The Antisocial Doctors Podcast
Join Dr. Rebecca Berens & Dr. Sonia Singh as they unpack viral health trends with curiosity, nuance, and compassion. No snark, no shame —just thoughtful conversations about what’s true, what’s hype, why we're drawn to it and how to find calm and clarity in the chaos of social media and online health advice.
The Antisocial Doctors Podcast
Episode 22: Are NAD Supplements Worth Trying?
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In this episode, we dig into the viral buzz around NAD+ and its precursors and ask the big question: are supplements or IV “drips” actually worth it? We share a real patient story that captures why these promises feel so tempting—especially when you’re anxious, exhausted, or desperate to feel better. We also discuss the surprising gap between what’s commonly claimed online and what’s actually been studied, including what we found when we looked closely at the available research and the red flags that stood out. If you’ve been curious about NAD+ for energy, longevity, recovery, or “inflammation,” this is the nuanced, evidence-focused conversation you’ve been looking for.
CORRECTION: In this episode we discussed the 2022 FDA ban on NMN being sold as a dietary supplement because it had been authorized for investigation as a drug. However, in September 2025, after industry petitions and a lawsuit, the FDA reversed this decision and concluded NMN can be marketed as a supplement after all.
00:00 Podcast Mission
01:18 NAD Episode Setup
01:44 Patient Brochure Story
05:35 Natural Versus Safe
07:37 Why NAD Is Trending
11:59 NAD Science Basics
13:54 Where NAD Comes From
15:49 Why NAD Matters
17:43 Human Evidence NR
20:28 Clinical Outcomes Matter
23:15 NR Trial Results
25:15 Long COVID Study
26:05 Switching To NMN
26:08 NMN vs NR Absorption
26:41 NMN Studies Overview
27:24 FDA Pulls NMN
28:12 NMN Results Reality Check
29:39 IV NAD No Evidence
30:16 Wellness Clinic Pilot Study
32:12 Infusion Side Effects
34:48 Flow Rate Red Flags
36:04 Labs Outcomes And Cost
38:47 Why IV Bars Are Risky
41:41 Clinical Takeaways
43:26 Patient Story Lupus Diagnosis
46:26 Wrap Up And Disclaimer
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📖 Read the full episode summary, sources, and resources on our Substack:
👉www.theantisocialdoctors.com
You're listening to The Anti-Social Doctors Podcast, hosted by me, Sonia Singh, a board-certified internal medicine physician with a master's in nutrition and a special interest in health anxiety.
Rebecca Berens MDAnd me, Rebecca Behrens, a board-certified family medicine physician with a special interest in disordered eating.
Sonia Singh MDWe're also millennial women, anxious moms, and curious humans navigating social media. We've seen firsthand how these platforms can be powerful tools for education and connection, but can also make us unwell.
Rebecca Berens MDThis podcast is meant to be the antidote to your doomscrolling, a solve for the anxiety, stress, guilt, shame, and confusion that comes from social media's messaging around health. In each episode, we discuss a health-related topic trending on social media with curiosity, nuance, evidence, humility, and compassion.
Sonia Singh MDThis is not your average debunking podcast. We wanna explore not just what is trending on social media, but why. Why are so many people drawn to this? What is the nugget of truth here? What are the facts? What can we learn from this as patients and doctors? No shame, no blame, no snark.
Rebecca Berens MDWe're so glad you're here.
Sonia Singh MDHi, Rebecca.
Rebecca Berens MDHi, Sonia.
Sonia Singh MDSo we're just gonna jump right in today, 'cause we're short on time, and this topic is honestly much bigger than I thought it was going to be. In my mind, I honestly was like, "Should we combine this with another topic? 'Cause maybe it's not gonna be big enough for a whole episode." And now I'm like, "Oh, no, it definitely needs its own episode." So the topic is NAD+ and its precursors, and whether supplementation or IV therapy with NAD is worth it, So I wanna start with a patient story, and it's funny, I knew I'd been asked about this a lot of times, so I just l- went in my patient messages app and I searched NAD and was like, "What questions have I gotten about this?" And I had seven results I've definitely been asked about this a lot. And the most interesting one, which is the one I decided would be a good one to talk about for this episode, was a patient who joined my practice with a lot of health anxiety, but a very specific flavor of health anxiety, where most of my health anxiety patients have a symptom or a feeling or a sensation in their body, and then immediately start jumping to the worst conclusion or assuming the worst about it. She was very different. She had anxiety mostly around medical stuff and medical interventions and treatments. And so when she had a feeling in her body, her first reaction was, "Oh, I can take care of this. I can fix this. I just have to do the right things, eat the right things, take the right supplements, do the right stuff, and I can fix this." So she was very afraid of,, all pharmaceuticals. She was very afraid of vaccinations. She was very afraid of sometimes even going to a specialist or doing a test, 'cause she was afraid it was going to result in someone telling her to do one of those things. So she was a very unique patient. But I wanted to mention her because I think there are probably a lot of other patients in a similar boat as that. And so she had been floating around, mostly in the alternative medicine world and kinda on her own, trying to solve her problems. And she was feeling fatigued, foggy bloated, had joint pains, had unexplained rashes was generally feeling very bad. And someone had finally talked her into coming to see me, a doctor. And we had kinda started on this journey of sort of sorting things out, but she was still very reluctant to I had seen her once, and I was like, "Okay there's definitely some lifestyle things we can improve, but I also think you need to see a rheumatologist." And she was "Oh, but I don't wanna go to see the rheumatologist, 'cause then they're gonna tell me I have a disease. Then they're gonna tell me I have to take a med, and I don't wanna do that." And so she was in this purgatory of my doctor agrees that something is wrong with me, and I'm inflamed, and I gotta do something about it." So she sent me this screenshot. It was a picture of a brochure at a wellness place that she was at, and it was a, a brochure for NAD+ infusions. And I'm gonna read you exactly what the brochure says. The brochure says, "NAD+ IV therapy, the foundation of youth. Nicotinamide adenine dinucleotide is critical to many body functions. Our NAD+ drip promotes healthier brain function, fights chronic fatigue, increases metabolism and energy, reduces body inflammation, and even potentially slows the aging process. This miracle molecule is mostly- regarded for its anti-aging properties and is considered the closest thing we have to a fountain of youth. So
Rebecca Berens MDanyway- Wow, that is powerful marketing
Sonia Singh MDmethod. She sent it to me, and she was just like, "This sounds like exactly what I need. It looks so promising." And what's so amazing about her message is she sent me that, and the next message was, "I just need something natural that isn't going to kill me." I was like, "Oh, my goodness no." Anything that sounds too good to be true, we have to pause and really scrutinize whether this thing is it. And I could see immediately when she sent me this brochure, why this would feel attractive to her, 'cause it literally checked every box of the things that she was wanting and felt like she could not get. And it was pitched as it just helps your body, make more of this thing that is really important for all these functions, and she perceived it, even though it was, gonna be infused in her through an IV, she perceived it as very natural. So I think that's a really good case example of, how these things are pitched to people and how appealing and attractive they can seem for a multitude of issues. And I can tell you at the end of the episode what ended up playing out with that patient. But I'm curious if you've had similar interactions with people or if... what you've heard about NAD infusions.
Rebecca Berens MDYeah, I feel like that flavor of health anxiety is actually the more common type that I see. And I understand it completely. Yeah. And it, I understand there is a lot of fear around side effects and harms from medical interventions. Medical intervention can be harmful. There's a lot of medical error and medical intervention-related harms that people experience, and so I don't want to downplay that, 'cause that is true. Yeah. Yeah. And I think that's where a lot of this comes from, right? But yeah, it is this sort of fallacy of oh, the natural things are safer, when in reality getting an IV at some random place of, God knows what for unclear reasons, like actually does have potential risks and harms to you. In Texas we just had a case of a woman- Yeah who died in a med spa getting an IV. And that, was in 2023, and it's being prosecuted now. So I think it's very important for us as physicians to be able to have informed conversations with patients about these things and help them understand the true risks and benefits and make a good decision, while also not just blowing them off and be- Yeah 'cause then that's just gonna send them right back into these potentially very harmful situations. So I'm very excited to hear about this 'cause I know very little about NAD+ in general. And I'm excited to hear what you learned.
Sonia Singh MDYeah. Just before we move on, I wanna say that I actually totally agree with you there is over-medicalization that happens, and over-pathologizing, and there is sometimes neglect to mention, like what are the ways that you could potentially improve your disease process or your wellbeing. I, there, th- sometimes that gets left out in medical conversations. So actually that's a big part of the reason I took on this patient. A lot of times when there's that deep distrust of the medical system, I worry whether we're ever gonna be able to build that relationship or whether we're gonna be aligned. But for her, I could see that it was like, it's a beautiful thing that you are so motivated to work so hard and do all the things that you can do, you know, to fix this thing. But we need to accept sometimes when it's not gonna work.
Rebecca Berens MDYeah.
Sonia Singh MDOr like in this case, save you from going down a path that you perceive to be safe and natural, but is really not at all, so anyway, yes, let's talk about... so that brochure summarized a lot of the claims. But- just to hit the highlights, a lot of people believe that, that social media will tell you that NAD+ and the precursors to NAD+ that help boost it are helpful for longevity, for energy, for optimizing your hormones or helping with fatigue, for recovery from the stress of life, the stress of sleep deprivation, the stress of drugs and alcohol or, general detoxification from all the toxins we are exposed to in our daily lives. How do they do that? A lot of people point to its role in repairing DNA, in hopefully slowing biological aging, in boosting your overall metabolic processes and your mitochondrial function. So there's a lot of very broad claims, which is funny 'cause it reminds me of our talk about peptides. It reminds me honestly, a little bit of our creatine conversation from a couple- weeks ago. So it's funny how a lot of these things, people will take some nugget and then, expand it to everything- Yeah that is currently in, people's minds as a concern, and say that it probably helps with that. Anyway, those were the claims around it. So- why is this so viral now? Actually very similar to the creatine conversation, I would say there has been a true evolution of the research on this topic. So NR, which is nicotinamide riboside, I'm just gonna say NR from now on so I don't get these all mixed up. NR was first described in 1944, but it was only in the early 2000s, around 2004, that they really elucidated the full role that it plays as a precursor for NAD and, how that impacts all of the functions of NAD. So most of the data on this is from the last 20 years, and most of the human data is really only from the last five or six years. So there has been more research on this topic. It's not like we just picked up something that's been around forever and decided it's the new hot thing. So I do think part of it is warranted. But the other reasons it's viral are things that we talk about a lot. Increased interest in longevity, increased interest in metabolic health, a lot of concern around inflammation generally, a lot more interest in optimization even for people who are feeling relatively well and don't have any diseases. I haven't seen hard data on this, but I would say there is an increase in fatigue, burnout, brain fog these nonspecific... burnout is, specific, but fatigue and brain fog are a little bit more nonspecific. These nonspecific manifestations of feeling unwell. I think fear around perimenopause has driven a lot of women to be like, "Oh my gosh, what can I do? What else can I do to be more proactive and prevent some of those things from happening to me?" I think increasing fear around exposures and toxins, and desire to do whatever we can to our bodies to counteract all of that. And then lastly, I do think the way this is pitched these products seem like true hacks. It kinda seems like, okay, so maybe the root cause is that you're not sleeping enough, or the root cause is that you're not exercising and you're sedentary. The root cause is that you have a lot of stress. But a lot of people will say I just can't sleep more. I have a newborn. I just can't have less stress. I just have a stressful job, and I just can't, get to the gym because I have an injury or, I don't have the time," or whatever it is. And so I think the way this is pitched, it gives you this impression of you can mitigate all of the bad effects of that stuff that you're doing by taking this and supporting your NAD+ stores, and therefore supporting all your metabolic functions and reducing inflammation, et cetera. Do you have anything to add in terms of why you think- I
Rebecca Berens MDmean, I think that, like the idea of... it's the idea of I wish there was a pill that could fix all my problems, and I know my problems are related to lifestyle, so this is like a thing I can take- Yes whether it's in p- I don't... whether it's in pill form or IV form that will undo the damage that I know I'm doing to myself. And like-
Sonia Singh MDYes I
Rebecca Berens MDthink we, we know logically that's not how that works. But it's, it does feel it feels like it makes sense from what you're describing, right? Yeah. And like- Yeah that marketing on that flyer, I was like, "Yeah, that sounds great. I'll take some of that," yes. But
Sonia Singh MDas I'm sure you're gonna get to- Oh, wait till you learn all about it. This is like- Oh, I'm- I had done some cursory searches on this when people have asked. Like I've said, I've been asked seven times in the last two years, and so I've done a little bit of looking at it. I did not even know the path of it. I realize now i did not know enough. And so now I'm so glad we're having this conversation, and hopefully other doctors will have this come to their ears and they will be able to educate their patients around this topic. So let's go through what the facts are about this with a little bit more context and a little bit more nuance and getting a little bit more in the weeds. So in order to have this conversation, unfortunately we have to talk about a lot of boring science. So get lots of science terms that even I keep having to go back and be like, "Okay, what was the name of this one again? What was it?" But you'll see, like, why it all becomes relevant. So- What is NAD+, first of all? I have seen this lumped in with peptides a lot of times. It is not a peptide, to be clear. So NAD+ is a pyridine nucleotide coenzyme, okay? And it is present in all living cells. It is a critical cofactor in reduction-oxidation reactions, and it is a substrate for a bunch of other important signaling enzymes. And o- the big enzymes that it's helping function in- include ones that are coordinating metabolism, involved in DNA repair, involved in gene expression, and involved in aging processes. So it's made up of two nucleotides, which are nicotinamide mononucleotide, which is NMN, so we wanna remember NMN, and adenosine monophosphate, which is AMP, which if you listened to the creatine episode, AMP, ADP, ATP, it's all part of that. It's all part of that whole pathway. So NAD exists as an oxidized form and as a reduced form. The oxidized form is NAD+, and the reduced form is NADH, and it cycles between those two in order to transfer electrons in different metabolic pathways. So what you need to know here is that NMN is one of the precursors or building blocks for NAD, and that it's involved in a billion different pathways and important processes in the body so it's involved in energy metabolism, ATP production, and then all those enzymes that I talked about for gene expression, stress response, DNA repair, immune function, a million things basically. It's in every cell, so it's doing a lot of different things. Okay, so where does NAD come from? The body generates NAD through a variety of different pathways. So it can be generated actually from tryptophan in the diet, which I thought was really interesting because there's so much mechanistic thinking in like the alternative medicine world. So if you're just like, they would look at something like this and be like, "Okay, so we just need to like supplement tryptophan. Just take a little more tryptophan." Turns out that doesn't work. That's not how it works. But it can be generated from tryptophan. It can also be generated from nicotinic acid, which is a, is one of the forms of B3. Another form of B3 that a lot of people are familiar with is niacin, which has been studied more extensively for various cardiovascular things. So those two things, nicotinic acid and tryptophan, can be acquired from the diet. It can also be made from all the different base products. So you can get it from nicotinamide, which is NAM, nicotinamide riboside, which is NR, and nicotinamide mononucleotide, which again is NMN. So like you can get those things in various forms and then use that to make it. And so this last one where you make it out of those precursors is the main pathway by which you make intracellular NAD+. So NAD can be in the bloodstream, but it also is intracellular. And so if you're trying to raise intracellular levels, the idea is you give the precursors, and the precursors can better get into the cell because they're not big and bulky like NAD. And then inside the cell it creates NAD+ which can then be used for all these processes. So the analogy that you can think of is like- NAD is like a couch that you're trying to take into an apartment with a small door. And it's easier to have the couch in pieces and to then take it into the apartment and then assemble it there so that you have it in the space that you need it.
Rebecca Berens MDI love that image. That's-
Sonia Singh MDOkay. Yeah. So NAD's the big, bulky couch, and NMN and NR are like it in pieces that you can take in and then assemble. So why do we care about NAD+ in humans? What is the clinical relevance? So we know that NAD+ declines with chronic disease, chronic inflammation, obesity and we know that specifically the levels decrease in certain tissues like brain, liver, heart, and muscle in disease states. There's some debate about whether it just decreases as you chronologically age or whether it's that you just have more of those disease processes or you're more likely to have those as you get older. But in most people, these levels are decreasing over time. And so things that seem to be associated with depletion are viral infections, chronic inflammatory states, obesity, metabolic disease. Most of that data, most, is in animal models, okay? Preclinical data on NAD precursors, so that's NR, NMN, NAM, nicotinic acid, the precursor molecules, like supplementation with those in preclinical models shows that it improves glucose and lipid metabolism, it reduces vascular dysfunction, and it protects against ischemic injury in cardiac cells. So when people say preclinical models, they mean not humans. So it means animals, rats, or test tubes. So we're not talking about clinical studies here. This data is all not in human beings. Mostly it is in animals. That being said, in animals, i- it is very promising and very strong. I am not gonna expend a lot of detail reviewing these. And again, if you go and listen to a Biohacker podcast, they're gonna go on and on about the things they saw in mouse brains and mouse livers and- pregnant obese mice. I did that research again. I listened to a podcast on this.
Rebecca Berens MDBless you.
Sonia Singh MDThey will go on and on and talk about that, but hopefully if people have listened to a few episodes of this podcast they have come to the conclusion that we cannot make decisions based on that, and we really wanna see human data, okay? So luckily there is some human data, so that's what I wanna spend more of our time talking about. The most clinical human data that we have is for NR, which is nicotinamide riboside, and NMN, which is nicotinamide mononucleotide, okay? And this is funny because in the wellness world, these are, like, two camps. There's a subreddit for each of these- where people are, like, fighting over what is the best way to supplement or boost your NAD+. Those are the two forms that are most well-studied and that we have the most data for. So there's a really good review article that's called Dietary Supplementation with NAD+ Boosting Compounds in Humans: Current Knowledge and Future Directions. If anyone is interested in this topic or wants to see the data for themselves or is "I just wanna do a deeper dive of this and really understand what the d- the research shows," highly recommend that article. It does a really nice job summarizing all the data we have from human trials and going through the nitty-gritty of what are the trends and what are the strengths and weaknesses of these studies. And it's a really good overview for someone who just wants to know more about this topic. And that will be linked in our in our Substack post. So- Let's talk about NR first. So for NR, they reviewed 12 studies of supplementation, which were at a variety of doses. So the doses ranged from two hundred and fifty milligrams to two thousand milligrams daily. And this is all oral, okay? We're not talking about IV yet, just oral. Most of these were placebo-controlled, but not all. The N, so the number of participants in the study, ranged from eight to forty, so these are all small, okay? But 12 is a decent number, and they're all relatively recent studies. So this was honestly more data than I was expecting there to be and the duration of the studies ranged from one week to twenty weeks. And the studies were mixed in terms of what population they were studying. So some were looking at healthy participants, and some were looking at very specific populations, people with a certain disease or overweight or a certain BMI. So what trends did they see? One of the big take-homes they saw was that treatment with oral supplementation of NR was generally safe and well-tolerated at the doses and durations that these were looking at. So we don't have the long-term safety data, but, for what was studied, it appeared to be very well-tolerated. They had no serious adverse events. The possible side effects that were reported were nausea, diarrhea, rashes, and leg cramps So overall, appears to be a fairly safe supplement. Now the other thing that they saw consistently in the studies was that supplementing with NR did increase blood NAD+ levels. So it appears that giving people this precursor is effective at getting into the body and increasing the circulating NAD+ levels. Now, that does not mean that we increased tissue levels, 'cause that would be a different measurement. That would be a different thing, right? But this is saying that it did increase it in the blood, okay? But that doesn't tell us anything. There's a lot of marketing materials that are just shown to boost NAD levels by 60%. Yeah. And you may say, "Oh my God, wow, yeah, 60% more of this magical nucleotide that I need for all these enzymes." But that's not what we care about. We care about is there a clinical outcome? We're not treating a number on a lab test. We're treating a human, right? We wanna see does this make them feel better? Yeah.
Rebecca Berens MDWas- I think, I feel like that concept in general is really poorly understood by the general population. And it... it's misconstrued also by all these wellness podcasters. It's like the idea of the outcome has to be a clinical outcome that matters to the patient. In the Family Medicine Journal, we have a section that's called POEM, Patient Oriented Evidence that Matters. Okay. And so it's not just does it make your blood pressure go up or down by X number of points? But does that actually result in any sort of- Clinical improvement in your life that you care about? The patient's not sitting there... I guess people now are sitting there measuring their blood pressure regularly. But previously, people were not measuring all this stuff. So it's like, okay, if it decreases your blood pressure by five points, does that actually change anything-
Sonia Singh MDFor you in terms of, like- why do we
Rebecca Berens MDcare about
Sonia Singh MDblood pressure?
Rebecca Berens MDYeah who cares, right? We care because
Sonia Singh MDof cardiovascular events- that might happen to the person,
Rebecca Berens MDright? Yeah. So it's important- we have- to know what is the downstream patient oriented result that matters, not just, like- That we care about the change in the number.
Sonia Singh MDYes. Yes. It's so funny, 'cause we get accused so much of "Oh, you're just getting treated like a number. You're just getting..." And in this case, we're trying to think about, are we just treating a number here? Are we just making the number look nicer, or are we doing something that's actually influencing your health? So anyway, that's a great segue because one study showed a reduction in blood pressure in the NR supplementation group by 2.5 millimeters of mercury, which is small, that's something. I recommend lifestyle diet changes that probably will reduce it five millimeters of mercury, so like it's not totally insignificant. But when they did correction for various confounders it was not statistically significant. And then there was later a larger trial looking specifically at BP that did not see any change with NR supplementation. That being said, there was a 2023 meta-analysis that was looking only at, cardiovascular related studies on NAD precursor supplementation, and they did report that in their meta-analysis they felt that overall it supported supplementation leading to this small, around the same amount, 2.5, 2 to 2.5 millimeters of mercury reduction in blood pressure at high doses. I could not read the full text of that study, so I don't really know why they came to a slightly different conclusion, but suffice to say, the data on blood pressure is mixed, and if there is an effect, it appears to be relatively small and, maybe more at the highest end of the doses. And these studies are very heterogeneous. Meaning we don't really know the ideal dose or the ideal population that would benefit from this based on what we have now. The strongest design study that was included was a randomized double-blind placebo-controlled trial, music to our ears- Wow 40 sedentary men, ages 40 to 70, with BMI over 30, who were put on 1,000 milligrams of NR twice a day for 12 weeks. And they were really convinced that this was going to improve their cardiometabolic outcomes. And what they found was that it did increase NAD breakdown products in the urine, so it appears that they're getting more NAD in the bloodstream at least, and then they're breaking it down and it's appearing in the urine. It did not appear to increase NAD in the skeletal muscle, so in this case, they were actually trying to track whether the levels in the muscle changed, and it did not. And it had no effect on insulin sensitivity, body composition, or any of the other metabolic health parameters that they measured. So this is something where, if you were just looking at the preclinical data, you would be like, "Slam dunk, this is gonna work. These people are gonna have benefit," and here you actually do the study and you set it up well and you put it in a population that, seems like they would have benefit based on what you know from animal studies, and it just doesn't pan out.
Rebecca Berens MDIt seems short though, for those endpoints I'm not surprised that is the result, but I'm also surprised that they only tested it for 12 weeks, 'cause I feel like would you expect a big change in 12 weeks
Sonia Singh MDin someone's mood? Sure, and I think, I think the people who support supplementation would say it's just expensive to do these trials, and so people only have so much budget, and they can only do them for so long. And maybe if we had better-" research funding for this. Yeah So if you could do something bigger and longer and more robust, we would see an effect, yeah. But this, I'm just reviewing what we've got. Yeah there appears to be no significant evidence that it improves exercise capacity. One interesting- And that
Rebecca Berens MDwould be a shorter term-
Sonia Singh MDYes
Rebecca Berens MDprobably result.
Sonia Singh MDYes. There were some small studies with walking, like six-minute walk tests in elderly patients, and there were a few studies that showed some improvement, but then there would be others that were a little stronger that did not show. So overall- Yeah there was not really an obvious trend towards improved exercise capacity. Now, one use case that I feel like I've heard a few times now is using this for long COVID. So I wanted to mention there was a randomized control trial where they did NR 2,000 milligrams dose, relatively high dose for long COVID patients. It was in 58 patients, so this was not included in this review that I mentioned. But they found that it, again, it raised NAD levels two to threefold, but did not produce any significant between group differences in fatigue severity. So again, there's this theoretical basis that COVID, because it's it causes this inflammatory state, depletes your NAD stores, and therefore, if we perhaps give these people back some NAD precursor and have them increase their NAD stores, that perhaps it would mitigate some of the long COVID effects. But again, it does not seem to pan out when you do the study.
Rebecca Berens MDYeah.
Sonia Singh MDSo that is a high level overview of the data for NR. So now let's talk about NMN. This is in the weeds, but it appears that NMN, when you give it to humans gets converted to NR by the gut microbiome, and then NR is what actually goes in and gets absorbed, and then your own cells use that as a precursor to make NAD. So it seems like kind of the common pathway is still NR, like everything's becoming NR. So I think recently there's been more of a leaning towards using NR because it seems to be the more direct way to get absorbed and get into cells and be used. But anyway, there's data on NMN too. So there were 13 studies that they reviewed, and interestingly, all of them were published 2021 to 2023. So these are all recent data. The size of the studies range from 17 participants to 108. The doses they used were like 250 milligrams to 1,250 milligrams, similar to the other one. Different patient populations. Some were healthy, some had diseases. The duration ranged from two weeks to 24 weeks, so 24 weeks was the longest one in the- in this category. And they did note that NMN used to be harder and more expensive to manufacture in a form that was bioavailable to humans, and only recently has that become not the case. And so that's part of the reason why there's been kind of this boom in studies of these precursors. Of note is, these studies all came out in the early 2020s, and then in 2022, the FDA actually announced that NMN can no longer be sold as a dietary supplement in the United States due to its authorization as an investigational new drug. So this is a really important thing to think about because Part of the definition of a supplement is that it's not being used to treat or prevent any specific disease, right? When there starts to be any indication that it is one of those things, then it actually moves into the drug category, so that should make you think about how you're thinking about supplements versus drugs in general, and what, they're useful for. So right now NMN is not as widely available, so I think that's another reason that NR has become more popular. So what trends did they see in that NMN data? Again, they saw that treatment was generally safe and well-tolerated, and I wanna make the caveat here that these studies means they didn't have any serious adverse effects, but you still have to take into account if you're going to take a supplement version of any of these, the r- the inherent risks of any kind of supplement, which is, risks of impurities or contamination or potency not being what it says on the bottle and, all of the things that come with decreased regulation of those products. But anyway, in the studies it was safe and well-tolerated. They did again see NAD levels increase in the circulation, and overall there was a few studies that showed some cardiometabolic benefit, but the majority showed no change in cardiometabolic health or physical function. So a few positive studies, a lot of null negative studies that didn't really show anything. That is the general overview on NAD and NMN. I did have... I remember having a patient ask me about NAD+ supplementation, and I think they may have even sent me a link. I can't recall now, but I remember at one point looking at a small trial in healthy adults that showed that it helped with fatigue, and I was "All right. Whatever. S- seems safe and well-tolerated. If you really wanna try it, you can try it. I don't have a huge problem with that." But now stepping back and looking at the whole of the data, which honestly seems like it's even evolved compared to four years ago- Yeah it doesn't really seem like there's a lot there to support its use at the moment, but it does appear to be safe and well-tolerated, so I will say that. Now, the biggest point I wanted to drive home in this episode is that IV NAD+ infusions have essentially no clinical data, okay? There is no evidence of safety and tolerability when given via an IV, and there is definitely no evidence that it is superior over taking something orally. This is a surprising amount of research on something like this. And- Yeah it's comforting to me that this has been studied as much as it has, and that I feel fairly confident that it's not gonna harm anybody if taken orally. That is not the case at all for IV, okay? The only study, the only published study I could find- On IV NAD or NAD precursor infusion was a study that I'm gonna put in quotes That was done at a commercial healthcare facility. So it's basically a wellness clinic in Austin, and they did a retrospective review of their EMR and compared patients that had gotten their IV NAD+ infusion to patients that had gotten their IV NR infusion. Okay? So I wanna tell you about this study 'cause it's... And again, if you're interested in this topic- Study
Rebecca Berens MDseems like a stretch, but-
Sonia Singh MDOkay. It's propaganda, okay? But- It's propaganda, but it's not good propaganda 'cause if you read it you're like, "Oh my God, this is terrible," so anyway, if you're at all interested in this topic, you have to go read this study, okay? And basically they had six patients who received their IV NAD+ loading dose, okay? And their loading dose is a daily infusion every day for four days, based on nothing. I, there's no evidence- I was
Rebecca Berens MDgonna say, like, why? Why is that
Sonia Singh MDa loading dose? There's no evidence in anything that I read that there needs to be a loading period, and that it needs to be four days, and it needs to be IV. Someone just made that up, okay? And then they had six patients who received the NR daily infusions, also as loading, which was four daily infusions of the IV. Okay. And then they had these people do blood tests before and after, and then they were making note of their adverse experiences, and the side effects, and things like that. Of note, there was no placebo group. There was no control group. There was no randomization. There was no blinding. There was no pre-specified endpoints. There was no hypothesis. They were just like, "We're gonna- It's like, we're just gonna study what hap- we're just gonna document what hap-" Yeah. "We're just gonna review what happened." So let me just read this to you so you know that I'm not even, exaggerating any of this. Okay, so all clients, the six people in the NAD group, reported moderate to severe abdominal cramping, diarrhea, nausea, vomiting, increased heart rate, pain in throat, congestion, and chest pressure during infusion. All six people who got this.
Rebecca Berens MDI'm fascinated that they came back after day one to do this again. Four more three
Sonia Singh MDmore times. I would love to know what kind of counseling is done before these people get this, because even in the podcast I listened to, they were like, "Yeah, it feels really bad to get these infusions." And so I was like, this seems to be, a known thing. They're just like, "Yeah it's bad. It feels bad." Anyway, so all six of them had this effect. Okay. These adverse experiences ceased immediately upon infusion completion. Thank you. Thank God. Yeah. Some, but not all, clients, N of five, so five out of the six, in the NR group experienced minor tongue, jaw, and arm tingling, and minor cramping during the infusion. Okay, so even in the NR group, which I think they're trying to say that is superior, is what kind of maybe the point of this whole thing. Five out of the six had tongue, jaw, arm tingling and minor cramping, okay? Which is not nothing. That is something, and then it said-
Rebecca Berens MDwhy is that happening? Like- that's a bad sign. Your body's giving you a-
Sonia Singh MDOkay, so I- a negative
Rebecca Berens MDfeedback. They, I,
Sonia Singh MDI don't know that they go deeply into this in this quote study, but on the podcast I listened to, he suggested that when you're injecting some of this IV, there's just a little bit of immune response that happens to this... I don't know. I... This is all speculative, 'cause I don't have a good source for this. Again, this is not a studied thing, so I don't-
Rebecca Berens MDYeah
Sonia Singh MDI don't
Rebecca Berens MDknow why- But, that, but that's the thing. To me, I'm like, if you're having that sort of reaction, your body is like, "I don't like this."
Sonia Singh MDYes
Rebecca Berens MDthis seems like potential for more serious side effects. We only have what, less than 20 people that we're talking about here. If we were to- Yes do this in hundreds of people what kind of other side effects could we expect that might be more serious? 'Cause this is, clearly it's doing something that your body does not like.
Sonia Singh MDYes.
Rebecca Berens MDYeah.
Sonia Singh MDOkay, so s- they also say, "Similar adverse experiences have been reported during NAD and NR infusion studies currently in preprint that were not unique to this administration." So that's basically their way of saying, "Yeah, we know this stuff happens with these infusions," and this not published study says that these things can happen with these infusions. They seem to be normalizing "Oh yeah, this is all just par for the course." Okay So they also were comparing infusion time. So when I later Googled this to see what places who sell this even pitch as the benefit of putting this in an IV and having it, is they were arguing that the NR infusion is better tolerated, and so it can be infused faster, so it's more efficient for you. And so they said, "Each client was allowed to control their own flow rate as tolerated." I have never heard of this being a thing. It is... Like, when you go to a hospital and you get an IV, you never can just be like, "Turn it up to 40cc." You can't control the rate. There is a pre-specified rate that is determined by, a professional, and that's what's used. So this
Rebecca Berens MDis used- 'Cause it's like there's boluses and then there's maintenance fluids, right? Yes. And sometimes it's not safe to bolus certain patients- so we don't let people just- Yeah ad lib. Exactly. Exactly. Control their flow rate. 'Cause it has to be determined appropriately based on their risk factors and health status. Yes.
Sonia Singh MDOkay. So the NAD group had an average IV infusion time of 96 minutes. So people are sitting there for an hour and a half. That's the average probably some at least two hours getting this infusion and having all of those adverse effects. Okay. And the NR group average time was 37 minutes. So They really cranked it up. They went very fast. And so 60% lower time than NAD. Now let's look at their outcomes in terms of their labs. No significant changes were observed in ALT, AST, hsCRP, BUN, creatinine, TSH. Alk Phos was significantly decreased in the NAD+ IV group but was still within the normal range. And the NR IV group had a significant reduction in their A1C, which was only 30 days later, which is pretty bizarre. And the NAD+ group had a significant reduction in their HDL, which is your good cholesterol, which you actually want to be high. That's not really a good outcome. But again, this was just checked 30 days later. Their LDLs did not change over the 30-day period. Also-
Rebecca Berens MDAlso this is such a small group of people. Were most of the people in one group on a medicine or doing something else that may have affected their-
Sonia Singh MDRebecca
Rebecca Berens MDDNA? Do
Sonia Singh MDyou think they determined that?
Rebecca Berens MDOh, of course not. But I'm just like, I c- it just, this just baffles me. Where was this published? group- I'm, I would love to know where this study was published because I'm like- I will tell you why did you publish this study?
Sonia Singh MDI will tell you where it was published. I'll tell you. It was published in Frontiers of Aging in February of 2026, hot off the presses.
Rebecca Berens MDSounds like a high quality-
Sonia Singh MDYes. It's described as a retrospective tolerability pilot study in a real world setting. So anyway, I don't know how they feel that this proves tolerability, 'cause to me it, it's, they're both intolerable. Sounds not tolerable. They both appear to be intolerable, okay?
Rebecca Berens MDAlso, tolerability is a, a thing you determine before you let it loose- Start
Sonia Singh MDgiving it to people on the
Rebecca Berens MDgeneral population. That's...
Sonia Singh MDOr have them pay you $1,000. Yeah. Okay. So yes, we have not talked about in the harms, we have to talk about the cost, right? Oral supplementation of these NAD precursors is could be 30 or $40, or maybe $150 for a fancy one for the month. The infusions, can be 300, 1,000, 1,000 plus depending on what other mix-ins you're putting in your mix- mix-ins is Cold Stone Creamery. I'm like- I was
Rebecca Berens MDgonna say. Marvel Lab.
Sonia Singh MDYeah. So yeah. These people in this commercial setting likely paid over $1,000 more than that 'cause this was four days of infusions. So I think before I had this vague idea of okay, NAD probably safe, as an oral supplement, and then my general approach to, like- Would I inject this IV is is there any benefit to injecting it as an IV? If not, do not do that because you're taking- Yeah on other risks like, infection, bleeding. Yeah. Various risks of breaking the skin and injecting something directly into your veins. But now that I have seen this, I'm like, truly there is no reason to do it, and it looks potentially quite harmful and, unpleasant and- Yeah expensive. And now to me, I am gonna be on the lookout if I ever see IV NAD+ or IV NR on anyone's list of services, that is an automatic big red flag that this person is maybe prioritizing profit over what is evidence-based and what is best for the patient. Because th- I cannot find any justification for-
Rebecca Berens MDBut I think we can- IVs we can probably say that of an IV bar in general. IVs in general, patients ask me about them a lot, and I always t- if you need IV fluids, it's because you can't tolerate fluids orally or there's some reason that you need to be rehydrated quickly, and we can't wait for oral or you're not tolerating oral, right? That's the indication that we use in regular medical settings to do something IV. 'Cause as you said, there are risks to- Yeah injection of anything in your vein. Breaking the skin has risks. You can have infection. You can have bruising. You can have pain. You can, blow the vein and have a bunch of swelling and phlebitis, which is inflammation of the vein. You can have thrombophlebitis, which is a clot associated with the inflammation in the vein. There's bad things that can happen. And the more times you get an IV, especially if it's an unnecessary one, it becomes then more difficult maybe to obtain proper IV access when you actually need it in an emergency 'cause the vein's been damaged so many times. Patients who are frequently in and out of the hospital or getting, chemo or whatever, they really struggle to get their blood drawn because their veins get so, blown from the repeated things. So the idea that you would do that recreationally To potentially then risk yourself in an emergency, it just... I just don't understand the people that do that and feel that it's like a safe and risk-free thing. And okay, if you're like hungover and dehydrated and you go get an IV, yeah, you're gonna feel better. But starting all the mix-ins, like you said, the mix-ins, yeah. That's the case that we had in Texas. That was what happened. The person who administered it was putting stuff in there that did not belong in there, had no idea what they were doing, and pushed it, and this person died in the med spa. Yeah. And that's the thing, once you start getting mix-ins, also, how do these things interact with each other? There's already known symptoms, so if you're having a negative response and they're like, "Oh, it's just that NAD flu," or whatever, then you get, you don't get appropriate attention until you're really ill. It's very dangerous. I feel like the, the IV bar in general for me is a huge red flag, but yeah, definitely the NAD+ is a particular red flag for me now.
Sonia Singh MDAnd the scary thing about it is because NAD is touted for so many different benefits, what I hear from patients is they'll be like, "I was hungover. They suggested NAD. I had a viral thing. They suggested NAD." I, no matter what- you go for, this can easily be applied to you and so- and somebody can say "Yeah, I think- Yeah this would help," and that is terrifying. That is truly terrifying to me. So anyway, what can we learn from this as doctors and humans? I honestly, I just got so hung up on this last part. I did not prep this part of the episode, so I don't know. What do you take home from this, Rebecca?
Rebecca Berens MDI think I'm interested actually to see that there is potential investigation of using like, what is it? The N- NMN is the one that has actually been pulled from supplements- Yeah because they're actually investigating it as a drug. Like that's interesting, right? Yeah. And so I think the point of this is not like these things are useless and there's no point. They might have a purpose, but let's- Yeah study it properly and find out the appropriate dose and route of administration and what it has benefits for, what it doesn't have benefits for before blanket recommending it. But yeah, I think the takeaway for me with the IV is like this is definitely not something I would want in an IV. It sounds very unpleasant and very unsafe on top of just the general safety concerns with recreational IV-
Sonia Singh MDI agree. I think, the, the strong pre- cl- preclinical data and the data for safety and tolerability make me feel like, okay, for somebody who f- like I really wanted to mention the long COVID study, 'cause I do feel- Yeah that's a case where we don't have good treatments for those people. Yeah. Or for people who are struggling with chronic pain or fibromyalgia or things that we- Yeah we've really exhausted all the evidence-based options, and they're looking for what else is there?" I would put this in the bucket orally as something that's like, okay, if you really wanna try it, okay. We'll- Yeah we'll monitor you and keep an eye on things and, give it a shot. But again, the question we always need to ask ourselves is in whom and for what reason, and what is the strength of the evidence for that? And so that conversation, I think, needs to be had before, we kinda make these blanket like, "Oh, it's the fountain of youth. It's great for everything," "everyone who's tired can take this." So I think that's definitely one of the take-home points. I kinda went over the way I would talk to a patient about this. But I wanted to go back to the patient that I mentioned at the top- Yes, please really quick and give you the update on her. So- after she messaged me about the NAD, I was like, "Hey, look let's revisit this. If you're still feeling bad and you're feeling really desperate for anything that will make you feel better, and you're r- reluctant to go to this rheumatologist please just come back and we'll talk about other things." And when we met she clearly was not drinking enough water. She had tiny kids and was not getting enough sleep. She was struggling to eat meals consistently. There were multiple things that, were potential areas of opportunity for her to improve. But I also could see that in her context of her life it was really hard to do those things, which is why I think it made this, this IV so tempting, because- Yeah she was just like, "I want to do those things, but it's really hard," and, she came to me saying "I just feel inflamed," and her labs also supported that she was inflamed. And so she ultimately did, after quite a while, go to the rheumatologist, and she had a diagnosis of lupus, and she'd probably- Oh my gosh been living with it for a really long time, and trying to sort of lifestyle and natural treatment her way out of it. And ultimately she needed somebody who was going to listen and to talk to her about, the real complications and what lifestyle interventions may or may not have been helpful, and what treatments medically, may or may not have been helpful. So e- I think she presents a great example of someone who on the outside would look like a great patient, 'cause they want to do you know, they want to do- Yeah everything. They're like, "I will do the work," "I will do it," but then when you actually look at the big picture and look at the realities of their life and the reality of their disease process that sometimes the solution is not what they would want, and that's what makes all of these other wellness products and interventions feel so tempting, and, compared to something like Plaquenil, like- the IV NAD is not safer, you
Rebecca Berens MDknow?
Sonia Singh MDNo. It really is not.
Rebecca Berens MDAnd especially, lupus, you have to treat your lupus. Lupus is a serious one, yeah. And that's- Yeah I think that's the other thing that frustrates me so much about the these fountain of youth or fix-all supplements and stuff, is people really are going to this instead of getting a proper diagnosis. And that's an example of some- that's a s- that's a serious diagnosis that ha- can have- Yeah really serious complications if it's not treated properly, right? And that's not to say that lifestyle shouldn't play a role in managing that condition, but- Yeah it's not a lifestyle alone condition,
Sonia Singh MDRight
Rebecca Berens MDto ever see,
Sonia Singh MDand It's an example where even if she had just done oral NAD precursors, and maybe she even was like, "Oh, I feel better when I'm taking these" that would still have been overall a bad thing for her. Yeah. Because it would've potentially delayed her getting an actual diagnosis- and getting treatment that's going to ultimately save her kidneys and her eyes and other- Yes parts of her body that, or joints that are, at risk. Yeah, I just think that, again, that's a theme with a lot of these wellness interventions or things that are pitched as more natural or less harmful or less side effects than pharmaceuticals is it really can delay or mask in just the same way as, taking a painkiller or something would delay or mask your diagnosis or your treatment. So anyway this is definitely one where I think if you're at all interested in this topic or you're kinda like, I think I kinda wanna try it," i- if you're a data nerd or a science nerd or if you're a fellow physician and you're like, "I wanna know more about this," this is one where I really think going to the primary literature and looking at some of the studies is very enlightening. We will have all of that on our Substack. So you can go to theantisocialdoctors.com. You'll see summary posts about each of the episodes there as well as our antidote, which is affirmations for patients and scripting that fellow clinicians can use when talking to patients on these topics and of course the list of references with links to all of the articles that we used in this episode. So that brings us to the end of the show. Thanks, Rebecca.
Rebecca Berens MDYeah. Thanks, Sonia.
Sonia Singh MDHey guys. Last but not least, we have a very important disclaimer. This podcast is intended for educational and entertainment purposes only. The content shared on this podcast, including but not limited to opinions, research, discussions, case examples, and commentary is not medical advice and should not be considered a substitute for professional medical evaluation, diagnosis, or treatment. Listening to this podcast does not establish a physician-patient relationship between you and the hosts. We are doctors, but not your doctors. Any medical topics discussed are presented for general informational purposes and may not apply to your individual circumstances. Always seek the advice of your own qualified healthcare professional regarding any questions you have about your health, medical conditions, or treatment options. Never disregard or delay medical advice because of something you've heard on this podcast. While the hosts are licensed physicians, the views and opinions expressed are our own and do not represent those of our employers, institutions, organizations, or professional societies with which we are affiliated. Although we do our best to stay up to date, please note that this podcast includes discussion of emerging research, evolving medical concepts, and differing professional opinions. Medicine is not static, and information may change over time. We, the hosts, make no guarantees about the accuracy, completeness, or applicability of this content, and we disclaim any liability for actions taken or not taken based on the information provided in this podcast. By listening to the Anti-Social Doctors podcast, you have agreed to these terms. Thanks again for joining us.