Program: Is NAD+ a miracle anti-ageing supplement?

Tegan Taylor: So Norman, it's time for me to test your Australianness once more. Are you a true Australian? 

Norman Swan: I like to think I am now, yes. A bit mixed, but yeah. 

Tegan Taylor: I mean, I think you've lived in Australia for longer than I have. This is the true test of an Australian though; do you like Vegemite?

Norman Swan: Look, that's a really interesting question because I hated Marmite.

Tegan Taylor: That's a controversial opinion.

Norman Swan: I could not stand it, so I avoided Vegemite thinking it was going to taste like Marmite. And then when I tasted it, I thought, oh, this is pretty good. 

Tegan Taylor: You must be the only person in history who likes salty, salty Vegemite more than sweet and salty Marmite, which I think I'll get my citizenship revoked if I say that I like it more, but Marmite is pretty tasty.

Norman Swan: No, no, no. Vegemite is just like Australians; straightforward.

Tegan Taylor: So the reason we're talking about Marmite and Vegemite specifically today has kind of got nothing to do with what we're talking about, which is kind of the point, and I'll explain it in just a second. 

Norman Swan: Yeah, it's today's mystery on What's That Rash?, where we answer your health questions.

Tegan Taylor: So we've actually got a couple of questions on the same topic today, Norman. This week, Sarah says, 'Now that I've hit 40 my social media feeds have turned into a nonstop parade of anti-aging ads,' and one of the big buzzwords Sarah is seeing making the rounds is NMN supplementation to boost NAD+ production, which claims to slow the aging process. Sarah wants to know is there any truth in this, and if so, are there long- or short-term side effects we need to consider? 

And Jamie has written in along similar lines, saying, 'I saw a video of an influencer injecting herself with something called NAD+ the other day, claiming it would give her an energy boost and help with anti-aging.' Jamie asks, 'What in the world is NAD+ and is that safe?'

Norman Swan: Good question. 

Tegan Taylor: Norman, what in the world is NAD+ and is it safe?

Norman Swan: Well, NAD+ is a chemical involved in energy production, energy management, but also control of oxidative stress where you've got biological rusting. It's getting towards one of the more fundamental processes biochemically that make us age, speed it up or slow it down. And NAD+ is the key molecule in this cycle of reactions, and you don't take NAD+ itself, you want to try and influence this pathway. That's what people are trying to do, and you take what are called boosters or precursors to boost your NAD levels in your cells, to affect this biochemical process. And NMN is one of the things that people take as a booster to try and boost their NAD, because it's part of that biochemical cycle. 

Tegan Taylor: It's a really complex biochemical, chemical reaction that we will actually get into. But I think it's good to know what the claims are around this, and because there is a lot of hype on social media, as always, and the sorts of things that it claims to do, like you kind of alluded to before, boosting energy levels, boosting concentration and memory, mental clarity. I've also seen claims around hormone balancing, metabolism and inflammation, which I think we need a What's That Rash? bingo card because that's basically a whole row of bingo card right there.

Norman Swan: That's right, without the bell. 

Tegan Taylor: Yeah, that's it. And then of course some news coverage is throwing around the phrase 'fountain of youth', which is just a giant red flag for me. 

Norman Swan: Exactly. Let's just go to basics here. It is not controversial to say that this substance called nicotinamide adenine dinucleotide (which can exist in two forms, plus and another substance called NADH) is part of chemical cycles which do influence the aging process. So that is relatively uncontroversial. The aging process is not fully understood, but we know that, for example, oxidative stress, energy metabolism, how mitochondria work, which are the energy factories in cells, all relate to how well our bodies work and how efficiently they work. And what's also not controversial is that as we age, our NAD+ levels decline in our cells. 

Tegan Taylor: But there's so many things that change when we age, and it's hard to know which ones are doing something and which ones are just kind of declining.

Norman Swan: Yeah, declining because we're aging, but not driving the aging process. So testosterone declines, for example, in both men and women as we age. The trouble is that when you give testosterone supplements, they don't seem to reverse aging. So is it an effect of aging just by the fact that you've had more time on this earth that they go down, rather than driving the process? Now, some people believe that when NAD+ reduces for whatever reason, if you actually could boost it you would reverse the aging process or slow it down, and that's the key debate. 

Tegan Taylor: I do think it's interesting that there's obviously research that's happened here, this is an actual molecule that's actually found in bodies, and scientists are trying to figure out what its role is. But what happens in this space often with anything to do with anti-aging or slowing down, decay and decline, is that that little whiff of science that might be done in a petri dish or in a mouse model gets blown up into something that's really, really big, with lots of promises around it by people who are trying to make money. And they can say that it's grounded in science, because in a sense it kind of is

Norman Swan: Well, that's right, and it's very powerful, this idea here, because the NAD+, these biochemical cycles affect how DNA repairs itself, it affects what's called cellular senescence, which is how when cells die, the dead cells or almost dead cells are dealt with, because if they're not cleared from the body quickly or efficiently, then they can actually have a toxic effect on the surrounding tissue and increase the aging of tissues, and it also affects how immune cells function. So there's a lot of stuff going on related to these metabolic pathways. 

Tegan Taylor: So obviously this substance is in people's bodies, and we say that it declines with age. How does it get there? Is our body making it?

Norman Swan: There are two processes. One is our body can make it for itself out of its own resources, using tryptophan. And so there's a metabolic cycle which is internal to the body. And then there is another one which is called salvage, and why it's called salvage is that it salvages a substance called nicotinamide, which is one of the group of vitamins called B3 vitamins, and it salvages that from the diet and from the body to manufacture NAD+. And that salvage cycle is where the focus is of NAD+ precursors or boosters. 

Tegan Taylor: So normally we'd be getting these from our diet, and then the supplementation is about, well, can I just stick it straight in my body, either in a pill or an injectable form?

Norman Swan: Correct. So people are taking NMN, which is nicotinamide mononucleotide. They're taking it as NR, which is nicotinamide riboside, which is the vitamin, to be brief. They're trying to do it through tryptophan, which is the other cycle, and nicotinic acid. There are foods which contain these substances, such as legumes, tofu, fish, seafood, dairy and so on. Guess what diet actually might increase your NAD+ precursors…

[Bell rings]

You've got it.

Tegan Taylor: I think I might know! This is it, those are healthy foods, so just eat foods that are good, right? 

Norman Swan: And of course, Vegemite. 

Tegan Taylor: Well, okay, let's talk about Vegemite for a second, because that was obviously our very confusing start to our chat today. The thing with Vegemite is that it famously, apart from containing a lot of salt, also contains B vitamins, and one of those vitamins is B3. And there was a story that I think provides a good cautionary tale a couple of years ago where there was a study that came out of a research institute here in Australia that was talking about birth defects and recurrent miscarriage, hugely distressing for people who have that, either losing multiple pregnancies or having a baby that's born with a birth defect, and often parents blame themselves. And the reasons behind these are often not clear, and this research paper discovered the mother could be deficient in vitamin B3, niacin, and that supplementation prevented birth defects with 100% success. 

A very important asterisk; it was research done in mice. So the mothers in question were mice, not humans, but the press around this discovery was breathless and very exciting. There were headlines like 'Could a simple vitamin prevent birth defects?' It was very, very hyped. And because vitamin B3 and niacin are maybe things that aren't in people's normal lexicon, in an effort to communicate this to the broad public, people reached for Vegemite as sort of 'the vitamin in Vegemite could be blah, blah, blah'. And so what you had, on one hand, was mice being supplemented with a particular vitamin to boost their NAD levels, to the actual message that people got in the community being 'eat Vegemite and your baby won't have a birth defect', which is of course completely wrong.

Norman Swan: You'd have to eat giant amounts…

Tegan Taylor: Bathtubs of Vegemite, and you would have so much salt, which is not good for your health. And so I think of that story as being an important message, I guess, to people like us, Norman, as science communicators, to make sure that in an effort to make something more understandable, you don't accidentally give really bad and maybe harmful advice or false promises. 

Norman Swan: Yeah, a really good point. So let's come to this idea of supplementation or precursors of NAD+. So the evidence is, when you give large doses of this to your favourite animal, the mouse, you do seem to get changes in energy metabolism. Mitochondria seem to work better. There are measures of biochemical aging. They do seem to slow down. So there is some evidence in animal models that boosting NAD levels when they've dropped due to aging can reverse some of these processes. The question is, does it work in humans? And there's no evidence that it does. And you think, well, why is that? Well, it's just that mice are not humans.

Tegan Taylor: Mice also only live for a couple of years. We live for a really long time. Often mouse models are really informative to give us a sense of what might happen over a lifetime, but we can't lean on them entirely.

Norman Swan: No, and it's an artificial situation on genetically selected mice in the laboratory. Here's what we don't know about NAD and NMN boosters. So when people get NMN boosters, they're sometimes getting massive doses of NMN boosters. And there's a thing called homeostasis where one of the reasons why we are such a resilient species is that we've got amazing balance mechanisms in our body. If our blood pressure goes up because we're anxious, there's another process for bringing our blood pressure down, if our stress hormones go up as a process to counteract them and bring them down, our body is in balance. And if something happens to our body that knocks us off balance, the body tries very hard to counteract that. NAD+ works at tiny, tiny amounts in our body, and if you're going to boost it through artificial high levels of these boosters, similar to, say, what animals get in an artificial circumstance, what's quite likely happening is the body saying, 'bugger off; if you perturb me, I'm going to fight against it'. So you might get an initial response over a short period of time, but then that initial response seems to disappear, and it's tantalising because they should work, but they don't, at the moment, seem to work. And where the smart money is going here is do you actually need to give tiny doses of NAD+ precursors in multiple forms to confuse the body or get in under the body's defences so that you're not shifting the body's homeostatic mechanisms, you're getting in under the surface.

Tegan Taylor: Norman, you're giving the supplement companies ammunition here to reformulate and probably charge more as well.

Norman Swan: Well, that's true, but the other problem you've got is taking it in a form that the body can use, and they haven't sorted that out either. There are small studies, there are inadequate studies, and we have not got a clue about what the right dose is.

Tegan Taylor: But when we do look at animal models, because they are good at giving us hints of where to look more, I suppose, NAD+ potentially plays a role in things like Alzheimer's disease and Parkinson's disease and Huntington's disease. 

Norman Swan: Well, it plays a role in everything. You could find anything that it plays a role in. Yeah, sure, it has an effect on brain cells. But the question that we got was; Is it dangerous to supplement too much of it? And there's a little bit of evidence from NMN boosters that maybe you can get gastric side effects. There's not a lot of evidence of harm. But equally, they've not been well studied, and not been well studied over extended periods of time. So on What's That Rash? we are not able to say whether it's safe or not. It looks as though they're safe, even in reasonable doses, but we can't be sure. 

Tegan Taylor: So flipping it around, one of the claims is that people are taking these supplements…and when I say claims, I'm talking about social media…is that people are deficient in NAD+. What do we know about a deficiency of NAD+?

Norman Swan: Well, we know in low-income countries where their diet is specifically from maize that they can become vitamin B deficient, particularly B3 deficient, and they can get a terrible condition called pellagra, and that does affect multiple organ systems and is a serious vitamin deficiency. And we know that NAD levels go down with aging, but that doesn't mean that you're NAD deficient. It may mean that for your age you've got the right levels of NAD in your body. We don't know whether or not that's a good thing or a bad thing, to have low NAD+ levels as you get older. The assumption is that it's bad and associated with the damage of aging, but it may not be. And also we don't know the effects of the gut microbiome; when you swallow one of these substances, do the bugs in your bowel have an effect on its absorption or even its transformation?

Tegan Taylor: Or is it juicing up those bugs…?

Norman Swan: Exactly.

Tegan Taylor: …if it's doing work inside cells? 

Norman Swan: You might have aging bugs in your microbiome, and that tarts them up. 

Tegan Taylor: The Fountain of Youth for your gut bugs, we love it. So to come back to Jamie and Sarah's questions, is there anything in this idea of NAD+ supplementation?

Norman Swan: My belief is there will be in the future, with a very different pattern to what we've got now. And if you're going to take this, you should certainly not take it in pregnancy because you've got no idea what's going to happen there. We have no idea what long-term use does to you. That simply has not been studied. So, great caution, and eat a healthy diet, exercise, and we know that those things help to slow down the biochemical processes of aging themselves. 

Tegan Taylor: Yeah, a healthy, well-rounded diet is probably giving us all of the NAD precursors that we need. 

Norman Swan: At least according to current research. Maybe in the future we'll have something, a little cocktail we could take, but we don't know what that is yet. 

Tegan Taylor: Yeah, I'm going to be waiting for the human studies, I'm not pinning everything on mouse studies personally. 

Norman Swan: No, no, no. 

Tegan Taylor: So if you have a question for us, be like Sarah and Jamie and send it to us, we are thatrash@abc.net.au, and it is also the place where you can send us your thoughts about things that we have spoken about in the past. And a couple of people, Norman, have written in about hay fever cures, which is of course what we were talking about just the other day.

Norman Swan: Yeah, Christopher writes, 'I used to have really bad hay fever, but I made some changes to my life around spring time that have made a world of difference and may benefit your listeners, the What's That Rashers. One, drying my clothes in the tumble-dryer during spring time to avoid pollen getting onto my clothes, drinking kombucha a few times a week and eating yogurt or kimchi to build up a variety of good gut bacteria, wearing an N95 mask during particularly bad days, and an air purifier.'

Tegan Taylor: So three of the four of those sound very straightforward to me. I'm really curious as to what we think about the kombucha, kimchi, yogurt intervention. 

Norman Swan: I'm going to take two on notice, because I think…we've done a What's That Rash? on apple cider vinegar, in other words fermented foods. I think we should do one on kombucha, yogurt and kimchi, just to see whether or not there's a difference there. So I think stay tuned for a future What's That Rash?.

Tegan Taylor: It's funny that you mentioned apple cider vinegar because Susan has also suffered from hay fever for decades and has used all sorts of medications. But she did hear on the ABC Science Show a few years ago that taking a teaspoon of apple cider vinegar with the mother each day in a glass of water would help manage her symptoms. And for her, she says, it does work, and she only takes antihistamine on pollen storm days. 

Norman Swan: Well, I think we're going to have to put that back into the What's That Rash? mix. We've now got two who are getting a benefit from fermented products, they say, from hay fever. Two doesn't make evidence, but it's really interesting, so let's follow that up. 

Tegan Taylor: Well, if you have…I think, Norman, this week we should ask people for their anti-aging cures.

Norman Swan: Absolutely. What are you doing to reverse the aging process? 

Tegan Taylor: Send us your anti-aging cures to thatrash@abc.net.au, and I can't wait to read them.

Norman Swan: And we'll see you next time. 

Tegan Taylor: See you then.