#393 ‒ AMA #85：药物与补充剂指南：如何确定该服用什么、该避开什么，以及如何判断它们是否对你有效

大家好。

Hey, everyone.

欢迎收听《Drive》播客的抢先版问答环节，也就是AMA。

Welcome to a sneak peek ask me anything or AMA episode of the drive podcast.

我是你们的主持人，阿提亚。

I'm your host, Attia.

在本集短片的最后，我会告诉大家如何完整收听这些问答集，以及我们为会员准备的其他大量福利。

At the end of this short episode, I'll explain how you can access the AMA episodes in full along with a ton of other membership benefits we've created.

你也可以现在就访问 peterattiamd.com/subscribe，了解更多详情。

Or you can learn more now by going to peterattiamd.com forward slash subscribe.

好了，不多说了，接下来是今天《问答环节》的抢先版内容。

So, without further delay, here's today's sneak peek of the Ask Me Anything episode.

欢迎来到《问答环节》第85期。

Welcome to Ask Me Anything, AMA Episode 85.

今天我们要聊的是药物和营养补充剂。

Today, we're talking about medications and supplements.

这是别人问我最多的问题之一，也是最容易出错的领域。

This is one of the topics I get asked about more than almost anything else and I think it's also one of the easiest areas to go wrong.

人们总爱问我某样东西好不好，该不该吃，但我觉得这些问题本身就不对劲。

People tend to ask me whether something is good or bad, whether they should take it or not, but those are I think kind of the wrong questions.

真正该问的是：针对某个具体的人、某个具体的问题，这个干预措施有没有道理？今天我就想跟大家说清楚这一点。

The right question is whether a specific intervention makes sense for a specific person with a specific problem and that's what I'm going try to get to today.

在这期节目中，我们会先讲清楚：搞清问题本身，比急着选方案重要得多。

So in this episode we'll cover why defining the problem matters more than picking the intervention.

药物或补充剂能干哪些事，以及为什么不同用途，对证据的要求也该不一样。

The different jobs a medication or supplement can do and why the evidence bar should move depending on the job.

怎么分辨有力的证据和薄弱的证据，光靠理论机制是远远不够的。

How to tell strong evidence from weak evidence and why mechanism alone isn't enough.

为什么你的基础风险不同，结果就完全不同，相对风险很容易骗人。

Why baseline risk changes everything and how relative risk can mislead you.

怎么真正想明白吃这些东西可能带来的真实代价。

How to think about the real downside of taking something.

副作用是有的，但还有成本、麻烦和机会成本。

Side effects, yes, but also cost, hassle and opportunity cost.

怎么判断你正在吃的补充剂是否真的有效。

How to determine whether the supplement you're taking is having any real effect.

怎么停止服用某种东西。

How to stop taking something.

为什么补充剂特别值得比人们通常给予的更多的怀疑。

Why supplements specifically deserve a lot more skepticism than people give them.

最后，我列了一个清单，列出了一些我觉得风险和回报还算值得的非处方补充剂。

And finally, the short list of over the counter supplements that I think are probably worth the risk reward trade off.

好了，不多说了，希望你们喜欢第85期问答。

So without further delay, I hope you enjoy AMA number 85.

彼得，欢迎来到又一期问答。

Peter, welcome to another AMA.

你最近怎么样？

Are doing?

非常好。

Very well.

谢谢。

Thanks.

不错。

Good.

今天我们就直接进入正题，聊聊药物和补充剂相关的话题。

We will get right into it today on AMA all around medications and supplements.

第一个问题：在服用任何药物或补充剂之前，你认为人们应该如何准确定义自己的问题，才能更有可能找到真正有效的解决方案，降低风险，而不是仅仅浪费钱，甚至在不知不觉中带来其他伤害？

So first question, before someone takes any medication or supplement, how do you think that they should define what the problem is in a way that increases the odds that they look for and pick interventions that actually benefit them and reduce risk opposed to at best waste money and at worse cause other harm that they don't know about.

我觉得，从思维模式的角度来看，这确实是大多数人面对补充剂时最大的难题，其实对处方药也一样适用。

You know, think this is actually one of the biggest challenges from a, from a sort of mental model standpoint is plaguing most people when they think about supplements in particular, but I think also frankly pharmaceuticals.

人们通常在定义问题时，抓错了层次。

So people are, I think typically defining the problem at the wrong level of abstraction.

他们会说：我想更健康，或者想更有精力，或者想活得更久。

So they'll say things like, I want to be healthier, or I want more energy, or I want to pursue better longevity.

但问题是，这些说法根本没法付诸行动。

And the challenge is that those are not really actionable problem definitions.

它们太模糊了，没法衡量，也很难证伪，等等。

They're vague, difficult to measure, very difficult to falsify, and things like that.

所以我建议，我们换个角度，聚焦在哪些是可以操作的指标或具体方面，对吧？

So I would suggest that we reframe this discussion around what would be actionable metrics or actionable parts, right?

比如，第一，得有个能被测量的指标；第二，得有个判断标准，用来衡量是否出问题；第三，我觉得还应该有个时间期限。

So one would be a metric that can be studied, two would be a threshold against which you would measure, and then I think a third potential one would be a time horizon.

那我到底该测什么？

So what am I measuring?

什么数值才说明真有问题，也意味着该采取行动了？

What level tells me that there's a problem and by extension a solution?

还有，我预期多久能看到变化？

And when do I expect that to happen?

如果你事先说不清这几点，那大概率还没准备好开始任何尝试。

So if you can't come up a priori with some sense of those things, you're probably not in a good spot to start anything.

举个具体的例子吧。

So, for example, let's use a tangible example.

别只说我的胆固醇不好，你应该说我的载脂蛋白B是每分升130毫克。

Instead of saying my cholesterol is bad, you would say my ApoB is one hundred and thirty milligrams per deciliter.

我想把它降到每分升60毫克以下，而且希望在六个月内达成。

I want to get it below sixty milligrams per deciliter and I'd like to do that in the next six months.

别只说我的睡眠不好，你应该说，每周有四五天我得花六十分钟才能睡着，我希望在两个月内把这个时间缩短到十分钟以内。

Instead of saying, you know, my sleep is bad, you might say it takes me sixty minutes to fall asleep on, you know, four or five nights a week, and I want to make that under ten minutes to fall asleep within two months.

这才是真正清晰的问题定义。

So that's a real problem definition.

接下来要考虑的是反事实情况。

The next question is the counterfactual.

如果我什么都不做，会怎么样？

What happens if I do nothing?

这个问题会不会显著增加风险、降低生活质量，或者引发其他后续影响？

Does this problem meaningfully increase risk, reduce quality of life or create some downstream consequence?

我觉得这个问题很重要，因为它能区分真正的问题和那些只是看起来能行动的事情。

So I think this question is important because it separates real problems from things that merely, you know, feel actionable.

这很关键，因为问题定义不清几乎肯定会带来某种虚假的正面结果。

And it matters because poor problem definition almost guarantees some sort of false positive.

如果问题模糊不清，几乎任何事都可能看起来像是起了作用。

So if the problem is vague, almost anything can look like it helped.

你某一周睡得好了一点，周二精力也稍微好了一些，某项指标略有改善，于是你就开始给自己编故事了。

You sleep a little better one week, your energy is a little better on Tuesday, one lab improves a little, and now you're telling yourself a story.

我们都这么做。

And we all do this.

说白了，我们天生就是爱讲故事的生物。

I mean, that's, we're storytelling machines.

我觉得这就是为什么很多人一吃就是好几年，却从没弄清楚自己到底有没有解决任何实际问题。

And I think that's how people end up taking things for years without ever knowing if they've solved anything real.

所以我觉得这里的规则其实可以很简单，对吧？

So I think the rule here could be pretty simple, right?

别一上来就盯着分子，先搞清楚问题是什么。

Do not start with the molecule, start with the problem.

要把问题定义得足够具体，具体到有可能被证明是错的。

Define tightly enough that you could actually be proven wrong.

如果你说不清衡量标准、阈值、时间线，甚至不做任何处理会有什么后果，那你根本不是在做干预决策。

So if you can't state metric, the threshold and the timeline, and even the consequences of doing nothing, you're not really making an intervention decision.

你这更像是在自己最爱的购物网站上冲动下单。

You're probably impulse shopping on, you know, your favorite website.

在看各种药物和保健品的时候，你怎么去思考和分类它们真正该完成的任务呢？

And when looking at different medications and supplements, how do you think about and maybe classify the quote unquote job that they would do?

根据这种分类，会不会影响你对证据的要求，或者你愿意承担的风险程度？

And based on that classification, does it change the evidence threshold you like to see and how much risk you're willing to tolerate?

一旦问题明确了，接下来该问的是：这个干预的目的是什么？

Well, once the problem is defined, I think the next question is asking, okay, what is the purpose of that intervention?

这很重要，因为不同的目的，需要的标准也完全不同。

And again, it matters because it requires different standards.

所以如果你没准确分类这个目标，就很可能用错证据标准，接受错误的风险水平。

So if you don't classify this job as you describe it correctly, you're very likely going to apply the wrong evidence threshold and accept the wrong amount of risk.

我觉得我们可以把这些分成四类。

So I think we could put these into four buckets.

疾病治疗、症状缓解、风险降低，还有我不太喜欢这个词，但实在得用——那就是优化。

Disease treatment, symptom relief, risk reduction, and I hate the term but I think we just need to use it and it's optimization.

表面上看它们好像差不多，实际上差别很大。

So they might sound sort of similar on the surface, but they're actually quite different.

如果目标是疾病治疗，那要求就很高，对吧？

So if the quote unquote job is disease treatment, the bar is high, right?

这个疗法能不能真正改善疾病？

Does this improve the disease in a meaningful way?

当然，这时候你可以接受更大的副作用，因为问题本身很严重，不作为的后果也很明确。

And of course here you would be willing to accept more downside because the underlying problem is serious and the counterfactual is strong.

假设你得了病却什么都不做，病情很可能会明显恶化。

Presumably if you have a disease and you do nothing, the disease will get significantly worse.

但与此同时，你还是需要更扎实的证据，最好是明确的临床结果试验，或者至少是经过充分验证的替代终点，而不是光靠一个动人的故事。

But at the same time, you're going to want stronger evidence, ideally hard outcome trials or at least some well validated surrogate endpoint, not just a compelling story.

如果目标是缓解症状，问题就不一样了。

Now, if the job is symptom relief, the question is a bit different.

患者是不是真的感觉更好了，或者功能有没有提升？

Does the person actually feel or function better?

这时候我们面对的是主观体验。

And here we're dealing with something that's subjective.

你或许可以接受一定的安慰剂风险，因为只要症状有明显改善，而副作用又很小，这种权衡还是值得的。

You may be willing to frankly tolerate placebo risk because if the symptoms meaningfully improve and the downside is low, that could still be a reasonable trade off.

如果目标是降低风险，那你处理的是一种人根本感觉不到的东西，按定义就是这样。

If the job is risk reduction, you're treating something that a person can't feel almost by definition.

所以这里的证据标准也得定得很高。

So the evidence bar again here needs to be pretty high.

通常这意味着要有明确的临床结果数据，或者至少是一个经过高度验证的替代指标。

That usually means hard outcomes when available, or again, at least a very validated surrogate marker.

而且在这里，并不是所有生物标志物都一样靠谱。

And again, not all biomarkers are equal here.

ApoB 是一个经过充分验证的替代生物标志物，但像某些模糊的炎症指标或者重金属这类东西，就不一定够格了——毕竟有人动不动就拿排毒之类的说法夸夸其谈。

ApoB is a very well validated surrogate biomarker, whereas, you know, some vague inflammatory marker or heavy metal is not necessarily going to be in that category as you're, you know, someone's pontificating about detoxifications or something like that.

如果目标是优化，那我觉得怀疑态度应该更高才对，对吧？

If the job is optimization, then I think skepticism should go up, right?

这里最容易出错，因为大多数人本来就很健康，预期的改善通常也很微小。

This is where error rates are highest, the person is usually starting from a relatively healthy baseline, and the expected effect is often small.

这些说法往往打着机制的旗号，但根本没法客观判断补充剂或药物到底有没有用，这就让你特别容易自欺欺人。

The claims are usually made in a mechanistic way, and there's generally no objective way to determine whether the supplement or medication is benefiting you, making your ability to basically fool yourself enormous.

所以我觉得，这正是我们今天聊这个话题的关键原因之一——大多数抗衰老干预措施，其实都是披着风险降低外衣的优化手段。

So, I think the challenge and probably the reason we're even doing this episode is in part because most of the longevity interventions are really optimizations masquerading as risk reductions.

它们借用的是预防、衰老、健康寿命、韧性、长寿这些词，但实际拿出的证据，更像是一些凭空猜测的优化方案，而不是真正的风险降低。

They kind of borrow the language of prevention, aging, health span, resilience, longevity, but the actual evidence that they put forth looks much more like speculative optimization interventions rather than true risk reduction.

我觉得这个区别真的很重要，对吧？

And I think this distinction really matters, right?

这种分类方式应该同时影响你的证据标准和风险承受能力。

This classification should change both your evidence threshold and your risk tolerance.

问题越严重、越具体，你可能就越能接受潜在的负面后果；而目标越空泛，你就越不该容忍任何风险。

I think the more serious and concrete the problem, the more downside you may be willing to keep, as I said, and the more speculative the goal, the less downside you should be willing to tolerate.

简单总结一下：如果你在考虑疾病治疗，那就得要求强有力的证据，但可以接受更高的风险。

So I guess to summarize that, if you're looking at disease treatment, you want to demand strong evidence, but you'll accept more risk.

如果是缓解症状，重点应该放在实际体验的效果上，但要警惕安慰剂效应和噪音，同时考虑安全性的未知因素。

If you're looking at symptom relief, you prioritize the actual lived benefit, but watch for placebo and noise and factor in the unknowns about safety.

如果是降低风险，你就得依赖经过验证的替代指标或硬性结果，不过后者通常很难获取。

Risk reduction, you're going to have to look at validated surrogates or hard outcomes, although the latter tends to be challenging.

如果是追求优化，那你理应保持高度怀疑，尤其是在安全性方面。

And if it's about optimization, you're going to default into a skeptical state, especially around safety.

彼得，咱们深入聊聊你刚才提到的一点，就是关于药物和补充剂的证据问题。

So Peter, let's double click on one of the things you briefly mentioned there, which is kind of evidence when looking at medications and supplements.

当人们在评估自己该用什么药或补充剂时，你常见到他们怎样混淆不同层级的证据？现实中该怎么避免这种错误？

So when people are evaluating how they're thinking about a medication supplement for themselves, what are common ways that you see people confuse the different tiers of evidence and how can people prevent that in practice?

那人们该怎么提高警惕呢？

So how can people be a little bit more aware?

当他们看到各种说法时，就能逐渐分辨出这些说法的可信度有多高。

So when they're looking at various claims, they start to understand how good those claims are.

感谢收听今天《The Drive》AMA的抢先版内容。

Thank you for listening to today's sneak peek AMA episode of The Drive.

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If you're interested in hearing the complete version of this AMA, you'll want to become a premium member.

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正因为如此，我们的工作完全依靠会员的支持才得以实现。

To do this, our work is made entirely possible by our members.

作为回报，我们会为会员提供专属内容和额外权益，远超免费内容的范围。

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所以，如果你想在这一领域提升自己的认知水平，我们的目标就是确保会员获得的回报远超订阅费用。

So if you wanna take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of the subscription.

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Premium membership includes several benefits.

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圈子里都说，没人能比得上我们的笔记质量。

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其次是每月一次的问答专场（AMA）。

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This is a great way to catch up on previous episodes without having to go back and listen to each one of them.

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