" The team then assessed the efficacy of UA by looking at cellular and mitochondrial health biomarkers in the participants' blood and muscle tissue. The results were compelling: UA stimulates mitochondrial biogenesis—the process by which cells increase mitochondrial mass—in the same way as regular exercise.
UA is the only known compound that re-establishes cells' ability to recycle defective mitochondria. "
The point of a biomarker is that we think/hope/hypothesize that we can use it as a surrogate for the thing we're actually interested in, so that we have something measurable on shorter timescales. Unfortunately, this assumption is often incorrect, and we won't actually know for years.
How do we often test for diabetes.. cancers.. many many clinical conditions? Biomarkers. So they are not practically unreliable in general.
What do you know about the particular biomarker employed in the study to say that it is unreliable ?
Long term degenerative conditions are some of the most difficult problems for such validation, due to time, cost, and the complexity of risk in real populations.
I don't know anything about how well the current study actually links to mitochondrial biogenesis, but I know that we don't have satisfactory interventional biomarkers for a process as complex as aging. By all means continue researching this, but I think it's eminently sensible to be skeptical at this point.
Improving ATP efficiency is huge... i agree with you it may not mean stronger bones and more elastic skin...but we do know aging (less elastic skin and weaker bones) is related to the bodies breakdown in ATP supply/demand/conversion.
I just don’t think you can gloss over mitochondria inprovement as no benefit...it’s literally an improvement in energy (more energy with less calories), it’s a benefit unto itself.
It's entirely plausible that, in the modern world, this is actually a negative.
Also, for all anyone knows, just "improving" mitochondria might also hurt due to increased production of free radicals and other strongly oxidizing species by those improved mitochondria.
In cancer, we see all the time the ability to get a cell we know is important into a tumor does not, necessarily, associate with clinical benefit. The same goes here. The ability to improve one small piece of biology does not mean, necessarily, that you will see a larger, emergent effect. Biology is much more complicated than that.
No...there are numerous studies on the proven benefits of improved mitochondrial function/capacity. One of the benefits is cellular anti-aging.
Also, you’re assuming that “cellular anti-aging” is good for your health. You could be right, but you could be wrong.
2) Lab evidence for a biomarker for a metabolic process is so far short of evidence of clinical improvement that it’s a joke. I will never stop deriding studies that point to proxy markers (or in this case, proxy proxy markers) as evidence of benefit. This has been proven to be inadequate so many times, across so many different studies, that it’s just not worth talking about anymore.
This is a perfectly fine and valid phase 1 study. It says “we have identified a dose range that doesn’t immediately sicken people.” That’s what phase 1 trials do. The rest is press release hype.
Nature Endocrinology Reviews is a relatively ranking journal in endocrinology - roughly second place, by impact factor. This didn’t get published there.
Nature Metabolism was only opened in 2017, as an online-only journal. It doesn’t even rank in the top 50 for endocrine and metabolism journals - granted, that may be in part because it doesn’t even have an impact factor yet (calculating impact factor requires two years of publication history preceding the year being calculated for. In 2020, we should see a 2019 IF.)
So, one can say they might be enormously prestigious, and we just won’t see until 2020. It’s more likely that people aren’t bothering publishing their best articles in a 0 IF journal, because in academic circles the Nature Subbrand is recognized as not inherently meaningful, so the 0 IF pub just hurts (unless you think your pub would otherwise end up in an unimpressive journal, and you want to gamble that the future IF will be higher and pay off.)
>>> The present study reveals that UA induces a molecular signature
response, in both the plasma and skeletal muscle of humans, resembling
that observed as a consequence of a regular exercise regimen.
The also selected sedentary people only (from their participant inclusion criteria). Note that this is somehow normal: I have been rejected twice in 2 clinical trials for mitochondrial myopathy because I was too fit.
>> body mass index 18-32 kg/m2 and demonstrated sedentary behavior
All the authors declare a conflict of interest with Amazentis. Nestlé just signed a partnership agreement with them  to help them develop the product.
I guess they are actively seeking the exercise in a pill product. If they make it, it would be one of the biggest blockbusters in the history of medicine.
"A compound called urolithin A (UA) was the focus of the study, after previous experiments with it showed promise in extending the lifespans of worms and mice. The compound appears to fight aging by improving the function of mitochondria – the energy-producing part of a cell – in a way similar to the benefits of exercise. While it's not found naturally in any known food, biomolecules in fruits like pomegranates and raspberries do break down into UA in the human gut"
Here's the study
Yellow raspberries seems to contain bigger amounts of ellagic acid than pomegranates
Not everyone’s body can create UA from these natural sources so the idea is to just make a pill for it that will work on anyone.
In other words, no one would fund a penicillin trial if they thought people could get by eating moldy bread from GNC.
What criterion does the FDA use to distinguish a food-derived chemical that needs to be treated as a drug, from one that’s still just seen as an extract/essence of the food itself, and therefore can be treated as a supplement? It seems very opaque to me.
If Wikipedia is correct, we should start eating yellow raspberries instead; they offer about seven times as much of the compound this study is investigating the effects of. https://en.wikipedia.org/wiki/Urolithin_A#Dietary_sources
But how much you'd need to eat for a clinically noteworthy benefit is the question. That's what the follow-on studies are for.
Link here, to save searching. http://pdf.amazentis.com/pdf/Nestl%C3%A9_Health_Science_&_Am...