Short answer: Both are sold for healthy aging, and the human evidence for each is small. Urolithin A has three trials, all linked to its maker, with some muscle gains but no change in their main outcomes.12 Spermidine's 12-month memory trial found no effect, and a 15 mg dose did not raise blood spermidine.34 No trial compared them.
| Urolithin A | Spermidine | |
|---|---|---|
| What it is | A compound gut bacteria make from substances in some foods; studied for mitophagy, the clearing of worn-out mitochondria5 | A polyamine; the trial product was a wheat germ extract3 |
| Longest trials | 4 months: 66 adults aged 65 to 90 on 1,000 mg a day, and middle-aged adults on one of two doses12 | 12 months: 100 adults aged 60 to 90 with memory complaints, 0.9 mg a day3 |
| Main outcome met? | No in both 4-month trials: peak power, 6-minute walk and peak muscle energy production did not differ from placebo21 | No: memory did not change compared with placebo3 |
| Other findings | Muscle strength about 12% higher; better hand and leg muscle endurance in older adults21 | Exploratory hints on inflammation and verbal memory3 |
| Reaches the blood? | Yes, at every dose tested in the first human trial5 | 15 mg a day for 5 days raised blood spermine, not spermidine4 |
| Side effects in trials | Adverse events did not differ from placebo in older adults1 | Adverse events balanced between groups over 12 months3 |
| Regulatory note | FDA closed a GRAS notice for use in foods with no questions (2018)6 | No FDA notice in the sources checked; supplements are not approved before sale7 |
In the first human study, single doses and 4 weeks of 500 or 1,000 mg a day were well tolerated in healthy older adults, reached the blood at every dose and changed markers of mitochondrial health.5
In 66 adults aged 65 to 90, 1,000 mg a day for 4 months improved muscle endurance in a hand muscle and a leg muscle, but the two main outcomes, 6-minute walk distance and peak muscle energy production, did not differ from placebo.1 In middle-aged adults given one of two doses for 4 months, muscle strength rose about 12%, but the main outcome, peak power, did not improve significantly.2 Several authors of that trial work for Amazentis, the maker, which sponsored it.2
In the SmartAge trial, 100 people aged 60 to 90 with self-reported memory decline took a spermidine-rich wheat germ extract (0.9 mg spermidine a day) or placebo for 12 months. Memory did not change compared with placebo, and neither did the other planned outcomes. Exploratory analyses hinted at effects on inflammation and verbal memory.3
A much larger dose may not help either. In 12 healthy adults, 15 mg a day for 5 days did not raise spermidine in blood or saliva; blood spermine rose instead.4
Neither has strong evidence. Urolithin A has more trials and some positive secondary results, but all of them involved the company that sells it, and none met its main goal. Spermidine's one long trial was negative, and it may not reach the blood as spermidine. These are dietary supplements: FDA does not approve them before they are sold.7 This is general information, not personal advice. More detail: the Urolithin A and Spermidine guides.