GLP-1药物的广泛使用与意外效果
主持人: 有一个数字让我震惊,当我了解到它的时候。这来自凯撒家庭基金会的一项民意调查。八分之一的美国人现在正在服用 GLP-1。八分之一。也许我不应该如此震惊,因为在我自己的社交圈里,这个数字更高。我出于某些原因尝试过这些药物,它们是一种奇怪的药物,对吗?它们不会让你减肥,它们会让你不想吃东西。它们就是这样做到的,对吗?但它们还会做所有这些其他事情。它们似乎能独立于减肥之外,保护人们的心脏健康。它们对肾脏、肝脏都有保护作用。关于痴呆症、阿尔茨海默症的研究正在进行中。它们对成瘾和欲望有各种奇怪的影响。但每个人都应该服用这些药吗?对于社会而言,能够获得以这种方式调节欲望的药物意味着什么?它们对病人意味着什么?对健康人又意味着什么?我一直想就此做一期节目,但不知道该如何着手。然后,Julia Beloo,她是《纽约时报》观点版撰稿人,也是《食物智能》一书的合著者,并且曾是我的同事,在 Vox 担任健康与科学记者,她开始对 GLP-1s 进行大量报道,并写了许多很棒的文章。她是我所认识的最好的健康与科学记者之一。她在科学方面非常深入,但又非常富有同情心,细致入微,不懈地与实际生活在医疗系统中的人们交流他们的经验。我想请她来听听她学到了什么。一如既往,我的邮箱是forclient.showy.times.com。Julia Beloo,欢迎来到节目。
Original English
Host: Here's a number that actually shocked me when I learned it. This from a Kaiser Family Foundation poll. One out of eight Americans is now taking a GLP-1. One out of eight. Maybe I shouldn't have been so shocked because the number is higher in my social circles. I have tried these uh for reasons I'll explain, but they're a strange medication, right? They don't make you lose weight. They make you not want to eat food. that like that's what they do, right? But then they do all these other things. They seem to protect people's heart health independent of losing weight. They're protective of kidneys, of livers. There is ongoing research about dementia, Alzheimer's. They have all these strange effects on addiction and desire. But should everyone be on these? Like, what does it mean for society to have access to drugs that regulate desire in this way? What do they mean for the sick? What do they mean for the well? I've wanted to do an episode on this for for a while, but haven't known quite how to approach it. And then Julia Beloo, who's a contributing writer at New York Times Opinion and co-author of the book Food Intelligence and also was a health and science reporter with me back at Vox, she started doing a lot of reporting on JLP1s and she's written a lot of great pieces on them. She is one of the best health and science reporters I have ever known. incredibly deep on the science, but really compassionate and detailed and relentless about talking to actual people about their experiences inside the health system. And I wanted to have her on to hear what she's been learning. As always, my email is forclient.showy.times.com. Julia Beloo, welcome to the show.
Julia Beloo: 非常感谢。很高兴能来到这里。
Original English
Julia Beloo: Thank you so much. It's a pleasure to be here.
主持人: 所以,这个数字让我震惊。根据凯撒家庭基金会的民意调查,八分之一的美国人目前正在服用 GLP-1。为什么会这样?
Original English
Host: So, I was shocked by this number. According to the Kaiser Family Foundation's poll, one in eight Americans are currently taking a GLP1. Why?
Julia Beloo: 是的,这对我来说也很惊讶。所以,我认为理解这一点的一个方式是,人们长期以来一直在寻找基本上是减肥的“魔药”,对吗?所以我想这是一部分原因。现在我们终于有了一种能与我们唯一拥有的另一种有效医疗干预措施相媲美的东西,那就是减肥手术。另一方面,有很多糖尿病患者。我认为这是我们看到这么多人服用这些药物的另一个原因。此外,我认为这些药物确实迎合了一个特殊的时刻,那就是算法社交媒体时代。它们无处不在。在美国,我们已经对药品营销采取了相对不受限制的方式。我们到处都能看到它们的广告。自疫情以来,我们看到远程医疗行业蓬勃发展,也围绕着这些药物。我想这就是为什么我们看到这些令人震惊的数字。
Original English
Julia Beloo: Yes, it was surprising to me, too. So, I think um one of the ways we can understand this is there's this very long history of people seeking out basically the magical elixir for weight loss, right? So, I think that's one piece of it. And now we finally have something that rivals the only other effective medical intervention we've had to help people lose weight, which is beriatric surgery. On the other hand, there's a lot of people who are living with diabetes. And I think that's another reason that that we see so many people who are on these drugs. In addition, I think these drugs have really met a particular moment, which is this algorithmic social media age. They're everywhere. Um, in the US, we already had this relatively unrestricted approach to marketing pharmaceuticals. Um, we see them advertised everywhere. we've seen this tele medicine kind of industry flourish since co but also around these drugs and um I think that's why we're seeing these kind of shocking numbers.
GLP-1药物对糖尿病患者的作用机制
主持人: 所以我想从人们实际上不太谈论的部分开始,那就是糖尿病,这是这些药物最初获批的用途。正如你所说,大量的美国人患有糖尿病,并且常常因此遭受可怕的健康后果,包括截肢和失明。这些药物对糖尿病患者有什么作用?
Original English
Host: So I want to start on the part of this that people actually don't talk about that much which is diabetes which is what these drugs are originally approved for as you say a huge number of Americans have diabetes and and have terrible health consequences often from it including limb amputation and and and blindness. What do these drugs do for diabetics?
Julia Beloo: 我们的身体自然会产生 GLP-1。所以,我们有一种在肠道、大脑中产生,以及在胰腺中较小程度上产生的激素。因此,基本上,它们是我们天然产生的一种激素的合成版本。而对于糖尿病而言,最大的突破在于它们只在血糖高的情况下刺激胰腺释放胰岛素。所以,它不像你服用胰岛素时,需要小心饮食,并且有低血糖水平的风险以及随之而来的危险。这些药物只在你的血糖偏高时刺激胰岛素分泌。因此,当研究人员在研究中尝试越来越高的剂量,以帮助糖尿病患者获得越来越多的益处时,他们开始在试验中发现这些减肥结果。所以人们开始自发地减肥,然后我们后来发现所有这些其他意想不到的益处。没有制药公司会预料到这一点。我们才刚刚进入所谓的“Ozempic 时代”。我认为我们才刚刚开始发现这些药物的益处和危害。
Original English
Julia Beloo: So, our bodies produce GLP-1 naturally. So, we have this hormone that's produced in our gut, in our brains, and to a lesser extent in the pancreas. So, basically, they're this synthetic version of a hormone we produce naturally. And the big breakthrough for diabetes was that they're stimulating the pancreas to release insulin only in the context of high blood sugar. So, it's not like when when you take insulin and you need to be careful about what you're eating and you're at risk of really low blood sugar levels and the dangers that come with that. These are only stimulating insulin secretion when your blood sugar is running high. So, as the re as researchers who are working on this are trying higher and higher doses to help people with diabetes get more and more benefit, they start to discover these weight loss um results in the trial. So people start to spontaneously lose weight and then later we're finding all these slew of other benefits that no one would have predicted. No pharma company would have bet on this. We're only at the beginning of what what's been called this Ozempic era. I think we're we're really just at the beginning of discovering the benefits and the harms of these drugs.
减肥效果:大脑与饥饿感
主持人: 好的。所以你有所认识,就是人们开始观察到糖尿病患者服用这些药物后开始减肥,并且不感到饥饿。当研究人员开始测试第一代 Ozempic 时,我们现在称之为 Wegovy,它的效应大小有多大?我们实际了解 Wegovy 在减肥方面能做什么?还有另一种更先进的药物,它有更多的作用机制,叫做 Tirzepatide,也叫 Zepbound。人们服用这些药物能减掉多少体重?
Original English
Host: Okay. So you have the recognition which is just something people begin observing that diabetics on these drugs begin to lose weight and they don't feel hungry and as researchers begin testing you know the first generation of this Ozempic what we now in that context call Wegovy how big is the effect size what do we actually know about what Wegovy does for weight loss there's another one which is slightly more advanced it has more mechanisms of action to his Tirzepatide which is also goes by Zepbound. How much weight do people lose on these?
Julia Beloo: 这取决于药物,但我们谈论的是大约 15%。这是我们第一次拥有一种药物,能够真正与更有效的减肥手术相媲美。关键在于它能降低食欲。所以它不是加速新陈代谢或能量消耗。GLP-1 是一种激素。最初的设想是这是一种肠道激素。或者说,那是很多人关注的重点,而我们只是,它在进食后释放,帮助人们发出饱腹信号。它帮助他们感到饱足,知道自己已经吃饱了,而我们只是在提供一个增强版的这种肠道激素。结果发现,实际上,你需要刺激大脑的 GLP-1 系统才能获得减肥效果。所以,一旦你达到这个大脑 GLP-1 系统,你才会干扰食欲。嗯,你写过或合著过一本关于新陈代谢的整本书。那本书的一个论点,也是这个领域书籍的一个论点,我认为人们没有充分认识到的是,饥饿是大脑的一种功能。它是大脑对周围世界的反应和预测的一种功能。我们总是认为,你知道,人们只是感到饥饿。然后,你知道,你应该用你的大脑来决定是否要吃东西,但你的大脑正在决定你是否感到饥饿。你正在与自己的本能作斗争。所以,我想让你花一分钟谈谈这个想法,即饥饿是胃的一种功能,而不是饥饿是大脑的一种功能,以及研究人员是如何从一个观点转向另一个观点的。
Original English
Julia Beloo: So it depends on the drug but we're talking like 15%. It's the first time we have a drug that really rivals the more effective types of beriatric surgery. The key point there is that it's turning down appetite. So it's not ramping up metabolism or energy burn. GLP-1 is a hormone. And the idea was that this is a gut hormone. um or that that's the the thing that a lot of people focused on and we're just and it it's released after eating and it helps people signal satiety. It helps them feel full and know that they've eaten and we're just giving a really souped up version of this um this gut hormone. And it turns out that actually you need to stimulate the brain GLP-1 system to get the weight loss effects. So you only interfere with appetite once you reach this brain GLP-1 system. Well, you've written or co-written a whole book about the metabolism. And one of the arguments of that book, one of the arguments of of books in this space that I think people don't appreciate is that hunger is a function of the brain. And it's a function of the brain's reaction and predictions about the world around it. And we we always have this idea that, you know, people just feel hungry. And then, you know, you should use your brain to decide if you want to eat, but your brain is deciding if you feel hungry. and and and you're sort of fighting its own instincts. So, I'd like you to spend a minute on this like idea that hunger is a function of the stomach versus hunger as a function of the brain and sort of how researchers moved from one to the other.
Julia Beloo: 是的。我们在书中描述它的方式,我们使用呼吸的比喻。所以如果我告诉你现在控制你的呼吸,比如慢一点呼吸,或者快一点呼吸,或者屏住呼吸,你可以在短时间内控制,但最终生理学将接管。嗯,我们吃什么也是如此。所以我们对我们的个人正餐和小吃有一种控制的错觉,但我们体内一直存在着一种内部信号的交响乐。而大脑就是这种交响乐的指挥。嗯,我们做出的决定远不是意识控制的产物,我认为很多人都没有意识到这一点。所以当你服用 GLP-1 时,你得到的是一个比你身体产生的更强效、更持久的版本,而且它必须到达大脑。理论是它会到达大脑中通常发出毒素在循环中的信号的区域。所以这会抑制你的食欲并增加你的恶心感。
Original English
Julia Beloo: Yeah. The way we describe it in the book, we use this analogy of breathing. So if I tell you like take control of your breath right now, like breathe more slowly or breathe more quickly or hold your breath, you can take control for short periods of time, but eventually physiology takes over. Um, and the same thing is true of what we eat. So we have this illusion of control over our individual meals and snacks, but there's this symphony of internal signals that's going on inside of us all the time. And the brain is sort of leading this symphony. And um the decisions we make are much less a product of conscious control that I think many people appreciate. So when you're taking a GLP1, you're getting a much higher longerlasting version of what your body produces and it has to reach the brain. And the the theory is that it's reaching into the part of the brain that usually signals that there's a toxin in circulation. And so that shuts down your appetite and increases your nausea.
主持人: 就像食物中毒或类似情况会引起的反应。
Original English
Host: Like what you would get during food poisoning or something.
Julia Beloo: 没错。或者你可能会遇到这些药物最常见的副作用,对吧?嗯,所以它达到了那个效果。
Original English
Julia Beloo: Exactly. or what you would have on a these are the most common side effects of these drugs, right? Um so so it reaches into that.
主持人: 所以我们发明的这种神奇药物,就是让你的大脑一直觉得自己有点中毒。
Original English
Host: So the wonder drug we've invented is we've made your brain slightly think it's being poisoned all the time.
Julia Beloo: 嗯,我想这是一种说法。当然。所以,这,所以……
Original English
Julia Beloo: Um I I think that's one way to put it. Absolutely. And so this so
主持人: 现代的产物。
Original English
Host: modernity baby.
Julia Beloo: 我知道。而且在我们完全毒性的食物环境中,对吗?它只是通过作用于这个 GLP-1 大脑系统来降低你的食欲。所以它在大脑中充当神经递质,并从那里作用于大脑的其他部分。嗯,是的,这是一个非常活跃的研究领域,但这就是底线,而这种食欲的降低是这些药物的关键特征。我认为 GLP-1s 有趣的一点是,我们基本上创造了一个自然界中不存在的食物环境,即超甜、超油、超咸、超高热量的食物。我们的大脑经过漫长时间的进化,将这些食物视为老虎机中“三樱桃”的奖励,并非常非常渴望它们。所以,我们把人们置于这种高度刺激的环境中,但我们并没有改变每个人的大脑,让他们在遇到高热量或高糖食物时降低饥饿感。所以我们一直在要求那些拥有“穴居人”大脑的人们(包括我自己在内),现在被现代工业化食品生产的成果所包围,玛氏公司投入了巨额研发资金来让我的孩子想要 M&M's,但这对人们不起作用,然后我们责怪他们,说他们没有很好地运用意志力和自制力。
Original English
Julia Beloo: I know. And in the context of our completely toxic food environment, right? It's just turning down your appetite by reaching into this GLP-1 brain system. So it acts as a neurotransmitter in the brain and from there reaches other parts of the brain. Um yeah this is something this is a very active area of research but that's the sort of bottom line and and this dialing down of appetite is the key key feature of these drugs. One of the things that I find interesting about the GLP-1s is we basically created this food environment that does not exist in nature of hypers sugary, hyper fatty, hyper salty, hyperc calorie dense foods. Our brains are evolved over very very long periods of time to treat those as getting you know three cherries on the slot machine and to really really want them. So, we've put people into this hyper stimulating environment, but we didn't change everybody's brain to turn down the level of hunger when you come into something that is very calorie dense or very sugar dense. And so we've been asking people with these like caveman all of us myself um with these caveman brains now surrounded by the fruits of modern industrialized food production where the Mars company is spending god knows how much on R&D to make my kids want M&M's and it doesn't work for people and then we blame them and tell them they've not done a good job exercising their willpower and self-control.
主持人: 我想你也是一个早期与体重作斗争的人。呃,我直到成年之前都非常非常胖。嗯,我在 16 岁的时候减掉了大约 60 磅,50 磅。从那以后,我一直在与我的食物欲望作斗争。就好像如果桌子上有一碗 Oreos,我们谈话的整个过程中,我 30% 的精力都在努力不吃那些 Oreos。
Original English
Host: I think you were also someone who struggled with weight earlier in your life. Uh, I was very very heavy until I was almost an adult. Um, like I lost like 60-ish pounds, 50-ish pounds when I was uh, 16. And then ever since like I fight my food desires. Like if we had a bowl of Oreos on this table, 30% of my mental energy the whole time we were talking did not eat the Oreos.
Julia Beloo: 对。是的。完全正确。我记得我们在华盛顿共进午餐时,我正在做大量关于肥胖的报道,你说:“我为什么是一个这样的人,如果巧克力蛋糕在那里,我大脑的 50% 都专注于巧克力蛋糕?”那时我没有很好的答案给你。嗯……
Original English
Julia Beloo: Right. Yeah. Ex. Absolutely. I remember we had lunch in Washington when I was doing lots of obesity reporting and you said why am I a person who if the chocolate cake is there like 50% of my brain is focused on the chocolate cake and I didn't have a good answer for you then. Um
主持人: 你现在有答案了吗?
Original English
Host: do you have one now?
Julia Beloo: 我有。是的。我认为是这样的,你知道,当我们思考像普通肥胖这样的问题时,肥胖有很多不同的类型。嗯,但大多数人患的是普通肥胖,它源于这些微小的、超过一千种基因变异,这些变异几乎都作用于大脑。所以你的神经生物学可能与那些不必与巧克力蛋糕作斗争的人不同。嗯,我实际上为了写这本书做了基因检测,我也是一个与体重作斗争的人,结果我发现我的遗传风险比 90% 以上的人口都要高。但这种风险在特定环境中不会被表达。但正如你所说,当你把像我们这样的人置于有很多 M&M's 和很多巧克力蛋糕的环境中时,它会变得困难得多。嗯,我认为大多数人没有这种,比如说,能够最终管理自己的环境以控制体重的特权,就像我们可能曾经拥有的那样。我有一个家人,嗯,我与他没有血缘关系,有一件事总是让我惊讶,她会点甜点,她喜欢甜点,她喜欢巧克力蛋糕,她会吃一半蛋糕,然后把剩下的一半带回家。我总是看着那个,然后我想,你身上发生的事情没有发生在我身上,或者可能反过来,我身上发生的事情没有发生在你身上。然后我感到在我生活的其他方面。呃,我可以抽烟或吸一口电子烟。我没有兴趣再来一口。它不会激发我的任何欲望。我可以喝一杯威士忌,然后剩下半杯,或者一杯葡萄酒,我并不特别想继续喝。我生活中有人与酗酒作斗争,我没有意志力。他们没有。
Original English
Julia Beloo: I do. Yeah. I think it's that you know so when when we think about something like common obesity so there's many different types of obesity. Um, but what most people have is called common obesity and it arises from these tiny like over a thousand genetic variants that all act almost all act in the brain. And so you have a neurobiology probably that's different from someone who doesn't have to fight the chocolate cake. Um, and I actually did genetic testing for the book and I'm also someone who struggled with my weight and I I turns out I have a higher genetic risk than like 90% of the population. But this risk in a particular environment won't be expressed. But as you said, when you put people like us in environments where there's lots of M&M's and lots of chocolate cake, it becomes much harder. Um, and I think most people don't have this um privilege, let's say, of being able to finally curate their environment to control their weight in maybe the way we might have had. I have a family member who uh I'm not related to by blood and one thing that always amazes me is she will order dessert and she loves dessert and she loves chocolate cake and she'll like eat half the cake and then take the rest home. And I always look at that and I think whatever is happening in you is not happening or me or or possibly vice versa whatever is happening in me is not happening in you. And then I feel in other ways elsewhere in my life. Uh I can have a cigarette or a puff on a vape. I have no interest in another. It does not exite any desire in me. I can have a whiskey and leave half of it or a glass of wine and I don't particularly want to keep going. And I've had people in my life who struggle with alcoholism and I don't have willpower. They don't.
主持人: 是的。他们身体里或心理上发生了一些事情,这绝对没有发生在我身上。
Original English
Host: Yes. something is happening in their bodies or in their minds absolutely that is not happening in mine.
Julia Beloo: 我一直认为我们因此责怪人们是如此残忍,因为常常是那些没有强烈欲望的人,责怪那些有欲望的人没有运用意志力。但那些人不是在运用意志力。我没有运用意志力来不抽更多烟。我不想抽。
Original English
Julia Beloo: And I've always thought the way we blame people for this is so cruel because it is so often people who don't have the propulsive desire, blaming people who do for not exercising willpower. But those people aren't exercising willpower. I'm not exercising willpower to not have more cigarettes. I don't want them.
主持人: 不,绝对是。我经常和我丈夫讨论这个问题。对于某些人来说,牌局就是对他们不利。嗯,有一个人对我的思考帮助很大,那就是 Robert Seapolski。他谈到我们有这些,嗯,由我们的基因创造的潜力或脆弱性,然后在不同的环境中,它们要么被表达或激活,要么不被表达,对吧?就像,你知道,做正确的事情,购买你知道你应该吃的食物,或者每天锻炼,当你上夜班,还要抚养孩子,而且你可能是单身妈妈或爸爸,或者其他任何情况时,这是极其困难的。就像,嗯,你将如何做所有这些,你知道你需要做的事情来保护你的健康,并对抗你可能拥有的这种神经生物学。所以你有了这个,你有了生物学和神经生物学的相互作用,就像你所说的,我们称之为意志力的东西,这是一个非常,非常不明确的概念,然后是环境。对我来说,环境这个问题真的很重要。我将以我自己为例,你知道,当我年轻很多的时候,我减掉了大量的体重。
Original English
Host: No, absolutely. I have this conversation all the time with my husband. For some people, the cards are just stacked against them. Um, one person that really helped my thinking on this was Robert Seapolski. He talks about how we have these um potentials or vulnerabilities that are created by our genetics and then in different environments, they're either expressed or activated or not not expressed, right? Like it's extremely hard to, you know, do the right thing to buy the foods that you know you should be eating or to exercise every day when you're working the night shift and you're raising kids and you're um maybe the single mom or dad or whatever it is like um how how are you going to do all like all the things that you know you need to be doing to protect your health and to fight against um this neurobiology that you might have. So you have this you have this interplay of biology neurobiology as you're as you're saying it this thing we call willpower which is a very a very poorly specified concept and then environment to me this question of environment is really important I'll I'll use myself as the example you know when I lost a lot of weight I mean when I was younger a lot younger
Julia Beloo: 一个高中生,无所事事。
Original English
Julia Beloo: a high school student with nothing to do
主持人: 而且我能够在年轻的时候真正保持住这一点。嗯,自从我有了孩子以来,我一直无法成功节食,因为我无法控制食物环境。
Original English
Host: and I was able to really really hold that when I was a young adult. Um, and I have not been able to diet successfully since I had kids because I can't control the food environment.
主持人: 而且我还可以控制很多其他事情。我有钱。我可以,你知道,去健身房。我的日程安排有一定的自主权。所以,正如你所说,当你加入夜班这样的事情,当你加入没有钱购买健康食品或去健身房这样的事情,当你加入有更多孩子或更少时间这样的事情,意志力在你有自主权或金钱来创造一种有助于某种生活方式的特定环境时,它的作用会非常非常不同,对吗?你是一个拥有私人厨师的好莱坞名人,而不是一个工作两份工作的四个孩子的单身母亲。而这种意志力就像大脑中某种不变的肌肉,而不是某种储备的自律,它会被耗尽,比如如果我睡眠不足,我就会吃得更多。
Original English
Host: And there's a lot of other things I can control. I have money. I can, you know, go to the gym. I have a certain amount of autonomy over my schedule. So, as you say, when you add in things like the night shift, when you add in not having the money to to to get healthy foods or or go to the gym, when you add in having more kids or less time, that we will power works very very differently when you're able to have the autonomy or the money to create a certain kind of environment around you that is conducive to living in a certain way, right? you're a Hollywood celebrity with a personal chef versus you're a single mother of four, you know, who works two jobs. And this idea that like willpower is some unchanging like muscle inside the mind as opposed to some reserved discipline that gets depleted like if I don't sleep enough, I eat more.
Julia Beloo: 对。绝对是。而且当你睡眠不足时,你就应该吃得更多。你绝对正确,我之前提到的这种内部信号的交响乐,它与我们的环境相互作用。所以,我非常欣赏你作为一名记者,以及对科学有深入了解的人,在 GLP-1s 方面的工作,你对他们进行了大量的采访,采访了许多不同类型的人,对我来说,这总是这场对话的残酷之处,他们一直在运用大量的持续意志力,不断地进行非常限制性的饮食,你知道,减掉 30 磅,然后又胖回来。对他们来说是什么感觉?嗯,对于那些体重减轻了很多的人来说,他们如何描述服用 GLP-1 的体验与不服用时的感受?
Original English
Julia Beloo: Right. Absolutely. And you're designed to eat more when you don't sleep enough. And you're absolutely right that this symphony of internal signals that I was referring to earlier, it's interplaying with our environments. So, one thing I've really appreciated about your work on the GLP-1s as a reporter and as somebody who's very deep in the science is you've done a tremendous amount of interviewing people on them and you've interviewed many of the kinds of people and again to me this has always been the cruelty of this conversation who were exercising a tremendous amount of constant willpower going on and off like very restrictive diets you know losing 30 lbs gaining it back. What is it like for them? Um, for the people who've seen huge amounts of of of weight loss, how do they describe the experience of being on a GLP1 versus what it's like off of one?
GLP-1药物的有效性与副作用
Julia Beloo: 我认为对于那些药物对减肥有效的人来说,最大的共同点是,他们突然有了这种他们一直在寻找的意志力,他们觉得自己以前没有足够的意志力,但现在突然有了。嗯,突然间,对多余的蛋糕或根本不吃蛋糕说不,就没那么难了。嗯,他们吃得更少,他们的食欲也改变了。就像他们完全,有很多关于“食物噪音”的讨论。当蛋糕在那里时,你的大脑有 30% 到 50% 都专注于蛋糕,或者你被 cravings 分心。很多人说这种情况就消失了。
Original English
Julia Beloo: I think the big common thread for people in whom the drugs are effective for weight loss is this idea that suddenly this willpower that they were always searching for that they feel they didn't have enough of, suddenly they have it. Um, suddenly it's not that hard to say no to the extra piece of cake or the cake altogether. um they're eating smaller portions, their cravings change. Like they have this complete there's a lot of discussion about food noise. When the cake is there, 30 to 50% of your brain is on the cake or you have cravings that distract you. A lot of people say that this just disappears.
主持人: 你刚才说,对那些药物有效的人。对谁有效,对谁无效,为什么?
Original English
Host: You said a second ago, for whom the drugs are effective. For whom are they effective and for whom aren't they effective and why?
Julia Beloo: 所以这是一个我们尚未完全理解的领域,但似乎有些人对药物非常敏感,而另一些人则不敏感,而且这可能也与基因有关。嗯,这是一种前沿科学领域。所以,我认为很多公司都在追求的目标是了解我们如何区分那些可能最初需要更高剂量的人,或者那些可能需要更低剂量的人,因为他们对药物非常敏感,副作用也很多,等等。他们反应如此强烈,或者减肥过快。嗯,所以人们的反应方式绝对存在这种差异。告诉我这些 GLP-1 药物的副作用。在研究中,人们通常不会长期服用它们。人们有时会因为费用而停药,但有时也会因为其他原因。比如,服用它们有什么不愉快的?可能会出什么问题?
Original English
Julia Beloo: So this is another area we don't fully understand but it seems like there are some people who are quite sensitive to the drugs and others who are insensitive to the drugs and there might be a genetic component to this too. um that that's sort of a frontier um area of science. And so I think the the quest that a lot of the companies are on is to understand like how how do we differentiate the people who might need higher doses initially or much lower doses because they're having um so much sensitivity to the drugs and side effects um and whatnot. They're having such a strong response or losing weight too fast. Um so there there absolutely is this variation in how people are responding. Tell me about the side effects of these GLP-1 drugs. In studies, people often don't stay on them that long. People do cycle off of them sometimes for cost, but sometimes for for other reasons. Like what what is unpleasant on them? What what can go wrong?
Julia Beloo: 所以,我们目前所知的最常见的副作用是胃肠道副作用。所以,恶心、呕吐、腹泻。嗯,这些是最常见的,但似乎还有其他潜在的新问题出现。所以有一些关于严重胃部问题、眼神经损伤的诉讼。嗯,所以眼睛损伤,嗯,我认为我们还没有明确的答案来确定这种情况有多常见,嗯,但是,但是这些诉讼的基础是人们没有被充分警告可能会发生这种情况。很多人似乎没有被警告的一件事是,你必须一直服用它们才能持续获得减肥益处。嗯,所以我认为很多人都有一个想法,我会减肥,我会学会如何正确饮食,然后我就会停药。我总是很惊讶,即使是那些从医生那里获得药物的人,似乎也没有…
Original English
Julia Beloo: So, the most common are that we know of right now are the gastrointestinal side effects. So, the nausea, the vomiting, the diarrhea. Um those those are the most common, but it seems like there's other emerging potential problems. So there are lawsuits around um severe stomach problems um damage to the ocular nerve um so so eye damage um and those I don't think we have clear answers on how common that is um and but but the basis of of those lawsuits is that people weren't properly warned that this could happen. One thing that a lot of people don't seem to be warned about is the fact that you have to stay on them to keep reaping the weight loss benefits. Um, so I think there's an idea that a lot of people have. I'll lose the weight, I'll learn how to eat properly, and then I'll go off the drugs. I'm I'm always surprised that even people who got the drugs from their doctors don't seem to
主持人: 人们停药后会发生什么?
Original English
Host: What happens when people go off the drugs?
Julia Beloo: 你往往会重新增重,并且…
Original English
Julia Beloo: You tend to regain the weight and
主持人: 你又会感到饥饿。那种被大脑抑制的食欲,通过作用于大脑 GLP-1 系统,那种效果消失了,你又回到了“食物噪音”,又回到了你之前的饥饿感。
Original English
Host: you just feel hungrier again. The the sort of resets exactly this this appetite that was suppressed through the brain um through through acting on on the brain GLP1 brain system, that effect is gone and you're back to the food noise. you're back to um yeah the hunger that you had before.
主持人: 这难道不是理所当然的吗?我听说过这个说法,而且在数据中也确实如此。但我想,我生命中的人们患有慢性病,他们一直在服药。你知道,你停止服用 Statins,效果就会消失。嗯,如果你是糖尿病患者,你必须继续服用胰岛素。我觉得这就像是,那些习惯用药物治疗急性病的人,不习惯用药物治疗慢性病。但我认为这正是问题的关键,这回到了谈话的开始,很多人仍然认为他们应该能够凭意志力摆脱困境,对吗?我认为这些药物有助于揭示我们是多么受生理学影响的产物,嗯,有了这个,你知道,你服用这种药物,突然之间,你又拥有了你一生中从未有过的意志力。嗯,但仍然存在这种期望。这就像任何其他饮食一样。嗯,这感觉就像一个人们没有被警告的地方。但正如你我所说,现在有这么多人在服用这些药物。而且我认为这些更罕见的副作用,我们将会开始了解更多。
Original English
Host: Isn't that pretty? I I've heard this and it's definitely true in the the data. But I guess like people in my life have chronic conditions and the drugs are on like they just have to stay on them. You know, you stop taking Statins and the effect goes away. Um if you're diabetic, you have to keep taking your insulin. That like I feel like that's like a like people who are used to drugs to treat acute conditions not being used to drugs to treat chronic conditions. But I think that this is the thing like that goes back to the beginning of the conversation that a lot of people still have this idea that they should just be able to will their way out of it, right? I think these drugs helped reveal how much we are products of our physiology and um that with this, you know, you take take this drug and suddenly again you have the willpower you you didn't have for your whole life. Um but there's still this expectation. It's like any other diet. And um that feels like a place where people haven't been warned. But as you as we've been saying, there are now so many people on the drugs. And I think these more rare side effects we're going to start to learn more about.
GLP-1药物与社会体型期望
主持人: 我想谈谈一个可能的社会副作用,那就是我们的文化对人们体型的期望长期以来一直具有惩罚性。嗯,特别是对女性和女孩具有惩罚性。我认为我们有趣地进入了一个时代,它们对男孩和男性越来越具有惩罚性,而且有一种“男性外表最大化”的说法,你知道,漫威电影中的那些家伙现在都练得非常壮,而且在服用各种不该服用的东西。你知道,如果你肥胖或超重,并且正在服用 GLP-1 来减肥,你知道,那很好。嗯,或者,你知道,为了保护你的心血管系统。但我认为它们大部分的文化影响来自名人和网红,他们突然出现,变得非常瘦,有时甚至是骨瘦如柴,以至于,你知道,当身体的自然饥饿信号回来时,这会更难做到。你知道,曾经有过一次大规模的身体积极运动,但在这个国家,那总是很艰难的。但你如何看待 GLP-1s 作为一个可能是一个,比如说,一个药物加速器,加速了相当危险的身体期望,因为现在好像是,如果你想看起来更瘦,为什么不直接服用 GLP-1 呢?
Original English
Host: I want to talk about a possible social side effect, which is the our cultures expectations for what people's bodies should look like have been punishing for a long time. Um particularly punishing for women and girls. I think we we've interestingly been entering an era where they're increasingly punishing on boys and men and there's this whole thing of like male looks maxing and uh you know the guys in the Marvel movies are completely jacked now and on all kinds of things you probably shouldn't be taking. And you know, if you're obese or overweight and you're taking a GLP-1 to lose weight, you know, great. Um, or to, you know, protect your cardiovascular system. But I think a lot of the cultural effect of them has come from celebrities and influencers who all of a sudden show up and are much thinner at times skeletal now in ways that you know when you have the body's natural hunger signals coming back at you is is harder to do. You know there was like this big body positivity movement and that was always going to be a very uphill climb in this country. But how do you think about GLP-1s as possibly a like a like a pharmaceutical accelerator of, you know, fairly dangerous body expectations because now it's like, well, if you want to look thinner, why not just go on to GLP1?
Julia Beloo: 我认为这绝对是一个奇怪的,嗯,在我们正在经历的这场对话和这个时刻。嗯,最让我感到不安的是,我与给儿童开这些药物的儿科医生交谈过。目前还没有针对这些药物和年轻人的饮食失调症的筛查,他们凭经验看到有人将这些药物作为辅助手段,本质上是为了治疗饮食失调症,并且在某种程度上加剧了饮食失调行为。健康即各种体型或肥胖积极主义或身体积极运动的一个潜在假设是,你无法控制自己的体型。因此,你必须接受它。我们以前做过手术。它没有那么容易获得或普及。但现在我们确实有这种药物,人们确实有选择,对吗?
Original English
Julia Beloo: I think that's that's absolutely a strange um in this conversation and in this in this moment that we're living in. Um the place that it freaks me out the most is um I talked to pediatricians who are prescribing the drugs in children. There's no screening yet for for these drugs and eating disorders in young people and and they've they anecdotally have seen people use these as aids for essentially eating disorders and and kind of exacerbating eating disordered behavior. One of the underlying assumptions of the health at every size or fat activism or body positivity movements um was that you can't control your body size. Therefore, you must accept it. We had surgery before. It wasn't as accessible or scalable. But now we do have this medication where people do have the option, right?
主持人: 或者至少是那些对它敏感的人…
Original English
Host: Or at least the ones who are sensitive to it
Julia Beloo: 还有那些能负担得起、能获得它以及所有这些的人,对吗?我们已经看到这些身体积极、肥胖积极主义运动中的有影响力的人站出来,真正纠结于开始服用这些药物并因此减肥。这些运动所做的一件非常重要的事情是,强调了肥胖者每天所面临的羞耻和污名,尤其是女性。所以,几年前有一篇很棒的经济学人文章,他们分析了薪酬惩罚的数据,他们非常出色地突出了肥胖者所面临的歧视和污名。但我认为,对于体重过重对健康的影响,存在着一种危险的粉饰,即使个体之间存在这种差异,但在人口层面,非常清楚的是,你的 BMI 越高,你面临的健康风险就越大。我曾与这些运动的参与者交谈过。他们有运动问题。嗯,他们有血糖问题。他们嗯,他们担心生育问题,他们非常感激现在能有一种药物可以帮助解决这些问题。这场辩论变得非常两极分化。要么你是接受肥胖的,要么是恐肥胖的。我认为我们现在正在走向介于两者之间的一些东西。
Original English
Julia Beloo: and the ones who can afford it and access it and all all of that, right? We've seen influential people in these the body positivity fat activism movement come forward and really grapple with starting on these drugs and um and losing weight on them. And one thing that those movements did that was really important was highlight how much shame and stigma people who are living with obesity face every day, especially women. So, like there was this great economist article a few years ago where they parsed the data on the pay penalty and they they did such a great job of highlighting the discrimination and stigma that people with obesity face. But I think there was really a dangerous glossing over of the health effects of carrying extra weight that even if there is this variation in individuals at the population level, it's very clear that the higher you go up the BMI ladder, the more um health risks you're you're carrying. I I've spoken to people who were part of these movements. They had issues with movement. Um they had problems with their blood sugar. They had um they were concerned about fertility and they were so grateful to be able to now have a medication that could help with those issues. That debate became very polarized. It was either you're fat accepting or fat phobic. And I think we're kind of moving to something maybe in between.
主持人: 但是,但是我同意你的观点。但是把辩论的这一面放在一边,对吧?那总是一种努力,与美国文化的主流背道而驰,主流文化非常坚信苗条是美德的同义词。你知道,我认识的人所担心的一件事,坦率地说,我也担心,我的意思是,我感觉我以前不会对年轻男孩有这种担忧。而现在我看到了“男性外表最大化”的兴起,它看起来很像以前女孩们接触到的那种有毒的饮食文化。你知道,很明显,你知道,Clevicular,他是这种现象的代表人物,他谈论了很多关于服用 GLP-1s 或某种形式的这些药物。我想知道,当社会顶层的人们更容易对自己的身体施加 hair24 未知水平的控制时,会发生什么。当他们使用这些疯狂的 GLP-1s 和肽类药物,你知道,还有防止脱发的药片以及其他一切,你知道,持续的肉毒杆菌注射时,这会如何渗透到社会底层。
Original English
Host: But but you but I take your point on that. But put put that side of the debate over here, right? That was always a like an like an effort that was running up against the mainstream of American culture, which believes very strongly in thinness as a synonym for virtue. And you know, one thing that the people I know are worried about and frankly that I'm worried about, I mean, I feel like I would not have had this concern for like young boys, which is what I have a while ago. And now I look at the rise of male looks maxers and it looks a lot like toxic diet culture you know that girls were exposed to before and you know and obviously you know Clevicular who's the uh avatar of that has talked a lot about being on you know GLP-1s or some some form of these drugs and I wonder what it's going to do when it is just that much easier for people at the top of society to exert like hair24 unknown levels of control over their bodies and when they're doing it with these like wild stacks of GLP-1s and peptides and you know uh pills to prevent hair loss and everything else you know constant Botox like that filters down.
Julia Beloo: 哦,当然。
Original English
Julia Beloo: Oh, absolutely.
主持人: 这使得理想变得既遥不可及,又让人付出更多痛苦才能达到。
Original English
Host: And it makes the the the ideal both like ever more unreachable and ever more punishing to try to reach.
Julia Beloo: 不,我经常思考孩子的问题,对吧?基本上有一个市场还没有像成年人那样被充分开发,那就是患有肥胖症和饮食引起的疾病的儿童。我认为现在大约只有 1% 的符合条件的儿童正在服用这些药物,但我认为这个数字预计会迅速飙升,特别是随着获取途径的扩大和药物以药丸形式出现。而且,如果我们对成年人有很多不了解的地方,那么对于在这些关键的生长发育阶段抑制食欲意味着什么,我们有更多不了解的地方。与此同时,嗯,饮食引起的疾病,如肥胖症和糖尿病,对年轻人尤其严重。嗯,对于糖尿病,例如,存在一些关于其与生长激素和胰岛素信号传导相互作用的问题,因为这种疾病发病非常猛烈,而且在年轻人身上很难治疗。所以现在我们有了这种治疗方法,或者说,这种能够真正帮助年轻人的东西,这是我们以前无法通过减肥手术实现的。但当我们在抑制食欲时,这会对他们意味着什么呢?不仅是那个年龄段的身体形象压力,还有对肌肉、骨骼、青春期所有这些方面的影响,对吧?我们即将让所有这些年轻人服用这些药物。我想到我的孩子以及他们将面临的压力。嗯,我想,我不知道你是否做过这个思想实验,但想象一下现在是胖乎乎的 16 岁的 Ezra。你会在 16 岁时服用这些药物吗?我想我会,你知道,我,我体重也波动很大,但我想在 17 或 18 岁时我就会肥胖了。我是否会推着我的父母说,你知道,我真的很想要 GLP-1。而我现在会怎么样?如果我服用了这些药物,我会有更快乐的童年,以及青春期和 20 岁出头吗?我是否会学会通过改变我的食物环境来饮食?我不知道。但年轻人现在在这种文化中成长所面临的压力,令人恐惧。它具有惩罚性。我为我的孩子们感到害怕,我希望会有某种纠正,但我不知道纠正是否会到来,或者如何到来,你知道。
Original English
Julia Beloo: No, I think about this a lot with kids, right? there's this basically this market that hasn't been tapped to the extent that the adults have which is children with obesity and diet-caused diseases and I think it's something like 1% of um children who are eligible are taking these drugs now but I think that number is expected to rise stratospherically um pretty quickly especially with the expanded access and going to pill form and there's so much there's if we if there's like a lot we don't know in adults there's so much we don't know about what it means to suppress appetite during these critical phases of growth and development. At at the same time, um diet caused diseases like obesity and diabetes, they hit young people particularly hard. Um and there's some question with diabetes for example about interactions with growth hormone and insulin signaling because the disease comes on so ferociously and it's so hard to treat in young people. So now we have this treatment or or thing that can actually help young people in a way we couldn't accept with beriatric surgery before. But what is it going to mean for them when we're yes blunting appetite um not only with the pressures on body image at that age but also on yeah your muscles, bones, um puberty, all these things, right? We're we're about to put all these young people on these drugs. Like I think about my kids and the pressures that they're going to face. Um, I think about I don't know if you've done this thought experiment, but imagine being like chubby 16-year-old Ezra now. Would you have gone on one of these drugs at 16? Like I I I've thought I would I have, you know, I I also I think my weight fluctuated a lot, but I think around 17 or 18 I would have had obesity. And would I would I have pushed like my parents to say, you know, I really wanted GLP-1. And where would I be now? Would I have had a happier childhood and like or teens and early 20s? Um, if I had one of these drugs, would I have learned to eat in the way that I've learned to eat by changing my food environment? I I don't know. Like I I've But the pressures I think young people are going to face now growing up in the culture that we have, it's it's scary. It's punishing. I'm terrified for my kids when I hope that there's some sort of correction, but I don't know if the correction is coming or how, you know.
GLP-1药物与心脏、痴呆症等疾病的体重无关益处
主持人: 所以,我们在这里进行的对话有点像我所说的第一轮关于 Ozempic 的报道热潮。然后,新的事情开始发生。当我开始更加密切关注时,发生了一些事情。有一项研究特别引起了我的注意,作为一名曾是医疗记者的人,这项研究表明,我们看到了各种心脏事件的死亡率大幅下降,但这些下降似乎与减肥无关,或者不需要与减肥相关。
Original English
Host: So, the conversation we've been having here sort of tracks what I would call like the first cycle of Ozempic coverage excitement. And then a new thing begins happening. And it's sort of when I began paying closer attention. There was a study that came out that particularly caught my eye as a former healthcare reporter, which was that we were seeing huge drops in mortality from any form of cardiac event, but the drops didn't seem to be connected or didn't need to be connected to losing weight.
Julia Beloo: 没错。是的。
Original English
Julia Beloo: That's right. Yeah.
主持人: 所以,你能解释一下我们当时看到了什么,以及这如何开始改变这里的故事吗?
Original English
Host: So, can you explain what we saw then and then how that begins to shift the story here?
Julia Beloo: 当然。是的。所以我们有一种药物在市场上用于治疗糖尿病,在糖尿病试验中,随着我们开始增加剂量,人们开始减肥。然后,现在任何上市的糖尿病药物都要求公司必须调查这些药物对心血管事件的影响,以寻找危害。所以他们正在寻找危害。这会增加心血管事件的风险吗?
Original English
Julia Beloo: Sure. Yes. So we have this drug that comes on the market for diabetes in the diabetes trials as as we start ramping up the doses people start to lose weight and then for any diabetes drug now that comes onto the market there's a requirement that companies must look into what these drugs do to cardiovascular events to look for harms. So so they were so the companies were looking for harms. Does this increase the risk of a cardiovascular event?
主持人: 过去的减肥药,比如 Fen-Phen,你知道,它们不是糖尿病药物,却确实增加了心血管事件的风险。对。我们以前也有过神奇的减肥药,但它们让人…
Original English
Host: Past past weight loss drugs like Fen-Phen, you know, which were not diabetes drugs like did increase the risk of cardiovascular events. Right. We've had wonder weight loss drugs before and they gave people
Julia Beloo: 心脏问题。
Original English
Julia Beloo: heart issues.
Julia Beloo: 没错。所以他们正在寻找危害,结果却发现了 20% 的风险降低。
Original English
Julia Beloo: Exactly. So, so, so they're looking for harms and instead they find this 20% risk reduction. And
主持人: 给我解释一下这有多大。
Original English
Host: put that in context for me. How big is that?
Julia Beloo: 很大。嗯,Statins 是一种针对这些疾病的药物,风险降低大约是 29%。真正重要的是,似乎研究人员从这些药物中发现的益处越来越多地是与体重无关的。换句话说,每个人都预期的是,你让人们减肥,身体的炎症会减少,嗯,脂肪和糖的新陈代谢会改善。所以也许,嗯,你会看到脂肪肝疾病或糖尿病或其他任何疾病的改善。但没有人预料到的是,你会开始看到这些与体重无关的益处,这适用于心脏,适用于肝脏,我认为肾脏,有一系列的益处似乎与体重无关。
Original English
Julia Beloo: It's big. Um, Statins are a drug that are targeting these conditions and the risk reduction is something like 29%. What's really significant about it is it seems that more and more of the benefits that researchers are discovering from these drugs seem to be weight independent. So in other words, what everyone expected is you make people lose weight, inflammation in the body goes down, um your metabolism of fat and sugar um improves. So maybe um you see improvements in fatty liver disease or your diabetes or whatever it is. But what no one predicted was that you would start to see these weight independent benefits and that that goes for the heart, it goes for the liver, I think the kidney, there's a slew of benefits that seem to be weight independent.
主持人: 可能会对痴呆症有益。嗯,我的理解是,通过观察,服用这些药物的人患痴呆症的风险似乎低得多。他们进行了一项研究,看看它是否能改善阿尔茨海默症患者的状况,但没有。但我们不确定它是否能预防阿尔茨海默症,有些人似乎认为阿尔茨海默症或痴呆症是代谢激活的。所以现在就有一个问题,它是否具有认知保护作用。所以阿尔茨海默症的试验,这些都是备受期待的随机对照试验,旨在了解这些药物在阿尔茨海默症中的作用,但它们的结果是负面的。所以这对社区和公司来说都是一个巨大的失望,但仍然存在一个问题,即在不同的人群中,或者不同的剂量,或者不同的药物,我们是否会看到益处?这是一个活跃的问题,对吗?
Original English
Host: There's possible benefits on dementia. Um I mean my understanding of this is that observationally people on these seem to have much lower risk of dementia. They did a study seeing if it uh a randomized control trial seeing if it improves people who have Alzheimer's and it didn't. But we're not sure about whether or not it can prevent Alzheimer's and some people seem to believe Alzheimer's or dementia are metabolically activated. And so now there's this whole question of does it is it cognitively protective. So the Alzheimer's trials, so these were really much anticipated um randomized control trials to see what would happen with um these drugs in Alzheimer's and they had negative results. And so it was a big disappointment um to the community and to the companies, but there is this question of in a different population or with a different dose or a different drug, will we see the benefits? And that's an active um question, right?
Julia Beloo: 是的。如果你及早干预,这是一个积极的问题和研究领域。所以我不认为这个案子已经结案了。睡眠呼吸暂停是一个大问题。睡眠呼吸暂停是与体重相关的。所以你需要减肥才能看到益处。这是这些药物现在被批准的另一个适应症。
Original English
Julia Beloo: Yeah. If you're intervening earlier, it's an active um question and area of study. So I don't think that case is closed. And sleep apnea is a big one. Sleep apnea is weight dependent. So you need to lose the weight to see the benefit. That's another indication that these drugs are approved for now.
GLP-1药物的作用机制与炎症、器官修复
主持人: 所以这些与体重无关的结果,它们有点打破了我们关于健康改善机制的理论。所以当医生和科学家试图理解这一点时,我们对药物的作用以及它如何帮助身体的认识是如何改变的?所以多伦多有一位研究员,Dan Ducker,他帮助发现了这类药物,他向我描述说,基本上有三个方面。所以第一个是减肥方面,这很清楚,它会帮助你减肥,你会从中获得益处。嗯,第二个方面是减少炎症。所以炎症是当你接触到病原体、感染和损伤时,你的身体会产生这种免疫反应,它可以发出愈合信号。但是当它以低水平进入某种过度活跃状态时,你就会出现慢性炎症,而这正是我们一直在谈论的许多疾病的标志。肥胖症、糖尿病、心血管疾病。这些药物似乎能降低炎症。它们似乎能降低炎症。对我来说,这是最令人兴奋的领域,因为我们过去有一些药物可以抑制炎症,比如类固醇,嗯,比如说,但你却让人们面临风险,因为你本质上是在抑制免疫系统。你让人们面临更高的癌症或其他感染的风险。但据我描述,GLP-1 似乎是炎症的微调器。所以它们有这种更微妙的方法,嗯,这是我们以前在医学上从未真正有过的。所以我们正在使用这些药物。所以 GLP-1,还有其他药物正在上市,比如双重和三重激动剂,它们使用的不仅仅是 GLP-1。问题是,我们是否会发现这些其他激素,我们可以用它们来微妙地操纵免疫系统和炎症?所以我们可能才刚刚开始。我认为另一个令人兴奋的方面是,我们可能会通过这些药物获得对免疫系统的惊人见解,这是我们以前从未有过的,因为我们无法进行这些更微妙的操纵。但第三个方面,这些药物似乎能帮助人们的第三种方式是直接靶向参与特定疾病的器官。所以,嗯,向肝脏发送信号以治愈脂肪肝疾病中的瘢痕,或者清除肝脏中的脂肪,嗯,或者任何可以促进肝脏或肾脏愈合的。这是这些药物似乎能帮助人们的第三种方式。
Original English
Host: So these weight independent results, they break our theory of the mechanism of health improvement here a little bit. So as doctors and scientists try to grapple with this, how does our sense of what the drug is doing and why it is helping the body change? So there's a researcher in Toronto, Dan Ducker, who helped discover this whole class of drugs and he described to me like let let basically there's these three buckets. So one is the weight loss bucket that's clear it's going to help you lose weight and you'll get the benefits from the weight loss. Um the second bucket is reducing inflammation. So inflammation is when you're exposed to a pathogen um an infection and injury, your body mounts this immune response and it can signal healing. But when it goes into kind of overdrive at low levels, you have this chronic inflammation and that's a hallmark of many of these diseases we've been talking about. Obesity, diabetes, cardiovascular disease. And these drugs seem to lower work on inflammation. They seem to lower inflammation. And this to me is the most exciting area because we've had drugs in the past that kind of shut down inflammation like steroids um let's say but but you put people at risk because you're essentially shutting down the immune system. You're putting people at higher risk for cancer or other infections. But the way this is described to me is that GLP-1 seem to act as these finetuners of inflammation. So they have this more subtle approach and um it's not something we've really had in medicine before. So we're using these drugs. So GLP-1 and there's other drugs that are coming on the market with like the dual and triple agonist um that use more than GLP-1. And the question is like are we going to discover these other hormones that we can subtly manipulate the immune system and inflammation with? And so we might just be at the beginning of this. And I think the other exciting facet of it is we might really get amazing insights into the immune system through these drugs that we haven't had before because we haven't been able to do these more subtle manipulations. But the third bucket that the the third way these drugs seem to help people is by directly targeting the organs that are involved in particular diseases. So, um sending signals to the liver to heal scarring involved in fatty liver disease or to clear the fat from the liver um or whatever it is to promote healing in the liver or the kidneys. That that's a third way these drugs seem to be helping people.
主持人: 它为什么要这样做?
Original English
Host: Why would it do any of that?
Julia Beloo: 你的猜测和我的一样好,但是,嗯,在小鼠模型中,有一些关于正在发生的事情的模型。嗯,但是这在我们体内是如何运作的,我们不知道。我的家族中有很多人患有心血管疾病,而且我的家人在年轻时就患上了这种病。当周围的人开始服用 GLP-1s 时,我开始阅读这些关于心脏事件的文章。嗯,我想,我是不是傻子,为什么不服用呢?几年后我们都会服用这种药物吗?所以我试过了。我想在一分钟内谈谈这种经历,但我想问一个基本问题,鉴于你刚才描述的这三个方面,以及它们似乎有助于治疗的这么多疾病。我越来越觉得,难道每个人都不应该服用低剂量的 Ozempic 或 Tirzepatide 吗?如果你看到了痴呆症可能减少(我们不完全确定),但体重减少,心血管事件减少,肝肾疾病减少,睡眠呼吸暂停改善,血糖改善,我们稍后会谈到成瘾和强迫症的发现,但这开始看起来像是我们应该在水中添加的东西。
Original English
Julia Beloo: Your guess is as good as but um there's models in mice of what's going on. Um but how this is working inside of us, we don't know. My family has a lot of cardiovascular disease in it that um has hit members of my family young. And as everybody sort of around me began going on GLP-1s, I began reading these things about cardiac events. Um I was like, well, am I an idiot for not being on one? Are we all going to be on one of these in a few years? And so I've tried them. I want to talk about that experience in a minute, but I want to ask that underlying question of you given these three buckets you just described and how many things they seem to be helping to treat. It increasingly seemed to me like shouldn't everybody be on lowd dose Ozempic or Tirzepatide if you're seeing reduction possible reductions in dementia that we don't really know but reductions in weight reductions in cardiovascular events reductions in liver and kidney disease reductions in sleep apnea improved blood sugar we'll talk about the addiction um and compulsivity findings later but it began to seem like a thing we should be putting in the water
主持人: 你知道,我也有同样的问题,你和我一样,我越深入研究科学,就越是这样想。我们与《时代杂志》合作,对 GLP-1 用户进行了一项民意调查,询问他们的经历如何。我进行这项调查时,认为我们会得到负面结果。我感觉媒体上很多头条新闻都对这些神奇药物过于乐观,但我们并没有报道人们服用这些药物的真实生活体验,包括副作用以及进出保险。而我们得到的结果是,人们普遍感觉良好,并获得了意想不到的益处,他们希望继续服用这种药物,原因并非药物的处方用途。这让我很惊讶,你们调查中 63% 的人表示,即使这种药物对减肥不起作用,他们也愿意继续服用。
Original English
Host: you know I had the same question is you and the the deeper I've gotten into the the deeper I dive into the science, the more I've wondered the same. We did this poll with the Times um for a piece on of GLP-1 users and asked them like what's your experience been like? And I went into that poll thinking we would get these kind of negative results. I I had a feeling that a lot of the headlines in the media had been quite triumphalist about these wonder drugs, but we weren't reporting what the lived experiences of people on these drugs was really like with the side effects and cycling in and out of insurance. And what we got back was people kind of generally feeling great and having benefits that they didn't expect and that they wanted to stay on the drug for benefits for for reasons other than which the drugs were prescribed. This was amazing to me that 63% of people in your survey said even if the drug didn't work for weight loss, they would want to stay on it.
Julia Beloo: 不,这真的让我震惊了。我没想到会这样。嗯,对我来说最惊人的故事之一是,有一位女士,她患有脑震荡后综合症近十年,她的生活基本上,我不想说被毁了,但她深受症状的折磨,她开始发现小鼠和细胞研究表明这些药物可能对脑震荡后综合症有益。所以她咨询了医生,获得了处方,然后尝试了。几天之内,她就开始感受到益处,现在她又回到了正常生活。嗯,但关键是我们还没有进行随机对照试验。我们没有高质量的证据来确定,这是否适用于所有脑震荡后综合症患者,80% 的人,还是像 2% 的人,我们不知道。此外,我们不了解这些药物是如何相互作用的。例如,如果你不幸服用其他类型的药物,比如癌症治疗药物或类似的东西,我们不知道这种免疫系统的微调(我之前提到的)在你服用免疫疗法时会如何运作。有太多的未知数,研究人员总是会很谨慎。但我几乎问所有我交谈过的研究人员这个问题,他们都说我们还没有到所有人都应该服用这种药物的阶段。我理解为什么研究人员必须说,我们不知道,但“我们不知道”实际上并不是那个问题的答案,对吧?你必须作为一个个体做出决定,你只有一次生命,而且你有可能患心脏病,有可能患痴呆症,有可能患肾脏病,有可能患所有这些不同的疾病。你必须看看这些研究,或者更重要的是对这些研究的报道,然后和你的医生说,你认为你是否应该服用这种似乎能调节炎症的药物,而炎症似乎是各种主要慢性病和急性病的原因。或者不服用。你知道,我认为你看到对这类药物进行如此激进的实验的一个原因是,因为它对健康人或慢性病患者都有这些影响,说“我们不知道,也许 12 年后我们会知道更多”。你实际上必须作为一个个体做出“是”或“否”的决定,因为如果你错过了五年对身体免受持续炎症的慢性影响的保护,你就错过了五年的保护,而且你已经积累了五年的损伤。我不知道。看起来可能如此,但我知道不同的医生对此有不同的看法。我觉得我们处于这样一个境地,它实际上非常微妙和棘手。
Original English
Julia Beloo: No, this was it shocked me. I did not expect this. Um, one of the most amazing stories to me is the woman who had um postconussion syndrome for almost a decade whose life was essentially I don't want to say shut down but it was she was suffering suffering deeply um with symptoms and she started to find mice and cell research suggesting these drugs could benefit postconussion syndrome. So, she talked to her doctor, she got the prescription, and she tries it. And within days, she starts to experience benefit, and now she's back to her normal life. Um, but the big key is we haven't done a randomized control trial on this. We don't have the high quality evidence to say, is this going to be everyone with postconussion syndrome, 80% of people or like 2%, we don't know. In addition, we don't understand the how these drugs interact. For example, if you were on, god forbid, but some other type of like a cancer therapeutic or something like this, we don't know how how does this fine-tuning of the immune system I talked about work when you're taking an imunotherapy, for example. There are so many unknowns and and researchers are always going to be cautious. But I ask almost all the researchers I talk to this question and they all say we're not at that stage where we should just all be on this. I understand why the researchers have to say well look we don't know but we don't know actually isn't an answer to that question right you have to make a decision like as a person with one life and a life where you have a chance of getting heart disease a chance of developing dementia a chance of developing kidney disease a chance of developing all these different things and you have to look at these studies or the coverage of these studies is more to the point and say or say with your doctor, do I think I should be on this thing that seems to modulate inflammation which appears to be a source cause of all kinds of major chronic and acute illnesses people develop or not. And you know, one reason I think you're seeing like really really aggressive experimentation particularly around this class of drugs is because something that has all these effects for the well or for the you know for chronic conditions saying well I don't know in 12 years maybe we'll know more. You actually kind of have to make a yes or no decision as a person because if you miss out on protecting your body from the chronic effects of ongoing inflammation for five years, you've missed out on 5 years of protection and you have accumulated 5 years of damage. I don't know. It sure seems like maybe, but I know different doctors feel differently about this. And I feel like we're in this place. It's actually like really tender and tricky.
主持人: 绝对是。但我认为我之前回答的问题是这个。它应该加到饮用水中吗?是的。我并不是真的想强制执行。
Original English
Host: Absolutely. But I think the question I was answering earlier was this. Should it be in the drinking water? Yes. I didn't mean to actually make it mandatory.
Julia Beloo: 不,不,不。但是是的,不,但是这个问题,Ezra,作为一个个体,鉴于你特殊的家族史和你潜在的疾病风险状况,或者你已经经历过的挣扎。你是否应该服用这种药物?这是一个你和你的医生应该好好讨论的问题,而且,嗯,获得处方并有人监控你。让我对这个 GLP-1 时代感到担忧的是,有多少人正在规避医疗系统。他们正在通过远程医疗获得这些门槛非常低的处方。嗯,他们正在通过 TikTok 上的网红等途径获取非法研究化学品。嗯,有如此多的热情,而且我看到这种情况在其他药物上也发生过。就好像它似乎能做一切事情,然后我们又将其回拨。我们还没有达到可以说把它加到饮用水中的阶段。所以,我服用了最低剂量的 Tirzepatide,大约 2.5 毫克,但我并没有像你们调查中的人那样有那种体验。呃,所以一方面,这就像是我尝试过的最有趣的药物之一,你知道,合法的或非法的,因为我似乎对它很敏感,突然间我就是不想吃东西,这是我以前从未有过的经历。就像活在别人的大脑里一样。我以前用老虎机做过比喻。这就像一个喜欢老虎机的赌徒,走到老虎机前,拉动拉杆,得到了三个樱桃,然后什么都没有亮起来。
Original English
Julia Beloo: No, no, no. But yeah, no, but this question of should you, Ezra, as an individual with your particular family history and your underlying disease risk profile or whatever you've struggled with um already. Should you be on the drug? That's a conversation people and you should certainly have with your doctor and um get the prescription and have someone monitor you. What scares me about this GLP-1 era is how many people are circumventing the medical system. They're getting these very low barrier um prescriptions through tele medicine. Um they're going to like elicit research chemicals through people like influencers on TikTok. Um there's so much enthusiasm and I've seen this happen with other drugs. It's like it seems to do everything and then we dial it back. We're not quite there yet that we can just say put it in the drinking water. So I went on the lowest dose of Tirzepatide and like two and a half um milligrams and I did not have the experience that people in your survey had. Uh so on the one hand it's like the most interesting drug or one of them that I've ever tried uh you know legal or non-legal because I seem to be sensitive to it and all of a sudden I just didn't want to eat which is never an experience I've had before. It was like living in somebody else's brain. The way I've described it to people, I used a slot machine analogy earlier. It's like being a gambler who loves slots and going up to a slot machine and pulling the thing and getting the three cherries and then nothing lights up.
主持人: 这让我觉得存在一种我甚至从未意识到的体验,那就是关于欲望。比如我会尝到一些东西,它很好吃,或者我闻到一些东西,我之前没有注意到它会触发另一种感觉,那就是欲望,因为对我来说,这些感觉是如此紧密相连。但突然之间,我会有同样的体验,然后欲望就不会被触发,我就会走过糖果碗而不停下来,或者我会在盘子里剩下半个卷饼。这在某种程度上是具有启发性的。但是,问题是它让我非常沮丧。
Original English
Host: It made me feel like that there was this level of experience that I hadn't even recognized I had, which was around desire. Like I would taste something and it would be good or I'd smell something and I hadn't noticed that the thing it would then trigger another feeling which was desire because like the feelings were so connected for me. But all of a sudden I would have that same I would have that same experience and then the desire wouldn't trigger and I would walk by the candy bowl and not stop or I would leave half the burrito on my plate and it was in a it was in a way revelatory. Um, the problem is it made me quite depressed.
Julia Beloo: 有趣。
Original English
Julia Beloo: Interesting.
GLP-1药物与奖励系统和成瘾行为
主持人: 而且是快感缺乏。无论是由于我吃得不够,还是发生了什么。但人们报告的更多能量、更多专注和更快乐,对我来说,它真的让体验变得平淡。
Original English
Host: And andhonic. And whether that was because I wasn't eating enough or or what what was going on. But the thing where people report more energy and and and more focus and feeling cheerier for me, it really doled experience.
Julia Beloo: 几乎听起来像是抗抑郁药的体验。嗯,这就是为什么我认为把我自己的经历带入进来很有趣,因为这里有一个整体的现象,它也在某种程度上作用于某种奖励机制,也许是多巴胺,但人们报告的不仅仅是减少食欲的欲望,而是减少做各种事情的欲望。少喝酒,少吸毒,少网购,然后这种快感缺乏的现象也被人报告。所以,你在你的报道中看到了关于整个奖励系统动力学的什么?
Original English
Julia Beloo: Almost sounds like an anti-depressant experience. Well, and that's why I think it's like interesting to bring in my own experience because there is this whole thing where it's working on some kind of reward mechanism too on maybe dopamine, but people are reporting not just a desire to eat less, but a desire to do all kinds of things less. Drink alcohol, take drugs, online shop, and then this anhidonia thing is also being reported by people. And so, what have you seen about the whole reward system dynamic of it in your reporting?
Julia Beloo: 是的。所以,这是一个非常令人兴奋的领域,我们对此投入了大量的关注,我认为特别是在媒体中,因为这些轶事非常惊人,而且我认为它们是真实的。我曾与报告过酗酒、吸烟欲望、性成瘾等各种成瘾行为逆转的人交谈过,这些药物似乎都能抑制这些行为。迄今为止的试验结果好坏参半,研究奖励机制的研究人员对这些结果能否持续抱有怀疑态度。据我描述,我们很早就知道,如果你让啮齿动物饥饿,它们更容易出现成瘾行为,比如它们更容易对可卡因上瘾或拉杆。所以饥饿与这些其他有动机的行为有重叠的途径,它可以增加成瘾行为的风险。嗯,似乎如此,所以一种解释是,一旦你服用这些药物一段时间,你的食欲开始正常化,你减掉了体重,你的饥饿感又开始正常化,那么成瘾的结果是否会持续下去。我认为很多人认为这些是治疗这些成瘾行为的明确疗法,但我认为在这方面我们还没有高质量的研究。
Original English
Julia Beloo: Yeah. So, this has been a very exciting area and one that we've paid a lot of attention to, I think, in particular in the media because the anecdotes are so startling and I think they're real. I've talked to people who have reported like reversals of um alcoholism, um the desire to smoke, um sex addiction, like any kind of addictive behavior you can imagine seem to be dialed down with these drugs. The trials to date have been mixed and the researchers who study reward are quite cynical that these results are going to endure. And the way it's been described to me is so for a long time we know that if you make rodents hungry, they're more likely to have addictive behaviors like they're more likely to get hooked on cocaine or push the lever. So hunger has this overlapping pathway with these other motivated behaviors and it can increase the risk of addictive behavior. Um it seems and so it's it it so one explanation is that once you've been on these drugs for a while and your appetite starts to normalize, you've lost the weight and your hunger starts to normalize again whether the results for addiction are going to actually endure after that. I think a lot of people think about these as like clear treatments for these addictive behaviors and that's where I think we don't have the the high quality research we want to have.
主持人: 嗯,这就是我假设有些人会出现快感缺乏,有些人会看到饮酒欲望降低的原因,这实际上不一定意味着它最终会被证明是一种明确的治疗方法,而是它正在干扰一个我们并不真正了解的系统。我的意思是,我,我觉得这次对话有趣的地方在于,我们基本上是在说我们对任何系统都不是很了解。我们不了解食欲系统。它的运作方式与我们假设的不同。心脏系统的运作方式与我们想象的不同。我们不知道炎症系统为什么会做出反应。奖励系统正在改变。我的意思是,人体是一个非常非常非常复杂的系统集合,而这似乎是对它们的一个复杂改变,在人口层面可能是积极的,但我们无法精确定义它是通过什么机制产生积极影响的,也无法告诉你它对谁是积极的,对谁是消极的,以及谁会真正减肥,谁不会,以及如何减肥。这实际上是一个非常奇怪的领域。
Original English
Host: Well, that my assumption of why some people were getting uh anhidonia, some people were seeing, you know, lower desire for drinking that that was actually not necessarily that it would end up proving to be a clear treatment, but that it is messing with a system we don't really understand. And I mean I I sort of think what's interesting about this whole conversation is we're basically saying we don't understand any of the systems very well. We don't understand the appetite system. It's working a different way than we hypothesized. The cardiac system is not doing what we thought it would be doing. We don't know why the inflammation system is responding. The reward system is changing. I mean the human body is a very very very complex set of systems and this seems to be a complex change to them that like at the population level is positive probably but not in a way where we can precisely define the mechanisms by which it is positive or tell you for whom it will be positive for whom it will be negative and who will actually lose weight and who won't and how It it's a very weird space actually.
Julia Beloo: 绝对是。是的。我真的觉得我们才刚刚开始。嗯,在我们发表了那篇我们进行民意调查并谈论了所有这些人们经历过的其他惊人益处的文章之后。我收到了很多关于奇怪的邮件,比如那些服用 SSRI 的人。所以他们正在服用抗抑郁药,然后他们开始服用 GLP-1,然后他们完全崩溃了。嗯,这不是我在随机对照试验中,或在研究中看到的,但这是人们经历过的。所以,我认为随着人们服用这些药物的规模,我们将会看到更多这样的情况。嗯,我们看到这些新药正在研发中。嗯,我们看到现在有口服形式的这些药物。这些药物正在变得非专利化。我们将看到越来越多的人服用这些药物,并了解更多关于它们的信息。我们有很多不了解的地方。那么现在正在出现的所有药物呢?所以我认识一些人正在从中国的一些复合药房获取 Retatrutide,Retatrutide 也许你可以解释一下,但它是礼来的另一种药物。礼来也生产 Zepbound,即 Tirzepatide 的变种,这正在进行试验,预计会在未来一段时间内获得批准,而且可能会产生巨大影响,但它的效果甚至比其他两种更好,但我真的不明白为什么我认识的所有这些人都在获取这种复合药物,他们无法监督,而现在市场上已经有非常好的 GLP-1 药物,你可以获得,并且对它们的生产方式完全信任。那么 Retatrutide 到底是怎么回事?为什么它在我的社区和我的社交媒体中都如此流行?
Original English
Julia Beloo: Absolutely. And and that's where Yeah. I feel I really feel this like there were just at the beginning of this um after we ran this piece where we did the poll and and talked about all these other surprising benefits people have experienced. I got lots of emails about weird like people who were on SSRI. So they were on anti-depressants and they start on a GLP-1 and they completely spiral. Um, and that's not something that I've seen show up in the randomized control trials or or in in um the research, but it's an experience that people have. So, I think we're going to have lots more of this at the scale that people are taking um these drugs. Um, we're seeing these these new drugs are coming down the pipeline. Um, we're seeing that there's now oral forms of these drugs available. The drugs are going generic. We're going to see more and more people on these drugs and learn much more about them. There's so much we don't know. What about all the drugs that are coming now? So I know people who are getting Retatrutide from some compounding pharmacy in China or something and Retatrutide maybe you can explain it but it's another Eli Lily drug eli also makes the makes Zepbound the Tirzepatide um variant and this is in trials now and it's expected that it will be approved in the next some amount of time and it'll probably be a big deal but it works even better than the other two but I don't really understand why all these people I know are getting a compounded thing fromies they can't like oversee when there are perfectly good GLP ones on the market now that you could get and have full confidence in the way they're being manufactured. Like what's going on with Reddit Tutread? Why is it like both like around my community and all over my social media feeds?
主持人: 哦,有趣。嗯,这说明了你是进入了健身算法还是?
Original English
Host: Oh, interesting. Um, this says something about are you in bodybuilding algorithms or
Julia Beloo: 不,这对我来说就是纯粹的 X 平台。
Original English
Julia Beloo: No, this is just straight up X for me.
主持人: 哦,有趣。好的,这很有趣。嗯,所以它仍然是一种正在研究中的化合物。它靶向三种激素受体。所以 Semaglutide,嗯 Ozempic,靶向一种。嗯,这就是我们在对话开始时谈到的,我们多年来对这些糖尿病药物进行了大量研究,我们可以相当自信地认为它们的安全配置文件。这些药物,嗯,自上市以来,比如 Mounjaro,比如 Tirzepatide 和 Retatrutide,它们靶向的不仅仅是 GLP-1。所以它们靶向其他激素受体,而我们没有这些药物的长期数据。
Original English
Host: Oh, interesting. Okay, that's interesting. Um so so it's still it's a research compound that's still under study. It's targeting three hormone receptors. So Semaglutide um Ozempic is targeting one. Um and this is where at the beginning of the conversation we talked about how we had this a lot of research on these diabetes drugs over many years and we could be fairly confident in their safety profile. these drugs um that have come on since um like Mounjaro, like so Tirzepatide and like Retatrutide, they're they're targeting more than just the GLP-1. So they're they're targeting other hormone receptors and we don't have long-term data on these drugs
Julia Beloo: 我认为那是一个非常重要的问题,很多人都忽视了,对吗?嗯,所以这种药物仍在研究中,但我们目前的研究表明,它似乎能更快、更显著地减轻体重,而且在长寿和健美以及社交媒体领域已经大受欢迎。
Original English
Julia Beloo: and I think that's a really important um thing that a lot of people overlook, right? Um, so, so this one is still under study, but in the research we have so far, it looks like it's causing faster and more dramatic weight loss and it's taken off in I think longevity and bodybuilding, social media.
新型肽类药物与生物黑客风潮
主持人: 我一直在看到关于它的论点是,它增加了能量消耗,似乎对你燃烧的卡路里量有某种独立的影响。是的,我不确定机制是什么,但那可能是合理的,它不仅仅是降低食欲,还在增加新陈代谢,也许这就是为什么人们能更快地减掉更多体重。嗯,但重点是,我们有这种新兴证据表明它可能比现有药物更有效。我认为这恰恰说明了围绕这些药物的狂热,人们不想等待 FDA 进行随机对照试验来批准这种药物。他们直接去找非法来源,嗯,试图购买这种仍然是研究化合物的药物。
Original English
Host: The the argument I keep seeing about it is it it increases energy use that it seems to have some independent effect on how much how on the calories you're burning. Yeah, I'm not sure what the mechanism um but that could make sense that it's not just reducing appetite, it's also increasing metabolism and maybe that's why people lose even more weight more quickly. Um but but the point is we have this emerging evidence that it might be even more effective than what's already available. And I think it just speaks to the frenzy around these drugs that people don't want to wait for the FDA to get the randomized control trials to approve the drug. they're going directly to illicit sources um and trying to buy the drug which is still a research compound.
Julia Beloo: 我认识的人以前在网上订购娱乐性药物,他们订购的是有趣的药物。现在,就像这些奇怪的…
Original English
Julia Beloo: People I knew who used to order drugs on the internet, they they were ordering fun drugs. Now it's like these weird
主持人: 吃得更少,更专注。我认为 GLP-1s 有趣的一点是,我的意思是,对于我们在这里谈论的一切,例如,那些可能想减一点体重,或者更重要的是那些可能想保护自己免受炎症困扰的人群。它们揭示了一个现实,那就是健康和生病之间并不是一个清晰的二元划分。我们现在有了糖尿病前期、高血压前期和更年期前期等类别,以前我们没有这些。我的意思是,我们不断扩大你应该担心的领域,我认为,当人们开始寻找化学方法来解决健康问题时,会有一个有趣的维度,因为事实是,对于很多人来说,获得足够的睡眠、定期去健身房和吃天然食物是很难的。如果你能给自己打一针或吃一颗药,人们都想要。你如何看待这种更广泛的转变,它不是新的,但现在正以更大的力量发生,即医学不再是治疗疾病的方式,而是优化健康的方式?你认为它是新的吗?它是旧的吗?
Original English
Host: eat less and focus more. One thing I think is interesting about the GLP-1s, I mean for everything we've talked about here is for instance, you know, the categories of who might want to lose a little bit of weight or even more so who might want to protect themselves from inflammation. They speak to this reality that the difference between well and sick is not this like clear binary thing. We now have these categories like pre-diabetic and prehypertensive and premenopausal and we didn't used to have them. I mean we keep expanding the space in which you should worry and I think that there is an interesting dimension as people start looking for like chemical answers to wellness because the truth is for a lot of people get enough sleep and go to the gym regularly and eat whole foods is hard. If you could just like give yourself a shot or take a pill, people want it. How do you think about the broader shift, which is not new, but it's happening with more force right now towards medicine as not a way of treating illness, but as a way of optimizing wellness? Do you see it as something new? Is that something old?
Julia Beloo: 我认为它可能更普遍,但我想我们必须小心。所以,就像如果你考虑美国公众,大多数人没有达到水果和蔬菜的最低每日摄入量,更不用说在此基础上个性化或优化他们的饮食了。大多数人睡眠不足。大多数人缺乏体育锻炼。我认为这才是大多数情况。
Original English
Julia Beloo: I think it's more pervasive maybe, but I think we have to be careful. So like in if you think about the American public like most people aren't eating the minimum daily requirements of fruits and vegetables let alone like personalizing or optimizing their diet beyond that. Most people aren't getting enough sleep. Most people aren't getting enough physical activity. And I think that's the majority. Right.
主持人: 对。我同意这一点。
Original English
Host: Right. That's I'm agreeing with that.
Julia Beloo: 是的。但是,但是我认为有一小部分人在媒体中得到了很多关注,他们对长寿和优化感兴趣。我认为想用药物来获得更健康而不是从疾病中康复,这并没有什么新鲜事。我们一直都在这样做,我们一直都有健康和保健的网红。但我想,如果你看看此刻的媒体环境,你会想到像 Rogan、Huberman 和 Attia 这样的大人物,然后你还有像 Brian Johnson 这样的时代媒体人物。他是一位前企业家,他试图永生不死,并且,你知道,他最终陷入了一种极其,极其密集的优化方案。我对这最终对他有益持怀疑态度,但你知道,我想这是他的生活。Clevicular 这种外表最大化的网红,他用锤子敲自己的头,服用各种疯狂的药物,你知道,前几天在直播中过量了,但你知道,他已经成为了一个在视频片段中获得数十亿次观看的人。我认为这与这种现象在媒体领域变得如此主导的方式有关,而且它不再有以前的限制。我的意思是,你当时在 Vox 报道 Dr. Oz 的时候,我知道你曾经做过报道,但在 Dr. Oz 身上发生的一件事是,它背后有一个电视网。我的意思是,有把关人。有些人不希望看到他们的股价下跌,如果出了问题。而现在,这是一个完全野蛮的西部,被算法兴趣所推动。我认为这会把我们推向一个真正注重长寿和优化的时期,因为会有资金,会有关注,所以,是的,我的意思是,这个国家很多人病得很重,他们需要的是慢性病的治疗,但我认为系统会真正推动去治疗那些不那么严重的人,他们是健康人,他们想变得更健康。
Original English
Julia Beloo: Yeah. But but then there is I think there is this minority that we pay a lot of attention to in the media um that that is interested in the longevity and the optimization. I don't think there's anything that new about wanting to use medicine to be more well as opposed to heal from illness. And we've been doing that forever and we've had health and wellness influencers forever. But I think if you look around the mediacape at this exact moment and you think about how big like Rogan and Huberman and Attia and then you have like Brian Johnson is one of the breakout media figures of the era. This sort of former entrepreneur who's trying to never die and is like the you know has like ended up in this incredibly incredibly intense regimen of optimization. Like I'm very skeptical this is ultimately going to be good for him but you know it's his life I guess. Clevicular this like look maxer streamer who like hits his head with a hammer and is on these like crazy stacks and you know oded the other day uh on a live stream but you know has become like is getting billions of views on his clips and I think there's something about the way like how dominant this has become in the media sphere and it doesn't have checks it used to have on it. I mean, you were talking I remember the coverage you would do at Vox of of Dr. Oz, but one of the things happening on Dr. Oz was like there was a network behind that. I mean, there were gatekeepers. There were people who didn't want to see their stock price go down if something went wrong. And now it's a complete wild west boosted by algorithmic interest. And I think it's going to push us into a real period of like a longevity and optimization focused system because like there's going to be money for it. there's going to be attention for it and so yeah I mean a lot of people in this country are very very sick and what they need is treatment for chronic illness but I think there's going to be a real push in the system towards treating these people who what they are is not very sick what they are is they are well and they want to be weller
主持人: 对,我们一直都有焦虑的健康人,而且人们一直都做一些非常疯狂的事情来优化他们的健康,正如你所说,但是扩音器变得更大,更碎片化,它在制造这种确认偏误方面更有效。我想到我妈妈,她被诊断出患有骨质疏松症,她当时正在考虑是否服用其中一种针对这种疾病的药物,结果她陷入了一个关于医生的 YouTube 兔子洞,那些医生对骨质疏松症药物非常怀疑,她变得非常害怕,她花了大约两年时间才开始服药。嗯,这种情况正在以我们以前从未见过的规模发生,对吗?但这种优化欲望,就像在我们的书中,我们发现了一个疯狂的例子,第一次世界大战后,炸药制造中有一种成分可以加速新陈代谢并导致人们减肥,斯坦福大学的医生们将其转变为一种药物,成千上万的人服用,并成为 FDA 的第一批目标之一。嗯,它有可怕的副作用,导致人们死亡,并引起眼部问题。嗯,所以我认为我们一直在追求这些疯狂的事情,是的,寻找魔术疗法,快速修复或改善我们的健康,但这些信息就在你眼前,它们通过算法进行精准投放,这是我们从未见过的。所以,我认为你触及了一个非常重要的问题,那就是这种媒体格局如何改变,不仅围绕着像 GLP-1s 这样的重磅 FDA 批准药物,而且围绕着更广泛的健康小贴士和优化器生态系统。
Original English
Host: right we we so we always had the worried well and like we've always people have always done really wild things to optimize their health as you're saying but the megaphone is so much bigger and more fragmented and it's so much more effective at creating this confirmation bias. Like I think about my mom who was diagnosed with osteoporosis and she was trying to decide whether to go on one of these um medicines it's available for the condition and she ended up in a complete YouTube rabbit hole of doctors who were really skeptical of osteoporosis drugs and she became quite frightened and and it took her like a couple of years to go on the medication. Um and this is happening at a scale that we've never seen before, right? But this desire to optimize like like in our book we found this wild example of after the first world war there was an ingredient in explosives manufacturing that sped up the metabolism and caused people to lose weight and doctors at Stanford pivoted and turned it into a drug that was taken by like hundreds of thousands of people and became one of the first targets of the FDA. Um and it had terrible side effects and c like killed people and caused eye problems and and um so so I think we've we've always done these wild things in search of yeah looking for the magic cure um the quick fix or bettering our health but the the in-your-facess of the messages and the the way they're targeted um with the algorithms this we've never seen. So, I think you're touching on something really important, which is how this media landscape has changed, not only around the blockbuster FDA approved drugs like the GLP-1s, but around this broader ecosystem of um yeah, wellness hacks and optimizers.
Julia Beloo: 我的意思是,这与你为《时代杂志》写过的一篇文章有关,那就是这些是第一批与我们痴迷于健康的算法时代相碰撞的重磅药物。是的,我的意思是,我肯定在 Reddit 上或 X 上某个时候点击过关于尝试内容的帖子,现在每次我打开系统、平台,我都会看到这些视频,人们告诉我 Reddit 尝试有多棒,而且现在人们从中国获取随机肽类药物的现象非常盛行。我不应该说随机,而是从他们无法真正判断其中含有哪些成分的地方订购肽类药物。嗯,《纽约客》测试了其中一些,发现其中很多含有铅或杂质或你不想要的东西,或者它们的剂量不对。就像那里出了问题。我们有了这些重磅药物,你可能期望每个人都会非常兴奋并服用它们,但它似乎已经演变成一场生物黑客的运动,就好像如果 Mounjaro 这样的东西能够存在,那么谁知道外面还有什么,你应该从中国订购并注射到自己体内,然后看看会发生什么,对吗?
Original English
Julia Beloo: I mean, this goes to something that you wrote about in your in in a piece you did for the Times, which is that these are the first blockbuster drugs to collide with our wellness obsessed algorithmic age. And yeah, I mean I must have clicked and at some point on Reddit who tried content on X and now every time I turn on the system, the platform, I get these videos from people like telling me how great Reddit tried and there's a huge boom in people just getting random peptides from China. I shouldn't say random, but ordering peptides from places where they can't really tell what's in them. Um, The New Yorker tested some of these and found uh a lot of them have lead or impurities or things you don't want or they're not at the right dose. Like there there's something wrong. We got these blockbuster drugs and you might expect everybody to be really excited and be on them, but it seems to have exploded into this biohacking moment in which it's like if something like Mounjaro could exist, well then who knows what is out there and you should order it from China and inject it into yourself and find out, right?
主持人: 你怎么看?
Original English
Host: Like what do you make of it?
Julia Beloo: 我认为它很完美,它是这个社交媒体算法时代的完美药物。嗯,因为它是视觉化的,对吧?它不像,你会有前后对比照片。我花了很多我不想承认的时间在不同的社交媒体上,比如 TikTok 和 Reddit 账户,你会看到视频和前后对比照片,以及人们的身体是如何变化的。嗯,我们生活在一种非常痴迷于外表的文化中。现在,人类在一个世纪甚至更长时间里一直追求的东西,我们第一次有了这种药物。嗯,所以它符合这个时刻。嗯,我想,我当时在写你提到的那篇文章时,做了一个思想实验,你知道,那会是什么样子?好的。所以当百忧解上市时,嗯,那又是一种重磅药物,那又是一种我们在文化上经历了一个重要时刻的药物,但当时没有远程医疗,所以你仍然需要去看医生才能获得处方,互联网也没有广泛使用,所以你无法从中国订购研究化合物,也没有社交媒体可以比较,你知道,你的个人经历并与世界分享。所以,是的,我们现在拥有所有这些,当我们拥有我们渴望已久的这种魔药时,对吗?减肥魔药。这么多人渴望这个。我们同时拥有所有这些其他事物,我认为这些事物共同创造了我们所处的这个时刻。
Original English
Julia Beloo: I think it it was it's sort of the perfect drug for this social media algorith al algorithmic age that we're in. Um because it's visual, right? It's not like like you have the before and after photos. You have I spend way more time than I'd like to admit on different social like TikTok and um Reddit accounts where you see the videos and the before and after photos and how people's bodies are transforming. Um, and we we're kind of living in this very appearance obsessed culture. And now for the first time again, we have this drug that does something that humans have quested after for like a century or more. Um, and and so it's meeting that moment. Um, I think like I was doing a thought experiment when I was working on that piece you mentioned about, you know, what would it have been like? Okay. So when Prozac came on the market um what what that was another blockbuster drug that was another drug where we had a cultural moment around it but we didn't have tele medicine so you still had to go to your doctor to get a prescription the internet wasn't in widespread use so you couldn't order a research compound from China there was no social media to compare you know do do your um person like compare your personal experiences and share them with the world so yeah we have all those things now when we have this this elixir that we've wanted for so long, right? The weight loss elixir. So many people have wanted this. We have it at the same time as we have all these other things that have just helped create, I think, the moment that we're in.
对权威的质疑与健康优化思潮
主持人: 我想这确实反映了我无意中告诉我的算法应该告诉我的内容。我看到很多人都在发布关于随机研究的帖子,这些研究并不是完整的随机对照试验,甚至很多都不是针对人类的,然后他们说:“看,看看这个惊人的机制,看看这些早期结果。”至少据他们说,他们正在进行复合制剂的定制和订购。我对这一点很着迷,因为对疫苗和 FDA 极度怀疑的人群与此之间存在一些奇怪的重叠。曾经,这被理解为对自然主义的偏好,认为这里存在一种原始主义的冲动。然而,一些对经过充分研究的药物持怀疑态度的人,现在却在订购完全未知的肽类药物。其中一些是为了减肥,但另一些只是为了增加能量消耗,或者治疗你的网球肘,或者,你知道,试图改善细胞再生。他们以不同的配方堆叠使用。这就像是对权威的不信任,但却相信未经证实的技术,这种方式让我觉得在文化上非常有趣。我很好奇,作为一个长期以来一直在这个领域的人,你对此有何看法。我想它有点,它有点结合在一起。所以也许甚至在疫情之前就已经酝酿了,但我们看到了对健康和健康优化的兴趣有所增加。
Original English
Host: I guess this does reflect what I've told my algorithm to to tell me, although not intentionally. I see so many people just posting about like random studies that are not full randomized control trials are often not even in human beings and being like see look at this amazing mechanism and look at these early results and at least according to them they're getting them compounded and and and ordering them and I'm fascinated by this because there is some weird overlap between the community of people who are incredibly skeptical of vaccines of the FDA. And at one point that was understood as a preference for naturalism that there was a primitivist impulse here. And yet some of these same people who were so skeptical about was what was a very wellstudied class of drugs are now ordering completely unknown forms of peptides. some which are about weight loss, but some of which are just to increase energy use or to cure your tennis elbow or to, you know, try to improve like, you know, cell regeneration. And they're stacking them in different formulations. Like it's like a mistrust of the authorities, but a belief in unproven technologies in a way that like that I find culturally very interesting. And I'm curious as somebody who's been around the space for a long time, what you've made of it. Well, I think it kind it kind of goes together. So maybe even it was brewing before the pandemic, but we've had this uptick in an appreciation, an interest in um health and health optimization.
Julia Beloo: 嗯,然后我们现在有了这些技术来传播关于健康优化的信息,特别是播客,它们通常由补充剂制造商赞助。他们不信任权威,我认为很多人在疫情之后对公共卫生和医疗机构感到相当愤世嫉俗,现在我们有了一个工具,实际上在疫情期间也得到了远程医疗的帮助,人们可以以他们以前无法做到的方式掌握自己的健康,然后这种“你可以自己做”的想法,但感觉这几乎是当今社交媒体的通行货币,你知道,你说有一项新研究,然后…
Original English
Julia Beloo: Um and then we have these technologies now to spread information about um health optimization, podcasts in particular, that are often sponsored by supplement makers. They're mistrustful of authority and a lot of people I think were left quite cynical after the pandemic of um public health and the medical establishment and now we have this vehicle actually that was helped also in the pandemic with tele medicine um where people can take their health in their own hands in a way that they haven't been able to before and then this this idea that you can just do it yourself but it it feels like that's almost the currency today of social media like you know you say there's this new study and this
主持人: 我发现了一个新的用途,现在我将在我的动态中推广它。嗯,
Original English
Host: I found this new use for something and now I'm going to promote it on my feeds. Um,
Julia Beloo: 嗯,我认为这反映了你必须信任某事物的方式。世界太复杂了,没有人能对它有第一手的了解。所以你可以信任 FDA 和 CDC 这样的既定权威机构,但如果你失去了对它们的信任,你仍然必须找到某种方式来决定什么该相信,什么不该相信。很多人选择个人声音,你知道,Andrew Huberman 或 Joe Rogan 或 Peter Attia,呃,或者更多进入玛哈世界的人。我甚至不是说他们一定腐败,但如果你身处媒体,例如,你每周都播客健康和保健节目,你必须找到新的内容来说。每周都在麦克风前说:“这是又一周,你应该吃天然食物,努力减少压力,睡个好觉。”这不会持久。即使撇开他们中有些人从补充剂公司或广告中获得分成的事实不谈,他们对下一个新事物有着巨大的偏见。
Original English
Julia Beloo: well, I think it reflects this way in which you have to trust something. The world is simply too complex for anybody to have firstirhand knowledge of very much of it at all. So you can trust established authorities like the FDA and the CDC, but if you lose trust in them, you have to still find some way of deciding what to believe and what not to believe. And a lot of people choose individual voices, you know, Andrew Huberman or Joe Rogan or Peter Attia, uh, or people further into the the Maha world. And I'm not even saying they're necessarily corrupt, but if you're in media, for instance, and you run a podcast on health and wellness week after week, you have to find new things to say. Just getting on the mic every week and saying, "Here's another week when you should eat whole foods and try to reduce your stress and sleep well, it doesn't last." Even putting aside the fact that some of them are getting a cut of either supplement companies or advertising for it, they have this huge bias towards the next new thing
主持人: 而且它一直都在那里,对吧?我的意思是,我职业生涯早期在 Vox 和你一起度过了一段很长时间,当时我一直在研究 Dr. Oz。我记得几年前采访他时,他说,你知道,我想我当时说的是,你为什么要在节目中介绍那些魔法和奇迹?你是一个心胸外科医生。你知道,这不是基于研究的。就是类似这样的问题,他说,你知道,如果我没有魔法和奇迹,我就没有节目了。嗯,我认为还有一点,就是你知道,我们拥有的关于如何优化健康的非常合理的建议,非常扎实的科学基础。它太无聊了。对。就像你说的。它就像是多睡一点,多进行社交,多吃蔬菜。你妈妈从你坐在高脚椅上就开始对你说的那些话。是的,但是要有一个播客或社交媒体动态,你需要有新的建议。我完全同意你的看法。
Original English
Host: and it was always there, right? I spent a lot of time earlier in my reporting career with you at Vox like looking at Dr. Oz and I remember once interviewing him years ago and he said, you know, that I I think I said like why do you have the magic and miracles on your show? Like you're you're a cardiothoracic surgeon. You know, this isn't um research base. It was a question like that and he said you know if I didn't have the magic in miracles I wouldn't have a show. Um I think there's also something that like the you know that the very sound advice the very sound scientific foundation we have for how to optimize your health. It's so boring. Right. It's what you said. It's like sleep more have social relationships. Eat more vegetables. The stuff your mom has been saying to you since you were in your high chair. And yeah, but to to have the podcast or to have the social media feed, you need to have this new advice. I totally agree with you.
公众对未经验证技术的追求与政府监管
Julia Beloo: 在我提出下一点之前,我想说,我认为注射自己或服用研究不足的肽类药物是一个愚蠢的想法,人们不应该这样做。所以,我真的想非常清楚地说明这一点,但在准备这一集并阅读一些肽类增强剂类型的人的说法时,他们的论点是,看,人们有权这样做。这是他们的身体。他们正在这样做,如果我们让他们从国内的复合制药商那里购买,我们可以监管和监督其生产过程,那会更好,而不是那些我们无法信任的中国“飞天”公司。
Original English
Julia Beloo: I I will say before I make this next point that I think injecting yourself or taking poorly studied peptides, it's a stupid idea and people shouldn't do it. So, I really want to say this very clearly, but in preparing this episode and reading what some of the peptide booster types are saying, their argument is, look, people have a right to do this. It is their body. They are doing it and it would be better if we let them buy them from domestic compounders whose processes we could regulate and oversee rather than these fly by night Chinese companies
主持人: 我们无法信任的。但是你如何看待平衡这个论点,比如看,人们正在这样做,这是他们的权利。嗯,我们应该允许他们获得安全制造的产品,而不是政府不希望你这样做,我们将努力让他们难以获得并增加风险,以便更多人,你知道,不要尝试。
Original English
Host: that we can't trust. But how do you think about balancing this this argument like look people are doing this it's their right. um we should allow them to get things that are safely made against this like the government doesn't want you doing this and we're going to try to make it hard to get them and increase the you know the risk so more people you know don't try.
Julia Beloo: 所以这个论点就是我们得到补充剂市场的方式。我们有,你知道,你知道补充剂是如何成为这种 FDA 的东西的历史吗?
Original English
Julia Beloo: So that argument is how we got the supplement market. We have you know do you know that the history of how supplements became kind of this thing that FDA
主持人: 嗯,那是因为补充剂制造商的特别推动,这是一场大规模的公众写信运动,还有有名人参与的电视广告,主题是“不要动我的补充剂。我有权使用这些补充剂。”来自拥有大型补充剂制造商的州的代表们,真的推动了这种宽松的监管环境。嗯,但正是这种论点,即美国人有权使用他们想用的补充剂,才有了我们今天围绕补充剂的监管制度。
Original English
Host: um it's that there there was a big campaign push in particular helped by supplement makers. It was like a massive letterw writing campaign on the part of the public um TV ads with famous actors and the thing was like don't touch my supplements. I have the right to use these supplements. representatives who were from states with um large supplement manufacturers really pushed to to have this kind of lacks regulatory environment. Um but it was this this argument that Americans have the right to use the supplements they want to use. That's why we have this regulatory regime around supplements that we have today.
Julia Beloo: 补充剂的论点究竟指向何方?你知道,你走进全食超市或者CVS,那里有很多补充剂,我不认为我们把它看作一场国家悲剧,其中很多补充剂的名字我甚至都不知道。所以,这是坏事还是好事?对。我是否对人们能够创建这些补充剂组合感到不安?我的意思是,并不是真的。如果你想服用肌酸或其他什么,去吧。
Original English
Julia Beloo: Which way does a supplement argument actually point? You know, you walk into Whole Foods or you walk into CVS and there's a lot of supplements and I don't think we see it as like a national tragedy and a lot of those supplements have names I don't even know. So, is that a bad thing or a good thing? Right. Am I upset people can create these supplement stacks? I mean, not really. If you want to take aine or whatever, go for it.
Julia Beloo: 我认为,我认为当人们被误导,并把稀缺资源用于对他们无益的事情上时,我确实认为这是一个问题。嗯,我个人认为,你知道,政府在保护公共健康和消费者方面扮演着角色。嗯,但这是一个非常敏感的话题,很多人,特别是在美国语境下,他们的想法是,你知道,你有权对自己的身体做你想做的事情,并获取你想要获取的产品。我,我,我想我在这方面持更保守的观点,但很多人肯定不同意我的看法。
Original English
Julia Beloo: I think I think when people are being misled and using like scarce resources on things that aren't going to help them, I think actually it is a problem. Um I I personally think like you know the government has a role in protecting public health and protecting consumers. Um, but it's a very sensitive topic and a lot of people, especially in the American context, it's this idea that, you know, you have the right to do what you want with your body and to access the the um products that you want to access. And like I I guess I have a more conservative view on that, but a lot of people definitely disagree with me.
主持人: 我的直觉是这会变成一场灾难。我个人的看法其实相当保守。我在这里试图扮演魔鬼的代言人,但似乎人们现在正在服用很多东西来促进细胞生长,这在短期内可能很好,但在某些情况下,长期来看具有非常可怕的致癌特性。我的意思是,我认为我们最终可能会意识到,人们开始兴奋的一些事情,你知道,对人们来说真的不好,这以前也发生过。我的意思是,我们之前谈到了 Fen-Phen 和类似的东西。我们确实有过人们对某些东西非常着迷,但它对你没有好处的时期。我们以前会把可卡因放在可口可乐里。
Original English
Host: I mean, my gut is that this is going to become a disaster. My my personal view is actually fairly conservative. I'm trying to be the devil's advocate here, but it seems like people are taking a lot of things right now to increase cell growth, which maybe is good in the short term, but has really frightening cancerous properties in some of these cases. In the long term, I mean, I think we might end up realizing that a couple of the things that people are starting to get excited about, you know, are really not good for folks, which has happened before. I mean, we were talking about Fen-Phen and things like that earlier. We have had periods where people got really into something and it wasn't good for you. We used to put cocaine in Coca-Cola.
Julia Beloo: 绝对是。是的。如果你了解医学史,就会发现这样的例子比比皆是。这也是为什么我总是以更保守的态度来看待这个问题。嗯,但我认为,是的,我们现在肯定处于一个巨大的实验中,是的,这些不同的事物正在碰撞,对吗?这种对健康、长寿和健康优化的兴趣,这些似乎无所不能的药物的可用性,以及人们在线上或药房购买的这些非处方变体。这是一场潜在的灾难,随时可能发生。我认为这些药物,以及更广泛的肽类和其他在文化上变得有影响力的东西,其深层吸引力在于,你知道,在某种程度上,我们都想要控制。控制我们的身体,控制我们的健康,控制我们永远不患上那些让我们所有人恐惧的疾病。一方面,如果你能够获得真正的控制可能性,如果 GLP-1s 在低剂量下确实能保护你免受心脏病侵害,那真是太棒了。呃,Statins 一直都很棒。如果这是真的,我有一个朋友,一个我非常非常关心的人,他的父母很年轻就死于痴呆症,我一直在非常密切地关注所有这些关于阿尔茨海默症的研究,你知道,因为如果它们能预防痴呆症,那么我希望我的朋友服用它们。所以,我并不是说想要保护自己是一种坏冲动。它不是。另一方面,对自己的身体和未来无休止的控制欲望,也可能在精神上具有毒性,因为你无法控制它。对吗?佛教的伟大洞见是,你知道,欲望和贪婪是痛苦的根源,你知道,我们越是欺骗自己相信我们能控制将要发生在我们身上的事情,那么当事情真正发生在我们身上时,我们就会觉得我们失败了。
Original English
Julia Beloo: Absolutely. Yeah. If you know anything about the history of medicine, it's littered with examples like this. And that's also why I always come at this um much more conservatively. Um but I I think yeah, we're we're we're definitely in this big experiment now where yeah, these these different things are colliding, right? this interest in wellness and longevity and health optimization, the availability of these drugs that seem to do everything and then these um these over-the-counter variants that people are accessing and buying online or in the pharmacy. It's a it's a potential disaster waiting to happen. One thing that I think is just a deep appeal of these drugs of of broader peptides and other things that are you know becoming culturally uh influential is you know what on some level we all want is control. Control over our bodies, control over our health, control over never getting the diseases that scare all of us. And on the one hand, if you are able to be given a real possibility for control, if it's true that the GLP-1s at low doses protect you against heart disease, amazing. Uh, Statins have been amazing. If it's true, I have a friend, somebody who I I I care about tremendously, whose parent died young of dementia, and I've been following all this Alzheimer's research on them, you know, very closely because if they're prophylactic against dementia, like I want my friend to take them. So, I'm not saying that wanting to protect yourself is a bad impulse. It isn't. On the other hand, a desire for endless control over your own body and future can be mentally poisonous too because you can't control it. Right? The the great insight of Buddhism is that you know desire and craving are the root of suffering and you know the more we trick ourselves into believing we can control what will happen to us then when things do happen to us we feel like we failed.
Julia Beloo: 绝对是。我认为我们生活在,特别是在控制食物和身体方面。我们生活在这样的食物环境中,对于大多数人来说,选择正确是如此困难。对吗?所以即使你正在服用 GLP-1,我也和很多这样的人谈过,他们并没有减掉他们想减的体重,嗯,因为他们有其他障碍,无法按照他们喜欢的方式饮食或锻炼。我们创造了这些系统和食物环境,使得大多数普通人几乎不可能做他们知道需要做的事情来保持健康。这正是我希望更多人关注的事情,嗯,希望当权者能够拉动更多的杠杆,从一开始就帮助预防这些疾病,这样我们就无需做诸如注射我们不了解长期影响的药物给年轻人之类的。我一点也不反对 GLP-1。我认为它们对许多人来说都是绝对的游戏规则改变者,我已经和朋友和家人谈论过。但我们正在对人群进行这项大规模实验,因为这些疾病确实是可以预防的。如果我们做我们早就知道需要做的事情,比如限制垃圾食品对儿童的营销,嗯,找出方法让健康食品更容易获得。这实际上让我很愤怒,作为一个以前与体重作斗争的人,我意识到这是可以预防的。我本不必遭受那样的痛苦。而像现在正在经历这些的那些孩子们,他们也不必遭受这样的痛苦。
Original English
Julia Beloo: Absolutely. We live I think we live in this in particular around controlling food and the body. We live in food environments that are so gamed against making the right choices for most people. Right? So even if you are on the GLP-1 and I've talked to many of these people, they're not losing the amount of weight they want to lose um because they have other barriers to eating the way or exercising the way they'd like to. We've created these systems and um food environments that make it literally impossible for most regular people to do the things that they know they need to be doing for their health. And that's something that I would love more attention paid to um by whoever's in power, like pulling more levers to help prevent these diseases from the first place so that we don't have to do things like um inject young people with drugs that we don't understand the long-term effects of. And I'm not anti-GLP1 at all. Like I think they've been absolute like game changers for so many people I've talked about for friends and family. But we're doing this big experiment on the population because of diseases that really are preventable. If we do the things that we've long known we need to do like restricting junk food marketing to kids, um figuring out ways to make healthy food more accessible. It actually it enrages me as a person who struggled with my weight before like this realization that this was preventable. I didn't have to suffer like that. And kids like the kids who are now going through this now, they don't have to suffer like this.
主持人: 我觉得我听这个论点已经很久了,就像你知道的,在我作为医疗记者职业生涯的开始。而且,你知道,我们讨论食物荒漠,如果我们在食物荒漠中建立好的超市会发生什么,我们已经在很多地方这样做了,但效果并不好。我对此变得非常愤世嫉俗。我的意思是,是的,如果每个人都能被更多的步行区环绕,并且有更好、更健康的食物,那会好得多。而且我认为你不应该被允许向儿童广告垃圾食品。我认为在儿童麦片上印上汪汪队立大功的这种做法应该是非法的。我认为我们允许对儿童进行无休止的广告宣传是完全疯狂的。它让每个父母在超市里的生活都变成了一场噩梦,包括我自己在内。对于整个社会来说,我认为问题在于人们想要那些对他们没有好处的东西。
Original English
Host: I feel like I've heard this argument as long as I've been touching this issue which like as you know the beginning of my career as a healthcare reporter and I, you know, we debate food deserts and what would happen if we put you know good grocery stores in food deserts and we did this in a bunch of places and it didn't really work. I I've become very cynical about this. I mean, yes, it would be much better if everybody had was like wrapped around with, you know, more walkable places to live and and better and healthy foods. And I don't think you should be able to advertise junk food at all to children. I think it should be illegal to have Paw Patrol on kids cereals. I think this whole thing where we allow endless advertising children is completely insane. And it makes every parent's life in the grocery store a nightmare, myself included. And for the society at large, I think the problem is people want things that aren't good for them.
Julia Beloo: 但我们从未做得足够。
Original English
Julia Beloo: But we've never done enough.
主持人: 但人们不希望你做得足够。
Original English
Host: But people don't want you to do enough.
Julia Beloo: 但是哪些人?我觉得…
Original English
Julia Beloo: But which people? I feel like
主持人: 投票的人,就像纽约发生的这件事一样。布隆伯格想对苏打水征税。
Original English
Host: the people who vote like this happened in in New York. Bloomberg wanted to tax sodas.
Julia Beloo: 他们几乎要把他赶出城。
Original English
Julia Beloo: They almost ran them out of town on a rail.
Julia Beloo: 好的。好的。不,但我认为情况正在改变。我认为越来越多的人正在抚养患有糖尿病和脂肪肝等疾病的孩子,他们意识到这是由食物环境造成的,我觉得那里的政治正在转变,但我们从未对我们的食物环境进行过根本性的改变。这需要很多很多杠杆才能真正看到影响,而这真的还没有做到。
Original English
Julia Beloo: Okay. Okay. No, but I think things are the politics of this are changing. I think like more and more people are raising kids with diseases like diabetes and fatty liver and they're aware that this is caused by the food environment and I feel like that that the politics there is shifting but we've never done the inversion of our food environment that we need to do. It's going to take many many levers to really see an impact and that really hasn't been done.
主持人: 我只是变得,我,我想你需要一种家长式作风的程度,我想我会说的是,在这个国家,没有一个司法管辖区,这种政治是成功的。我们不能指着一个地方,一个州,一个城市说我们做到了那么多。如果能做到,我将是第一个说我们应该这样做的人。
Original English
Host: I've just become I I think you would need a level of paternalism for that that I guess what I would say about it is that there is not a single jurisdiction in this entire country where the politics of that have worked. Like we cannot point at one thing, one place, one state, one city where we've been able to do that much. If it were there to do, I would be the first one to say we should do it.
Julia Beloo: 但我不认为它能做到。就像公共卫生界,我们在致命疫情之后,或者说在疫情期间,试图让人们接种疫苗。
Original English
Julia Beloo: But I don't think it's there to do. like the public health community like we tried to get people to take vaccines in the like aftermath or the the the math during a deadly pandemic
主持人: 这导致了在我一生中最大的公共卫生反弹,RFK Jr. 现在是卫生和公共服务部长。人们对家长式作风的敏感度非常非常高,这是一种非常强大的政治力量。
Original English
Host: and it led to like the largest public health backlash um in my lifetime such an RFK Junior is now the secretary of health and human services people's sensitivity to paternalism is very very very high it's a very potent political force
Julia Beloo: 但我认为我所谈论的,以及我们在书中写到的,并不是要拿走人们的炸鸡或M&M's。而是要创造一个食物环境,让健康的选择与不健康的选择一样容易获得。所以,我现在住在法国,显然那里的政治完全不同。那里不缺巧克力店,不缺我可以买牛角包的地方,所有这些我知道我不应该每天吃的东西。但健康的选择也同样容易获得。所以他们做了很多事情,比如在每个区都有新鲜食物市场。嗯,他们通过土地利用规划,自 19 世纪末以来,将超市的规模最小化,比如利用学校午餐作为杠杆,健康地喂养儿童。随着时间的推移,他们对这意味着什么变得越来越前卫。他们拉动所有这些不同的杠杆。但我们现在讨论的,我认为是围绕慢性病创造这种监管环境。比如,你如何保护公众免受肥胖症、糖尿病、心血管疾病等疾病的侵害?现在这似乎是不可能的,因为它确实涉及对食物环境的根本性改变。但美国在一百多年前就做到了这一点,对吗?当我们开始保护人们免受急性食物中毒的侵害时,那简直就是狂野西部。当时他们会把小牛脑放到牛奶里,还会把砖粉染色食物,还会放铅。这就是 FDA 的由来。这也是 Upton Sinclair 的书出版后,USDA 的肉类检验计划的由来。但我听明白了。这将非常困难。我确实认为政治正在改变。所以我们现在处于这样一个时刻,像加利福尼亚州和西弗吉尼亚州都在考虑,你知道,做一些事情,比如在学校午餐中减少超加工食品,嗯,以及禁止某些添加剂。嗯,所以,所以真正政治上不同的地方,以及像 Robert F. Kennedy Jr. 和特朗普,以及前 FDA 局长 David Kesler 这样的人。嗯,他们对饮食引起的疾病的说法,你已经无法分辨是谁说的了。
Original English
Julia Beloo: but I think one thing that I'm talking about and that that we write about in the book it's not about taking people's fried chicken or their M&M's away. It's about making a food environment where the healthy options are as accessible as the unhealthy stuff. And and so so I'm living now in France and obviously the politics are completely different. There's no shortage of chocoliers of places where I can buy croissant bos like all these things that I know I shouldn't be eating every day. But as accessible are the healthy options. So they they've done things like fresh um food markets in every district. Um they minimize the size of grocery stores um through land use planning since the late 1800s like using school lunches as a lever to feed children healthfully. And over time they've become more and more avancgard about what that actually means. They pull all these different levers. But what we're what we're talking about I think is creating this regulatory environment around chronic disease. like how do you protect the public from developing these diseases like obesity, diabetes, cardiovascular disease? And it seems like impossible now because it does involve these radical changes to the food environment. But America did this over 100 years ago, right? When we started to protect people against acute food poisoning, it was just it was wild west. They were putting calf brains in milk at this time and putting like brick dust to dye food in a certain way and lead. That's where the FDA came from. And that's where the meat inspection program of the USDA came from after um like the the publication of Upton Sinclair's book. And but I hear you. It's going to be very difficult. I do think the politics are changing. So we're in a moment where like places like California and West Virginia are both looking at, you know, doing things like reducing ultrarocessed foods in school lunches and um banning certain additives. Um, so, so really politically distinct places and people like Robert F. Kennedy Jr. and Trump and the former FDA commissioner David Kesler. Um, what they're saying about diet caused diseases, you can't tell who's saying it anymore.
主持人: 那是真的。但我对肯尼迪的能力感到极其失望。我一直非常失望地看到,即使是玛哈中我认为有道理的部分,也没有取得任何进展。对吧?你现在会看到肯尼迪,就像他吃他的炸薯条一样,你知道,他会去那些快餐店,你知道,如果他们真的想让美国,嗯,美国食物环境变得更好,他们就可以做到。与此同时,美国总统却让 RFK Jr. 在拍照时吃麦当劳。
Original English
Host: That's true. But I've been extremely disappointed by the abil by Kennedy. I've been extremely disappointed to see that even the parts of Maha that I thought made sense like have made it nowhere. right? You will watch Kennedy now at like like eating his call fried French fries and you know go into um like these fast food restaurants that you know if they really wanted to make America the um American food environment better like they could. Meanwhile, the president of the United States is like forcing RFK Jr. to eat McDonald's and photo ops,
Julia Beloo: 对吧?就像他们实际的意愿,当涉及到它时,去对抗行业是极其低的。
Original English
Julia Beloo: right? Like their actual willingness when it came down to it to take on industry was extremely low.
主持人: 不,绝对是。
Original English
Host: No, absolutely.
Julia Beloo: 是的。就像,如果你听他们说什么,那很好。他们有没有做任何能持续改变人们食物环境的事情?我真希望看到玛哈禁止向儿童做广告。他们没有。
Original English
Julia Beloo: Like Yeah. Like if you listen to what they're saying, it's fine. Have they done anything that will in a sustained way change the food environment for people? I would love to have seen Maha ban, you know, advertising to kids. They didn't.
主持人: 不。我的看法是,你知道,新的营养指南发布了,它有一个很棒的信息,那就是“吃真食物”,对吧?但没有人做任何事情来让那些真正努力负担和获取真食物的人更容易吃到那些食物。对。就像,SNAP 的人数减少了大约 300 万,而且这是政府让人们越来越难做到的事情。
Original English
Host: No. The way I think about it is we, you know, you had the the new nutrition guidelines come out which had this great message, eat real food, right? But no one is doing anything to make it easier for the people who actually really struggle to afford and access real food to to to eat that food. Right. It's like there's something like 3 million fewer people on SNAP and that's something that the administr the administration has made it more and more difficult for people
Julia Beloo: 那里正在继续实施大规模削减。
Original English
Julia Beloo: huge cuts are are continuing to go into effect there.
主持人: 而且,嗯,曾经有一些项目旨在为学校午餐提供本地和新鲜的农产品,但这些项目已经被削减了。然后有很多像,嗯,在边缘进行微调,你知道,用甘蔗糖代替高果糖玉米糖浆,或者关注某些食品添加剂,但如果你真的想帮助更多美国人吃真食物,这些在整个系统中只是微不足道的问题。你将不得不做更多的事情,你将不得不关注社会中那些依靠食品券的人群,例如。嗯,所以,我完全同意。我认为很多言论都是正确的。就像,这是我第一次在政治层面看到人们谈论食物环境,并说,你知道,这些疾病是可以预防的,它们是由这些环境因素引起的,嗯,减轻了个人身上的压力。但随后提出的许多解决方案也集中在个人身上,比如给美国人更多的可穿戴设备和连续血糖监测仪。这不是我认为我们实际需要的干预强度。
Original English
Host: And um and there there were programs to make um local and fresh produce available for school lunches and those have been cut. And then there's a lot of like um tweaking at the edges of you know swap out high fructose corn syrup with cane sugar or focusing on certain food additives and there's such marginal problems in in the greater system if you really want to help more Americans eat real food. You're going to have to do a lot more than that and you're going to have to focus on the segments of society that were on food stamps for example. Um so so I completely agree. I think a lot of the rhetoric has been in the right place. Like this is the first time I've seen at that political level people talking about the food environment and saying, you know, these diseases are preventable and they are caused by these environmental factors um taking the taking the pressure off individuals. But then a lot of the solutions that have been proposed have also been focused on individuals like give Americans more wearable devices and and continuous glucose monitors. It's not the intensity of the intervention that I think we we actually need.
推荐书籍
主持人: 那么,我们最后一个问题。你有什么三本书想推荐给听众?
Original English
Host: Then always was our final question. What are three books you'd recommend to the audience?
Julia Beloo: 我在写书时,有三本书确实塑造了我的思想。嗯,一本是 Robert Seapolski 的《Behave》。嗯,他又写了另一本书《Determined》,关于,嗯,基本上它是一种反自由意志的论证。嗯,但他从一个非常有趣的,嗯,重要的角度来看待这个问题。另一本是 Deb Blum 的《Poison Squad》。这本书通过一位前 USDA 化学家的传记,精彩地回顾了帮助建立 FDA 以及我们拥有的许多食品法规和其他消费者保护法律的研究。嗯,我喜欢那本书。我真正喜欢的第三本书是 Chris Vanelikin 的《Ultra-Processed People》。这本书真的是一篇论战文章,而且比我在我的书中所持的观点更激烈,但我认为那是一本关于超加工食品的非常有启发性且引人入胜的书。
Original English
Julia Beloo: Three books that really shaped my thinking as I was writing um my book. Um one was Behave by Robert Seapolski. Um he wrote another book Determined about um basically it's an argument against free will. Um but he comes at this I think from a really interesting um and important angle. Another one is Deb Blum's Poison Squad. And this is like an excellent look through a biography of one of the of a former chemist at the USDA who did research that helped lead to the establishment of the FDA and a lot of the food regulations and other types of consumer protection laws that we have. Um, I love that book. The third book that I really enjoyed was Ultra-Processed People by Chris Vanelikin. And this is really a palemic um and much more than um where where I ended up coming down in my book, but I I thought that was a really illuminating um and fascinating book on ultrarocessed foods.
主持人: Julia Blues,非常感谢你。
Original English
Host: Julie Blues, thank you very much.
Julia Beloo: 非常感谢你。
Original English
Julia Beloo: Thank you so much.
📌 文中提及的人物和组织
公司/组织: Kaiser Family Foundation, New York Times Opinion, Vox, Mars Company, FDA, USDA, Eli Lily
产品/模型: GLP-1, Ozempic, Mounjaro, Zepbound, Tirzepatide, Retatrutide, Fen-Phen, Prozac, Statins