Latest / The Antisocial Doctors Podcast / Episode 22: Are NAD Supplements Worth Trying?

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Episode 22: Are NAD Supplements Worth Trying? · The Antisocial Doctors Podcast

• 1:27
  Sonia Singh MD: 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.
• 1:38
  Rebecca Berens MD: And me, Rebecca Behrens, a board-certified family medicine physician with a special interest in disordered eating.
• 1:43
  Sonia Singh MD: We're also millennial women, anxious moms, and curious humans navigating social media.
• 1:48
  Sonia Singh MD: We've seen firsthand how these platforms can be powerful tools for education and connection, but can also make us unwell.
• 1:56
  Rebecca Berens MD: This 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.
• 2:05
  Rebecca Berens MD: In each episode, we discuss a health-related topic trending on social media with curiosity, nuance, evidence, humility, and compassion.
• 2:12
  Sonia Singh MD: This is not your average debunking podcast.
• 2:15
  Sonia Singh MD: We wanna explore not just what is trending on social media, but why.
• 2:18
  Sonia Singh MD: Why are so many people drawn to this?
• 2:20
  Sonia Singh MD: What is the nugget of truth here?
• 2:21
  Sonia Singh MD: What are the facts?
• 2:23
  Sonia Singh MD: What can we learn from this as patients and doctors?
• 2:25
  Sonia Singh MD: No shame, no blame, no snark.
• 2:27
  Rebecca Berens MD: We're so glad you're here.
• 2:43
  Sonia Singh MD: Hi, Rebecca.
• 2:44
  Rebecca Berens MD: Hi, Sonia.
• 2:46
  Sonia Singh MD: So 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.
• 2:53
  Sonia Singh MD: In my mind, I honestly was like,"Should we combine this with another topic?
• 2:56
  Sonia Singh MD: '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.
• 3:27
  Sonia Singh MD: 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.
• 3:50
  Sonia Singh MD: She was very different.
• 3:51
  Sonia Singh MD: She had anxiety mostly around medical stuff and medical interventions and treatments.
• 3:57
  Sonia Singh MD: And so when she had a feeling in her body, her first reaction was,"Oh, I can take care of this.
• 4:01
  Sonia Singh MD: I can fix this.
• 4:02
  Sonia Singh MD: 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.
• 4:13
  Sonia Singh MD: She was very afraid of vaccinations.
• 4:15
  Sonia Singh MD: 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.
• 4:23
  Sonia Singh MD: So she was a very unique patient.
• 4:26
  Sonia Singh MD: But I wanted to mention her because I think there are probably a lot of other patients in a similar boat as that.
• 4:32
  Sonia Singh MD: And so she had been floating around, mostly in the alternative medicine world and kinda on her own, trying to solve her problems.
• 4:39
  Sonia Singh MD: And she was feeling fatigued, foggy bloated, had joint pains, had unexplained rashes was generally feeling very bad.
• 4:48
  Sonia Singh MD: And someone had finally talked her into coming to see me, a doctor.
• 4:52
  Sonia Singh MD: 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.
• 5:09
  Sonia Singh MD: 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.
• 5:19
  Sonia Singh MD: It was a picture of a brochure at a wellness place that she was at, and it was a, a brochure for NAD+ infusions.
• 5:26
  Sonia Singh MD: And I'm gonna read you exactly what the brochure says.
• 5:28
  Sonia Singh MD: The brochure says,"NAD+ IV therapy, the foundation of youth.
• 5:33
  Sonia Singh MD: Nicotinamide adenine dinucleotide is critical to many body functions.
• 5:37
  Sonia Singh MD: Our NAD+ drip promotes healthier brain function, fights chronic fatigue, increases metabolism and energy, reduces body inflammation, and even potentially slows the aging process.
• 5:47
  Sonia Singh MD: This miracle molecule is mostly- regarded for its anti-aging properties and is considered the closest thing we have to a fountain of youth.
• 5:55
  Sonia Singh MD: So
• 5:56
  Rebecca Berens MD: anyway- Wow, that is powerful marketing
• 5:58
  Sonia Singh MD: method.
• 5:58
  Sonia Singh MD: She sent it to me, and she was just like,"This sounds like exactly what I need.
• 6:03
  Sonia Singh MD: 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.
• 6:20
  Sonia Singh MD: 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.
• 6:30
  Sonia Singh MD: 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.
• 6:42
  Sonia Singh MD: 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.
• 6:53
  Sonia Singh MD: And I can tell you at the end of the episode what ended up playing out with that patient.
• 6:56
  Sonia Singh MD: But I'm curious if you've had similar interactions with people or if...
• 7:00
  Sonia Singh MD: what you've heard about NAD infusions.
• 7:02
  Rebecca Berens MD: Yeah, I feel like that flavor of health anxiety is actually the more common type that I see.
• 7:07
  Rebecca Berens MD: And I understand it completely.
• 7:09
  Rebecca Berens MD: Yeah.
• 7:09
  Rebecca Berens MD: And it, I understand there is a lot of fear around side effects and harms from medical interventions.
• 7:16
  Rebecca Berens MD: Medical intervention can be harmful.
• 7:18
  Rebecca Berens MD: 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.
• 7:26
  Rebecca Berens MD: Yeah.
• 7:26
  Rebecca Berens MD: Yeah.
• 7:26
  Rebecca Berens MD: And I think that's where a lot of this comes from, right?
• 7:28
  Rebecca Berens MD: 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.
• 7:41
  Rebecca Berens MD: In Texas we just had a case of a woman- Yeah who died in a med spa getting an IV.
• 7:46
  Rebecca Berens MD: And that, was in 2023, and it's being prosecuted now.
• 7:49
  Rebecca Berens MD: 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.
• 8:07
  Rebecca Berens MD: So I'm very excited to hear about this'cause I know very little about NAD+ in general.
• 8:12
  Rebecca Berens MD: And I'm excited to hear what you learned.
• 8:14
  Sonia Singh MD: Yeah.
• 8:15
  Sonia Singh MD: 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.
• 8:29
  Sonia Singh MD: I, there, th- sometimes that gets left out in medical conversations.
• 8:32
  Sonia Singh MD: So actually that's a big part of the reason I took on this patient.
• 8:34
  Sonia Singh MD: 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.
• 8:42
  Sonia Singh MD: 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.
• 8:51
  Sonia Singh MD: But we need to accept sometimes when it's not gonna work.
• 8:54
  Rebecca Berens MD: Yeah.
• 8:54
  Sonia Singh MD: Or 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...
• 9:02
  Sonia Singh MD: so that brochure summarized a lot of the claims.
• 9:05
  Sonia Singh MD: 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.
• 9:32
  Sonia Singh MD: How do they do that?
• 9:33
  Sonia Singh MD: 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.
• 9:45
  Sonia Singh MD: So there's a lot of very broad claims, which is funny'cause it reminds me of our talk about peptides.
• 9:51
  Sonia Singh MD: It reminds me honestly, a little bit of our creatine conversation from a couple- weeks ago.
• 9:55
  Sonia Singh MD: 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.
• 10:07
  Sonia Singh MD: Anyway, those were the claims around it.
• 10:09
  Sonia Singh MD: So- why is this so viral now?
• 10:12
  Sonia Singh MD: Actually very similar to the creatine conversation, I would say there has been a true evolution of the research on this topic.
• 10:18
  Sonia Singh MD: So NR, which is nicotinamide riboside, I'm just gonna say NR from now on so I don't get these all mixed up.
• 10:25
  Sonia Singh MD: 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.
• 10:39
  Sonia Singh MD: 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.
• 10:46
  Sonia Singh MD: So there has been more research on this topic.
• 10:49
  Sonia Singh MD: It's not like we just picked up something that's been around forever and decided it's the new hot thing.
• 10:53
  Sonia Singh MD: So I do think part of it is warranted.
• 10:56
  Sonia Singh MD: But the other reasons it's viral are things that we talk about a lot.
• 10:59
  Sonia Singh MD: 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.
• 11:11
  Sonia Singh MD: I haven't seen hard data on this, but I would say there is an increase in fatigue, burnout, brain fog these nonspecific...
• 11:19
  Sonia Singh MD: burnout is, specific, but fatigue and brain fog are a little bit more nonspecific.
• 11:22
  Sonia Singh MD: These nonspecific manifestations of feeling unwell.
• 11:25
  Sonia Singh MD: I think fear around perimenopause has driven a lot of women to be like,"Oh my gosh, what can I do?
• 11:29
  Sonia Singh MD: 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.
• 11:43
  Sonia Singh MD: And then lastly, I do think the way this is pitched these products seem like true hacks.
• 11:50
  Sonia Singh MD: 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.
• 11:57
  Sonia Singh MD: The root cause is that you have a lot of stress.
• 11:59
  Sonia Singh MD: But a lot of people will say I just can't sleep more.
• 12:02
  Sonia Singh MD: I have a newborn.
• 12:02
  Sonia Singh MD: I just can't have less stress.
• 12:04
  Sonia Singh MD: 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.
• 12:10
  Sonia Singh MD: 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.
• 12:28
  Sonia Singh MD: Do you have anything to add in terms of why you think- I
• 12:30
  Rebecca Berens MD: mean, I think that, like the idea of...
• 12:35
  Rebecca Berens MD: 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...
• 12:45
  Rebecca Berens MD: whether it's in pill form or IV form that will undo the damage that I know I'm doing to myself.
• 12:49
  Rebecca Berens MD: And like-
• 12:49
  Sonia Singh MD: Yes I
• 12:50
  Rebecca Berens MD: think we, we know logically that's not how that works.
• 12:54
  Rebecca Berens MD: But it's, it does feel it feels like it makes sense from what you're describing, right?
• 13:00
  Rebecca Berens MD: Yeah.
• 13:00
  Rebecca Berens MD: And like- Yeah that marketing on that flyer, I was like,"Yeah, that sounds great.
• 13:03
  Rebecca Berens MD: I'll take some of that," yes.
• 13:04
  Rebecca Berens MD: But
• 13:04
  Sonia Singh MD: as I'm sure you're gonna get to- Oh, wait till you learn all about it.
• 13:06
  Sonia Singh MD: This is like- Oh, I'm- I had done some cursory searches on this when people have asked.
• 13:10
  Sonia Singh MD: 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.
• 13:15
  Sonia Singh MD: I did not even know the path of it.
• 13:17
  Sonia Singh MD: I realize now i did not know enough.
• 13:19
  Sonia Singh MD: 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.
• 13:26
  Sonia Singh MD: 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.
• 13:33
  Sonia Singh MD: So in order to have this conversation, unfortunately we have to talk about a lot of boring science.
• 13:38
  Sonia Singh MD: 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?
• 13:45
  Sonia Singh MD: What was it?" But you'll see, like, why it all becomes relevant.
• 13:48
  Sonia Singh MD: So- What is NAD+, first of all?
• 13:51
  Sonia Singh MD: I have seen this lumped in with peptides a lot of times.
• 13:54
  Sonia Singh MD: It is not a peptide, to be clear.
• 13:56
  Sonia Singh MD: So NAD+ is a pyridine nucleotide coenzyme, okay?
• 14:01
  Sonia Singh MD: And it is present in all living cells.
• 14:03
  Sonia Singh MD: It is a critical cofactor in reduction-oxidation reactions, and it is a substrate for a bunch of other important signaling enzymes.
• 14:13
  Sonia Singh MD: 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.
• 14:26
  Sonia Singh MD: 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.
• 14:44
  Sonia Singh MD: It's all part of that whole pathway.
• 14:46
  Sonia Singh MD: So NAD exists as an oxidized form and as a reduced form.
• 14:50
  Sonia Singh MD: 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.
• 14:59
  Sonia Singh MD: 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.
• 15:20
  Sonia Singh MD: It's in every cell, so it's doing a lot of different things.
• 15:22
  Sonia Singh MD: Okay, so where does NAD come from?
• 15:24
  Sonia Singh MD: The body generates NAD through a variety of different pathways.
• 15:27
  Sonia Singh MD: 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.
• 15:36
  Sonia Singh MD: 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.
• 15:40
  Sonia Singh MD: Just take a little more tryptophan." Turns out that doesn't work.
• 15:43
  Sonia Singh MD: That's not how it works.
• 15:44
  Sonia Singh MD: But it can be generated from tryptophan.
• 15:46
  Sonia Singh MD: It can also be generated from nicotinic acid, which is a, is one of the forms of B3.
• 15:52
  Sonia Singh MD: Another form of B3 that a lot of people are familiar with is niacin, which has been studied more extensively for various cardiovascular things.
• 15:59
  Sonia Singh MD: So those two things, nicotinic acid and tryptophan, can be acquired from the diet.
• 16:03
  Sonia Singh MD: It can also be made from all the different base products.
• 16:06
  Sonia Singh MD: So you can get it from nicotinamide, which is NAM, nicotinamide riboside, which is NR, and nicotinamide mononucleotide, which again is NMN.
• 16:17
  Sonia Singh MD: So like you can get those things in various forms and then use that to make it.
• 16:21
  Sonia Singh MD: And so this last one where you make it out of those precursors is the main pathway by which you make intracellular NAD+.
• 16:29
  Sonia Singh MD: So NAD can be in the bloodstream, but it also is intracellular.
• 16:33
  Sonia Singh MD: 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.
• 16:43
  Sonia Singh MD: And then inside the cell it creates NAD+ which can then be used for all these processes.
• 16:48
  Sonia Singh MD: 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.
• 16:56
  Sonia Singh MD: 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.
• 17:05
  Rebecca Berens MD: I love that image.
• 17:05
  Rebecca Berens MD: That's-
• 17:05
  Sonia Singh MD: Okay.
• 17:06
  Sonia Singh MD: Yeah.
• 17:06
  Sonia Singh MD: So NAD's the big, bulky couch, and NMN and NR are like it in pieces that you can take in and then assemble.
• 17:16
  Sonia Singh MD: So why do we care about NAD+ in humans?
• 17:19
  Sonia Singh MD: What is the clinical relevance?
• 17:21
  Sonia Singh MD: 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.
• 17:35
  Sonia Singh MD: 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.
• 17:45
  Sonia Singh MD: But in most people, these levels are decreasing over time.
• 17:50
  Sonia Singh MD: And so things that seem to be associated with depletion are viral infections, chronic inflammatory states, obesity, metabolic disease.
• 17:57
  Sonia Singh MD: Most of that data, most, is in animal models, okay?
• 18:02
  Sonia Singh MD: 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.
• 18:23
  Sonia Singh MD: So when people say preclinical models, they mean not humans.
• 18:27
  Sonia Singh MD: So it means animals, rats, or test tubes.
• 18:30
  Sonia Singh MD: So we're not talking about clinical studies here.
• 18:33
  Sonia Singh MD: This data is all not in human beings.
• 18:36
  Sonia Singh MD: Mostly it is in animals.
• 18:38
  Sonia Singh MD: That being said, in animals, i- it is very promising and very strong.
• 18:43
  Sonia Singh MD: I am not gonna expend a lot of detail reviewing these.
• 18:46
  Sonia Singh MD: 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.
• 18:54
  Sonia Singh MD: I did that research again.
• 18:56
  Sonia Singh MD: I listened to a podcast on this.
• 18:57
  Rebecca Berens MD: Bless you.
• 18:58
  Sonia Singh MD: They 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?
• 19:10
  Sonia Singh MD: So luckily there is some human data, so that's what I wanna spend more of our time talking about.
• 19:16
  Sonia Singh MD: The most clinical human data that we have is for NR, which is nicotinamide riboside, and NMN, which is nicotinamide mononucleotide, okay?
• 19:26
  Sonia Singh MD: And this is funny because in the wellness world, these are, like, two camps.
• 19:29
  Sonia Singh MD: 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+.
• 19:36
  Sonia Singh MD: Those are the two forms that are most well-studied and that we have the most data for.
• 19:41
  Sonia Singh MD: So there's a really good review article that's called Dietary Supplementation with NAD+ Boosting Compounds in Humans: Current Knowledge and Future Directions.
• 19:49
  Sonia Singh MD: 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.
• 19:59
  Sonia Singh MD: 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.
• 20:08
  Sonia Singh MD: And it's a really good overview for someone who just wants to know more about this topic.
• 20:11
  Sonia Singh MD: And that will be linked in our in our Substack post.
• 20:14
  Sonia Singh MD: So- Let's talk about NR first.
• 20:17
  Sonia Singh MD: So for NR, they reviewed 12 studies of supplementation, which were at a variety of doses.
• 20:23
  Sonia Singh MD: So the doses ranged from two hundred and fifty milligrams to two thousand milligrams daily.
• 20:26
  Sonia Singh MD: And this is all oral, okay?
• 20:28
  Sonia Singh MD: We're not talking about IV yet, just oral.
• 20:30
  Sonia Singh MD: Most of these were placebo-controlled, but not all.
• 20:33
  Sonia Singh MD: The N, so the number of participants in the study, ranged from eight to forty, so these are all small, okay?
• 20:40
  Sonia Singh MD: But 12 is a decent number, and they're all relatively recent studies.
• 20:43
  Sonia Singh MD: 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.
• 20:51
  Sonia Singh MD: And the studies were mixed in terms of what population they were studying.
• 20:54
  Sonia Singh MD: 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.
• 21:01
  Sonia Singh MD: So what trends did they see?
• 21:02
  Sonia Singh MD: 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.
• 21:12
  Sonia Singh MD: So we don't have the long-term safety data, but, for what was studied, it appeared to be very well-tolerated.
• 21:18
  Sonia Singh MD: They had no serious adverse events.
• 21:19
  Sonia Singh MD: The possible side effects that were reported were nausea, diarrhea, rashes, and leg cramps So overall, appears to be a fairly safe supplement.
• 21:29
  Sonia Singh MD: Now the other thing that they saw consistently in the studies was that supplementing with NR did increase blood NAD+ levels.
• 21:36
  Sonia Singh MD: So it appears that giving people this precursor is effective at getting into the body and increasing the circulating NAD+ levels.
• 21:45
  Sonia Singh MD: Now, that does not mean that we increased tissue levels,'cause that would be a different measurement.
• 21:50
  Sonia Singh MD: That would be a different thing, right?
• 21:51
  Sonia Singh MD: But this is saying that it did increase it in the blood, okay?
• 21:55
  Sonia Singh MD: But that doesn't tell us anything.
• 21:57
  Sonia Singh MD: There's a lot of marketing materials that are just shown to boost NAD levels by 60%.
• 22:02
  Sonia Singh MD: Yeah.
• 22:02
  Sonia Singh MD: 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.
• 22:10
  Sonia Singh MD: We care about is there a clinical outcome?
• 22:12
  Sonia Singh MD: We're not treating a number on a lab test.
• 22:14
  Sonia Singh MD: We're treating a human, right?
• 22:16
  Sonia Singh MD: We wanna see does this make them feel better?
• 22:18
  Sonia Singh MD: Yeah.
• 22:18
  Rebecca Berens MD: Was- I think, I feel like that concept in general is really poorly understood by the general population.
• 22:25
  Rebecca Berens MD: And it...
• 22:25
  Rebecca Berens MD: it's misconstrued also by all these wellness podcasters.
• 22:28
  Rebecca Berens MD: It's like the idea of the outcome has to be a clinical outcome that matters to the patient.
• 22:33
  Rebecca Berens MD: In the Family Medicine Journal, we have a section that's called POEM, Patient Oriented Evidence that Matters.
• 22:38
  Rebecca Berens MD: Okay.
• 22:38
  Rebecca Berens MD: And so it's not just does it make your blood pressure go up or down by X number of points?
• 22:43
  Rebecca Berens MD: But does that actually result in any sort of- Clinical improvement in your life that you care about?
• 22:48
  Rebecca Berens MD: The patient's not sitting there...
• 22:49
  Rebecca Berens MD: I guess people now are sitting there measuring their blood pressure regularly.
• 22:52
  Rebecca Berens MD: But previously, people were not measuring all this stuff.
• 22:54
  Rebecca Berens MD: So it's like, okay, if it decreases your blood pressure by five points, does that actually change anything-
• 23:00
  Sonia Singh MD: For you in terms of, like- why do we
• 23:01
  Rebecca Berens MD: care about
• 23:01
  Sonia Singh MD: blood pressure?
• 23:02
  Rebecca Berens MD: Yeah who cares, right?
• 23:02
  Rebecca Berens MD: We care because
• 23:03
  Sonia Singh MD: of cardiovascular events- that might happen to the person,
• 23:05
  Rebecca Berens MD: right?
• 23:05
  Rebecca Berens MD: Yeah.
• 23:05
  Rebecca Berens MD: 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.
• 23:13
  Sonia Singh MD: Yes.
• 23:14
  Sonia Singh MD: Yes.
• 23:14
  Sonia Singh MD: It's so funny,'cause we get accused so much of"Oh, you're just getting treated like a number.
• 23:18
  Sonia Singh MD: You're just getting..." And in this case, we're trying to think about, are we just treating a number here?
• 23:23
  Sonia Singh MD: Are we just making the number look nicer, or are we doing something that's actually influencing your health?
• 23:26
  Sonia Singh MD: 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.
• 23:37
  Sonia Singh MD: I recommend lifestyle diet changes that probably will reduce it five millimeters of mercury, so like it's not totally insignificant.
• 23:43
  Sonia Singh MD: But when they did correction for various confounders it was not statistically significant.
• 23:48
  Sonia Singh MD: And then there was later a larger trial looking specifically at BP that did not see any change with NR supplementation.
• 23:54
  Sonia Singh MD: 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.
• 24:18
  Sonia Singh MD: 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.
• 24:34
  Sonia Singh MD: And these studies are very heterogeneous.
• 24:36
  Sonia Singh MD: Meaning we don't really know the ideal dose or the ideal population that would benefit from this based on what we have now.
• 24:43
  Sonia Singh MD: 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.
• 24:59
  Sonia Singh MD: And they were really convinced that this was going to improve their cardiometabolic outcomes.
• 25:04
  Sonia Singh MD: 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.
• 25:15
  Sonia Singh MD: 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.
• 25:22
  Sonia Singh MD: And it had no effect on insulin sensitivity, body composition, or any of the other metabolic health parameters that they measured.
• 25:28
  Sonia Singh MD: So this is something where, if you were just looking at the preclinical data, you would be like,"Slam dunk, this is gonna work.
• 25:34
  Sonia Singh MD: 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.
• 25:47
  Rebecca Berens MD: It 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
• 25:59
  Sonia Singh MD: in someone's mood?
• 26:00
  Sonia Singh MD: 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.
• 26:09
  Sonia Singh MD: And maybe if we had better-" research funding for this.
• 26:12
  Sonia Singh MD: Yeah So if you could do something bigger and longer and more robust, we would see an effect, yeah.
• 26:16
  Sonia Singh MD: But this, I'm just reviewing what we've got.
• 26:19
  Sonia Singh MD: Yeah there appears to be no significant evidence that it improves exercise capacity.
• 26:23
  Sonia Singh MD: One interesting- And that
• 26:24
  Rebecca Berens MD: would be a shorter term-
• 26:26
  Sonia Singh MD: Yes
• 26:26
  Rebecca Berens MD: probably result.
• 26:27
  Sonia Singh MD: Yes.
• 26:28
  Sonia Singh MD: 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.
• 26:37
  Sonia Singh MD: So overall- Yeah there was not really an obvious trend towards improved exercise capacity.
• 26:42
  Sonia Singh MD: Now, one use case that I feel like I've heard a few times now is using this for long COVID.
• 26:47
  Sonia Singh MD: 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.
• 26:54
  Sonia Singh MD: It was in 58 patients, so this was not included in this review that I mentioned.
• 26:59
  Sonia Singh MD: 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.
• 27:08
  Sonia Singh MD: 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.
• 27:26
  Sonia Singh MD: But again, it does not seem to pan out when you do the study.
• 27:30
  Rebecca Berens MD: Yeah.
• 27:30
  Sonia Singh MD: So that is a high level overview of the data for NR.
• 27:32
  Sonia Singh MD: So now let's talk about NMN.
• 27:35
  Sonia Singh MD: 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.
• 27:52
  Sonia Singh MD: So it seems like kind of the common pathway is still NR, like everything's becoming NR.
• 27:57
  Sonia Singh MD: 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.
• 28:07
  Sonia Singh MD: But anyway, there's data on NMN too.
• 28:09
  Sonia Singh MD: So there were 13 studies that they reviewed, and interestingly, all of them were published 2021 to 2023.
• 28:15
  Sonia Singh MD: So these are all recent data.
• 28:16
  Sonia Singh MD: The size of the studies range from 17 participants to 108.
• 28:20
  Sonia Singh MD: The doses they used were like 250 milligrams to 1,250 milligrams, similar to the other one.
• 28:25
  Sonia Singh MD: Different patient populations.
• 28:26
  Sonia Singh MD: Some were healthy, some had diseases.
• 28:28
  Sonia Singh MD: The duration ranged from two weeks to 24 weeks, so 24 weeks was the longest one in the- in this category.
• 28:34
  Sonia Singh MD: 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.
• 28:46
  Sonia Singh MD: And so that's part of the reason why there's been kind of this boom in studies of these precursors.
• 28:51
  Sonia Singh MD: 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.
• 29:06
  Sonia Singh MD: 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?
• 29:17
  Sonia Singh MD: 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.
• 29:33
  Sonia Singh MD: So right now NMN is not as widely available, so I think that's another reason that NR has become more popular.
• 29:39
  Sonia Singh MD: So what trends did they see in that NMN data?
• 29:42
  Sonia Singh MD: 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.
• 30:05
  Sonia Singh MD: But anyway, in the studies it was safe and well-tolerated.
• 30:08
  Sonia Singh MD: 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.
• 30:23
  Sonia Singh MD: So a few positive studies, a lot of null negative studies that didn't really show anything.
• 30:28
  Sonia Singh MD: That is the general overview on NAD and NMN.
• 30:32
  Sonia Singh MD: I did have...
• 30:33
  Sonia Singh MD: I remember having a patient ask me about NAD+ supplementation, and I think they may have even sent me a link.
• 30:38
  Sonia Singh MD: 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.
• 30:44
  Sonia Singh MD: Whatever.
• 30:45
  Sonia Singh MD: S- seems safe and well-tolerated.
• 30:47
  Sonia Singh MD: If you really wanna try it, you can try it.
• 30:49
  Sonia Singh MD: 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.
• 31:06
  Sonia Singh MD: Now, the biggest point I wanted to drive home in this episode is that IV NAD+ infusions have essentially no clinical data, okay?
• 31:17
  Sonia Singh MD: 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.
• 31:27
  Sonia Singh MD: This is a surprising amount of research on something like this.
• 31:32
  Sonia Singh MD: 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.
• 31:41
  Sonia Singh MD: That is not the case at all for IV, okay?
• 31:44
  Sonia Singh MD: 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.
• 31:59
  Sonia Singh MD: 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.
• 32:16
  Sonia Singh MD: Okay?
• 32:16
  Sonia Singh MD: So I wanna tell you about this study'cause it's...
• 32:19
  Sonia Singh MD: And again, if you're interested in this topic- Study
• 32:21
  Rebecca Berens MD: seems like a stretch, but-
• 32:22
  Sonia Singh MD: Okay.
• 32:23
  Sonia Singh MD: It's propaganda, okay?
• 32:24
  Sonia Singh MD: 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?
• 32:33
  Sonia Singh MD: And basically they had six patients who received their IV NAD+ loading dose, okay?
• 32:41
  Sonia Singh MD: And their loading dose is a daily infusion every day for four days, based on nothing.
• 32:47
  Sonia Singh MD: I, there's no evidence- I was
• 32:48
  Rebecca Berens MD: gonna say, like, why?
• 32:49
  Rebecca Berens MD: Why is that
• 32:49
  Sonia Singh MD: a loading dose?
• 32:50
  Sonia Singh MD: 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.
• 32:56
  Sonia Singh MD: Someone just made that up, okay?
• 32:59
  Sonia Singh MD: And then they had six patients who received the NR daily infusions, also as loading, which was four daily infusions of the IV.
• 33:08
  Sonia Singh MD: Okay.
• 33:09
  Sonia Singh MD: 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.
• 33:20
  Sonia Singh MD: Of note, there was no placebo group.
• 33:22
  Sonia Singh MD: There was no control group.
• 33:23
  Sonia Singh MD: There was no randomization.
• 33:24
  Sonia Singh MD: There was no blinding.
• 33:26
  Sonia Singh MD: There was no pre-specified endpoints.
• 33:28
  Sonia Singh MD: There was no hypothesis.
• 33:30
  Sonia Singh MD: 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.
• 33:33
  Sonia Singh MD: "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.
• 33:39
  Sonia Singh MD: 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.
• 33:54
  Sonia Singh MD: All six people who got this.
• 33:57
  Rebecca Berens MD: I'm fascinated that they came back after day one to do this again.
• 34:03
  Rebecca Berens MD: Four more three
• 34:04
  Sonia Singh MD: more times.
• 34:04
  Sonia Singh MD: 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.
• 34:18
  Sonia Singh MD: They're just like,"Yeah it's bad.
• 34:19
  Sonia Singh MD: It feels bad." Anyway, so all six of them had this effect.
• 34:22
  Sonia Singh MD: Okay.
• 34:23
  Sonia Singh MD: These adverse experiences ceased immediately upon infusion completion.
• 34:27
  Sonia Singh MD: Thank you.
• 34:28
  Sonia Singh MD: Thank God.
• 34:29
  Sonia Singh MD: Yeah.
• 34:30
  Sonia Singh MD: 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.
• 34:41
  Sonia Singh MD: 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.
• 34:48
  Sonia Singh MD: Five out of the six had tongue, jaw, arm tingling and minor cramping, okay?
• 34:53
  Sonia Singh MD: Which is not nothing.
• 34:54
  Sonia Singh MD: That is something, and then it said-
• 34:56
  Rebecca Berens MD: why is that happening?
• 34:57
  Rebecca Berens MD: Like- that's a bad sign.
• 34:59
  Rebecca Berens MD: Your body's giving you a-
• 35:00
  Sonia Singh MD: Okay, so I- a negative
• 35:01
  Rebecca Berens MD: feedback.
• 35:01
  Rebecca Berens MD: They, I,
• 35:02
  Sonia Singh MD: I 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...
• 35:16
  Sonia Singh MD: I don't know.
• 35:16
  Sonia Singh MD: I...
• 35:17
  Sonia Singh MD: This is all speculative,'cause I don't have a good source for this.
• 35:20
  Sonia Singh MD: Again, this is not a studied thing, so I don't-
• 35:22
  Rebecca Berens MD: Yeah
• 35:23
  Sonia Singh MD: I don't
• 35:23
  Rebecca Berens MD: know why- But, that, but that's the thing.
• 35:24
  Rebecca Berens MD: To me, I'm like, if you're having that sort of reaction, your body is like,"I don't like this."
• 35:27
  Sonia Singh MD: Yes
• 35:28
  Rebecca Berens MD: this seems like potential for more serious side effects.
• 35:31
  Rebecca Berens MD: We only have what, less than 20 people that we're talking about here.
• 35:35
  Rebecca Berens MD: 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?
• 35:41
  Rebecca Berens MD: 'Cause this is, clearly it's doing something that your body does not like.
• 35:47
  Sonia Singh MD: Yes.
• 35:47
  Rebecca Berens MD: Yeah.
• 35:48
  Sonia Singh MD: Okay, 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.
• 36:08
  Sonia Singh MD: They seem to be normalizing"Oh yeah, this is all just par for the course." Okay So they also were comparing infusion time.
• 36:15
  Sonia Singh MD: 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.
• 36:30
  Sonia Singh MD: 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.
• 36:39
  Sonia Singh MD: It is...
• 36:40
  Sonia Singh MD: 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.
• 36:47
  Sonia Singh MD: There is a pre-specified rate that is determined by, a professional, and that's what's used.
• 36:53
  Sonia Singh MD: So this
• 36:54
  Rebecca Berens MD: is used-'Cause it's like there's boluses and then there's maintenance fluids, right?
• 36:57
  Rebecca Berens MD: Yes.
• 36:57
  Rebecca Berens MD: And sometimes it's not safe to bolus certain patients- so we don't let people just- Yeah ad lib.
• 37:01
  Rebecca Berens MD: Exactly.
• 37:02
  Rebecca Berens MD: Exactly.
• 37:04
  Rebecca Berens MD: Control their flow rate.
• 37:04
  Rebecca Berens MD: 'Cause it has to be determined appropriately based on their risk factors and health status.
• 37:09
  Rebecca Berens MD: Yes.
• 37:10
  Sonia Singh MD: Okay.
• 37:11
  Sonia Singh MD: So the NAD group had an average IV infusion time of 96 minutes.
• 37:15
  Sonia Singh MD: So people are sitting there for an hour and a half.
• 37:17
  Sonia Singh MD: That's the average probably some at least two hours getting this infusion and having all of those adverse effects.
• 37:22
  Sonia Singh MD: Okay.
• 37:23
  Sonia Singh MD: And the NR group average time was 37 minutes.
• 37:26
  Sonia Singh MD: So They really cranked it up.
• 37:27
  Sonia Singh MD: They went very fast.
• 37:28
  Sonia Singh MD: And so 60% lower time than NAD.
• 37:31
  Sonia Singh MD: Now let's look at their outcomes in terms of their labs.
• 37:33
  Sonia Singh MD: No significant changes were observed in ALT, AST, hsCRP, BUN, creatinine, TSH.
• 37:39
  Sonia Singh MD: Alk Phos was significantly decreased in the NAD+ IV group but was still within the normal range.
• 37:46
  Sonia Singh MD: And the NR IV group had a significant reduction in their A1C, which was only 30 days later, which is pretty bizarre.
• 37:53
  Sonia Singh MD: And the NAD+ group had a significant reduction in their HDL, which is your good cholesterol, which you actually want to be high.
• 38:02
  Sonia Singh MD: That's not really a good outcome.
• 38:04
  Sonia Singh MD: But again, this was just checked 30 days later.
• 38:06
  Sonia Singh MD: Their LDLs did not change over the 30-day period.
• 38:09
  Sonia Singh MD: Also-
• 38:09
  Rebecca Berens MD: Also this is such a small group of people.
• 38:11
  Rebecca Berens MD: Were most of the people in one group on a medicine or doing something else that may have affected their-
• 38:17
  Sonia Singh MD: Rebecca
• 38:17
  Rebecca Berens MD: DNA?
• 38:17
  Rebecca Berens MD: Do
• 38:18
  Sonia Singh MD: you think they determined that?
• 38:20
  Rebecca Berens MD: Oh, of course not.
• 38:21
  Rebecca Berens MD: But I'm just like, I c- it just, this just baffles me.
• 38:24
  Rebecca Berens MD: Where was this published?
• 38:25
  Rebecca Berens MD: 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?
• 38:31
  Sonia Singh MD: I will tell you where it was published.
• 38:32
  Sonia Singh MD: I'll tell you.
• 38:33
  Sonia Singh MD: It was published in Frontiers of Aging in February of 2026, hot off the presses.
• 38:40
  Rebecca Berens MD: Sounds like a high quality-
• 38:42
  Sonia Singh MD: Yes.
• 38:43
  Sonia Singh MD: It's described as a retrospective tolerability pilot study in a real world setting.
• 38:49
  Sonia Singh MD: So anyway, I don't know how they feel that this proves tolerability,'cause to me it, it's, they're both intolerable.
• 38:54
  Sonia Singh MD: Sounds not tolerable.
• 38:54
  Sonia Singh MD: They both appear to be intolerable, okay?
• 38:58
  Rebecca Berens MD: Also, tolerability is a, a thing you determine before you let it loose- Start
• 39:01
  Sonia Singh MD: giving it to people on the
• 39:02
  Rebecca Berens MD: general population.
• 39:03
  Rebecca Berens MD: That's...
• 39:04
  Sonia Singh MD: Or have them pay you$1,000.
• 39:06
  Sonia Singh MD: Yeah.
• 39:06
  Sonia Singh MD: Okay.
• 39:07
  Sonia Singh MD: So yes, we have not talked about in the harms, we have to talk about the cost, right?
• 39:10
  Sonia Singh MD: Oral supplementation of these NAD precursors is could be 30 or$40, or maybe$150 for a fancy one for the month.
• 39:19
  Sonia Singh MD: 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.
• 39:28
  Sonia Singh MD: I'm like- I was
• 39:29
  Rebecca Berens MD: gonna say.
• 39:30
  Rebecca Berens MD: Marvel Lab.
• 39:31
  Sonia Singh MD: Yeah.
• 39:32
  Sonia Singh MD: So yeah.
• 39:33
  Sonia Singh MD: These people in this commercial setting likely paid over$1,000 more than that'cause this was four days of infusions.
• 39:40
  Sonia Singh MD: 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?
• 39:54
  Sonia Singh MD: If not, do not do that because you're taking- Yeah on other risks like, infection, bleeding.
• 39:59
  Sonia Singh MD: Yeah.
• 39:59
  Sonia Singh MD: Various risks of breaking the skin and injecting something directly into your veins.
• 40:04
  Sonia Singh MD: 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.
• 40:15
  Sonia Singh MD: 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.
• 40:37
  Sonia Singh MD: Because th- I cannot find any justification for-
• 40:41
  Rebecca Berens MD: But I think we can- IVs we can probably say that of an IV bar in general.
• 40:45
  Rebecca Berens MD: 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?
• 40:58
  Rebecca Berens MD: That's the indication that we use in regular medical settings to do something IV.
• 41:03
  Rebecca Berens MD: 'Cause as you said, there are risks to- Yeah injection of anything in your vein.
• 41:07
  Rebecca Berens MD: Breaking the skin has risks.
• 41:09
  Rebecca Berens MD: You can have infection.
• 41:10
  Rebecca Berens MD: You can have bruising.
• 41:11
  Rebecca Berens MD: You can have pain.
• 41:12
  Rebecca Berens MD: You can, blow the vein and have a bunch of swelling and phlebitis, which is inflammation of the vein.
• 41:17
  Rebecca Berens MD: You can have thrombophlebitis, which is a clot associated with the inflammation in the vein.
• 41:21
  Rebecca Berens MD: There's bad things that can happen.
• 41:23
  Rebecca Berens MD: 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.
• 41:35
  Rebecca Berens MD: 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.
• 41:45
  Rebecca Berens MD: So the idea that you would do that recreationally To potentially then risk yourself in an emergency, it just...
• 41:52
  Rebecca Berens MD: I just don't understand the people that do that and feel that it's like a safe and risk-free thing.
• 41:59
  Rebecca Berens MD: And okay, if you're like hungover and dehydrated and you go get an IV, yeah, you're gonna feel better.
• 42:04
  Rebecca Berens MD: But starting all the mix-ins, like you said, the mix-ins, yeah.
• 42:06
  Rebecca Berens MD: That's the case that we had in Texas.
• 42:08
  Rebecca Berens MD: That was what happened.
• 42:08
  Rebecca Berens MD: 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.
• 42:19
  Rebecca Berens MD: Yeah.
• 42:19
  Rebecca Berens MD: And that's the thing, once you start getting mix-ins, also, how do these things interact with each other?
• 42:24
  Rebecca Berens MD: 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.
• 42:34
  Rebecca Berens MD: It's very dangerous.
• 42:35
  Rebecca Berens MD: 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.
• 42:45
  Sonia Singh MD: And 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.
• 42:54
  Sonia Singh MD: They suggested NAD.
• 42:55
  Sonia Singh MD: I had a viral thing.
• 42:56
  Sonia Singh MD: 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.
• 43:06
  Sonia Singh MD: That is truly terrifying to me.
• 43:08
  Sonia Singh MD: So anyway, what can we learn from this as doctors and humans?
• 43:12
  Sonia Singh MD: I honestly, I just got so hung up on this last part.
• 43:16
  Sonia Singh MD: I did not prep this part of the episode, so I don't know.
• 43:18
  Sonia Singh MD: What do you take home from this, Rebecca?
• 43:20
  Rebecca Berens MD: I think I'm interested actually to see that there is potential investigation of using like, what is it?
• 43:26
  Rebecca Berens MD: The N- NMN is the one that has actually been pulled from supplements- Yeah because they're actually investigating it as a drug.
• 43:32
  Rebecca Berens MD: Like that's interesting, right?
• 43:33
  Rebecca Berens MD: Yeah.
• 43:33
  Rebecca Berens MD: And so I think the point of this is not like these things are useless and there's no point.
• 43:37
  Rebecca Berens MD: 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.
• 43:49
  Rebecca Berens MD: But yeah, I think the takeaway for me with the IV is like this is definitely not something I would want in an IV.
• 43:55
  Rebecca Berens MD: It sounds very unpleasant and very unsafe on top of just the general safety concerns with recreational IV-
• 44:02
  Sonia Singh MD: I agree.
• 44:03
  Sonia Singh MD: 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.
• 44:15
  Sonia Singh MD: Yeah.
• 44:15
  Sonia Singh MD: 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.
• 44:28
  Sonia Singh MD: We'll- Yeah we'll monitor you and keep an eye on things and, give it a shot.
• 44:31
  Sonia Singh MD: 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?
• 44:38
  Sonia Singh MD: And so that conversation, I think, needs to be had before, we kinda make these blanket like,"Oh, it's the fountain of youth.
• 44:45
  Sonia Singh MD: It's great for everything,""everyone who's tired can take this." So I think that's definitely one of the take-home points.
• 44:50
  Sonia Singh MD: I kinda went over the way I would talk to a patient about this.
• 44:53
  Sonia Singh MD: 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.
• 44:58
  Sonia Singh MD: So- after she messaged me about the NAD, I was like,"Hey, look let's revisit this.
• 45:03
  Sonia Singh MD: 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.
• 45:15
  Sonia Singh MD: She had tiny kids and was not getting enough sleep.
• 45:17
  Sonia Singh MD: She was struggling to eat meals consistently.
• 45:20
  Sonia Singh MD: There were multiple things that, were potential areas of opportunity for her to improve.
• 45:25
  Sonia Singh MD: 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.
• 45:40
  Sonia Singh MD: 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.
• 45:53
  Sonia Singh MD: 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.
• 46:06
  Sonia Singh MD: 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.
• 46:16
  Sonia Singh MD: 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
• 46:40
  Rebecca Berens MD: know?
• 46:41
  Sonia Singh MD: No.
• 46:41
  Sonia Singh MD: It really is not.
• 46:42
  Rebecca Berens MD: And especially, lupus, you have to treat your lupus.
• 46:45
  Rebecca Berens MD: Lupus is a serious one, yeah.
• 46:46
  Rebecca Berens MD: 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.
• 46:58
  Rebecca Berens MD: 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?
• 47:05
  Rebecca Berens MD: 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,
• 47:14
  Sonia Singh MD: Right
• 47:14
  Rebecca Berens MD: to ever see,
• 47:14
  Sonia Singh MD: and 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.
• 47:26
  Sonia Singh MD: Yeah.
• 47:26
  Sonia Singh MD: 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.
• 47:36
  Sonia Singh MD: 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.
• 47:53
  Sonia Singh MD: 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.
• 48:13
  Sonia Singh MD: We will have all of that on our Substack.
• 48:16
  Sonia Singh MD: So you can go to theantisocialdoctors.com.
• 48:18
  Sonia Singh MD: 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.
• 48:33
  Sonia Singh MD: So that brings us to the end of the show.
• 48:35
  Sonia Singh MD: Thanks, Rebecca.
• 48:37
  Rebecca Berens MD: Yeah.
• 48:37
  Rebecca Berens MD: Thanks, Sonia.
• 48:41
  Sonia Singh MD: Hey guys.
• 48:42
  Sonia Singh MD: Last but not least, we have a very important disclaimer.
• 48:46
  Sonia Singh MD: This podcast is intended for educational and entertainment purposes only.
• 48:50
  Sonia Singh MD: 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.
• 49:04
  Sonia Singh MD: Listening to this podcast does not establish a physician-patient relationship between you and the hosts.
• 49:10
  Sonia Singh MD: We are doctors, but not your doctors.
• 49:12
  Sonia Singh MD: Any medical topics discussed are presented for general informational purposes and may not apply to your individual circumstances.
• 49:19
  Sonia Singh MD: Always seek the advice of your own qualified healthcare professional regarding any questions you have about your health, medical conditions, or treatment options.
• 49:27
  Sonia Singh MD: Never disregard or delay medical advice because of something you've heard on this podcast.
• 49:32
  Sonia Singh MD: 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.
• 49:43
  Sonia Singh MD: 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.
• 49:52
  Sonia Singh MD: Medicine is not static, and information may change over time.
• 49:56
  Sonia Singh MD: 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.
• 50:08
  Sonia Singh MD: By listening to the Anti-Social Doctors podcast, you have agreed to these terms.
• 50:12
  Sonia Singh MD: Thanks again for joining us.