#369 ‒ 重新思考蛋白质需求：运动表现、肌肉维持与长寿，以及肌酸补充和桑拿使用的心理与生理益处 | Rhonda Patrick博士

随着这个探索继续，假设你查看那些研究每日每公斤3克蛋白质的数据，我认为任何看过数据的人都会认同，在每日3克摄入量上你获得的益处与每日2克摄入量相比并无实质提升。

And as you continue this journey, let's say you look at the data of which there are some studies looking at three grams per kilogram per day, which I think anybody who looks at the data would argue you're not really getting a benefit at three grams per day that you aren't getting at two grams per day.

曲线正在趋于饱和。

The curve is saturating.

此时你正触及肌肉蛋白质合成的渐近线。

You're hitting an asymptote of muscle protein synthesis at that point.

所以人们选择摄入如此多蛋白质可能另有原因，比如饱腹感这类因素。

So there may be other reasons a person would choose to consume that much protein, satiety and things of that nature.

但从纯粹的合成代谢角度看，在正常条件下（暂不考虑健美运动），你已触及饱和曲线，却找不到任何证据表明这会造成危害。

But from a purely anabolic reason, under normal conditions, let's leave bodybuilding out of it, you're sort of hit the saturation curve but can't seem to find the evidence that is causing any harm.

无论是实验证据还是流行病学证据，都完全找不到相关危害依据。

This is experimental evidence, even epidemiologic evidence, just no evidence.

不过话说回来，我们不要操之过急。

But that said, let's not get ahead of ourselves.

让我们回到已确立的新基准线上。

Let's go back to we've established a new floor.

没有人应该摄入少于每天每公斤体重1.2克的蛋白质。

There is nobody that should be consuming less than 1.2 grams of protein per kilogram per day.

当我们把摄入量从1.2克增加到1.6克时会发生什么？

What happens as we start to increase that from 1.2 to 1.6?

这正是我需要请教斯图·菲利普斯等专家的时候。

This again is where I turn to the experts like Stu Phillips.

事实上，他做了一项非常出色的荟萃分析，研究了约49项针对成年人进行的对照试验。

In fact, he did a really great meta analysis looking at about 49 different studies in adults that were undergoing controlled trials.

这些试验包括单纯抗阻训练，以及抗阻训练结合蛋白质补充。

Resistance training alone or resistance training plus supplemental protein.

而蛋白质补充量最高达到了1.6克，实际上甚至超过了这个数值。

And the supplemental protein went up to 1.6 well, actually went up above that.

但这项研究真正发现的是，即使只是从每天每公斤体重1.2克增加到1.6克，相比单纯训练的人群，受试者获得了约27%更多的瘦体重和10%更强的肌肉力量。

But what was really found in that study was that even going from, like, 1.2 grams per kilogram body weight per day, obviously, to 1.6 grams per kilogram body weight, people gained about 27% more lean body mass and 10% more muscle strength compared to just training alone.

同样的训练计划，只是增加了蛋白质摄入。

Same training, just adding the protein.

这个效果相当显著。

That's pretty big.

我正想说这比我预期的要大，尤其是在力量方面。

I was going to say that is bigger than I would expect, especially on the strength side.

在力量方面。

In the strength side.

所以蛋白质本身，但如果你从供需角度来思考这个问题。

So the protein itself but if you think about it in a way, we're talking about supply and demand.

现在我们讨论的是更优化，稍微更优化一些。

So now we're talking about more optimal, a little more optimal.

我们讨论的是正在进行训练的人群。

We're talking about people that are training.

这是第一点。

That's number one.

你必须进行训练。

You need to be training.

如果我们讨论的是最佳蛋白质摄入量，那你必须进行训练。

If we're talking about optimal protein intake, you need to be training.

当你训练时，实际上是在分解肌肉。

And then what's happening when you're training is you're breaking down muscle.

你需要蛋白质来支持肌肉的修复和重建。

You need protein to support the repair of that muscle and the rebuilding of it.

所以这在某种程度上是合理的。

And so that makes sense in a way.

不过确实，我对力量方面的数据也感到惊讶。

But yeah, I was surprised by the strength as well.

实际上，一旦超过1.6克，仍然能看到

Really, once you went above 1.6 grams, there were still increases in

肌肉的增长，是的。

muscle Yeah.

蛋白质，但增长曲线正在放缓。

Protein But the curve is slowing down.

我喜欢斯图·菲利普斯用的那个比喻。

I like the analogy that Stu Phillips uses.

他说，就像你有一块湿毛巾，你拧它想把水挤出来，大部分水在每公斤体重1.6克蛋白质时就已经挤出来了。

He says, like, if you have like a wet washcloth, you squeeze it to get all the water out, most of that water is coming out at 1.6 grams per kilogram body weight.

但你可以继续稍微再拧一下，还能挤出一点水来。

But you can keep squeezing a little, and you're still getting some water out.

只是边际效应而已。

It's just marginal.

就像大多数人不在乎那点差别。

It's like most people don't care about that difference.

但有些人会在意。

Some people do.

假设你是那种痴迷于增加肌肉量的人。

Now let's say you're someone that's obsessed with banking muscle mass.

你就会在意这个。

You're gonna care about that.

假设你是一名高水平运动员，那肯定需要超过1.6克的标准。

Let's say you're a high level athlete, definitely gonna have to go above 1.6.

这时你就会进入每公斤体重两克到二点二克的摄入范围。

That's when you get into the more two, two point two grams per kilogram body weight.

所以那些进行高强度训练的人群，无论是耐力训练还是力量训练、抗阻训练。

So people that are doing a high level of training, whether that's endurance or strength training, resistance training.

因为耐力运动员其实一直在与分解代谢作斗争。

Because endurance athletes, I mean, they're you are battling being catabolic.

我认为更理想的证据表明，每公斤体重1.6克是基准值。

I think the evidence for more optimal, you're talking about 1.6 grams per kilogram body weight.

超过这个标准还能获得边际效益，最高可达每公斤体重两克到二点二克。

You can get marginal benefits above that, Up to like two, two point two grams per kilogram body weight.

但重申一次，这针对的是真正在刻苦训练的人群。

But again, that's people that are really training.

是啊，我觉得这跟载脂蛋白B与心血管疾病的关系有相似之处。

Yeah, to me there's an analogy here with ApoB and cardiovascular disease.

那么，如果你审视这三方面的证据。

So, if you look at the three bodies of evidence.

也就是说，你查看所有的流行病学数据，所有的临床试验数据，以及所有的孟德尔随机化数据，并将每一项都绘制在图表上。

So, you look at all of the epidemiologic data, if you look at all of the clinical trial data and if you look at all of the Mendelian randomization data and you plot every single one of them on a graph.

有一张精美的图表会展示这一点，我们将在节目说明中附上。

And there's a beautiful graph which we'll include in the show notes that does this.

在x轴上，数据是以LDL-C（低密度脂蛋白胆固醇）为单位呈现的。

So, on the x axis, and it's done in LDL C.

重申一下，LDL-C和APOB（载脂蛋白B）可以很方便地放在一起观察。

Again, LDL C, APOB, easy to view them together.

在x轴上，LDL-C的数值是递减的。

So, on the x axis, you have LDL C going down.

从160、140、120、100、80到60。

So, from 160, 140, 120, 100, eighty, sixty.

也就是说，LDL-C呈下降趋势。

So, descending LDL C.

在y轴上，显示的是死亡率，心血管疾病死亡率。

And on the y axis, you have mortality, cardiovascular mortality.

不出所料，所有这些点都呈下降趋势。

So, not surprisingly, all of these point down.

随着LDL C水平降低，心血管疾病死亡率也随之下降。

As LDL C goes lower, cardiovascular mortality goes lower.

但有趣的是，你可以看到曲线上有几个关键转折点开始产生更大影响。

What's interesting though is you can see that there are different points in the curve at which it starts to matter more.

到某个阶段后曲线会趋于平缓。

And at some point it flattens out.

继续降低指标带来的收益就会递减。

You don't get as much benefit from reduction.

因此我们可以用同样的论点来讨论：什么水平才是最优的？

And so we could use the same argument of, well, what is optimal?

因为我们这里采用的是逆向推导。

Cause we're doing the reverse here.

这里，数值越低越好，与蛋白质水平升高相反。

Here, lower is better as opposed to going up on protein.

但彼得·利比的分析表明，当ApoB降至30毫克每分升时，心血管疾病仍会持续显著减少。

But Peter Libby has done an analysis that has demonstrated that you will continue to see a meaningful reduction in cardiovascular disease as ApoB heads towards thirty milligrams per deciliter.

30毫克每分升对大多数人来说是非常低的水平。

Thirty milligrams per deciliter is really low by most people's standards.

作为参考，60毫克每分升大约处于人群水平的第五百分位。

For context, sixty milligrams per deciliter is about the fifth percentile at the population level.

30毫克每分升大约相当于儿童的数值。

Thirty milligrams per deciliter is about what a child is.

我们出生时ApoB水平相对较低，随着年龄增长会不断上升。

So we're born with relatively low levels of ApoB and as we age, they just keep going up and up and up.

这当然是推动心血管疾病发展的因素之一——ApoB的持续升高。

Which of course is one of the things that's driving cardiovascular disease is this rise in ApoB.

那么问题就变成了：需要降到多低才合适？

So, the question then becomes, how low do you need to go?

每个人都应该将ApoB维持在30毫克每分升的水平吗？

Should everybody be walking around at thirty milligrams per deciliter?

这是消除动脉粥样硬化性心血管疾病的解决方案吗？

Is that the solution to eliminating ASCVD?

答案很可能是否定的。

And the answer is probably not.

这可能取决于你既往的暴露程度。

It probably depends on your previous exposure though.

所以，如果我接诊的患者已经放置了两个支架并有严重的病变负担，我绝对会让他们把ApoB控制在30毫克每分升——哪怕需要联合三种药物来实现。

So, if I have a patient who's already had two stents placed and has a significant burden of disease, you bet your bottom line they're at thirty milligrams per deciliter of ApoB, even if we have to put three drugs on them to make sure that's the case.

因为他们的病变负担和终生ApoB暴露水平实在太高了。

Because their burden of disease and their lifetime exposure to ApoB has been so high.

但如果面对一位40岁、冠状动脉完全健康且ApoB维持在60毫克每分升的人，我认为无需任何干预。

But if I have an individual who's 40 years old, who has perfectly pristine coronary arteries and is walking around with an ApoB of sixty milligrams per deciliter, I don't think you need to do a thing.

我觉得他们保持现状就很好。

I think they're just fine.

再次强调，我认为问题在于人们难以理解这种细微差别——何时值得二次施压，何时粗略施压就已足够。

And again, it's the inability, I think, for people to understand that level of nuance and understanding when it's worth the second squeeze versus when just the sloppy squeeze is good enough.

对于像我这样渴望理解细微差别的人来说，这非常令人沮丧。

It's very frustrating for a person like me who craves nuance.

同意。

Agreed.

我喜欢这个比喻。

I love that analogy.

我认为这个比喻很完美，因为确实大多数训练者可能从每公斤体重1.6克的摄入量中获益良多。

I think it's perfect because I do think most people that are training probably are getting a great amount of benefit from 1.6 grams per kilogram body weight.

但这并不意味着超过这个量就不能获得更多收益。

But that doesn't mean you can't go above that and still get a little more benefit.

当然，当你进入能量赤字阶段时也是如此。

Certainly, when you start to get into that energy deficit phase as well.

所以我们之前是在讨论精英耐力运动员。

So we were talking about elite endurance athletes.

这是造成能量赤字的一种方式。

That's one way to be in an energy deficit.

但也有人正积极尝试减脂增肌。

But there's also people that are actively trying to lose fat, gain muscle.

如果你想同时减脂增肌，就必须摄入大量蛋白质。

If you want to lose fat and gain muscle at the same time, you're going to have to take in a lot of protein.

是的。

Yeah.

所以这是另一个非常重要的点。

So that's another very important point.

我想指出的另一点是，你们仍在处理一个不对称的目标。

Another point I want to make is you're still dealing with an asymmetric target.

我们建议患者更接近两克的标准。

We tell our patients to be closer to two.

要知道这会让那些反对高蛋白饮食的人彻底抓狂。

Now, know that's just going to get a whole bunch of people on the anti protein train just losing their mind.

我都能想象到观众看到这段视频时磷酸化反应爆发的样子。

I can just see the phosphorylation going off right now as they're watching this clip.

这家伙怎么能如此不负责任，建议病人每公斤体重摄入两克蛋白质？

How is this guy so irresponsible to tell his patients to eat two grams of protein per kilogram of body weight?

他难道没听到朗达刚说的话吗？

Didn't he just hear what Rhonda said?

对大多数人来说1.6克就足够了。

1.6 is good enough for most people.

可我的病人毕竟不是生活在实验室里。

Well, my patients unfortunately don't live in labs.

遗憾的是朗达，我的病人都生活在这里。

Unfortunately, Rhonda, my patients live in this place.

这个地方叫现实世界。

It's called the real world.

而在现实世界里，你不可能总是达成目标。

And in the real world, you can't always hit your targets.

有时能做到，有时做不到。

Some days you do, some days you don't.

有时在旅行，有时没有。

Some days you're traveling, some days you're not.

有时能解决，有时不能。

Some days you can figure it out, some days you can't.

所以如果我建议某人达到1.6克，某天他们摄入1.2克，另一天1.7克，又一天1.5克，再一天1.9克，平均下来可能达到1.6克。

So, if I'm telling somebody to hit one point six and one day they're at 1.2, another day they're at 1.7, another day they're at 1.5, another day they're at 1.9, On average, they might hit 1.6.

但低于目标的天数与高于目标的天数相比如何？

But how many days were they below versus how many days were they above?

假设两者天数相等。

Let's just say it's an equal split.

但我们刚刚确认这条曲线的形状是这样的。

But we've just established the shape of this curve is like this.

这意味着每当你低于目标时，负面影响远大于高于目标时的正面影响。

So that means every day you're below, the downside is much greater than the upside of being above.

换句话说，你超出标准的日子并不能弥补你你低于标准的日子。

In other words, all the days you're above are not making up for all the days you're below.

所以我真正想做的是调整这个范围，让你的最低日摄入量是1.6克，最高日摄入量可能是2.2克。

So what I'd really like to do is shift the range so that your low day is 1.6 and your high day is maybe 2.2.

然后你猜怎么着？

And then guess what?

这样你就永远不会出现氨基酸摄入不足的日子。

You don't have days where you are ever ever amino acid restricted.

这就是现实世界中真正照顾病人的人与那些在Substack上写文章、对临床运动医学一窍不通的门外汉之间的区别。

And this is the difference between people who take care of people in the real world and bozos who write on Substack who don't know the first thing about clinical medicine when it comes to managing athletes and people who have to fend for themselves every day with every meal.

这就是为什么我如此厌倦讨论这个话题，但我认为我们有必要谈一谈。

And this is why I'm so tired of talking about this, but I feel we need to talk about it.

如果你坐在这里听这些内容感到困惑，并且想问：天啊，我每天应该吃两克吗？

If you're sitting there listening to this and you're confused and you're asking, Oh my god, should I be eating two grams per day?

是的，差不多就是这样。

Yeah, more or less.

这样，即使你只摄入1.6克，也能确信自己没问题。

And that way if you fall short at 1.6, you can be confident that you're okay.

但如果你以1.6克为目标，遇到状态不佳时（这种情况难免），当跌到1.2克时，你可能就在退步了，第二天也无法弥补回来。

But if you're aiming at 1.6 and you have a bad day and you will, when you hit 1.2, you might be taking a step backwards and you won't make up for it the next day.

根据个人经验，我可以说把目标定高些其实更明智，因为我总是达不到那个标准

I can just tell you from personal experience, it's actually smarter to aim higher because I'm constantly not meeting the one point

我不是

I am not.

事情是这样的。

This is the thing.

人们看我就像看一台蛋白质摄入机器，首先我并不是。

People look at me like I'm a protein eating machine, which first of all, I'm not.

但其次，我也很难达到自己的目标。

But secondly, I have a hard time hitting my goals too.

我很忙，会错过正餐，有时我们就是会吃低蛋白的餐食，不管什么原因。

I'm busy, I miss meals, sometimes we just have a low protein meal like for whatever reason.

我的孩子们晚餐想吃意大利面，而我们真的就只有意面和酱料。

My kids want to have pasta for dinner and we literally have pasta and sauce.

这里面根本没什么蛋白质可言。

There's no freaking protein in this anyway.

所以如果你没有厨师为你准备每一餐——除非是在餐厅吃饭，否则我从来没有任何厨师为我备餐——要每天达到这些目标是非常困难的。

So it's very difficult if you don't have a chef preparing your every meal, and I never have a chef preparing any of my meals unless I'm out at a restaurant, to hit these targets every day.

对。

Right.

我正在思考这个问题，因为我们提到1.22克是基本门槛。

I was thinking about this because we mentioned the 1.2 being the sort of the minimum buy in.

每公斤1.6克的目标并不只是针对那些稍微训练的人。

The 1.6 grams per kilogram bottle isn't necessarily just for people training a little bit.

也包括不训练的老年人——我们讨论过合成代谢抵抗问题，他们同样需要双倍蛋白质摄入。

It's also older adults that are not training because we talked about the anabolic resistance, them needing twice as much protein as well.

所以你这里说的提高到两倍量，就是为了确保平均至少能达到1.6克。

And so what you're talking about here is going up to two so that you can really have an average at least of 1.6.

你正在达到那个平均值。

You're getting that average.

我绝不想低于那个标准。

I never want to fall below that.

低于它。

Below it.

关键在于我知道自己每天都在训练。

That's really the point is I know I'm training every single day.

那我是不是练得像疯了一样？

Now am I training like a madman?

不是。

No.

但每周七天，我都在做有氧运动或健身房训练。

But seven days a week, I'm either doing some form of cardio or something in the gym.

所以我知道如果低于1.6克，我就会倒退。

So, it's just I know that I'm gonna take steps backwards if I'm below 1.6.

所以我要超额摄入，这样即使状态不佳时也能保持1.6克。

So, I'm gonna overshoot so that my down day is 1.6.

即便偶尔摄入量达到2.5克又怎样？反正最终都会回归基准值。

And if my up day is 2.5 once in a while, who cares because that gets to the next point.

数据拿出来看看。

Show me the data.

拿出证据证明每天每公斤体重摄入2.5克蛋白质有丝毫危害。

Show me the data that eating 2.5 grams of protein per kilogram per day is even remotely harmful.

我至今还在等这个数据。

I'm still waiting for it.

我仍在等待相关研究数据。

I'm still waiting for the data.

大卫·艾利森最近在领英发文，本质上是在向全行业发起挑战。

David Allison wrote a piece on LinkedIn recently where it was basically a call to anyone.

只要拿出符合这些标准的研究数据给我看就行。

Just show me the data that meet these criteria.

这种持续时间的人体临床试验，哒哒哒哒哒。

Human clinical trial of this duration, da da da da da.

一片寂静。

Nothing but crickets.

是啊。

Yeah.

我是说，确实也没见过任何人体数据。

I mean, haven't seen any human data either for sure.

我最近看到的最负面数据是一项研究，观察了ICU患者的全肠外营养，问题是：我们是否应该给这些人大量补充蛋白质？

The most negative data I saw recently was a study that looked at total parenteral nutrition in ICU patients where the question was, hey, should we be ramming high amounts of protein in these people?

你能说的最负面结论就是它没有益处。

The And most negative thing you could say is it had no benefit.

这很有趣。

And that's interesting.

没错。

Yeah.

也许我们不应该给重症监护病房的患者通过中心静脉输注高蛋白全肠外营养。

So maybe we shouldn't be ramming high protein total parenteral nutrition into the central veins of critically ill ICU patients.

但这并没有伤害他们。

But it didn't harm them.

对吧。

Right.

如果有人会受到伤害，我认为那应该是肾衰竭患者。

And if anybody's gonna be harmed, I would think it's the people that are in renal failure.

没错，正是如此。

Yeah, exactly.

我还没看过那份数据。

I haven't seen that data We

我们还没有具体讨论过孕期或青春期的蛋白质需求。

haven't spoken specifically about pregnancy or adolescence.

关于蛋白质需求我们了解多少？

What do we know about protein requirements?

因为现在显然有正在怀孕或将会怀孕的女性在听我们讲话。

Because there are clearly women listening to us right now who are pregnant or who will be pregnant.

我不认为有青少年在听我们说话，但我敢肯定有青少年的父母在听。

And I don't think there are any adolescents listening to us, but I bet there are parents of adolescents.

那么我们应该给这些人什么样的指导呢？

So what kind of guidance would we want to give these folks?

它

It

在孕期和青少年时期会增加。

goes up with pregnancy and also adolescents.

意思是，所以

Mean, so

有正式的推荐吗？

Are there formal recommendations?

我不记得了。

I don't remember.

再次强调，关键是要略高于RDA（推荐膳食摄入量）标准，我们已经证实那是不够的。

Again, it's all about, like, going a little bit above what's the RDA, and we've already established that's not enough.

所以老实说，我认为如果听众从本期节目中学到什么，那就是明白每天每公斤体重0.8克的蛋白质摄入量是远远不够的。

So, I mean, honestly, I think if people are listening to this episode just knowing that 0.8 grams per kilogram body weight per day is just not enough.

即便我们没能达成其他共识，这也是本期节目最核心的要点。

So if we accomplish nothing else, that's the single most important take home message here.

我确实认为这很重要，因为所有人都在参考那些指南。

I really think it is because everyone looks at those guidelines.

是啊。

Yeah.

这真的很滑稽。

It's really funny.

前几天我吃东西时看到包装上的蛋白质含量——具体数值我忘了，但标注了占每日需求量的百分比，显然这个标准定得异常低。

The other day I was eating something and I forget how much protein it had in it, but it had percent of daily requirement, but it was obviously baked to a very low number.

我记得当时我儿子和我一起看包装，他说了句话，具体数字我记不清了。

Because I remember my son was looking at it with me and he goes, I forgot what the number was.

这真的占你每日蛋白质需求的40%吗？

Is that really like 40% of your daily protein requirement?

而且从来都是相对较低的。我说，不是的。

And was ever relatively And I said, no.

但我实在没精力跟他解释RDA标准。

But I just didn't have the energy to explain the RDA to him.

所以我就说，不，这个完全是错的。

So I was like, No, this is just wrong.

你可以忽略这个。

You can ignore this.

生长发育期也是蛋白质需求的重要阶段，对吧？

Growing is also an important time for protein, right?

因为这些氨基酸和必需氨基酸会激活IGF-1生长激素，这对生长发育非常关键。

Because these amino acids and the essential amino acids are activating IGF-one growth hormone and that's really important for growth.

我记得有研究对比过给婴幼儿食用鸡蛋、牛奶和某种素食蛋白，结果明显显示鸡蛋是最优选择。

I know there were studies done in like infants and toddlers that were given egg versus milk versus some kind of vegan protein and it was clear that the egg was the winner here.

摄入更多必需氨基酸的蛋白质对长高很重要。

Giving protein with more essential amino acids was important for growing taller.

这也是我作为母亲一直在考虑的事情。

And that's always something that I, as a mom, think about.

我总是想办法让儿子摄入足够的蛋白质。

I'm always trying to get protein in my son.

而且孩子们活动量更大。

Plus, the kids are more active.

孩子们的运动量更大。

Kids are more physically active.

青少年们都在参加体育运动之类的活动。

They're doing sports and things like that, adolescents.

所以满足蛋白质需求真的很重要。

So it's really important to get the protein requirements.

我还没有深入研究那些数据的所有细节。

I haven't dug into all the nuance of that data.

在我看来，青少年虽然接近成人身材，蛋白质需求也应该是每公斤1.2克左右。

The way I look at it is it's got to be like a 1.2, even though that's in the adult.

一般来说，体型接近成人的青少年，蛋白质需求大约是每公斤1.2克。

It's more like a 1.2 gram per kilogram for an adolescent who's pretty close in body size to an adult, generally speaking.

他们开始长得相当高了。

They start growing pretty tall.

是啊。

Yeah.

我觉得孩子们的蛋白质摄入至少应该在1.2到1.6克每公斤体重。

I mean, I would think for kids it should be at least the 1.2 to 1.6.

看看我家孩子的活动量，简直让我觉得自己像个懒人。

Just look at the activity level of my kids is they make me look sedentary.

好的。

Okay.

关于蛋白质这个话题，还有什么想说的可以帮助消除外界的一些困惑吗？

Anything else we want to say on the topic of protein to help with some of the confusion that is out there?

我认为我们应该讨论一些关于mTOR作用机制、癌症等问题的误解。

I think we should talk a little bit about some of the misconstrued understanding of mechanisms of action around mTOR, cancer, stuff like that.

我想补充的是关于热量限制的问题，比如进行间歇性断食的人群，或者任何试图进行身体重组（增肌减脂）的人。

I would say the other thing would be the calorie restriction, people doing intermittent fasting, people doing anything if they're to be body recomposition, the gaining of muscle and losing fat.

我认为这是一个非常特定的人群，对他们来说高蛋白摄入至关重要。

I think that is a very specific group of or population of people where the high protein intake is critical.

因为当处于热量赤字状态时，你的身体会不断消耗肌肉储备。

Because if you're in a caloric deficit, you really are battling your body pulling from your muscle reserve.

如果你在进行抗阻训练，那会有些帮助，但你肯定不会增长肌肉。

If you're resistance training, that helps somewhat, but you're certainly not gonna gain muscle.

我们刚才讨论过要趁年轻时尽可能多地储备肌肉。

And we just talked about wanting to bank as much muscle as possible as we're younger while we can.

对吧？

Right?

因为我们最终会开始动用那些储备，所以需要保留它们。

Because we need that reserve because we're gonna start pulling from it eventually.

因此我认为这就是为什么你会看到非常高的数字，甚至超过2.2克。

And so I think that that's where you start to get really high numbers, 2.2 even higher.

你可以找到相关研究，比如每公斤体重摄入3克蛋白质。

You can find studies out there, it's like three grams per kilogram per body weight.

在这种情境下，超过1.6克似乎也很关键，当你达到每天每公斤体重2.2克时，因为这会让你在增肌方面更具优势，结合抗阻训练促进肌肉蛋白质合成，而且正如你提到的，它更具饱腹感，还有一点产热效应。

Going above the 1.6 in this scenario seems to be key as well when you're getting up to that 2.2 grams per kilogram body weight per day because it does give you a little bit more edge over gaining muscle, muscle protein synthesis in combination with resistance training, as well as it's like you mentioned, it's satiating, little bit thermogenic.

我不确定这是否是主要机制，但我认为主要机制就是你确实想要防止这种分解代谢。

I don't know if that's the big mechanism here, but I think the big mechanism here is just you're really wanting to prevent this catabolism.

所以我认为这是另一个重要的观点。

So I think that's just another important point.

因为有很多人都在进行间歇性断食和时间限制性饮食。

Because there are a lot of people that do intermittent fasting, time restricted eating.

他们正尝试进行身体重组，增加肌肉，减少脂肪。

They're trying to do body recomp, gain muscle, lose fat.

我认为很多人对此很感兴趣。

I think a lot people are interested in that.

我人生中有那么一段时期，整整一年里，我制定了非常专注的目标：减重增肌。

There was one period in my life when over the course of a year, I made a very dedicated goal to lose body weight and gain muscle.

所以我想看看，这到底能不能实现？

So I wanted to see like, could this be done?

确实需要相当程度的间歇性禁食，或者更准确地说，是限时进食。

And it did require quite a bit of intermittent fasting or time restricted eating, I suppose, to be more accurate.

但需要关注蛋白质摄入的程度简直令人难以置信。

But the amount of attention I had to pay to protein intake was pretty incredible.

而我采取的做法看似矛盾——我并非因为相信禁食状态能带来益处才进行间歇性禁食。

And what I did that seems counterintuitive because I wasn't intermittent fasting because I believed that a fasted state was producing some benefit.

有些人会想：'如果我不吃早餐，就能启动细胞自噬之类的机制'

There are some people who think that, Well, if I don't eat breakfast, I'm kicking off some autophagy or something.

不不

No, no.

这纯粹是热量限制的策略

It was purely a caloric restriction ploy.

因此，我的禁食窗口期并不妨碍摄入液态蛋白质。

So, my fasting window did not prevent consuming liquid protein.

换句话说，虽然我不吃早餐或午餐（确实如此），每天只吃一顿晚餐，但在非进食时段我仍会饮用蛋白质奶昔。

In other words, if I wasn't eating breakfast or lunch, which I wasn't, I was only having a meal a day, which was dinner, but I would still consume protein shakes outside of those windows.

否则我永远无法达到蛋白质摄入目标。

Otherwise, I could never hit the protein target.

所以，我处于热量赤字但氨基酸过剩的状态。

So, I was in a caloric deficit but in amino acid excess.

再说一次，通过液态蛋白质很容易实现这点，因为你基本上只摄入乳清蛋白，获得的热量相对较少。

And again, you can actually do that with liquid protein pretty easily because basically all you're getting is getting relatively few calories because you're just consuming whey protein.

你喝这么多奶昔有没有出现肠胃问题？

Did you have any like GI problems consuming so many shakes?

没有，但我做了很多尝试。

No, but I did a lot of experimentation.

最终我选定了一个品牌。

So ultimately, I settled on a brand.

我现在一时想不起它的名字了。

I'm blanking on the name of it now.

我跟这些人没有任何关系，但我现在想不起他们的名字了。

I have no affiliation with these guys and I'm blanking on their name.

是叫Ascent吗？

Ascent, maybe?

这个名字有印象吗？

Does that ring a bell?

我真的很喜欢他们。

I really like them.

我要再次推荐他们，因为这是我唯一发现可以直接用水冲调且不会结块的蛋白粉。

Again, I'll give them a shout out because one, it was the only protein I found I could mix directly in water and not have it be lumpy.

我甚至不需要搅拌机。

I didn't even need a blender.

这听起来可能有点傻，但每天要洗两次搅拌机有时真的会让我懒得做奶昔。

This sounds silly but the hassle of me having to like wash a blender twice a day was sometimes an impediment to not making a shake.

所以只要把平时一勺或两勺的蛋白粉放进玻璃杯加水，用叉子搅拌就能直接喝，而且完全没有结块。

So just to be able to put the scoop or two scoops I would usually put into a glass with water and mix it with a fork and actually drink it and have it be totally fine and not lumpy.

我不知道他们怎么做到的，但这太神奇了。

I don't know how they do this but it was amazing.

实际喝起来味道也不错。

It actually tasted fine.

我不太喜欢甜饮料，但这个甜度刚好。

I don't like sweet drinks that much but it was not too sweet.

而且完全没有肠胃不适的问题。

And absolutely no GI issues at all.

而有些纯蛋清蛋白粉，我就很不喜欢它们对肠胃的刺激感。

Whereas sometimes the pure egg proteins, I didn't like the feeling on my gut.

总之不知为何这个对我特别有效。

So for whatever reason that worked for me.

但说到你的观点，如果要用那种方式重新计算营养摄入，确实又是另一个层次的挑战了。

But to your point, it's another level of challenge if you're trying to re comp in that way.

或者使用GLP-1受体激动剂的人，对吧？

Or people on GLP-one, right, receptor agonist.

对吧？

Right?

我不知道正常吃饭和喝蛋白奶昔的难度差异有多大。

And I don't know how difficult it is to eat a meal versus like take a protein shake.

你几乎全天都处于饱腹状态。

You're satiated pretty much all the time.

你根本没有真正的食欲。

You don't have a real appetite.

而且消化速度也变慢了。

But also digestion is slowed.

所以如果你要摄入更多蛋白质，我不清楚这会产生什么影响。

So if you're like consuming more protein, I don't know how that all affects.

我们在患者身上经常被问到这个问题。

We've seen in our patients I get asked this all the time.

我估计我们15%到20%的患者在使用替尔泽肽。

I would say fifteen to twenty percent of our patients are on tirzepatide.

和五年前我们刚开始给患者使用司美格鲁肽时不同，那时我们眼睁睁看着这些人的肌肉流失。

And unlike five years ago when we started using semaglutide in patients and were just watching muscle fall off these people.

坦白说，五年前我的观点是：我对这些药物持保留态度。

And frankly, my point of view five years ago was, I don't know about these drugs.

我认为对某些人确实有益，但潜在风险也很大。

I think there's some benefit in some people but I think there's a lot of downside.

而如今我认为几乎所有人都能安全使用这些药物。

I today think that virtually anybody can use these drugs safely.

这里说的安全，不仅仅是指字面上的安全。

By safely, I don't just mean in the obvious sense of the word.

还包括对长期肌肉健康的安全性。

I mean safely for long term muscle health as well.

但这需要极其审慎的关注。

But it requires a ton of deliberate attention.

所以，我很高兴你提到这一点。

So, I'm glad you brought it up.

这正是你需要使用易消化蛋白质来源的人群。

This is exactly the group of people who you wanna be using easy to digest protein sources.

如果你在使用替尔泽肽，你其实不会想吃牛排。

And if you're on tirzepatide, you don't really want a steak.

你也不会想要一大块鸡胸肉。

You don't really want to have a big chicken breast.

你可能连煎蛋卷都不想吃。

You might not want to even have an omelet.

但如果我们必须确保你达到1.6克的目标，你可能需要喝大量液体奶昔。

But if we have to make sure you're hitting that 1.6, you might be doing a bunch of liquid shakes.

是的，我们可以坐在这里嘲笑加工食品，说人们不得不靠喝奶昔为生有多恶心。

And yeah, we can sit here and poo poo processed food and say, how disgusting is it that people have to resort to eating shakes?

好吧，就这样。

Okay, fine.

但如果替代方案是他们无法获取足够蛋白质，而他们正在服用导致厌食的药物，我们也清楚其负面影响。

But if the alternative is they're not getting enough protein and they're on a drug that is making them anorexic, we also know the downside of that.

嗯，答案很明显。

Well, answer is clear.

对吧？

Right?

你肯定不想失去肌肉量。

You don't wanna be losing muscle mass for sure.

我的观点是我们会在前后进行DEXA扫描。

My point is we do DEXA before and after.

我们没有看到像采用V1方案时出现的那种肌肉流失情况。

We're not seeing the type of muscle loss we saw with our V1 approach to this.

用的是哪种剂量？

What kind of dose?

他们是在用较高剂量吗？

Are they on like a higher dose?

不。

No.

我是说，替尔泽肽的起始剂量是2.5毫克。

I mean, think for tirzepatide starts at two point five.

有些人在这个剂量下就能获得足够的疗效。

Some people are getting enough benefit there.

我认为我们的治疗理念是：稳扎稳打才能赢得比赛。

I mean, other thing that I think our approach has been is that slow and steady wins the race.

我们确实看到过一些案例数据。

So, we've seen anecdotally some data.

3据我听到的其他案例和我们观察到的，这些药物用用停停可能不是好主意。

I've heard from others and we've seen it as well that yo yoing on and off these drugs is probably a bad idea.

所以我总是告诉患者：与其让你用10毫克剂量快速减重又反弹，不如保持2.5毫克剂量直到出现更好的新药——我宁愿选择这种方案。

So, I always tell a patient, look, I'd probably rather you were on two point five milligrams until there was a new drug that we felt was even better than you're on ten milligrams, you lose a ton of weight, you come off, you gain, you go back on, you lose.

这种反复折腾的用药方式可能很糟糕。

The idea of being on a saw is probably a bad idea.

我认为数据显示，大约十毫克剂量时你已获得大部分疗效。

I think the data suggest you're getting most of the value by about ten milligrams.

所以当你增加到十二点五和十五毫克这两种最高剂量时，虽然仍有效果，

So, once you go to twelve point five and fifteen, which are the two highest doses, you're still getting a benefit.

但就像大多数药物一样，最低剂量时就能获得主要疗效。

But it's like most drugs, you're getting most of the benefit at the lowest dose.

因此五到七点五毫克的替尔泽肽可能是疗效最显著的剂量区间。

So five to seven point five milligrams of tirzepatide is probably where you're getting the majority of the benefit.

我宁愿患者循序渐进地用药，而不是追求最快最大幅度的减重效果。

I'd much rather a patient be sort of slow and steady on it as opposed to try to go for maximum and rapid weight loss.

你对那些关于心脏问题或骨质流失的数据怎么看？

What do you think about some of that data on like heart issues or bone loss?

这些会让你感到担忧吗？

Does that concern you at all?

当然。

Sure.

我认为所有这些都需要关注。

I think it all does.

我是说，我觉得所有这些情况都必须引起重视。

Mean, I think all of this stuff has to be paid attention to.

而我认为问题又回到了这其中有多少是由于训练导致的？

And I think the question again comes back to how much of that is occurring due to training?

有多少是因为氨基酸摄入减少和训练缺失造成的？

How much of that is happening due to the loss of amino acid intake and the loss of training.

还有神经精神方面的影响，那是另一个值得关注的点。

Or the neuropsychiatric, that's another one on the eyes.

我感兴趣的是，我们在这么多不同组织上都有这些GLP-1受体。

What I'm interested in is we have these GLP-one receptors like on so many different tissues.

从系统层面看，它究竟如何产生益处？

Systemically, like how is it beneficial?

还是说它并无益处？

Is it not beneficial?

我不确定我们是否真的了解。

I don't know that we really know.

我们掌握的数据显示确实存在积极效果。

We have data where there's obviously positive effects.

可以看到服用这类GLP-1受体激动剂的人群阿尔茨海默病发病率有所降低。

You see like reduced Alzheimer's disease incidence with people taking these GLP-one receptor agonists.

但这其中有多少是减重带来的效果呢？

But how much of that is due to like weight loss?

我们对此进行了大量研究——有趣的是，我们最近还就此做过一期播客，专门探讨了这个问题：GLP-1受体激动剂最终是否会被证明具有抗衰老保护作用？

We've looked into this a lot because it's funny, we did a podcast on this somewhat recently where I went through this particular question, which is, will GLP-one receptor agonists ultimately prove to be gero protective?

我提出了一个非常独特的定义标准——即与减重效果无关的抗衰老保护。

I came up with a very obscure way to define that, which is independent of weight loss.

显然从宏观层面看，它们确实具有抗衰老作用——因为当应用于患有2型糖尿病和严重肥胖的人群时，通过纠正代谢功能障碍，寿命将会延长。

Because obviously, at the macro level, they're going to be gero protective because if you apply them to people with type two diabetes and significant obesity and you correct the metabolic dysfunction, you're going to live longer.

因此从这个角度来看，它是一种抗衰老保护剂。

So, by that regard, it's a gero protective agent.

但真正的问题是，如果你对一个体重正常、没有二型糖尿病但可能有较高阿尔茨海默病风险的人进行微量给药。

But the real question is, if you take a person who is of normal weight, who does not have type two diabetes, but maybe has a higher risk for Alzheimer's disease, and you microdose them.

也就是说，每天给他们2.5毫克的剂量——顺便说一句，我们确实在一些没有肥胖但患有罕见代谢疾病的患者中这样做。

So, you're giving them two point five milligrams per day, which by the way, we are doing in some patients for obscure metabolic condition without obesity.

所以我们有些糖尿病患者本身已经处于极低体重状态。

So, we have patients who have diabetes but are already at very low body weight.

实际上我们诊所里就有两位这样的患者。

We have two patients actually in our practice in this regard.

在与播客前嘉宾拉尔夫·迪弗兰科进行了大量详细反复讨论后，我们意识到这些患者用药方案中至少有一个组成部分将是GLP-1受体激动剂。

After lots of detailed back and forth machination with Ralph DiFranco, who's a previous guest on the podcast, we sort of realized that at least one component of the drug regimen for these patients was going to be a GLP-one agonist.

当时给BMI指数23的人使用替尔泽肽看起来非常反直觉。

Now, it seemed very counterintuitive to give tirzepatide to people who have a BMI of twenty three.

但我们成功做到了不让他们减重。

But we've been able to do it without them losing weight.

再次强调，通过非常谨慎的营养策略，这对他们糖尿病的影响是深远的。

So again, very careful strategies around nutrition and the effect on their diabetes is profound.

他们的代谢状况看起来更健康了。

They're looking more metabolically healthy.

天啊。

Oh my god.

这些病例非常有趣，也许在某个时候（当然是以匿名方式）会值得讨论——当你遇到OGTT结果完全无法辨认的情况时。

These are really interesting cases that maybe at some point, obviously in a de identified way, would be interesting to talk about where you have OGTTs that are unrecognizable.

你根本无法相信一个外表看起来正常的人，其代谢功能紊乱的程度会如此严重。

You simply cannot believe the degree of metabolic dysfunction in a person who otherwise looks the way they look.

尤其有一个病例，情况非常令人困惑，即使我们做了所有基因检测，也完全找不到答案。

And in one case in particular, it was so confusing that even all the genetic testing we did, we simply couldn't figure out an answer for this.

我们无法理解在没有正式 1 型糖尿病正式诊断的情况下，β 细胞疲劳是从何而来的●●●来的。

We couldn't understand where the beta cell fatigue was coming from absent a formal diagnosis of type one diabetes.

在使用 2.5 毫克替尔泽肽治疗三个月内，这位患者的 OGTT 检测结果已几乎恢复正常，我预计大约六个月后就会完全正常。

And within three months of being on two point five milligrams of tirzepatide, this individual's OGTT had almost normalized and I suspect by about six months it will.

这太神奇了。

That's fascinating.

而且我们做到了这一点，且没有任何体重减轻。

And we've managed to do this without any weight loss.

所以，对我来说这是个有趣的问题。

So, this to me is the interesting question.

当你观察一些阿尔茨海默病的生物标志物时，它们正在显著改善，这就引出了一个问题：对于高风险个体，这应该成为治疗方案的一部分吗？

Which is when you look at some of the Alzheimer's biomarkers, which are improving, improving significantly, it begs the question, should this be part of the playbook for an individual who's at high risk?

特别是考虑到我们现在——我认为——真正理解了如何确保人们不会减重、不会流失肌肉量，因此我推测也不会损失骨密度和其他所有这些重要的指标。

Especially given that we now, I think, really understand how to make sure people don't lose weight and don't lose lean mass And therefore, I suspect don't lose bone density and all these other things that matter.

就像你说的，如果你在进行这种微剂量治疗，可能不会感到那么饱足。

Or like you said, if you're doing this microdose, maybe you're not gonna be as satiated.

比如，你还是会有些许食欲，因为剂量实在太低了。

Like, you'll still have somewhat of an appetite because you're on such a low dose.

也许会产生一点效果。

Maybe you're gonna do have a little bit of an effect.

我们还观察到一些其他奇怪的现象，虽然只是个案。

We've also seen some other weird things anecdotally.

患者告诉我们，当他们将药物注射到腹部脂肪层（皮下脂肪）时，其抑制食欲的效果比注射到腿部或臀部更明显。

Patients have told us that when they inject in the abdomen, the fat, the sub Q fat of the abdomen, basically the anorexic effects are greater than if you inject in the leg or butt.

我们对此进行了研究，有一些机制性数据表明，腹部注射时可能会增强迷走神经张力。

And we looked into this and there was some mechanistic data to suggest that maybe you're getting more vagal tone when you inject in the abdomen.

再次声明，我并不知道这些说法是否准确。

Again, I just don't know if any of these things are correct.

这些都需要进一步研究。

They would need to be studied.

但同样，这将是十分重要的数据点。

But again, that would be a very important piece of data.

如果能找到某个注射部位可以最小化药物的厌食效应，对某些人来说这会是优势而非缺陷。

If there's a location you can inject this where you minimize the anorexic effect of the drug again, for some people that would be a feature, not a bug.

对另一些人来说则可能是缺陷而非优势。

For some people that would be a bug as opposed to a feature.

所以你必须学会如何正确使用这个工具。

So you have to understand how to use the tool.

嗯。

Yeah.

这让我想起我们应该指出的一个问题。

This just reminded me of something that we should have pointed out.

谈到蛋白质需求，每公斤体重需要多少克，我认为这很重要，就像我们刚才讨论的肥胖和超重人群。

Talking about the protein requirements, grams per kilogram body weight, I do think it's important like, we were just talking about obese people overweight.

我很高兴你提到这点。

I'm glad you brought this up.

对。

Yeah.

没错。

Exactly.

就像大多数人不会去做DEXA扫描来了解自己的瘦体重。

Where it's like, most people aren't gonna do a DEXA scan to see what their lean body mass is.

但归根结底，我认为——而且我和多位专家（布拉德·舍恩菲尔德、菲利普斯等）交流过——他们都同意，如果你是超重或肥胖人群，就不应该按实际体重来计算蛋白质需求，那样需求量会高得离谱。

But ultimately, I think, know, and I've talked to a variety of experts, Brad Schoenfeld, two Phillips, they agree that really, if you're someone that's overweight or obese, you shouldn't be calculating it based on your actual weight because your protein require way too high.

这更像是你的目标体重。

It's more like your target weight.

如果你能实际测量你的瘦体重，那会更好。

If you empirically could measure your lean body mass, that would be better.

不过，是的，我只是想指出这一点。

But, yeah, I just wanted to point that out.

嗯。

Yep.

我很高兴你这么做了。

And I'm glad you did.

没错。

So that's right.

对大多数人来说，这可能不是什么大问题。

For most people, probably not much of an issue.

但如果你现在体重300磅，而你的理想体重是220磅，你不需要DEXA扫描也能明白这一点。

But if you're at three hundred pounds right now and your ideal body weight is two twenty, you don't need a DEXA to figure that out.

DEXA扫描确实有帮助，但大多数体重三百磅的人会想起，天啊，高中毕业时我才二百二十磅，那是我理想的体重。

A DEXA can help but most people who are three hundred pounds remember, gosh, at the end of high school, I was two twenty, that was my good weight.

或者也许，你知道，高中毕业时我两百磅，那会儿的牛仔裤可能再也穿不下了。

Or maybe, you know, the end of high school, I was two hundred pounds, which is I'll probably never get back into those jeans again.

但到我大学一年级结束时，体重涨到了二百二十磅。

But by the end of my freshman year of college, I was two twenty.

那对我来说算是个不错的体重，之后情况就开始走下坡路了。

That was kind of a good weight for me and then it's just kind of gone downhill from there.

你之前有过这个骨科问题。

You had this orthopedic.

这就是你体重达到三百磅的故事。

There's the story of how you got to be three hundred pounds.

是的。

Yeah.

大多数人能想明白。

Most people can figure out.

对。

Right.

二百二十磅可能是我的目标体重，这也是我应该追求的。

Two twenty is probably my goal weight and that's what I should be targeting.

是的。

Yeah.

所以你提出了一个很好的观点，就是我们如何调和以下矛盾？

So you made a great point, which is how do we reconcile the following?

热量限制作为一种干预手段，作为抗衰老干预措施，是文献记载中最古老的方法。

So caloric restriction as an intervention, as a Giro protective intervention is the oldest one in the book.

据我所知，在非基因干预手段中，从长期效果来看，没有哪种干预措施能在实验动物身上产生如此一致的结果。

I'm not really aware of an intervention where a non genetic intervention that has, from a longer standing perspective, produced a more consistent outcome in terms of laboratory animals.

当你限制它们的热量摄入时，它们的寿命就会延长。

Where you restrict them of calories and they're gonna live longer.

所以，据我所知，只有两种干预措施在所有四种生物模型（酵母、蠕虫、果蝇和哺乳动物啮齿类）中都延长了寿命。

So, again, to my knowledge, there are only two interventions that have extended life across all four models of organisms from yeast, worms, flies and mammals, rodents.

那就是热量限制和雷帕霉素。

And that is caloric restriction and rapamycin.

它们有一个共同点。

And they have something in common.

就是两者都会导致mTOR的下调。

Which is they both result in the down regulation of mTOR.

我们刚才提到的亮氨酸，是激活mTOR最重要的氨基酸。

So, we also know that an amino acid you just mentioned a moment ago called leucine is the single most important of all the amino acids at turning up mTOR.

那么我们该如何理解蛋白质似乎对你有益，但mTOR的下降似乎也对你有益，至少在另一个方面？

So how can we reconcile the idea that protein seems to be good for you but mTOR going down seems to be good for you, at least in another way?

嗯，首先

Well, for one

我是在开玩笑，因为你知道我知道这个问题的答案。

I'm being very facetious because you know I know the answer to this question.

天哪，我们该从哪里开始呢？

And it's like, oh gosh, where do we start?

因为我们就别管线虫和果蝇那些研究了，谁在乎呢？

Because let's ignore the worm and the fly and all that because who cares?

我是说，就连啮齿类动物的研究结果都很难直接套用。

I mean, even the rodents, it's a stretch.

你知道还有什么会激活mTOR吗？

You know what else turns on mTOR?

运动。

Exercise.

体育活动，机械力会激活我们肌肉中的mTOR。

Physical activity, mechanical force turns it on in our muscle.

我们知道运动是对健康最有益的事情之一。

And we know exercise is, like, one of the best things that we can do for our health.

我认为在这里，为了简化理解，最好的思考方式是：你希望mTOR在你的骨骼肌中保持活跃。

I think here, I think for simplicity, the best way to think about this is that you want mTOR active in your skeletal muscle.

你希望它在你的骨骼肌中保持活跃。

You want it active in your skeletal muscle.

你并不总是希望它在全身系统中保持活跃。

You don't necessarily always want it active systemically.

但如果你在锻炼、四处活动，并摄入蛋白质，它就会流向你的肌肉。

But if you are exercising, if you're moving around, and you're taking your protein, it's going to your muscle.

这一点我们确切知道。

We know that for a fact.

我之前谈到过合成代谢抵抗，以及运动如何通过增加亮氨酸转运蛋白的表达来对抗这种情况。

I talked about anabolic resistance and how exercise can counter that while it's increasing the leucine transporter, the expression of leucine transporter.

它促使亮氨酸和其他支链氨基酸进入骨骼肌。

It's causing leucine and other branched chain amino acids to go up into skeletal muscle.

多项人体研究已经证实了这一点。

Multiple human studies have shown this.

这些都是示踪研究，数据完美，无可争议。

These are tracer studies, beautiful data, no argument.

运动促使亮氨酸和其他支链氨基酸被骨骼肌吸收——这正是你希望它们去的地方，从而激活mTOR，增加肌肉蛋白质合成。

Exercise causes leucine and other branched chain amino acids to be taken up into skeletal muscle where you want it to be so that it activates mTOR, increases muscle protein synthesis.

关于mTOR的失活问题，无论是通过蛋白质限制还是雷帕霉素，这个话题足够做长达数小时的播客来讨论所有细微数据，因为其中存在性别差异、啮齿动物差异等各种不同情况。

When it comes to deactivating mTOR, whether that's through protein restriction or rapamycin, that would be like an hours long podcast talking about all the nuance data there because there's all sorts of differences with sex, differences in rodents.

你了解所有这些数据。

You're aware of all this data.

关于蛋白质限制，我最重要的观点是，让我们先讨论一点。

My biggest thing here with the protein restriction, let's talk about one.

我确实在研究生院花了六年时间用小鼠做实验。

I did spent six years in grad school working with mice.

我做过大量动物研究。

I did a lot of animal studies.

这些老鼠被关在小笼子里。

These mice are in a small cage.

它们没有身体活动。

They are not physically active.

它们不会到处跑动。

They are not running around.

我是说，它们会稍微动一动。

I mean, they move a little bit.

它们没有受到威胁。

They're not under threat.

它们没有受到威胁。

They're not under threat.

它们是随意进食的。

They're being fed ad libidum.

它们想吃多少蛋白质就吃多少。

They're just being fed as much protein as they want.

完全恒温的环境。

Perfectly thermoregulated.

它们不会接触到流感或新冠病毒等任何会让它们病倒几周的病毒。 000。

They're not being exposed to influenza or COVID, whatever viruses, anything that's going to take them out for a period of a couple of weeks.

它们处于无菌环境中。

They're in a sterile environment.

它们很快乐。

They're happy.

它们很快乐，仅此而已。

They're happy and that's it.

人类不是老鼠。

People are not mice.

我们之前讨论过，随着年龄增长，我们会暴露在传染病中。

We talked about earlier, as we get older, we're being exposed to infectious diseases.

这些事情会让我们几周内无法活动。

Things are gonna make us immobile for a period of weeks.

这对我们来说是毁灭性的，特别是当这些情况累积起来，今年发生一次，明年又发生一次，你就会逐渐失去肌肉量。

And that is devastating to us, especially when you add them up, and they happen this year, and then the next year it happens again, and then you're just losing that muscle mass.

然后你就达到了残疾临界点。

And then you reach that disability threshold.

你提到了卢克·范·伦讨论过这些曲线。

You talked about Luke Van Lune talking about those curves.

这非常明显。

It's very clear.

我是说，你可以看到数据中有一个残疾阈值。

I mean, you can see the data where there's a disability threshold.

当你经历足够多的这些分解代谢危机事件——比如因为手术或流感等原因导致一段时间无法活动时。

You get enough of these catabolic crisis events where you're just immobile for a certain period of time because you've had a surgery or you've had the flu or whatever has kept you inactive.

这些老鼠不会遇到这种情况。

That doesn't happen to these mice.

因此蛋白质对人类更为重要，因为我们显然需要维持肌肉量，并且需要尽早储备。

So protein is much more important to humans because we, of course, need that muscle mass and we need to bank it early.

这一点我们已经明确了。

We've established that.

我认为这里一个非常重要的区别是：我们不能仅仅看老鼠的实验数据就断定限制蛋白质摄入能让它们活得更久且状态良好。

And I think that's a really important difference here is that we can't just look at the data in mice and go, Oh, you can restrict them from protein and they live longer and they're fine.

因为它们不会经历这些分解代谢危机。

Well, they're not going through these catabolic crises.

它们不会经历这些长时间不活动、导致肌肉大量流失的阶段，不会达到残疾阈值，情况完全不同。

They're not going through these points of not moving for a period of time for like losing all this muscle mass, then not happening and they reach this disability threshold and then it's very different.

所以我认为这是首要指出的重要区别。

So I think that's first and foremost important to point out.

第二点是，如果我们讨论蛋白质摄入量，我想我们都认同最理想的情况不是让一个久坐不动的人随心所欲地摄入蛋白质。

The second thing is is that if we're talking about protein intake, I think that you and I agree the optimal scenario here isn't a sedentary person just sitting there eating as much protein as they want.

不是这样的。

No.

他们需要运动，保持身体活跃。

They need to be moving, physically active.

这才是关键所在。

That's the whole point.

你通过增加蛋白质摄入来支持身体活动。

You're supporting your physical activity by increasing your protein intake.

因此在这种情况下，激活mTOR的氨基酸会流向骨骼肌。

And so in that scenario, again, the amino acids that are activating mTOR are going to skeletal muscle.

这已经被证实了。

Like that's been shown.

亮氨酸正在进入骨骼肌。

Leucine is going into skeletal muscle.

所以谁在乎你是否摄入更多

So who cares if you're taking in more

我认为这是个非常重要的观点，Rhonda，我甚至想更进一步说，如果你让我为活跃人群制定最佳营养策略，再为久坐人群制定最佳营养策略，两者会大不相同。

I think that's such an important point, Rhonda, I would even go one step further, which is if you told me come up with the optimal nutrition strategy for the individual who is active and then come up with the optimal nutrition strategy for a person who is going to be sedentary, they would be very different.

我会尝试说服那个久坐的人改变习惯。

I'm going to try to talk that sedentary person into not being sedentary.

但如果最后我做不到，如果那个人说，我什么都不想做，只想坐在电脑前。

But if at the end of the day, I can't, if that individual says, I don't want to do anything, I just want to sit in front of my computer.

你知道吗？

You know what?

可能适当限制热量摄入是合理的，因为我无法通过活动来解决你的代谢问题。

It probably makes sense to be a little bit caloric restricted because I can't solve your metabolic challenge through activity.

但如果我至少能通过营养限制来解决呢？

But what if I could at least solve it through nutrition restriction?

再次强调，我认为问题在于人们无法理解这两种状态截然不同。

Again, think it's the inability of people to understand that those are very different states.

你不能用同样的方式对待这两种人。

You cannot treat those two people the same way.

没错。

Right.

瓦尔特·隆戈等人多年前发表过一项研究。

There was a study by Valter Longo, of all people, like years ago, came out.

那是一项大型队列研究，比较了植物性与肉类来源的膳食蛋白质摄入。

It was a large cohort study looking at dietary protein intake from vegetable versus meat sources.

我们都知道肉类来源含有更高水平的必需氨基酸，比如亮氨酸。

And we all know that meat sources have higher levels of essential amino acids like leucine.

研究考察了全因死亡率，并再次验证了你从其他研究中听过无数次的结论：素食者的全因死亡率确实低于肉食者。

All cause mortality was looked at and the same statement that you've heard millions of times from other studies about, Okay, vegans have a lower all cause mortality than meat eaters.

结果发现，当你真正开始分析数据并校正诸多混杂因素后，那些保持运动、不肥胖或超重、不吸烟、不过量饮酒的肉食者，

Well, turns out when you actually start to analyze the data and correct for a lot of confounding factors, meat eaters that were physically active, were not obese or overweight, didn't smoke, didn't drink excessive alcohol.

换句话说，他们并不具备所有这些不健康的生活方式因素。

So in other words, they didn't have all these unhealthy lifestyle factors.

他们的死亡率与素食者相同。

They had the same mortality rate as the vegans.

所以我认为这也是个很好的观点，就像...好吧。

So I think that also is a good point here where it's like, okay.

如果你是个久坐不动还吸烟的人，或者有其他不健康的生活方式因素，也许你不需要过分纠结蛋白质摄入。

If you're gonna be a sedentary person that's smoking and if if you have unhealthy lifestyle factors, maybe you don't need to be so obsessed.

你当然要确保至少获得最低限度的蛋白质，因为你不希望处于缺乏状态。但如果你整天坐着、吸烟、超重却不对这些蛋白质做任何利用，就没必要持续激活mTOR通路。

You definitely wanna make sure you're at least getting the minimal amount of protein because you don't wanna be in the deficit, But you don't wanna necessarily just be constantly activating mTOR if you're just gonna sit around and smoke and be overweight and not do anything with that protein.

是啊。

Yeah.

我认为这场讨论中缺失的另一关键点是——这正是我觉得炎症可以作为一个绝佳类比的地方。

And the other thing I think that is missing from this discussion, this is where I think inflammation serves as a great analogy.

我认为大多数人表面上都明白，炎症系统持续处于开启状态是不好的。

So I think most people on the surface understand that a constant on state of the inflammatory system would be bad.

但当然，如果你完全没有炎症反应，那同样也不好。

But of course, if you had no inflammatory response, that would be also bad.

所以，理想状态是当你需要炎症时才开启，否则就关闭。

So, the ideal state is inflammation when you need it, otherwise off.

需要时开启炎症反应，不需要时关闭。

Inflammation when you need it, otherwise off.

我认为这可能是正确的思考方式，即我们希望mTOR在需要工作时开启，在不需要时保持相对静默。

And I think that's probably the right way to think about this, which is we want mTOR on when it has a job to do and we want it relatively silent when we don't.

而且我认为如果雷帕霉素具有抗衰老保护作用（我说的'如果'是指对人类而言）。

And I think if rapamycin is gero protective, and when I say if, I mean in humans.

我认为它在大多数物种中都具有明确的保护作用。

I think it's unambiguously protective across most species.

但我们仍然不知道目标物种是否能从这种药物中受益，顺便说一句，我们可能永远都不会知道。

But we still don't know if the species of interest is going to benefit from this drug and we may never by the way.