Can NAD+ Precursors NR and NMN Make You Young Again?
Right now, the closest thing we have to a safe, accessible anti-aging pill are NAD+ precursors; namely, NR and NMN. Learn (and watch) how they can work to make you biologically younger.
THIS IS a story about how scientists learned about how NAD+ precursors, NR and NMN, might make you biologically younger than your chronological years. They have the potential to increase your healthspan, if not your lifespan, say these scientists.
NAD+ is a coenzyme found in all living cells, and vital to metabolism and hundreds of other biological processes. Unfortunately, it declines dramatically as we age and thereby can negatively impact our healthspan, those years in which we live healthily.
Healthspan is the key thing to focus on here. No one wants to live beyond the normal human lifespan if that means more years in a nursing home, but what about living as long as you can with robust health?
That’s what “healthspan” is all about. Wouldn’t be amazing if you became biologically younger than your chronological years, as is geneticist and age researcher Dr. David Sinclair?
In this article, you’ll discover:
Let’s dig in…
Sirtuins, The Gene-whisperer
Dr. Sinclair is 50 years old, does not have a single grey hair in his head, and his blood and genetic tests show that his biological age is 31.4, even though he’s a workaholic and hardly ever exercises. (1)
His secret? Dr. Sinclair has discovered a way to activate a type of protein in his body called “sirtuins”, and so apparently can you with either of two precursors that activate a gene called NAD+, short for the oxidized form of “nicotinamide adenine dinucleotide”.
The story of NAD+ and its precursors begins with the discovery of how sirutins can potentially turn back the aging clock.
Sirtuins — nicknamed “the longevity genes” — are a family of seven proteins that play a role in aging by controlling cellular health through regulating biological pathways, and turning certain genes on and off, thereby protecting cells from age-related decline.
Different types of sirtuins induce the formation of new mitochondria and keep up the length of telomeres (the end caps on DNA associated with longevity). Overall, sirtuins are relevant to obesity, Alzheimer’s, kidney disease, liver disease, inflammatory diseases, osteoporosis, and cancer. (2, 3)
Geneticist Dr. Amar Klar discovered the first siritun in the 1970s. He called it SIR2. In the 1990s, researchers found other genes that were similar in structure to SIR2, which were collectively named “sirtuins”. (4)
In 1991, one of Dr. Sinclair’s’ mentors, biologist Leonard Guarente (now Professor of Biology at MIT) worked with him, alongside of Dr. Brain Kennedy (now head of the Buck Institute for Aging) and Dr. Nick Austriaco (now Professor of Biology at Providence college) to identify SIR2 as a gene that promoted longevity, at least in yeast. Later, working mostly independently, Drs. Sinclair and Guarente discovered that coenzyme NAD+ was needed to activate SIR2.
Although their potential anti-aging effects are intriguing, a limiting attribute of sirtuins is that they can only function in the presence of NAD+. As Dr. Guarente puts it:
“Without NAD+, SIR2 does nothing”. (5)
And although that statement is correct, it turns out that NAD+ needs a push too via NAD+ precursors. But before we delve into that, a brief digression on calorie restriction (“CR”) is worthwhile.
CR, The Anti-aging Gold Standard
“Animals on a low-calorie diet tend to age more slowly”, says Dr. Guarente in an interview done by Elysium Health’s online magazine, Endpoints. Such animals stay healthier longer, and live longer.
The reason that it happens, says Guarente, is that under those conditions of a boom-bust cycle of food availability where oftentimes there was little or no food, an animal that evolved a mechanism to conserve energy by not reproducing and not aging as fast as normal would have a better chance than its neighbor of being able to reproduce and propagate the species if food came along at a later date. From an evolutionary perspective, this animal would have an advantage. That’s how evolution works.
“We think there is a mechanism for recognizing that food is scarce and slowing down aging under those conditions. It just so happens that our own research led us to own of the pathways that we think mediates the effects of calorie restriction. That is sirtuins. What we found in yeast, worms, flies, and in rodents is that SIR2 genes do deliver the benefits of calorie restrictions when activated.
“Calorie restriction sends the signal to upregulate the activity of sirtuins and they deliver the health benefits, including slowing down aging. That’s why we’re in a position now, I think, to be able to consider intervening in this process and to sustain health for longer by activating sirtuins. There’s a translational path to do that because of findings made by many labs across the world.”
Now that you have a better understanding about how sirutins can improve health outcomes and healthspan through the same biological pathway as does CR, let’s continue with their relationship to NAD+.
NAD+ — Your Cellular Powerhouse
If CR is the “gold standard”, than NAD+ is “the golden nucleotide”, which is how some scientists refer to it. Scientific American refers to is as the “linchpin of energy metabolism”. What everyone knows who has studied it, is that coenzyme NAD+ has become a prized molecule in recent years. This is so because of its central role in biological functions, the recent discovery that NAD+ levels decline in a wide variety of species (including humans) as they age, and its potential to positively affect human health through supplementation. (6)
NAD+ is vital to metabolism and hundreds of other biological processes. Imagine if sirtuins were a car, then NAD+ is the fuel and fluids that enable it to run. Just as a car cannot operate without fuel and fluids, your body can’t function without NAD+. The problem is that like many of our biological functions, the amount of NAD+ produced in our bodies declines over time.
NAD+ plays its vital role in our energy metabolism and proper cell functioning mainly through its effect on the functioning of our mitochondria, power plants in our cells that turn food and oxygen into energy.
NAD+ is critical to support the body’s response to stress, as NAD+ is used by these enzymes to modulate cellular activity in response to extrinsic and intrinsic assaults, including those triggered by environmental toxins, pro-inflammatory foods, microbes such as viruses and bacterium, trauma, disease, and even chronic use of medication.
NAD+ is essential for continued health, wellness, and strength – we cannot improve our healthspan without ensuring that our bodies produce enough amounts of this coenzyme.
Human clinical data is beginning to emerge about NAD+, but the majority of the science right now comes from animals studies. Studies show, among other things, that increasing NAD+ levels in mice can restore muscle function, enhance regeneration in the brain, and protect against the diabetic effects of high fat diets. (7)
That’s all well and good for mice, but what about us Homo sapiens? Turns out, human trails have been done and more are underway.
The aforementioned Dr. Guarente led a study of NAD+ in a clinical trail human trial in November 2017. It was a double-blind, randomized, placebo-controlled clinical trial, published in the peer-reviewed journal Nature Partner Journals: Aging and Mechanisms of Disease, and showed an increase NAD+ levels by an average of:
- 40% in adults taking 250 mg of NR (“nicotinamide riboside”), a NAD+ precursor similar to NMN and 50 mg of pterostilbene, a polyphenol found in blueberries; and
- 90% in adults taking a double dose — 500 mg of NR and 100 mg of pterostilbene. (8)
These results are eye opening – as in mice and men (and women too), the studies show that NAD+ seems to turn back the clock.
Boost Your NAD+ with NR and NMN
As I wrote at the start of this article, NR and NMN are NAD+ precursors. In biology a “precursor” is a chemical that is transformed into another compound, as in the course of a chemical reaction. An often used example is that cholesterol is a precursor of testosterone: one begets the other.
NR is short for “nicotinamide riboside”. NMN is short for ”nicotinamide mononucleotide”. They are the most potent precursors to NAD+. Between them, NR has been the most studied. Dr. Guarente’s supplement, Basis, is the one used in the human trials of NAD+ summarized above, and it has NR.
Dr. Sinclair, the man we began this piece describing as biologically younger than his chronological years, has done studies on both NR and NMN. Time Magazine reported on one of Dr. Sinclair’s research studies on NMN in its March 2017 edition titled, Scientists Can Reverse DNA Aging In Mice:
“Sinclair put drops of NAD+ into the water of a group of mice, and within a couple of hours, their NAD+ levels started to rise. Within the first week, the scientists saw obvious age reversal in muscle and improvements in DNA repair”. (9)
Apparently, both NR and NMN are effective at boosting NAD+, which then activates your sirutins to improve health outcomes and healthspan, but which one is better?
Currently, I don’t think the answer is known.
Due to the success of Elysium Health’s Basis (the supplement formulated by Dr. Guarente), it and its NR ingredient are the most prominent of the two precursors. The company and its product gets a alot of press, their human trail (rare for supplements) using their formuation garnered impressive results and on August 14, 2018, Elysium Health announced that Basis is now NSF International Certified for Sport.
Elysium wrote me about this last bit, and I quote:
“The rigorous evaluation process assesses numerous quality components to confirm that products do not contain any of approximately 270+ substances banned by major athletic organizations, including the NFL, MLB, NHL, and PGA. Building upon the independent testing standard product certification program developed by NSF International strictly for dietary supplements, NSF Certified for Sport helps athletes make safe decisions when choosing sports supplements and products.”
This is all great, and it’s why I’ve taken Basis for more than two years, but none of it means that its NR precursor to NAD+ is better than NMN.
In a December 2016 publication in Cell Metabolism, NMN was shown to effectively mitigate the age-associated physiological decline in mice. Without any negative effects, NMN suppressed age-associated body weight gain, enhanced energy metabolism, promoted physical activity, improved insulin sensitivity and plasma lipid profile, and improved eye function.
For the biological literate of you, know that in the study, NMN also prevented age-associated gene expression changes in key metabolic organs and enhanced mitochondrial oxidative metabolism and mitonuclear protein imbalance in skeletal muscle.
The scientists concluded:
“NMN is an effective anti-aging intervention that could be translated to humans.” (10)
This is also what Dr. Sinclair is now attempting to prove. In March 2017, a review of his work with an international, Harvard-led team of scientists confirmed that treating mice with the NMN improved their cells’ ability to repair DNA damage caused by radiation exposure or old age.
“The cells of the old mice were indistinguishable from the young mice, after just one week of treatment”, said Sinclair. (11)
So significant have been the results of these NMR studies on biological aging, that Dr. Sinclair is pursuing both human trials using the precursor and seeking to making NMR into a pharmaceutical drug, an worthy goal, perhaps, but one that will take years to create and get FDA approval.
Meanwhile, your biological clock is ticking, and it’s not ticking in reverse. Thankfully, you don’t have to wait for an NMN drug.
The Enhanced Bioavailability of NMN
How much of a drug or supplement actually enters your bloodstream is more important than the amount swallowed.
In the Harvard-led study referenced above, Dr. Sinclair’s team dosed the drinking water of the mice at 400 mg of NMN per kg of bodyweight. This equates to several grams per day in humans, which would be many times greater than recommended doses, as well a very expensive.
The bioavailability of both the NR and NMN precursors to NAD+ are restricted by the process of digestion and liver metabolism. (12)
An injected form of either NR or NMN is not tenable for most people, but a sublingual (under the tongue) formulation works great. The absorption of molecules delivered through the sublingual route can be three to ten times greater than the oral route, only surpassed by direct IV injection. (13)
Prohealth now offers a highly absorbable, sublingual form of NMN called NMN Pro that they claim is more bioavailable than both other forms of NMN as well as all NR-containing supplements. This supplement enables 125 mg of NMN to be absorbed into the blood vessels under the tongue and thereby avoid becoming dissipated in the gastrointestinal tract.
So far, the NAD+ precursor molecule NMN in sublingual form is the closest thing we have to a safe “anti-aging pill”. If that’s intriguing to you, try Prohealth’s brand new NMN Pro.
As mentioned, I’ve used Basis for more than two years and can not discern a difference in my health or overall well-being that can be attributable to it alone. But this is typical of my experience with supplements — I tend to take those that the science supports as efficacious, not just if I can tell a difference.
I have not tried Prohealth’s NMN Pro, although I intend to right away. My friend and Prohealth’s Founder, Rich Carson, tells me that the product has been useful to him, as it provides him a pronounced surge in energy that he needs given that his health is compromised by myalgic encephalomyelitis, the new term for chronic fatigue syndrome (“ME/CFS”).
I’ll report back to my Subscriber’s once I’ve had some experience with NMN Pro.
(Disclaimer: I’m an Elysium Health and Prohealth affiliate, which means if you buy Basis or NMN Pro from any of the links in this article, I get to buy a latte. This doesn’t affect what you pay whatsoever.)
Note: Cycle Your Supplements
Remember these four things:
- Sirutins are proteins that play role in aging by controlling cellular health through regulating biological pathways, and turning certain genes on and off, thereby protecting cells from age-related decline.
- NAD+ is a molecule needed to activate sirutins, and is vital to metabolism and hundreds of other biological processes. Unfortunately, it declines as we age, and without it we’re dead.
- Many studies, including a human trial, show that two NAD+ precursors — NR and NMN — can boost NAD+
- Two tested, credible supplment ingredients that, respectively, boost NAD+ are Basis and NMN Pro.