A Coda to the C60 in Olive Oil Saga
The matter of buckminsterfullerene (C60) in olive oil is an instructive example of how bad work can lead a field astray for some time, but is ultimately squashed. Back in 2012, a paper was published claiming a sizable effect on life span in rats via treatment with C60 in olive oil. There were red flags at the time: it was published in a journal outside the field of aging research, used a very small number of animals, and the size of the effect on life span was just too large to be credible. Peer review would have sunk this paper if submitted to an aging-focused journal. C60 is an antioxidant, so even if it is acting in the best possible way for antioxidants to act (i.e. targeting mitochondria while leaving the rest of the cell alone) it shouldn't be doing much better than other existing mitochondrially targeted antioxidants, many of which have a fair amount of published animal data to reference.
Unfortunately, one can't ignore large effect sizes, even when they are implausible and the study that produced them looks dubious. I said at the time that this was likely to go nowhere, didn't look good on the face of it, but nonetheless people were going to spend funds on trying to replicate it and dig into the biochemistry. It took a couple of years for those efforts to start up in earnest. The Methuselah Foundation funded some of this work, alongside Longecity and a few other organizations. The Ichor Therapeutics team carried out the heavy lifting. From the get-go, the work case doubt on the original paper, discovering that C60 in olive oil is quite challenging to formulate in ways that prevent toxicity. It took some years of working at the problem to carry out a reasonable animal study.
Now, eight years later, the results of that labor are published. As suspected, this is a dead end, and that initial 2012 paper looks the worse for someone taking the time to properly close the door on this line of work. This exercise illustrates why one should apply an appropriate level of skepticism to what one reads in the literature, and why journal boards should refrain from publishing data that lies outside their area of specialty. It also shows the self-correcting nature of scientific progress at work: replication is vital, as that is how errors are checked and removed once they take place. It takes far too long and costs far too much, but remains the least worst option.
C60 in olive oil causes light-dependent toxicity and does not extend lifespan in mice
C60 is a potent antioxidant that has been reported to substantially extend the lifespan of rodents when formulated in olive oil (C60-OO) or extra virgin olive oil (C60-EVOO). Despite there being no regulated form of C60-OO, people have begun obtaining it from online sources and dosing it to themselves or their pets, presumably with the assumption of safety and efficacy.
In this study, we obtain C60-OO from a sample of online vendors, and find marked discrepancies in appearance, impurity profile, concentration, and activity relative to pristine C60-OO formulated in-house. We additionally find that pristine C60-OO causes no acute toxicity in a rodent model but does form toxic species that can cause significant morbidity and mortality in mice in under 2 weeks when exposed to light levels consistent with ambient light.
Intraperitoneal injections of C60-OO did not affect the lifespan of CB6F1 female mice. Finally, we conduct a lifespan and health span study in males and females C57BL/6 J mice comparing oral treatment with pristine C60-EVOO and EVOO alone versus untreated controls. We failed to observe significant lifespan and health span benefits of C60-EVOO or EVOO supplementation compared to untreated controls, both starting the treatment in adult or old age. Our results call into question the biological benefit of C60-OO in aging.