Your stack has four good molecules and one missing step

Open the cabinet of anyone who takes longevity seriously and you will find some combination of the same four things: an NAD+ precursor, CoQ10, creatine, and lately spermidine. Each of them has a defensible reason to be there. Each is doing something at the cellular level.

And yet the pile keeps growing, because none of them is doing the thing that actually degrades with age. Adding more fuel to an engine is not the same as replacing the parts of the engine that have stopped working. Your mitochondria have a maintenance crew, and the crew slows down decades before you notice it.

What follows is not a comparison written by an outsider. It is the comparison Timeline publishes on its own science page, next to the trials it paid for and the results that did not go its way.

The one row that reorders the ranking

Timeline scores five compounds on four criteria. Three of the four criteria are the ones you would expect. The first is the one that matters, and it is the one where the stack falls apart.

Read the top row again. Creatine, CoQ10 and NAD+ get a clean no. Spermidine gets a partial. On Timeline's own scoring, only one compound on that list directly triggers mitophagy.

Which raises the obvious question: what is mitophagy, and why would you care whether something triggers it?

The cleanup crew that slows down in your 30s

Timeline's explanation is short enough to quote in full. "Mitochondria are the batteries that make your cells work." By their account, "90% of your body's energy comes from mitochondria." And "these cellular batteries start wearing out in your 30s."

The body has a process for that. It is called mitophagy, and Timeline describes it as "the crucial pathway that removes dysfunctional mitochondria." Broken units get identified, dismantled and recycled, and fresh ones get built in their place.

Then, in Timeline's words: "But in your 30s mitophagy starts to slow down." The consequence follows directly. "Old, damaged mitochondria build up, draining cellular energy." And the part you eventually notice: "You get weaker, feel fatigued, and your skin visibly ages."

Source: timeline.com/science/how-it-works and timeline.com/faq, where the company writes that "muscle function starts to decline in our 30s as our mitochondria, our cellular powerhouses, start to break down and lose their efficiency."

This is the gap in the stack. NAD+ and CoQ10 sit close to energy production. Creatine buffers energy in the muscle. Spermidine touches autophagy more broadly. None of them is a dedicated instruction to clear the broken units out.

The molecule, and why your gut probably is not making enough of it

The compound that does this is Urolithin A, which Timeline calls "a rare postbiotic molecule." You do not eat it. It is formed in the gut, downstream of foods like pomegranates, berries and nuts, by bacteria that break down their polyphenols.

That last part is the problem. Timeline's position, published in its FAQ, is blunt: "Only 30 to 40% of the population possesses the specific gut microbiome required to convert dietary precursors into Urolithin A, and even then, conversion is inconsistent."

Their own bioavailability study puts a number on the baseline. Only 12% of subjects had detectable levels of Urolithin A to begin with. After drinking pomegranate juice, roughly 40% converted the precursors. The company's summary line for consumers is simpler: "Only 1 in 3 people can get enough Urolithin A from diet alone."

And if you happen to be one of the converters? Timeline says you would still need to drink six glasses of pomegranate juice a day to reach the equivalent of the 500 mg dose used in its trials.

Sources: timeline.com/faq and the NOURISH bioavailability study listed at timeline.com/studies.

Four numbers, with the asterisks left on

Supplement marketing usually strips the footnotes. Timeline's are worth keeping, because they tell you exactly who was studied and for how long. These are the four results the company leads with, and the journals that published them.

* and ** are Timeline's own reference markers. Both footnotes are reproduced in full at the bottom of this page, unedited. Study index: timeline.com/studies.

Note what the strength number is not. It is not a claim about athletes, and it is not a claim about the gym. The trial ran in sedentary, middle-aged adults with an average BMI of 29.52, and the measure was hamstring strength in knee extension and flexion. The company states that explicitly, in a footnote, on the product page.

The section most supplement pages delete

Timeline publishes its own null results. Not buried, not reworded: on the studies page, in the same table as the wins, in the same plain summaries. That is unusual enough to be the strongest argument on this page, so here they are in the company's own words.

A company that leads with a failed primary endpoint is telling you something about how it treats the rest of its data. Timeline's studies page opens with the line: "At our core, we stand against pseudoscience."

What actually happens, and when

Timeline maps the sequence on its own site. Reproduced here in full, in the company's wording.

Source: timeline.com/science/how-it-works.

Who is behind the research

Timeline was founded in 2007 by MDs and PhDs at EPFL, the Swiss Federal Institute of Technology in Lausanne. The company reports 18+ years of research, 25 human clinical trials involving over 900 participants, more than 500 studies on Urolithin A, and 80 patents on Mitopure.

Quotes as published at timeline.com/testimonials and timeline.com/about.

What people taking it report

Reviews published at timeline.com/reviews, quoted as written. Individual results vary, and Timeline says so itself in the section above.

The practical part

Certifications and pricing as published at timeline.com, checked 3 August 2026.

One last thing worth saying

Nothing here argues that you should throw out the creatine. Timeline's own table gives creatine a yes on complete human clinical trials, and a yes is a yes. The argument is narrower than that, and it is the argument the table makes: your stack is full of molecules that feed the system, and empty of anything that clears it.

Mitophagy starts slowing in your 30s and does not speed back up on its own. Four months is the honest minimum. The company will tell you itself that you may not feel a thing in week one.

That is a strange way to sell a supplement, which is exactly why it is worth a look.