Dr Charles Brenner, the developer of the intellectual property behind ChromaDex’s Tru Niagen, on all things metabolism, NAD and NR clinical trials.
Longevity.Technology: Following the launch of the Longevity.Technology supplements report, we caught up with Dr Charles Brenner to ask for his take on how longevity supplements could contribute to healthy aging and whether the longevity supplements that you can take today could be making verified health claims in the future.
Check out our video interview with Dr Brenner:
Dr Charles Brenner on…
Metabolism and NAD:
When most people think about metabolism, they think about it as the food you eat as the input and the energy (ATP) that you get out as the output. That is maybe only about 20% of the metabolism. Metabolism is a conversion of everything that we eat into literally everything that we are. Every molecule in my body was made by the metabolism … It turns out there are four NAD coenzymes, and they are responsible for transferring the electrons that makes it all possible. So this really is the key to life.
Aging puts metabolism under attack:
Back in the time I used to give seminars in person I would ask for a show of hands: how many people would like to hop on a flight to Ibiza? In this scenario you might be leaving from somewhere in North America, travelling across many time zones, spending the day sitting out in the sun, listening to loud music, eating a lot of food and drinking wine late into the evening. Everybody would raise their hand. Every single one of those things; the noise, the overeating, the alcohol metabolism, the sun, the air, the time-zone disruption, every single one would disturb the NAD system in multiple different ways.
And the recovery process requires NAD. Whether NAD directly declines from aging or episodically due to incidents of metabolic stress? I do not know the answer to that question. There are a lot of people out there that just say NAD declines with aging. I am not so sure about that. I think that it is secondary to inflammatory processes and metabolic insults.
Aging as a disease:
I personally do not consider aging to be a disease, I consider it to be correlative with disease complications. I do consider aging to be something that we are all hopefully enjoying and that we are maintaining our resiliency as much as possible. But I think that trials should be based upon repair resiliency, anti-inflammation, and other things that are quantifiable.
Clinical endpoints for NAD and NR:
It comes from what we and others initially did in rodents. For example, when you overfeed a mouse, and you can make a mouse fat and diabetic in something like eight weeks, you can treat that mouse in eight weeks. If you do that in a mouse you get better glycaemic control, it controls its fatty liver, and it even preserves the diabetic nerve so that the diabetic nerve damage does not get any worse and might even be fully protected. There are positive results in rats on chemotherapeutic neuropathy, there is positive results in mice and various mitochondrial diseases, and protection noise induced hearing loss.
All this rodent data is hypothesis generating in terms of human clinical trial activity … There is a placebo-controlled trial that includes NR, amongst three other supplements, that shows much faster recovery to COVID-19 in Turkey. So there is a lot of clinical trial activity, but the question is what are going to be the endpoints that will allow us to, in the future, be able to make health claims that are not just promotional and that are very evidence based.
Making health claims as a supplement:
So, there is a bottle that says Tru Niagen and it says that there are no health claims, right? It is not for a disease or a condition. Consumers take Tru Niagen because they have read about it and the amazing things it does in rodents. We have shown it is safe in humans and that is has promising activities, potentially in lowering blood pressure of people that have moderately elevated blood pressure. People try it and may personally experience better recovery times, you know, feel better in work outs. Going forward what ChromaDex needs to do really is wait for sufficient data from peer reviewed, placebo controlled, clinical trials that would allow us to make health claims.
The benefits of taking NR instead of NMN:
NR is a nucleoside. Nucleosides go into cells and nucleoside kinase put a phosphate on. When the phosphate is put on inside cells NR is turned into NMN. NMN then has one more biosynthetic step to turn into NAD. And then one more step to turn into NADP. Some people have proposed NMN as an NAD precursor vitamin. It is not a vitamin because it has a phosphate on it. Compounds with phosphate do not go into cells. So, you go to a lot of trouble as a chemist to put the phosphate on in order for the phosphate to have to be removed by cells anyway.