Fight Aging!

There is a certain class of supplement manufacturer that follows the hype rather than the science: hype enables the ability to take cheap substances, obfuscate and market, and charge a sizeable premium. I think that the most offensive thing about the publicly available materials for the Leap Years supplement for dogs (referred to as LY-D6/2 here) is that they do not tell customers exactly what is in it. It is claimed to be some kind of vitamin B3 derivative to upregulate NAD+ and some kind of plant extract senolytic (likely fisetin or quercetin), both categories that have received a lot of attention in recent years.

On the one hand, pharmacological NAD+ upregulation is likely less effective than exercise. On the other hand, some senolytics are interesting, but many are only slightly senolytic. Of the well-known plant extracts, fisetin is interesting, but still lacking any published data in a species other than mice, while quercetin may be a component of the senolytic combination of dasatinib and quercetin, but is not meaningfully senolytic on its own. Given that Leap Years don't tell us which they are using, or how large the dose is, there isn't much that can be said about the prospects of the supplement strategy in advance. This is straightforwardly bad behavior on the part of this organization.

The only good thing I can find to say about this group is that they at least published the results of a study in dogs in the only significant benefit occurred in an owner-reported measure of cognitive function. There was no benefit to physical activity and frailty. One can draw no conclusions about any of this that are useful to the broader field because, again, we have no idea what is in this supplement.

A randomized, controlled clinical trial demonstrates improved owner-assessed cognitive function in senior dogs receiving a senolytic and NAD+ precursor combination

Age-related decline in mobility and cognition are associated with cellular senescence and NAD+ depletion in dogs and people. A combination of a novel NAD+ precursor and senolytic, LY-D6/2, was examined in this randomized controlled trial. Seventy dogs with mild to moderate cognitive impairment were enrolled and allocated into placebo, low dose, or full dose groups. Primary outcomes were change in cognitive impairment measured with the owner-reported Canine Cognitive Dysfunction Rating (CCDR) scale and change in activity measured with physical activity monitors.

This randomized controlled blinded trial is one of the first of its kind, evaluating an anti-aging supplement that targets two hallmarks of aging in senior dogs. This clinical trial used a pragmatic approach that included dogs with mild to moderate cognitive impairment who met age, weight and relatively broad health criteria. Dogs were followed to a primary endpoint at 3 months and a secondary endpoint at 6 months.

Fifty-nine dogs completed evaluations at the 3-month primary endpoint, and 51 reached the 6-month secondary endpoint. There was a significant difference in CCDR score across treatment groups from baseline to the primary endpoint with the largest decrease in the full dose group. No difference was detected between groups using in house cognitive testing. There were no significant differences between groups in changes in measured activity. The proportion of dogs that improved in frailty and owner-reported activity levels and happiness was higher in the full dose group than other groups, however this difference was not significant. Adverse events occurred equally across groups.