The Youth Restoring Benefits Of NAD+
By Scott Rahway
Since the year 2001, Life Extension® has been seeking a way to reverse a mechanism of aging that may not be adequately addressed by the healthy lifestyle choices most members currently follow.
Normal aging is accompanied by a noticeable increase in fatigue and loss of motivation. The tiredness we outwardly feel reflects inward impairment of cellular functions critical to sustaining life.
NAD+ is the term used in the scientific literature to describe a cellular compound called nicotinamide adenine dinucleotide.
NAD+ is found in every cell in the body and is essential to life.1,2 NAD+ enables the transfer of energy from the foods we eat to vital cell functions. It is also required to “turn off” genes that accelerate degenerative aging processes.3,4
As NAD+ levels decline, mitochondrial function is impaired, resulting in fewer mitochondria surviving.3,5 This vicious cycle of mitochondrial depletion results in many of the physical symptoms of aging.
The challenge we at Life Extension have faced over the past 13 years is finding an efficient way for aging humans to affordably boost their NAD+ cellular levels.
In 2001, one of our researchers developed an effective NAD+ boosting sublingual lozenge, but it only maintained stability for a short time period. As you’ll read in this article, an effective NAD+ cell boosting technology has finally become available.
Prominent universities have been investigating NAD+ as a potential therapy for age-related degenerative disease.6 Compelling research shows that NAD+ has a unique ability to protect tissues, induce DNA repair, and increase life span.2,7,8
It has long been known that NAD+ plays an important role in transferring energy released from glucose and fatty acids to the mitochondria so that it can be converted into cellular energy.2,9 Without sufficient NAD+, energy transfer in the cells breaks down, resulting in age-accelerating mitochondrial dysfunction.5,10,11
NAD+ is an essential cofactor of key enzymes responsible for longevity called sirtuins.5,12,13 While resveratrol is well known for sirtuin activation, evidence indicates it does so indirectly,14,15 whereas NAD+ directly activates sirtuins to regulate the genes of aging.2,16
Sirtuins, specifically SIRT1 and SIRT3, are intimately related to longevity through their control of gene expression and require NAD+ for their activity.2,3,10,17-19
Research into the sirtuins continues to yield substantial information on how to control aging. By activating these sirtuins, we’re able to gain control over one of our body’s anti-aging “switches.” SIRT enzymes “turn off” certain genes that promote aging, such as those involved in inflammation,20,21 in fat synthesis and storage,22,23 and in blood sugar management.3,22,23
SIRT enzymes are activated by calorie restriction, the proven means of reliably extending life span in all organisms.2,24 The way calorie restriction activates anti-aging sirtuins is by increasing cellular NAD+.2,25,26
Consequences Of Falling NAD+ Levels
NAD+ is found in every single cell in the body,1 and is essential for efficient energy transfer from foods to tissues. NAD+ is also required for turning off genes that accelerate aging.4
From a cellular energy standpoint, lower levels of NAD+ reduce mitochondrial function, with fewer energy-rich ATP molecules being produced, and fewer mitochondria produced.5,11 This vicious cycle results in many of the physical symptoms of aging.
The age-related decrease in NAD+ causes defects in both energy- and gene-related functions to accumulate. These defects feed on one another to produce the disorders we typically identify as aging.10 The consequences of a decline in NAD+ levels and subsequent reduction in SIRT 1 and SIRT 3 enzymes are:
- Neurodegeneration in the brain,10,27,28
- Vascular inflammation, producing damage to blood vessels that can result in stroke or heart attack, 27,29,30
- Increased fat storage in the liver, which can lead to nonalcoholic fatty liver disease (NAFLD),31-33
- Increased fat production and deposition in white adipose tissue, the primary fat storage form found in dangerous belly fat,34,35
- Insulin resistance, preventing cells from appropriately removing glucose from blood, producing higher blood sugar levels and leading directly to metabolic syndrome,30,36,37
- Fatigue, loss of muscle strength, and fatty infiltration of muscles, resulting in reduced fatty acid oxidation (“burning”), thereby depriving muscles of their normal sources of energy.38,39
To avoid these degenerative processes, it is essential that steps be taken to optimize the amount of NAD+ in our bodies.
By increasing intracellular NAD+ levels, age-related mitochondrial dysfunction can be reversed.5 One of the ways to accomplish this is by engaging in major calorie restriction, which has been proven to raise NAD+ levels and in experimental organisms tested to date, to extend life span.5,25 But most people find significant calorie restriction to be nearly impossible in practice.
Fortunately, a method has been developed to increase NAD+ levels without having to alter dietary patterns, though Life Extension remains a strong advocate of calorie restriction for those able to consistently do it.
A Natural NAD+ Booster
Researchers have discovered a form of vitamin B3 that converts in the body to NAD+.40,41
Vitamin B3 is involved in over 400 enzymatic reactions throughout the body and is essential for production and management of cellular energy.42 A new patented form of this vitamin called nicotinamide riboside has been found to increase NAD+ levels and in the process, provide an extraordinary range of longevity benefits that promises to change how we combat aging.
Directly boosting NAD+ with nicotinamide riboside presents a new and effective strategy for preventing the natural decline in cellular energy as we age by promoting youthful vitality.
Studies have shown that nicotinamide riboside switches “off” the genes of aging, extends life span, increases endurance, improves cognitive function, activates sirtuins, and enhances cellular energy.3,43 These benefits add up to a system-wide slowing and reversal of certain aging processes. Nicotinamide riboside accomplishes this NAD+ boosting effect without the irritating skin flushing and rash caused by the standard forms of vitamin B3.41
Initial Studies On Nicotinamide Riboside
In their investigations into the effects of nicotinamide riboside on life span, scientists used a strain of yeast known to have a relatively short average life span of about 8.3 generations.3,44 When the yeast was treated with nicotinamide riboside, the average life span nearly doubled, to 16.1 generations. On this model of life span extension, ordinary vitamin B3 had no effect compared to the dramatic longevity benefit shown with nicotinamide riboside.3
Nicotinamide riboside is a dynamic compound that works through multiple mechanisms to promote life extension. Most dramatic are its effects on longevity and metabolism, as shown by recent laboratory studies.
One critical mechanism in oxygen-consuming organisms is mitochondrial function.45 Mitochondria, the tiny, intracellular “furnaces” that power cellular processes, are sites of intense electrical and chemical activity.46,47 They can readily “burn out,” contributing to the aging of tissues, and hence, of organs and entire organisms.
In a model commonly used to study life span modifications, the roundworm C. elegans could be made to survive as much as 16% longer when supplemented with nicotinamide riboside. This life span extension was demonstrated to result from a roughly 50% increase in healthy mitochondrial oxygen consumption, a measure of mitochondrial efficiency.48
These benefits are what one would predict from nicotinamide riboside supplementation, which raises levels of the NAD+ needed to safely move electrons through the mitochondria.43 We have long known that ineffective mitochondrial electron transport is an age-accelerating process.43,49,50
When pursuing additional lab studies, scientists found that supplementing mice with nicotinamide riboside reduced many dangerous factors of aging. The mice showed increased energy and improved insulin sensitivity, both factors indicating optimal vitality. In this study, scientists also demonstrated that nicotinamide riboside supplementation increased energy metabolism while protecting the animals against the metabolic abnormalities induced by a high-fat diet.43 For the study, the mice were fed a high-fat diet with either no supplementation (control), or nicotinamide riboside for 12 or 16 weeks.
On a treadmill test, the supplemented animals fed a high-fat diet ran more than 33% further than the control mice, demonstrating a dramatic increase in muscle endurance and performance.43
The supplemented mice also gained significantly less weight while on the high-fat diet compared to control animals. And in supplemented animals fed either the high-fat or a normal diet, insulin sensitivity (the ability to remove sugar efficiently from the blood) was greatly improved, compared with control animals.
Remarkably, these results were all attained without any differences in food intake or total physical activity between supplemented and control mice.43 The supplemented animals lost weight, performed better at exercise, and managed their blood glucose better purely as a result of nicotinamide riboside-induced increases in calorie-burning (measured by increased oxygen consumption rates). This was confirmed by the observation that when the supplemented mice were exposed to prolonged cold conditions, they had significantly less body temperature loss compared to controls, the result of increased conversion of calories to heat.
Detailed analysis of the mice in this study revealed that supplementation with nicotinamide riboside had produced a significant increase in essential NAD+ levels, resulting in the activation of the critical life span-extending enzymes SIRT1 and SIRT3.43 Supplementation with nicotinamide riboside also improved the numbers and function of mitochondria, the intracellular powerhouses that release energy from food; poor mitochondrial function is a known age-accelerator.
Nicotinamide Riboside Protects Brain Cells
As cases of dementia and Alzheimer’s reach epidemic proportions in the aging population, pharmaceutical companies are aggressively researching brain protective compounds.51,52 Nicotinamide riboside with its ability to directly increase NAD+ is providing promising brain benefits.
A recent lab study demonstrated the ability of nicotinamide riboside to protect brain cells in advanced age.9 For the study, mice engineered to develop Alzheimer’s disease were treated with nicotinamide riboside beginning at middle age (5 to 6 months) and lasting into old age (10 to 11 months).
The supplemented animals had significant improvements in their cognitive function in challenging laboratory tests of exploring new objects.9 This improvement was shown to be associated with significantly reduced brain levels of beta-amyloid plaques, the abnormal protein that triggers much of the neuronal death and dysfunction in Alzheimer’s disease. Intriguingly, supplementation had the added benefit of raising levels of the metabolic regulatory complex called PGC-1-alpha. Studies have shown that low levels of PGC-1-alpha have been associated with increased dangerous beta-amyloid deposition.9
The mechanisms by which these effects were achieved were found to include significant increases in brain levels of NAD+ (the result of supplementation with nicotinamide riboside), and consequently activated enzymes involved in cellular energy production and energy release from glucose.9
In a similar study of neuroprotection, nicotinamide riboside was shown to delay the degeneration of axons, the “communication cables” of nerve cells that carry impulses over long distances.53,54 When these communication cables deteriorate, tingling, weakness, numbness, and loss of motor function can occur as a result.55-57 The mechanism behind this benefit was shown to be a significant 20-fold increase in the enzyme that converts nicotinamide riboside to NAD+.54
Other studies in mammalian cells in culture demonstrate that nicotinamide riboside treatment increases NAD+ concentrations inside of cells by up to 2.7-fold,58 and that administering nicotinamide riboside can improve NAD+ related deficiencies in animal and yeast cells.24