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Most patients on antidepressants are told they can’t take methylene blue, even for brain fog. Steven E. Warren, a physician and longevity medicine clinician, joins Kevin to discuss his KevinMD article “51 cases that reframe methylene blue serotonin syndrome.” You’ll hear why 50 of the 51 published serotonin-syndrome cases involved high-dose IV methylene blue given under anesthesia, mostly during parathyroid surgery, rather than the low oral doses used in outpatient longevity practice. Steven walks through the Goldilocks dosing posture he uses for patients with brain fog, why he screens every patient’s full medication list for interactions before starting, and why he tells every patient there are no randomized trials behind methylene blue. He also describes the broader longevity practice he sees daily: patients stacking peptides from the gym, megadosing vitamin D from podcasts, and ordering supplements off Amazon without quality control. If you’re a clinician fielding methylene blue questions or a patient considering it, listen for the questions Steven thinks should be asked before starting any unstudied supplement.
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Transcript
Kevin Pho: Hi, and welcome to the show. Subscribe at KevinMD.com/podcast. Today, we welcome Steven Warren. He’s a longevity medicine physician. Today’s KevinMD article is “51 cases that reframe methylene blue serotonin syndrome.” Steven, welcome to the show.
Steven E. Warren: Hey, nice to meet you, and nice to be here on the show.
Kevin Pho: All right. First time, so it’s great. So let’s briefly share your story and then tell us why you decided to write this particular article on KevinMD.
Steven E. Warren: Well, the thing is, I’ve been doing medicine for 45 years. I went to medical school at George Washington and got my degree there, and also a doctor of public administration dealing in public health.
And when I got done, I was going to practice, after my four-year residency, practice in Salt Lake, and the senator at the time said, “No, we have, you’re a National Health Service Corps doctor, so we need you to go to a different place.” And so they took me and sent me to a very rural area in Utah. Matter of fact, it was the size of the state of Rhode Island.
I was the only doctor there for nine years. And so I did thousands of deliveries, I did general surgery. I did everything. I didn’t have labs, didn’t have X-rays very often, it was a small little hospital. But the things I saw in this rural community down in Canyonlands area, down below Moab, I learned a lot during that period of time.
Wasn’t happy, but by the time I finished, I never saw my house for 10 years and practicing medicine. Then I came back up to Salt Lake and tried to practice for a large medical group and realized I couldn’t be told what to do after being by myself for 10 years. And so I ended up getting into long-term care and hospice work.
So 25 years, I ran 14 nursing homes, assisted livings, hospice groups, developed some big hospice groups, and did a lot in that particular area. And then along the way, dealt a little bit in some alternative medicine. I did some work in chakra for years and dealt in some other particular areas for a while.
And then the nursing home business, I started having too many patients dying on too many meds, and I said, “I can’t do this anymore. I can’t have people dying on 23 meds.” Every time I’d stop their meds, they’d get out the hospice bed and leave because they were being overdone. So I went back to sort of the roots that I was doing in that rural community, which was listening to patients, which is a rare problem.
Listening to them, what their problem is, try to get to the root cause, and try to solve it without medications as often as I used to, and trying to listen to them. And once I’d listened to them and say, “Oh, let’s do this, let’s try that,” I was getting better success. So over the last 10 years I’ve been doing everything from hormones to peptides to stem cells to PRP. I do a lot of those on my fluoroscopy scope. But it’s getting back to trying to help people feel better every day, increase their longevity, but at the same time have them, as they get older, start feeling better so they can do the same things they did in their 20s and 30s. And so that’s where I’m at right now, is trying to help patients get that youthfulness again, but doing it without tons of medications, but trying to get them to feel a lot better.
Kevin Pho: All right. Tell us about this latest article here.
Steven E. Warren: So what happened is, right after COVID, as you probably know and a lot of your folks listening will know, we had all those people coming in that had brain fog. They couldn’t think, they couldn’t function. Young kids in their 20s and 30s that couldn’t go back to work because they couldn’t focus on their work and what’s going on. And I remembered both in medical school, in the ICUs that I worked in, and when I worked down in this rural community, that I used methylene blue IV to get rid of that brain fog. We used it at that time in the cardiovascular shock units, we used it in the ICUs.
And I said, “Hey, let me give it a try. Nothing else is helping.” So I started doing some IV methylene blue on some of these patients, and lo and behold, within a week they were coming back saying, “My brain fog’s gone.” One or two doses IV, they started feeling better. And I said, “Well, hate to give people IV methylene blue all the time. I need to look at it in a different form.” So I looked out and found some different forms of methylene blue, more orally than not, and started giving them to patients.
And then what happened was patients would come in from either their other primary care doctors or they come in from the pharmacist saying, “Hey, I’m on an SSRI. I’m on this medication, I’m on that medication, and my doctors say that I’ll get serotonin syndrome if I take any of these medications.” And during those 25 years that I was in the nursing home, I did mostly geriatric psychiatry, and if I was going to see serotonin syndrome with people on 20 meds, I would’ve seen it, and I’ve never seen it before.
So I started looking into it. Why is there this, what’s going on? Why in the community there’s such an uproar about methylene blue and SSRIs or any of the MAO inhibitors? I mean, there’s a whole group of those medications. And what’s going on? So I started looking at the literature and, as the article shows, that there’s like 51 cases out there, and 50 of them were patients that were getting high-dose IV methylene blue, mainly for parathyroid surgery, when they were trying to find out where a lesion was.
Sometimes in the gut when I’d do surgery years ago, I’d give them IV methylene blue, and if there was a hole in the gut I’d see the blue coming out of that gut and know where the hole was. So I started looking at it and realized that all those cases were methylene blue that were given while they were under anesthesia with one whopping dose.
So it’d go right in their system, past the liver, and go across the blood-brain barrier, and that’s where we could get some serotonin syndrome. The one article I think that was with the person on oral, it was just a weird case of, they were on a lot of different medications and just started taking methylene blue sort of randomly a little bit at the time, and they had a mild case of methylene blue.
But trying to find any literature on the right dose of methylene blue in helping patients, I found no correlation between the right dose of methylene blue and serotonin syndrome. And so, if you read about methylene blue, there’s all the controversy, like it turns your brain blue, it does X, Y, and Z. But the bottom line is that those are using high doses. When people are using very high doses they’re going to get some of those problems. It’s sort of the Goldilocks principle. At the low dose, the methylene blue doesn’t work. Real high doses causes all the problems. You have to find that sweet spot in between.
And when we get that small dose, like five milligrams, and even take five milligrams two or three times a day, if you are on an SSRI, and especially on a high, high dose of any of those medications. There’s a whole list of them. A lot of people are taking tramadol or a triptan and an SSRI, so they stack it a little bit. But most of the time if they’re taking those medications all through the day, and taking their methylene blue divided, like five milligrams two or three times a day, we’re going to get the benefits of the methylene blue helping the mitochondria feel better, but not get all the serotonin effects.
And so that’s what the article’s about, to try to educate people that there’s more to the story than just, “Hey, can’t take methylene blue if you’re on an SSRI,” because a lot of the times, at least in my experience, once they’re on the methylene blue and we’re fixing them up, they don’t need the SSRI in some cases.
So that’s what I wanted to get out, is to have people look at literature from a different viewpoint. Just don’t take whatever’s said out there and say, “That’s the gospel truth,” and stick with it. But do some research, find out what the real bottom line is.
Kevin Pho: So I looked at some of the literature regarding the potential efficacy of methylene blue when it comes to brain fog, and a lot of the studies are kind of small trials or in vitro. And as far as I know, there are not any randomized controlled trials that show efficacy for methylene blue and brain fog. Is that the reading that you’re getting as well?
Steven E. Warren: I think it’s the same reading. I don’t think, again, since there’s no money in it, and you and I know if there’s not money in a product, nobody does the studies on it. So most of my literature and the blogs we read and the people I talk to, it’s mostly feedback you get from your patients that their brain fog is gone, their memory improves, they feel so much better. And the theory, if you look at the theory and the physiology of it, how it works in the respiratory chain, there’s a lot of merit to it, but no one’s going to spend any money doing a study on it because they can’t patent it and they can’t make a lot of claims on it. No one’s going to spend millions of dollars.
Kevin Pho: In your experience, is it a pretty universal reaction in terms of how people can feel improved symptoms when taking methylene blue? Just from your own patient panel, what’s the success rate you have?
Steven E. Warren: I have to say at least 90 percent or 95 percent. I rarely have anybody. I mean, I take it, because when they come in to get the methylene blue products, it seems to go off the shelf, or when they bring them in, everybody claims that they’re having good experiences. I had a 77-year-old lady that I put on it because she said she’s getting dementia, and felt like she couldn’t remember the names of the dogs in her neighborhood.
She’s a property manager, couldn’t remember the people’s names. And so I put her on a little bit of methylene blue two or three times a day. And she came back three months later and I said, “So how you doing?” She says, “Well, let me tell you about methylene blue.” She said, “Not only can I remember all the dogs’ names, I can remember all 150 clients’ names. I now know every one of their addresses.” And so that’s, I basically get that from a lot of patients.
The older patients call up and say they’re taking their loved ones out of their assisted livings that are in the Alzheimer’s units. I’m getting young people saying they feel better, their brain fog’s gone, they can go function better at work. So I’ve never had any negative experiences. I mean, there’s the blue urine, but we say it’s not a dye in that fact, it’s not permanent. But I just have too many people coming in and saying they’re feeling so much better on it. So to me, if I educate them about if they’re taking other meds, how to take it and how to do the right dose of methylene blue, and I have not had any problems that way.
Kevin Pho: When you talk to patients about potentially starting them on methylene blue, do you say a lot of data is kind of anecdotal? There aren’t any randomized trials? Are you upfront about the lack of data?
Steven E. Warren: Yeah, I do tell them that. I just tell them there’s no data out there, and the same thing I just told you, because no one’s going to spend the money. But it’s been around for, what, 120 years, the methylene blue. And if there was going to be a lot of problems with it, we’d have seen it in the literature. But I tell them, “There’s no trials on it. Give it a try. We’re going to start these low doses of it.” And I go through all their med lists to make sure there’s no hidden things that could be drug-drug interactions with it. And if I don’t see any of that, I warn them about that. And I said, “If you start a new drug from your doctor, let me know so we can see if there’s some drug-drug interaction.” And by just telling people, I said, “Go try it. If it doesn’t work, fine. If it works, great for you.” And that’s what I usually try to relay it to patients, to tell them there’s no real trials on it, but sometimes the trial one works really well.
Kevin Pho: Now, what are the downsides for methylene blue, other than the potential serotonin syndrome? And for those who aren’t familiar with serotonin syndrome, just give us, like, a 20-second synopsis of what exactly that is.
Steven E. Warren: Serotonin syndrome just, like I said, I’ve never seen it, and I should have been seeing it over the years. But mostly the problem with the mental confusion and the blood pressure problems, there’s just a whole slew of different symptoms they’ll get when they get the serotonin syndrome. And sometimes there’s, I had a drug rep the other day came in, and in the state of Wyoming there’s some doctor over there’s diagnosed serotonin syndrome on 20 patients. So he sees some confusion on people and immediately says they have serotonin syndrome. But it’s pretty dramatic with the drops of blood pressure and the confusion and some numbness and a lot of complaints that way, is what I’ve seen when I read about it.
Kevin Pho: Sure. Is it expensive?
Steven E. Warren: Methylene blue? No, they’re cheap. It’s very, very inexpensive and I think a month’s worth, the one I’m using right now is around $30 to $40 a month if they’re taking it at the right dose. So it’s very inexpensive, and I’ve not had anybody complain of any nausea with it. The only side effect I tell people to watch for is they’re going to have blue urine. And also there’s another sort of interesting thing, that if your urine, if you have a really true quality methylene blue, sometimes your urine’s going to be dark blue, sometimes it’s going to be light blue, sometimes it’s going to be clear.
And that’s because it’s dealing with that redox oxidation property in your body. There’s that experiment you did in high school or college when you’d take a bottle of methylene blue, you’d add, like, sugar to it, oxidize it, shake it, and all go clear. And it’s that leuco methylene blue, and then you’d put a drop of something else in it, turn back blue again. If you have constant blue urine, a really dark blue urine every day you’re taking a product with methylene blue in, you’re probably getting a poor methylene blue because it’s not doing its job.
Kevin Pho: Now, methylene blue, as you said, there are not any clinical trials on it, and there are a lot of supplements in the longevity medicine space that also don’t have any randomized controlled trials, right? So there’s kind of a little bit of tension between what we’re doing here and what physicians are taught in medical school in terms of following the evidence and all that. So how do you walk the line, that tension between some of the supplements that you prescribe versus what doctors are taught today in terms of following the evidence?
Steven E. Warren: Well, this is sort of interesting. Like I said, when I went to this rural area, the two doctors that had been there for 40 years left town and left me there. And so the patients would come up and say, “Hey, Doctor So-and-So would give us this medication for this problem.” And I’d say, “No. In medical school I learned that’s not good for you.” And so when you got tired of people pounding on your door since they knew where you lived, and you say, “Well, let me see if there’s any side effects. Well, there’s no side effects, let’s try it,” and they got better. I suddenly realized that not everything in medical school was taught to me, and that I need to do my own research myself, listen to patients, listen to their stories, try it on, and if there’s no real side effects. But basically doing my own research to find out if it’s going to work or not, because I’m finding out that medical school didn’t teach me everything, and that there’s a lot more information out there, and that we’re having to change every day.
I mean, I’m learning something new every day, and that’s what I’m trying to. Some of the things I’m doing now is trying to encourage colleagues to read every day, study a little bit every day, and realize that medicine’s changing all the time, and just don’t think that what you were taught 10, 15 years ago is staying the same. Things are changing, and we need to look at it from our own perspective. Do your own reading. Trial on patients. Tell them that this has not been tried as a big clinical trial, but we’ve had some evidence that it works on other people. And build up your own repertoire of what works and what doesn’t work.
I was shocked on how many things that these old doctors used to do that I was told in medical school wouldn’t work, and suddenly it’s working on patients. And so if I wasn’t getting the side effects, it’s worth trying. But I’m learning that I can learn something new every day, and that not everything I learned in medical school is true. Not necessarily true, that there’s more to the story than what we’re being taught.
Kevin Pho: Now how about going the other way? Have you ever encountered any supplements that you used to prescribe but then realized that it definitively didn’t work or had harmful side effects and you stopped prescribing those supplements?
Steven E. Warren: That’s a good question. I’ll tell you one thing right now that I’m a little frustrated about, and this is the big fad right now in this country, is peptides. I started doing peptides like seven, eight years ago, and I’d use one peptide, then I’d use another peptide, then I’d take breaks in patients. And nowadays you’re having my patients walk in that are getting off the streets or off the internet, they’re taking three or four different peptides at the same time, and they’re just getting all these side effects. And I’m saying, “Stop.” It’s the same thing as taking regular pharmaceutical drugs. You take too many, you’re going to get side effects.
And that’s the problem I’m seeing right now, is that people hear so much on the internet or whatever they’re reading, and they want to try it, and it’s easy access right now on the Amazon to get a lot of things. So they’re walking in with some signs and symptoms, and I go through their supplements, half the time I have to throw them in the garbage because they’re either taking four products that all have the same ingredients in it, or they’re stacking these peptides that shouldn’t even be stacked together because someone, one of their gym buddies told them to do it.
And with that easy access right now, we’re going to run into a lot of problems if we don’t know what we’re talking about and trying to help people realize that they just can’t do that, and to take breaks. Every time I do a certain peptide for two or three months, I’ll take a break for two or three months from the body because you don’t want to change it, you don’t want to overwhelm it. But boy, I’m tired right now of people walking in taking three or four peptides that actually do the same thing, and they’re stacking them and they wonder why they’re having problems.
Kevin Pho: Now, when patients go on TikTok and they hear from a podcast about something that doesn’t have a lot of clinical data behind it, should they be skeptical of it? What kind of questions should they ask physicians like yourself in terms of whether these supplements that haven’t been studied or have a lot of data behind them, what kind of questions should they ask before they consider a trial of it?
Steven E. Warren: Well, I have sort of a, I call it the no bull sort of program where I first say have they done a lot of quality control? Because if they’re going to take a product, I want to tell them to find the COA on it and get whether it’s been done for sterility and the heavy metals in it to make sure it’s a quality product first of all because there’s so much trash out there. And if it’s dirt cheap, I can tell them they got a bad product, because some of the good products cost money.
And then I say to them, “You don’t want to, you need to start slow and go, start at a low dose and go slow up on it if you’re going to do it.” I tell my experience I’ve had with other patients over the years. I’ve had good experience with this supplement. I haven’t with this other one. You shouldn’t take it. And that’s what I do. One of the more common ones I saw in the last few weeks is people taking too much vitamin D. Because they hear you need vitamin D, and so they’re walking in taking 20, 30,000 units of vitamin D a day because they heard it on some podcast because it’s good for you, and suddenly they’re, as you know, vitamin D toxicity is a big problem. It causes heart arrhythmias, causes neurological problems. And since it’s fat soluble, it takes months to get the levels to go down. So, and there’s not an antidote to reverse it.
And so I’m trying to tell people to be skeptical of what they hear. They can come and ask me, and then I try to look it up and see if there’s anything that’s a problem with it. But I really want to make sure it’s good quality before they start putting it in their body. And I said my office is not an experiment for them. They need to make sure things are quality control. If I cost more than somebody else, it’s because I want good quality products, and that they need to check with me on it because there’s so much out there on Amazon now it’s scary. As physicians and providers, we need to be up on it ourselves, need to do reading and understanding everything, and know the products ourselves really well before we can talk about it too. That’s a problem.
Kevin Pho: Now, what do you say about the physician critics who sometimes dismiss longevity medicine, especially if there’s not a lot of clinical data behind what you prescribe? And there’s a profit motive, right? Because a lot of longevity clinicians, they sell what they prescribe as well. So what do you say to those physician critics?
Steven E. Warren: That’s a hard one, because I’m sort of on both sides of the pictures after doing the regular medicine for so many years. I try to tell them there is some merit out there. There’s a lot of good things. Years and years and years ago, people lived for a long period of time, and so I start with the basics of good nutrition and exercise and items like that. And then I tell them, “There’s some good things out there. At least try it.” But you need to tell your patients to watch for side effects and just not believe everything they hear on the internet. But again, a lot of doctors, when they went to medical school, that’s what they were told, and they stick with that when there’s a lot of things they need to open up their minds or we’d be in trouble in our country if we didn’t open up our minds and look at other things.
And so I tell them they at least need to read about it and read some cons, make up their own decision. If they want to try it themselves, try it themselves, but they need to realize there are some good products out there that help people live longer, but mainly feel better during that period of time.
Kevin Pho: We’re talking to Steven Warren. He’s a physician and longevity medicine clinician. Today’s KevinMD article is “51 cases that reframe methylene blue serotonin syndrome.” Steven, let’s end with some take-home messages that you want to leave with the KevinMD audience.
Steven E. Warren: Well, I think just for the people in the audience, I just need them to realize, get a good quality product, read about it, always start really low dose and increase it. And to the physicians and providers out there, for them to do some studying themselves, read about it, understand it, ask questions, and then together we can make some progress in longevity and keeping us feeling better as we age.
Kevin Pho: Steven, thank you so much for sharing your perspective and insight. Thanks again for coming on the show.
Steven E. Warren: Thank you so much. Appreciate it.
