Rejuvant published a study in which an epigenetic clock showed reversal of age in people who take their supplement (R). 

This supplement contains alpha-ketoglutarate (AKG), vitamin D for women, and vitamin A for men.

Alpha-ketoglutarate is one of the 12 ingredients in our longevity supplement NOVOS Core, and given we follow all developments regarding alpha-ketoglutarate closely, we were very curious about this study!

First, a quick primer about alpha-ketoglutarate

Alpha-ketoglutarate, also called alpha-ketoglutaric acid, is a very interesting substance for longevity with a lot of science supporting its benefits.

Alpha-ketoglutarate has shown to extend lifespan and healthspan in multiple species (R,R,R,R,R), and has been associated with improvements in aging-related diseases and health in humans, like protecting organs against damage (R,R,R,R,R) and improving bone health in women (R,R)

Alpha-ketoglutarate’s health and longevity effects are due to multiple mechanisms.

For example, AKG helps to maintain a healthy epigenome by acting as a substrate for epigenetic enzymes (TET enzymes).

Alpha-ketoglutaric acid can also improve mitochondrial health and metabolism. AKG protects stem cells against aging and improves bone and gut health.

We find there is a lot of good science supporting AKG as a longevity supplement, and that’s why we have added it to NOVOS Core, along with 11 other powerful longevity substances.

In NOVOS Core, we use a dose of alpha-ketoglutaric acid (1100 mg), which is a bit higher than the dose of AKG in Rejuvant’s supplements (1000 mg). 

We also added various longevity ingredients that work synergistically with AKG, like vitamin C (which is also a substrate for the same TET enzymes that AKG targets), glycine and pterostilbene. 

Learn more about AKG and its impact on aging and longevity here.   

A quick primer about epigenetic clocks 

In this study, an epigenetic clock was used to measure aging. 

Epigenetic clocks try to measure people’s biological age. Everyone has a chronological age (the age on your passport), but if you live unhealthy for example, you will be biologically “older” (i.e. age faster), and will therefore have a higher biological age. 

Epigenetic clocks look at many different parts of the epigenome to determine one’s real biological age. But what’s the epigenome? 

The epigenome determines which genes are active or inactive. One way the epigenome achieves this is by methylating specific parts of the DNA. 

Methylating means that small molecules (methyl groups) are put on the DNA, so that this DNA becomes inactive. 

Epigenetic clocks see if there is a methyl group in hundreds if not thousands of different places in the DNA. From this pattern, algorithms can estimate your biological age. 

You can learn more about the role of the epigenome in aging on this page. 

We also wrote about epigenetic clocks here.

So what about the Rejuvant study?

In this study, 42 individuals were given the Rejuvant supplement for an average period of 7 months.

According to the researchers, people who took AKG were on average 8 years younger. That’s a lot! In fact, it’s way too much according to all the epigenetic clock experts we spoke with. 

Firstly, the epigenetic clock that was used in this study, TruAge from TruMe, is not a very accurate epigenetic clock.

The median absolute error (MEA) is 4 years, as compared to much better epigenetic clocks available that have MEAs around 2.5 to 2.9 years. The R-squared (also a measure of accuracy) is 0.59, which is not good; ideally it should be higher than 0.90. 

Furthermore, this TruAge (TruMe) clock has not made its algorithm publicly available, so scientists have no way of testing how their clock works and if it works. We just have to take their word for it. 

Ideally, Rejuvant should have used an epigenetic clock of which the algorithm is publicly available, and that has been used by other, independent scientists which have further validated and published about the clock in their research. One example could be a recent version of the Horvath clock.

Additionally, in this study, saliva was used for the epigenetic clock measurements. This means people’s saliva was collected with a swab, and the epigenome of cells found in saliva (e.g. epithelial cells) was analyzed.

However, saliva is less accurate than blood for epigenetic clocks. The most accurate epigenetic clocks are blood-based ones, which analyze the epigenome of cells present in the blood.

As the researchers point out themselves, the study didn’t have a placebo-controlled group. For these kinds of studies, it’s important to have a placebo-controlled group.

The placebo effect should not be underestimated. If people are told that they are taking a pill that could improve their health, they may become healthier, whether the pill works or not.

The placebo effect can be very powerful; it can lower blood pressure, lead to a few pounds of weight loss, improve cholesterol levels — all without any “active” ingredient.

Conclusion 

An average reduction of 8 years is too good to be true. This “age reversal” has been measured with an inaccurate epigenetic clock that also has not been checked and validated by other scientists.

Furthermore, there was no placebo group to compare with. 

However, this study is a great start for supplement companies that take science in high regard, and that use science-based ingredients, as opposed to many other supplement companies that still use antioxidants, herbs or other substances that don’t slow down aging. 

It’s  great that Rejuvant wants to use scientific methods (like epigenetic clocks) to further corroborate their formulations.

However, we believe that there are more accurate epigenetic clocks that should have been used. And more importantly, we believe there are many more interesting longevity substances besides alpha-ketoglutarate, such as fisetin, pterostilbene, glucosamine, low-dose lithium, and others to slow down aging. 

Furthermore, it’s important not to use one main anti-aging ingredient, but use multiple substances that act on multiple aging mechanisms simultaneously and in a synergistic way. 

After all, aging is a complex process caused by many different mechanisms, and addressing just one or a few of them is not going to make a sufficiently large dent in the aging process. 

That is why we created NOVOS Core, the first longevity supplement containing 12 ingredients that work together to slow down aging acting on at least 10 aging mechanisms. 

Learn more here.