How does the body produce NAD+?

NAD+ can be synthesized from dietary sources like tryptophan and niacin (Vitamin B3). However, the primary source is through a recycling mechanism called the NAD+ salvage pathway, which regenerates NAD+ from byproducts.

What are NAD+ boosters like Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN)?

NR and NMN are precursors to NAD+ that are available as supplements. Animal studies show they can raise NAD+ levels and potentially ameliorate age-related decline, though human data is still emerging.

What are the potential benefits of NR and NMN shown in animal studies?

In animals, NR and NMN have shown potential to improve metabolic health, insulin sensitivity, endurance, reverse mitochondrial damage, and benefit brain function, including neurogenesis and cognitive decline.

Does NMN or NR supplementation come with any cancer risks?

One study showed NMN accelerated cancer growth in mice with a specific type of pancreatic cancer driven by senescent cells. While this doesn't mean NR or NMN cause cancer in general, it highlights a potential concern in specific contexts.

What are the challenges in translating animal study results on NAD+ boosters to humans?

Key challenges include the high doses used in animal studies which are often much higher than what's tested in humans, and questions about bioavailability – whether these boosters can reach all necessary tissues directly and effectively across the blood-brain barrier.

What does current human research say about NR and NMN supplements?

Human studies on NR show it can increase NAD+ levels in white blood cells and potentially affect blood pressure. No published evidence exists for oral NMN supplementation in humans yet. Overall, more long-term studies are needed.

Is direct NAD+ supplementation via injection a viable option?

Direct NAD+ injection has shown some promise in raising NAD+ levels in specific tissues like the brain and heart in mice. However, its bioavailability is poor orally, and its effectiveness and safety via IV in humans are largely unexplored.

NAD+ in Aging: Role of Nicotinamide Riboside and Nicotinamide Mononucleotide

FoundMyFitness

Science & Technology3 min read31 min video

Jan 28, 2020|669,845 views|16,887|1,383

NAD+nicotinamide riboside nicotinamide mononucleotide nmn nr senescence SASP senescence-associated secretory phenotype metabolism aging longevity healthspan

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Key Moments

TL;DR

NAD+'s decline with age impacts health. Boosters like NR & NMN show promise, but human data is limited.

Key Insights

NAD+ is vital for cellular energy, DNA repair, and activating longevity-related sirtuins.

NAD+ levels naturally decline with age, contributing to various hallmarks of aging.

Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are popular NAD+ boosters.

Animal studies show NR and NMN can ameliorate age-related decline and improve health markers.

Research suggests caution regarding NAD+ boosters and cancer growth, particularly in specific contexts.

Human studies show NR can increase NAD+ levels in blood cells, but long-term effects and optimal doses are unclear.

THE ESSENTIAL ROLE OF NAD+ IN CELLULAR FUNCTION

NAD+ is a critical molecule essential for life, playing a central role in energy metabolism, DNA repair, and activating sirtuins, which are key regulators of health span and longevity. Its involvement in redox reactions is fundamental for producing ATP, the cell's energy currency. Furthermore, NAD+ is a cofactor for PARP1, an enzyme crucial for repairing DNA damage, and for sirtuins, which control gene expression involved in metabolic processes and stress responses. Without sufficient NAD+, cells cannot maintain proper energy production or genomic stability, leading to a cascade of age-related dysfunctions.

NAD+ DEPLETION AND ITS CONNECTION TO AGING

NAD+ levels significantly decrease with age across various tissues, particularly those with high metabolic demands like the brain, muscle, and heart. This decline is linked to numerous hallmarks of aging, including mitochondrial dysfunction, impaired glucose metabolism, and increased DNA damage. The reasons for this depletion are multifaceted, involving both decreased synthesis and recycling capabilities alongside increased consumption due to chronic inflammation and heightened DNA repair demands. This reduction in NAD+ predisposes organisms to age-related diseases and a general decline in physiological function.

NAD+ BOOSTERS: NICOTINAMIDE RIBOSIDE AND MONONUCLEOTIDE

Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) have emerged as popular supplements marketed as 'NAD+ boosters.' These molecules are precursors that can be converted into NAD+ within the body. While found in trace amounts in some foods, their efficacy and safety at supplemental doses are primarily supported by animal studies. These studies suggest that high doses of NR and NMN can effectively raise NAD+ levels and potentially reverse or mitigate various age-associated physiological declines in rodents, impacting metabolic health, endurance, and even cognitive function.

PRECLINICAL FINDINGS AND THE CANCER CONUNDRUM

Extensive animal research indicates that NR and NMN can offer significant health benefits, from improving insulin sensitivity and endurance to reversing mitochondrial damage and muscle atrophy. They have also shown positive effects on brain health in animal models. However, a critical concern arises from a study showing that NMN can accelerate pancreatic cancer growth in mice, particularly in contexts where senescent cells drive tumor progression. This suggests a potential caveat for NAD+ boosters in specific cancer types, although it does not necessarily imply that these supplements cause cancer universally.

TRANSLATING ANIMAL DATA TO HUMAN APPLICATION

Translating the promising animal data to humans presents several challenges. The doses used in many rodent studies are exceptionally high, often requiring oral doses equivalent to several grams per day for humans, and in some cases, injections rather than oral administration. Furthermore, questions remain about the bioavailability and tissue distribution of NR and NMN. While they may enter the liver effectively, their direct transport and conversion to NAD+ in other tissues, especially the brain, is less clear, with much of the conversion potentially relying on the salvage pathway, which has its own regulatory limitations.

INITIAL HUMAN CLINICAL TRIALS AND FUTURE DIRECTIONS

Early human clinical trials, primarily focused on NR, have demonstrated its ability to increase NAD+ levels in white blood cells and whole blood in a dose-dependent manner. Some studies suggest potential benefits for blood pressure and liver enzymes, though it's difficult to attribute these solely to NR. However, NR and NMN have not shown effects on metabolic function or exercise capacity in humans to date. Crucially, long-term safety and efficacy studies in humans are lacking. While the data is encouraging, further research is required to fully understand the optimal dosing, long-term effects, and safe application of these NAD+ boosters in human populations.

Mentioned in This Episode

●Supplements

●Concepts

Common Questions

NAD+ is a crucial molecule for life, vital for energy metabolism, DNA repair, and activating longevity-related proteins like sirtuins. NAD+ levels naturally decline with age, contributing to many aging hallmarks and age-related diseases.

Topics

Nicotinamide Mononucleotide Energy Metabolism Preclinical Studies Human Trials

Mentioned in this video

supplementNicotinamide Mononucleotide

Another NAD+ precursor and 'NAD+ booster'. Animal studies suggest health benefits in metabolic health, heart function, and cognition. A study also showed it accelerated cancer growth in a specific context.

conceptNAD+ Salvage Pathway

The predominant pathway for NAD+ production, involving the conversion of nicotinamide into nicotinamide mononucleotide and then NAD+. This pathway is subject to feedback inhibition by NAD+.

conceptPARP 1

An enzyme crucial for DNA repair that requires a large amount of NAD+ for activation. Higher PARP 1 activity is correlated with increased lifespan in mammals.

supplementNiacin

Vitamin B3, found in foods like lean meats and vegetables. Its three forms (nicotinamide, nicotinic acid, nicotinamide riboside) can be used to synthesize NAD+.

supplementPterostilbene

A natural compound found in blueberries, similar to resveratrol, that activates sirtuins. It was included in one human study with nicotinamide riboside and showed potential effects on blood pressure.

supplementNAD

A crucial molecule for life, involved in energy metabolism, DNA repair, and sirtuin activation. Its levels decrease with age, contributing to hallmarks of aging.