Journal Club with Dr. Peter Attia | Metformin for Longevity & The Power of Belief Effects
Andrew Huberman:
安德鲁·休伯曼：
Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life.
欢迎来到休伯曼实验室播客，我们在这里讨论科学和基于科学的日常生活工具。
I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine.
我是安德鲁·胡伯曼，斯坦福大学医学院神经生物学和眼科教授。
Today marks the first journal club episode between myself and Dr. Peter Attia.
今天是我和彼得·阿提亚博士之间的第一场日记俱乐部活动。
For any of you that are not familiar with Dr. Peter Attia, he is a medical doctor, an MD, who is an expert in all aspects of health and lifespan.
对于不熟悉 Peter Attia 博士的人来说，他是一名医学博士、医学博士，是健康和寿命各个方面的专家。
He is the author of a best-selling book entitled "Outlive," which is a phenomenal resource on all things health span and lifespan, and he is the host of the very popular podcast, "The Drive," where he interviews various experts in all domains of medicine and scientists as well.
他是一本名为《Outlive》的畅销书的作者，该书是关于健康和寿命方面的非凡资源，他也是非常受欢迎的播客“The Drive”的主持人，在播客中他还采访了医学各个领域的专家和科学家。
Today, Peter and I hold our first online collaborative journal club.
今天，彼得和我举办了我们的第一个在线协作期刊俱乐部。
For those of you that aren't familiar with what a journal club is, a journal club is a common practice in graduate school and/or medical school, whereby students get together to discuss one or two papers, to critique those papers, and to really compare their own conclusions of those papers with the conclusions of the authors and to highlight any key takeaways.
对于那些不熟悉什么是期刊俱乐部的人来说，期刊俱乐部是研究生院和/或医学院的常见做法，学生们聚在一起讨论一两篇论文，批评这些论文，并将自己对这些论文的结论与作者的结论进行真正的比较，并突出任何关键要点。
Peter and I have been wanting to do a journal club together for a very long time, and we decided to do that journal club and to record it for you.
彼得和我长期以来一直想一起举办一个日记俱乐部，我们决定举办那个日记俱乐部并为您录制它。
So today you will be sitting in on the first Huberman Attia Journal Club.
所以今天您将参加第一届胡伯曼·阿蒂亚日记俱乐部。
By the way, it could just have easily been called the Attia Huberman Journal Club.
顺便说一句，它可以很容易地被称为“阿蒂亚·胡伯曼期刊俱乐部”。
And we will discuss two papers.
我们将讨论两篇论文。
First, Peter is going to discuss a paper on metformin, which is a drug that many people are interested in for its potential role in longevity.
首先，彼得将讨论一篇关于二甲双胍的论文，这种药物因其在长寿方面的潜在作用而引起许多人的兴趣。
I want to highlight potential there.
我想强调那里的潜力。
He's going to compare that paper to previous findings on metformin, and by the end of that discussion, he will advise as to whether or not he himself would take metformin and whether or not other people might be well-advised or ill-advised to take metformin based on the data in that paper and at this time.
他将将该论文与之前关于二甲双胍的研究结果进行比较，并在讨论结束时，他将根据该论文中的数据和此时的数据，就他本人是否服用二甲双胍以及其他人服用二甲双胍是否明智提出建议。
Then I present a paper which is about the placebo effect.
然后我提出了一篇关于安慰剂效应的论文。
I have to imagine that most of you have heard of the placebo effect, but what's interesting about the paper that we discuss today is that it shows that the placebo effect can actually follow a dose response.
我想你们大多数人都听说过安慰剂效应，但我们今天讨论的这篇论文的有趣之处在于，它表明安慰剂效应实际上可以遵循剂量反应。
So it's not just all or none.
所以这不仅仅是全有或全无的问题。
It actually is the case that you can scale the degree of placebo effect depending on whether or not you're thinking you're taking low doses, moderate doses, or high doses of a particular drug.
事实上，你可以根据你是否认为自己正在服用低剂量、中等剂量或高剂量的特定药物来衡量安慰剂效应的程度。
And the particular drug that's discussed in the paper that I cover is nicotine.
我所报道的论文中讨论的特定药物是尼古丁。
So for those of you that are interested in cognitive enhancement by way of pharmacology, or frankly for people who are simply interested in how our beliefs can shape our physiology, I think you'll find that discussion to be very interesting.
因此，对于那些对通过药理学增强认知能力感兴趣的人，或者坦率地说，对于那些只是对我们的信念如何塑造我们的生理学感兴趣的人，我认为您会发现这个讨论非常有趣。
So by the end of today's episode, you will not only have learned about two novel sets of findings, one in the realm of longevity as it relates to metformin, and another in the realm of neurobiology and placebos or placebo effects, but you will also learn how a journal club is conducted.
因此，在今天的节目结束时，您不仅会了解两组新颖的发现，一组是与二甲双胍相关的长寿领域，另一组是神经生物学和安慰剂或安慰剂效应领域，而且您还将了解期刊俱乐部是如何进行的。
I think you'll see in observing how we parse these papers and discuss them, even arguing in them at times, that what scientists and clinicians do is they take a look at the existing peer-reviewed research, and they look at that peer-reviewed research with a fresh eye, asking, "Does this paper really show what it claims to show or not?" And in some cases, the answer is yes, and in other cases, the answer is no. What I know is for certain is that by the end of today's episode, you will learn a lot of science, you'll learn a lot about health practices, some of which you may want to apply or avoid, and you'll learn a lot about how science and medicine is carried out.
我想你会发现，在观察我们如何解析这些论文并讨论它们，甚至有时在其中争论时，科学家和临床医生所做的是，他们审视现有的同行评审研究，他们以全新的眼光看待同行评审的研究，问：“这篇论文是否真的展示了它声称展示的内容？”在某些情况下，答案是肯定的，而在其他情况下，答案是否定的。我可以肯定的是，在今天的节目结束时，您将学到很多科学知识，您将学到很多有关健康实践的知识，其中一些您可能想要应用或避免，并且您将学到很多有关科学和医学如何进行的知识。
Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford.
在开始之前，我想强调一下，这个播客与我在斯坦福大学的教学和研究角色是分开的。
It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public.
然而，我的愿望和努力的一部分是向公众提供有关科学和科学相关工具的零成本消费者信息。
In keeping with that theme, I'd like to thank the sponsors of today's podcast.
为了与这个主题保持一致，我要感谢今天播客的赞助商。
And now for my journal club discussion with Dr. Peter Attia.
现在是我与 Peter Attia 博士进行期刊俱乐部讨论。
Peter, so good to have you here.
彼得，很高兴你能来到这里。
Dr. Peter Attia:
彼得·阿蒂亚博士：
So great to be here, my friend.
很高兴来到这里，我的朋友。
Andrew Huberman:
安德鲁·休伯曼：
This is something that you and I have been wanting to do for a while, and it's basically something that we do all the time, which is to peruse the literature and find papers that we are excited about for whatever reason.
这是你和我一直想做的事情，而且基本上是我们一直在做的事情，那就是仔细阅读文献并找到我们出于某种原因感到兴奋的论文。
And oftentimes that will lead to a text dialogue or a phone call or both.
通常这会导致文本对话或电话，或两者兼而有之。
But this time we've opted to try talking about these papers that we find particularly exciting in real-time for the first time as this podcast format.
但这一次我们选择尝试以这种播客形式实时讨论这些我们发现特别令人兴奋的论文。
First of all, so that people can get some sense of why we're so excited about these papers.
首先，让人们能够了解为什么我们对这些论文如此兴奋。
We do feel that people should know about these findings.
我们确实认为人们应该了解这些发现。
And second of all, that it's an opportunity for people to learn how to dissect information and think about the papers they hear about in the news, the papers they might download from PubMed if they're inclined.
其次，这是一个机会让人们学习如何剖析信息并思考他们在新闻中听到的论文，如果他们愿意的话，他们可以从 PubMed 下载论文。
And also just to start thinking like scientists and clinicians and get a better sense of what it looks like to pick through a paper, the good, the bad, and the ugly.
也只是为了开始像科学家和临床医生一样思考，更好地了解如何挑选一篇论文，好的、坏的和丑陋的。
So we're flying a little blind here, which is fun.
所以我们在这里有点盲目，这很有趣。
I'm definitely excited for all the above reasons.
由于上述所有原因，我绝对感到兴奋。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
You and I have been talking about this for some time and actually we used to run a journal club inside the practice where once a month, one person would just pick a paper and we would go through it in kind of a formal journal club presentation.
你和我已经讨论这个问题有一段时间了，实际上我们曾经在实践中经营过一个期刊俱乐部，每月一次，一个人会挑选一篇论文，我们会以正式的期刊俱乐部演示的形式进行浏览。
We'd gotten away from it for the last year just because we've been a little stretched thin.
去年我们摆脱了它只是因为我们有点捉襟见肘。
I think it's something we need to resume because it's a great way to learn, and it's a skill.
我认为这是我们需要恢复的事情，因为这是一种很好的学习方式，而且是一项技能。
People probably ask you all the time, because I know I get asked all the time, "Hey, what are the dos and don'ts of interpreting scientific papers?
人们可能一直在问你，因为我知道我一直被问到，“嘿，解释科学论文该做什么和不该做什么？
Is it enough to just read the abstract?"
只读摘要就够了吗？”
Andrew Huberman:
安德鲁·休伯曼：
No.
不。
Dr. Peter Attia:
彼得·阿蒂亚博士：
And usually the answer is, well, no. But the how-to is tougher, and I think the two papers we've chosen today illustrate two opposite ends of the spectrum.
通常答案是，不。但操作方法更难，我认为我们今天选择的两篇论文说明了这个范围的两个相反的极端。
You're going to obviously talk about something that we're going to probably get into the technical nature of the assays, the limitations, et cetera.
显然，您将讨论一些我们可能会涉及测定的技术性质、局限性等的问题。
And the paper ultimately I've chosen to present, although I apologize, I'm surprising you with this up until a few minutes ago, is actually a very straightforward, simple epidemiologic paper that I think has important significance.
我最终选择提交的论文实际上是一篇非常直接、简单的流行病学论文，尽管我很抱歉，但直到几分钟前我才让你们感到惊讶，我认为它具有重要意义。
I had originally gone down the rabbit hole on a ...
我最初是在……的时候掉进兔子洞的。
a much more nuanced paper about ATP binding cassettes in cholesterol absorption.
关于胆固醇吸收中 ATP 结合盒的更细致的论文。
But ultimately, I thought this one might be more interesting to a broader audience.
但最终，我认为这可能对更广泛的受众来说更有趣。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
By the way, I got to tell you a funny story.
顺便说一句，我要告诉你一个有趣的故事。
So I had a dream last night about you.
所以昨晚我做了一个关于你的梦。
And in this dream, you were obsessed with making this certain drink that was like your elixir, and it had all of these crazy ingredients in it.
在这个梦中，你痴迷于制作这种某种饮料，它就像你的灵丹妙药，里面含有所有这些疯狂的成分。
Andrew Huberman:
安德鲁·休伯曼：
Supplements.
补充品。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Tons of supplements in it.
里面有大量的补品。
But the one thing I remembered when I woke up, because I forgot most of them, I was really trying so hard to remember them.
但当我醒来时我记得一件事，因为我忘记了大部分，我真的很努力地记住它们。
One thing that you had in it was dew.
里面有一种东西就是露水。
You had to collect a certain amount of dew off the leaves every morning to put into this drink.
每天早上你必须从叶子上收集一定量的露水才能放入这种饮料中。
It was like, just-
就像，只是——
Andrew Huberman:
安德鲁·休伯曼：
It sounds like something that I would do.
这听起来像是我会做的事情。
Yeah
是啊
Dr. Peter Attia:
彼得·阿蒂亚博士：
...
...
But here's the best part.
但这是最好的部分。
You had a thermos of this stuff that had to be with you everywhere, and all of your clothing had to be tailored with a special pocket that you could put the thermos into so that you were never without the special Andrew drink.
你有一个这种东西的保温瓶，必须随身携带，你所有的衣服都必须定制一个特殊的口袋，你可以把保温瓶放进去，这样你就永远不会没有特殊的安德鲁饮料。
And again, you know how dreams, when you're having them, seem so logical and real, and then you wake up and you're like, "That doesn't even make sense.
再说一次，你知道，当你做梦时，它们看起来是如此合乎逻辑和真实，然后你醒来，你会想，“这甚至没有意义。
Why would he want the thermos in his shirt?
他为什么要把保温瓶放在衬衫里？
That would warm it up." But boy, it was a realistic dream, and there were lots of things in it, including dew.
这会让它变暖。”但是孩子，这是一个现实的梦，里面有很多东西，包括露水。
Special dew off the leaves every morning.
每天早上叶子上都会有特别的露水。
Andrew Huberman:
安德鲁·休伯曼：
I love it.
我喜欢它。
Well, it's not that far from reality.
嗯，这离现实并不遥远。
I'm a big fan of yerba mate.
我是马黛茶的忠实粉丝。
I'm drinking it right now, in fact.
事实上，我现在正在喝它。
Dr. Peter Attia:
彼得·阿蒂亚博士：
As am I.
我也是。
Andrew Huberman:
安德鲁·休伯曼：
In its many forms, usually the loose leaf.
有多种形式，通常是散叶。
I don't tend to drink it out of the gourd.
我不太喜欢从葫芦里喝它。
My dad's Argentine, so that's where I picked it up.
我父亲是阿根廷人，所以我就是从那里学到的。
I started drinking it when I was five years old or younger, which I don't recommend people do.
我五岁或更小的时候就开始喝它，我不建议人们这样做。
It's heavily caffeinated.
它含有大量咖啡因。
Don't drink the smoked versions either, folks.
伙计们，也不要喝熏制的。
I think those are potentially carcinogenic.
我认为这些都有潜在的致癌性。
But this thing that you describe of carrying around the thermos close to the body, if you are ever in Uruguay, or if you ever spot grown men in a restaurant anywhere in the world carrying a thermos with them and to their meals and hugging it close, chances are they're Uruguayan.
但是你所描述的将保温瓶贴近身体随身携带的事情，如果你曾经在乌拉圭，或者如果你曾经在世界任何地方的一家餐馆里看到成年男子随身携带保温瓶并在吃饭时紧紧拥抱它，那么他们很可能是乌拉圭人。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Mm.
嗯。
Andrew Huberman:
安德鲁·休伯曼：
And they're drinking yerba mate.
他们正在喝马黛茶。
They drink it usually after their meals.
他们通常在饭后喝。
It's supposed to be good for your digestion.
应该对你的消化有好处。
So it's not that far from-
所以距离并不远——
Dr. Peter Attia:
彼得·阿蒂亚博士：
There you go
就这样吧
Andrew Huberman:
安德鲁·休伯曼：
...
...
reality.
现实。
I don't carry the thermos, but I do drink mate every day.
我不带保温瓶，但我每天都会喝马黛茶。
And I'm going to start collecting dew off the leaves.
我要开始收集树叶上的露水。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Just a few drops every morning.
每天早上只需几滴。
Just as you brew it.
就像你酿造它一样。
Andrew Huberman:
安德鲁·休伯曼：
Oh, my.
哦，我的。
Some other time we can talk about dreams.
其他时间我们可以谈论梦想。
Recently, I've been doing some dream exploration.
最近，我一直在做一些梦的探索。
I've had some absolutely transformative dreams for the first time in my life.
我一生中第一次有了一些绝对变革性的梦想。
One dream in particular that allowed me to feel something I've never felt before and has catalyzed a large number of important decisions in a way that no other experience, waking or sleep, has ever impacted me.
尤其是一个梦，它让我感受到了以前从未有过的感觉，并以一种其他经历（无论是清醒还是睡眠）从未对我产生过影响的方式催化了大量重要的决定。
And this was drug-free, et cetera.
而且这是不含毒品的，等等。
Dr. Peter Attia:
彼得·阿蒂亚博士：
And do you think you could have had that dream-- We don't have to get into it if you don't want to talk about it now, but was there a lot of work you had to do to prepare for that dream to have taken place?
你认为你可能有那个梦想吗？如果你现在不想谈论它，我们就不必讨论它，但是你需要做很多工作来准备这个梦想的实现吗？
Andrew Huberman:
安德鲁·休伯曼：
Oh, yes.
哦，是的。
Yeah.
是的。
At least 18 months of intensive analysis type work with a very skilled psychiatrist, but I wasn't trying to seed the dream.
与一位非常熟练的精神科医生一起进行了至少 18 个月的密集分析型工作，但我并不是想播下梦想的种子。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
It was just I was at a sticking point with a certain process in my life, and then I was taking a walk while waking and realized that my brain, my subconscious, was going to keep working on this.
只是我正处于生活中某个过程的关键点，然后我醒来时散步，意识到我的大脑，我的潜意识，将继续处理这个问题。
I just decided it's going to keep working on it.
我刚刚决定继续努力。
And then two nights later, I traveled to a meeting in Aspen, and I had the most profound dream ever, where I was able to sense something and feel something I've always wanted to feel as so real within the dream.
两天后的晚上，我去阿斯彭参加一个会议，我做了一个有史以来最深刻的梦，在那里我能够感觉到一些东西，感受到一些我一直想在梦中感受到的真实的东西。
Woke up, knew it was a dream, and realized this is what people close to me that I respect have been talking about.
醒来，知道这是一个梦，并意识到这就是我尊敬的我身边的人一直在谈论的事情。
But I was able to feel it, and therefore-
但我能够感觉到它，因此——
Dr. Peter Attia:
彼得·阿蒂亚博士：
Mm
毫米
Andrew Huberman:
安德鲁·休伯曼：
...
...
I can actually access this in my waking life.
我实际上可以在清醒的生活中访问它。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
It was absolutely transformative for me.
这对我来说绝对是变革性的。
Anyway, sometime I can share more details with you or the audience, but for now, maybe we should talk about these papers.
不管怎样，有时我可以与你或观众分享更多细节，但现在，也许我们应该谈谈这些论文。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Very well.
很好。
Andrew Huberman:
安德鲁·休伯曼：
Who should go first?
谁应该先走？
Dr. Peter Attia:
彼得·阿蒂亚博士：
I'm happy to go first.
我很高兴先走。
Andrew Huberman:
安德鲁·休伯曼：
Great, yeah.
太棒了，是的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
This was a pretty straightforward paper.
这是一篇非常简单的论文。
So, we're going to talk about a paper titled "Reassessing the Evidence of a Survival Advantage in Type 2 Diabetics Treated with Metformin Compared with Controls Without Diabetes: A Retrospective Cohort Study." This is by Matthew Thomas Keyes and colleagues.
因此，我们将讨论一篇题为“重新评估二甲双胍治疗的 2 型糖尿病患者与没有糖尿病的对照组相比的生存优势的证据：一项回顾性队列研究”的论文。这是马修·托马斯·凯斯 (Matthew Thomas Keyes) 及其同事撰写的。
This was published last fall.
这是去年秋天发表的。
Why is this paper important?
为什么这篇论文很重要？
So this paper is important because in 2014, Banister published a paper that I think in many ways kind of got the world very excited about metformin.
所以这篇论文很重要，因为 2014 年，Banister 发表了一篇论文，我认为这篇论文在很多方面都让全世界对二甲双胍感到兴奋。
So this is almost 10 years ago.
所以这已经是差不多10年前的事了。
And I'm sure many people have heard about this paper, even if they're not familiar with it, but they've heard the concept of the paper.
我相信很多人都听说过这篇论文，即使他们不熟悉它，但他们也听说过这篇论文的概念。
And in many ways, it's the paper that has led to the excitement around the potential for geroprotection with metformin.
从很多方面来说，正是这篇论文引发了人们对二甲双胍的老年保护潜力的兴奋。
And I should probably just define for the audience what geroprotection means.
我也许应该为观众定义老年保护的含义。
When we think of-
当我们想到——
Andrew Huberman:
安德鲁·休伯曼：
And probably also, sorry to interrupt, what metformin is, just for the uninformed.
很抱歉打扰一下，二甲双胍是什么，可能只是针对不知情的人。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
That's a great point.
这是一个很好的观点。
So I'll start with the latter.
所以我将从后者开始。
So metformin is a drug that has been used for many years.
所以二甲双胍是一种已经使用多年的药物。
Depends where it was first approved, I think was in Europe.
取决于它首先在哪里获得批准，我认为是在欧洲。
But call it directionally 50 plus years of use as a first-line agent for patients with type 2 diabetes.
但我们可以直接称其为 2 型糖尿病患者的一线药物，已有 50 多年的使用历史。
In the US, maybe 40 plus years.
在美国，可能有 40 多年。
So this is a drug that's been around forever, trade name Glucophage, or brand name.
所以这是一种永远存在的药物，商品名格华止，或品牌名称。
But again, it's a generic drug today.
但同样，今天它是一种仿制药。
The mechanism by which metformin works is debated hotly.
二甲双胍的作用机制引起了激烈的争论。
But what I think is not debated is the immediate thing that metformin does, which is it inhibits complex one of the mitochondria.
但我认为没有争议的是二甲双胍的直接作用，即它抑制线粒体复合体之一。
So again, maybe just taking a step back So the mitochondria, as everybody thinks of those, is the cellular engine for making ATP.
再说一次，也许只是退一步所以，正如每个人所认为的那样，线粒体是制造 ATP 的细胞引擎。
So the most efficient way that we make ATP is through oxidative phosphorylation, where we take either fatty acid pieces or a breakdown product of glucose once it's partially metabolized to pyruvate.
因此，我们制造 ATP 最有效的方法是通过氧化磷酸化，在葡萄糖部分代谢为丙酮酸后，我们会获取脂肪酸片段或葡萄糖的分解产物。
We put that into an electron transport chain, and we basically trade chemical energy for electrons that can then be used to make phosphates onto ADP.
我们将其放入电子传输链中，基本上用化学能换取电子，然后电子可用于在 ADP 上制造磷酸盐。
You think of everything you do.
你所做的一切都会想到。
Eating is taking the chemical energy in food, taking the energy that's in those bonds, making electrical energy in the mitochondria.
饮食是获取食物中的化学能，获取这些化学键中的能量，在线粒体中产生电能。
Those electrons pump a gradient that allow you to make ATP.
这些电子泵出梯度，使您能够生成 ATP。
To give a sense of how primal and important this is, if you block that process completely, you die.
为了让大家明白这是多么原始和重要，如果你完全阻止这个过程，你就会死。
So everybody's probably heard of cyanide, right?
大家可能都听说过氰化物，对吧？
Cyanide is something that is incredibly toxic, even at the smallest doses.
氰化物的毒性非常大，即使剂量很小。
Cyanide is a complete blocker of this process.
氰化物完全阻碍了这一过程。
And if my memory serves me correctly, I think it blocks complex four of the mitochondria.
如果我没记错的话，我认为它会阻断线粒体的复合体四。
I don't know if you recall if it complex three or complex four.
我不知道你是否还记得它是复数三还是复数四。
Andrew Huberman:
安德鲁·休伯曼：
I know a lot about toxins that impact the nervous system, but I don't know a lot about poisons.
我对影响神经系统的毒素了解很多，但对毒药了解不多。
Dr. Peter Attia:
彼得·阿蒂亚博士：
The mitochondria, yeah.
线粒体，是的。
Andrew Huberman:
安德鲁·休伯曼：
But if ever you want to have some fun, we can talk about all the dangerous stuff that animals make and insects make and how they kill you.
但如果你想找点乐子，我们可以谈谈动物和昆虫制造的所有危险物质以及它们如何杀死你。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah, like the prototoxin-
是的，就像原毒素一样——
Andrew Huberman:
安德鲁·休伯曼：
That's always my favorite topic
这永远是我最喜欢的话题
Dr. Peter Attia:
彼得·阿蒂亚博士：
...
...
and all these things that block sodium channels.
以及所有这些阻碍钠通道的东西。
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Alpha-latrotoxin, bungaro-- I really geek out on this stuff because it allows me to talk about neuroscience, animals, and scary stuff.
Alpha-latrotoxin、bungaro——我真的很喜欢这些东西，因为它让我可以谈论神经科学、动物和可怕的东西。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
It combines it.
它结合了它。
So we could do that sometime for fun.
所以我们有时可以为了好玩而这样做。
Maybe at the end if we have a few moments.
如果我们有一些时间的话，也许在最后。
Dr. Peter Attia:
彼得·阿蒂亚博士：
So something like cyanide that is a very potent inhibitor of this electron transport chain will kill you instantly.
因此，像氰化物这样的东西是电子传递链的一种非常有效的抑制剂，它会立即杀死你。
People understand that, of course, a drop of cyanide, and you would be dead literally instantaneously.
人们当然知道，一滴氰化物，你就会立即死亡。
So metformin works at the first of those complexes.
因此，二甲双胍对第一个复合物起作用。
I believe there are four, if my memory serves correctly, four electron transport chain complexes.
如果我没记错的话，我相信有四个电子传输链复合体。
But of course, it's not a complete inhibition of it.
但当然，这并不是完全抑制它。
It's just a weak blocker of that.
它只是一个微弱的阻止者。
And the net effect of that is what?
其最终效果是什么？
So the net effect of that is that it changes the ratio of adenosine monophosphate to adenosine diphosphate.
因此，其净效应是它改变了单磷酸腺苷与二磷酸腺苷的比率。
What's less clear is why does that have a benefit in diabetics?
不太清楚的是为什么这对糖尿病患者有好处？
Because what it unambiguously does is reduces the amount of glucose that the liver puts out.
因为它明确的作用是减少肝脏排出的葡萄糖量。
So hepatic glucose output is one of the fundamental problems that's happening in type 2 diabetes.
因此，肝葡萄糖输出是 2 型糖尿病中发生的基本问题之一。
You may recall, I think we talked about this even on a previous podcast, you and I sitting here with normal blood sugar have about five grams of glucose in our total circulation.
您可能还记得，我想我们甚至在之前的播客中也讨论过这一点，您和我坐在这里，血糖正常，我们的总循环中大约有五克葡萄糖。
That's it, five grams.
就这样，五克。
Think about how quickly the brain will go through that.
想想大脑会以多快的速度完成这个过程。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Within minutes.
几分钟之内。
So the only thing that keeps us alive is our liver's ability to titrate out glucose.
因此，唯一让我们活着的是我们的肝脏滴定葡萄糖的能力。
And if it puts out too much, for example, if the glucose level was consistently two teaspoons, you would have type 2 diabetes.
如果释放过多，例如，如果血糖水平始终为两茶匙，那么您就会患上 2 型糖尿病。
So the difference between being metabolically healthy and having profound type 2 diabetes is one teaspoon of glucose in your bloodstream.
因此，代谢健康与患有严重 2 型糖尿病之间的区别就在于血液中的一茶匙葡萄糖。
So the ability of the liver to tamp down on high glucose output is important.
因此，肝脏抑制高葡萄糖输出的能力很重要。
Metformin seems to do that.
二甲双胍似乎可以做到这一点。
So-
所以——
Andrew Huberman:
安德鲁·休伯曼：
Can I just ask one question?
我可以只问一个问题吗？
Is it fair to provide this overly simplified summary of the biochemistry, which is that when we eat, the food is broken down, but the breaking of bonds creates energy that then our cells can use in the form of ATP, and the mitochondria are central to that process.
提供这种过于简化的生物化学总结是否公平，即当我们吃东西时，食物会被分解，但化学键的断裂会产生能量，然后我们的细胞可以以 ATP 的形式使用这些能量，而线粒体是该过程的核心。
And that metformin is partially short-circuiting the energy production process.
二甲双胍正在部分缩短能量生产过程。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yep.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And so even though we are eating, when we have metformin in our system, presumably, there is going to be less net glucose.
因此，即使我们正在吃东西，当我们的系统中含有二甲双胍时，大概净葡萄糖也会减少。
The bonds are going to be broken down.
债券将被打破。
We're chewing, we're digesting, but less of that is turned into blood sugar, glucose.
我们正在咀嚼，我们正在消化，但转化为血糖、葡萄糖的物质却较少。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Well, sort of.
嗯，有点像。
It's not depriving you of ultimately storing that energy.
它并不会剥夺您最终储存该能量的能力。
What it's doing is changing the way the body partitions fuel.
它的作用是改变身体分配燃料的方式。
That's probably a better way to think about it to be a little bit more accurate.
这可能是一种更好的思考方式，可以更准确一些。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Peter Attia:
彼得·阿蒂亚博士：
For example, it's not depriving you of the calories that are in that glucose.
例如，它不会剥夺您葡萄糖中的卡路里。
That would be fantastic, but that's not-
那真是太棒了，但那不是——
Andrew Huberman:
安德鲁·休伯曼：
That was the Olestra program.
这就是 Olestra 计划。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Olestra, that's right, yeah.
奥莱斯特拉，没错，是的。
Andrew Huberman:
安德鲁·休伯曼：
Remember the Olestra from the '90s?
还记得 90 年代的 Olestra 吗？
Olestra, folks, for those of you who don't remember, by the way, if you ever ate this stuff, you'd remember.
奥利斯特拉，伙计们，对于那些不记得的人来说，顺便说一句，如果你曾经吃过这个东西，你就会记得。
Because it was a fat that was not easily digested.
因为它是一种不易消化的脂肪。
It had analogous to plant fiber or something like that.
它类似于植物纤维或类似的东西。
So it was being put into potato chips and whatnot, and the idea was that people would simply excrete it.
因此，它被放入薯片之类的东西中，其想法是人们可以简单地将其排出体外。
And I don't know what happened except that people got a lot of stomach aches and-
我不知道发生了什么，只知道人们胃痛得很厉害，而且——
Dr. Peter Attia:
彼得·阿蒂亚博士：
Well, the anal seepage
嗯，肛门渗液
Andrew Huberman:
安德鲁·休伯曼：
...
...
everyone got fatter in the world.
世界上每个人都变胖了。
We know that.
我们知道这一点。
Dr. Peter Attia:
彼得·阿蒂亚博士：
The anal seepage is what really did that product in.
肛门渗漏才是该产品的真正作用。
Andrew Huberman:
安德鲁·休伯曼：
Anal seepage.
肛门渗液。
Only a physician, because after all, Peter's a clinician, a physician, an MD, and I'm not, could find an appropriate term to describe-
只有医生，因为毕竟，彼得是一名临床医生、一名医生、一名医学博士，而我不是，才能找到一个合适的术语来描述——
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
what this is.
这是什么。
Dr. Peter Attia:
彼得·阿蒂亚博士：
When you have that much fat malabsorption-
当你有那么多脂肪吸收不良时-
Andrew Huberman:
安德鲁·休伯曼：
Mm
毫米
Dr. Peter Attia:
彼得·阿蒂亚博士：
...
...
you start to have accidents.
你开始发生事故。
Andrew Huberman:
安德鲁·休伯曼：
Wow.
哇。
And so-
所以——
Dr. Peter Attia:
彼得·阿蒂亚博士：
So that did away with that product.
这样就取消了该产品。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Yeah.
是的。
It was either that or the diaper industry was-
要么是这样，要么尿布行业是——
Dr. Peter Attia:
彼得·阿蒂亚博士：
That's right
没错
Andrew Huberman:
安德鲁·休伯曼：
...
...
going to really take off.
将会真正起飞。
Dr. Peter Attia:
彼得·阿蒂亚博士：
All right.
好吧。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
That's why you don't hear about Olestra.
这就是为什么您没有听说过 Olestra。
Dr. Peter Attia:
彼得·阿蒂亚博士：
That's right.
没错。
So we've got this drug metformin.
所以我们有这种药物二甲双胍。
It's considered a perfect first-line agent for people with type 2 diabetes.
它被认为是 2 型糖尿病患者的完美一线药物。
So again, what's happening when you have type 2 diabetes?
那么，当您患有 2 型糖尿病时会发生什么？
The primary insult probably occurs in the muscles, and it is insulin resistance.
主要的损伤可能发生在肌肉中，那就是胰岛素抵抗。
Everybody hears that term.
每个人都听说过这个词。
What does it mean?
这是什么意思？
Insulin is a peptide.
胰岛素是一种肽。
It binds to a receptor on a cell.
它与细胞上的受体结合。
So let's just talk about it through the lens of the muscle, because the muscle is responsible for most glucose disposal.
因此，让我们从肌肉的角度来讨论它，因为肌肉负责大部分葡萄糖的处理。
It gets glucose out of the circulation.
它将葡萄糖从循环中排出。
High glucose is toxic.
高血糖是有毒的。
We have to put it away, and we want to put most of it into our muscles.
我们必须把它收起来，我们要把大部分投入到我们的肌肉中。
That's where we store 75% to 80% of it.
这是我们存储 75% 到 80% 的地方。
When insulin binds to the insulin receptor, a tyrosine kinase is triggered inside.
当胰岛素与胰岛素受体结合时，内部会触发酪氨酸激酶。
So just Ignore all that, but a chemical reaction takes place inside the cell that leads to a phosphorylation, so an ATP donates a phosphate group, and a transporter, just think of a little tunnel, like a little straw, goes up through the level of the cell, and now glucose can freely flow in.
所以忽略所有这些，但细胞内部会发生化学反应，导致磷酸化，因此 ATP 会提供磷酸基团，而转运蛋白，只需想象一个小隧道，就像一根小稻草，向上穿过细胞水平，现在葡萄糖可以自由流动。
So I'm sure you've talked a lot about this with your audience.
所以我确信您已经与观众讨论过很多这个问题。
Things that move against gradients need pumps to move them.
逆梯度移动的物体需要泵来移动它们。
Things that move with gradients don't.
随梯度移动的物体则不会。
Glucose is moving with its gradient into the cell.
葡萄糖以其梯度进入细胞。
It doesn't need active transport, but it does need the transporter put there.
它不需要主动传输，但确实需要放置在那里的传输器。
That requires the energy, and that's the job of insulin.
这需要能量，这就是胰岛素的作用。
Andrew Huberman:
安德鲁·休伯曼：
By the way, I did not know that.
顺便说一句，我不知道这一点。
I certainly know active and passive transport as it relates to neurotransmitter and ion flow.
我当然知道主动和被动运输，因为它与神经递质和离子流有关。
But I'd never heard that when insulin binds to a cell, that literally a little straw is placed into the membrane of the cell.
但我从未听说过，当胰岛素与细胞结合时，实际上是将一根小吸管放入细胞膜中。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Glucose doesn't need a pump to move it in.
葡萄糖不需要泵来输送。
Andrew Huberman:
安德鲁·休伯曼：
That is cool.
那很酷。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Because there's much more glucose outside the cell than inside, so it's just .
因为细胞外的葡萄糖比细胞内多得多，所以它只是 。
But the energy required is to move the straw up to the cell.
但所需的能量是将吸管向上移动到细胞中。
So-
所以——
Andrew Huberman:
安德鲁·休伯曼：
Cell biology is so cool.
细胞生物学太酷了。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah, it is.
是的，确实如此。
So what happens is, and Gerald Shulman at Yale did the best work on elucidating this, as the intramuscular fat increases, and by intramuscular, I mean intracellular fat, triacylglycerides and diacylglycerides accumulate in a muscle cell, that signal gets interrupted.
耶鲁大学的杰拉尔德·舒尔曼（Gerald Shulman）在阐明这一点方面做了最好的工作，随着肌内脂肪的增加，我所说的肌内脂肪，我的意思是细胞内脂肪、三酰甘油和二酰甘油在肌肉细胞中积聚，该信号就会被中断。
Andrew Huberman:
安德鲁·休伯曼：
Mm.
嗯。
Dr. Peter Attia:
彼得·阿蒂亚博士：
And all of a sudden, I'm making these numbers up, if you used to need two units of insulin to trigger the little transporter, now you need three, and then you need four, and then you need five.
突然间，我编造了这些数字，如果你过去需要两个单位的胰岛素来触发小转运蛋白，现在你需要三个，然后你需要四个，然后你需要五个。
You need more and more insulin to get the thing up.
你需要越来越多的胰岛素才能恢复正常。
That is the definition of insulin resistance.
这就是胰岛素抵抗的定义。
Andrew Huberman:
安德鲁·休伯曼：
Mm.
嗯。
Dr. Peter Attia:
彼得·阿蒂亚博士：
The cell is becoming resistant to the effect of insulin.
细胞对胰岛素的作用产生抵抗力。
And therefore, the early mark of insulin resistance, the canary in the coal mine, is not an increase in glucose.
因此，胰岛素抵抗的早期标志（煤矿里的金丝雀）并不是葡萄糖的增加。
It's an increase in insulin.
这是胰岛素的增加。
So normal glycemia with hyperinsulinemia, especially postprandial, meaning after you eat hyperinsulinemia, is the thing that tells you, hey, you're five, 10 years away from this being a real problem.
因此，正常血糖伴高胰岛素血症，尤其是餐后血糖，即您吃高胰岛素血症后的血糖，会告诉您，嘿，您距离这成为真正的问题还有五到十年的时间。
So fast-forward many steps down the line, someone with type 2 diabetes has long passed that system.
如此快进了许多步骤，患有 2 型糖尿病的人早已通过了这个系统。
Now, not only are they insulin resistant, where they just need a boatload of insulin, which is made by the pancreas, to get glucose out of the circulation, but now that system's not even working well.
现在，他们不仅有胰岛素抵抗，他们只需要大量由胰腺产生的胰岛素，就能将葡萄糖从循环中排出，而且现在该系统甚至无法正常工作。
And now they're not getting glucose into the cell.
现在他们无法让葡萄糖进入细胞。
So now their glucose level is elevated, and even though it's continually being chewed up and used up, because again, the brain alone would account for most of that glucose disposal, the liver is now becoming insulin resistant as well.
所以现在他们的葡萄糖水平升高了，尽管它不断地被咀嚼和消耗，因为同样，大脑本身就占了大部分葡萄糖的处理量，肝脏现在也变得胰岛素抵抗。
And now the liver isn't able to regulate how much glucose to put into circulation, and it's overdoing it.
现在肝脏无法调节进入循环的葡萄糖量，而且过量了。
So now you have too much glucose being pumped into the circulation by the liver, and you have the muscles that can't dispose of it.
现在，肝脏将过多的葡萄糖泵入循环系统，而肌肉却无法处理这些葡萄糖。
And it's really a vicious, brutal cascade because the same problem of fat accumulating in the muscle is now starting to happen in the pancreas.
这确实是一个恶性、残酷的级联反应，因为肌肉中脂肪堆积的同样问题现在也开始出现在胰腺中。
And now the relatively few cells in the pancreas, called beta cells, that make insulin, are undergoing inflammation due to the fat accumulation within the pancreas itself.
现在，胰腺中相对较少的产生胰岛素的细胞（称为β细胞）由于胰腺本身内的脂肪堆积而发生炎症。
And so now the thing that you need to make more insulin is less effective at making insulin.
所以现在你需要制造更多胰岛素的东西在制造胰岛素方面的效率降低了。
So ultimately, way down the line, a person with type 2 diabetes might actually even require insulin exogenously.
因此，最终，2 型糖尿病患者实际上可能需要外源性胰岛素。
Andrew Huberman:
安德鲁·休伯曼：
Could you share with us a few of the causes of type 2 diabetes, of insulin resistance?
您能否与我们分享一些导致 2 型糖尿病和胰岛素抵抗的原因？
One, it sounds like, is accumulating too much fat.
一，听起来像是积累了太多的脂肪。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
So energy imbalance would be an enormous one.
因此，能源失衡将是一个巨大的问题。
Inactivity or insufficient activity is probably the single most important.
不活动或活动不足可能是最重要的一个。
So when Gerald Shulman was running clinical trials at Yale, they would be recruiting undergrads to study, obviously, because you're typically recruiting young people.
因此，当杰拉尔德·舒尔曼在耶鲁大学进行临床试验时，他们显然会招募本科生来学习，因为通常会招募年轻人。
And they would be doing these very detailed mechanistic studies where they would require actual tissue biopsies.
他们将进行这些非常详细的机制研究，其中需要实际的组织活检。
So you're going to biopsy somebody's quadriceps and actually look at what's happening in the muscle.
所以你要对某人的股四头肌进行活组织检查，并实际观察肌肉中发生的情况。
Well, I remember him telling me this when I interviewed him on my podcast.
嗯，我记得当我在播客上采访他时他告诉了我这一点。
He said the most important criteria of the people we interviewed is-- Because they were still lean.
他说我们采访的人最重要的标准是——因为他们仍然很瘦。
These weren't people that were overweight, but they had to be inactive.
这些人并不超重，但他们必须不运动。
You couldn't have active people in these studies.
这些研究中不可能有活跃的人。
So exercising is one of the most important things you're going to do to ward off insulin resistance.
因此，锻炼是预防胰岛素抵抗最重要的事情之一。
But there are other things that can cause insulin resistance.
但还有其他因素可能导致胰岛素抵抗。
Sleep deprivation has a profound impact on insulin resistance.
睡眠不足对胰岛素抵抗有着深远的影响。
I think we probably talked about this previously, but if you do some very elegant mechanistic studies where you sleep deprive people, you let them only sleep for four hours for a week, you'll reduce their glucose disposal by about half.
我想我们之前可能讨论过这个问题，但是如果你做一些非常优雅的机制研究，让人们睡眠不足，让他们一周只睡四个小时，你就会将他们的葡萄糖消耗量减少大约一半。
Andrew Huberman:
安德鲁·休伯曼：
Wow.
哇。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Which is, that's a staggering amount of-- You're basically inducing profound insulin resistance in just a week of sleep deprivation.
也就是说，这是一个惊人的数量——在短短一周的睡眠不足中，你基本上就引发了严重的胰岛素抵抗。
Hypercortisolemia is another factor.
高皮质醇血症是另一个因素。
And then obviously energy imbalance.
然后明显的能量不平衡。
So when you're accumulating excess energy, when you're getting fatter, if you start spilling that fat outside of the subcutaneous fat cells into the muscle, into the liver, into the pancreas, all those things are exacerbating it.
因此，当你积累过多的能量时，当你变得越来越胖时，如果你开始将皮下脂肪细胞外的脂肪溢出到肌肉、肝脏、胰腺中，所有这些都会加剧情况。
Andrew Huberman:
安德鲁·休伯曼：
Got it.
明白了。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Okay.
好的。
So enter metformin, first-line drug.
因此，一线药物二甲双胍应运而生。
So every drug you give a person with type 2 diabetes is trying to address part of this chain.
因此，您给 2 型糖尿病患者服用的每一种药物都试图解决这个链条的一部分。
So some of the drugs tell you to make more insulin.
所以有些药物会告诉你要制造更多的胰岛素。
That's one of the strategies.
这是策略之一。
So here are drugs like sulfonylureas.
这里有磺酰脲类药物。
They tell the body, "Make more insulin." Other drugs, like insulin, just give you more of the insulin thing.
他们告诉身体，“制造更多的胰岛素。”其他药物，例如胰岛素，只会给您提供更多的胰岛素作用。
Metformin tackles the problem elsewhere.
二甲双胍在其他方面解决了这个问题。
It tamps down glucose by addressing the hepatic glucose output channel.
它通过处理肝葡萄糖输出通道来抑制葡萄糖。
GLP-1 agonists are another drug.
GLP-1 激动剂是另一种药物。
They increase insulin sensitivity, initially causing you to also make more insulin.
它们会增加胰岛素敏感性，最初会导致您产生更多胰岛素。
GLP-
GLP-
Andrew Huberman:
安德鲁·休伯曼：
So that's Ozempic?
这就是奥泽姆皮克吗？
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And is it true that berberine is more or less the poor man's metformin?
小檗碱或多或少是穷人的二甲双胍，这是真的吗？
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yep.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
It's from a tree bark.
它来自树皮。
It just happens to have the same properties of-
它恰好具有相同的属性-
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
And by the way, metformin-
顺便说一下，二甲双胍——
Andrew Huberman:
安德鲁·休伯曼：
...
...
of reducing mTOR and reducing blood glucose.
减少 mTOR 和降低血糖。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
And metformin, by the way, occurs from a lilac plant in France.
顺便说一句，二甲双胍是从法国的紫丁香植物中提取的。
That's where it was discovered.
这就是它被发现的地方。
So metformin is also based on a substance found in nature.
因此二甲双胍也是基于自然界中发现的物质。
Andrew Huberman:
安德鲁·休伯曼：
So you need a prescription for metformin.
所以您需要二甲双胍处方。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yep.
是的。
Andrew Huberman:
安德鲁·休伯曼：
You don't need a prescription for berberine.
您不需要小檗碱处方。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Correct.
正确。
Andrew Huberman:
安德鲁·休伯曼：
But yeah, we can talk about berberine a little bit later.
但是，是的，我们可以稍后再讨论小檗碱。
I had a couple great experiences with berberine and a couple bad experiences-
我对小檗碱有过一些美好的经历，也有一些糟糕的经历——
Dr. Peter Attia:
彼得·阿蒂亚博士：
Interesting
有趣
Andrew Huberman:
安德鲁·休伯曼：
...
...
with berberine.
与小檗碱。
Yeah.
是的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
So, maybe taking one step back from this.
所以，也许可以退后一步。
In 2011, I became very interested in metformin personally, just reading about it, obsessing over it, and just somehow decided, I should be taking this.
2011 年，我个人对二甲双胍非常感兴趣，只是阅读了有关它的文章，对它着迷，然后不知何故决定，我应该服用它。
So I actually began taking metformin.
所以我实际上开始服用二甲双胍。
I still remember exactly when I started.
我还清楚地记得我开始的时候。
I started it in May of 2011, and I realized that because I was on a trip with a bunch of buddies.
我从 2011 年 5 月开始，我意识到这一点是因为我和一群朋友一起旅行。
We went to the Berkshire Hathaway shareholder meeting, which is the Buffett shareholder meeting, and it was a fun thing to do.
我们去参加了伯克希尔哈撒韦公司的股东大会，也就是巴菲特的股东大会，这是一件很有趣的事情。
And I remember being so sick the whole time because I didn't titrate up the dose of metformin.
我记得我一直病得很厉害，因为我没有滴定二甲双胍的剂量。
I just went straight to two grams a day, which is the full dose.
我直接每天服用两克，这是完整剂量。
And we went to this-
我们去了这个-
Andrew Huberman:
安德鲁·休伯曼：
Is that characteristic of your approach to things?
这是你处理事情的特点吗？
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yes.
是的。
I think that's safe to say.
我认为可以肯定地说。
Andrew Huberman:
安德鲁·休伯曼：
Next time, I'll give you a thermos of this dew that I collect in the morning.
下次，我会给你一瓶我早上收集的露水。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Oh, really?
哦，真的吗？
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
So I remember being so sick that the whole time we were in Nebraska, or Omaha, I guess, we went to Dairy Queen, because you do all the Buffett things when you're there, right?
所以我记得我病得很重，以至于我们在内布拉斯加州或奥马哈的整个时间里，我猜我们去了冰雪皇后，因为当你在那里时，你会做所有巴菲特的事情，对吧？
I couldn't have an ice cream at Dairy Queen.
我不能在冰雪皇后吃冰淇淋。
Andrew Huberman:
安德鲁·休伯曼：
You couldn't?
你不能吗？
Dr. Peter Attia:
彼得·阿蒂亚博士：
I mean, I couldn't.
我的意思是，我不能。
I'm so nauseous.
我好恶心啊
Andrew Huberman:
安德鲁·休伯曼：
Oh, because I would say if you've got metformin in your system, you're going to buffer glucose.
哦，因为我想说如果你的系统中有二甲双胍，你就会缓冲葡萄糖。
You could have four ice cream cones and probably feel fine.
你可以吃四个蛋卷冰淇淋，可能会感觉很好。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Except I couldn't keep anything down.
但我无法保留任何东西。
I was so nauseous.
我太恶心了。
Andrew Huberman:
安德鲁·休伯曼：
That's uncomfortable.
这很不舒服。
Dr. Peter Attia:
彼得·阿蒂亚博士：
So clearly metformin has this side effect initially, which is a little bit of appetite suppression.
很明显，二甲双胍最初有这种副作用，即有点抑制食欲。
But regardless, that's the story on metformin.
但无论如何，这就是二甲双胍的故事。
There are a lot of reasons I was interested in it.
我对此感兴趣的原因有很多。
I wasn't thinking true geroprotection.
我没想到真正的老年保护。
That term wasn't in my vernacular at the time.
我当时的白话里还没有这个词。
But what I was thinking is, "Hey, this is going to help you buffer glucose better.
但我在想的是，“嘿，这将帮助你更好地缓冲葡萄糖。
It's got to be better." And this was sort of my first foray into self-experimentation.
它必须变得更好。”这是我第一次尝试自我实验。
Andrew Huberman:
安德鲁·休伯曼：
Do you want to define geroprotection?
您想定义老年保护吗？
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
It's a good term to define.
这是一个很好定义的术语。
Andrew Huberman:
安德鲁·休伯曼：
Geriatric, gero.
老年病，杰罗。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
So gero from geriatric, old, protection, so protection from aging.
所以 gero 免受老年、衰老、保护，因此保护免受衰老。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Peter Attia:
彼得·阿蒂亚博士：
And when we talk about a drug like metformin or rapamycin or even NAD, NR, these things, the idea is we're talking about them as geroprotective to signal that they are drugs that are not targeting a specific disease of aging.
当我们谈论二甲双胍或雷帕霉素，甚至 NAD、NR 等药物时，我们的想法是，我们谈论它们具有老年保护作用，以表明它们不是针对特定衰老疾病的药物。
For example, a PCSK9 inhibitor is sort of geroprotective, but it's targeting one specific pathway, which is cardiovascular disease and dyslipidemia.
例如，PCSK9 抑制剂具有老年保护作用，但它针对的是一种特定途径，即心血管疾病和血脂异常。
Whereas the idea is a geroprotective agent would target hallmarks of aging.
而这个想法是一种老年保护剂，可以针对衰老的特征。
There are nine hallmarks of aging.
衰老有九个特征。
Please don't ask me to recite them.
请不要让我背诵它们。
I've never been able to get all nine straight, but people know what we're talking about, right?
我从来没能获得九连胜，但人们知道我们在说什么，对吧？
So decreased autophagy, increased senescence, decreased nutrient sensing or defective nutrient sensing, proteomic instability, genomic instability, methylation, all of these things, epigenetic changes.
因此，自噬减少，衰老增加，营养感应减弱或营养感应缺陷，蛋白质组不稳定，基因组不稳定，甲基化，所有这些都是表观遗传变化。
Those are all the nine hallmarks of aging.
这些都是衰老的九个标志。
Andrew Huberman:
安德鲁·休伯曼：
You got seven.
你有七个。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
So a geroprotective agent would target those deep down biologic hallmarks of aging.
因此，老年保护剂将针对衰老的深层生物学特征。
And in 2014, a paper came out by Bannister that basically got the world focused on this problem.
2014年，班尼斯特发表的一篇论文基本上让全世界都关注这个问题。
By the world, I mean the world of anti-aging.
我所说的世界，是指抗衰老的世界。
So what Bannister and colleagues did was they took a registry from the UK, and they got a set of patients who were on metformin with type 2 diabetes, but only metformin.
因此，班尼斯特和同事所做的就是从英国进行了登记，他们收集了一组服用二甲双胍的 2 型糖尿病患者，但只服用二甲双胍。
So these were people who had just progressed to diabetes.
这些人刚刚患上糖尿病。
They were not put on any other drug, just metformin.
他们没有服用任何其他药物，只服用二甲双胍。
And then they found from the same registry, a group of matched controls.
然后他们从同一个注册表中找到了一组匹配的控件。
So this is a standard way that epidemiologic studies are done because, again, you don't have the luxury of doing the randomization, so you're trying to account for all the biases that could exist by saying, "We're going to take people who look just like that person with diabetes, so can we match them for age, sex, socioeconomic status, blood pressure, BMI, everything we can?
所以这是流行病学研究的标准方法，因为你没有机会进行随机化，所以你试图解释所有可能存在的偏见，说：“我们要选择那些看起来像那个糖尿病患者的人，所以我们可以在年龄、性别、社会经济地位、血压、体重指数等方面匹配他们吗？
And then let's look at what happened to them over time." Now, again, this is all happening in the future, so you're looking into the past.
然后让我们看看随着时间的推移他们发生了什么。”现在，这一切都发生在未来，所以你正在回顾过去。
It's retrospective in that sense.
从这个意义上说，这是回顾性的。
And so let me just pull up the table here so I can walk through.
让我把桌子拉到这里，这样我就可以走过来了。
And this is not in the paper we talked about, but I think this is an important background.
而这并不是我们谈到的论文中，但我认为这是一个重要的背景。
So they did something that at the time I didn't really notice.
所以他们做了一些当时我没有真正注意到的事情。
I didn't notice what they did.
我没有注意到他们做了什么。
I probably did and I forgot, but I didn't notice this until about five years ago when I went back and looked at the paper.
我可能注意到了，但我忘记了，但直到大约五年前我回去看报纸时才注意到这一点。
And they did something called informative censoring.
他们做了一种叫做信息审查的事情。
So the way the study worked is if you were put on metformin, we're going to follow you.
因此，这项研究的工作方式是，如果您服用二甲双胍，我们将跟踪您。
If you're not on metformin, we're going to follow you, and we're going to track the number of deaths from any cause that occur.
如果您没有服用二甲双胍，我们将跟踪您，并且我们将追踪任何原因导致的死亡人数。
This is called all-cause mortality or ACM, and it's really the gold standard in a trial of this nature, or a study of this nature, or even a clinical trial.
这称为全因死亡率或 ACM，它确实是此类性质的试验、此类性质的研究、甚至临床试验的黄金标准。
You want to know how much are people dying from anything, because we're trying to prevent or delay death of all causes.
您想知道有多少人死于任何原因，因为我们正在努力预防或延迟所有原因的死亡。
Informative censoring says if a person who's on metformin deviates from that inclusion criteria, we will not count them in the final assessment.
信息审查表明，如果服用二甲双胍的人偏离了纳入标准，我们不会将其计入最终评估。
So how are the ways that that can happen?
那么，如何实现这一点呢？
Well, one, the person can be lost to follow-up.
嗯，第一，这个人可能会失去后续行动。
Two, they can just stop taking their metformin.
第二，他们可以停止服用二甲双胍。
Three, and more commonly, they can progress to needing a more significant drug.
第三，更常见的是，他们可能会发展到需要更有效的药物。
So all of those patients were excluded from the study.
因此，所有这些患者都被排除在研究之外。
So think about that for a moment.
请考虑一下。
This is, in my opinion, a significant limitation of this study, because what you're basically doing is saying, we're only going to consider the patients who were on metformin, stayed on metformin, and never progressed through it, and we're going to compare those to people who were not having type 2 diabetes.
在我看来，这是这项研究的一个重大局限性，因为你基本上所做的就是说，我们只会考虑那些正在服用二甲双胍、继续服用二甲双胍并且从未取得进展的患者，我们将把这些患者与没有患有 2 型糖尿病的患者进行比较。
So an analogy here would be, imagine we're going to do a study of Two groups that we think are almost identical.
因此，这里的类比是，假设我们要对我们认为几乎相同的两个群体进行研究。
One of them are smokers, and the other are identical in every way, but they're not smokers.
其中一个是吸烟者，另一个在各方面都相同，但他们不是吸烟者。
And we're going to follow them to see which ones get lung cancer.
我们将跟踪他们，看看哪些人患有肺癌。
But every time somebody dies in the smoking group, we stop counting them.
但每当吸烟组有人死亡时，我们就不再统计他们。
When you get to the end, you're going to have a less significant view of the health status of that group.
当你到达最后时，你对该群体的健康状况的看法将会变得不那么重要。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Peter Attia:
彼得·阿蒂亚博士：
So with that caveat, the Banister study found a very interesting result, which was the crude death rate was-- And by the way, the way these are done, this is also one of the challenges of epidemiology, is the math gets much more complicated.
因此，带着这个警告，巴尼斯特的研究发现了一个非常有趣的结果，那就是粗死亡率是——顺便说一句，这些的完成方式，这也是流行病学的挑战之一，数学变得更加复杂。
You have to normalize death rate for the amount of time you study the people.
你必须根据你研究人群的时间将死亡率标准化。
So everything is normalized to 1,000 person years.
所以一切都标准化为 1,000 人年。
So the crude death rate in the group of people with type 2 diabetes who were on metformin, including the censoring, was 14.4.
因此，服用二甲双胍的 2 型糖尿病患者的粗死亡率（包括审查）为 14.4。
So 14.4 deaths occurred per thousand patient years.
因此每千患者年有 14.4 人死亡。
If you looked at the control group, it was 15.2.
如果你看一下对照组，结果是 15.2。
This was a startling result, and I remember reading this in, again, 2014, and being like, "Holy crap.
这是一个令人震惊的结果，我记得在 2014 年再次读到这篇文章时，我的感觉是，“天哪。
This is really amazing."
这真是太神奇了。”
Andrew Huberman:
安德鲁·休伯曼：
Could you explain why?
你能解释一下为什么吗？
Because I hear those numbers, and they don't seem that striking.
因为我听到这些数字，而且它们看起来并不那么引人注目。
It's a difference of about a year and a half.
两者相差一年半左右。
Now, of course, a difference of about a year and a half in lifespan is remarkable.
当然，现在寿命相差大约一年半是非常显着的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Well, and actually, it doesn't even translate to that.
好吧，实际上，它甚至没有转化为这一点。
So taking a step back, type 2 diabetes on average will shorten your life by six years.
因此退一步来说，2 型糖尿病平均会使您的寿命缩短六年。
Andrew Huberman:
安德鲁·休伯曼：
I see.
我明白了。
Dr. Peter Attia:
彼得·阿蒂亚博士：
So that's the actuarial difference between having type 2 diabetes and not, all comers.
这就是患有 2 型糖尿病和未患 2 型糖尿病之间的精算差异。
But you're right.
但你是对的。
This is not a huge difference.
这并不是一个很大的区别。
It's only a difference of a little less than one year of life per thousand patient years studied.
研究中每千名患者年的寿命仅存在不到一年的差异。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
And by the way, Peter just pointed out my math was wrong when I said about a year and a half.
顺便说一句，当我说大约一年半时，彼得刚刚指出我的数学是错误的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
But the point here is you would expect the people in the metformin group to have a far worse outcome, i.e. to have a far worse crude death rate.
但这里的要点是，您会期望二甲双胍组的人有更糟糕的结果，即粗死亡率更差。
And the fact that it was statistically significant in the other direction, and it turned out on what's called a Cox proportional hazard, which is where you actually model the difference in lifespan.
事实上，它在另一个方向上具有统计显着性，结果是所谓的 Cox 比例风险，这就是您实际对寿命差异进行建模的地方。
The people who took metformin and had diabetes had a 15%, 1-5, 15% relative reduction in all-cause death over 2.8 years, which was the median duration of follow-up compared to the non-
服用二甲双胍并患有糖尿病的人在 2.8 年内全因死亡相对减少了 15%、1-5、15%，这是与非服用二甲双胍的患者相比的中位随访时间。
Andrew Huberman:
安德鲁·休伯曼：
Well, that seems to be the number that makes me go, "Wow."
嗯，这个数字似乎让我发出“哇”的感叹。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Right?
对吗？
Could you repeat those numbers again?
你能再重复一遍这些数字吗？
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yep.
是的。
So 15% reduction in all-cause mortality over 2.8 years.
因此，2.8 年内全因死亡率降低了 15%。
Andrew Huberman:
安德鲁·休伯曼：
That's a big deal.
这是一件大事。
Dr. Peter Attia:
彼得·阿蒂亚博士：
It is.
是的。
And again, there's no clear explanation for it unless you believe that metformin is doing something beyond helping you lower blood glucose.
再说一次，除非您相信二甲双胍除了帮助您降低血糖之外还有其他作用，否则对此没有明确的解释。
Because the difference in blood glucose between these two people was still in favor of the non-diabetics.
因为这两个人之间的血糖差异仍然有利于非糖尿病患者。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Peter Attia:
彼得·阿蒂亚博士：
So again, the proponents of metformin being a geroprotective agent, and I put myself in this category at one point.
再说一次，二甲双胍的支持者是一种老年保护剂，而我曾经将自己归入这一类别。
I would put myself today in the category of undecided, but at the time, I very much believed this was a very good suggestion that metformin was doing other things.
今天我会把自己归入犹豫不决的范畴，但当时，我非常相信这是一个很好的建议，二甲双胍正在做其他事情。
You mentioned a couple already.
你已经提到了几个。
Metformin is a weak inhibitor of mTOR.
二甲双胍是 mTOR 的弱抑制剂。
Metformin reduces inflammation.
二甲双胍可减轻炎症。
Metformin potentially tamps down on senescent cells and their secretory products.
二甲双胍可能会抑制衰老细胞及其分泌产物。
There are lots of things metformin could be doing that are off target, and it might be that those things are conferring the advantage.
二甲双胍有很多可能偏离目标的作用，而这些作用可能会带来优势。
So fast-forward until a year ago, and I think most people took the Banister study as kind of the best evidence we have for the benefits of metformin, and I'm sure you've had lots of people come up to you and ask you, "Should I be on metformin?
快进到一年前，我想大多数人都将班尼斯特研究视为我们所掌握的二甲双胍益处的最佳证据，我相信有很多人来找你问你，“我应该服用二甲双胍吗？
Should I be on metformin?" I probably get asked that question almost as much as I'm asked any question, outside of dew.
我应该服用二甲双胍吗？”除了露水之外，我被问到这个问题的次数可能几乎和我被问到的任何问题一样多。
People definitely want to know if you should be consuming dew.
人们肯定想知道你是否应该食用露水。
But after that, it's metformin.
但在那之后，它是二甲双胍。
Andrew Huberman:
安德鲁·休伯曼：
Fresh off the leaves-
刚摘下叶子——
Dr. Peter Attia:
彼得·阿蒂亚博士：
Has to be
必须是
Andrew Huberman:
安德鲁·休伯曼：
...
...
while viewing morning sunlight.
当观看早晨的阳光时。
Dr. Peter Attia:
彼得·阿蒂亚博士：
So okay.
那么好吧。
So let's fast-forward to now, the paper that I wanted to spend a few more minutes on.
让我们快进到现在，我想再花几分钟讨论的论文。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, and thanks for that background.
是的，谢谢你的背景。
I'm still dazzled by the insertion of the straw by way of insulin.
我仍然对通过胰岛素插入吸管感到眼花缭乱。
I don't think I've ever heard that described.
我想我从来没有听过这样的描述。
I need to go get a better textbook.
我需要去买一本更好的教科书。
Dr. Peter Attia:
彼得·阿蒂亚博士：
It's a pretty short straw, in fairness.
公平地说，这是一根很短的稻草。
It's just a little transport.
这只是一个小交通工具。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Just to give people a sense of why I'm so dazzled by it, I am always fascinated by how quickly, how efficiently, and how specifically biology can create these little protein complexes that do something really important.
只是为了让人们明白为什么我对它如此着迷，我总是着迷于生物学如何快速、高效和具体地创造出这些小的蛋白质复合物，这些蛋白质复合物可以做一些真正重要的事情。
You're talking about an on-demand creation of a portal, right?
您说的是按需创建门户，对吧？
These are cells engineering their own machinery in real time in response to chemical signals.
这些细胞实时设计自己的机器以响应化学信号。
Dr. Peter Attia:
彼得·阿蒂亚博士：
But remind me-
但提醒我——
Andrew Huberman:
安德鲁·休伯曼：
It's great
太棒了
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
But I'm sort of rusty on my neuroscience, but an action potential works in reverse the same way.
但我对我的神经科学有点生疏，但动作电位以同样的方式反向工作。
You need the ATP gradient to restore the gradient, but once the action potential fires, it's passive outside, right?
你需要 ATP 梯度来恢复梯度，但是一旦动作电位激发，它就处于被动状态，对吧？
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
So what Peter's referring to is the way that neurons become electrically active is by the flow of ions from the outside of the cell to the inside of the cell, and we have both active conductances, meaning they're triggered by electrical changes in the gradients via changes in electrical potential, and then there are passive gradients where things can just flow back and forth until there's a balance equal inside and outside the cell.
所以彼得指的是神经元变得电活跃的方式是通过离子从细胞外部流到细胞内部，我们有两种主动电导，这意味着它们是通过电位变化由梯度的电变化触发的，然后还有被动梯度，东西可以来回流动，直到细胞内外达到平衡。
I think what's different is that there's some movement of a lot of stuff inside of neurons when neurotransmitters like dopamine binds to its receptor, and then a bunch of It's like a bucket brigade that gets kicked off internally.
我认为不同的是，当像多巴胺这样的神经递质与其受体结合时，神经元内部的很多东西都会发生一些运动，然后一堆像水桶大队一样在内部启动。
But it's not often that you hear about receptors getting inserted into cells very quickly.
但你很少听说受体很快插入细胞。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah, I see your point.
是的，我明白你的意思。
Andrew Huberman:
安德鲁·休伯曼：
Normally, you have to go through a process of transcribing genes and making sure that the specific proteins are made, and then those are long, slow things that take place over the course of many hours or days.
通常，你必须经历一个转录基因的过程，并确保制造出特定的蛋白质，然后这些都是漫长而缓慢的过程，需要几个小时或几天的时间才能完成。
What you're talking about is a real on-demand insertion of-
你所说的是真正的按需插入-
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah, it works in minutes
是的，几分钟后就可以了
Andrew Huberman:
安德鲁·休伯曼：
...
...
of a channel.
一个通道的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yep.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And it makes sense as to why that would be required, but it's just oh, so very cool.
为什么需要这样做是有道理的，但它只是哦，非常酷。
Dr. Peter Attia:
彼得·阿蒂亚博士：
It's cool.
很酷。
Yep.
是的。
So Keyes and colleagues came along and said: We would like to redo the entire Banister analysis.
于是凯斯和同事过来说道：我们想重做整个巴尼斯特分析。
And I think their motivation for it was the interest in this topic is through the roof.
我认为他们这样做的动机是对这个话题的兴趣非常浓厚。
There is a clinical trial called the TAME trial that is, I think, pretty much funded now and may be getting underway soon.
我认为，有一项名为 TAME 试验的临床试验目前已经获得了相当多的资金，并且可能很快就会开始。
The TAME trial, which is an important trial, is going to try to ask this question prospectively and through random assignment.
TAME 试验是一项重要的试验，它将尝试通过随机分配前瞻性地提出这个问题。
So-
所以——
Andrew Huberman:
安德鲁·休伯曼：
So this is the Targeting Aging with Metformin trial, TAME.
这就是二甲双胍靶向衰老试验 TAME。
Dr. Peter Attia:
彼得·阿蒂亚博士：
That's correct.
这是正确的。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Nir Barzilai is probably the senior PI on that.
Nir Barzilai 可能是这方面的高级 PI。
And I think in many ways, the Banister study, along with some other studies, but of lesser significance, probably provided some of the motivation for the TAME trial.
我认为，从很多方面来说，巴尼斯特研究以及其他一些意义较小的研究可能为 TAME 试验提供了一些动机。
So they said, "Okay, look, we're going to do this.
所以他们说：“好吧，看，我们就这么做。
We're going to use a different cohort of people." So the first study that we just talked about, the Banister study, used, I believe it was roughly they sampled 95,000 subjects from a UK biobank.
我们将使用不同的人群。”所以我们刚才谈到的第一项研究，即巴尼斯特研究，我相信他们从英国生物库中抽取了大约 95,000 名受试者。
Here, they used a larger sample.
在这里，他们使用了更大的样本。
They did about half a million people sampled from-
他们对大约 50 万人进行了抽样调查——
Andrew Huberman:
安德鲁·休伯曼：
Wow
哇
Dr. Peter Attia:
彼得·阿蒂亚博士：
...
...
a Danish health registry.
丹麦健康登记处。
And they did something pretty elegant.
他们做了一些非常优雅的事情。
They created two groups to study.
他们创建了两个小组进行研究。
So the first was just a standard replication of what Banister did, which was just a group of people with and without diabetic that they tried to match as perfectly as possible.
所以第一个只是巴尼斯特所做的标准复制，这只是一群患有和没有糖尿病的人，他们试图尽可能完美地匹配。
But then they did a second analysis in parallel with discordant twins.
但随后他们对不一致的双胞胎进行了第二次分析。
So same-sex twins that only differed in that one had diabetes and one didn't.
同性双胞胎的唯一区别在于，一个患有糖尿病，一个没有。
I thought this was very elegant because here you have a degree of genetic similarity, and you have similar environmental factors during childhood that might allow you to see if there's any sort of difference in signal.
我认为这非常优雅，因为这里有一定程度的遗传相似性，并且童年时期有相似的环境因素，这可能会让你看到信号是否存在任何差异。
So now turning this back into a little bit of a journal club, virtually any clinical paper you're going to read, table one is the characteristics of the people in the study.
所以现在把它变成一个期刊俱乐部，几乎任何你要读的临床论文，表一是研究中的人的特征。
You always want to take a look at that.
你总是想看看那个。
So when I look at table one here, you can see it's-- And by the way, just for people watching this, we're going to make all these papers and figures available.
因此，当我查看这里的表一时，您可以看到它——顺便说一下，我们将向观看此内容的人们提供所有这些论文和数据。
So if you're-- We'll have nice show notes that'll make all this clear.
所以如果你——我们会有很好的演出笔记来让这一切变得清晰。
So table one in the Keyes paper shows the baseline characteristics.
因此，凯斯论文中的表一显示了基线特征。
And again, it's almost always going to be the first table in a paper.
再说一遍，它几乎总是论文中的第一个表格。
Usually, the first figure in the paper is a study design.
通常，论文中的第一个图是研究设计。
It's usually a flow chart that says, "These were the inclusion criteria.
它通常是一个流程图，上面写着：“这些是纳入标准。
These were all the people that got excluded.
这些都是被排除在外的人。
This is how we randomized," et cetera.
这就是我们随机化的方式，”等等。
And you can see here that there are four columns.
您可以在这里看到有四列。
So the first two are the singletons.
所以前两个是单例。
These are people who are not related.
这些人是没有血缘关系的人。
And then the second two are the twins who are matched.
然后第二个是匹配的双胞胎。
And you can see, remember how I said they sampled about 500,000 people?
你可以看到，还记得我说过他们对大约 500,000 人进行了抽样吗？
You can see the numbers.
你可以看到数字。
So they got 7,842 singletons on metformin, the same number than they pulled out matched without diabetes.
因此，他们获得了 7,842 名服用二甲双胍的单身人士，与他们抽取的未患有糖尿病的匹配人数相同。
On the twins, they got 976 on metformin with diabetes, and then, by definition, 976 co-twins without them.
在这对双胞胎中，有 976 名患有糖尿病的患者服用了二甲双胍，而根据定义，另外 976 名双胞胎则没有服用二甲双胍。
And you look at all these characteristics.
你看看所有这些特征。
What was their age upon entry?
他们入境时的年龄是多少？
How many were men?
有多少人是男性？
What was the year of indexing when we got them?
我们得到它们时索引是哪一年的？
What medications were they on?
他们服用什么药物？
What was their highest level of education, marital status, et cetera?
他们的最高教育水平、婚姻状况等是什么？
The one thing I want to call out here that really cannot be matched in a study like this, so this is a very important limitation, is the medication.
我想在这里指出的一件事在这样的研究中确实无法匹配，所以这是一个非常重要的限制，那就是药物。
So look at that column, Andrew.
所以看看那个专栏，安德鲁。
Notice how pretty much everything else is perfectly matched until you get to the medication list.
请注意，在您看到药物清单之前，几乎所有其他东西都是完美匹配的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, it's all over the place.
是的，到处都是。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
It's not even close.
还差得很远。
They're nowhere near matched, right?
他们根本不匹配，对吧？
In other words, just to give you a couple of examples, right?
换句话说，只是给你举几个例子，对吧？
And let's just talk about the singletons because it's basically the same story on the twins.
我们只讨论单身人士，因为双胞胎的情况基本相同。
If you look at what fraction of the people with type 2 diabetes are on lipid-lowering medication, it's 45.6% versus 15.4% in the matched without diabetes.
如果你看看 2 型糖尿病患者服用降脂药物的比例是 45.6%，而没有糖尿病的患者则为 15.4%。
It's a 3X difference.
这是 3 倍的差异。
What about antiplatelet therapy?
抗血小板治疗怎么样？
That's 30% versus 14%.
分别是 30% 和 14%。
Antihypertensives, 63% versus-
抗高血压药，63% 对比-
Andrew Huberman:
安德鲁·休伯曼：
Right
右
Dr. Peter Attia:
彼得·阿蒂亚博士：
...
...
31%.
31%。
Andrew Huberman:
安德鲁·休伯曼：
Because people who have one health issue and are taking metformin are likely to have other health issues.
因为患有一种健康问题并正在服用二甲双胍的人可能会出现其他健康问题。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Exactly.
正是如此。
So this is, again, a fundamental flaw of epidemiology.
因此，这又是流行病学的一个根本缺陷。
You can never remove all the confounders.
你永远无法消除所有的混杂因素。
Andrew Huberman:
安德鲁·休伯曼：
Ugh.
呃。
This is why I became an experimental scientist.
这就是我成为一名实验科学家的原因。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So that we could control variables.
这样我们就可以控制变量。
Dr. Peter Attia:
彼得·阿蒂亚博士：
That's right, because without random assignment, you cannot control every variable.
没错，因为如果没有随机分配，您就无法控制每个变量。
Now, you'll see in a moment when we get into the analysis, they go through three levels of corrections, but they can never correct this medication one.
现在，当我们进入分析时，您会看到，他们经历了三个级别的纠正，但他们永远无法纠正这种药物。
So just keep that in the back of your mind.
所以请记住这一点。
Okay.
好的。
So the two big things that were done in this experiment, or in this survey, or study, to differentiate it from Banister was, one, the twin trick, which I think is pretty cool.
因此，在这个实验、调查或研究中，为了将其与班尼斯特区分开来，我们做了两件大事，一是双胞胎技巧，我认为这非常酷。
The second thing that they did was they did a sensitivity analysis with and without informative censoring.
他们做的第二件事是在有或没有信息审查的情况下进行了敏感性分析。
So one of the other things they wanted to know was, hey, does it really matter if we don't count the metformin patients who progress?
因此，他们想知道的另一件事是，嘿，如果我们不计算进展的二甲双胍患者，这真的很重要吗？
So let's see what transcribed.
那么我们来看看转录了什么。
So the next figure, figure two-- Pardon me.
所以下一个图，图二——请原谅。
The next table, table two, walks you through the crude mortality rate in each of the groups.
下一张表（表二）将带您了解每组的粗死亡率。
So the most important row, I think, in this table is the one that says crude mortality per thousand person years.
因此，我认为该表中最重要的一行是每千人年粗死亡率。
Now, you recall that in the previous study, in the Banister study, those were On the ballpark of about 15 per.
现在，您还记得在之前的 Banister 研究中，这些大约为 15%。
Okay, so let's look at each of these.
好的，让我们分别看看。
So in the singletons, so the non-twins who were not diabetic, it was 16.86.
所以在单身人士中，也就是没有患糖尿病的非双胞胎中，这个数字是 16.86。
Andrew Huberman:
安德鲁·休伯曼：
And could you put a little more contour on what this 1,000 person years-
你能否对这 1,000 人年有更多的轮廓-
Dr. Peter Attia:
彼得·阿蒂亚博士：
What it is?
它是什么？
Andrew Huberman:
安德鲁·休伯曼：
Are you talking about pooling the lifespans of a bunch of different people until you get to the number 1,000?
你是在谈论将一群不同的人的寿命汇总起来直到达到 1,000 吗？
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Because this-
因为这个——
Andrew Huberman:
安德鲁·休伯曼：
So you're normalizing not-- So it's not who's going to live 1,000 years, because-
所以你正在正常化——所以这不是谁会活1000岁的问题，因为——
Dr. Peter Attia:
彼得·阿蒂亚博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
no one's expecting that.
没有人期待这一点。
So you've got some people that are going to live 76 years, 52 years, 91 years, and you're pooling all of those until you hit 1,000.
因此，有些人的寿命将达到 76 岁、52 岁、91 岁，然后将所有这些人的寿命汇总起来，直到达到 1,000 岁。
And then that becomes a normalized division.
然后这就变成了标准化的划分。
You're basically like, so let's say the control group, you're asking if there were 1,000 person years available to live, how likely is it that this person would live another 15?
你基本上就像，假设对照组，你问如果有 1,000 人年可活，这个人再活 15 年的可能性有多大？
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
So a couple ways to think about it.
所以有几种思考方法。
So taking a step back, we always have to have some way of normalizing.
因此，退一步来说，我们总是必须有某种方式来实现正常化。
So when we talk about the mortality from a disease like cancer in the population, we report it as what's the mortality rate per, and it's typically per 100,000 persons.
因此，当我们谈论人口中癌症等疾病的死亡率时，我们将其报告为每人的死亡率，通常是每 10 万人。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
So-
所以——
Andrew Huberman:
安德鲁·休伯曼：
That's a much more intuitive way to express it
这是一种更直观的表达方式
Dr. Peter Attia:
彼得·阿蒂亚博士：
It is, but the reason we can do it that way is because we're literally looking at how many people died this calendar year, and we divide it by the number of people in that age group.
确实如此，但我们之所以能这样做，是因为我们实际上是在统计今年有多少人死亡，然后将其除以该年龄段的人数。
So it's typically what you're doing when you look at aged groups in buckets of decades.
因此，当您观察数十年的老年人群时，这通常是您正在做的事情。
So that's why we can say the highest mortality is people 90 and up.
这就是为什么我们可以说死亡率最高的是90岁及以上的人。
Even though the absolute number of deaths is small, it's because there's not that many people there, right?
虽然死亡的绝对数字很小，但那是因为那里的人不多吧？
The majority of deaths in absolute terms probably occur in the seventh decade.
从绝对值来看，大多数死亡可能发生在七十岁。
But as you go up, because the denominator is shrinking, you have to normalize to it.
但当你上升时，因为分母正在缩小，你必须对其进行标准化。
So we just normalize to the number of people.
所以我们只是将人数归一化。
Here are all the people that started the year, here are all the people that ended the year.
这里是所有开始这一年的人，这里是所有结束这一年的人。
What's the death rate?
死亡率是多少？
Why are these done in a slightly more complicated way?
为什么这些要以稍微复杂的方式完成？
Because we don't follow these people for their whole lives.
因为我们不会跟随这些人一生。
We're only following them for a period of observation, in this case, roughly three years.
我们只是跟踪他们一段时间的观察，在这种情况下，大约是三年。
So to say something like, we have a crude death rate of five deaths per 1,000 person years, one way to think about that is if you had 1,000 people and you followed them for one year, you'd expect five to die.
可以这么说，我们的粗死亡率是每 1,000 人每年有 5 人死亡，一种思考方式是，如果你有 1,000 人，并且你跟踪他们一年，你会预计有 5 人死亡。
If you had 500 people and you followed them for two years, you expect five to die.
如果你有 500 人，并且你跟踪他们两年，你预计会有 5 人死亡。
If you have 1,000 people and you follow them for one year, you expect five to die.
如果你有 1,000 人，并且你跟踪他们一年，你预计会有 5 人死亡。
Those would all be considered equivalent mortalities.
这些都将被视为同等死亡率。
Andrew Huberman:
安德鲁·休伯曼：
Great.
太棒了。
Thank you for clarifying that.
感谢您澄清这一点。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
No, this stuff is-- I find epidemiology, when you get in the weeds, is way more complicated than following the basics of experimental stuff where you get to push all this stuff into the garbage bin and just say, "We're going to take this number of people, we're going to exclude this group, we're going to randomize, we're going to see what happens."
不，我发现流行病学，当你深入了解时，比遵循实验材料的基础知识要复杂得多，在实验材料中你可以将所有这些东西推入垃圾桶，然后说，“我们将吸收这么多人，我们将排除这个群体，我们将随机化，我们将看看会发生什么。”
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
That's like the paper we'll talk about next.
这就像我们接下来要讨论的论文。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yep.
是的。
So when you adjust for age, and they don't show it in this table, it's only in the text, when you adjust for age, a very important check to do is what is the crude death rate of the people on metformin who are not twins versus who are twins?
所以，当你调整年龄时，他们没有在这个表中显示，它只在文本中显示，当你调整年龄时，一个非常重要的检查是服用二甲双胍的非双胞胎和双胞胎的粗死亡率是多少？
Now, in this table, they look different because it's 24.93 for the metformin group and 21.68 for the twin group that's on metformin.
现在，在此表中，它们看起来有所不同，因为二甲双胍组为 24.93，而服用二甲双胍的双胞胎组为 21.68。
When you adjust for age, they're almost identical.
当你根据年龄进行调整时，它们几乎是相同的。
It goes from 24.93 to 24.7.
它从 24.93 变为 24.7。
One other point I'll make here for people who are going to be looking at this table is you'll notice there are parentheses after every one of these numbers.
我要向那些将要查看此表的人指出的另一点是，您会注意到每个数字后面都有括号。
What does that offer in there?
那里提供什么？
Those parentheses are offering the 95% confidence interval.
这些括号提供了 95% 的置信区间。
So for example, to take the number 24.93 is the crude death rate of how many people are dying who take metformin.
例如，数字 24.93 是服用二甲双胍的死亡人数的粗死亡率。
What it's telling you is we're 95% confident that the actual number is between 23.23 and 26.64.
它告诉您的是，我们有 95% 的信心认为实际数字在 23.23 到 26.64 之间。
If a 95% confidence interval does not cross the number zero, it's statistically significant.
如果 95% 的置信区间不跨越数字零，则具有统计显着性。
Okay, so the first thing that just jumps out at you, I think when you look at this, is there's clearly a difference here between the people who have diabetes and those who don't.
好吧，我想当你看到这个时，你首先想到的第一件事是，患有糖尿病的人和没有糖尿病的人之间存在明显的差异。
It complicates the study a little bit because it's basically two studies in one, but you're comparing 95, pardon me, 24.93 to 16.86, which by the way remains after age adjustment.
它使研究变得有点复杂，因为它基本上是两项研究合二为一，但你正在比较 95，请原谅我，24.93 和 16.86，顺便说一句，在年龄调整后仍然如此。
When you go to the twin group, it's 24.73 to 12.94.
当你去双子组时，它是24.73到12.94。
Andrew Huberman:
安德鲁·休伯曼：
So maybe just to zoom out for that, what you're describing, if I understand correctly, is this crude deaths per 1,000 person years, let's just talk about the singletons, the non-twins-
所以也许只是为了缩小这个范围，如果我理解正确的话，你所描述的是每千人年的粗略死亡人数，让我们只谈谈单身人士，非双胞胎——
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
is 16.86.
是 16.86。
So 16.86 people die, and some people are probably thinking, "How can .86 of a person die?" Well, it's not always whole numbers, but there's a bad joke to be made here.
那么 16.86 人死亡，有些人可能会想，“一个人怎么会死 0.86 人呢？”好吧，它并不总是整数，但这里有一个糟糕的笑话。
But-
但是——
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah, just call it 17 versus 25.
是的，就叫它17对25吧。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
17 deaths per 1,000 versus 25 deaths.
每 1,000 人中有 17 人死亡，而每 1,000 人中有 25 人死亡。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yep.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And the 25 is in the folks that took metformin.
25 是服用二甲双胍的人群。
Now, that to the naive listener, and to me means, oh, metformin basically kills you, right?
现在，对于天真的听众和我来说，这意味着，哦，二甲双胍基本上会杀死你，对吗？
Not faster, or you're more likely to die.
不能更快，否则你更有可能死。
But we have to remember that these people have a major health issue that the other group does not have.
但我们必须记住，这些人有其他群体没有的重大健康问题。
Dr. Peter Attia:
彼得·阿蒂亚博士：
That's right.
没错。
Andrew Huberman:
安德鲁·休伯曼：
Because people weren't assigned drug or not assigned drug, it wasn't placebo drug.
因为人们没有被分配药物或没有被分配药物，所以它不是安慰剂药物。
It's let's look at people taking this drug for a bad health issue and compare to everyone else.
让我们看看那些因健康问题而服用这种药物的人，并与其他人进行比较。
Dr. Peter Attia:
彼得·阿蒂亚博士：
That's right.
没错。
So now you have to go into, and I'll just skip the next figure, but the next figure is a Kaplan-Meier curve.
所以现在你必须进入，我将跳过下一个图，但下一个图是卡普兰-迈耶曲线。
I think it's actually worth looking at it because they show up in all sorts of studies.
我认为这实际上值得一看，因为它们出现在各种研究中。
So if you look at figure one, it's a Kaplan-Meier curve, which is a mortality curve.
所以如果你看一下图一，它是一条卡普兰-迈耶曲线，也就是死亡率曲线。
So you'll see these in any study that is looking at death, and this can be prospective, randomized, this can be retrospective, but these are always going to show up.
所以你会在任何研究死亡的研究中看到这些，这可以是前瞻性的、随机的，也可以是回顾性的，但这些总是会出现。
And I think it's really worth understanding what a Kaplan-Meier curve shows you.
我认为了解卡普兰-迈耶曲线所显示的内容确实值得。
So on the x-axis is always time, and on the y-axis is always the cumulative survival.
因此，x 轴始终是时间，y 轴始终是累积生存率。
So it's a curve that always goes from zero to one, 1 or 100%, and it's always decreasing monotonically, meaning it can only go down or stay flat, it can never go back up.
所以它是一条总是从 0 到 1、1 或 100% 的曲线，而且它总是单调递减，这意味着它只能下降或保持平坦，永远不会上升。
So that's what a cumulative mortality curve looks like.
这就是累积死亡率曲线的样子。
Andrew Huberman:
安德鲁·休伯曼：
Now we're looking at, you're starting at alive and you're looking at how many people die for every year that passes.
现在我们正在考虑，你一开始还活着，你正在考虑每年有多少人死亡。
Dr. Peter Attia:
彼得·阿蒂亚博士：
That's right.
没错。
And in each curve, there's one on the left, which is the matched singletons, and there's one on the right, which are the discordant twins.
在每条曲线中，左边有一个，这是匹配的单例，右边有一个，这是不一致的双胞胎。
You have two lines.
你有两条线。
You have those that were on metformin with type 2 diabetes, and you have their matched controls.
有服用二甲双胍治疗 2 型糖尿病的患者，也有与之匹配的对照组。
And in this figure, the matched controls are the darker lines, and the people with type 2 diabetes on metformin, that's the lighter line.
在该图中，匹配的对照是较暗的线，而服用二甲双胍的 2 型糖尿病患者是较浅的线。
You'll also notice, and I like the way they've done it here, they've got shading around each one.
你还会注意到，我喜欢他们在这里所做的方式，他们在每个周围都有阴影。
Andrew Huberman:
安德鲁·休伯曼：
And we should mention for those that are just listening, that in both of these graphs, the downward trending line from the controls, so again, non-diabetic, not taking metformin, is above the line corresponding to the diabetics who are taking metformin.
我们应该向那些刚刚听的人提一下，在这两张图中，对照组的下降趋势线（因此，非糖尿病患者、不服用二甲双胍）高于与服用二甲双胍的糖尿病患者相对应的线。
Put crudely, the people who are taking metformin that have diabetes are dying at a faster rate for every single year examined.
粗略地说，每接受一年检查，服用二甲双胍的糖尿病患者的死亡率就会加快。
The two lines do not overlap except at the beginning when everyone's alive.
除了一开始每个人都还活着的时候，两条线不会重叠。
It's like a foot race, where basically the people with metformin and diabetes are falling behind and dying as they fall.
这就像一场赛跑，基本上患有二甲双胍和糖尿病的人都落后了，并在摔倒时死亡。
Dr. Peter Attia:
彼得·阿蒂亚博士：
That's right, and I'm glad you brought up a good point.
是的，我很高兴你提出了一个很好的观点。
It's not uncommon in treatments to see Kaplan-Meier curves cross.
在治疗中，卡普兰-迈耶曲线交叉并不罕见。
They don't have to.
他们不必这样做。
It's not a requirement that they never cross.
这并不是要求他们永远不会跨越。
It's only a requirement that they're monotonically decreasing or staying flat.
只是要求它们单调递减或保持平坦。
So I've seen cancer treatment drugs where they have two drugs going head to head in a cancer treatment, and one starts out looking really, really bad, but then all of a sudden it flattens while the other one goes bad, and then it actually crosses and goes underneath.
所以我见过癌症治疗药物，其中两种药物在癌症治疗中针锋相对，其中一种开始看起来非常非常糟糕，但突然它变平，而另一种则变坏，然后它实际上交叉并进入下面。
But that's not the case here.
但这里的情况并非如此。
So to your point, the people with diabetes taking metformin, in both the matched singletons and the discordance, are dropping much faster, and they always stay below.
因此，就您的观点而言，服用二甲双胍的糖尿病患者，无论是匹配的单身患者还是不一致的患者，下降速度都要快得多，而且总是保持在较低水平。
And I was just going to say that the shading is just showing you a 95% confidence interval.
我只是想说，阴影只是向您显示 95% 的置信区间。
So you're just putting basically error bars along this.
所以你只是把基本的误差线放在上面。
So if this were experimental data, if you were doing an experiment with a group of mice and you were watching their survival and you'd have error bars on this, which you're actually measuring.
因此，如果这是实验数据，如果您正在对一组小鼠进行实验并观察它们的生存情况，那么您实际上会在测量时出现误差线。
So because you have much more data here, you're just showing this in this fashion.
因为这里有更多的数据，所以您只是以这种方式显示它。
Andrew Huberman:
安德鲁·休伯曼：
For those that haven't been familiarized with statistics, no problem.
对于那些不熟悉统计数据的人来说，没问题。
Error bars correspond to if you were just going to measure the heights of a room full of 10th graders, there's going to be a range, right?
误差线相当于如果您要测量一个满是十年级学生的房间的高度，就会有一个范围，对吗？
You'll have the very tall kid and the very shorter kid, and you'll have the short kid and the medium kid.
你会有一个很高的孩子和一个很矮的孩子，你会有一个矮的孩子和一个中等的孩子。
And so there's a range.
所以有一个范围。
There's going to be an average, a mean, and then there'll be standard deviations and standard errors.
会有一个平均值，一个平均数，然后会有标准差和标准误差。
And so these confidence intervals just give a sense of how much range.
因此，这些置信区间只是给出了范围的大小。
Some people die early, some people die late, within a given year, they're going to be different ages.
有的人死得早，有的人死得晚，一年之内，他们的年龄是不同的。
So these error bars can account for a lot of different forms of variability.
因此，这些误差线可以解释许多不同形式的变异性。
Here, you're talking about the variability is how many people in each group die.
在这里，您所说的变异性是指每组中有多少人死亡。
We're not tracking one diabetic taking metformin versus a control.
我们没有追踪服用二甲双胍的糖尿病患者与对照组的情况。
I should have asked this earlier, but-
我应该早点问这个问题的，但是——
Dr. Peter Attia:
彼得·阿蒂亚博士：
Well, and it's also a mathematical model at this point, too, that's smoothing it out.
嗯，此时它也是一个数学模型，它正在对其进行平滑处理。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Because notice it's running for the full eight years, even though they're only following people for typically, I think the median was three or four years at a time.
因为请注意，它已经运行了整整八年，尽管他们通常只是跟踪人们，但我认为中位数一次是三到四年。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Peter Attia:
彼得·阿蒂亚博士：
So they're using this quite complicated type of mathematics called a Cox proportional hazard, which is what generates hazard ratios.
因此，他们使用了一种相当复杂的数学类型，称为 Cox 比例风险，这就是生成风险比的原因。
And basically, any model has to have some error in it, and so they're basically saying this is the error.
基本上，任何模型都必须有一些错误，所以他们基本上说这就是错误。
So you could argue when you look at that figure, we don't know exactly where the line is in there, but we know it's in that shaded area.
因此，当您查看该图时，您可能会争论，我们不知道该线的确切位置，但我们知道它位于该阴影区域。
Andrew Huberman:
安德鲁·休伯曼：
Am I-
我是不是——
Dr. Peter Attia:
彼得·阿蒂亚博士：
Sorry, one other point.
抱歉，还有一点。
If those shaded areas overlapped, you couldn't really make the conclusion.
如果这些阴影区域重叠，你就无法真正得出结论。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Peter Attia:
彼得·阿蒂亚博士：
You wouldn't know for sure that one is different from the other.
您无法确定其中一个与另一个不同。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, that's actually a good opportunity to raise a common myth, which is a lot of people when they look at a paper, let's say it's a bar graph.
是的，这实际上是一个很好的机会来提出一个常见的神话，即很多人在看一篇论文时，假设它是一个条形图。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And they see these error bars, and they will say, people often think, "Oh, if the error bars overlap, it's not a significant difference.
他们看到这些误差线，他们会说，人们经常想，“哦，如果误差线重叠，那就不是显着差异。
But if the error bars don't overlap, meaning there's enough separation, then that's a real and meaningful difference." And that's not always the case.
但如果误差线不重叠，意味着有足够的分离，那么这就是真正且有意义的差异。”但情况并非总是如此。
It depends a lot on the form of the experiment.
这在很大程度上取决于实验的形式。
I often see some of the more robust Twitter battles over how people are reading graphs, and I think it's important to remember that you run the statistics, hopefully the correct statistics for the sample.
我经常看到一些关于人们如何阅读图表的更激烈的 Twitter 争论，我认为重要的是要记住你运行了统计数据，希望样本的统计数据是正确的。
But determining significance, whether or not the result could be due to something other than chance, of course, your confidence in that increases as it becomes typically p values, p less than 0.00001% chance that it's due to chance, right?
但是要确定显着性，无论结果是否可能是由于偶然之外的其他因素造成的，当然，您对此的信心会随着它通常变成 p 值而增加，p 小于 0.00001% 的机会，这是由于偶然，对吧？
So very low probability, less than 0.05 tends to be the gold standard cutoff.
所以概率非常低，小于 0.05 往往是黄金标准截止值。
But when you're talking about data like these, which are repeated measures over time, people are dropping out literally over time.
但当你谈论这样的数据时，随着时间的推移，这些数据是重复测量的，人们实际上会随着时间的推移而退出。
You're saying they've modeled it to make predictions as to what would happen.
你是说他们已经对其进行了建模来预测会发生什么。
We're not necessarily looking at raw data points here.
我们不一定要在这里查看原始数据点。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah, the raw data was in the previous table.
是的，原始数据在上表中。
That's now taken and run through this Cox model, and it's smoothed out.
现在，我们将其运用到 Cox 模型中，并对其进行了平滑处理。
Andrew Huberman:
安德鲁·休伯曼：
Got it.
明白了。
Dr. Peter Attia:
彼得·阿蒂亚博士：
And to your point about the bar graphs, yeah, I think the other thing you always want to understand is just because something doesn't achieve statistical significance, the only way you can say it's not significant is you have to know what it was powered to detect.
至于你关于条形图的观点，是的，我认为你总是想理解的另一件事只是因为某些东西没有达到统计显着性，你可以说它不显着的唯一方法是你必须知道它能够检测到什么。
And statistical power is a very important concept that probably doesn't get discussed enough.
统计功效是一个非常重要的概念，但可能没有得到足够的讨论。
But before you do an experiment, you have to have an expectation of what you believe the difference is between the groups, and you have to determine the number of samples you will need to assess whether or not that difference is there or not.
但在进行实验之前，您必须对各组之间的差异有一个预期，并且必须确定评估该差异是否存在所需的样本数量。
So you use something, it's called a power table, and you would go to the power table.
所以你使用一些东西，它被称为功率表，你会去功率表。
So if you're doing treatment A versus treatment B, and you say, "Well, look, I think treatment A is going to have a 50% response, and I think treatment B will have a 65% response," you literally go to a power table that says 50% response, 15% difference.
因此，如果您进行治疗 A 与治疗 B 比较，并且您说，“嗯，看，我认为治疗 A 将有 50% 的反应，我认为治疗 B 将有 65% 的反应”，您实际上会看到一个功效表，上面显示 50% 的反应，15% 的差异。
That gives you a place on the grid.
这让你在网格上占有一席之地。
And I want to be 90% sure that I'm right, so 90% power.
我想要 90% 确定我是对的，所以有 90% 的力量。
So there's going to be a statistician listening to this who's going to want to kill me, but this is directionally the way we would describe it.
因此，会有一位统计学家听到这个消息，他会想要杀了我，但这就是我们描述它的方向性方式。
And that tells you this is how many animals or people you would need in this study.
这告诉您在这项研究中需要多少动物或人。
You're going to need 147 in each group.
每组需要 147 个人。
And by the way, if you now do the experiment with 147 and you fail to find significance, you can comfortably say there is no statistical difference, at least up to that 15%.
顺便说一句，如果你现在用 147 进行实验，但没有发现显着性，你可以轻松地说没有统计差异，至少没有达到 15%。
There may be a difference at 10%, but you weren't powered to look at 10%.
10% 可能会有差异，但你没有能力去看 10%。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
And very important point that you're making.
你提出的非常重要的一点。
Another point that's just a more general one about statistics in general, the way to reduce variability in a data set is to increase sample size.
另一点是关于一般统计学的更普遍的一点，减少数据集中变异性的方法是增加样本量。
That makes sense.
这是有道理的。
If I just walk into a 10th grade class and go, "Yeah, I'm going to measure height," and I look up by the first three kids that I see, and I happen to look over there, and it's the three that all play on the volleyball team together, my sample size is small, and I'm likely to get a skewed representation, in this case, taller than average.
如果我走进十年级班级，说：“是的，我要测量身高”，然后我抬头看到我看到的前三个孩子，我碰巧朝那边看了一眼，发现这三个孩子一起在排球队打球，我的样本量很小，而且我很可能会得到一个倾斜的表示，在这种情况下，比平均身高高。
So increasing sample size tends to decrease variation.
因此，增加样本量往往会减少变异。
So that's why when you hear about a study from the UK Biobank or from half a million Danish citizens, like for instance, in this study, those are enormous sample sizes.
因此，这就是为什么当您听到英国生物银行或 50 万丹麦公民的一项研究（例如这项研究）时，您会发现这些样本量非常大。
So even though this is not an experimental study, it's an epidemiological observational study, there's tremendous power by way of the enormous number of subjects in the study.
因此，尽管这不是一项实验研究，而是一项流行病学观察研究，但由于研究对象数量众多，因此具有巨大的力量。
Dr. Peter Attia:
彼得·阿蒂亚博士：
And that's the way that epidemiology will make up for its deficit.
这就是流行病学弥补其缺陷的方式。
So you could never do a randomized assignment study on half a million people.
所以你永远不可能对五十万人进行随机分配研究。
So epidemiology makes up for its biggest limitation, which is it can never compensate for inherent biases by saying we can do infinite duration if we want.
因此，流行病学弥补了它最大的局限性，那就是它永远无法通过说如果我们愿意的话我们可以无限期地来弥补固有的偏见。
We could survey people over the course of their lives, and we can have the biggest sample size possible because this is relatively cheap.
我们可以对人们的一生进行调查，并且我们可以拥有尽可能大的样本量，因为这相对便宜。
The cost of actually doing an experiment where you have tens of thousands of people is prohibitive.
实际进行一个有数万人参与的实验的成本是令人望而却步的。
If you look at the Women's Health Initiative, which was a five-year study on, I don't know, what was it?
如果你看一下“妇女健康倡议”，这是一项为期五年的研究，我不知道它是什么？
50,000 women.
50,000 名女性。
That was a billion-dollar study.
那是一项耗资十亿美元的研究。
Andrew Huberman:
安德鲁·休伯曼：
Whew.
呼。
Dr. Peter Attia:
彼得·阿蒂亚博士：
So this is the balancing act between epidemiology and randomized prospective experiments.
所以这是流行病学和随机前瞻性实验之间的平衡行为。
And so they both offer something, but you just have to know the blind spots of each one.
所以他们都提供了一些东西，但你只需要知道每个人的盲点。
So let's just wrap this up.
让我们总结一下吧。
Let's just go to table four, which I think is the most important table in here, which now lays out the final results in terms of the hazard ratio.
让我们看看表四，我认为这是这里最重要的表，它现在列出了风险比的最终结果。
So this is the way we want to really be thinking about this.
所以这就是我们想要真正思考这个问题的方式。
So again, hazard ratios, these are important things to understand.
再次强调，风险比是需要理解的重要内容。
A hazard ratio is a number, and you always subtract one from the hazard ratio, and that tells you if it's a positive number.
风险比是一个数字，您总是从风险比中减去一，这会告诉您它是否为正数。
Sorry, if it's a number greater than one, you subtract one, and that tells you the relative harm.
抱歉，如果它是一个大于一的数字，您减去一，这就会告诉您相对危害。
So if the hazard ratio is 1.5, you subtract one.
因此，如果风险比为 1.5，则减去 1。
.5 is a 50% increase in risk.
.5 表示风险增加 50%。
If the number is negative, you may recall on the Banister paper, the hazard ratio was .85.
如果数字为负，您可能还记得 Banister 论文中的风险比为 0.85。
So that means it's a 15% reduction in relative risk.
这意味着相对风险降低了 15%。
And here you can see all the hazard ratios are positive.
在这里你可以看到所有的风险比都是正的。
So what it's telling you here is, and I'm going to walk through this because there's a lot of information packed here.
所以它在这里告诉你的是，我将逐步介绍这一点，因为这里包含了大量信息。
You've got singletons, you've got twins.
你有单胞胎，也有双胞胎。
They're showing you three different ways that they do it.
他们向您展示了三种不同的方法。
They do an unadjusted model.
他们做了一个未经调整的模型。
If you just look at the singletons with and without metformin, and you make no adjustments, the hazard ratio is 1.48, meaning the people on metformin had a 48% greater chance of dying in any given year than their non-diabetic counterpart.
如果您只观察服用和未服用二甲双胍的单身人士，并且不进行任何调整，则风险比为 1.48，这意味着服用二甲双胍的人在任何一年中的死亡几率比非糖尿病患者高 48%。
Andrew Huberman:
安德鲁·休伯曼：
The only reason I'm smiling, it's not because I enjoy people dying, quite to the contrary, is that this is novel for me in that I've read some epidemiological studies before, but it's not normally where I spend the majority of my time.
我微笑的唯一原因不是因为我喜欢人们的死亡，恰恰相反，这对我来说很新奇，因为我以前读过一些流行病学研究，但通常不是我花大部分时间的地方。
But up until now, I was thinking, "Okay, people taking metformin are dying more than those that aren't." I'm just relieved to know that I wasn't looking at all this backwards.
但到目前为止，我一直在想，“好吧，服用二甲双胍的人比不服用二甲双胍的人死亡率更高。”我很欣慰地知道我没有倒着看这一切。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
So they're dying more, but of course, we don't have a group that's taking metformin who doesn't have diabetes, and we don't have a group who has diabetes and is taking metformin plus something else.
所以他们的死亡率更高，但当然，我们没有一组服用二甲双胍但没有患有糖尿病，也没有一组患有糖尿病但同时服用二甲双胍和其他药物。
So again, we're only dealing with these constrained populations.
再说一遍，我们只处理这些受限人群。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Now, there's another arm to this study that I'm not getting into because it adds more complexity, which is they also have another group that's got diabetes, takes metformin, and takes sulfonylureas, which is a bigger drug, and those people die even more.
现在，这项研究还有另一个部分，我没有进入，因为它增加了更多的复杂性，即他们还有另一组患有糖尿病、服用二甲双胍和磺酰脲类药物的人，这是一种更大的药物，这些人的死亡率更高。
Andrew Huberman:
安德鲁·休伯曼：
Whoa.
哇哦。
So okay.
那么好吧。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Which again, speaks to the point, right?
这又说到了重点，对吧？
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Dr. Peter Attia:
彼得·阿蒂亚博士：
The more you need these medications, they're never able to erase the effect of diabetes.
您越需要这些药物，它们永远无法消除糖尿病的影响。
Andrew Huberman:
安德鲁·休伯曼：
But in this case, it seems that they might be possibly accelerating death due to diabetes.
但在这种情况下，他们似乎可能会加速糖尿病导致的死亡。
Possibly.
可能吧。
Dr. Peter Attia:
彼得·阿蒂亚博士：
We could never know that from this because we would need to see diabetics who don't take metformin, who take nothing.
我们永远无法从中知道这一点，因为我们需要看那些不服用二甲双胍、不服用任何药物的糖尿病患者。
And I would bet that they would do even worse.
我敢打赌他们会做得更糟。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Peter Attia:
彼得·阿蒂亚博士：
So my intuition is that the metformin is helping, but not helping nearly as much as we thought before.
所以我的直觉是二甲双胍有帮助，但没有我们之前想象的那么多。
So my point is they make another set of adjustments.
所以我的观点是他们做了另一组调整。
They say, "Okay, well look, in the first one, in the unadjusted model, we only matched for age and gender." Okay, that's pretty crude.
他们说：“好吧，好吧，在第一个模型中，在未经调整的模型中，我们只匹配年龄和性别。”好吧，这很粗糙。
What if we adjust for the medications they're on, the cardiovascular, psychiatric, pulmonary, dementia meds, and marital status?
如果我们根据他们所服用的药物（心血管、精神、肺、痴呆药物和婚姻状况）进行调整会怎样？
I don't know why they threw marital status in there, but they did.
我不知道他们为什么把婚姻状况放在那里，但他们这样做了。
Andrew Huberman:
安德鲁·休伯曼：
I don't know.
我不知道。
Maybe being married or unmarried can accelerate-
也许结婚或未婚可以加速——
Dr. Peter Attia:
彼得·阿蒂亚博士：
I'm sure it can, but it just seems like a random thing to throw in with all their meds.
我确信可以，但与他们所有的药物一起投入似乎是一个随机的事情。
I would've personally done that adjustment higher up.
我个人会在更高的位置进行调整。
But nevertheless, if you do that, all of a sudden the hazard ratio drops from 1.48 to 1.32, which means yep, you still have a 32% greater chance of dying in any given year.
但尽管如此，如果你这样做，风险比会突然从 1.48 下降到 1.32，这意味着，是的，你在任何一年中死亡的几率仍然会增加 32%。
All right.
好的。
What if we also adjust for the highest level of education along with any of the other covariates?
如果我们还针对最高教育水平以及任何其他协变量进行调整会怎么样？
Well, that doesn't really change it at all.
嗯，这并没有真正改变它。
It ends up at 1.33 or a 33% chance increase in death.
最终死亡概率增加 1.33，即 33%。
Okay.
好的。
Andrew Huberman:
安德鲁·休伯曼：
I always knew that more school wasn't going to save me.
我一直都知道更多的学校并不能拯救我。
Dr. Peter Attia:
彼得·阿蒂亚博士：
It's not doing jack.
这不是在做杰克。
So now let's do it for the twins.
现在让我们为双胞胎做这件事。
If you do the twin study, which you could argue is a slightly purer study because you at least have one genetic and environmental thing that you've attached, the unadjusted model is brutal, 2.15.
如果你进行双胞胎研究，你可能会认为这是一项稍微纯粹的研究，因为你至少附加了一项遗传和环境因素，那么未经调整的模型是残酷的，2.15。
That's 115%.
那是115%。
Think about this.
想想这个。
These are twins who in theory are the same in every way except one has diabetes and one doesn't, and the one with diabetes on metformin still has 115% greater chance of dying than the non-diabetic co-twin.
这些双胞胎理论上在各方面都是一样的，除了一个患有糖尿病而另一个没有，而且服用二甲双胍治疗的糖尿病患者的死亡几率仍然比非糖尿病双胞胎高出 115%。
Andrew Huberman:
安德鲁·休伯曼：
Brutal.
残酷。
Dr. Peter Attia:
彼得·阿蒂亚博士：
When you make that first adjustment of all the meds and marital status, you bring it down to a 70% increase in risk, and when you throw education in, it goes up to an 80% chance of risk.
当你对所有药物和婚姻状况进行第一次调整时，风险增加的可能性会降低到 70%，而当你加入教育后，风险增加的可能性会增加到 80%。
Now, they did this really cool thing, which was they did the analysis on with and without censoring.
现在，他们做了一件非常酷的事情，那就是他们在有审查和没有审查的情况下进行了分析。
So everything I just said here was based on no censoring.
所以我刚才在这里所说的一切都是基于没有审查。
Andrew Huberman:
安德鲁·休伯曼：
Tell me about censoring.
告诉我有关审查的事情。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Censoring is when you stop counting the metformin people who have died.
审查是指停止计算二甲双胍死亡人数。
Andrew Huberman:
安德鲁·休伯曼：
Mm.
嗯。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Okay.
好的。
So in the Singleton group, when you unadjust it, and the reason I'm doing the unadjusted is that's where they did the sensitivity analysis.
因此，在 Singleton 组中，当您取消调整它时，我进行未调整的原因是他们进行了敏感性分析。
I don't think it really matters that much.
我认为这并不那么重要。
You just have to draw a line in the sand somewhere.
你只需要在沙子上的某个地方画一条线即可。
You'll recall that that was a 48% chance of increased mortality, all-cause mortality, if you stop counting, pardon me, if you don't censor, meaning if you include everybody, including when people on metformin with diabetes die.
你会记得，死亡率增加的可能性是 48%，全因死亡率，如果你停止计算，请原谅我，如果你不进行审查，这意味着如果你包括所有人，包括服用二甲双胍的糖尿病患者死亡的情况。
If you censor them, it comes down to 1.39.
如果你审查它们，它会下降到 1.39。
In other words, this is a very important finding, it did not undo the benefits that we saw in the Banister study.
换句话说，这是一个非常重要的发现，它并没有抵消我们在巴尼斯特研究中看到的好处。
Banister saw a 15% reduction in mortality when they censored.
班尼斯特在进行审查后发现死亡率降低了 15%。
When Keyes censored, it got better, but not that much better.
当凯斯进行审查时，情况有所改善，但也没有好多少。
It went from 48% to 39%.
它从 48% 上升到 39%。
In the twins, it went from 115% down to only 97%.
在双胞胎中，这一比例从 115% 下降到只有 97%。
So in some ways, this presents a little bit of an enigma because it's not entirely clear to me, having read these papers many times, exactly why Banister found such a different response.
因此，在某些方面，这有点令人费解，因为在多次阅读这些论文后，我并不完全清楚巴尼斯特为何会得出如此不同的反应。
There's another technical detail of this paper, which is you can see on the right side of table four, they did something called a nested case control.
本文还有另一个技术细节，您可以在表四的右侧看到，他们做了一些称为嵌套案例控制的事情。
But you'll see, and I was going to go into a long explanation of what nested case controls are.
但你会看到，我将详细解释什么是嵌套案例控件。
It's another pretty elegant way to do case control studies where you sample by year, and you don't count all the cases at the end, you count them one by one.
这是进行病例对照研究的另一种非常优雅的方法，您按年份进行采样，并且最后不会计算所有病例，而是一个一个地计数。
I don't think it's worth getting into, Andrew, because it doesn't change the answer.
安德鲁，我认为这不值得讨论，因为它不会改变答案。
You can see it changes it just slightly, but it doesn't change the point.
你可以看到它只是稍微改变了一点，但它并没有改变要点。
The point here is the Keyes paper makes it undeniably clear that in that population, there was no advantage offered by metformin that undid the disadvantage of having type 2 diabetes.
这里的要点是，Keyes 的论文无可否认地清楚地表明，在该人群中，二甲双胍并没有提供任何优势来消除 2 型糖尿病的劣势。
This does not mean that metformin wasn't helping them, because we don't know what these people would've been like without metformin.
这并不意味着二甲双胍对他们没有帮助，因为我们不知道如果没有二甲双胍，这些人会是什么样子。
It could be that this bought them a 50% reduction in relative mortality to where they'd been.
这可能使他们的相对死亡率比原来降低了 50%。
But what it says is, in a way, this is what you would've expected.
但从某种程度上来说，它所说的正是你所期望的。
This is what you would've expected 10 years ago before the Banister paper came out.
这是 10 年前班尼斯特论文发表之前你所预料到的。
Andrew Huberman:
安德鲁·休伯曼：
Or maybe even before metformin was used, because in some ways it's saying, what is the likelihood that sick people who are on a lot of medication are going to die compared to not sick people who aren't on a lot of medication?
或者甚至可能在使用二甲双胍之前，因为在某些方面它说的是，与没有服用大量药物的未患病者相比，服用大量药物的病人死亡的可能性有多大？
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yep.
是的。
Andrew Huberman:
安德鲁·休伯曼：
It's not quite that simple in the sense that, as you said, there are ways to try and isolate the metformin contribution somewhat.
正如您所说，从某种意义上说，事情并不那么简单，有一些方法可以尝试在一定程度上隔离二甲双胍的作用。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yep.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Because they're on a bunch of other meds.
因为他们正在服用一堆其他药物。
And presumably that was done and analyzed in other figures where they can sort of try and-- They can never attach the results specifically to metformin, right?
想必这是在其他数据中完成和分析的，他们可以尝试——他们永远不能将结果专门附加到二甲双胍上，对吗？
But there must be some way of weighting the percentage that are on psychiatric meds or not on psychiatric meds.
但必须有某种方法来衡量服用精神科药物或不服用精神科药物的百分比。
There's some way to tease out whether or not there's actually some contribution of metformin to this result.
有一些方法可以弄清楚二甲双胍是否真的对这个结果有一定的贡献。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Well, that's what they're doing in the partial adjustment, is they're actually doing their best to say-
那么他们在局部调整中就是这么做的,他们实际上是在尽力说——
Andrew Huberman:
安德鲁·休伯曼：
Oh, right.
哦，对了。
Married or not married.
已婚或未婚。
They're going variable by variable.
它们会随着变量的变化而变化。
Dr. Peter Attia:
彼得·阿蒂亚博士：
They're going drug by drug all the way through.
他们自始至终都在用一种药物。
High blood pressure, non-high blood pressure, smoking, non-smoking, et cetera.
高血压、非高血压、吸烟、不吸烟等等。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
And the way they would do that presumably is by saying, okay, married, not married.
他们这样做的方式大概是说，好吧，结婚了，不结婚了。
That's a simple one.
这很简单。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Are you on lipid-lowering meds?
您正在服用降脂药吗？
Yes or no. Okay.
是还是不是。好的。
You are not, you are not.
你不是，你不是。
They-
他们——
Andrew Huberman:
安德鲁·休伯曼：
And then comparing those groups.
然后比较这些组。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
So no differences jumping out that can be purely explained by these other variables.
因此，没有任何差异可以纯粹由这些其他变量来解释。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yes.
是的。
Although, again, this is a great opportunity to talk about why no matter how slick you are, no matter how slick your model is, you can't control for everything.
不过，这又是一个很好的机会来谈论为什么无论你多么狡猾，无论你的模型多么狡猾，你都无法控制一切。
There is a reason that, to my knowledge, virtually every study that compares meat eaters to non-meat eaters finds an advantage amongst the non-meat eaters.
据我所知，几乎所有比较肉食者和非肉食者的研究都发现非肉食者具有优势，这是有原因的。
And we can talk about all the-
我们可以谈论所有-
Andrew Huberman:
安德鲁·休伯曼：
Lifespan advantage.
寿命优势。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yes.
是的。
Or disease incidence studies.
或疾病发病率研究。
And yeah, it might be tempting to say, well, therefore, eating meat is bad, until you realize that it takes a lot of work to not eat meat.
是的，你可能会忍不住说，好吧，因此，吃肉是不好的，直到你意识到不吃肉需要付出很多努力。
For most people, that's a very significant decision a person makes.
对于大多数人来说，这是一个非常重要的决定。
And for a person to make that decision, they probably have a very high conviction about the benefit of that to their health.
对于做出这个决定的人来说，他们可能非常确信这对他们的健康有益。
And it is probably the case that they're making other changes with respect to their health as well that are a little more difficult to measure.
很可能他们也在健康方面做出了其他一些更难以衡量的改变。
Now, there's a million other problems with that.
现在，还有一百万个其他问题。
I picked a silly example because the whole meat discussion then gets into, well, when we say eating meat, what do we mean?
我选择了一个愚蠢的例子，因为整个肉类讨论会陷入，好吧，当我们说吃肉时，我们的意思是什么？
Like, does that-
比如说，是不是——
Andrew Huberman:
安德鲁·休伯曼：
We're not talking about like deli meat versus grass-fed.
我们不是在谈论熟食肉与草饲肉之类的问题。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Exactly.
正是如此。
And then there's other things.
然后还有其他事情。
Andrew Huberman:
安德鲁·休伯曼：
Or a deer that you hunted with your bow-
或者你用弓猎杀的鹿——
Dr. Peter Attia:
彼得·阿蒂亚博士：
That's right
没错
Andrew Huberman:
安德鲁·休伯曼：
...
...
that was totally different.
那是完全不同的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
So how do we get into all those things?
那么我们如何进入所有这些事情呢？
But my point is, it's very difficult to quantify some of the intangible differences.
但我的观点是，量化一些无形的差异是非常困难的。
And I think that even a study that goes to great lengths, as this one does, epidemiologically, to make these corrections can never make the corrections.
我认为，即使是一项像本次流行病学研究那样竭尽全力做出这些纠正的研究也永远无法做出纠正。
And so for me, the big takeaway of this study is, one, this makes much more sense to me than the Banister paper, which never really made sense to me.
所以对我来说，这项研究的最大收获是，第一，这对我来说比班尼斯特论文更有意义，而班尼斯特论文对我来说从来没有真正意义。
And again, I was first critical of the Banister paper in 2018, about four years after it came out.
再说一次，我第一次批评班尼斯特的论文是在 2018 年，大约在该论文发表四年后。
That's about the time I stopped taking metformin, by the way.
顺便说一句，那是我停止服用二甲双胍的时间。
I stopped taking it for a different reason, which we can talk about in a sec.
我出于不同的原因停止服用它，我们稍后会讨论这个原因。
But that was the first time I went back and said, "Wait a minute.
但那是我第一次回去说：“等一下。
This informative censoring thing is a little fishy." And I think we weren't looking at a true group of real type 2 diabetics.
这种信息审查有点可疑。”我认为我们并不是在研究真正的 2 型糖尿病患者群体。
Now, that said, maybe it doesn't matter.
现在，话虽如此，也许这并不重要。
In other words, maybe-- And even the Keys paper doesn't tell us that metformin wouldn't be beneficial, because it could be that those people, if they were on nothing, as their matched cohorts were on nothing, would have been dying at a hazard ratio of three, and this brought it down to 1.5, in which case you would say there is some gero protection there.
换句话说，也许——甚至 Keys 的论文也没有告诉我们二甲双胍不会有任何益处，因为如果这些人什么都不服用，就像他们的匹配队列什么都不服用一样，他们的死亡风险比可能为 3，而这将其降至 1.5，在这种情况下，你会说那里有一些杰罗保护。
It is putting the brakes on this process.
它正在阻碍这一进程。
All of this is to say, absent a randomized control trial, we will never know the answer.
所有这一切都意味着，如果没有随机对照试验，我们永远不会知道答案。
But this-
但这——
Andrew Huberman:
安德鲁·休伯曼：
Has there been a randomized control trial in metformin?
二甲双胍是否有过随机对照试验？
Dr. Peter Attia:
彼得·阿蒂亚博士：
Not of this nature.
不是这个性质的。
Not when it comes to a hard outcome.
当涉及到一个艰难的结果时就不是这样了。
Now, there has been-
现在，已经出现了——
Andrew Huberman:
安德鲁·休伯曼：
Really?
真的吗？
Why not
为什么不呢
Dr. Peter Attia:
彼得·阿蒂亚博士：
...
...
in the ITP.
在 ITP 中。
So the Interventions Testing Program, which is the gold standard for animal studies, which is run out of three labs.
因此，干预测试计划是动物研究的黄金标准，由三个实验室运行。
So it's an NIH-funded program that's run out of three labs.
这是一个由美国国立卫生研究院资助的项目，由三个实验室组成。
They basically test molecules for gero protection.
他们基本上测试分子的老年保护作用。
The ITP was the first study that really put rapamycin on the map in 2009.
2009 年，ITP 是第一项真正让雷帕霉素名声大噪的研究。
That was the study that fortuitously demonstrated that even when rapamycin was given very late in life, it was given to 60-month-old mice, it still afforded them a 15% lifespan extension.
这项研究偶然证明，即使在生命很晚的时候给予 60 个月大的小鼠雷帕霉素，它仍然可以使它们的寿命延长 15%。
Andrew Huberman:
安德鲁·休伯曼：
Has a similar study been done in humans?
在人类身上进行过类似的研究吗？
I mean, it's hard to-- No, you can't really control with rapamycin.
我的意思是，这很难——不，你不能用雷帕霉素真正控制。
Dr. Peter Attia:
彼得·阿蒂亚博士：
No. But when the ITP studied metformin, it did not succeed.
没有。但是当 ITP 研究二甲双胍时，并没有成功。
So there have not been that many drugs that have worked in the ITP.
因此，对 ITP 有效的药物并不多。
The ITP is very rigorous, right?
ITP很严格吧？
It doesn't use an inbred strain of mice.
它不使用近交系小鼠。
It is done concurrently in three labs with very large sample sizing.
它是在三个实验室同时进行的，样本量非常大。
And so when something works in the ITP, it's pretty exciting.
因此，当 ITP 中的某项工作发挥作用时，这是非常令人兴奋的。
Rapamycin has been studied several times.
雷帕霉素已被研究多次。
It's always worked.
它总是有效的。
Another one we should talk about at a subsequent time is 17 alpha-estradiol.
我们稍后要讨论的另一个是 17 α-雌二醇。
This continues to work in male mice, and it produces comparable effects to rapamycin.
这在雄性小鼠中继续发挥作用，并且产生与雷帕霉素相当的效果。
Andrew Huberman:
安德鲁·休伯曼：
Estrogen.
雌激素。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Doesn't work in female mice.
对雌性小鼠不起作用。
Andrew Huberman:
安德鲁·休伯曼：
Makes-
使-
Dr. Peter Attia:
彼得·阿蒂亚博士：
But this is alpha, not beta.
但这是阿尔法，而不是贝塔。
So this is 17 alpha-estradiol, not beta-estradiol, which is the estradiol that is bioavailable in all of us.
所以这是 17 α-雌二醇，而不是 β-雌二醇，β-雌二醇是我们所有人都可以生物利用的雌二醇。
Andrew Huberman:
安德鲁·休伯曼：
And just as a brief aside, I think you and I basically agree that unless it's a problem, males, we're talking post-puberty, should try and have their estrogen as high as possible without having negative symptomology because of the importance of estrogen for libido, for brain function, tissue-
顺便说一句，我认为你和我基本上都同意，除非这是一个问题，否则男性，我们谈论的是青春期后，应该尝试让他们的雌激素尽可能高，而不会出现阴性症状，因为雌激素对性欲、大脑功能、组织的重要性 -
Dr. Peter Attia:
彼得·阿蒂亚博士：
Bone health
骨骼健康
Andrew Huberman:
安德鲁·休伯曼：
...
...
health, bone health.
健康，骨骼健康。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Body composition, maybe.
也许是身体成分。
Andrew Huberman:
安德鲁·休伯曼：
So this idea of crushing estrogen and raising testosterone is just silly, right?
所以这种抑制雌激素和提高睾酮激素的想法很愚蠢，对吧？
Let's just leave raising testosterone out of it, but many of the approaches to raising testosterone that are pharmacologic in nature also raise estrogen.
我们先不考虑提高睾酮水平，但许多提高睾酮水平的方法本质上是药理学的，同时也会提高雌激素。
A lot of people try and push down on estrogen, and that is just, again, unless people are getting hyperestrogenic effects like gynecomastia or other issues, is the exact wrong direction to go.
很多人试图降低雌激素的水平，但这又是一个完全错误的方向，除非人们出现男性乳房发育症或其他问题等高雌激素效应。
You want estrogen high.
你想要高雌激素。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Estrogen is a very important hormone for men and women.
雌激素对于男性和女性来说都是非常重要的激素。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, that's good.
是的，那很好。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Canagliflozin, an SGLT2 inhibitor, also very successful in the ITP, but again, interestingly, metformin not.
Canagliflozin 是一种 SGLT2 抑制剂，在 ITP 治疗中也非常成功，但有趣的是，二甲双胍则不然。
So metformin has failed in the ITP.
所以二甲双胍治疗ITP失败了。
Andrew Huberman:
安德鲁·休伯曼：
So you no longer take metformin?
那么您不再服用二甲双胍吗？
Dr. Peter Attia:
彼得·阿蒂亚博士：
I stopped five years ago.
我五年前就停下来了。
Andrew Huberman:
安德鲁·休伯曼：
I mean, you're not a diabetic, so presumably you were taking it to-
我的意思是，你不是糖尿病患者，所以大概你服用它是为了-
Dr. Peter Attia:
彼得·阿蒂亚博士：
I was taking it for gero protection
我服用它是为了保护杰罗
Andrew Huberman:
安德鲁·休伯曼：
...
...
to buffer blood glucose-
缓冲血糖——
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
in order to potentially live longer.
为了有可能活得更长。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yes, exactly.
是的，完全正确。
And the reason I stopped, and this will be the last thing before we move on-
我停下来的原因，这将是我们继续前进之前的最后一件事-
Andrew Huberman:
安德鲁·休伯曼：
Well, because you couldn't go to the Dairy Queen at the buffet event.
嗯，因为你不能去冰品皇后参加自助餐活动。
Dr. Peter Attia:
彼得·阿蒂亚博士：
No. Finally, the nausea went away after a few weeks or a month, maybe.
不。也许几周或一个月后，恶心感终于消失了。
But once I got really into lactate testing, I noticed how high my lactate was at rest.
但一旦我真正开始进行乳酸测试，我就注意到我在休息时的乳酸有多高。
So a resting fasted lactate in a healthy person should be below one, like somewhere between .3, .6 millimole.
因此，健康人的静息空腹乳酸应低于 1，例如 0.3 至 0.6 毫摩尔之间。
And only when you start to exercise should lactate go up.
只有当你开始运动时，乳酸才会上升。
And in 2018 was when I started ...
2018 年我开始...
blood testing for my zone two.
对我的第二区进行血液检测。
So previously, when I was doing zone two testing, I was just going off my power meter and heart rate.
所以之前，当我进行第二区测试时，我只是关闭功率计和心率。
But this is after I'd met Inigo San Milan, and I started wanting to use the lactate threshold of two millimole as my determinant of where to put my wattage on the bike.
但这是在我遇到 Inigo San Milan 之后，我开始想要使用 2 毫摩尔的乳酸阈值作为我在自行车上放置瓦数的决定因素。
And I'm doing finger pricks before I start, and I'm like 1.6 millimole, and I'm like, "What the hell is going on?
在开始之前我会先刺破手指，我的血量大概是 1.6 毫摩尔，然后我就想，“到底是怎么回事？
I can't be 1.6 if I'm-
我不可能是 1.6，如果我-
Andrew Huberman:
安德鲁·休伯曼：
This is if you ran the flight of stairs up the back of the Empire State Building.
这是如果您沿着帝国大厦后面的楼梯爬上的情况。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Well, no, that would put me a lot higher, right?
嗯，不，那会让我更高，对吧？
But, and when I-
但是，当我——
Andrew Huberman:
安德鲁·休伯曼：
I was being generous to your fitness.
我对你的健身很慷慨。
Dr. Peter Attia:
彼得·阿蒂亚博士：
No, but that's when I started doing a little digging and realized, oh, you know what?
不，但就在那时我开始进行一些挖掘并意识到，哦，你知道吗？
This totally makes sense.
这完全有道理。
If you have a weak mitochondrial toxin-
如果您的线粒体毒素较弱-
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Peter Attia:
彼得·阿蒂亚博士：
...
...
what are you going to do?
你要做什么？
You're going to shunt more glucose into pyruvate and more pyruvate into lactate.
您将把更多的葡萄糖分流成丙酮酸，并将更多的丙酮酸分流成乳酸。
I'm anaerobic-
我是厌氧菌--
Andrew Huberman:
安德鲁·休伯曼：
Yeah, you need an alternative
是的，你需要一个替代方案
Dr. Peter Attia:
彼得·阿蒂亚博士：
...
...
at a baseline.
处于基线。
Fuel source.
燃料来源。
That's right.
没错。
So, and then my zone two numbers just seemed off.
所以，然后我的二区号码似乎不对劲。
My lactate seemed like-
我的乳酸看起来像-
Andrew Huberman:
安德鲁·休伯曼：
Could you feel it?
你能感觉到吗？
Sorry to interrupt.
抱歉打扰。
Dr. Peter Attia:
彼得·阿蒂亚博士：
No. That's okay.
不，没关系。
Andrew Huberman:
安德鲁·休伯曼：
But could you feel it in your body?
但你能在你的身体里感受到它吗？
Because maybe now I'll just briefly describe.
因为也许现在我会简单描述一下。
I took berberine.
我服用了小檗碱。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
During the period of maybe somewhere in the 2012 to 2015 stretch, I don't recall the exact date.
大概是 2012 年到 2015 年期间的某个时间段，我不记得确切的日期了。
Dr. Peter Attia:
彼得·阿蒂亚博士：
And what were you taking it for?
你拿它来干什么？
Andrew Huberman:
安德鲁·休伯曼：
Well, I'll tell you.
好吧，我告诉你。
So I was and I still am a big fan of Tim Ferriss's slow carbohydrate diet.
所以我过去是、现在仍然是蒂姆·费里斯慢碳水化合物饮食的忠实粉丝。
Because I like to eat meat and vegetables and starches.
因为我喜欢吃肉、蔬菜和淀粉。
I'm an omnivore.
我是杂食动物。
And I found that it worked very quickly, got me very lean.
我发现它见效非常快，让我变得非常瘦。
I could exercise, I could think, I could sleep.
我可以锻炼，我可以思考，我可以睡觉。
A lot of my rationale for following one eating regimen or another, what I eat, is to enjoy myself, but also have mental energy.
我遵循一种或另一种饮食习惯的很多理由，我吃的东西，是为了享受自己，但也有精神能量。
Because if I can't sleep at night, I'm not going to replenish.
因为如果我晚上睡不着，我就不会补充。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yep.
是的。
Andrew Huberman:
安德鲁·休伯曼：
If I don't replenish, I'm going to feel like garbage.
如果我不补充，我会觉得自己像个垃圾。
I don't care how lean I am or, well, you know.
我不在乎我有多瘦，或者，你知道。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yep.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So I found the slow carb diet, which was in "The 4-Hour Body," to be a very good plan for me.
所以我发现“四小时健身”中的慢碳水化合物饮食对我来说是一个非常好的计划。
It was pretty easy.
这很容易。
You drop some things like bread, et cetera.
你掉了一些东西，比如面包等等。
You don't drink calories, except after a resistance training session, et cetera.
你不会喝卡路里，除非是在阻力训练之后等等。
But one day a week, you have this so-called cheat day, and on the cheat day anything goes.
但每周有一天，你会有所谓的作弊日，在作弊日，任何事情都会发生。
And so I would eat croissants and then I'd alternate to sweet stuff, and then I'd go to pizza.
所以我会吃羊角面包，然后我会改吃甜食，然后我会去吃披萨。
And by the end of the day, you don't want to look at an item of food at all.
到一天结束时，您根本不想看任何食物。
So the only modification I made to the slow carb diet, 4-Hour Body thing, was the day after the cheat day, I wouldn't eat.
因此，我对慢碳水化合物饮食、4 小时健身计划所做的唯一修改是在作弊日后的第二天，我不吃东西。
I would just fast.
我会禁食。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Mm.
嗯。
Andrew Huberman:
安德鲁·休伯曼：
And I had no problem doing that because it was just basically...
我这样做没有任何问题，因为它基本上......
Well, since you said, what was it?
好吧，既然你都说了，那是什么？
Anal-
肛门-
Dr. Peter Attia:
彼得·阿蒂亚博士：
Anal seepage.
肛门渗液。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, anal seepage.
是的，肛门渗液。
I did not have that, but since you said that I won't up the ante here, but I'll at least match your anal seepage comment by saying, I had, let's just call it, profound gastric distress after eating like that the next day.
我没有，但既然你说我不会在这里提高赌注，但我至少会说，我第二天吃了这样的东西后，我有，我们就这么称呼它，严重的胃部不适。
So the last thing you want to do is eat any food.
所以你最不想做的就是吃任何食物。
I would just hydrate.
我只想补充水分。
And oftentimes to try and get some exercise.
并且经常尝试进行一些锻炼。
And what I read was that berberine, poor man's metformin, could buffer blood glucose and in some ways make me feel less sick when ingesting all these calories and in many cases, spiking my blood sugar and insulin, because you're having ice cream, et cetera.
我读到的是，小檗碱，穷人的二甲双胍，可以缓冲血糖，并在某种程度上让我在摄入所有这些卡路里时感觉不那么恶心，而且在许多情况下，会增加我的血糖和胰岛素，因为你正在吃冰淇淋等。
And indeed, it worked.
事实上，它确实有效。
So if I took berberine, and I don't recall the milligram count, and then I ate 12 donuts, I felt fine.
因此，如果我服用小檗碱，并且我不记得毫克数，然后我吃了 12 个甜甜圈，我感觉很好。
It was as if I had eaten one donut.
就好像我吃了一个甜甜圈。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Wow.
哇。
Andrew Huberman:
安德鲁·休伯曼：
I felt sort of okay in my body, and I felt much, much better.
我感觉自己的身体还不错，而且感觉好多了。
Now, presumably because it's buffering the spikes in blood sugar, I wasn't crashing in the afternoon nap and that whole thing.
现在，大概是因为它可以缓冲血糖的峰值，所以我在下午小睡时就没有崩溃了。
But-
但是——
Dr. Peter Attia:
彼得·阿蒂亚博士：
And do you remember how much you were taking?
你还记得你服用了多少吗？
Andrew Huberman:
安德鲁·休伯曼：
I think it was a couple hundred milligrams.
我认为有几百毫克。
Does that sound about right?
听起来对吗？
It was a bright yellow capsule.
这是一个亮黄色的胶囊。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I forget the source.
我忘记了来源。
But in any case, one thing I noticed was that if I took berberine and I did not ingest a profound number of carbohydrates very soon afterwards, I got brutal headaches.
但无论如何，我注意到的一件事是，如果我服用小檗碱并且随后没有摄入大量碳水化合物，我就会感到剧烈的头痛。
I think I was hypoglycemic.
我想我是低血糖了。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Mm.
嗯。
Andrew Huberman:
安德鲁·休伯曼：
I didn't measure it, but I just felt I had headaches, I didn't feel good.
我没有量，只是感觉头疼，感觉不太好。
And then I would eat a pizza or two and feel fine.
然后我会吃一两个披萨，感觉很好。
And so I realized that berberine was putting me on this lower blood sugar state.
所以我意识到小檗碱使我处于低血糖状态。
That was the logic anyway.
无论如何，这就是逻辑。
And it allowed me to eat these cheat foods.
它让我可以吃这些作弊食物。
But when I cycled off of the 4-Hour, because I don't follow the slow carb diet anymore, although I might again at some point.
但是当我停止 4 小时骑行时，因为我不再遵循慢碳水化合物饮食，尽管我可能会在某个时候再次遵循。
When I stopped doing those cheat days, I didn't have any reason to take the berberine, and I feared that I wasn't ingesting enough carbohydrates in order to really justify trying to buffer my blood glucose.
当我停止那些作弊的日子时，我没有任何理由服用小檗碱，而且我担心我没有摄入足够的碳水化合物来真正证明尝试缓冲我的血糖是合理的。
Also, my blood glucose tends to be fairly low.
此外，我的血糖往往相当低。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Did you ever try acarbose?
您尝试过阿卡波糖吗？
Andrew Huberman:
安德鲁·休伯曼：
No. What is that?
不，那是什么？
Dr. Peter Attia:
彼得·阿蒂亚博士：
So acarbose is a-
所以阿卡波糖是-
Andrew Huberman:
安德鲁·休伯曼：
Another glucose disposal agent?
另一种葡萄糖处理剂？
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
It's actually a drug, but it works more in the gut, and it just prevents glucose absorption.
它实际上是一种药物，但它更多地在肠道中起作用，并且它只是阻止葡萄糖吸收。
Andrew Huberman:
安德鲁·休伯曼：
Mm.
嗯。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Acarbose is another one of those drugs that actually found a survival benefit in the ITP.
阿卡波糖是另一种确实对 ITP 具有生存益处的药物。
And it was a very interesting finding because the thesis for testing it, the ITP is a very clever system.
这是一个非常有趣的发现，因为测试它的论文 ITP 是一个非常聪明的系统。
Anybody can nominate a candidate to be tested.
任何人都可以提名一名候选人进行测试。
And then the panel over there reviews it, and they decide, "Yep, this is interesting.
然后那边的小组对其进行审查，他们决定，“是的，这很有趣。
We'll go ahead and study it." So when, I think David Allison nominated acarbose to be studied, the rationale was it would be a caloric restriction mimetic because you would literally just fail to absorb, I don't know, make up some number, right?
我们将继续研究它。”因此，当我认为大卫·艾利森提名阿卡波糖进行研究时，理由是它将是一种热量限制模拟物，因为你实际上无法吸收，我不知道，编造一些数字，对吧？
15 to 20% of your carbohydrates would not be absorbed, and therefore the mice would effectively be calorically restricted, which would-
15% 到 20% 的碳水化合物不会被吸收，因此小鼠的热量会受到有效限制，这会-
Andrew Huberman:
安德鲁·休伯曼：
They would just pass them out.
他们会把它们传递出去。
Dr. Peter Attia:
彼得·阿蒂亚博士：
That's right.
没错。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
And what happened was really interesting.
发生的事情真的很有趣。
One, the mice lived longer on acarbose.
第一，服用阿卡波糖的小鼠寿命更长。
But two, they didn't weigh any less.
但有两个，它们的重量并没有减轻。
So they lived longer, but not through calorie restriction.
所以他们活得更长，但不是通过限制卡路里摄入。
Andrew Huberman:
安德鲁·休伯曼：
That's interesting.
这很有趣。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yes.
是的。
And the speculation is they lived longer because they had lower glucose and lower insulin.
据推测，他们的寿命更长是因为他们的血糖和胰岛素水平较低。
Andrew Huberman:
安德鲁·休伯曼：
And I don't want to send us down some rabbit holes here, but there are all sorts of interesting ideas about, for instance, that some forms of dementia might be so-called type three diabetes, the diabetes of the brain, and so things like berberine, metformin, lowering blood glucose, ketogenic diets, et cetera, might be beneficial there.
我不想在这里让我们陷入一些兔子洞，但是有各种各样有趣的想法，例如，某些形式的痴呆症可能是所谓的三型糖尿病，即大脑的糖尿病，因此黄连素、二甲双胍、降低血糖、生酮饮食等可能是有益的。
There's a lot to explore here, and I know you've explored a lot of that on your podcast.
这里有很多东西值得探索，我知道您已经在播客中探索了很多内容。
I've done far less of that.
我做的事情要少得多。
But, well, at least it seems that we know the following things for sure.
但是，至少看来我们确实知道以下事情。
One, you don't want insulin too high nor too low.
第一，您不希望胰岛素太高或太低。
You don't want blood glucose too high nor too low.
您不希望血糖过高或过低。
If the buffering systems for that are disrupted, clearly exercise, meaning regular exercise, is the best way to keep that system in check.
如果缓冲系统被破坏，显然锻炼，即定期锻炼，是控制该系统的最佳方法。
But in the absence of that tool, or I would say in addition to that tool, is there any glucose disposal agent, because that's what we're talking about here, metformin, berberine, acarbose, et cetera, that you take on a regular basis because you have that much confidence in it?
但在没有这个工具的情况下，或者我会说除了这个工具之外，还有没有任何葡萄糖处理剂，因为这就是我们在这里讨论的二甲双胍、小檗碱、阿卡波糖等等，你定期服用，因为你对它有那么大的信心？
Dr. Peter Attia:
彼得·阿蒂亚博士：
The only one that I take is an SGLT2 inhibitor.
我唯一服用的药物是 SGLT2 抑制剂。
So this is a class of drug that is used by people with type 2 diabetes, which I don't have, but because of my faith in the mechanistic studies of this drug, coupled with its results in the ITP, coupled with the human trial results that show profound benefit in non-diabetics taking it even for heart failure, I think there's something very special about that drug.
这是一类 2 型糖尿病患者使用的药物，我没有，但由于我对这种药物的机制研究的信心，加上它在 ITP 中的结果，再加上人体试验结果显示，服用该药物对非糖尿病患者甚至心力衰竭也有深远的益处，我认为该药物有一些非常特别的地方。
Actually, that was another paper I was thinking about presenting this time.
事实上，这是我这次想展示的另一篇论文。
Maybe we'll do that the next time.
也许下次我们会这样做。
Andrew Huberman:
安德鲁·休伯曼：
But do you believe in caloric restriction as a way to extend life, or are you more of the do the right behaviors, and that's covered in your book "Outlive" and elsewhere on your podcast, and buffer blood glucose?
但是，您是否相信热量限制是延长寿命的一种方式，还是您更倾向于采取正确的行为（这在您的《Outlive》一书和播客的其他地方都有介绍）并缓冲血糖？
Obviously, you believe in buffering blood glucose in addition to just doing all the right behaviors.
显然，除了采取所有正确的行为之外，您还相信缓冲血糖。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah, I think you can uncouple a little bit the buffering of blood glucose from the caloric deficit.
是的，我认为你可以将血糖缓冲与热量不足分开。
So, I think you can be in a reasonable energy balance and buffer glucose with good sleep hygiene, lots of exercise, and just thoughtful eating without having to go into a calorie deficit.
所以，我认为你可以通过良好的睡眠卫生、大量的锻炼和周到的饮食来保持合理的能量平衡和缓冲血糖，而不必陷入卡路里不足。
So, it's not entirely clear if profound caloric restriction would offer a survival advantage to humans, even if it were tolerable to most, which it's not.
因此，目前还不完全清楚严格的热量限制是否会给人类带来生存优势，即使它对大多数人来说是可以忍受的，但事实并非如此。
Right?
正确的？
So for most people, it's just off the table.
所以对于大多数人来说，这是不可能的。
Right?
正确的？
If I said, "Andrew, you need to eat 30% fewer calories for the rest of your life."
如果我说：“安德鲁，你余生需要少吃 30% 的卡路里。”
Andrew Huberman:
安德鲁·休伯曼：
I'll live 30% fewer years.
我的寿命将减少 30%。
Thank you.
谢谢。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
There's just not many people who are willing to sign up for that, so it's kind of a moot point.
只是没有多少人愿意报名参加，所以这是一个有争议的问题。
But the question is, do you need to be fasting all the time?
但问题是，你需要一直禁食吗？
Do you need to be doing all of these other things?
您需要做所有这些其他事情吗？
And the answer appears to be, outside of using them as tools to manage energy balance, it's not clear.
答案似乎是，除了将它们用作管理能量平衡的工具之外，尚不清楚。
Right?
正确的？
And energy balance probably plays a greater role in glucose homeostasis from a nutrition standpoint, than the individual constituents of the meal.
从营养的角度来看，能量平衡可能比膳食的各个成分在葡萄糖稳态中发挥更大的作用。
Now, that's not entirely true.
现在，这并不完全正确。
I can imagine a scenario where a person could be in a negative energy balance eating Twix bars all day and drinking Big Gulps.
我可以想象一个场景，一个人可能会处于负能量平衡状态，整天吃 Twix 能量棒，喝 Big Gulps。
But I also don't think that's a very sustainable thing to do, because if by definition I'm going to put you in negative energy balance consuming that much crap, I'm going to destroy you.
但我也不认为这是一件非常可持续的事情，因为如果按照定义我会让你处于负能量平衡状态，消耗那么多垃圾，我就会毁掉你。
You're going to feel so miserable.
你会感觉很痛苦。
You're going to be starving.
你会饿死的。
Right?
正确的？
You're not going to be satiated eating pure garbage and being in caloric deficit.
你不会因为吃纯粹的垃圾和热量不足而感到满足。
You're going to end up having to go into caloric excess.
你最终将不得不摄入过量的热量。
So that's why it's an interesting thought experiment.
这就是为什么这是一个有趣的思想实验。
I don't think it's a very practical experiment.
我认为这不是一个非常实用的实验。
For a person to be generally satiated and in energy balance, they're probably eating about the right stuff.
对于一个人来说，要总体感到满足并保持能量平衡，他们可能吃的是正确的东西。
But I don't think that the specific macros matter as much as I used to think.
但我认为具体的宏并不像我以前想象的那么重要。
Andrew Huberman:
安德鲁·休伯曼：
I'm a believer in getting most of my nutrients from unprocessed or minimally processed sources, simply because it allows me to eat foods I like-
我坚信从未经加工或最低限度加工的来源中获取大部分营养，仅仅是因为它可以让我吃我喜欢的食物 -
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and more of them.
还有更多。
And I just love to eat.
我就是喜欢吃。
I so physically enjoy the sensation of chewing that I'll just eat cucumber slices for fun.
我非常享受咀嚼的感觉，所以我会吃黄瓜片来取乐。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Right?
对吗？
That's not my only form of fun, fortunately.
幸运的是，这不是我唯一的乐趣。
This is an amazing paper, for the simple reason that it provides a wonderful tutorial of the benefits and drawbacks of this type of work.
这是一篇令人惊叹的论文，原因很简单，它提供了关于此类工作的优点和缺点的精彩教程。
And I think it's also wonderful because we hear a lot about metformin, rapamycin, and these anti-aging approaches, but I was not aware that there was any study of such a large population of people, so it's pretty interesting.
我认为这也很棒，因为我们听说了很多关于二甲双胍、雷帕霉素和这些抗衰老方法的信息，但我不知道有针对如此大量人群的研究，所以这非常有趣。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
So I think it remains to be seen if-- And my patients often ask me, "Hey, should I be on metformin?" And I give them a much, much, much, much shorter version of what we just talked about.
所以我认为还有待观察——我的病人经常问我，“嘿，我应该服用二甲双胍吗？”我给他们提供了我们刚才谈论的内容的一个非常非常短的版本。
And I say, look, if the TAME study, which should answer this question more definitively, right?
我说，看看，如果 TAME 研究应该更明确地回答这个问题，对吧？
This is taking a group of non-diabetics and randomizing them to placebo versus metformin and studying for specific disease outcomes.
该研究将一组非糖尿病患者随机分为安慰剂组和二甲双胍组，并研究特定的疾病结果。
If the TAME study ends up demonstrating that there is a geroprotective benefit of metformin, I'll reconsider everything.
如果 TAME 研究最终证明二甲双胍具有老年保护作用，我会重新考虑一切。
Right?
正确的？
So I think we just have to, I think, all walk around with an appropriate degree of humility around what we know and what we don't know.
所以我认为我们必须以适当的谦逊态度对待我们所知道和不知道的事情。
But I would say right now, the epidemiology, the animal data, my own personal experience with its impact on my lactate production and exercise performance, there's a whole other rabbit hole we could go down another time, which is the impact on hypertrophy and strength, which appears to be attenuated as well by metformin.
但我现在要说的是，流行病学、动物数据、我个人的经验以及它对我的乳酸产生和运动表现的影响，还有一个我们可以下次再研究的另一个兔子洞，那就是对肥大和力量的影响，二甲双胍似乎也会减弱这种影响。
I still prescribe it to patients all the time if they're insulin resistant, for sure.
当然，如果患者有胰岛素抵抗，我仍然会一直给他们开这种药。
It's still a valuable drug, but I don't think of it as a great tool for the person who's insulin sensitive and exercising a lot.
它仍然是一种有价值的药物，但我不认为它对于胰岛素敏感和经常锻炼的人来说是一个很好的工具。
Andrew Huberman:
安德鲁·休伯曼：
I can't help but ask this question.
我忍不住要问这个问题。
Do you think there's any longevity benefit to short periods of caloric restriction?
您认为短期热量限制对长寿有好处吗？
So for instance, I decide to-- By the way, I haven't done this, but let's say I were to decide to fast and do a one meal a day type thing where I'm going to be in a slight caloric deficit, 500 to 1,000 calories for a couple of days, and then go back to eating the way that I ate before, that short caloric restriction/fast.
举例来说，我决定——顺便说一下，我还没有这样做，但假设我决定禁食，每天只吃一顿饭，这样我会出现轻微的热量不足，几天内摄入 500 到 1,000 卡路里，然后回到以前的饮食方式，即短暂的热量限制/禁食。
Is there any benefit to it in terms of cellular health?
它对细胞健康有什么好处吗？
Can you sort of reset the system?
能不能重装一下系统？
Is there any idea that the The changes, the clearing of senescent cells that we hear about, autophagy, that in the short term, you can glean a lot of benefits and then go back to your regular pattern of eating, and then periodically, once every couple of weeks or once a month, just fast for a day or two.
有没有什么想法，我们听说过的改变，清除衰老细胞，自噬，在短期内，你可以得到很多好处，然后回到你的常规饮食模式，然后定期，每几周一次或每月一次，禁食一两天。
Is there any benefit to that that's purely in the domain of longevity?
纯粹在长寿方面有什么好处吗？
Because there's a discipline function there, there's a flexibility function, there's probably an insulin sensitivity function, but is there any evidence that it can help us live longer?
因为那里有纪律功能，有灵活性功能，可能还有胰岛素敏感性功能，但有任何证据表明它可以帮助我们活得更长吗？
Dr. Peter Attia:
彼得·阿蒂亚博士：
I think the short answer is no. For two reasons.
我认为简短的答案是否定的。有两个原因。
One, I don't think that that duration would be sufficient if one is going to take that approach.
第一，如果要采取这种方法，我认为这个持续时间还不够。
But two, even if you went with something longer, like what I used to do, right?
但第二，即使你选择更长的东西，就像我以前做的那样，对吧？
I used to do seven days of water only per quarter, three days per month.
我以前每季度只浇7天水，每月浇水3天。
But I was basically always like, it would be three-day fast, three-day fast, seven-day fast.
但我基本上总是喜欢，三天禁食，三天禁食，七天禁食。
Just imagine doing that all year, rotating, rotating, rotating.
想象一下一整年都这样，旋转、旋转、旋转。
For many years, I did that.
多年来，我都是这样做的。
Now, I certainly believed, and to this day, I would say I have no idea if that provided a benefit.
现在，我当然相信，直到今天，我会说我不知道这是否会带来好处。
But my thesis was, the downside of this is relatively circumscribed, which is profound misery for a few days, and what I didn't appreciate at the time, which I obviously now look back at and realize, is muscle mass lost.
但我的论点是，这样做的缺点是相对有限的，这会是几天的深刻痛苦，而我当时没有意识到的是，我现在回想起来并意识到，是肌肉质量的损失。
It's very difficult to gain back the muscle cumulatively after all of that loss.
在所有损失之后，要逐渐恢复肌肉是非常困难的。
But my thought was exactly as you said, like there's got to be a resetting of the system here.
但我的想法正如你所说，就像这里必须重置系统一样。
This must be sufficiently long enough to trigger all of those systems.
这必须足够长才能触发所有这些系统。
But you're getting at a bigger problem with geroscience, which I'm really hoping the epigenetic field comes to the rescue on.
但你遇到了老年科学的一个更大的问题，我真的希望表观遗传学领域能够解决这个问题。
It has not come close to it to date, which is we don't have biomarkers around true metrics of aging.
迄今为止，它还没有接近这一目标，也就是说，我们还没有真正的衰老指标的生物标志物。
Everything we have to date stinks.
我们迄今为止所拥有的一切都发臭了。
So we're really good at using molecules or interventions for which we have biomarkers, right?
所以我们真的很擅长使用我们拥有生物标志物的分子或干预措施，对吧？
Like when you lift weights, you can look at how much weight you're lifting.
就像举重时一样，您可以查看举起的重量。
You can look at your DEXA scan and see how much muscle mass you're generating.
您可以查看您的 DEXA 扫描，看看您产生了多少肌肉质量。
Like those are biomarkers.
就像那些生物标志物一样。
Those are giving you outputs that say, "My input is good," or, "My input needs to be modified." When you take a sleep supplement, you can look at your Eight Sleep and go, "Oh, my sleep is getting better." Like there's a biomarker.
这些输出会告诉您“我的输入很好”或“我的输入需要修改”。当您服用睡眠补充剂时，您可以查看您的八睡眠并说，“哦，我的睡眠越来越好。”就像有一个生物标记一样。
When you take metformin, when you take rapamycin, when you fast, we don't have a biomarker that gives us any insight into whether or not we're moving in the right direction, and if we are, are we taking enough?
当你服用二甲双胍、当你服用雷帕霉素、当你禁食时，我们没有生物标志物可以让我们了解我们是否在朝着正确的方向前进，如果是，我们服用的剂量是否足够？
We just don't know.
我们只是不知道。
So I often get asked, like what's the single most important topic you would want to see more research dollars put to in terms of this space, and it's unquestionably this.
因此，我经常被问到，您希望在这个领域投入更多研究资金的最重要的主题是什么，毫无疑问就是这个。
As unsexy as it is, like who cares about biomarkers?
尽管它并不性感，但谁会关心生物标志物呢？
But without them, I don't think we're going to get great answers because you can't do most of the experiments you and I would dream up.
但如果没有它们，我认为我们不会得到很好的答案，因为你无法完成你和我梦想的大部分实验。
Andrew Huberman:
安德鲁·休伯曼：
Got it.
明白了。
Well, I'm grateful that you're sitting across the table from me telling me all this and that everyone can hear this.
好吧，我很感激你坐在我桌子对面告诉我这一切，并且每个人都能听到。
But again, we will put a link to the papers, plural, that Peter just described.
但是，我们将再次添加一个指向彼得刚刚描述的复数论文的链接。
And for those of you that are listening and not watching, hopefully you were able to track the general themes and takeaways, and it is fun to go to these papers.
对于那些正在听而不是在看的人，希望您能够跟踪一般主题和要点，并且阅读这些论文很有趣。
You see these big stacks of numbers, and it can be a little bit overwhelming.
你看到这些大堆的数字，可能有点让人不知所措。
But my additional suggestion on parsing papers is notice that Peter said that he's read it several times.
但我对解析论文的额外建议是，请注意彼得说他已经读过好几遍了。
Unlike a newspaper article or an Instagram post, with a paper you're not necessarily going to get it the first time.
与报纸文章或 Instagram 帖子不同，报纸文章您不一定会在第一时间获得。
You certainly won't get everything.
你当然不会得到一切。
So I think spending some time with papers for me means reading it and then reading it again a little bit later or-
所以我认为花一些时间阅读论文对我来说意味着阅读它，然后稍后再阅读它，或者-
Dr. Peter Attia:
彼得·阿蒂亚博士：
And tell me-
并告诉我——
Andrew Huberman:
安德鲁·休伯曼：
...
...
one figure at a time.
一次一个数字。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah, I was just about to say, because I kind of have a way that I do it, but I'm curious as to how you do it.
是的，我正要说，因为我有办法做到这一点，但我很好奇你是如何做到的。
Like if you're encountering a paper for the first time, do you have an order in which you like to go through the-- Do you read it sequentially, or do you look at the figures first?
就像你第一次遇到一篇论文一样，你是否有一个你喜欢阅读的顺序——你是按顺序阅读它，还是先看数字？
I mean, how do you go through it?
我的意思是，你如何度过这一切？
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Unless it's an area that I know very, very well, where I can skip to some things before reading it the whole way through, my process is always the same.
除非这是一个我非常非常了解的领域，我可以在通读之前跳到某些内容，否则我的过程总是相同的。
And actually, this is fun because I used to teach a class when I was a professor at UC San Diego, called Neural Circuits in Health and Disease, and it was an evening course that grew very quickly from 50 students to 400 plus students, and we would do exactly this.
事实上，这很有趣，因为当我在加州大学圣地亚哥分校担任教授时，我曾教过一门课程，名为《健康与疾病中的神经回路》，这是一门晚间课程，学生人数从 50 名学生迅速增加到 400 多名学生，我们正是这样做的。
We would parse papers.
我们会解析论文。
And I had everyone ask what I called the four questions, and it wasn't exactly four questions, but I have a little three-by-five card next to me or a piece of a main half-by-11 paper typically, and when I sit down with a paper, I want to figure out what is the question they're asking.
我让每个人都问我所说的四个问题，这并不完全是四个问题，但我旁边有一张 3×5 的小卡片，或者通常是一张 11×11 的主要论文，当我坐下来拿着一张论文时，我想弄清楚他们在问什么问题。
What's the general question?
一般问题是什么？
What's the specific question?
具体问题是什么？
And I write down the question.
我写下这个问题。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Mm.
嗯。
Andrew Huberman:
安德鲁·休伯曼：
Then what was the approach?
那么采取什么方法呢？
How did they test that question?
他们如何测试这个问题？
And sometimes that can get a bit detailed.
有时这可能会变得有点详细。
You can get into immunohistochemistry, and they did a PCR for this.
你可以研究免疫组织化学，他们为此做了 PCR。
It's not so important for most people that they understand every method, but it is worthwhile that if you encounter a method like PCR or chromatography or fMRI, that you at least look up on the internet what its purpose is.
对于大多数人来说，了解每种方法并不那么重要，但值得的是，如果您遇到 PCR、色谱或功能磁共振成像等方法，您至少应该在互联网上查找其目的是什么。
Okay?
好的？
That will help a lot.
这会有很大帮助。
And then it was what they found, and there you can usually figure out what they believe they found, anyway, by reading the figure headers.
然后就是他们发现的东西，无论如何，你通常可以通过阅读图标题来弄清楚他们认为他们发现了什么。
Right?
正确的？
Figure one.
图一。
Here's the header.
这是标题。
Typically, if it's an experimental paper, it will tell you what they want you to think they found.
通常，如果这是一篇实验论文，它会告诉你他们希望你认为他们发现了什么。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Mm.
嗯。
Andrew Huberman:
安德鲁·休伯曼：
And then I tend to want to know the conclusion of the study.
然后我倾向于想知道研究的结论。
And then this is really the key one, and this is the one that would really distinguish the high-performing students from the others You have to go back at the end and ask whether or not the conclusions, the major conclusions drawn in the paper, are really substantiated by what they found and what they did.
这确实是关键的一点，这才是真正将表现优异的学生与其他学生区分开来的一点。你必须在最后回头问一下，论文中得出的主要结论是否真的被他们的发现和所做的所证实。
And that involves some thinking.
这需要一些思考。
It involves really spending some time thinking about what they identified.
这需要真正花一些时间思考他们发现了什么。
Now, this isn't something that anyone can do straight off the bat.
现在，这不是任何人都可以立即做到的事情。
It's a skill that you develop over time, and different papers require different formats.
这是一项随着时间的推移而发展的技能，不同的论文需要不同的格式。
But those four questions really form the cornerstone of teaching undergraduates, and I think graduate students as well, of how to read a paper.
但这四个问题确实构成了教授本科生以及研究生如何阅读论文的基石。
And, again, it's something that can be cultivated, and it's still how I approach papers.
再说一次，这是可以培养的，而且这仍然是我处理论文的方式。
So what I do typically is I'll read title, abstract.
所以我通常做的就是阅读标题和摘要。
I usually then will skip to the figures and see how much of it I can digest without reading the text, and then go back and read the text.
然后我通常会跳到图表，看看在不阅读文本的情况下我能消化多少内容，然后再回去阅读文本。
But in fairness, great journals like "Science," like "Nature," oftentimes will pack so much information, and the Cell Press journals too, into each figure, and it's coded with no definition of the acronyms, that almost always I'm into the introduction and results within a couple of minutes wondering what the hell this acronym is or that acronym is.
但公平地说，像《科学》、《自然》这样的伟大期刊，通常会在每个图中包含如此多的信息，《细胞出版社》期刊也是如此，而且它的编码没有缩写词的定义，几乎总是我在几分钟内进入介绍和结果，想知道这个缩写词是什么或那个缩写词到底是什么。
And it's just wild how much nomenclature there really is.
确实有如此多的术语。
I can't remember, was it you or was it our friend Paul Conti when he was here, who said that...
我不记得了，是你还是我们的朋友保罗·孔蒂在这儿时说的……
Oh, no, I'm sorry.
哦，不，对不起。
It was neither.
两者都不是。
It was chair of ophthalmology at Stanford, Dr. Geoffrey Goldberg, who was a guest on the podcast recently, who off-camera, I think it was, told us that if you look at the total number of words and terms that a physician leaving medical school owns in their mind and their vocabulary, it's the equivalent of two additional full languages of fluency beyond their native language.
斯坦福大学眼科主任杰弗里·戈德堡博士（Dr. Geoffrey Goldberg）最近在播客中担任嘉宾，我认为他在镜头外告诉我们，如果你看看一位离开医学院的医生在他们的头脑和词汇量中拥有的单词和术语的总数，这相当于在他们的母语之外额外增加了两种完整的流利语言。
So you're trilingual at least.
所以你至少会说三种语言。
Now, do you speak a language other than English?
现在，你会说英语以外的语言吗？
Dr. Peter Attia:
彼得·阿蒂亚博士：
Poorly.
很糟糕。
Andrew Huberman:
安德鲁·休伯曼：
Okay, so you're at least trilingual and probably more.
好吧，所以你至少会说三种语言，甚至可能更多。
So no one is expected to be able to parse these papers the first time through without substantial training.
因此，没有人能够在没有经过大量培训的情况下第一次解析这些论文。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
No, I think that's a great format.
不，我认为这是一个很棒的格式。
And you're absolutely right.
你是完全正确的。
I have a different way that I do it when I'm familiar with the subject matter versus when I'm not.
当我熟悉主题时和不熟悉主题时，我的做法是不同的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, how do you do it?
是啊，你怎么做呢？
Dr. Peter Attia:
彼得·阿蒂亚博士：
Well, again, if I'm reading papers that are something that I know really well, I can basically glean everything I need to know from the figures.
好吧，再说一次，如果我正在阅读我非常了解的论文，我基本上可以从数据中收集我需要知道的一切。
And then sometimes I'll just do a quick skim on methods.
有时我会快速浏览一下方法。
But I don't need to read the discussion, I don't need to read the intro, I don't need to read anything else.
但我不需要阅读讨论，我不需要阅读简介，我不需要阅读其他任何内容。
If it's something that I know less about, then I usually do exactly what you say.
如果是我不太了解的事情，那么我通常会完全按照你说的去做。
I try to start with the figures.
我尝试从数字开始。
I usually end up generating more questions like, "What do you mean?
我通常最终会产生更多问题，例如“你是什么意思？
What is this?
这是什么？
How did they do that?" And then I got to go back and read methods typically.
他们是怎么做到的？”然后我通常要回去阅读方法。
And one of the other things that's probably worth mentioning is a lot of papers these days have supplemental information that are not attached to the paper.
另一件可能值得一提的事情是，现在很多论文都有未附加到论文中的补充信息。
So, you're amazed at how much stuff gets put in the supplemental section.
因此，您会对补充部分中放置的内容感到惊讶。
And the reason for that, of course, is that the journals are very specific on the format and length of a paper.
当然，原因是期刊对论文的格式和长度非常具体。
So a lot of the times when you're submitting something, if you want to put any additional information in there, it can't go in the main article, it has to go in the supplemental figure.
因此，很多时候，当您提交某些内容时，如果您想在其中添加任何附加信息，它不能放在主文章中，而必须放在补充图中。
So even for this paper, there were a couple of the numbers I spouted off that I had to pull out of the supplemental paper.
因此，即使对于这篇论文，我也不得不从补充论文中取出一些我滔滔不绝的数字。
For example, when they did the sensitivity analysis on the censoring versus non-censoring, that was in the supplemental figure.
例如，当他们对审查与非审查进行敏感性分析时，这是在补充图中。
That was actually not even in the paper we presented.
实际上，这甚至没有出现在我们提交的论文中。
Andrew Huberman:
安德鲁·休伯曼：
Well, should we pivot to this other paper?
那么，我们应该转向另一篇论文吗？
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
It's a very different sort of paper.
这是一种非常不同的纸张。
It's an experimental paper where there's a manipulation.
这是一篇实验论文，其中存在操纵。
I must say, I love, love, love this paper, and I don't often say that about papers.
我必须说，我爱、爱、爱这篇论文，但我不经常对论文这么说。
I'm so excited about this paper for so many reasons, but I want to give a couple of caveats up front.
出于多种原因，我对这篇论文感到非常兴奋，但我想预先提出一些警告。
First of all, the paper is not published yet.
首先，论文还没有发表。
The only reason I was able to get this paper is because it's on bioRxiv.
我能够得到这篇论文的唯一原因是它在 bioRxiv 上。
There's a new trend over the last, I would say, five, six years, of people posting the papers that they've submitted to journals for peer review online so that people can look at them prior to those papers being peer reviewed.
我想说，过去五六年出现了一种新趋势，人们将他们提交给期刊进行同行评审的论文发布到网上，以便人们可以在这些论文进行同行评审之前查看它们。
So there is a strong possibility that the final version of this paper, which again, we will provide a link to, is going to look different, maybe even quite a bit different than the one that we're going to discuss.
因此，本文的最终版本（我们将再次提供链接）很有可能看起来会有所不同，甚至可能与我们将要讨论的版本有很大不同。
Nonetheless, there are a couple of things that make me confident in the data that we're about to talk about.
尽管如此，有几件事让我对我们即将讨论的数据充满信心。
First of all, the group that published this paper is really playing in their wheelhouse.
首先，发表这篇论文的团队确实是在自作聪明。
This is what they do.
这就是他们所做的。
And they publish a lot of really nice papers in this area.
他们在这个领域发表了很多非常好的论文。
I'm going to mispronounce her first name, but I think it's Chaoyi Ge, who's at the Icahn School of Medicine at Mount Sinai, runs a laboratory there studying addiction in humans, and the first author of the paper is Ofer Pearl.
我会念错她的名字，但我认为她是西奈山伊坎医学院的 Chaoyi Ge，在那里经营着一个研究人类成瘾的实验室，这篇论文的第一作者是 Ofer Pearl。
This paper is wild.
这张纸很狂野。
And I'll just give you a couple of the takeaways first as a bit of a hook to hopefully entice people into listening further, because this is an important paper.
我首先会给你们一些要点，作为一点吸引，希望吸引人们进一步倾听，因为这是一篇重要的论文。
This paper basically addresses how our beliefs about the drugs we take impacts how they affect us at a real level, not just at a subjective level, but at a biological level.
这篇论文主要讨论了我们对所服用药物的信念如何影响它们在真实水平上对我们的影响，不仅是在主观水平上，而且是在生物学水平上。
So just to back up a little bit, a former guest on this podcast, Dr. Ali Crum, whose name is actually Alia Crum, but she goes by Ali Crum, talked about belief effects.
稍微支持一下，这个播客的一位前嘉宾 Ali Crum 博士（她的名字实际上是 Alia Crum，但她的昵称是 Ali Crum）谈到了信念效应。
Belief effects are different than placebo effects.
信念效应与安慰剂效应不同。
Placebo effects are really just category effects.
安慰剂效应实际上只是类别效应。
It's, "Okay, I'm going to give you this pill, Peter, and I'm going to tell you that this pill is molecule X5952, and that it's going to make your memory better." And then I give you a memory test, right?
它是，“好吧，我要给你这颗药丸，彼得，我要告诉你，这颗药丸是分子 X5952，它会让你的记忆力更好。”然后我给你做一个记忆测试，对吗？
And your group performs better than the people in the control group who I give a pill to and I say, "This is just a placebo." Or there are other variants on this where people will get a drug and you tell them it's placebo.
你们组的表现比对照组的人要好，我给对照组的人服用药物，然后我说：“这只是安慰剂。”或者还有其他变体，人们会得到一种药物，而你告诉他们这是安慰剂。
They'll get a placebo, you tell them it's drug.
他们会得到安慰剂，你告诉他们这是药物。
It's It's a binary thing.
这是一个二进制的东西。
It's an on or an off thing.
这是一个开或关的事情。
You're either in the drug group or the placebo group, and you're either told that you're getting drug or placebo.
您要么属于药物组，要么属于安慰剂组，并且您要么被告知您正在服用药物，要么属于安慰剂组。
And we know that placebo effects exist.
我们知道安慰剂效应的存在。
In fact, one of the crueler ones, I was never the subject of this, but there was kind of lore in high school that kids would do this mean thing.
事实上，最残酷的事情之一是，我从来都不是这件事的对象，但高中时有一种传说，孩子们会做这种卑鄙的事情。
It's a form of bullying, I really don't like it, where they'd get some kid at a party to drink alcohol-free beer, and then that kid would start acting drunk, and then they'd go, "Got you.
这是一种欺凌行为，我真的不喜欢这样，他们会让一些孩子在聚会上喝不含酒精的啤酒，然后那个孩子就会开始表现得喝醉了，然后他们就会说，“抓住你了。
It doesn't even have alcohol in it." Now, that's a mean joke, and just reminds me of some of the horrors of high school.
里面连酒精都没有。”现在，这是一个卑鄙的笑话，让我想起了高中时的一些恐怖。
Maybe that's why I didn't go very often, which I also don't suggest.
也许这就是我不常去的原因，我也不建议这样做。
But no, it's a mean joke, but it speaks to the placebo effect, right?
但不，这是一个卑鄙的笑话，但它说明了安慰剂效应，对吧？
And there's also a social context effect.
还有社会背景效应。
So placebo effects are real.
所以安慰剂效应是真实存在的。
We know this.
我们知道这一点。
Belief effects are different.
信念的影响是不同的。
Belief effects are not A or B, placebo or non-placebo.
信念效应不是 A 或 B，也不是安慰剂或非安慰剂。
Belief effects have a lot of knowledge to enrich one's belief about a certain something that can shift their psychology and physiology one way or the other.
信念效应有很多知识可以丰富一个人对某种事物的信念，从而以某种方式改变他们的心理和生理。
And I think the best examples of these belief effects really do come from Alia Crum's lab in the psychology department at Stanford, although some of this work she did prior to getting to Stanford.
我认为这些信念效应的最佳例子确实来自斯坦福大学心理学系的 Alia Crum 实验室，尽管其中一些工作是她在进入斯坦福大学之前完成的。
For instance, if people are put into a group where they watch a brief video, just a few minutes of video about how stress really limits our performance, let's say at archery or at mathematics or at music or at public speaking, and then you test them in any of those domains or other domains in a stressful circumstance, they perform less well.
例如，如果人们被分成一组，观看一段简短的视频，几分钟的视频，讲述压力如何真正限制我们的表现，比如说射箭、数学、音乐或公开演讲，然后你在压力环境下测试他们在这些领域或其他领域的表现，他们的表现就会较差。
Okay?
好的？
And we know they perform less well by virtue of a heightened stress response.
我们知道，由于压力反应加剧，他们的表现较差。
You can measure heart rate, you can measure stroke volume of the heart, you can measure peripheral blood flow, which goes down when people are stressed, narrowing of vision, et cetera.
你可以测量心率，你可以测量心脏的每搏输出量，你可以测量外周血流量，当人们有压力、视力变窄等时，外周血流量会下降。
You take a different group of people and randomly assign them to another group where now they're being told that stress enhances performance.
你将不同的一组人随机分配到另一组，现在他们被告知压力可以提高绩效。
It mobilizes resources, it narrows your vision such that you can perform tasks better, et cetera.
它调动资源，缩小你的视野，以便你可以更好地执行任务，等等。
And their performance increases above a control group that receives just useless information.
他们的表现比只接收无用信息的对照组有所提高。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
Or at least useless as it relates to the task.
或者至少是无用的，因为它与任务相关。
So in both cases, by the way, the groups are being told the truth.
顺便说一句，在这两种情况下，这些团体都被告知了真相。
Stress can be depleting or it can enhance performance.
压力可能会消耗精力，也可能会提高绩效。
But this is different than placebo because now it's scaling according to the amount and the type of information that they're getting.
但这与安慰剂不同，因为现在它根据他们获得的信息的数量和类型进行缩放。
Dr. Peter Attia:
彼得·阿蒂亚博士：
And can you give me a sense of magnitude of benefit or detriment that one could experience in a situation like the one you just described?
您能否告诉我，在您刚才描述的情况下，人们可能会经历到多大的好处或损害？
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
So it's striking.
所以这很引人注目。
They're opposite in direction.
他们的方向相反。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yep.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So the stress gets us worse, let's say, I think that if we were to just put a rough percentage on this, it would be somewhere between 10 and 30% worse at performance-
所以压力让我们变得更糟，比方说，我认为如果我们只给出一个粗略的百分比，那么性能会下降 10% 到 30%——
Dr. Peter Attia:
彼得·阿蒂亚博士：
Wow
哇
Andrew Huberman:
安德鲁·休伯曼：
...
...
than the control group.
比对照组。
And stress is enhancing is approximately equivalent improvement, so they're in opposite directions.
而压力的增强大约是等价的增强，所以它们的方向相反。
Even more striking is the studies that Alia's lab did, and others, looking at, for instance, you give people a milkshake, you tell them it's a high-calorie milkshake, has a lot of nutrients, and then you measure ghrelin secretion in the blood.
更引人注目的是阿莉亚实验室和其他实验室所做的研究，例如，你给人们一杯奶昔，你告诉他们这是一种高热量奶昔，含有大量营养物质，然后你测量血液中生长素释放肽的分泌。
And ghrelin is a marker of hunger that increases the longer it's been since you've eaten.
生长素释放肽是饥饿的标志，进食时间越长，饥饿素的水平就会越高。
And what you notice is that it suppresses ghrelin to a great degree and for a long period of time.
您会注意到，它会在很大程度上并长时间地抑制生长素释放肽。
You give another group a shake, you tell them it's a low-calorie shake, that it's got some nutrients in it, but that it doesn't have much fat, not much sugar, et cetera.
你给另一组人一杯奶昔，你告诉他们这是一种低热量奶昔，里面有一些营养成分，但没有太多脂肪，没有太多糖，等等。
They drink the shake, less ghrelin suppression.
他们喝了奶昔，减少了胃饥饿素的抑制。
Dr. Peter Attia:
彼得·阿蒂亚博士：
And it's the same shake.
这是同样的震动。
Andrew Huberman:
安德鲁·休伯曼：
And it's the same shake.
这是同样的震动。
And satiety lines up with that also in that study.
在那项研究中，饱腹感也与此相符。
And then the third one, which is also pretty striking, is they took hotel workers, they gave them a short tutorial or naught, informing them that moving around during the day and vacuuming and doing all that kind of thing is great.
第三个，也相当引人注目，是他们给酒店工作人员提供了一个简短的教程，或者什么也没有，告诉他们白天走动、吸尘和做所有类似的事情是很棒的。
It helps you lower your BMI, which is great for your health.
它可以帮助您降低体重指数，这对您的健康很有好处。
You incentivize them, and then you let them out into the wild of their everyday job.
你激励他们，然后让他们投入到日常工作中。
You measure their activity levels.
您测量他们的活动水平。
The two groups don't differ.
两组没有区别。
They're doing roughly the same task, leaning down, cleaning out trash cans, et cetera.
他们正在做大致相同的任务，弯下腰，清理垃圾桶，等等。
Guess what?
你猜怎么着？
The group that was informed about the health benefits of exercise lose 12% more weight compared to the other group.
与另一组相比，被告知运动对健康有益的一组体重减轻了 12%。
Dr. Peter Attia:
彼得·阿蒂亚博士：
And no difference in actual movement?
和实际运动没有区别吗？
Andrew Huberman:
安德鲁·休伯曼：
Apparently not.
显然不是。
Now, how could that be?
现在，怎么可能呢？
Literally, this was sparked by, in Alia's words, this was sparked by her graduate advisor saying, "What if all the effects of exercise are placebo?" Which is not what anyone really believes, but I love that anecdote that Alia told us because it just really speaks to how really smart people think.
从字面上看，这是由阿莉亚所说的，这是由她的研究生导师说的引发的，“如果运动的所有效果都是安慰剂怎么办？”这并不是任何人真正相信的，但我喜欢阿莉亚告诉我们的轶事，因为它确实说明了聪明人的想法。
They sit back and they go, "Yeah, exercise obviously has benefits," but what if a lot of the benefits are that you tell yourself it's good for you and the brain can actually activate these mechanisms in the body?
他们坐下来然后说：“是的，运动显然有好处”，但是如果很多好处是你告诉自己这对你有好处并且大脑实际上可以激活体内的这些机制呢？
And why wouldn't that be the case?
为什么情况不会如此呢？
Because the nervous system extends through both.
因为神经系统贯穿两者。
Dr. Peter Attia:
彼得·阿蒂亚博士：
So interesting.
太有趣了。
Andrew Huberman:
安德鲁·休伯曼：
So interesting.
太有趣了。
Okay, so fast-forward to this study, which is really about belief effects, not placebo effects.
好的，快进到这项研究，它实际上是关于信念效应，而不是安慰剂效应。
And to make a long story short, we know that nicotine, vaped, smoked, dipped, or snuffed, or these little ZYN pouches, or taken in capsule form, does improve cognitive performance.
长话短说，我们知道尼古丁，无论是吸电子烟、熏、浸还是吸，或者这些小 ZYN 袋，或以胶囊形式服用，确实可以改善认知能力。
I'm not suggesting people run out and start doing any of those things.
我并不是建议人们跑出去开始做任何这些事情。
I did a whole episode on nicotine.
我用尼古丁做了一整集。
The delivery device often will kill you some other way or is bad for you.
输送装置通常会以其他方式杀死你或者对你有害。
But it causes vasoconstriction, which is also not good for certain people, but nicotine is cognitive enhancing.
但它会导致血管收缩，这对某些人来说也不好，但尼古丁可以增强认知能力。
Why?
为什么？
Well, you have a couple sites in the brain, namely in the basal forebrain, nucleus basalis, in the back of the brain, structures like locus coeruleus, but also what's called, it's got a funny name, the pedunculopontine nucleus, which is this nucleus in the pons, in the back of the brain, in the brain stem, that sends those little axon wires into the thalamus.
大脑中有几个部位，即基底前脑、基底核，位于大脑后部，其结构类似于蓝斑，还有一个有趣的名字，桥脚核，就是脑桥中的核，位于大脑后部、脑干中，它将那些小轴突线发送到丘脑。
The thalamus is a gateway for sensory information.
丘脑是感觉信息的门户。
And in the thalamus, the visual information, the auditory information, it has nicotinic receptors.
在丘脑中，视觉信息、听觉信息，它有烟碱受体。
And when the pedunculopontine nucleus releases nicotine or when you ingest nicotine, what it does is it increases the signal-to-noise of information coming in through your senses.
当桥脚核释放尼古丁或摄入尼古丁时，它会增加通过感官传入的信息的信噪比。
So the fidelity of the signal that gets up to your cortex, which is your conscious perception of those senses, is increased.
因此，到达皮层（即您对这些感官的有意识感知）的信号的保真度会增加。
Dr. Peter Attia:
彼得·阿蒂亚博士：
And how much endogenous nicotine do we produce?
我们会产生多少内源性尼古丁？
Andrew Huberman:
安德鲁·休伯曼：
Ooh.
哦。
Well, it's going to be acetylcholine binding to nicotinic receptors.
嗯，这将是乙酰胆碱与烟碱受体的结合。
Dr. Peter Attia:
彼得·阿蒂亚博士：
I see.
我明白了。
We're not making nicotine.
我们不生产尼古丁。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
We're not making nicotine.
我们不生产尼古丁。
Dr. Peter Attia:
彼得·阿蒂亚博士：
We're just binding.
我们只是绑定而已。
So this is a nicotinic- Acetylcholine receptor
这是烟碱乙酰胆碱受体
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Of which there are at least seven and probably 14 subtypes.
其中至少有 7 种，可能有 14 种亚型。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Okay.
好的。
Andrew Huberman:
安德鲁·休伯曼：
So, right.
所以，对。
They're called nicotinic receptors in an annoying way, in the same way that cannabinoid receptors are called cannabinoid receptors.
它们以一种烦人的方式被称为烟碱受体，就像大麻素受体被称为大麻素受体一样。
But then everyone thinks, "Oh, those receptors are there because we're supposed to smoke pot," or, "Those receptors are there because we're supposed to ingest nicotine." No. The drugs that we use to study those-
但随后每个人都会想，“哦，这些受体在那里是因为我们应该吸大麻，”或者，“那些受体在那里是因为我们应该摄入尼古丁。”不。我们用来研究这些的药物-
Dr. Peter Attia:
彼得·阿蒂亚博士：
The drug is named after the receptor
该药物以受体命名
Andrew Huberman:
安德鲁·休伯曼：
That's right.
没错。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Exactly.
确切地。
Receptor is named after the drug.
受体以药物命名。
And so the important thing to know is that whether or not it's basal forebrain or pedunculopontine nucleus or locus coeruleus, that at least in the brain, because we're not talking about muscle where acetylcholine does something else via nicotinic receptors, in general, it just tends to be a signal-to-noise enhancer.
因此，要知道的重要一点是，无论是基底前脑、桥脚核还是蓝斑，至少在大脑中，因为我们不是在谈论乙酰胆碱通过烟碱受体做其他事情的肌肉，一般来说，它只是一种信噪比增强剂。
And so for the non-engineering types out there, no problem.
因此对于非工程类型来说，没有问题。
Signal-to-noise, just imagine I'm talking right now and there's a lot of static in the background.
信噪比，想象一下我现在正在说话，背景中有很多静电。
There are two ways for you to be able to hear me more clearly.
有两种方法可以让您更清楚地听到我的声音。
We can reduce the static, or I can increase the fidelity, the volume, and the clarity of what I'm saying.
我们可以减少静电，或者我可以提高我所说内容的保真度、音量和清晰度。
Okay?
好的？
For instance.
例如。
And that's really what acetylcholine does.
这确实是乙酰胆碱的作用。
That's why when people smoke a cigarette, they get that boost of nicotine and they just feel clearer.
这就是为什么当人们吸烟时，他们会得到尼古丁的刺激，并且感觉更清醒。
It really works.
它确实有效。
The other thing that happens is the thalamus sends information to a couple of places.
发生的另一件事是丘脑将信息发送到几个地方。
First of all, it sends information to the reward centers of the brain, the mesolimbic reward pathway that releases dopamine, and typically when nicotine is increased in our system, dopamine goes up.
首先，它将信息发送到大脑的奖励中心，即释放多巴胺的中脑边缘奖励通路，通常当我们系统中的尼古丁增加时，多巴胺就会增加。
That's one of the reasons why nicotine is reinforcing.
这就是尼古丁增强的原因之一。
We just like it.
我们只是喜欢它。
We seek it out.
我们寻找它。
They've done beautiful experiments with honeybees even where you put nicotine on certain plants, or it comes from certain plants and they'll forage there more.
他们用蜜蜂做了漂亮的实验，即使你把尼古丁放在某些植物上，或者尼古丁来自某些植物，它们也会在那里觅食更多。
You get them kind of buzzed.
你让他们有点兴奋。
That was a pun.
这是一个双关语。
Bad pun.
不好的双关语。
In any event, there's also an output from this thing, the thalamus, to the ventromedial prefrontal cortex, which is an area of the forebrain that really allows us to limit our focus and our attention for sake of learning.
无论如何，丘脑这个东西也有一个输出到腹内侧前额叶皮层，这是前脑的一个区域，真正允许我们为了学习而限制我们的注意力和注意力。
It allows us to pay attention.
它让我们能够集中注意力。
This is the circuit-
这是电路——
Dr. Peter Attia:
彼得·阿蒂亚博士：
You talked about this in your fantastic podcast on stimulants
你在关于兴奋剂的精彩播客中谈到了这一点
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
On ADHD.
关于多动症。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So typically ADHD drugs, so things like Adderall, Vyvanse, methamphetamine for that matter, Ritalin.
通常是 ADHD 药物，比如 Adderall、Vyvanse、甲基苯丙胺、利他林。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Why it's counterintuitive that a stimulant would be a treatment for someone with difficulty focusing.
为什么兴奋剂可以治疗注意力不集中的人是违反直觉的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
In young kids who have difficulty focusing, if you give them something they love, they're like a laser.
对于注意力不集中的小孩子来说，如果你给他们一些他们喜欢的东西，他们就像一道激光。
And the reason is that ventromedial prefrontal cortex circuit engages when the kid is interested and engaged.
原因是当孩子感兴趣并投入时，腹内侧前额叶皮层回路就会参与进来。
But kids with ADD, ADHD tend to have a hard time engaging their mind for other types of tasks, and other types of tasks are important for getting through life.
但是患有注意力缺陷多动症（ADD）的孩子往往很难将注意力集中在其他类型的任务上，而其他类型的任务对于度过一生很重要。
And it turns out that giving those stimulant drugs, in many cases, can enhance the function of that circuit, and it can strengthen so that ideally, the kids don't need the drugs in the long run, although that's not often the way that it plays out.
事实证明，在许多情况下，给予这些兴奋剂药物可以增强该回路的功能，并且可以加强这种功能，以便理想情况下，从长远来看，孩子们不需要这些药物，尽管情况并非如此。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Mm.
嗯。
Andrew Huberman:
安德鲁·休伯曼：
And there are other ways to get at this.
还有其他方法可以实现这一点。
There's now a big battle out there.
现在外面正在发生一场大战。
Is ADHD real?
多动症是真的吗？
Is it not real?
难道不是真的吗？
Of course, it's real.
当然，这是真的。
Does every kid need ADHD meds?
每个孩子都需要多动症药物吗？
No. Are there other things like nutrition, more playtime outside, et cetera, that can help improve their symptoms without drugs?
没有。是否有其他方法（例如营养、更多的户外活动时间等）可以帮助改善症状而无需药物？
Yes.
是的。
Is the combination of all those things together known to be most beneficial?
所有这些事情的结合在一起是否是最有益的？
Yes.
是的。
Are the dosages given too high and generally should be titrated down?
剂量是否太高并且通常应该逐渐减少？
Maybe.
或许。
Some kids need a lot, some kids need a little.
有些孩子需要很多，有些孩子需要一点。
I probably just gained and lost a few enemies there.
我可能刚刚在那里赢得和失去了一些敌人。
So, the point is that these circuits are hardwired circuits.
所以，重点是这些电路是硬连线电路。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Sorry.
抱歉。
One other question, Andrew.
还有一个问题，安德鲁。
If my memory serves correctly, doesn't nicotine potentially have a calming effect as well?
如果我的记忆正确的话，尼古丁不是也有潜在的镇静作用吗？
And that seems a bit counterintuitive to the focusing one.
这对于聚焦来说似乎有点违反直觉。
Is it a dose effect or a timing effect?
是剂量效应还是时间效应？
How does that work?
这是如何运作的？
Andrew Huberman:
安德鲁·休伯曼：
Yeah, it's a dosing effect.
是的，这是剂量效应。
So the interesting thing about nicotine is that it can enhance focus in the brain, but in the periphery, it actually provides some muscle relaxation.
所以尼古丁的有趣之处在于它可以增强大脑的注意力，但在外周，它实际上提供了一些肌肉放松。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Mm.
嗯。
Andrew Huberman:
安德鲁·休伯曼：
So it's kind of the perfect drug, if you think about it.
所以如果你仔细想想的话，它是一种完美的药物。
Again, I was reflecting on this, how when we were growing up, people would smoke on plane.
我再次反思这一点，在我们成长的过程中，人们会在飞机上吸烟。
They had a smoking section on the plane.
他们在飞机上设有吸烟区。
People smoked all the time, and now hardly anyone smokes for all the obvious reasons.
人们一直在吸烟，而现在几乎没有人因为所有显而易见的原因而吸烟。
But yeah, it provides that really ideal balance between being alert but being mellow and relaxed in the body.
但是，是的，它提供了身体警觉与柔和和放松之间真正理想的平衡。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So, hence its reinforcing properties.
因此，它具有增强性能。
Okay.
好的。
This study is remarkable because what they did is they had people come into the laboratory, they gave them a vape pen.
这项研究非常了不起，因为他们所做的是让人们进入实验室，给他们一支电子烟笔。
These are smokers, so these are experienced smokers.
这些人都是吸烟者，所以他们都是经验丰富的吸烟者。
Typically, there's a washout before they come in, so they're not smoking for a bit, so they can clear their system of nicotine, and they measure-
通常情况下，他们进来之前会进行一次清洗，所以他们不会吸烟一段时间，这样他们就可以清除尼古丁系统，然后他们测量-
Dr. Peter Attia:
彼得·阿蒂亚博士：
How long is that needed?
需要多长时间？
Andrew Huberman:
安德鲁·休伯曼：
Typically, it's a couple of days.
通常需要几天的时间。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Oh, okay.
哦，好吧。
Wow.
哇。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Which must be miserable for those people.
对于那些人来说一定很痛苦。
Dr. Peter Attia:
彼得·阿蒂亚博士：
That must be absolutely insane.
那一定是绝对疯狂的。
Andrew Huberman:
安德鲁·休伯曼：
It must be miserable.
一定很惨吧。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Because they can't have Nicorette gum or anything.
因为他们不能吃尼古丁口香糖什么的。
Andrew Huberman:
安德鲁·休伯曼：
No, nothing.
不，没什么。
They must be dying.
他们一定快死了。
And I wonder how many cheat.
我想知道有多少人作弊。
Dr. Peter Attia:
彼得·阿蒂亚博士：
But they can measure carbon monoxide, right?
但他们可以测量一氧化碳，对吧？
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
They measure carbon monoxide, and they're measuring nicotine in the blood as well.
他们测量一氧化碳，也测量血液中的尼古丁。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So they do a good job there.
所以他们在那里做得很好。
So then what they do is they have them vape, and they're vaping either a low, medium, or high dose of nicotine.
那么他们所做的就是让他们吸电子烟，他们吸的是低、中或高剂量的尼古丁。
The dosages don't really matter, because tolerance varies, et cetera.
剂量并不重要，因为耐受性各不相同，等等。
And then they are putting them into a functional magnetic resonance imaging machine, so where they can look at...
然后他们将它们放入功能性磁共振成像机中，这样他们就可以看到......
It's really blood flow, it's really hemodynamic response.
这确实是血流，这确实是血流动力学反应。
For those of you that want to know, it's the ratio of the oxygenated to deoxygenated blood because when blood will flow to neurons that are active to give it oxygen, and then it's deoxygenated, and then there's a change in what's called the BOLD signal.
对于那些想知道的人来说，它是含氧血液与脱氧血液的比率，因为当血液流向活跃的神经元以提供氧气时，然后它就会脱氧，然后就会出现所谓的 BOLD 信号的变化。
So fMRI, when you see these hotspots in the brain, is really just looking at blood flow.
所以，当你看到大脑中的这些热点时，功能磁共振成像实际上只是在观察血流。
And then there's some interesting physics around it.
然后还有一些有趣的物理学围绕它。
And I'll probably get this wrong, but I'll take an attempt at it so that I get beat up a little bit by the physicists and engineers.
我可能会弄错，但我会尝试一下，这样我就会被物理学家和工程师打败。
Do you remember the right-hand rule?
你还记得右手定则吗？
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yep.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Okay, so do I have this right?
好吧，那我有这个权利吗？
Correct.
正确的。
The right-hand rule, if you put your thumb out with your index finger, your middle finger, and your thumb facing up, I think that the thumb represents the direction of the charge, right?
右手定则，如果你把大拇指伸出，食指、中指、大拇指朝上，我想大拇指就代表了电荷的方向，对吗？
And then isn't the electromagnetic field is the downward-facing figure, and then it's...
然后电磁场不就是向下的图形吗，然后...
Do I have that right?
我有这个权利吗？
I have to look this up.
我必须查一下这个。
Dr. Peter Attia:
彼得·阿蒂亚博士：
I actually don't know really, no.
我其实真的不知道，不。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Well, someone will look it up.
嗯，会有人查的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But what you do is when you put a person's head in this big magnet and then you pulse the magnet, what happens is the oxygenated and deoxygenated blood, it interacts with the magnetic field differently, and that difference in signal can be detected.
但是，当你将一个人的头放入这个大磁铁中，然后对磁铁施加脉冲时，会发生含氧和脱氧的血液，它与磁场的相互作用不同，并且可以检测到信号的差异。
And you can see that in the form of activated brain areas.
你可以通过激活大脑区域的形式看到这一点。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
MRI all works by proton detection.
MRI 都是通过质子检测来工作的。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Peter Attia:
彼得·阿蒂亚博士：
So presumably there's a difference in the proton signal-
所以推测质子信号存在差异-
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Peter Attia:
彼得·阿蒂亚博士：
...
...
when you have high oxygen versus low oxygen concentration.
当您的氧气浓度较高与氧气浓度较低时。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Yep.
是的。
That's right.
这是正确的。
And what they'll do is they'll pulse with the magnet because my understanding is that, and this is definitely getting beyond my expertise, but that the spin orientation of the protons, then it's going to relax back at a different rate as well.
他们要做的是用磁铁发出脉冲，因为我的理解是，这肯定超出了我的专业知识，但是质子的自旋方向，然后它也会以不同的速率松弛回来。
So by the relaxation at a different rate, you can also get not just resting state activation, like, oh, look at a banana, what areas of the brain light up?
因此，通过以不同的速率放松，您不仅可以激活静息状态，就像，哦，看看一根香蕉，大脑的哪些区域会亮起来？
But you can look at connectivity between areas and how one area is driving the activity of another area.
但您可以查看区域之间的连接性以及一个区域如何驱动另一个区域的活动。
So very powerful technique.
所以非常强大的技术。
So what they do is they put people in a scanner and then you'll like this because you have a back-
所以他们所做的就是把人放在扫描仪中，然后你会喜欢这个，因为你有一个背部-
Dr. Peter Attia:
彼得·阿蒂亚博士：
What are the limitations of fMRI?
功能磁共振成像有哪些局限性？
Andrew Huberman:
安德鲁·休伯曼：
Oh.
哦。
Dr. Peter Attia:
彼得·阿蒂亚博士：
In terms of, how fine is the resolution?
就分辨率而言，分辨率有多精细？
Where are the blind spots of the technique?
技术盲点在哪里？
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
So resolution, you can get down to sub-centimeter.
因此分辨率可以达到亚厘米级。
They talk about it always in these paper as the voxels, which are these little-
他们在这些论文中总是将其称为体素，这些小-
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yep
是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
cubic pixels things.
立方像素的东西。
Sub-centimeter, but you're not going to get down to millimeter.
亚厘米，但不会降到毫米。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Okay.
好的。
Andrew Huberman:
安德鲁·休伯曼：
There are a number of little confounds that maybe we won't go into now that have been basically worked out over the last 10 years by doing the following.
有许多小困惑，也许我们现在不会讨论，但在过去 10 年里，我们已经通过执行以下操作基本上解决了这些问题。
You can't just give somebody a stimulus compared to nothing.
你不能只是给某人一个与什么都没有相比的刺激。
I'll just tell you the experiment.
我只告诉你这个实验。
It was discovered, for instance, that when someone would move their right hand, because when you're in the MRI, I just went for one of these recently for a clinical, not a problem, but just for a diagnostic scan, you're leaning back and you can move your right hand a bit.
例如，人们发现，当有人移动右手时，因为当你在核磁共振检查中时，我最近只是为了临床而去做其中一个，不是问题，只是为了诊断扫描，你向后靠，你可以移动你的右手一点。
And they would see an area in the motor cortex lighting up, but what they noticed was that the area corresponding to the left hand was also lighting up.
他们会看到运动皮层中的一个区域亮起来，但他们注意到与左手相对应的区域也亮了。
So what you really have to do is you have to look at resting state.
所以你真正要做的就是观察静息状态。
How much are they lighting up-
他们点亮了多少——
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
And you subtract that
然后你减去它
Andrew Huberman:
安德鲁·休伯曼：
...
...
just at rest, and then subtract that out.
就在休息时，然后减去它。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So now you'll always see resting state versus activation state.
因此，现在您将始终看到静息状态与激活状态。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Wasn't there a really funny study done as a spoof maybe a decade ago that put a dead salmon into an MRI machine?
大约十年前，不是有一项非常有趣的恶搞研究将死鲑鱼放入核磁共振仪中吗？
Andrew Huberman:
安德鲁·休伯曼：
No.
不。
Dr. Peter Attia:
彼得·阿蒂亚博士：
They did an fMRI of a dead salmon that demonstrated some interesting signal.
他们对死鲑鱼进行了功能磁共振成像，显示出一些有趣的信号。
Andrew Huberman:
安德鲁·休伯曼：
No, I didn't know that one.
不，我不认识那个人。
But it-
但它——
Dr. Peter Attia:
彼得·阿蒂亚博士：
We got to find this one for the show notes.
我们必须找到这个作为演出笔记。
Andrew Huberman:
安德鲁·休伯曼：
Oh, yeah.
哦，是的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
We should do one of these wild papers ones.
我们应该做一篇这样的狂野论文。
There are papers of people putting, don't do this folks, putting elephants on LSD that were published in science and things like that, like crazy experiments.
有些人在《科学》杂志上发表了一些论文，比如疯狂的实验，有人说，不要这样做，伙计们，给大象服用迷幻药。
We should definitely do a crazy experiments journal club.
我们绝对应该做一个疯狂的实验期刊俱乐部。
In any event, you can get a sense of which brain areas are active and when with fairly high spatial resolution, fairly high, and pretty good temporal resolution on the order of hundreds of milliseconds.
无论如何，您都可以了解哪些大脑区域处于活动状态，以及何时具有相当高的空间分辨率、相当高和相当好的时间分辨率（大约数百毫秒）。
But it's not ultra-fast because a lot of neural transmission is happening on the tens of milliseconds, especially when you're in talking about auditory processing.
但它并不是超快，因为大量的神经传输是在几十毫秒内发生的，特别是当你谈论听觉处理时。
Okay.
好的。
So they put people into the scanner, and then they give them essentially a task that's designed to engage the thalamus, known to engage the thalamus reward centers and the ventromedial prefrontal cortex, and it's a very simple game.
因此，他们将人们放入扫描仪中，然后他们本质上给他们一项旨在调动丘脑的任务，众所周知，调动丘脑奖励中心和腹内侧前额叶皮层，这是一个非常简单的游戏。
You'll like this because you have a background in finance.
您会喜欢这个，因为您有金融背景。
You let people watch a market.
你让人们观看市场。
Okay, here's the stock market, or you could say, or the price of peas, it doesn't really matter.
好吧，这里是股市，或者你可以说，或者豌豆的价格，这并不重要。
It goes up, it goes down, and they're looking at a squiggle line, then it stops, and then they have the option, but they have to pick one option.
它上升，它下降，他们看着一条曲线，然后它停止，然后他们有选择，但他们必须选择一个选项。
They're either going to invest a certain number of the 100 units that you've given them, or they can short it.
他们要么投资您给他们的 100 单位中的一定数量，要么做空。
They can say, "Oh, it's going to go down," and try and make money on the prediction it's going to go down.
他们可以说，“哦，它会下跌”，并尝试通过预测它会下跌来赚钱。
You could explain shorting better than I could, for sure.
当然，你可以比我更好地解释做空。
So depending on whether or not they get the prediction right or wrong, they get more points or they lose points, and they're going to be rewarded in real money at the end of the experiment.
因此，根据他们的预测正确还是错误，他们会获得更多分数或失去分数，并且在实验结束时他们将获得真实的金钱奖励。
So this is going to engage this type of circuitry.
所以这将涉及这种类型的电路。
Now remember, these groups were given a vape pen prior to this, where they vaped what they were told is either a low, medium, or high dose of nicotine, and they do this task.
现在请记住，在此之前，这些小组被给予了一支电子烟笔，他们被告知吸食的是低、中或高剂量的尼古丁，然后他们就完成了这项任务。
The goal is not to get them to perform better on the task.
目标不是让他们在任务上表现得更好。
The goal is to engage the specific brain areas that are relevant to this kind of error and reward type circuits.
目标是调动与这种错误和奖励类型回路相关的特定大脑区域。
And we know that this task does that.
我们知道这个任务就是这样做的。
So that includes the thalamus, that includes the mesolimbic reward pathway and dopamine, it includes the ventromedial prefrontal cortex.
因此，这包括丘脑，包括中脑边缘奖励通路和多巴胺，还包括腹内侧前额叶皮层。
First of all, they measure nicotine in the blood.
首先，他们测量血液中的尼古丁。
They are measuring how much people vaped.
他们正在测量人们吸电子烟的量。
They were very careful about this.
他们对此非常小心。
One of the nice things about the vape pen, for the sake of experiment, again, not recommending people vape, but they can measure how much nicotine is left in the vape pen before or after.
电子烟笔的好处之一是，为了实验的目的，再次强调，不建议人们电子烟，但他们可以测量电子烟笔在使用之前或之后还剩下多少尼古丁。
They can measure how long they inhaled, how long they held it in.
他们可以测量自己吸气的时间、憋气的时间。
There's a lot that you can do that's harder to do with a cigarette.
有很多事情你可以做，而用香烟却很难做到。
Okay.
好的。
They measured people's belief as to whether or not they got low, medium, or high amounts of nicotine.
他们测量了人们对尼古丁含量是否低、中、高的信念。
And it's-
这是——
Dr. Peter Attia:
彼得·阿蒂亚博士：
They were told.
他们被告知。
Andrew Huberman:
安德鲁·休伯曼：
They were told they got either this is a low amount, a medium amount-
他们被告知，他们得到的金额要么是低量，要么是中等量——
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
or a high amount.
或数额较大。
And then, of course, they looked at brain area activation during this task.
当然，他们还观察了这项任务期间大脑区域的激活情况。
And what they found was very straightforward.
他们的发现非常简单。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Sorry, they were all given the same amount.
抱歉，他们都得到了相同的金额。
Andrew Huberman:
安德鲁·休伯曼：
Yes.
是的。
This is the sneak.
这就是潜行。
I was going to offer it as a punchline-
我本来想把它作为一个妙语——
Dr. Peter Attia:
彼得·阿蒂亚博士：
Oh, okay
哦，好吧
Andrew Huberman:
安德鲁·休伯曼：
...
...
but that's okay.
但没关系。
No, I think that the cool thing about this experiment is that the subjects are unaware that they all got the exact same amount of relatively low nicotine-containing vape pen.
不，我认为这个实验最酷的一点是，受试者没有意识到他们都得到了完全相同数量的尼古丁含量相对较低的电子烟笔。
And they're measuring it from their bloodstream, so they all have fairly low levels of nicotine, but one group was told, "You got a lot," one group was told, "You got a medium amount," and the other was told, "You got a little bit."
他们通过血液进行测量，所以他们的尼古丁含量都相当低，但一组被告知，“你得到了很多”，一组被告知，“你得到了中等量”，而另一组被告知，“你得到了一点点。”
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Now, a number of things happened, but the most interesting things are the following.
现在，发生了很多事情，但最有趣的事情如下。
First of all, people's subjective feeling of being on the drug matches what they were told.
首先，人们对吸毒的主观感觉与他们被告知的相符。
So if they were told, "Hey, this is a high amount of nicotine." Like, "Yeah, it feels like a high amount of nicotine." And these are experienced smokers.
因此，如果他们被告知，“嘿，这是高含量的尼古丁。”就像，“是的，感觉尼古丁含量很高。”这些都是经验丰富的吸烟者。
If it was a medium amount, they're like, "Yeah, that feels like a medium amount." And if it was a low amount, they think it was a low amount.
如果是中等数量，他们会说，“是的，感觉就像中等数量。”如果数额很低，他们就会认为数额很低。
Now that's perhaps not so surprising.
现在这也许并不那么令人惊讶。
That's you're just tricking people.
那是你在忽悠人而已。
Dr. Peter Attia:
彼得·阿蒂亚博士：
That's the placebo in a sense.
从某种意义上说，这就是安慰剂。
Andrew Huberman:
安德鲁·休伯曼：
That's the placebo effect.
这就是安慰剂效应。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But if you look at the activation of the thalamus in the exact regions where you would predict acetylcholine transmission to impact the function of the thalamus, so these include areas like what's called the centromedian nucleus, the ventroposterior nucleus, the names really don't matter, but these are areas involved in attention.
但是，如果你观察丘脑的激活情况，你会预测乙酰胆碱传输会影响丘脑功能，这些区域包括所谓的中心正中核、腹后核等区域，名称实际上并不重要，但这些区域涉及注意力。
It scales with what they thought they got in the vape pen.
它与他们认为在电子烟笔中得到的东西成比例。
Meaning if you were told that you got a low amount of nicotine, you got a little bit of activation in these areas.
这意味着，如果您被告知尼古丁含量较低，您的这些区域就会被激活。
If you were told that you got a medium amount of nicotine and that's what you vaped, then you had medium amounts or moderate amounts of activation, and if you were told you got high amounts of nicotine, you got a high degree of activation.
如果你被告知你含有中等量的尼古丁并且这就是你吸的电子烟，那么你就会有中等量或中等量的激活，如果你被告知你含有大量尼古丁，那么你会得到高度激活。
And the performance on the task, believe it or not, scales with it somewhat.
无论你相信与否，任务的表现都会在一定程度上与之相关。
So keep in mind, everyone got the exact same amount of nicotine in reality.
因此请记住，实际上每个人摄入的尼古丁量都是完全相同的。
So here, the belief effect isn't just changing what one subjectively experiences.
所以在这里，信念效应不仅仅是改变一个人的主观体验。
Oh, this is the effect of high nicotine or low nicotine.
哦，这就是高尼古丁或者低尼古丁的效果。
It actually is changing the way that the brain responds to the belief.
它实际上正在改变大脑对信念的反应方式。
And that to me is absolutely wild.
这对我来说绝对是疯狂的。
Now, there are a couple of other things that could have confounded this.
现在，还有其他一些事情可能会混淆这一点。
First of all, it could have been that if you believe you got a lot of nicotine, you're just faster, or you're reading the lines better, or your response time to hit the button is quicker.
首先，如果你相信自己摄入了很多尼古丁，那么你的速度可能会更快，或者你读台词的能力更好，或者你按下按钮的反应时间更快。
I tell you you have a drug that's going to improve reaction time.
我告诉你你有一种药物可以改善反应时间。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
You might believe that about nicotine, and so you're quicker on the trigger, and you're getting, they have a deci-
你可能相信尼古丁，所以你会更快地触发，然后你就会明白，他们有一个决定-
Dr. Peter Attia:
彼得·阿蒂亚博士：
More activation as a result.
结果是更多的激活。
Andrew Huberman:
安德鲁·休伯曼：
More activation.
更多激活。
They rule that out.
他们排除了这一点。
They also rule out the possibility-
他们还排除了这种可能性——
Dr. Peter Attia:
彼得·阿蒂亚博士：
How do they rule that out?
他们如何排除这种情况？
Andrew Huberman:
安德鲁·休伯曼：
By looking at rates of pressing.
通过观察按压率。
Dr. Peter Attia:
彼得·阿蒂亚博士：
And there was no difference.
没有什么区别。
Andrew Huberman:
安德鲁·休伯曼：
Nothing.
什么也没有。
And in sensory areas of the brain that would represent that kind of difference, they don't see that.
在代表这种差异的大脑感觉区域中，他们看不到这一点。
The other thing that is very clear is that the connection between the thalamus and the ventral medial prefrontal cortex, that pathway scales in the most beautiful way, such that people that were told they had smoked a low or vaped a low amount of nicotine got a subtle activation of that pathway.
另一件非常清楚的事情是，丘脑和腹侧内侧前额叶皮层之间的连接，该通路以最美丽的方式扩展，因此，那些被告知吸了少量尼古丁或吸少量尼古丁的人会微妙地激活该通路。
People that were told that they got a moderate amount of nicotine got a more robust activation of that pathway.
被告知摄入适量尼古丁的人会更强烈地激活该通路。
And the people that were told that they got a high amount of nicotine in the vape pen saw a very robust activation of the thalamus to this ventral prefrontal cortical pathway.
被告知在电子烟笔中吸入大量尼古丁的人发现，丘脑对这条腹侧前额皮质通路的激活非常强烈。
Now, of course, this is all happening under the hood of the skull, simply on the basis of what they were told and what they believe.
当然，现在这一切都发生在头骨的引擎盖下，仅仅基于他们被告知的和他们相信的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
And technically, the fMRI is showing the activation of those two areas, and that's how you can infer-
从技术上讲，功能磁共振成像显示了这两个区域的激活，这就是你可以推断的方式——
Andrew Huberman:
安德鲁·休伯曼：
That's right
没错
Dr. Peter Attia:
彼得·阿蒂亚博士：
...
...
the strength of that connection.
这种联系的强度。
Andrew Huberman:
安德鲁·休伯曼：
That's right.
没错。
There's a separate method called diffuser tensor imaging, which was developed, I believe, out of the group in Minnesota.
有一种单独的方法称为扩散张量成像，我相信它是由明尼苏达州的小组开发的。
Minnesota has a very robust group in terms of neuroimaging, that can measure activation in fiber pathways.
明尼苏达州在神经影像学方面拥有非常强大的团队，可以测量纤维通路的激活。
This is not that, but you can look at the timing of activation, and it's a known, what we call monosynaptic pathway.
事实并非如此，但你可以看看激活的时间，这是一个已知的，我们称之为单突触途径。
So we haven't talked so much about figures here, but I guess if we were going to look at any one figure, and I can just describe it for the audience that doesn't have the figure in front of them.
所以我们在这里没有过多谈论人物，但我想如果我们要看任何一个人物，我可以为面前没有人物的观众描述它。
Let's see.
让我们来看看。
Probably the most important figure is figure 2.
最重要的数字可能是图 2。
Remember I said I like to read the titles of figures, which is that the belief about nicotine strength induced a dose-dependent response in the thalamus.
请记住，我说过我喜欢阅读图表的标题，即对尼古丁强度的信念会引起丘脑的剂量依赖性反应。
And figure 2B can tell you if they believe that they got more nicotine, that's essentially the response that they saw.
图 2B 可以告诉您他们是否认为自己摄入了更多尼古丁，这本质上就是他们看到的反应。
Or sorry, panel E, if you look at the belief rating as a function of the estimate in the thalamus of how much activation there was, it's a mess when you look at all the dots at once, but if you just separate it out by high, medium, and low, you run the statistics, what you find is that there's a gradual increase, but a legitimate one, from low to medium to high.
或者抱歉，E 组，如果你将信念评级视为丘脑中激活程度估计的函数，那么当你同时查看所有点时，结果会很混乱，但如果你只是将其按高、中、低分开，然后运行统计数据，你会发现逐渐增加，但从低到中到高是合法的。
In other words, if I tell you this is a high dose of nicotine, your brain will react as if it's a high dose of nicotine.
换句话说，如果我告诉你这是高剂量的尼古丁，你的大脑就会做出反应，就好像这是高剂量的尼古丁一样。
Now, what they didn't do was give people zero nicotine.
现在，他们没有做的是给人们零尼古丁。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah, I was about to say, there's a control that's missing here, right?
是的，我正想说，这里缺少一个控件，对吧？
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
So what they didn't do is give people zero nicotine and then tell them, "This is a high amount of nicotine." Sort of the equivalent of the cruel high school experiment.
所以他们没有做的是给人们零尼古丁，然后告诉他们，“这是高含量的尼古丁。”有点类似于残酷的高中实验。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
No alcohol, but then the kid acts drunk.
没有喝酒，但孩子却表现得喝醉了。
Now, in the high school example, it's unclear whether or not the kid actually felt drunk or not.
现在，在高中的例子中，尚不清楚孩子是否真的感到喝醉了。
It's unclear whether or not they had been drunk previously, if they even knew what it would be like to feel drunk, et cetera, and there's the social context.
目前还不清楚他们以前是否喝醉过，是否知道喝醉的感觉等等，还有社会背景。
What I find just outrageous and outrageously interesting about this study is simply that what we are told about the dose of a drug changes the way that our physiology responds to the dose of the drug.
我发现这项研究令人震惊和令人震惊的有趣之处在于，我们被告知的有关药物剂量的信息改变了我们的生理机能对药物剂量的反应方式。
And in my understanding, this is the first study to ever look at dose dependence of belief effects, right?
据我了解，这是第一项研究信念效应的剂量依赖性的研究，对吗？
And why would that be important?
为什么这很重要？
Well, for almost every study of drugs, you look at a dose-dependent curve.
嗯，几乎每一项药物研究都会观察剂量依赖性曲线。
You look at zero, low dose, medium dose, high dose.
你看零剂量、低剂量、中剂量、高剂量。
And here they clearly are seeing a dose-dependent response simply to the understanding of what they expect the drug ought to do.
在这里，他们显然看到了剂量依赖性反应，仅仅是为了了解他们期望药物应该做什么。
In other words, you can bypass pharmacology somewhat, right?
换句话说，你可以在某种程度上绕过药理学，对吗？
Dr. Peter Attia:
彼得·阿蒂亚博士：
Now, look at figure 2B.
现在，看图 2B。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Am I reading this correctly?
我读得正确吗？
So it's got four bars on there.
所以那里有四个酒吧。
You've got the group who were told they got a low dose, the group who was told they got a medium dose, the group that was told they had a high dose, and then these healthy controls-
有一组被告知他们服用了低剂量，一组被告知他们服用了中等剂量，一组被告知他们服用了高剂量，然后是这些健康对照 -
Andrew Huberman:
安德鲁·休伯曼：
Right
右
Dr. Peter Attia:
彼得·阿蒂亚博士：
...
...
who presumably were non-smokers who were just put in the machine.
他们大概是刚被放进机器的不吸烟者。
Andrew Huberman:
安德鲁·休伯曼：
That's right.
没错。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
This is measuring parameter estimate.
这是测量参数估计。
Is that referring to their ability to play the trading game?
这是指他们玩交易游戏的能力吗？
Andrew Huberman:
安德鲁·休伯曼：
The parameter estimate is the activation, reward-related activities from an independent thalamus mask, right?
参数估计是来自独立丘脑掩模的激活、奖励相关活动，对吧？
So what they're doing is they're just saying, if we just look at the thalamus, what is the level of activation?
所以他们所做的只是说，如果我们只看丘脑，激活水平是多少？
Dr. Peter Attia:
彼得·阿蒂亚博士：
I see.
我明白了。
So this suggests that the only statistical difference was between The low and the high.
因此，这表明唯一的统计差异存在于低值和高值之间。
Andrew Huberman:
安德鲁·休伯曼：
That's right.
没错。
Dr. Peter Attia:
彼得·阿蒂亚博士：
And nobody else was statistically different.
没有其他人在统计上有所不同。
Andrew Huberman:
安德鲁·休伯曼：
That's right.
没错。
Dr. Peter Attia:
彼得·阿蒂亚博士：
But that's not the whole story?
但这还不是故事的全部？
Andrew Huberman:
安德鲁·休伯曼：
No, that's not the whole story.
不，这不是故事的全部。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Okay.
好的。
Andrew Huberman:
安德鲁·休伯曼：
So when you look at the output from the thalamus to the ventromedial prefrontal cortex, that's where you start to identify the-
因此，当您查看从丘脑到腹内侧前额叶皮层的输出时，您就会开始识别-
Dr. Peter Attia:
彼得·阿蒂亚博士：
Is that figure 4?
是图4吗？
Andrew Huberman:
安德鲁·休伯曼：
Yes.
是的。
So this is where you see figure 4B.
这就是您看到图 4B 的地方。
If you look at parameter estimates, so this is the degree of activation between the thalamus and the ventromedial prefrontal cortex, and it's called the instructed belief.
如果你看一下参数估计，这就是丘脑和腹内侧前额叶皮层之间的激活程度，它被称为指导信念。
You can see that there's a low, medium, and high scatter of dots for each, and that each one of those is significant.
您可以看到每个点都有低、中、高分布，并且每个点都很重要。
Dr. Peter Attia:
彼得·阿蒂亚博士：
So isn't it interesting that at the thalamus, which is, and you'll immediately appreciate my stupidity when it comes to neuroscience, which is more proximate to the nicotinamide or nicotine, the nicotinamide, what do you call it?
那么，在丘脑，这不是很有趣吗？当谈到神经科学时，你会立即意识到我的愚蠢，它更接近烟酰胺或尼古丁，烟酰胺，你怎么称呼它？
The nicotine acetylcholine receptor.
尼古丁乙酰胆碱受体。
You have a lower difference of signal strength, and somehow that got amplified as it made its way forward in the brain?
你的信号强度差异较小，但不知何故，当它在大脑中传播时，信号强度差异被放大了？
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Does that surprise you?
这让你感到惊讶吗？
Andrew Huberman:
安德鲁·休伯曼：
It is surprising, and it surprised them as well.
这很令人惊讶，也让他们感到惊讶。
The interpretation they give, again, as we were talking about before, important to match their conclusions against what they actually found, which is what we're doing here.
正如我们之前讨论的那样，他们给出的解释对于将他们的结论与他们实际发现的结果相匹配很重要，这就是我们在这里所做的。
The interpretation that they give is that it doesn't take much nicotinic receptor occupancy in the thalamus to activate this pathway, but they too were surprised that they could not detect a raw difference in the activation of the thalamus.
他们给出的解释是，丘脑中不需要占用太多烟碱受体即可激活该通路，但他们也惊讶地发现，他们无法检测到丘脑激活的原始差异。
But in terms of its output to the prefrontal cortex, that's when the difference showed up.
但就其对前额皮质的输出而言，差异就出现了。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Because that figure 4B is more convincing than figure 2 because even figure 2E, if you read the fine print, the R, the correlation coefficient is 0.27.
因为图 4B 比图 2 更有说服力，因为即使是图 2E，如果您阅读细则 R，相关系数也是 0.27。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, it's weak.
是的，很弱。
Dr. Peter Attia:
彼得·阿蒂亚博士：
It's not that strong.
没那么强。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Right.
正确的。
It's weak.
它很弱。
Dr. Peter Attia:
彼得·阿蒂亚博士：
So at the thalamus, it's kind of like, eh, there might be a signal.
所以在丘脑，有点像，呃，可能有一个信号。
By the way, this goes back to our earlier discussion.
顺便说一句，这又回到了我们之前的讨论。
There could be a huge signal here and we're underpowered.
这里可能有很大的信号，而我们的动力不足。
How many subjects were in this?
这里面有多少科目？
You wouldn't have a lot of subjects in this experiment.
这个实验中不会有很多受试者。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
No, and this just speaks to the general challenge of doing this kind of work.
不，这只是说明了从事此类工作的普遍挑战。
It's hard to get a lot of people in and through the scanner.
让很多人进入并通过扫描仪是很困难的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah, and it's expensive.
是的，而且很贵。
Andrew Huberman:
安德鲁·休伯曼：
And it's expensive.
而且价格昂贵。
I should know this, but we can go back to the methods and I'll-
我应该知道这一点，但我们可以回到方法上，我会-
Dr. Peter Attia:
彼得·阿蒂亚博士：
But you can sort of just look at the number of dots on here.
但你可以只看这里的点数。
It's in the low tens, right?
是低几十吧？
Andrew Huberman:
安德鲁·休伯曼：
Yep.
是的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
It's like 40, 30, something like that.
好像是40岁、30岁之类的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
So it's possible you do this with-
所以你可以这样做-
Andrew Huberman:
安德鲁·休伯曼：
It's not your Danish study.
这不是你的丹麦研究。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah, you do this with a thousand people, this could all be statistically significant.
是的，如果你对一千个人做这件事，这可能都具有统计意义。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
So they talk about this.
所以他们谈论这个。
Based on this, we estimate that an N of 20, N is sample size, in each belief condition, the final sample would provide 90% power to detect an effect of this magnitude at an alpha of 0.5 and a two-tailed test.
基于此，我们估计 N 为 20，N 是样本大小，在每个置信条件下，最终样本将提供 90% 的功效来检测 0.5 的 alpha 和双尾检验的这种量级的影响。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Okay, so that's them referring to what we just talked about-
好吧，这就是我们刚才谈到的——
Andrew Huberman:
安德鲁·休伯曼：
Yeah
是啊
Dr. Peter Attia:
彼得·阿蒂亚博士：
...
...
which is-
这是-
Andrew Huberman:
安德鲁·休伯曼：
The power analysis
功率分析
Dr. Peter Attia:
彼得·阿蒂亚博士：
...
...
we believe at 90% confidence to get an alpha of 0.05, which means we'll want to be 95% confidence, we need 60 people.
我们相信在 90% 的置信度下可以得到 0.05 的 alpha，这意味着我们想要达到 95% 的置信度，我们需要 60 个人。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Dr. Peter Attia:
彼得·阿蒂亚博士：
20 per group.
每组20人。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Yeah.
是的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
But if the difference is smaller than what they expected, they'll miss out on some of the significance, which that looks like they're missing between the medium and high group.
但如果差异比他们预期的要小，他们就会错过一些重要意义，这看起来是他们在中组和高组之间所缺失的。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Yep.
是的。
And I too was surprised that they did not see a difference between the medium and the high group, but they did in the output of the thalamus.
我也很惊讶他们没有看到中组和高组之间的差异，但他们在丘脑的输出上看到了差异。
I was also surprised that they didn't see a difference.
我也很惊讶他们没有看到差异。
This is kind of interesting in its own right.
这本身就很有趣。
In figure 3 talks about their belief about nicotine strength did not modulate the reward response, the dopamine response.
图 3 讨论了他们对尼古丁强度的信念并没有调节奖励反应，即多巴胺反应。
Dr. Peter Attia:
彼得·阿蒂亚博士：
How was that measured?
这是如何测量的？
Also just in fMRI flag.
也只是在 fMRI 标志中。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, exactly.
是的，完全正确。
So if you look at figure 3B, other people can't see it, but basically-
所以如果你看图3B，其他人看不到它，但基本上-
Dr. Peter Attia:
彼得·阿蒂亚博士：
Oh, yeah
哦，是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
what you'll see is that there's no difference between these different groups in terms of the amount of activation in these reward pathways if people got a low, medium, or high amount of nicotine.
你会看到，如果人们摄入的尼古丁量低、中或高，这些不同群体在这些奖励途径的激活量方面没有差异。
Now, that actually could be leveraged, I believe, if somebody were trying to quit nicotine, for instance-
现在，我相信，如果有人试图戒掉尼古丁，这实际上是可以利用的，例如——
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and they were going to do that by progressively reducing the amount of nicotine that they were taking, but you told them that it was the same amount from one day to the next, you could whittle it down presumably to a low amount before taking it to zero.
他们将通过逐步减少尼古丁的摄入量来做到这一点，但你告诉他们，每一天的尼古丁量都是相同的，你可以将其减少到一个较低的量，然后再减少到零。
And if they believed it to be a greater amount, then it might actually not disrupt their reward pathways, meaning presumably they'd feel rewarded by whatever nicotine they were bringing in.
如果他们认为含量更高，那么实际上可能不会扰乱他们的奖励途径，这意味着他们可能会因为摄入的尼古丁而感到奖励。
Dr. Peter Attia:
彼得·阿蒂亚博士：
What would be your prediction if this experiment were repeated, but it was done exactly the same way with non-smokers?
如果重复这个实验，但对非吸烟者以完全相同的方式进行，你的预测是什么？
Andrew Huberman:
安德鲁·休伯曼：
Well, one thing that's sort of interesting, you asked about potential sources of artifact problems with fMRI.
嗯，一件有趣的事情是，您询问了功能磁共振成像伪影问题的潜在来源。
One of the challenges that they note in this study was you have to stay very still in the machine, but the subjects were constantly coughing because they're smokers .
他们在这项研究中指出的挑战之一是你必须在机器中保持静止，但受试者不断咳嗽，因为他们是吸烟者。
So presumably the data would be higher fidelity.
因此推测数据的保真度会更高。
Started chuckling at that one, but I had to read that one twice.
看到那一篇我开始咯咯笑，但我不得不读两遍。
I was like, "Oh, that makes sense.
我当时想，“哦，这是有道理的。
They're smokers, they're coughing.
他们是吸烟者，他们咳嗽。
They can't stay still, so movement artifact." But in all seriousness, I think that for people that are naive to nicotine, even a small amount of nicotine is likely to get this pathway activated to such a great degree, sort of like the first time effect of pretty much any drug.
他们不能保持静止，所以是运动神器。”但严肃地说，我认为对于那些对尼古丁不熟悉的人来说，即使是少量的尼古丁也可能使这条通路被激活到如此大的程度，有点像几乎任何药物的首次作用。
Dr. Peter Attia:
彼得·阿蒂亚博士：
But I wonder if they would be more or less susceptible to the belief system.
但我想知道他们是否会或多或少地受到信仰体系的影响。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, that's a really good question.
是的，这是一个非常好的问题。
Right, because they have no prior to compare it to.
是的，因为他们没有先例可以比较。
Dr. Peter Attia:
彼得·阿蒂亚博士：
They have no experience to compare it to with respect to the obviously beneficial effects of nicotine that the smokers are well used to.
他们没有经验可以将其与吸烟者已经习惯的尼古丁的明显有益作用进行比较。
Andrew Huberman:
安德鲁·休伯曼：
So this is the poor kid that got duped into thinking the non-alcoholic beer had alcohol.
所以这个可怜的孩子被骗了，以为不含酒精的啤酒含有酒精。
Though they're actually the winner we know because it didn't have so an alcohol.
尽管我们知道他们实际上是赢家，因为它没有那么酒精。
Alcohol is bad for you.
酒精对你不好。
So in the end, that kid wins and the other ones lose.
所以最后，那个孩子赢了，其他孩子输了。
Poetic justice.
诗意的正义。
But that kid having never been actually drunk before, presumably would experience it more-
但那小子从来没有真正喝醉过，想必体会会更多——
Dr. Peter Attia:
彼得·阿蒂亚博士：
I would feel like they'd be more susceptible potentially
我觉得他们可能更容易受到影响
Andrew Huberman:
安德鲁·休伯曼：
...
...
more susceptible.
更容易受到影响。
That's my guess as well.
这也是我的猜测。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So my glee for this experiment is not, or this paper rather, is not because I think it's the be all, end all, or it's a perfect experiment.
所以我对这个实验的喜悦，或者更确切地说，这篇论文，并不是因为我认为这是一切，结束一切，或者这是一个完美的实验。
I just think it's so very cool that they're starting to explore dose dependence of belief because that has all sorts of implications.
我只是觉得这太酷了，他们开始探索信念的剂量依赖性，因为这有各种各样的含义。
Use your imagination, folks.
发挥你的想象力，伙计们。
Whether or not we're talking about a drug We're talking about a behavioral intervention.
无论我们是否在谈论药物，我们都在谈论行为干预。
We're talking about a vaccine, and I'm not referring to any one specific vaccine, I'm just talking to vaccines generally.
我们谈论的是一种疫苗，我并不是指任何一种特定的疫苗，我只是泛指疫苗。
I'm talking about psychoactive drugs.
我说的是精神药物。
I'm talking about illicit drugs.
我说的是违禁药物。
I'm talking about antidepressants.
我说的是抗抑郁药。
I'm talking about all the sorts of drugs we were talking about before, metformin, et cetera.
我说的是我们之前讨论过的所有药物，二甲双胍等等。
Just throw our arms around all of it.
只需用我们的双臂拥抱这一切即可。
What we believe about the effects of a drug, presumably, in addition to what we believe about how much we're taking and what those effects ought to be, clearly are impacting at least the way that our brain reacts to those drugs.
我们对药物作用的看法，大概，除了我们对服用多少以及这些作用应该是什么的看法之外，显然至少会影响我们的大脑对这些药物的反应方式。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
It's very interesting.
这很有趣。
When you consider how many drugs that have peripheral effects or peripheral outputs begin with central issues.
当您考虑有多少具有外周作用或外周输出的药物时，首先要考虑核心问题。
So again, I think the GLP-1 agonists are such a great example of this.
我再次认为 GLP-1 激动剂就是一个很好的例子。
Andrew Huberman:
安德鲁·休伯曼：
Ozempic.
臭氧。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
I don't think anybody fully understands exactly how they're working, but it's hard to argue that they're impacting, that the GLP-1 analog is having a central impact.
我认为没有人完全理解它们是如何工作的，但很难说它们正在产生影响，GLP-1 类似物正在产生核心影响。
It's doing something in the brain that is leading to a reduction of appetite.
它在大脑中做一些事情，导致食欲下降。
Andrew Huberman:
安德鲁·休伯曼：
We believe that.
我们相信这一点。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
And I think the mouse data point to different areas of the hypothalamus that are related to satiety.
我认为小鼠数据指向与饱腹感相关的下丘脑的不同区域。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yep.
是的。
Andrew Huberman:
安德鲁·休伯曼：
That it's at least possible.
这至少是可能的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
There's no quicker way to make a mouse overeat or undereat than by lesioning its hypothalamus, depending on where you do so.
没有比损害老鼠的下丘脑更快地让老鼠吃得过多或过少的方法了，这取决于你这样做的部位。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Peter Attia:
彼得·阿蒂亚博士：
So presumably, these drugs work there.
所以想必这些药物在那里起作用。
But again, it speaks to what do you need to believe in order for that to be the case?
但同样，它说明了你需要相信什么才能实现这一点？
Andrew Huberman:
安德鲁·休伯曼：
Have they done placebo trials there, where people get something and they're told this is-
他们在那里做过安慰剂试验，人们得到一些东西，然后他们被告知这是-
Dr. Peter Attia:
彼得·阿蒂亚博士：
Oh, they do.
哦，他们确实这么做了。
Of course, those drugs have all been tested via placebo, and the placebo groups don't do anywhere near as well.
当然，这些药物都是通过安慰剂进行测试的，而安慰剂组的效果却相差甚远。
That's how we know that there's activity of the drug.
这就是我们知道药物有活性的方式。
But again, that's a little bit different than being told you are absolutely getting it, right?
但同样，这与被告知你绝对明白有点不同，对吧？
Because in the RCTs, you're just told you might be getting it, you might not be getting it.
因为在随机对照试验中，你只是被告知你可能会得到它，你可能不会得到它。
So it's not quite the same as this experiment.
所以它和这个实验不太一样。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Peter Attia:
彼得·阿蒂亚博士：
This experiment is one level up, where you're being told, "No, you're absolutely getting it." You're just getting different doses of it.
这个实验更上一层楼，你会被告知：“不，你绝对明白了。”你只是得到了不同剂量的它。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
To take this to maybe the ADHD realm, let's say a kid has been on ADHD meds for a while, and the parents, for whatever reason, the physician decide they want to cut back on the dosage.
举个可能的多动症领域，假设一个孩子已经服用多动症药物一段时间了，而父母，无论出于何种原因，医生决定减少剂量。
But if they were to tell the kid it's the same dosage they've always been taking and it's had a certain positive effect for them, according to the results, at least in this paper, which are not definitive, but are interesting, the lower dose may be as effective simply on the basis of belief.
但是，如果他们告诉孩子，这与他们一直服用的剂量相同，并且对他们有一定的积极作用，根据结果，至少在这篇论文中，这不是确定的，但很有趣，那么较低的剂量可能只是基于信念而有效。
And this is the part that makes it so cool to me, is that and it's not a kid tricking themselves or the parents tricking the kid so much as the brain activation is corresponding to the belief, right?
这就是让我觉得很酷的部分，这不是孩子欺骗自己，也不是父母欺骗孩子，而是大脑的激活与信念相对应，对吗？
Dr. Peter Attia:
彼得·阿蒂亚博士：
Wow.
哇。
Andrew Huberman:
安德鲁·休伯曼：
So that's where this-
所以这就是这个——
Dr. Peter Attia:
彼得·阿蒂亚博士：
No, that's very cool
不，那太酷了
Andrew Huberman:
安德鲁·休伯曼：
...
...
this is why, because it's done in the brain, it gets to these kind of abstract, nearly mystical, but not quite mystical aspects of belief effects, which is that your brain is a prediction-making machine.
这就是为什么，因为它是在大脑中完成的，所以它会产生信念效应的这些抽象的、近乎神秘的、但并不完全神秘的方面，即你的大脑是一个预测机器。
It's a data interpretation machine.
这是一个数据解释机器。
But it's clear that one of the more important pieces of data are your beliefs about how these things impact you.
但很明显，更重要的数据之一是您对这些事情如何影响您的信念。
So it's not that this bypasses physiology.
所以这并不是说这绕过了生理学。
People aren't deluding themselves.
人们并没有欺骗自己。
The thalamus is behaving as if it's a high dose when it's the same dose as the low dose group.
当丘脑的剂量与低剂量组相同时，丘脑的表现就好像是高剂量组。
It's wild.
它很狂野。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
I think of the implications, for example, with blood pressure, right?
例如，我想到了血压的影响，对吗？
We don't really understand essential hypertension, which is the majority of people walking around with high blood pressure.
我们并不真正了解原发性高血压，即大多数人患有高血压。
It's unclear etiology.
病因尚不清楚。
So lots of people being treated.
所以很多人都在接受治疗。
How do we know that the belief system about it can't be changed?
我们怎么知道关于它的信仰体系不能改变？
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Peter Attia:
彼得·阿蒂亚博士：
And yeah, this is eye-opening.
是的，这令人大开眼界。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
It's cool stuff.
这是很酷的东西。
And Ali Crum is onto some other really cool stuff, like for instance, just to highlight where these belief effects are starting to show up.
Ali Crum 正在研究其他一些非常酷的东西，例如，只是为了强调这些信念效应开始出现的地方。
If you tell a group that the side effects of a drug that they're taking are evidence that the drug really works for the purpose that they're taking it, even though those side effects are kind of annoying, people report the experience as less awful, and they report more relief from the primary symptoms that they're trying to target.
如果你告诉一群人，他们正在服用的药物的副作用证明该药物确实对他们服用的目的有效，即使这些副作用有点烦人，人们也会报告说这种经历不那么可怕，并且他们报告说他们试图针对的主要症状得到了更多缓解。
So our belief about what side effects are-
所以我们对副作用的看法是——
Dr. Peter Attia:
彼得·阿蒂亚博士：
That's so interesting
太有趣了
Andrew Huberman:
安德鲁·休伯曼：
...
...
can really impact how quickly and how compatible we feel about how quickly a drug works, excuse me, and how compatible we feel that drug is with our entire life.
确实会影响我们对药物起效的速度和兼容性的感觉，对不起，以及我们对药物与我们整个生活的兼容性的感觉。
So what if we call them something else?
那么如果我们称它们为其他名称又如何呢？
Like not side effects, but like additional benefits or something.
不是副作用，而是额外的好处或其他什么。
It's kind of crazy.
这有点疯狂。
And you don't want to lie to people, obviously, but you also don't want to send yourself in the opposite direction, which is reading the list of side effects of a drug and then developing all of those side effects, and then maybe later coming to the understanding that some of those were raised through belief effects.
显然，你不想对人们撒谎，但你也不想让自己走向相反的方向，即阅读药物的副作用列表，然后产生所有这些副作用，然后也许后来认识到其中一些副作用是通过信念效应引起的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
We definitely see that.
我们肯定看到了这一点。
That's the nocebo effect, right?
这就是反安慰剂效应，对吧？
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Dr. Peter Attia:
彼得·阿蒂亚博士：
That's the one we see a lot with all sorts of drugs.
这是我们在各种药物中经常看到的。
And it's tough because how do you know which is which?
这很困难，因为你怎么知道哪个是哪个？
And I think there are some people who are really impacted by that, and it makes it very difficult for them to take any sort of pharmacologic agent because they can't help but incur every possible side effect.
我认为有些人确实受到了影响，这使得他们很难服用任何药物，因为他们情不自禁地会产生各种可能的副作用。
Andrew Huberman:
安德鲁·休伯曼：
Is it true that medical students often will start developing the symptoms of the different diseases that they're learning about?
医学生是否经常会开始出现他们正在学习的不同疾病的症状？
Is that true?
这是真的吗？
Dr. Peter Attia:
彼得·阿蒂亚博士：
Well, I'll tell you, I do think that in medical school, you start to think of the zebras more than the horses all the time.
好吧，我告诉你，我确实认为在医学院，你开始更多地想到斑马而不是马。
Andrew Huberman:
安德鲁·休伯曼：
Love that phrase.
喜欢这句话。
Dr. Peter Attia:
彼得·阿蒂亚博士：
You know what I'm referring to, right?
你知道我指的是什么，对吧？
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
You see footprints, you see hoof prints, you should think of horses, but of course, medical students, you only think of the zebras.
你看到脚印，你看到蹄印，你应该想到马，但当然，医学生，你只想到斑马。
There are some really funny things in medical school, like there are certain conditions that you spend so much time thinking about that you have a very warped sense of their prevalence.
医学院里有一些非常有趣的事情，比如某些情况，你花了很多时间思考，以至于你对它们的普遍性有一种非常扭曲的感觉。
In medical school, there's this condition called sarcoidosis.
在医学院，有一种叫做结节病的病症。
I feel like we never stop talking about sarcoidosis.
我觉得我们永远不会停止谈论结节病。
I've seen like Three cases in my life.
我一生中见过这样的三个案例。
It's just not that common.
只是这种情况并不常见。
Andrew Huberman:
安德鲁·休伯曼：
Does it provide a great teaching tool or something?
它提供了一个很棒的教学工具还是什么？
Dr. Peter Attia:
彼得·阿蒂亚博士：
I don't know.
我不知道。
Some of these things I don't know.
其中一些事情我不知道。
How much time did we spend talking about situs inversus?
我们花了多少时间讨论逆位？
This is when people embryologically have a reversed rotation and everything in their body is flipped.
这是当人们在胚胎上发生反向旋转时，他们体内的所有东西都会翻转。
Literally, everything is flipped.
从字面上看，一切都颠倒了。
Andrew Huberman:
安德鲁·休伯曼：
Wild.
狂野。
Dr. Peter Attia:
彼得·阿蒂亚博士：
So their heart is on their right side, their liver is on the left side, their appendix is on the left side.
所以他们的心脏在右侧，肝脏在左侧，阑尾在左侧。
And so I'm not making this up.
所以这不是我编造的。
Andrew Huberman:
安德鲁·休伯曼：
How common is this?
这种情况有多常见？
Dr. Peter Attia:
彼得·阿蒂亚博士：
I've never seen it, okay?
我从来没见过，好吗？
Andrew Huberman:
安德鲁·休伯曼：
I was thinking about boxing and the liver shot.
我想到了拳击和肝脏射击。
You could easily be going for the wrong side of the body.
你很容易就会走错身体的一侧。
Dr. Peter Attia:
彼得·阿蒂亚博士：
No, I swear to God, as a medical student, if you were told someone had left-sided lower quadrant pain, to which the answer is almost assuredly they have diverticulitis, you'd think, "They could have appendicitis in the context of situs inversus." The fact that that would even register in the top 10 things that it could possibly be.
不，我向上帝发誓，作为一名医学生，如果你被告知有人患有左侧下腹疼痛，答案几乎肯定是他们患有憩室炎，你会想，“他们可能患有逆位性阑尾炎。”事实上，这甚至可能被列入前十名。
Andrew Huberman:
安德鲁·休伯曼：
Wild.
狂野。
Dr. Peter Attia:
彼得·阿蒂亚博士：
But yes, you just have a totally warped sense of what's out there.
但是，是的，你对外面的事物有一种完全扭曲的感觉。
Andrew Huberman:
安德鲁·休伯曼：
Oh, man.
哦，伙计。
Well, this has been pure pleasure for me.
嗯，这对我来说是纯粹的快乐。
I don't know about you.
我不了解你。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
This has been-
这已经是——
Andrew Huberman:
安德鲁·休伯曼：
I don't know about our listeners, but for me, this is among the things that I just delight in, and even more so because you're the one across the table from me teaching me about these incredible findings.
我不知道我们的听众如何，但对我来说，这是我喜欢的事情之一，更重要的是，因为你是我坐在桌子对面的人，教我这些令人难以置信的发现。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Well, likewise.
嗯，同样。
Andrew Huberman:
安德鲁·休伯曼：
And the gaps in those findings, which are equally incredible because they're equally important to know about.
这些发现中的差距同样令人难以置信，因为了解它们同样重要。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
So let's do this again in Austin.
让我们在奥斯汀再做一次。
Andrew Huberman:
安德鲁·休伯曼：
Absolutely.
绝对的。
Next time on your home court.
下次在你的主场。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Very well.
很好。
And bring a little bit of that dew if you've got it.
如果有的话，带一点露水来。
Andrew Huberman:
安德鲁·休伯曼：
Oh, yeah.
哦，是的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
I'll bring a low, medium, and high amount.
我会带低、中、高量的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
A low, medium, and high dose.
有低、中、高剂量。
Andrew Huberman:
安德鲁·休伯曼：
Thanks, Peter.
谢谢，彼得。
You're the best.
你是最棒的。
Dr. Peter Attia:
彼得·阿蒂亚博士：
Thanks, sir.
谢谢，先生。
Andrew Huberman:
安德鲁·休伯曼：
Thank you for joining me for today's Journal Club discussion with Dr. Peter Attia.
感谢您参加今天与 Peter Attia 博士在期刊俱乐部的讨论。
If you're learning from and/or enjoying this podcast, please subscribe to our YouTube channel.
如果您正在学习和/或喜欢此播客，请订阅我们的 YouTube 频道。
That's a terrific zero-cost way to support us.
这是支持我们的绝佳零成本方式。
In addition, please subscribe to the podcast on both Spotify and Apple.
此外，请在 Spotify 和 Apple 上订阅该播客。
And on both Spotify and Apple, you can leave us up to a five-star review.
在 Spotify 和 Apple 上，您都可以给我们五星级的评价。
If you have questions for me or comments about the podcast or guests that you'd like me to consider hosting on the Huberman Lab podcast, please put those in the comments section on YouTube.
如果您对我有疑问或对您希望我考虑在 Huberman Lab 播客上主持的播客或嘉宾有意见，请将这些意见放在 YouTube 的评论部分。
I do read all the comments.
我确实阅读了所有评论。
Please also check out the sponsors mentioned at the beginning and throughout today's episode.
另请查看今天节目开头和整个节目中提到的赞助商。
That's the best way to support this podcast.
这是支持这个播客的最佳方式。
Not so much on today's episode, but on many previous episodes of the Huberman Lab podcast, we discuss supplements.
今天的节目不多，但在 Huberman 实验室播客的许多以前的节目中，我们讨论了补充剂。
While supplements aren't necessary for everybody, many people derive tremendous benefit from them, for things like enhancing sleep, for hormone support, and for focus.
虽然补充剂并不是每个人都需要的，但许多人都从它们中获得了巨大的好处，例如增强睡眠、激素支持和注意力集中。
The Huberman Lab podcast has partnered with Momentous Supplements.
Huberman Lab 播客与 Momentous Supplements 合作。
If you'd like to access the supplements discussed on the Huberman Lab podcast, you can go to Live Momentous, spelled O-U-S, so it's livemomentous.com/huberman, and you can also receive 20% off.
如果您想访问 Huberman Lab 播客上讨论的补充品，您可以访问 Live Momentous，拼写为 O-U-S，即 livemomentous.com/huberman，您还可以获得 20% 的折扣。
Again, that's livemomentous, spelled O-U-S, .com/huberman.
再说一遍，这很生动，拼写为 O-U-S，.com/huberman。
If you haven't already subscribed to our Neural Network Newsletter, our Neural Network Newsletter is a completely zero-cost monthly newsletter that includes summaries of podcast episodes as well as protocols.
如果您还没有订阅我们的神经网络新闻通讯，我们的神经网络新闻通讯是完全零成本的每月新闻通讯，其中包括播客剧集和协议的摘要。
That is short PDFs describing, for instance, tools to improve sleep, tools to improve neuroplasticity.
这是简短的 PDF，描述了例如改善睡眠的工具、改善神经可塑性的工具。
We talk about deliberate cold exposure, fitness, various aspects of mental health.
我们谈论刻意的寒冷暴露、健身、心理健康的各个方面。
Again, all completely zero cost.
再次强调，一切完全零成本。
And to sign up, you simply go to hubermanlab.com, go over to the menu in the corner, scroll down to Newsletter, and provide your email.
要注册，您只需访问 hubermanlab.com，转到角落的菜单，向下滚动到新闻通讯，然后提供您的电子邮件。
We do not share your email with anybody.
我们不会与任何人分享您的电子邮件。
If you're not already following me on social media, I am hubermanlab on all platforms.
如果您还没有在社交媒体上关注我，我是所有平台上的 hubermanlab。
So that's Instagram, Twitter, Threads, LinkedIn, and Facebook.
这就是 Instagram、Twitter、Threads、LinkedIn 和 Facebook。
And at all of those places, I talk about science and science-related tools, some of which overlaps with the content of the Huberman Lab podcast, but much of which is distinct from the content of the Huberman Lab podcast.
在所有这些地方，我谈论科学和与科学相关的工具，其中一些与胡伯曼实验室播客的内容重叠，但其中大部分与胡伯曼实验室播客的内容不同。
Again, it's hubermanlab on all social media platforms.
再说一遍，所有社交媒体平台上都是 hubermanlab。
Thank you once again for joining me for today's Journal Club discussion with Dr. Peter Attia.
再次感谢您参加今天的期刊俱乐部与 Peter Attia 博士的讨论。
And last but certainly not least, thank you for your interest in science.
最后但并非最不重要的一点是，感谢您对科学的兴趣。