This Longevity Supplement for Autophagy: Food vs Pill

There's a longevity supplement that the internet tells you to buy. In animals it extends lifespan by up to 25%. In humans, the people who eat the most of it have roughly a 30% lower risk of dying than the people who eat the least. But the actual clinical trials on this supplement have been mostly disappointing. Except for one recent study that I'm going to talk about later. It's called spermidine. And yes, the name comes exactly from what you think about. Spermidine was first discovered in semen. But fortunately there are much better ways to get it. Spermidine is naturally found throughout your body. And in foods like wheat germ, soybeans, mushrooms, legumes and cheese. And I've said it before, I'm not taking spermidine supplements. Because the evidence mostly points to food. And in this video I'm going to break it all down. So what is spermidine? Spermidine is a naturally occurring polyamine. Despite the weird name, polyamines are essential molecules that are involved in cell growth, gene regulation, immune function, oxidative stress response, inflammation and autophagy. The last one is more interesting for longevity. Autophagy translates into self-eating. It's one of your cell's recycling systems. Damaged proteins and cellular components get broken down and they're recycled instead of being allowed to accumulate. That's why autophagy is an essential process for longevity. Autophagy declines during aging and spermidine appears to be one of the molecules that helps to turn it back on. That's why researchers were so interested in it as a molecule for longevity. The animal research on spermidine is quite interesting. In one study, mice given spermidine saw improvements across several markers of cardiovascular aging. Cardiac autophagy, mitophagy, mitochondrial respiration, cardiomyocyte mechanical properties and inflammation. More importantly, lifelong spermidine supplementation extended their median lifespan. And even when supplementation wasn't started until the mice were already 18 months old, their survival still improved. Another mouse study found spermidine extended lifespan by up to roughly 25% while also protecting against liver fibrosis and liver carcinoma. Similar longevity effects have been reported across yeast, worms, flies and honeybees. So based on purely animal research, spermidine looks extremely promising. But we're not mice. Although we cheese, spermidine supplementation in humans is a bit more complicated. We obviously don't have clinical trials looking at if spermidine supplements or spermidine food would extend human lifespan. But we have some observational studies about what happens to people who eat the most spermidine. One of the most interesting studies followed 829 adults for roughly 20 years. Researchers estimated how much spermidine they consumed from their diets. The lowest intake group ate less than 9.1 mg per day. The highest group ate over 11.6 mg per day. And the higher spermidine intake was associated with lower mortality. The highest intake group had roughly a 30% lower risk of death compared to the lowest group. That's quite impressive. A separate analysis of the US NHANES population found the same pattern. Higher dietary spermidine intake, mostly from vegetables, legumes, cereals, nuts and cheese, was linked to lower all-cause and cardiovascular mortality. So we do have plenty of datasets to show that dietary spermidine intake might be beneficial for longevity. And we can be a little bit more certain of the longevity benefits because the animal research directly pinpoints spermidine as the causal mechanism for the increase in lifespan. In humans we don't have that kind of causal evidence because it's based on observational studies on people who eat spermidine from foods. Higher spermidine intake is associated with lower mortality but spermidine-rich foods include whole grains, legumes, vegetables, mushrooms, cheese and nuts. People eating more of these foods may simply have healthier diets and healthier lifestyles. So spermidine extends lifespan in animals, that's supported. Higher dietary spermidine is associated with human longevity, that's also supported. Is it spermidine that extends human lifespan? We don't know that, but it does extend lifespan in animals. When it comes to spermidine supplements, then that's definitely not been demonstrated to extend human lifespan. And this is exactly why I don't think about longevity supplements all the time. What matters is how your overall health actually stacks up. So I created a 3-minute health percentile assessment inside my top 1% health community. It looks at your biomarkers, fitness status, body composition and shows you your health percent score. Plus there's programs to actually improve your health markers and get to top 1% health. Link down below. So what about the studies on spermidine supplements? We do have some human randomness trials on spermidine, but they're mostly small, short and focused on cognition rather than general longevity. One study in 45 older adults with neurocognitive impairment found that eating a spermidine-rich diet, which provided at least 3.3 mg a day for one year, improved MMSC cognitive scores by an average of 5 points. That sounds quite impressive, but here's the caveat. In this study there was no control group and the study wasn't blinded. So we don't know if the results were because of spermidine or because of something else. Another small study in 30 older adults with subjective cognitive decline found that the spermidine-rich supplement improved memory performance after 3 months compared to placebo. This one was a randomized double-blind placebo-controlled study, but it was still a very small pilot study. So the results should be replicated in a larger trial. The best known and largest study on spermidine and cognition was published in JAMA in 2022. Researchers randomized 100 older adults with subjective cognitive decline to a spermidine-rich plant extract or placebo for 12 months. The supplement provided about 0.9 mg a day of spermidine. And after a year, it didn't significantly improve memory compared to placebo. Now here's the problem with this trial. Although they didn't see any results, they still gave a very small dose of spermidine, 0.9 mg. And remember the observational studies, the threshold for the lowest mortality risk was 11.6 mg a day. So it might be that the 0.9 mg dose was just too small. And you might need a much larger dose to see an effect. But regardless, currently I think it's very weak evidence to suggest that spermidine would improve cognition. This brings me to a new 2026 human trial. And this has me a little bit more optimistic about spermidine supplementation. Older adults received 6 mg a day of spermidine for 13 weeks after COVID vaccination. What they found was that spermidine dramatically increased vaccine-specific antibodies, improved memory B-cell responses, increased neutralizing antibody activity, and reduced immune cell senescence markers, including p16 and DNA damage. So although it's a small pilot study, it has me rethinking spermidine a little bit. Maybe spermidine can improve immune system response after vaccination or something else like that. Now to be honest, there's not that much research about spermidine as a supplement, so it's still a new field of research. But this improved vaccination response is one of the first studies that actually shows spermidine does anything positive. There is another positive trial on spermidine, but it found that spermidine reduced cortisol and increased DHEA, which isn't a very significant result, but it's still something. So what's the most practical takeaway from the research on spermidine? If you want spermidine, you don't necessarily need the supplement. Some foods contain a lot of supplement. Based on the observational studies, you want to aim for at least 11.6 mg of spermidine per day. Here's the highest foods. From approximately 100 grams, you get a lot of spermidine from wheat germ, 24 mg. Dried soybeans, 21 mg. Natto, 20 mg. Aged cheddar cheese, 20 mg. Mushrooms, 9 mg. Ground beef, 7 mg. Green peas, 6.5 mg. Pears, 5.5 mg. Rice bran, 5 mg. Broccoli, 3 mg. And chickpeas, 3 mg. So if you eat various types of foods, you get 11.6 mg and more spermidine from just whole foods. You don't necessarily need the supplements for the longevity benefits. And we don't even know if the longevity benefits seen in those studies is because of spermidine or it's because of just eating these healthy foods. Regardless, just eat these foods. And when it comes to the supplementation of spermidine, then so far you can't really say that it improves cognition or that it would have other health benefits. As I said, the only positive result so far is the enhanced vaccine response in elderly people who have lower immune system function. So there might be something there, but we need more trials for that. I'm not taking spermidine because of these reasons. I'm only getting spermidine from foods. Things like mushrooms, cheese, different types of vegetables, different types of legumes, etc. And if you want to know where your own health actually stands, take my 3-minute health percentile assessment in my top 1% health community. It'll show you your health percentile score, your biggest bottlenecks, and give you programs to move you closer to top 1% and even top 0.1% health. Link down below.