While it is common to measure age chronologically, research is establishing that biological age is a better marker to determine the length of ones healthspan. This is because our biological age can be influenced by many components including genetics, lifestyle, and disease. A recent study published in Aging (DOI: https://doi.org/10.18632/aging.203736) demonstrated that Rejuvant, a timed-release CaAKG (calcium alpha-ketoglutarate) with vitamins, is a potential life-extending formulation. After seven months of use, Rejuvant decreased the biological age of participants by an average of eight years, in the TruAge DNA methylation test.

Brian K. Kennedy, Ph.D., one of the lead authors of the study noted that the results suggest that Rejuvant is an intriguing candidate to affect human aging and that the results are encouraging for increasing health span in both men and women.

Tune in to hear about: 

• How Rejuvant supports healthy ageing
• What frequency and dosage provides the most benefit?
• Which demographics respond best to healthy ageing supplementation
• Strategies to extend health span

Guest: Dr Brian Kennedy, Professor and Director of the Centre for Healthy Ageing, National University of Singapore

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Welcome to the Vitafoods Insights podcast. Join us as we explore the latest science and innovation, helping the global health and nutrition industry connect, develop, and progress. Today's host is Ajay Paul, graduate fellow.

Hello and welcome to another Vitafoods Insights podcast episode. Today we'll be talking about Rejuvant®, a potential life extending compound formulation with alpha ketoglutarate and vitamins. I'm delighted to be joined by Dr. Brian Kennedy. Dr. Kennedy earned a PhD from the Massachusetts Institute of Technology and has established an international reputation for his work in the fundamental biology of ageing. He's currently Professor and Director of the Centre for healthy ageing at the National University of Singapore. Thanks for joining me today, Dr. Kennedy.

Anytime, it's my pleasure.

I thought we could kick things off with an overview of this supplement. Could you describe for us what is Rejuvant®? In terms of maybe its ingredients or formulation? And what do we know about the supplement, in terms of how it works, and how it supports healthy ageing?

It derived from studies and animal models. And so it started off with a collaborator Gordon Lithgow at the Buck Institute, and we were looking for combinations of natural products that extended lifespan in worms. And then we took those combinations and tested them in mice. Surprisingly, we got different effects in male and female animals. And so, in males, what we found is that alpha ketoglutarate plus a low dose of vitamin A was really beneficial in reducing frailty. But in females, it was alpha ketoglutarate, plus a low dose of vitamin D. So AKG's in both, but we use different vitamins for the gender specific component of the supplement. And another thing I should point out is that the time released nature of this is very important, we think that the mechanism of action, particularly AKG, involves getting the supplement to the intestines. And so we have a slow release formulation, and Rejuvant® that allows it to be released slowly over a 12 hour window as opposed to all of it getting released in the stomach and being lost. So that's taken a lot of work to go into that. In terms of mechanism, you know, we're still sorting that out, we see all kinds of beneficial effects of AKG, including improved adult stem cell function, improved metabolism, altered microbiome, and changes in the DNA methylation patterns. So we're trying to sort out which of those are the primary effects of AKG, and which might be secondary effects right now.

Amazing. And I did look at a recent study that was published by you. And it did mention an effect on the biological age. Could you speak more to that?

Yeah, so we used a triage DNA methylation test, which looks at the relative DNA methylation of several sites in the genome. And this DNA methylation patterns are probably the best biomarkers of ageing right now. There have been many different clocks of ageing that have been derived from that. So instead of chronologic ageing, we're measuring what we call biologic ageing. And, you know, by looking at people of the same age that chronologically that they look like they're ageing at different rates. It's been very hard to measure that until recently, and now we have methods where we think we can do that. So we had 42 people that were buying the Rejuvant® product, and they took the methylation test at time zero, and then again, an average of seven months later, and they found they could reverse their DNA methylation age by about eight years. Now, I have to give you some cautions for this study. This is not a placebo controlled study. This is a retrospective study of users. And we're doing those placebo controlled studies now. So we thought it was important to publish this data because it's a very interesting observation, but it's not a full on clinical trial yet. And so we have to wait for those results.

Yeah, amazing, very interesting results from that. But it's interesting as well, that you're still looking at other trials to do to sort of solidify the findings you found. So in terms of the supplement and dosage and frequency, what sort of is the ideal dosage and frequency you take to see these benefits?

We suggest two pills a day, which is, I think it's a gram of alpha ketoglutarate, which is a relatively low dose. It's very possible that higher doses might be more beneficial, and we're testing that now in animal models, but I would not encourage people to do that at the moment because we haven't got that test back yet. This is a very safe molecule, though. It's been tested in very high dose and other clinical studies with no toxicity profiles. It's called grass, it's generally regarded as safe, as are the vitamins in the product, so we don't foresee any safety issues, but we don't know what the optimum dose is yet to impact ageing, and we're doing those kinds of dosing studies now with animals.

Is there any information about when these benefits might start to saturate and it turns into more maintenance? Or has that not been investigated as of yet?

We don't know when the saturation might be. And so we need to do more time duration studies in animals to see if things continue to get better, or if it saturates at some point. Part of ageing interventions like rapamycin, it's a drug that's been tested in animal models, it does saturate and extends lifespan of mice about 15% to 30%, but you can't get higher than that. So it's possible that this will saturate. It's also possible that if you stop taking it, the biologic age may revert back. So we don't know the answer to that question yet, either. So there's still a lot to be learned. But we're really excited about what we've seen so far.

Okay, thanks. In terms of demographics, I know you mentioned that there is a slight difference with gender. Is there differences in maybe in terms of age, that would have an impact on the supplement? And maybe there's certain ages that would benefit more from taking this and others?

Yeah, this is a very interesting question. With all ageing interventions right now, whether you can intervene very late in lifespan, or you have to do it early or middle age. And we're still doing this for all the different potential longevity factors out there. Again, in the study that we published, we saw that people that were chronologically older, responded better. And among younger people, those people that were biologically older than their chronological age, at the starting point. In other words, this assay is correct. They're not ageing that well, they're the ones that responded better as well. So they may be that people that are later stages, respond better to the supplement. And I don't know if that will be true of this supplement, or all in ageing interventions. It's still so early in the human studies that we don't have a lot of answers yet. But that's what appeared to be the case for the Rejuvant®, is that, those people that were further along the process responded better.

Currently this project rejuven whereabouts geographically? Is it available in at the moment? And are there any targeted geographies coming up?

So the Rejuvant® product is available online at the moment, so it's definitely available in the United States. I think it can be shipped to Europe as well. And we've just started supplying it in Southeast Asia. There's an attempt to bring it to other international markets as well, and that's proceeding as fast as possible.

You did mention that Rejuvant® was quite a safe substance to take. Do you know of any sort of regulatory challenges in any markets about just the formulation of this product? Or is it just regularly known as being quite safe?

Well, it's generally regarded as safe. And so in the US, that means it can be used in products. Different countries have different rules and regulations. And in some cases, if a product's not actively being developed, it'll be taken off the safe list, and then you have to petition to put it back on. And so I'm not the person that's looking at all the different countries and territories. It's been approved in Singapore recently, I know that, and I expect that it will be considered safe in all markets, but everyone has their own regulations right now so.

What sort of advice or strategies would you recommend to someone who's looking to extend their health span? it doesn't have to be specifically with supplements, but in general sense.

Your mother told you something worth listening to: eat right, exercise, get your sleep and maintain stress levels at a reasonable level. I mean, this works. And she may not have given you all the details on it, but she had the right idea. So if you can maintain a sustainable cardiovascular exercise programme with a little bit of resistance training, eat a diet that is not too high in calories, and preferentially is relatively low in animal protein, if you can manage your stress levels so that you're not stressed all the time, and if you sleep well as you get older, which is a little bit harder to control yourself, but it's important. Those are all things associated with healthy longevity or increased health span. I think these supplements are exciting because they may have impacts on their own as we're starting to see. But ideally, you're going to want to take supplements along with having a healthy lifestyle to get the maximum effect I suspect in the end. So even though pills might be coming online, it doesn't mean you shouldn't you know, pay attention to, I mean, a healthy approach to life as well.

Yeah, of course, it's not supposed to be a one fix all kind of thing. You got to take steps in your own life, that's what you're saying, through all these different avenues for health nutrition and healthy ageing and all of that.

I think the exciting thing though, is we're getting to a point where we're understanding the pathways that modulate ageing. And if you're a mouse, we've got you, we already know how to extend lifespan. But most of people listening are not mice. So I suspect that we need to get a lot more validation in humans, both with supplements and drugs. But you can see from studies like this Rejuvant®, and others that are beginning done that I think we're on the right path, and in the near future, I suspect it will be possible to really impact the rate of biologic ageing, which is an exciting possibility.

Definitely is. Before we wrap things up, do you have any final thoughts you'd like to share about Rejuvant® or healthy ageing with our listeners?

I just would point out that, you know, while this is still not a clinically completely controlled study with placebo group, it's pretty exciting findings. And this is a safe product. And we think it's having an impact. It really depends on where you are in this process. If you want to wait till all the validations done, that's fine. If you want to be an early adopter and try and see what happens, I think it's a safe thing to try. So it's up to you.

Amazing. Well, thanks again, Dr. Kennedy, for coming on today and sharing all these great insights about Rejuvant®.

Thank you. Thanks for having me.

Thank you, also to our listeners for tuning in. If you're interested in learning more about Rejuvant® make sure to check out the hyperlink available in the shownotes. And if you like our show, make sure to subscribe, follow the Vitafoods Insights Podcast and feel free also to recommend the show to any friends or colleagues you think would like it. Thanks for tuning in and see you soon.

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