Rhonda: I mentioned before we started filming, I mentioned to you a pretty recent randomized controlled clinical trial with vitamin D supplementation in a population that started off unhealthy. So, these were obese African Americans, which were very low in vitamin D. African Americans tend to be the lowest in vitamin D because they have a natural sunscreen. And so, they were given 4,000 IUs of vitamin D a day and after, I can't remember how long the trial was, a certain period of time, their epigenetic clocks were measured at baseline and after, and their epigenetic clocks, Horvath, the Horvath Clock was used, it basically was reduced by 1.8 years or something like that. And you mentioned the significance is a little...the sample size is small, and so it's kind of like, well, it's a start.

Steve Horvath: I mean, it's an exciting finding. I think it was based on 51 people, and it's a nice finding. It would be brilliant if a simple intervention as taking a vitamin D supplement actually affected the epigenetic age. I agree with the authors. We just need larger studies to validate it, you know, but in general, as you know, clinical trials are very expensive and that's a real bottleneck in all sorts of anti-aging interventions. We really wish, on the one hand, private industry would find merit in investing in clinical trials. Obviously, also the government plays a role, but what we really need is really dozens if not hundreds of clinical trials. Why? Just to have a chance for serendipity. Maybe it is as simple as a vitamin D supplement, but maybe you need something much more radical like, for example, a modification of the Yamanaka cocktail, you know. Or it could be plasma transfusions or so, you know. We as a field need to experiment, you know, with what kind of interventions work. It could be hormones, by the way, you know. It could be a hormone intervention, and so on. 

Rhonda: When you mention, obviously, do you see...? I'm going to change topics here, but I don't want to because, you know, the intervention trials are important. As you mentioned, it may have some effect, it may not have a big effect. But, you know, even if a combination of factors like, you know, getting your fish intake, which you've shown to also...seems to be related to...

Steve Horvath: Yeah. Interestingly, according to GrimAge, we did find that people who used omega-3 supplements of fish oil, they were actually aging more slowly, and we thought this was a nice little insight. 

Rhonda: Oh, that's interesting because I take fish oil supplements.

Steve Horvath: Me too. Because what happened is, I want to say six months ago, there was a publication, really very large-scale clinical trials looking at fish oil supplementation, and they did not observe any benefits. And I said, "Oh, my God, I wasted all these years eating fish oil." But then we analyzed really an observational study, and that's our problem, our study was an epidemiological study, I want to say the Women's Health Initiative, and there we did see this association that women who took fish oil supplements were aging more slowly according to GrimAge, you know.

Rhonda: Wow. And I'll just add a note to that study. You mentioned the big VITAL D study, which was a vitamin D and omega-3, a huge study. There was no effect on the primary outcome, which was looking at all combined cardiovascular-related events. However, when you specifically looked at like heart attack versus stroke, there was a strong effect.