Thanks to a recent article in Time Magazine, Nicotinamide Riboside and NAD replenishment are getting a lot of attention. Because I have been taking NR for 18 months, and have been following the science closely, I will attempt to explain in lay terms what the fuss is all about, and why I tell all my friends and family over age 50 to take Tru Niagen.
I don’t know whether I want to live forever.
But I know that I don’t want to grow old right now.
So anything that helps resist the symptoms of aging
is something I care about.
The maladies of aging are many and varied — hearing, eyesight, nerves, muscles, skin, memory, and more. It doesn’t feel like one thing goes wrong; everything goes wrong, in an across-the-board cascading collapse.
The First Clue
The first clue that aging might have a central cause is that some animals, by doing a single thing, live longer. That single thing is fasting. Eating less helps many animals live longer, from yeast to worms to monkeys.
Could there be a unified cause of aging — something so fundamental that it works the same in very different types of animals?
The Second Clue
The second clue that aging has a central cause is a much stronger hint, and it comes from some very rare genetic diseases.
In Hutchinson–Gilford progeria syndrome, Werner syndrome, and Cockayne syndrome, genetic defects lead to premature aging, including symptoms like from hardening of the arteries, hair loss, joint stiffness, glaucoma, hearing loss, osteoporosis, and more.
Although in each of the three conditions a different gene is affected, what they share in common is that the broken gene plays a role in DNA repair.
This kind of evidence supports DNA Misrepair-Accumulation Aging Theory, which proposes that aging results from a buildup of DNA errors. if your cells’ DNA repair mechanisms are broken, the same symptoms of aging occur, just a whole lot sooner.
But What About Healthy Individuals?
This raises the question of whether even in healthy individuals there is something that impairs the DNA repair process over time — something that could be treated.
Plus, there is the mystery of calorie deprivation. Is it possible that calorie restriction somehow stimulates or strengthens the body’s natural DNA repair mechanisms? And if so, could there be another way to strengthen the DNA repair mechanisms, something that mimics the effect of calorie restriction, but without the misery?
Some whales and sharks live hundreds of years, and their cells aren’t that different from ours, except that the long-lived species have better DNA repair mechanisms. “Aging is a program,” says commenter Bill Walker, “written into the DNA memory in each of our cells…Rewrite the program…and you re-write the health span.”
Into the Cells!
The final piece of the puzzle involves the cell mitochondria, which generate the energy that cells need to do their work and to fight off stresses — including the stresses that damage DNA, like toxins and radiation.
Your mitochondria — ALL mitochondria — are powered by a molecule called NAD — Nicotinamide Adenine Dinucleotide. It looks like this:
Although our food contains NAD, the NAD in our food gets broken down into things like Nicotinamide (NAM), which our body then must salvage back into NAD.
But as we age, our ability to salvage NAM into NAD declines, and, worse, the reverse starts to occur — the processes that churn NAD into NAM increase!
The result is that NAD levels throughout the body are reduced when we get older. Reduced NAD levels means that all kinds of cells — skin cells, nerve cells, muscle cells, organ cells — run out of the energy they need, not only to do their job in the body, but also to defend against stresses, like radiation, temperature, and toxins that can harm the cell’s structure or DNA.
Moreover, NAD is also required for the activity of an enzyme called PARP, which is important for DNA repair. We saw earlier that DNA repair is crucial to health pspan. Recent data show that neurons accumulate mutations with age, and PARP activity would counteract this. As DNA damage accumulates, PARP consumes more NAD, making it less available to sirtuins.
That means that NAD holds two keys to cellular health — the energy to protect against stresses as well as the ability to repair any DNA damage that does occur.
So if NAD levels drop, the inevitable result is increasing damage to our cells, which we experience as aging. But the cellular damage resulting from aging is only inevitable if we can’t find a way of replenishing our declining NAD levels.
Happily, vitamin precursors offer our body an alternative way of making NAD as the NAD salvage pathway becomes less effective.
The big breakthrough occurred in 2004, when Dartmouth researcher Dr. Charles Brenner discovered that waning cellular NAD levels can be replenished by giving the cells access to a related substance, Nicotinamide Riboside, or NR, which gets turned into NAD.
NR is the most valuable of the vitamin precursors because:
1) NR can be used in every cell and tissue (unlike tryptophan and Niacin),
2) A high dose NR does not cause flushing (like NIacin),
3) A high dose NR does not inhibit sirtuins (like NAM),
4) The capacity to use NR does not decline in aging (like NAM),
5) Stressed cells induce the NR pathway.
NR is a natural substance; it is a form of Vitamin B3. It is found in milk, but only in very minute quantities (you’d have to drink 75 gallons of milk per day to end up with all the NAD you need).
Soon scientists discovered a stable form of NR that could be orally ingested, and a way to mass produce it.
A small lab company called ChromaDex licensed Dr. Brenner’s patents, and in 2013 first made NR available to the public as “Niagen.”
The availability of Niagen allowed researchers around the world to begin studying the effect of NR supplementation on a range of age-related maladies. Over 120 studies are underway to better understand the effects of NR on immune systems, heart health, cognition, physiological function, neurological health, metabolic health, cancer, Alzheimer’s, and more. You can read about some of those studies here.
The Early Results Have Been Stunning:
The Scripps Institute found that NAD replenishment with Niagen halted the progression of breast cancer and strongly reduced metastasis.
The National Institute on Aging determined that NAD replenishment with Niagen prevented and even repaired Alzheimer’s in mice.
The University of Iowa showed that NAD replenishment with Niagen protected against heart disease.
Dr. Brenner’s teams also showed that NAD replenishment protected against neuropathy caused by diabetes and chemotherapy (at least in mice and rats).
Should My Friends and Family Take It?
Every day we hear about new discoveries that turn out to be nothing. For example Resveratrol was hailed as a wonder drug to prevent aging, but then it turned out to have poor bioavailability when ingested — in other words, the resveratrol you ate never made it past your stomach and did little for your cells.
The questions for potential early adopters of Niagen are
(1) Is it safe, and
(2) Does it work?
The answers appear to be yes.
What we know about safety is that — like the other B vitamins — it is a natural substance, generally recognized as safe by the FDA. B vitamins are water-soluble, so they do not accumulate in the body like fat soluble vitamins A and E. Human testing of Niagen showed no adverse effects or toxicity below 1,000 mg per day.
As for effectiveness, we know from human studies that ingesting NR increases NAD availability to cells, and that if you take more NR then more NAD becomes available.
What we do NOT know yet, because the human studies have not been done — and it will take a decade to work out all the details — is all the different age-related maladies that may be mitigated or eliminated by NR. We don’t know the optimal dose, or how that changes with age, or how much it varies by individual. We also don’t know the conditions that will decrease the efficacy (e.g., maybe NAD replenishment improves insulin-resistance, but only for high-fat diets and not high carb diets, or vice versa). Similarly, NR appears to defeat breast cancer, but maybe not all breast cancers, but also maybe some other types of cancer — we don’t know yet.
We don’t ever know all that happens when we take a nutritional supplement. Vitamin C is an anti-oxidant, but the precise threat from oxidation in any particular individual at any particular time is unknown. We simply understand that the Vitamin C is likely be helpful should trouble arise.
The trouble we face with NAD depletion depends on our age. If we are younger, we probably don’t have a problem. If we are older, we probably do have a problem.
And failing to replenish depleted NAD could result in many of the worst symptoms of aging, including neurodegenerative diseases like Parkinson’s Disease and Alzheimers.
NR supplementation is currently the most effective and easily available method for replenishing NAD.
So the potential benefits are enormous, and the potential costs are modest — far less costly, anyway, than the kinds of expensive medicines that get deployed when things really go bad, like the cost of chemotherapy drugs or the drugs used to control Parkinson’s disease.
That’s why I strongly and frequently urge all of my friends and family over 50 to try Niagen.
Q: Should I take Tru Niagen or Elysium Basis?
A: I recommend Tru Niagen, because I don’t trust Elysium as a company, and I don’t like their business model. I am a former Elysium Basis customer.
However, the nicotinamide riboside in Elysium’s Basis appears to be the same as the nicotinamide riboside in Tru Niagen, so they probably have the same effect, although we don’t know for sure, because there is no known toxicological testing on Basis, and Basis also includes pterostilbene, which is itself a mixed bag because pterostilbene offers some benefits, but may also elevate cholesterol.
Q: What about NMN — Nicotinamide Mononucelotide — instead?
A: NMN is another NAD precursor, and so it might have an effect similar to NR. However, it currently appears be more expensive, less available, and far behind in the clinical studies, so we don’t know lots about potentially subtle yet important differences (e.g., variations in sirtuin activation).
Also, NMN has a phosphate on it that has to be removed (yielding NR) before it can elevate NAD. So NR is also a more direct way of accomplishing this.
However, over time a wide variety of NAD precursors may emerge, and research may show some of them to be more effective and less expensive.
Also, superior combinations might emerge. For example, pterostilbene and the NR appear to work synergistically. And a common antioxidant flavonoid called Quercetin may inhibit an enzyme (CD38) that destroys NAD.
It’s a good thing to watch whether NMN or some other alternative, or some combination, eventually replaces NR as the best method of replenishing NAD.
Q: You have taken it, so what was your experience?
A: Niagen cured two chronic conditions I suffered from, Restless Legs Syndrome (RLS) and Irritable Bowel Syndrome (IBS). That’s why I got excited about it. I also just feel generally better, but that is hard to measure with precision. Others I know have seen an end to leg cramps, and bruise less easily, or otherwise have improved skin.
I own shares in ChromaDex, the company that makes Niagen, although I have no official role with the company.
Anyone who believes that ChromaDex might own patents on a Fountain of Youth could be forgiven for wondering whether they should consider buying a piece of the company. It is an unusual opportunity, since most tiny companies with big dreams are privately held, and so normal people can’t buy shares.
ChromaDex probably wishes that it WERE privately held, because by becoming a public company it exposed itself to a number of significant risks, such as hostile takeovers and short attacks, which have in fact left the company embroiled in costly litigation.
One company, Elysium Health, which allegedly concocted a “nefariously conceived plan” to significantly harm ChromaDex has, among other things, attempted to have some of ChromaDex’s patents invalidated, presumably so it could sell ChromaDex’s product without having to pay for it.
Whether ChromaDex eventually succeeds or fails as a company is not a sure thing, and depends on many factors, such as the quality of their intellectual property, their ability to defend against pirates, how the science evolves with NR, and whether comparable or better alternative methods of elevating NAD emerge. So I don’t particularly recommend that anybody enter the high-risk world of microcap nutraceuticals.
But regardless of whether being a ChromaDex shareholder is a good thing, I feel pretty certain that being a ChromaDex customer is a good thing.