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In this “Ask Me Anything” (AMA) episode, Peter explores how to think critically about medications and supplements by focusing not on whether an intervention is inherently “good” or “bad,” but on whether it makes sense for a specific person with a specific problem. He explains why clearly defining the problem matters more than choosing the intervention itself, how the intended purpose of a medication or supplement should influence the standard of evidence required, and why mechanistic reasoning alone is rarely enough to justify taking something. Peter also examines how baseline risk shapes the true benefit of an intervention, why relative risk statistics can be misleading without proper context, and how to weigh not only side effects, but also cost, inconvenience, and opportunity cost when deciding whether something is worth taking. Additionally, he discusses practical ways to evaluate whether a supplement is actually having a meaningful effect, how to think about discontinuing therapies, why supplements deserve far more skepticism than they often receive, and the small group of over-the-counter supplements he believes may offer a reasonable risk-reward trade-off.

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We discuss:

• How to properly define health problems before considering medications or supplements [1:45];
• How the intended purpose of an intervention should determine evidence standards and risk tolerance [5:00];
• Understanding the hierarchy of evidence for medications and supplements and avoiding the mistake of treating weak evidence as clinical proof [9:00];
• Why mechanistic explanations can be misleading when evaluating longevity interventions [13:15];
• How baseline risk—and the distinction between relative and absolute risk reduction—changes the real-world benefit of medications and supplements [18:15];
• Thinking beyond side effects: the many forms of downside associated with medications and supplements [22:45];
• Why medications and supplements require different standards of trust and evidence [26:00];
• How to structure meaningful self-experiments with medications and supplements to determine if it’s they’re working [30:30];
• How to monitor the effects of medications and supplements without fooling yourself [32:30];
• How to periodically reevaluate and potentially discontinue medications and supplements [35:15];
• The biggest risks and failure modes of over-the-counter supplements: efficacy, poor quality control, contamination, interactions, toxicity, and marketing-driven overuse [38:30];
• Why the US supplement regulatory system creates unreliable products [41:45];
• A practical framework for evaluating medications and supplements [46:30];
• Over-the-counter supplements with the best balance of evidence and low downside risk [48:00]; and
• More.

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