a night or something like that instead of doing something like this. [SPEAKER_00]: So really it's eliciting the person's concern seeing if there are strong medical reasons to do it.

53:47 [SPEAKER_00]: And then if not, then kind of a trip trying to work through and adjust those expectations as needed. [SPEAKER_01]: Yep. [SPEAKER_01]: The last part about the new guidelines is that when supplementation is indicated, the guidelines stronger prefer a daily lower dose administration over the intermittent high dose like bolus therapy like those taking 50,000 or even 100,000.

54:08 [SPEAKER_01]: I use once a week or once a month. [SPEAKER_01]: These high doses may actually increase the risk of complications in certain populations, whereas daily dosing tends to mimic the natural physiology more closely. [SPEAKER_01]: So as we close this out, the case of the soldier we discussed today is a reminder of why these guidelines matter and why evidence matters.

54:29 [SPEAKER_01]: More isn't necessarily better. [SPEAKER_01]: Now for most people listening to this, those under the age of 75, [SPEAKER_01]: Probably don't need vitamin D supplement unless there's a specific reason for you to do so. [SPEAKER_01]: Chasing a specific lab number does not tend to improve health outcomes just in and of itself, as always, it's nuanced.

54:49 [SPEAKER_01]: So if you have a specific medical condition like inflammatory bowel disease, if you've had your GI tract sergerized, like metabolic bariatric surgery, yeah, these guidelines don't really apply to you. [SPEAKER_01]: You should follow your doctor's [SPEAKER_01]: Vitamin D's supplementation is probably not going to turn you into an elite level power lifter or a pro bodybuilder.

55:12 [SPEAKER_01]: Austin, any final thoughts on the soldier with the leaky skeleton before we close the books on this case? [SPEAKER_00]: No, that was a super interesting case and I'm glad that we were able to get to a resolution and find a sufficient explanation for the whole thing. [SPEAKER_00]: You mentioned that for lifters, the vitamin D is not super likely to be a total game changer for them.

55:32 [SPEAKER_00]: A slight interesting correlate to that, I guess, is not in the strength training barbell based population, but rather in the endurance and definitely in the ultra endurance world. [SPEAKER_00]: Those folks are at risk for a variety of reasons of what are called bone stress injuries and things like that, especially as we've talked about before in the context of inadequate calorie intake and low energy availability, especially when people get very thin.

55:54 [SPEAKER_00]: And that's actually a situation where I have advice and folks to take some vitamin D. There are some evidence that it can lower the risk of bone stress injuries and things like that coming up in that population. [SPEAKER_00]: I know that that's a tiny sliver if any of our regular listening audience, but that's another situation where it would actually be [SPEAKER_00]: to supplement definitely under monitored situations like you're getting the levels checked over time because that's a common issue in that population.

56:19 [SPEAKER_01]: Yeah. [SPEAKER_01]: And that's usually for people with a relatively high volume of training, super high volume. [SPEAKER_01]: three hours a week of conditioning. [SPEAKER_01]: That does not count as high volume. [SPEAKER_01]: All right, so that's it for this medical mystery episode of the Barton Medicine podcast.

56:34 [SPEAKER_01]: If you enjoyed this format, let us know in the comments or on the forum. [SPEAKER_01]: We've got a lot of new stuff coming your way this year. [SPEAKER_01]: If you want to support what we do, head to Barton Medicine.com, check out our stuff before you go anywhere. [SPEAKER_01]: Please leave us a five star rating and a review.

56:46 [SPEAKER_01]: It'll really help strive traffic to our podcast. [SPEAKER_01]: So we can keep bringing you all the latest nuance and health fitness. [SPEAKER_01]: For everyone at Barbell Medicine, I'm Dr. Jordan Feigenbaum, special shout out to Dr. Austin Brocky for joining us. [SPEAKER_01]: We'll see you on the next episode.