#109 如何提高NAD水平以对抗炎症、改善恢复和延缓衰老 | 查尔斯·布伦纳博士

人们已经尝试过，比如有一项长期新冠研究，所有入组的参与者都患有长期新冠。

People have tried, you know, to see so there is a long COVID study, in which all of the people that are enrolled have long COVID.

他们主诉存在执行功能障碍、抑郁、睡眠质量下降和情绪问题。

So they have complaints about their executive function, depression, their sleep quality, their mood.

最近有一项研究，我想是在过去一两个月内发布的。

And there was a recent study, I think, in the last month or two.

这是吴等人做的研究，发表在《柳叶刀·电子临床医学》之类的期刊上。

It's Wu et al, and I think it's Lancet e met clinical medicine or something like that.

我是那篇论文的合著者，论文显示组内有改善。

I'm a coauthor on the paper that shows that there's within group improvements.

所以，这还不是金标准——即接受NR治疗的组在研究结束时显著优于安慰剂组，但组内比较显示：当人们将服用NR前后的执行功能进行对比时，出现了改善，而安慰剂组没有这种改善。

So, again, this is not quite the gold standard of placebo controlled NR group is superior to the placebo group at the end of the study, but it's, within group meaning when people compared their baseline level of executive function to their executive function when they were on NR, there's an improvement that was not seen in the placebo group.

有人研究过这种改善是否与炎症状态有关吗？

Did anyone look at whether or not that improvement correlated with inflammatory status?

也就是说，基线炎症水平较高的人，是否

So baseline inflammatory status being higher and that being

减少了。

reduced.

但这是一个非常棒的假设，Guzman医生应该去研究一下。

But that's a beautiful hypothesis that doctor Guzman should should look at.

所以如果你在听这段话，Guzman医生，请务必关注一下炎症状态。

So if you're listening to this doctor Guzman, make sure you if you look at the the inflammatory status.

而且你知道，现在有很多证据表明，甚至有人体试验中，人们被注射了脂多糖以引发炎症，或注射生理盐水作为对照。

And then, you know, because I would think, you know, there's lots of evidence now that you can even there's even, you know, human trials where people are injected with lipopolysaccharide, which induces inflammation or a or a saline control.

是的。

Yeah.

你可以影响情绪。

And you can affect mood.

可以降低情绪。

Can depress the mood.

你可以抑制认知功能，因为炎症会影响大脑功能。

You can depress cognitive function because inflammation affects brain function.

嗯嗯。

Mhmm.

所以，我的意思是，我觉得这可以说是一个相当合理的推测——如果你有，嗯。

So, I mean, I I feel like it's a pretty I would say I I would feel comfortable speculating that if you have yeah.

如果你有一个人，不管出于什么原因，基础炎症水平很高，比如酗酒、肥胖、长期睡眠不足，不管是什么，有很多因素都会导致这种情况。

If you have someone with a, you know, high inflammatory status baseline, for whatever reason, alcoholism, obesity, chronic sleep deprivation, whatever it is, there's many many things that can get you there.

对吧？

Right?

嗯嗯。

Mhmm.

如果你能通过生活方式和饮食来降低这种炎症，那当然是最理想的。

That if you can, you know, either reduce that inflammation, obviously, lifestyle and diet, that would be ideal.

或者，如果你服用烟酰胺核糖苷，帮助补充一些NAD，以缓解炎症，是的。

And or if you take the nicotinamide riboside, you know, to help replenish some of that NAD to help with the inflammation Yeah.

这样你也会对一些功能指标产生影响。

That you would affect, you know, some of the functional outputs as well.

是的。

Yeah.

那么，我是说，这其实引出了一个问题，很多人正在服用提升NAD的补充剂。

So how would I'm you know, I and that kinda gets to this thing, you know, and a lot of people are taking there's a lot of people that are taking NAD boosting supplements.

你对他们有什么看法？

And what do you think for them?

他们应该去检测一下血液中的NAD水平吗？

Like, should they go get their NAD blood levels measured?

有没有什么功能性测试能让他们真正知道这些补充剂是否有效？

Is there any sort of, you know, functional test that they can do to really know if it's working?

还是说这就像健身效果一样，只能凭感觉？

Or is it just kind of like a like like the fitness improvements.

对吧？

Right?

假设他们正在锻炼，并且服用了NAD。

Let's say they are working out and they take the NAD.

比如，他们应该测量握力或者你的VOC吗？

Like, should they be measuring their grip strength or their, you know, VOC?

让我在这里说明一下我的COI。

So let me let me cover my COI right here.

对吧？

Right?

是的。

Yes.

我们就这样做吧。

Let's do that.

这太完美了。

So This is perfect.

是的。

Yeah.

最初，是我的技术催生了烟酰胺核糖和NAD增强产业。

So so it was initially my technology that turned into the nicotinamide riboside and NAD boosting industry.

我是Niagen公司的首席科学顾问，Niagen生产这种Niagen片剂。

So I'm chief scientific advisor of Niagen, which makes this Niagen pill.

对吧？

Right?

我同时也是NADMED公司的首席科学顾问，NADMED是一家NAD检测公司。

I'm also chief scientific advisor of NADMED, which is an NAD testing company.

我认为Niagen在健康衰老人群中是否有应用价值？

Do I think there's a use case for Niagen in people in healthy aging?

是的。

Yes.

基于八项随机临床试验，这些研究显示了其抗炎益处，在外周动脉疾病中取得了积极结果，还有一些具有提示性积极结果的试验，比如我们讨论过的长期新冠。

On the basis of eight randomized clinical trials showing anti inflammatory benefits in people, positive trial in peripheral artery disease, and some of these suggestively positive trials like long COVID, which which we talked about.

我认为NAD检测对人们有价值吗？

Do I think that there is a value of NAD testing in people?

在临床试验中肯定有价值。

Definitely in clinical trials.

对吧？

Right?

所以这家公司的NADMED提供用于临床试验观察的试剂盒和试剂。

So this company, NADMED, provides, you know, kits and reagents for clinical trial observations.

有些人会购买这些试剂盒。

People some individual people buy the kit kits.

你认为它有应用场景吗？

Do I think that there's a use case for it?

没有。

No.

我不这么认为。

I don't.

好的。

Okay.

我有点同意你的看法。

I'm kinda I'm kinda with you on that.

我觉得大家可能都知道他们在增加用量。

I feel like it's probably known that they're increasing it.

所以，如果他们从Niagen购买烟酰胺核糖，摄入后六到八小时，他们的NAD水平就会提升。

So they're they're, if they're if they're buying, you know, nicotinamide riboside from Niagen, it's gonna boost their NADs, like, six to eight hours after ingestion.

他们的NAD水平会更高。

Their NAD is higher.

比如，你吃阿司匹林的时候，需要做质谱分析来确认你是否服用了阿司匹林吗？

Like, do you do you go to when if you take an aspirin, do you need to do a mass spec to see whether you ingest an aspirin?

我不觉得这有什么实际用途。

I I don't I don't see the use case for that.

而且可能存在个体差异。

And there's probably some individual variability.

对吧？

Right?

是的。

Right.

好了。

There.

但再次强调，在临床试验的背景下，如果我们招募了50个人，试图弄清楚谁是应答者、谁是非应答者——这其实正涉及你所提出的问题。

So so but again, in the context of a clinical trial, right, if we've enrolled 50 people and we're trying to figure out, you know, we had some responders and some non responders, right, which is kinda getting into the questions that you're you're asking.

它和某些因素有关联吗？

Did it correlate with blah blah blah?

所以在临床试验的背景下，你是否想知道它是否与炎症标志物相关？

So now you in the context of a clinical trial, you wanted did it correlate with inflammatory markers?

它是否与他们的血液反应方式相关？

Did it correlate with the way their blood responded?

他们的血液反应有什么异常之处吗？

Is there anything unusual about the way their blood responded?

但我认为，对于那些过度担忧的健康人群，存在太多不必要的担心和过度检测，这其实没什么帮助。

But I think that there's kind of a lot of over worrying and over testing in of the worried well, and I don't think that that's very helpful.

我同意。

I agree.

你得学会选择要争什么。

You have to choose your battles.

否则你会把自己逼疯的。

Otherwise, you're gonna drive yourself nuts.

就像我之前说的，我们接下来会再多聊聊NAD前体。

And like I said, we're gonna get a little bit more into the NAD precursors.

我其实想先结束一下关于生活方式的话题。

I'm like, I kinda wanna wrap up this lifestyle Yeah.

饮食和生活方式，是的。

Diet lifestyle Yeah.

那些支持NAD的因素。

You know, factors that are supporting NAD.

我们之前谈过摄入方面，但我想再聊聊支持NAD的系统。

We talked about that are consuming, but I wanna talk a little bit about the supporting systems for NAD.

对我来说，运动永远是最重要的。

And for me, exercise is always at the top of everything.

所以我想从这里开始。

So I'd love to start there.

运动是如何影响NAD的？哪种类型的运动更有利于提高NAD水平？

How how does exercise affect NAD, and what type of exercise would be better for increasing NAD?

是有氧运动吗？

Would it be aerobic?

是力量训练，还是抗阻训练？

Would it be, you know, strength training, resistance training?

两者都是。

Both.

我能为我认为两者都有效提出理由，但无论哪种

I can come up with rationales for why I think both would be But either

你知道，你实际进行的运动，永远比你计划做或希望做的运动要好得多。

you know that the exercise that you do is infinitely better than the exercise that you plan to do or wish you did.

是的。

Yeah.

对吧？

Right?

完全正确。

Totally.

所以，有总比没有好。

So so anything's better than nothing.

是的。

Yeah.

而且，我们确实有一些临床证据表明，运动能促进NAD生物合成酶的基因表达。

And and we do have some clinical evidence showing that exercise leads to an increase in the gene expression of NAD biosynthetic enzymes.

我最近和德国的一个团队发表了这项研究，但我记不清他们具体做了哪种运动。

So I recently published that with a group in Germany, and I can't remember what kind of exercise that they did.

但确实有证据表明，运动的人会激活许多转录通路和基因表达通路，你知道，我不太喜欢用‘抗衰老’这个词，但这些通路与年轻状态有关。

But, yeah, there's there's evidence that people that, exercise, you're boosting a lot of transcription pathways and gene expression path pathways that are you know, I hate the word rejuvenating, but it's that are associated with youth and

我的意思是，运动时线粒体生物合成会增加。

I mean, mitochondrial biogenesis goes up when you exercise.

那是一种 rejuvenating。

That's a rejuvenating.

是的。

Yep.

是的。

Yep.

是的。

Yep.

你得知道，有些流行词可能会被过度使用。

You you have to kinda there are buzzwords that can you you kind of get, you know, overplayed.

对。

Yeah.

但对。

But Yeah.

但当它是真的时，它就是真的。

But it when it's true, it's true.

对吧？

Right?

没错。

It's true.

对。

True.

线粒体生物发生是否也参与了NAD水平的升高？当你产生更多线粒体时？

Does does mitochondrial biogenesis play a role in some of the NAD increases as well if you're making more mitochondria?

这是否是一种适应性反应，身体在说：我们需要更多的NAD？

Is it like an adaptation where the body's like, we need more of this, you know, NAD around?

是的。

Yeah.

所以

So

就像这种反应。

like this, like, response.

关键的转录因子对NAD系统做出反应，然后你会产生更多的线粒体，实现更好的β氧化。

Key transcription factor that responds to the NAD system, and then, you know, you make more mitochondria, you have better beta oxidation.

NAD在运动恢复中起什么作用？

How does NAD play a role in exercise recovery?

比如从运动中恢复，这其实是修复过程的一部分。

Like recovering from and now I mean, like, that that's part of the repair.

对吧？

Right?

所以你认为它有帮助。

So you imagine it helps.

但是

But

是的。

So yeah.

那些体育训练师、职业足球俱乐部和大学体育项目的负责人，他们大量购买Niagen，并且对此深信不疑。

The the the, the sports trainers and the heads of, you know, professional football clubs and and college, athletic programs that buy, you know, Niagen by the tub swear by this.

关于这一点，没有太多严格的安慰剂对照数据，但有教练们的使用经验。

So there's not a lot of rigorous placebo controlled data on it, but there's trainer data.

是的。

Yeah.

Anic Anac。

Anic Anac.

Anac。

Anac.

对。

Yeah.

比如，有几张照片显示，Niagen的两位顾问——我和哈佛大学的鲁道夫·坦西教授——曾与比尔·贝利奇克教练以及40岁的汤姆·布雷迪一起出现。

There's, you know, and there's there's, like, photos of, two advisers of Niagen, myself and and doctor Rudolph Tansey, who's a professor at Harvard, you know, with Bill Belichick when he was the coach of the New England Patriots and and the coach of of a 40 year old Tom Brady.

因此，人们普遍知道爱国者队多年来一直在使用Niagen。

So it's well known that the Patriots, took Niagen for for many years.

我其实并不知道他们在贝利奇克离开后是否还在使用。

I don't actually know whether they're still taking it post Belichick.

但它被广泛用于训练室，原因是帮助恢复。

But, it's in a lot of, training rooms for the reason of recovery.

有运动生理学家对研究这个感兴趣吗？

Have any of the exercise physiology scientists become interested in in looking at this?

是的。

Yeah.

我认为这确实需要在实验室的运动生理学科学中进行研究，因为你可以进行这类试验。

I think that it's something that really needs to be studied in, you know, laboratory exercise physiology science, because you can do those kinds of trials.

对吧？

Right?

你可以让人在自行车上拼命锻炼，然后看看他们第二天还能不能同样卖力地锻炼。

You can you can work people really hard on a bicycle and, you know, see whether you can work them as hard the following day.

对吧？

Right?

对。

Yeah.

而且不仅仅是恢复，还包括表现。

And all and not just recovery, but in performance.

我的意思是，如果你消耗了更多的NAD，你的肌肉就在更努力地工作。

I mean, you'd think if you're taxing the NADs that you're consuming more NAD, your muscles are working harder.

就像你所说的，你的适应机制是增加了转录。

And like you said, your adapt adaptation is that you're increasing transcription.

你会知道，那些负责生成更多NAD的基因或酶都会被上调。

You're gonna you know, whatever these genes or enzymes important for making more NAD are gonna be increased.

你会产生更多的NAD，因为你的身体知道你用得更多了。

You're gonna make more NAD because your because your body knows I'm using more.

我需要对此做出反应。

I need to, like, respond to that.

如果补充前体物质，看看是否也有益处，这会很有趣。

It it would be interesting to know if you supplemented with the precursor, if that also was beneficial.

对。

Right.

我猜是的。

I would assume Yeah.

确实如此。

It would be.

对。

Right.

那很好。

Would be nice.

协同作用。

Synergistic.

对。

Right.

是的。

Yeah.

Exactly就是这样。

It would be exactly.

如果有人能真正证明这一点，那就太好了。

It would be nice for someone to actually prove that.

我们之前稍微聊了一下昼夜节律生物学以及与你的昼夜节律不同步的问题。

We talked a little bit about circadian biology and being out of sync with your circadian rhythm.

我想稍微深入一下这个话题。

I wanna kind of get to that.

但在那之前，我认为更多人熟悉的其实是急性睡眠不足。

But before getting there, I think something that even more people are familiar with is like acute sleep loss.

比如，假设你只有一晚。

Like, you have let's say you have one night.

你比平时更晚出去社交。

You're out socializing later than usual.

你上床的时间也更晚。

You get to bed later.

但第二天还得照常起床。

You have to wake up at the same time.

你睡少了。

You miss sleep.

对吧？

Right?

是的。

Mhmm.

这会对NAD系统产生什么影响？

How does that affect the NAD system?

现在是这样吗？

Is it now?

我并不

I'm not

不确定我们是否有确凿的数据，因为说实话，可能已经有可用的小鼠实验了。

sure that we have hard data on it because I don't I mean, the there probably are accessible mouse experiments.

我不知道你有多看重这些，因为你可以对小鼠做一些事情，比如改变房间的光照，或者在不正常的时间给它们喂食，然后可能测量NAD系统的变化。

I don't know how much you would value them because you can do things, you know, with mice where you, change the lighting around in the room or give them food in weird times per day, and you could potentially measure changes in the NAD system.

但要开展这样的人体试验会很难。

But, it would be hard to enroll human trials like that.

是的。

Yeah.

我想在这方面并没有太多实证数据。

I guess there's no it's not there's not a lot of empirical data on that.

如果我要对此进行推测，我相信你也会同意，至少在急性情况下，确实会出现炎症状态的升高。

If I were to speculate on this, and I'm sure you would agree, like, at least in this certainly with acute, you do get an increase in inflammatory status.

但我认为慢性睡眠不足的影响更为显著。

But I would say more so with chronic sleep deprivation.

比如，一个新妈妈，或者任何长期处于睡眠碎片化状态的人。

Let's say you have a new mom or, you know, like, who's just getting constant fragmented sleep.

我们知道，炎症状态确实会升高。

Like, we do know that inflammatory, you know, the inflammatory status is increased.

人们在长期睡眠不足时，体内的炎症生物标志物水平会升高。

Like, people have more inflammatory biomarkers that are elevated with chronic sleep loss.

是的。

Yeah.

不过，我想跟你讲讲一位新妈妈的情况。

Well, I do wanna tell you about a new mom, though.

因为我可以跟你讲讲新妈妈小鼠和大鼠的情况。

Because I can tell you about, new mother mice and and rats.

我想我们是在2019年发表的这项研究。

We published this, I think, in 2019.

所以我们当时有个想法：如果让特别肥胖的雌性小鼠怀孕，它们会将代谢综合征传给后代。

So we had this idea that if we had really overweight female mice that, they'd be conferring, a metabolic syndrome to their offspring.

但这是我们第一次尝试让肥胖的小鼠怀孕。

But it's our first time trying to get fat mice to be pregnant.

明白吗？

Okay?

而且，

And,

我们有一组小鼠食用对照饮食，±烟酰胺核苷；另一组食用高脂饮食，±烟酰胺核苷。

so we had mice that were on control diets, plus or minus nicotinamide riboside, and we had mice that were on high fat diets, plus or minus nicotinamide riboside.

但在高脂组中，我们没能获得足够多的肥胖母鼠完成妊娠并生下幼鼠。

And we simply didn't get enough fat mice to be pregnant and go to term with their baby mice in the fat group.

但在对照组中，发生了一些有趣的现象——我们的繁殖成功率非常理想。

But in the control group, something interesting happened, which is we had perfect fertility.

我们有母鼠要么补充了NR，要么没有补充，我们能够追踪它们的后代。

We had mice that were whose whose moms were either supplemented with an NR or not, and we were able to follow their offspring.

我们发现，补充了NR的母鼠所生的后代在断奶时具有更好的瘦体重，并且这种优势能持续终生。

And what we found is that the offspring of supplemented mothers had better lean mass, at the time of weaning that they were able to maintain for their whole lives.

它们的运动和身体发育更快，比如在平衡木测试中的表现更好，前提是母鼠接受了补充。

They had faster, mechanical physical development, so their performance on, like, a balance beam type thing was better if the mom was supplemented.

它们的恐惧和焦虑水平更低，尽管在小鼠身上测试这些情绪有一定局限性。

They had lower fear and anxiety to the degree to which you can test such things in in mice.

它们在莫里斯水迷宫中的表现更佳，而且如果母鼠接受了补充，成年后海马体神经发生也更旺盛。

So they did better on a Morris water maze, and they even had better adult hippocampal neurogenesis if the mom had been supplemented.

这非常有趣。

This is very interesting.

我的意思是，对我来说，这里有两个想法在同时发生。

I mean, I think, for me, in my brain, two things are going on here.

第一，我们在讨论生育能力。

One, we're talking about fertility.

我在想线粒体健康。

I'm thinking mitochondrial health.

我在想所有这些。

I'm thinking all this.

是的。

Yeah.

对。

Yeah.

第二，如果这些怀孕的小鼠在整个孕期都摄入烟酰胺核糖，那么我就转向基因调控了。

And two, I'm thinking, if these if these pregnant mice were taking nicotinamide riboside throughout pregnancy, then I'm shifting to gene regulation.

所以是的。

So Yeah.

是的。

Yeah.

你们有没有看过那些，

Did you guys look at any of the Well,

所以，小鼠断奶时的体重非常重要，因为母亲在哺乳期传递的热量越多，幼鼠的肌肉和脂肪就越多，其一生的健康状况也就越好。

so so the the weight at weaning of a mouse is really important because the more, you do calorie transfer from the mom from lactation, right, then the more, you know, muscle and fat the baby has and the kind of the better life course it has.

嗯。

Mhmm.

结果发现，补充了NR的新妈妈们体重管理得更好。

So it turns out that the NR supplemented new moms also had better weight management.

对吧？

Right?

这仅仅是热量传递的问题。

And it was simply calorie transfer.

它们产生了更多的乳汁。

They produced more milk.

补充了NR的母鼠产生的乳汁比未补充的母鼠更多，而且可能含有更高水平的生物活性物质。

The NR supplemented moms produced more milk than the non supplemented moms, and potentially, it was higher in bioactives as well.

我们实际上并不知道。

We don't actually know.

我们还没有对补充组和未补充组母鼠的乳汁进行全面的成分分析。

We don't have a full characterization of the milk from the supplemented moms versus the non supplemented moms.

所以可能存在一些非常特殊的脂肪酸，或者微生物组发生了改变。

So there may have been very specialized fatty acids or altered microbiome.

可能的原因有很多。

There's a whole bunch of different things it could be.

对吧？

Right?

但乳汁中的总热量也更多。

But it was also more bulk calories.

真有趣。

So Interesting.

是的。

Yeah.

组蛋白去乙酰化酶属于表观遗传学。

Histone deacetylase is epigenetic.

我在想，这是否也可能是一个可能性，比如

I'm thinking, are we is that, like, a possibility as well in terms of

对。

Yeah.

可能有很多不同的因素在起作用，但我们发现的一点是，新妈妈的肝脏不仅向乳腺系统输送蛋白质、脂肪和碳水化合物以支持乳汁合成，

There could be a lot of different things going on, but one of the things that we found is that a new mother's liver, not only is it distributing protein, fat, and carbohydrate to the mammary system for the mammary biosynthetic lactation Yeah.

合成程序，还在输送NAD前体。

Biosynthetic program, it's also distributing NAD precursors.

因此，补充NR的母亲乳腺中的NAD水平显著升高。

So the mammary NAD in NR supplemented mothers was greatly increased.

很有趣。

Interesting.

实际上，未补充的妈妈肝脏中的NAD系统会下降。

And, actually, the liver NAD system declines in a non supplemented mother.

血液中的NAD代谢组会增加，并主要在乳腺中积累，以支持乳腺的生物合成程序。

The blood NAD metabolome increases, and it basically accumulates in the mammary in order to support the mammary biosynthetic program.

我们待会儿要谈谈安全性之类的问题。

I we are gonna talk about safety and stuff.

我有点跳题了，但既然我们说到这个话题了

We're I'm jumping ahead on myself, but since we're on this topic

是的。

Yeah.

关于怀孕，我一直有个原则，就是尽量停掉所有那些补充剂，只保留最基本的。

Do you I mean, with pregnancy, it's always like it's always my, you know, rule that I like to sort of get off all the, like, dozens of supplements I'm taking and go down to the essentials.

对吧？

Right?

我们知道这是安全且重要的。

That we know is safe, important.

嗯哼。

Mhmm.

有没有理由认为在怀孕期间服用烟酰胺核糖苷不安全，还是说这是某种

Is there any reason to believe that taking nicotinamide riboside during pregnancy would not be safe, or is that something that

没有任何数据。

There's there's no data.

来自动物研究。

From the animal study.

没有人类数据。

No human data.

没有人类数据。

There's no human data.

对。

Right.

然而，你知道，自从我们团队发表了这项研究后，我们就接到了加州大学戴维斯分校和萨克拉门托整个研究母乳喂养及母乳模型系统的团队的电话。

However, you know, as soon as our group published this work, we got calls from UC Davis and the whole group in Sacramento that works on human lactation and model system lactation.

所以，盖尔曼医生和加州大学戴维斯分校的其他几位专家是全球母乳喂养领域最顶尖的权威。

So, doctor Gehrman and a number of other folks at at UC Davis are some of the biggest experts in lactation in the world.

他们也开始规划一些大型动物试验以及人体试验。

And they started planning some large animal trials as well as human trials.

他们其中的一个想法是，早产儿的母亲通常无法产生足够的乳汁。

So one of their ideas was that preemie moms of preemies don't generally produce enough milk.

因为这一点你非常清楚：新妈妈体内的变化通常与婴儿的发育同步。

Because you know this very very well is that your the the things that are happening in the new mom's body are kind of in sync with baby development.

对吧？

Right?

所以如果婴儿因为某种原因提前出生，母亲的乳腺系统通常还没准备好大量产奶，而此时却有一个非常小的新生儿，有着巨大的营养需求。

And so if baby, for some reason, comes out really early, mom's mammary system is not generally ready to produce a lot of milk, and you have a a new very small baby that has major nutritional needs.

因此，我相信他们已经计划了一项针对早产儿母亲的母乳喂养研究。

So I believe that they have planned a human lactation study with moms of preemies.

我认为加州大学戴维斯分校还有一些其他研究正在进行或计划中。

And I think that there are some other studies that are being done or being planned at UC Davis.

关于哺乳方面，是这样的。

Well, at with the with the lactation.

这很有趣。

That's interesting.

我一直觉得，从生育角度来看，尝试烟酰胺核糖可能并不是个坏主意。

I always I mean, it sounds like for like, fertility wise, it's always you know, it might not be a bad idea to try the nicotinamide riboside.

事实上，我认识一些生育医生确实推荐Tru Niagen。

I do actually know some fertility doctors that do recommend Tru Niagen, by the way.

是的。

Yeah.

对。

Yeah.

好的。

Yeah.

所以关于生育方面。

So For fertility.

我们知道这项研究正在进行。

We know that it's being done.

你知道，这是一个类似于运动教练领先于随机试验的领域。

You know, this is an this is an area where, you know, it's a little bit like the sports trainers being out, ahead of randomized trials.

动物实验的结果非常显著，而且安全性数据通常令人安心，因此有很多女性在备孕或怀孕期间每天服用500毫克或一克的Tru Niagen。

The animal results are so strong and that generally the safety data are so, you know, comforting that there are a lot of women that are, you know, presumably taking five hundred milligrams or a gram of niagen, you know, per day during pregnancy or to get pregnant.

这会是你们动物实验中对应的人体等效剂量吗？

Would that be the the human equivalent dose from from your animal study?

会是大约500毫克左右吗？

Would it be something like five hundred milligrams?

临床剂量通常每天大约一克。

Clinical doses are generally around a gram a day.

一克。

A gram.

那相当于两粒TruNiagen

So that would be like two truniagen

胶囊。

capsules.

不同的配方。

Different Different formulation.

是的。

Yeah.

好的。

Okay.

但确实如此。

But yeah.

好的。

Okay.

很有趣。

Fascinating.

我想再回过头来谈谈睡眠问题，因为您至少有一些关于昼夜节律紊乱的临床前证据。

And I would like to kind of just circle back to the the sleep because you do have some at least preclinical evidence on disrupted circadian rhythms.

是的。

Yeah.

在美国，有很多轮班工作者。

There are many many people in The United States who are shift workers.

对。

Yeah.

我们依赖他们。

We rely upon them.

感谢你们所做的一切工作。

Thank you for all the work you do.

我们有护士、医生、消防员、警察。

We've got nurses, doctors, firemen, policemen.

我的意思是，还有大量其他轮班工作者。

I mean, there's just and and there's a ton of other shift workers.

对吧？

Right?

他们在为我们的社会做出大量非常重要的工作

They're doing a lot of really important work to help our society out

是的。

Yep.

以牺牲他们自己的健康为代价。

At the cost of their own health.

你提到，与你的昼夜节律不同步。

And you mentioned that that that being out of sync with your circadian rhythm.

这可能是指轮班工作。

So that could be shift work.

也可能是跨越时区旅行。

It could be traveling to another time zone.

是的。

Yep.

对吧？

Right?

我们称之为时差。

Jet lag as we call it.

对于那些长期处于昼夜节律与工作时间不一致的人，

For those individuals that are, you know, either under chronic, you know, circadian misalignment with their

是的。

Yeah.

无论是因为工作，还是因为旅行跨越时区而经历这种情况。

With their work, or if they're just experiencing it because they're traveling in a different time zone.

你认为有哪些好的策略可以帮助他们减轻对NAD系统的影响？

What do you think would be some good strategies to help them mitigate the effects on NAD system?

我的意思是，补充剂会起作用吗？还是说光照暴露？

I mean, would supplementation come in there, or would it be, you know, bright light exposure?

我们从之前提到的内容中听说过的那些方法。

The things that we've heard of from Right.

你知道的，那些时间生物学家。

You know, the chronobiologists.

对。

Right.

比如褪黑素、接受强光照射，如果是轮班工作者，尝试限时进食，不要一整天都吃东西，类似这样的方法。

Like melatonin, getting bright light exposure, trying to time restricted eating if you're a shift worker, trying to not eat all throughout the day, like things like that.

是的。

Yeah.

我的意思是，临床经验和个人实践都非常有价值。

So I mean, this is something that, you know, clinical and human experience is very valuable.

对吧？

Right?

所以那些经常这么做、已经摸索出方法的人会告诉你，如果他们要进行国际旅行——我下周一就要去——就把日历调整到目的地时区。

So people that do it a lot that have figured out a way to do it will tell you that they set their if they're gonna be taking an international trip, which I'm taking on Monday, set your calendar to where you're going to be.

试着在他们睡觉的时候睡觉。

Think about trying to sleep when they're sleeping.

在当地的早上六点或七点左右接受明亮的阳光。

Get bright sunlight at, you know, six or 7AM their time.

我认为这可能是Niagen的一个潜在应用场景。

If you I think this this is a potential use case for for Niagen.

所以，早上接受明亮的阳光，或许还可以补充烟酰胺核糖。

So, you know, bright sunlight and, you know, potentially nicotinamide riboside at that morning time.

特别是如果你平时早上服用Niagen，那么当你跨越时区旅行时，可能会经历一个奇怪的一天，时长可能是14小时或40小时，具体取决于你旅行的方向。

So and in particularly, if you've been taking Niagen in in the morning, You might have a weird day that is only fourteen hours or forty hours depending on which direction you're going.

所以你会经历一个很奇怪的一天，必须熬过去，然后通过阳光和活动重新调整生物钟。

And so you're gonna have a weird day that you have to get through, and then you you try to re reset with sunlight and activity.

你刚刚让我脑子里冒出了一个非常有趣的问题，接下来我们要讨论的就是NAD补充剂之类的内容。

You just brought up a really interesting question in my brain, and that is and the next thing we're getting into is the NAD supplementation and all of that.

但在那之前，你提到你或许会在早上服用烟酰胺核糖。

But before we get there, you said you were talking about taking nicotinamide riboside perhaps in the morning.

服用时间真的有影响吗？

Does the timing of when you take it actually matter?

假设你呢，你知道的，你状态还不错。

So let's say you you're, you know, you're okay.

我有两个问题。

I have two questions.

是的。

Yeah.

这是一个。

That's one.

timing，这个时间点重要吗？

The timing does the timing matter?

因为你提到过，你会在血液循环中得到一种提升。

Because you did mention that that you get this boost in your in your circulation.

我不知道服用补充剂后多久会出现这种效果。

I don't know how many hours after taking the supplement.

但另外，比如说，你是个轮班工作者，或者你在跨越时区，你的NAD系统被打乱了，很多方面都受影响，但这只是其中之一。

But also, let's say, like, let's say you are, you know, a shift worker or you are changing time zones, and your NAD system's disrupted, lots of things are disrupted, but that's one of many things.

你知道的吧？

You know?

这真的会影响你的能量水平吗？

Is that is that really gonna is that gonna affect your energy levels?

比如，NAD水平下降，一种合理的推测是你会感到精力更低，认知上也会如此。

Like, the NAD being down, one way to presume it would, you would feel lower energy, like, cognitively.

你觉得通过补充剂能恢复这一点吗？

And is that something that you think could be replenished through supplementation?

我知道你在让我猜测，这对你来说很难。

I know you I'm asking you to speculate, which is hard for you.

我知道。

I know.

我尽量基于证据来谈。

Like, I I try to be evidence based here.

我能告诉你的是，NR并不像兴奋剂。

What I can tell you is that, NR is doesn't feel like a stimulant.

不。

No.

对吧？

Right?

是的。

Yeah.

大多数人早上服用。

Most people take it in the morning.

没有理由不早上服用，因为身体获取微量营养素和宏量营养素的方式是一样的。

There's not a me, it's logical to take it in the morning because, the way your body gets micronutrients and macronutrients is the same.

对吧？

Right?

如果你吃了一盘肝脏，你会在同一餐中摄入蛋白质、脂肪、少量碳水化合物和微量营养素。

Is that we if if if you were eating, you know, a plate of of of liver, you'd be getting protein, fat, a little bit of carbohydrate, and micronutrient in the same meal.

对吧？

Right?

微量营养素进入细胞以重建辅酶，而宏量营养素则进入肝脏和肠道，被分解并依赖辅酶转化为ATP。

The micronutrients are going into your cells to rebuild coenzymes, and the macronutrients are going into your your liver and intestine and breaking down and depending upon coenzymes for their conversion to ATP.

所以对我来说，早上醒来，我支持吃早餐，我不是那种受限制的人。

So to me, waking up in the morning, and I'm on team breakfast, I'm not restricted guy.

你知道，我早上会服用Niagen。

You know, I take Niagen in the morning.

我喝咖啡，然后工作。

I have coffee, and I and I and I work.

因此，这对轮班工作者可能很有价值，假设有人上夜班，比如晚上11点开始工作，早上9:30醒来，那么他们很可能在上午10点吃早餐。

So it could well be valuable for shift workers, presumably if somebody has night shifts and let's say they start work at 11PM and they wake up at 09:30PM, then they're presumably having breakfast at 10AM.

我会

And I would

10点。

10PM.

我想，抱歉。

Think or sorry.

晚上10点。

10PM.

所以我认为，这个人会在他们工作周期开始时喝咖啡并服用Niagen。

So I think that that person would probably have coffee and Niagen at that beginning of their work cycle.

为了

To

对我来说，这是

me, that's

他们的早晨。

Their morning.

最合理的做法是

The most logical way of doing

它。

it.

好的。

Okay.

我们来深入探讨一下。

Let's get into this.

我的意思是，希望到现在为止，大家都已经认同自己知道NAD是什么了。

I mean, hopefully, by now, everyone's convinced they know what NAD is.

至少，大家认同它对能量至关重要。

They're convinced it's important, at the very least, for energy.

对吧？

Right?

如果还不止这些，比如修复，嗯。

If not more, repair Mhmm.

调控基因。

Regulating genes.

嗯。

Mhmm.

我的意思是，很多方面。

I mean, a lot of things.

对吧？

Right?

但我认为能量这一点对很多人来说最突出。

But I think energy stands out to a lot of people.

嗯。

Mhmm.

你能跟大家解释一下我知道他们心里都在问的问题吗？为什么我不能直接补充NAD？

Can you please tell people and explain to them the question I know that's in their minds, which is why can't I just supplement with NAD?

为什么我必须服用像烟酰胺核糖这样的前体？

Why do I have to take this precursor like nicotinamide riboside?

所以也许你可以解释一下为什么是这样，顺便谈一谈烟酰胺核糖和烟酰胺单核苷酸的区别。

So maybe you could talk about why that is, and also maybe just touch on nicotinamide riboside versus nicotinamide mononucleotide.

那是另一种前体。

That's another precursor.

是的。

Yeah.

是的。

Yeah.

所以，问题本质上在于磷酸基团。

So basically, the the issue is phosphates.

你知道，含有磷酸基团的化合物无法进入细胞。

So, you know, compounds with phosphates don't get into cells.

因此，能够进入细胞的最大的NAD片段就是烟酰胺核糖。

So the biggest piece of NAD that can get into a cell is nicotinamide riboside.

它进入细胞后，会被烟酰胺核糖激酶磷酸化，加上一个磷酸基团，然后另一个酶会再添加一个被称为AMP的基团，最终形成含有两个磷酸基团的二核苷酸。

It gets into cells, nicotinamide riboside kinase, then phosphorylates it, puts a phosphate group on it, then there's another enzyme that comes along that adds what's called an AMP group to it, and then it's a dinucleotide that has two phosphates on it.

烟酸不含磷酸基团。

Nicotinic acid does not have phosphates.

烟酰胺也不含磷酸基团。

Nicotinamide does not have phosphates.

两者都被视为NAD的前体维生素。

Both of them are considered NAD precursor vitamins.

烟酸的问题在于高剂量会导致皮肤潮红。

Problem with nicotinic acid is high doses of it cause flushing.

所以，如果你试图摄入足够的烟酸来提升NAD水平，你可能会感到一种不舒服的发热感。

So if you're trying to take enough nicotinic acid to boost NAD, you're probably gonna feel kind of an uncomfortable hot flash type type experience.

尽管如此，有些心脏病医生仍推荐它用于调节血脂，因此它有很长的人体使用历史。

That said, there's some cardiologists that recommend it for lipid regulation, and so it has a long, you know, human experience.

烟酰胺长期以来一直存在于食物供应中，通常剂量很低。

Nicotinamide has been in the food supply for a long time, usually pretty low dose.

它可能存在于每一种复合维生素中。

It's in probably every multivitamin.

我们知道它非常安全。

We know it's really safe.

我们知道它具有防癌作用，这一点对这类分子来说非常有利；它们曾在澳大利亚进行过测试，那里皮肤癌的发病率非常高。

We know that it's cancer preventative, which is a very good thing about this class of molecules is that they were tested in Australia, you know, where there's a very high incidence of skin cancer.

对吧？

Right?

因此，剂量高到足以开展一项前瞻性、预防性的临床试验，以观察烟酰胺补充是否能降低皮肤癌风险，结果确实有效。

So high that you can do a perspective, preventative clinical trial to see whether nicotinamide supplementation lowers the risk of skin cancer, and it does.

对吧？

Right?

所以烟酰胺非常安全。

So nicotinamide is really safe.

你认为这与DNA损伤修复有关吗？

Do think that has to do with DNA damage repair?

是的。

Yeah.

是的。

Yeah.

是的。

Yeah.

因此，烟酰胺核苷可能是最优质的NAD前体，因为在多种代谢应激状态下，NR激酶通路都会被上调。

And so so nicotinamide riboside is probably the kind of premium, NAD precursor in the sense that the NR kinase pathway gets upregulated in a lot of conditions of metabolic stress.

在衰竭的心脏或受损的神经元中，烟酰胺核糖激酶1号和2号基因会被上调。

So in the failing heart, in a, damaged neuron, nicotinamide riboside kinase one and two genes get upregulated.

因此，NR在许多烟酰胺无效的小鼠模型中却有效。

And so that's why NR, you know, works in a lot of mouse models in which nicotinamide doesn't work.

比如在心力衰竭实验中，烟酰胺实际上无法提升衰竭心脏中的NAD水平。

Like in the heart failure experiments, nicotinamide can't actually boost the NAD in the failing heart.

因为在衰竭的心脏中，它过度表达了一种名为NMRK2的基因，即烟酰胺核糖激酶2号。

Because in the failing heart, it's overexpressing a gene called NMRK two, nicotinamide riboside kinase two.

所以，衰竭的心脏实际上是想获取整个核苷，以提升其NAD系统。

So the failing heart is sort of looking for the whole nucleoside in order to boost its NAD system.

所以，并不是说烟酰胺核糖更容易到达那里。

So it's not that it's necessarily easier for nicotinamide riboside to get there.

哦，你刚才问到了NAD和NMN。

Oh, well, you asked about NAD and NMN.

对吧？

Right?

是的。

Well yeah.

NAD。

NAD.

所以，如果你口服的话，NAD根本无法进入细胞内部。

So NAD is not even getting in inside of cells

嗯。

Well

本质上，如果你是口服的话。

essentially, if you're taking it orally.

有个有趣的现象，人们开始注射NAD。

There's a there's a funny thing where people started, injecting.

对吧？

Right?

对。

Yeah.

我们来谈一谈这个。

Let's get to that.

NAD静脉滴注。

N a d NAD IV drips.

是的。

Yeah.

那么，你有没有跟做过这个的人聊过？

So so and then, have you ever talked to anybody that has done that?

他们跟你说过这有多疼吗？

Did they tell you how painful it is?

没有。

No.

他们说的是自己感觉有多好，精力有多充沛。

They talked about how great they felt and how they had energy.

是的。

Yeah.

但它是通过几个小时的时间缓慢输注的，在此期间，人们会经历一种先天免疫反应，因为NAD无法进入细胞，NMN也无法进入细胞。

But it's a it's delivered over a several hour period in which the people experience an innate immune response because NAD can't get into cells, neither can NMN get into cells.

所以这些化合物会分解成NR或更小的分子。

So these compounds break down into NR or something smaller.

对。

Right.

因此，NAD可能会先分解成NMN，然后再变成NR。

So NAD is breaking down into probably breaks down into NMN first and then to NR.

然后NR才能进入细胞。

And then NR can get into cells.

烟酰胺可以进入细胞。

Nicotinamide can get into cells.

烟酸。

Nicotinic acid.

这就是我们所讨论的NAD输液的作用机制。

This is the mechanism for the n I NAD drips that we're talking about.

对吧？

Right?

是的。

Yeah.

对。

Yeah.

没错。

Right.

现在实际上有一种Niagen Plus，是一种静脉注射级别的烟酰胺核糖，不会引起疼痛。

There's actually now a Niagen plus, which is like a drip grade nicotinamide riboside, which is not painful.

但你

But That you

可以通过静脉注射进行。

can do in a drip.

你可以静脉注射。

That you can IV.

静脉注射。

Drip.

再说一遍，口服Niagen的临床数据比静脉注射要广泛得多。

Again, the clinical data behind oral Niagen is much more extensive than IV.

不过，有一些小鼠实验表明，静脉注射的NR比口服NR能更深入地分布到不同组织中。

That said that said, there are some, you know, mouse experiments where intravenous NR goes further into different tissues than oral NR.

为什么会这样？

Why is that?

整个生物分布的问题，也就是药代动力学。

So the whole biodistribution, you know, thing is that's pharmacokinetics.

你可以获得更高的浓度

You can get higher levels

通过静脉注射，你可能能向心脏或其他组织输送更多的NR。

You of potentially can deliver more NR to the heart or to other tissues through IV.

所以我认为，未来我们会看到更多关于静脉注射给药方式在疾病相关方面的数据。

So I think that in the future, we're gonna have more, you know, disease relevant data from IV delivery.

所以我很高兴现在有临床级的静脉注射NR，但截至2026年1月，口服NR的数据仍然多得多。

So I'm happy that there is, you know, clinical grade intravenous NR, but there's much more data today in January 2026 on oral NR.

我们知道它是安全的。

We know it's safe.

我们知道它能提升NAD水平。

We know it boosts NAD.

静脉注射是一种还在发展的产品，但如今临床研究界也已能使用它。

IV is something that is kind of a, you know, developing product, and, but it's now available to the clinical research community as well.

好的。

Okay.

对于正在听的朋友们，简单总结一下吧。

Well, just for people that are listening here, just summarize.

因为我知道，你们其实可以在网上买到口服NAD补充剂。

Because I know that you can actually go online and buy an NAD oral supplement.

那根本没用。

That is not going to work.

对吧？

Right?

它会分解的。

Well, it's gonna break down.

我的意思是，NAD分子量的一半，或者40%左右，都是NR。

I mean, half of the molecular weight or 40 or some percent of the molecular weight of NAD is NR.

所以它会分解，被消化，大概只能释放出一小部分分子量作为NAD的促进剂。

So it's gonna break down into, you know, so it'll be digested and deliver presumably deliver some small fraction of the total molecular weight as an NAD booster.

好的。

Okay.

所以它本身不是NAD，技术上讲，NMN你可以争论它是不是前体。

So it's not NAD itself, you know, I technically, NMN is you can argue whether it's a precursor.

它算是NR的前体，而NR又是细胞内NAD的前体。

It's sort of a precursor of NR, which is a precursor to cellular NAD.

但同样，NMN会分解成NR，然后NR进入细胞后又重新变成NMN和NAD。

But, again, NMN breaks down to NR, and then that gets into cells and becomes NMN and NAD again.

我以为NR会被分解成NMN。

I thought NR got broken down to NMN.

不，不是这样的。

Well, no.

NR会被磷酸化，转化为NMN。

NR gets phosphorylated, gets converted up to NMN.

好的。

Okay.

NMN上面有一个磷酸基团。

NMN has a phosphate on it.

但这就很奇怪了，作为一个化学家，你为什么要给NR加上磷酸基团来生成NMN，而NMN又必须降解回NR才能进入细胞呢？

But that so it's a it's a funny thing, like, why as a chemist would you put a phosphate onto NR to produce NMN when NMN has to be degraded down to NR in order to get into cells.

但它很流行。

But it's popular.

对吧？

Right?

它被许多研究人员推广开来，而关于NMN的问题在于，你是否能获得经过纯度和安全性验证的材料。

It was popularized by a number of researchers, and the question with NMN is whether you can get, pure safety tested material.

有一些报告显示，20种标称为NMN的产品中，有17种并不含有NMN，或者未达到标签所宣称的含量。

There are some reports that 17 out of 20 products labeled as NMN don't have NMN in it or don't meet meet the label claims.

有些听众对NR和NMN都很熟悉。

Some people so some people that are listening are familiar with both NR and NMN.

有些人则是第一次听说这些，但他们确实知道NAD。

Some people, this is the first time they're, like, hearing about all this, but they do know about NAD.

我知道很多人是这么想的：他们觉得NMN离产生NAD更近一步。

You know, when the I I know I know a lot of people, the way they think about it is they think, well, NMN is one step closer to producing NAD.

是的，确实是这样。

That's that's

在细胞内。

In a the cell.

对。

Yes.

在细胞内。

In the cell.

这是一种普遍的想法，很多人的脑海里都有这种观念。

That's a general, like, idea that's that's kind of in a lot of people's minds.

那我为什么不直接补充这个过程更接近的环节呢？

So why wouldn't I just supplement with the closer part of this process?

对吧？

Right?

不过那样的话。

That way though.

是的。

Yeah.

为什么不是这样运作的呢？

Why doesn't it work that way?

这是因为NMN带有一个磷酸基团，阻止了它进入细胞。

Well, it doesn't work because the NMN has a phosphate group that precludes its transport into the cell.