In a rare appearance, Chromadex Founder and current Executive Chairman Frank Jaksch joined the “Cellular Health: The Next Big Market Opportunity“ webcast last week to discuss NAD, Nicotinamide Riboside “NR” (FAQs) (Anecdotes), NMN (FAQs and Anecdotes), aging and more. According to his bio, Jaksch is not your ordinary Executive Chairman. He currently oversees research, strategy, and operations for ChromaDex, with a focus on scientific and novel products for the pharmaceutical and nutraceutical markets. During this webcast, Jaksch had a lot of substantive things to say. As a result, we’re posting a transcript of his entire ~10-minute presentation.

Frank Jaksch, Executive Chairman at Chromadex (Remarks begin at the 33:50 mark of the webcast):

Aging Explained

“By 2050, the world’s population aged 60 years and older is expected to total 2 billion, up from 900 million in 2015. 

The average life expectancy for Americans is approaching 80 years now.

People today may be living longer.

However they are NOT living healthier as they age.

So, let’s start by looking at the World Health Organization’s definition of aging:

“At the biological level, aging results from the impact of the accumulation of a wide variety of molecular and cellular damage over time.“

What that really means is that cellular damage or dysfunction IS aging.

Chronological vs Biological Age

If we really want to start getting a grip on what aging is, we need to start looking at “biological age” vs. “chronological age” — which really means we need to look at physiological markers or bio markers to assess age, not time.

There was a great study that was published in 2015, the “Quantification of Biological Aging in Young Adults”, by Belsky et al. which followed 1000 young adults from their birth in 1972-73 to the age of 38.

What their data showed is that most participants’ biological age was close to their chronological age. However many of them looked older and many looked younger, at least biologically.

What I found even more interesting from that study was that the signs of biological aging going wrong started in their mid to late 20s.

9 Hallmarks of Aging

Another landmark publication in 2013, “The Hallmarks of Aging”, which is one of the most heavily cited publications in aging research today, established the 9 main areas of cellular function that become dysregulated with age.

These hallmarks are:

  1. Genomic instability
  2. telomere attrition
  3. epigenetic alterations
  4. loss of proteostasis
  5. deregulated nutrient sensing
  6. mitochondrial dysfunction
  7. cellular senescence
  8. stem cell exhaustion
  9. altered intercellular communication.

Our main interest over the last few years with NR (“Nicotinamide Riboside“) has been mitochondrial dysfunction.

However, mounting evidence has linked compromised NAD+ status to the hallmarks of aging.

A 2017 review showed that NAD plays a central role in all 9 hallmarks of aging.

Cellular Health, Aging and NAD deficiency

From a cellular health, aging, and NAD deficiency standpoint, we lose up to 50% of our NAD+ levels between the ages of 40 and 60.

As we age, NAD production becomes disrupted or is disrupted.

More on that later.

Also, as we age, NAD demand increases with increased cellular repair activity.

And there’s a lot of published research that has shown now that almost all cellular repair mechanisms are highly NAD dependent.

A simple way of looking at this is basic supply and demand.

As NAD supply is decreasing with age, the demand for NAD is increasing — primarily from the increased cellular repair.

Eventually there won’t be enough NAD to supply cellular energy metabolism and cellular repair.

So what this means is that NAD+ deficiency is a nutrient deficiency of aging.

NAD+ Levels Are Not Constant

So, if we look at NAD beyond the cell and we look at NAD levels decrease in diseases and conditions, we can see that NAD declines.

There are now hundreds of peer reviewed published studies that show NAD levels are dysregulated in many diseases or conditions.

If we look at NAD with aging, the upper left side of this slide, we can also see that NAD declines in most tissues associated with research that’s published on aging.

However, the most active areas of research are liver, kidney, heart and brain.

ChromaDex has developed an extensive external collaborative research program we call CERP to organize and sponsor this type of research.

What sets Nicotinamide Riboside (NR) apart from other precursors?

Until Dr. Charles Brenner who was at Dartmouth at the time identified the unique NRK pathway for utilizing NR in 2004, there were 3 known pathways to synthesize NAD.

One is the The De Novo pathway which uses Tryptophan.

There’s the Preiss-Handler pathway which uses Nicotinic acid.

And the salvage pathway which uses Nicotinamide.

All 3 of these pathways are knocked down with cellular stress or age, which disrupts NAD production.

What sets NR apart from these other NAD precursors, is that while these other pathways are being knocked down, the NRK pathway is upregulated.

That means that cells are seeking NR to rescue or restore NAD production.

So NR is uniquely positioned especially in damaged cells to restore NAD production.

Nicotinamide Riboside (NR)

Nicotinamide Riboside (NR) is a ribose derivative of niacinamide.

NR is present in the food supply.

It is a naturally occurring metabolite in milk.

However it is only found in trace amounts.

So, diet alone will not provide enough NR to provide a meaningful benefit to restore disrupted NAD production.

Through the NRK pathway discovered by Dr. Brenner, NR is converted to another precursor, Nicotinamide Mononucleotide or NMN.

You may have been hearing about NMN.

I will talk more about that at the end of this presentation.

200+ Preclinical and Clinical Studies

Since ChromaDex launched NR in 2013, we have seen a tremendous amount of interest in the research community on NR as an NAD precursor.

Since 2013, ChromaDex has signed up over 200 collaborative preclinical and clinical research studies with prestigious universities worldwide.

This research program has led to hundreds of peer review published science on NR as a highly effective NAD precursor.

As a result, there are now over 50 clinical trials completed or ongoing which are posted on ClinicalTrials.gov.

So, outside of the interest we’re seeing in the consumer products side of things, there’s been a tremendous amount of research on NR coming from these collaborative studies.

200 of these over the latest 6 or 7 years is a pretty incredible number.

ChromaDex KGK Study

I’ll highlight one of those.

Separate from that collaborative research, ChromaDex has also made significant investments in clinical research on NR.

The first large clinical trial we did with KGK, which was published in Nature Scientific Reports was an 8-week, randomized, double-blind, placebo-controlled study in 140 healthy overweight adults supplemented with three different daily doses.

So we did 3 doses of 100mg, 3 doses at 300mg and 3 doses at 1g.

And we looked at the kinetics and dose-dependent effects of chronic Niagen or NR supplementation.

On average, study participants consuming 300 mg/day experienced a statistically significant 51% increase in whole blood NAD+ within two weeks. And that increase was maintained throughout the remainder of that eight-week study.

The 1000 mg/day dose led to a 142% increase in NAD+ levels which was also sustained through the remainder of the study.

The study also further validated the safety and efficacy when used consistently over time.

The results of this study directly support the NAD-boosting efficacy of NR.

That has also been validated in probably more than 10 clinical trials that have been completed on Nicotinamide Riboside (NR).

NR vs NMN

As I mentioned before, you may be hearing about another NAD precursor called NMN.

There is a lot of highly misleading information going around about NMN.

NMN is the phosphorylated metabolite of NR

Despite what you may be hearing — our opinion and others — there is no known transporter for NMN.

What does that mean?

The only way NMN can enter the cell is that it’s converted into Nicotinamide Riboside (NR) by an enzyme called CD73.

So, if you wanted to take NMN as a supplement you would have to take more than 600mg to be anywhere near equivalent to 300mg dose of NR.

Other shortcomings?

There’s very little published clinical research on NMN to date.

NR has been successfully notified in the US by the FDA with both GRAS and NDI.

NMN has not.

It’s also been notified successfully in many other countries including the EU.

NMN has not.

So, our stance on this is as long as there is a cost effective supply of NR, there is no reason to take NMN especially with the risks out there — considering that there’s very little if any safety data or clinical studies to substantiate it so far.”

RELATED:

  • FAQs on taking NAD boosting vitamin supplement Nicotinamide Riboside (NR) can be found HERE.
  • NR supplementation may have helped sufferers of these diseases & conditions (Consumer Reviews)

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