Life Extension Magazine®

Scientist taking sample DNA after adding NAD+ for energy

New Resveratrol and NAD+ Suggestions

Resveratrol promotes longevity by activating proteins called sirtuins. For sirtuins to function, they require the coenzyme NAD+. Maturing people can derive considerable benefit by taking more NAD+ precursors with modest dose resveratrol. NAD+ is vital for youthful cell function including DNA repair.

Scientifically reviewed by Dr. Gary Gonzalez, MD, in August 2023. Written by: William Faloon.

William Faloon
William Faloon

NAD+ is a coenzyme found in all living cells. It is essential for energy production and DNA repair.1-3

In 2014, we introduced a NAD+ precursor called nicotinamide riboside.4 When you take nicotinamide riboside, it converts to NAD+ in your cells, where it facilitates regenerative processes.5

The most important NAD+ benefit is promoting rapid DNA repair and fueling beneficial longevity proteins.2,3,6,7

Resveratrol favorably enhances the activation of cellular sirtuin proteins.8 NAD+ is required for our sirtuins to function.7,9,10

As we age, NAD+ levels plummet, which impedes the ability of resveratrol to deliver its benefits.11-14

In 2003, we introduced resveratrol based on its ability to activate sirtuin longevity factors.15,16

Genetic research we conducted back then indicated that biologically meaningful resveratrol dosing for humans might be as low as 20 mg a day.16,17 Subsequent studies suggested higher resveratrol intake.18,19

Based on our interpretation of emerging evidence, we have reformulated our premium supplements to provide more NAD+ precursor (nicotinamide riboside) with lower resveratrol.

You’re going to learn about potential age-reversal benefits of boosting cellular NAD+ later this year. This article will provide a summary of what’s been uncovered in recent published studies.

NAD+ is required for healthy cellular functions including DNA repair.1-3

The amount of damage inflicted to cellular DNA is grossly underestimated. Be it background radiation or normal metabolic processes, our DNA is constantly “broken” and then “repaired” using specialized coenzymes like NAD+.

Failure to repair damaged DNA can result in cell death or transformation into malignant or senescent states.

NAD+ levels markedly decline with age.11-14 NAD+ deficit manifests clinically in the form of degenerative disorders of the brain,20-23 heart,24-26 and other tissues.27,28

In animal studies, regenerative effects have been observed in the brain when NAD+ is restored.29,30

Sleep quality deteriorates with normal aging in many people. Restoring youthful NAD+ levels in the brain may support a healthy circadian rhythm.31

Loss of NAD+ activity is linked to type II diabetes. In mice, administration of an NAD+ precursor restores insulin sensitivity and protects against the diabetic impact of a high-fat diet.6,32,33

Resveratrol and NAD+

Image with Caption

Resveratrol has become a popular dietary supplement because of its ability to activate sirtuin proteins in our cells.34

When sirtuins are activated, the effect is delayed aging, which has been demonstrated in a wide spectrum of experimental models, including mammals.35-44

Sirtuins that are activated by resveratrol require NAD+ as their energy substrate. Loss of NAD+ impedes beneficial sirtuin function.7,10,45

Younger people have high NAD+ levels that enable them to benefit from the sirtuin-boosting effects of resveratrol.

To improve the functionality of sirtuin proteins, it makes sense for maturing individuals to boost their NAD+ levels.

The good news is that a precursor to NAD+ can be found in nicotinamide riboside supplements. New dosage recommendations can enable older people to restore cellular NAD+ to more youthful profiles.

NAD+ Benefits More Than Just Sirtuins

The favorable effect of resveratrol in promoting sirtuin activity is well established. For sirtuins to function properly, they must have sufficient NAD+ to fuel their activity.7,10

Protecting against pathological aging, however, requires more than securing sirtuin structure-function. We must also ensure the following two types of DNA damage are repaired:

  • Single-strand DNA breaks occur often and are usually fixed by nutrients that most of you supplement with today.
  • Double-strand DNA breaks are more difficult to restore. Left unrepaired, double-strand breaks create cellular havoc that can lead to systemic degeneration.

A critical enzyme that repairs double-strand DNA breaks is PARP1.46-48 For the PARP1 enzyme to function it requires lots of NAD+.49,50

When it comes to protecting against cancer, a tumor suppressor called p53 protects against runaway cell propagation.

NAD+ supports p53 activation to help thwart malignant transformation.51-53

Nutrients That Facilitate DNA Repair

People seeking to extend their lifespans today avoid toxins (such as tobacco smoke and overcooked food) that damage DNA.

Vitamin D has been shown to play an important role in DNA repair, which helps explain why people with higher levels of vitamin D show lower rates of most degenerative diseases.70,76-78

Folic acid also plays a role in maintaining certain DNA repair mechanisms.79-85

Many of the supplements we take daily help facilitate DNA repair. The box below provides a partial listing of these nutrients.

Up until now, no nutrient could accelerate DNA repair to the magnitude needed to induce possible age-reversal benefits. That may have changed based on data showing remarkable DNA repair occurring when the amount of NAD+ (nicotinamide adenine dinucleotide) is increased in our cells.3,86

DNA Repair Activators

Fish Oil87-89 Vitamin B1290 Vitamin E91 Vitamin C92 Nicotinamide86
CoQ1093 Zinc94 Magnesium95,96 Selenium97 Polyphenols98-100
Grape Seed Extract101,102 Curcumin103,104 Carotenoids105-107 Vitamin B6108,109  

Magnitude of Daily DNA Damage

Image with Caption
Damaged DNA

Few people understand the degree of daily damage inflicted to their cellular DNA.

To put this into perspective, a study analyzed how many double-stranded DNA breaks occur per cell each day. The number turned out to be 10 DNA breaks per cell every day.54

Your cells require NAD+ to facilitate repair of DNA breaks. Sufficient NAD+ is needed for the PARP1 repair enzyme to function.49,50,55

Imagine every dividing cell in your body undergoing ten double-stranded DNA breaks per day and NOT being repaired because your NAD+ is depleted from aging, or from outside abuse such as excess alcohol and toxic food ingestion.

It explains many degenerative pathologies that occur as aging cells lose their NAD+.

Repairing DNA breaks will probably go a long way towards preventing cells from turning malignant. That’s because NAD+ helps maintain activity of cell division regulators like p53.51-53

Restoring Youthful Cell Functionality

Restoring Youthful Cell Functionality  

As we age, beneficial genes that support cell health “turn off” while detrimental genes overexpress.

Nutrients like curcumin help suppress genes that generate system-wide inflammation.56-59

Likewise, omega-3s60-66 and vitamin D67-70 favorably impact hundreds of genes that protect against degenerative illnesses.

To reverse the accumulation of damage inflicted to cellular DNA, we should support the efficient function of PARP1 enzymes.

PARP1 facilitates DNA repair via multiple mechanisms.

Higher NAD+ cell levels enable PARP1 to function properly.49,71,72

Aging creates a chaotic environment in the brain that can make sound sleep difficult.73 As DNA is repaired, we regain youthful cell functionality that can result in improved overall health.

Combining resveratrol with more nicotinamide riboside supports healthy cellular NAD+ levels,73 which are important to support anti-aging enymes like PARP1 and BubR1.71,74,75

BubR1 is an enzyme that protects against chromosome instability. According to one study, sustained high-level expression of BubR1provides a unique opportunity to extend healthy lifespan”.75

Some of you may find these new acronyms like PARP1 a bit confusing.

I hope you appreciate (as I do) how rapidly our understanding of aging is expanding, along with accessible ways to reverse many degenerative changes.

Boosting Your NAD+  

Take Control by Boosting Your NAD+

George Church, PhD, is a Harvard professor pioneering CRISPR/Cas9 gene editing technology.110,111

Once perfected, Dr. Church has publicly stated that this will enable aging humans to “edit” their genes in a way that will empower them to regain youth.

We’ve reported on Dr. Church’s research in past issues of Life Extension Magazine®.110,111 This age-reversal gene-editing technology is predicted to be perfected in the next 5-10 years.

In the meantime, we can exert significant control over cellular health factors by taking more nicotinamide riboside. This will boost NAD+ blood levels several fold.5

How our genes are expressed and their stability determines whether we retain healthy vitality or suffer relentless degeneration.

Nutrients like curcumin,112,113 fish oil,60-63 folate,114-116 and vitamin D70,117-119 promote youthful genomic stability.

The box below displays additional benefits one can obtain by boosting cellular NAD+.

This can be accomplished by supplementing with 250 mg each day of nicotinamide riboside that converts to NAD+ in your body.

We may recommend higher nicotinamide riboside doses in coming months as scientific data emerges.

For longer life,

For Longer Life

William Faloon, Co-Founder
Life Extension Foundation
Buyers Club

What Should Cancer Patients Being Treated With Chemo or Radiation Therapy Do?
Cancer Patients

Cancer chemotherapy drugs function via several destructive mechanisms, but the ultimate objective is to inflict massive damage to DNA so that cancer cells are destroyed. Radiation does this by directly breaking DNA strands.

One way cancer cells escape complete eradication after exposure to chemotherapy or radiation is to repair damaged DNA via a wide range of survival mechanisms.

Some studies suggest adding “DNA repair inhibitor” drugs might enable conventional chemo/radiation therapies to kill more cancer cells.

The downside to DNA repair inhibitors is they might increase the toxicity of chemo/radiation therapy to healthy cells and thus create more serious side effects. To cite a conclusion from a published study on this topic:

“With the addition of DNA repair inhibitors, standard chemotherapy could become more effective but also more toxic.”120

What the above conclusion alludes to is that adding drugs that impede DNA repair might make chemotherapy more effective, but in the process make the chemotherapy more toxic. A major limiting factor to chemotherapy is toxicity so severe that patients are forced to discontinue therapy even when it is demonstrating efficacy.

For example, one of many toxic side effects of chemotherapy is painful neuropathy.121-124 Cancer patients who take steps to boost their NAD+ levels have experienced relief from fatigue.125 Animals given nicotinamide riboside experienced reductions in chemotherapy-induced neuropathy.126

Another side effect of certain chemotherapy drugs and radiation to the chest is heart failure.127-132 Nutrients like coenzyme Q10 have been shown to protect against this cardiac damage133-135 and improve survival in cancer patients.136-139 Conventional oncologists are largely unaware of this clinical research.

As it relates to supplementation with higher-dose nicotinamide riboside, we’ve reviewed numerous published studies and it is not possible to reach a rational consensus as to what actively-treated cancer patients should do as it relates to boosting their cellular NAD+.

Out of an abundance of caution, we suggest cancer patients undergoing chemotherapy or radiation avoid higher-dose NAD+ during therapy and for a reasonable period after.

The conundrum cancer patients have faced for decades are arguments from many oncologists to take no supplements during chemo/radiation therapy. The concern is the nutrients might protect malignant cells from destruction.

Opposing this conventional view are numerous studies demonstrating that nutritional and herbal supplements do not interfere with the effectiveness of chemotherapy or radiation therapy. Furthermore, a myriad of controlled studies show marked survival improvements when cancer patients supplement with nutrients that boost immune function and protect against treatment side effects.140-159

Stated simply, malignant cells can preferentially “hijack” many of the same factors healthy cells require for survival. There is thus a delicate theoretical balance as to what cancer patients should do during conventional treatment. For updated guidance on nutrients, hormones and off-label drugs that actively-treated cancer patients should consider, refer to our updated protocols at:



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