July 14, 2026In This Article
Previously, I’ve listed glucosamine, a medicine used to treat knee and joint issues, as a B-Tier intervention for reducing all-cause mortality. I stopped believing in the benefits of glucosamine after reading about Vitamin E. In the late 1990s, Vitamin E was considered a longevity drug, and several observational studies had shown a large reduction in all-cause mortality from those who took vitamin E supplements. In the early 2000s, the medical industry began randomized controlled tests of Vitamin E, first on people with cardiovascular disease (CVD) symptoms, and then, later on, in healthy people as well. The results were bad. If anything, Vitamin E supplementation increased the chance of death.1 The difference was due to the healthy-user bias and was proven decades earlier, in 1980, with the Coronary Drug Project (CDP).2 While the CDP found people who took their medicine prescriptions had reduced mortality, they found virtually the same reduction in mortality (~50%) in people who received a placebo sugar-pill instead of the medicine. Basically, people who are disciplined enough to take their daily medicine live longer, even if that medicine is worthless.
While glucosamine doesn’t have the same RCTs to show that it doesn’t reduce ACM, it has the same signature as Vitamin E (self-selected users who take their pills faithfully) and about the same observed benefit, but without even having the plausible biological description of how a knee medicine would increase lifespan.
At least I’m not alone in my overestimation of the benefits of a pill. Let’s take a look at the other popular “longevity drugs,” including recent study findings:
Food in a Pill
One approach commonly used to look for longevity drugs is to extract components of healthy food to serve as a supplement. Unfortunately, looking for the component in foods often identifies something that is a marker for high consumption of that food, but doesn’t cause the healthy benefits, or the extraction and distillation process loses important parts of the chemical.
Vitamin E isn’t the only multivitamin thought to extend life. Vitamin D, Vitamin C, or multivitamins have all gone through popular periods as extending life. Unfortunately, RCTs have shown that all of these, including multivitamins, are at best neutral for lifespan and possibly harmful.3
Fish oil — a fish diet is a fundamental part of the Mediterranean Diet, and there have been many attempts to bottle the benefits of fish in a pill. These focus on the various forms of fat in fish oil, like Omega-3, EPA, and DHA. Unfortunately, fat isn’t shelf-stable over longer periods, and putting it in little capsules in a jar doesn’t save it from going rancid.4 The RCTs on fish oil supplements have generally come up null for RCT benefits.5 More concerningly, a recent study on dementia, which generally tracks overall longevity, found that regular fish oil supplementation increases risk of dementia, apparently due to the oils going rancid in the capsules.6
Fake Fasting
For their size, naked mole rats live nearly as long as humans, yet reportedly take remarkably few longevity supplements.Dedicated Unagers already know that calorie restriction longevity benefits are a myth, but it was thought that Calorie Restriction (CR) was a proven way to extend life. CR is a hard road—hunger, chills, low sex drive, and worse—low muscle mass. Particularly in the face of the Last Boss of Death, frailty and the loss of muscle mass with fasting are devastating. But that hasn’t stopped many from trying to find a magic longevity pill that delivers the benefits of CR without the costs.
Resveratrol — Hailed as the source of red wine drinkers’ longevity, this was supposed to replicate some CR benefits without the restriction, but thanks to a lucky dye misfire causing a false positive, David Sinclair was able to sell his resveratrol company for $720 million to GlaxoSmithKline. Two years later, they dropped the drug.7
NMN, NAD+ — Not content with $720 million for bad longevity science, Sinclair then hyped up a different molecule, NMN, and claimed, “No, this is the CR mimic!” He started a company again and plied the FDA to ban NMN supplements so only his company could sell it. Didn’t matter, since the RCTs showed it was as useless as resveratrol for longevity.8
Rapamycin is often given legendary treatment — a strange chemical made by a bacterium found only on Easter Island, kept in a refrigerator for years before it was found to extend lifespan in animals… But that doesn’t really matter, because humans are not lab animals, and the RCTs in humans for longevity failed.9 Rapamycin also reduces immune system responses (it improves organ transplant success), which raises concerns that the protected lab animals it extends life in might not do as well outside of a disease-protected lab. It also reduces muscle growth, making humans more vulnerable to the grim reaper of frailty.
Treatments, Not Longevity
The final category looks at the long list of medicines discovered over the ages and hopes that some of them are effective for more than just the malady they’re normally prescribed for.
Aspirin is the first of these. Long used as a painkiller, it also has shown benefits for thinning blood, which seemed to help CVD survivors of strokes and heart attacks. In the 1990s, a daily baby aspirin became popular among the senior set. Unfortunately, along with the thinner blood, aspirin can also cause hemorrhagic strokes (a different kind of stroke from CVD-caused ones) from blood being too thin, and also stomach lesions and bleeding.10 Stop taking unless recommended by your doctor.
Good reason to take aspirin approachingMetformin reduces blood sugar levels and is powerful in treating diabetes. Early tests wondered if the benefits were so good that even people without diabetes would live longer with it. Unfortunately, the RCTs showed no benefit in longevity for people without diabetes, and an unfortunate reduction in muscle gains from strength training.11
Potassium supplements, which I have taken before when my blood pressure was getting high, also fit this category. As a treatment for blood pressure, it can be more effective than reducing salt (for example, with NuSalt or LoSalt replacing table salt), but likely has little benefit for those with normal blood pressure.
GLP-1 drugs (Ozempic, Mounjaro, Retatrutide, etc.) are the latest treatment that has been hypothesized to not only fix a condition (of overweight), but also generally extend life. Early studies have shown that GLP-1 drugs have additional benefits for addiction and seem to improve biomarkers before major weight loss.12 That’s exciting for fans of GLP-1 drugs, but weight loss commonly improves biomarkers when the weight is first starting to drop.
Other “Longevity Drugs” not Covered in this Post
This list isn’t nearly exhaustive. I also considered discussing Taurine, GlyNAC, Spermidine, and Senolytics, but the short story is their impact is questionable, and they largely haven’t even reached the RCT stage to confirm what impact they have.
The Next Generation of Longevity
And yet, GLP-1 drugs have been used to treat diabetes since 2005! Up until the industry confirmed its power in treating obesity, the choices for treating obesity with medicine were just as thin as longevity drugs are today. There were no options that would reliably cause significant weight loss, and several were removed from the market for being dangerous to boot.
This is the true Ozempic Challenge. When will a pill or injection that helps healthy people live noticeably longer be found, the way GLP-1 drugs have revolutionized weight loss? Hopefully, coming soon to a pharmacy near you!
