Nicotinamide Riboside: Benefits for Health Span and Lifespan

 

If you want to live a longer and healthier life, there are several factors that appear to boost your chances. These include regular exercise, getting enough sleep, shedding excess weight, eating a calorie-restricted diet, limiting alcohol consumption, and not smoking.1, 2

Certain nutrients have also been identified to play a role in the promotion of longevity, and one of these has recently been validated for its efficacy across numerous animal and human studies for the treatment of several age-related disorders.3

Growing scientific interest in nicotinamide riboside (NR) is currently underway with a significant number of clinical trials indicating a wide range of health benefits associated with many metabolic disturbances, neurodegenerative disorders, cardiovascular diseases, neural and cognitive functions, muscular and kidney injuries, and ageing.4

What exactly is nicotinamide riboside?

Nicotinamide riboside is a member of the vitamin B3 family but is quite distinct from the more familiar forms, such as niacin and nicotinamide.

The most notable difference between NR and other types of B3 vitamins is its ability to bypass a limiting biochemical step, thus increasing the production of a coenzyme vital for cellular health, known as NAD+. As an essential biological activator NAD+ is a critical cofactor for many metabolic pathways and is central to cell signalling and the production of ATP and cellular energy.

Research has also shown that NAD+ levels decline as a function of the ageing process, free radical damage, chronic inflammation, and excess consumption of calories. 6 - 9, 12
Consequently, maintaining NAD+ levels is a fundamental feature of longevity and offers an encouraging strategy for delaying the onset of ageing and improving healthspan.5, 14 - 17

NR can therefore play an important role in boosting blood levels of NAD+ to provide a range of benefits including promoting cellular energy, improving mitochondrial biogenesis and function, and promoting health span and life span extension.10

This is supported by research in which scientists noted that human blood NAD+ can rise as much as 2.7-fold with a single oral dose of NR. The same researchers also showed that blood levels of NAD+ increased proportionally with the dose of NR provided. 11

What happens when you take nicotinamide riboside?

Once consumed, NR is rapidly converted to NAD+ which acts as a much-needed cofactor for cellular energy production, DNA damage repair, immune functions, and gene expression.12

We know from animal studies that supplementing with NR can also improve muscle generation, cardiovascular function, and glucose metabolism as well as reduce cholesterol levels and neuroinflammation. 18 – 26, 31 – 33, 35

Human studies have demonstrated that NR increases NAD+ in skeletal muscle and exerts anti-inflammatory properties. These studies also revealed that, by increasing NAD+ levels, supplemental NR decreased protein damage, restored mitochondrial function, and reduced DNA damage associated with neurological disorders. 13, 29

Further human studies looking at cardiovascular risk factors have demonstrated NR supplementation resulted in a 2-fold increase in NAD+ with an associated reduction in blood triglycerides and glucose levels in type 2 diabetes patients.27 Other human studies resulted in decreased blood pressure, reduced aortic stiffness, lowered levels of circulating inflammatory markers and increased metabolic rate. 28, 29, 30, 37

An additional response to raised NAD+ levels is a corresponding activation of a group of enzymes called sirtuins. This family of signalling proteins appears to be associated with healthy ageing and increased lifespan by repairing damaged DNA, improving stress resilience, and reducing systemic inflammation. 38, 39, 40

NAD+ also plays a significant role in the production of another group of enzymes known as poly-ADP-ribose-polymerases (PARPs), which repair damaged DNA. Studies have indicated that higher PARP activity is associated with less DNA damage and a longer lifespan. 41, 42

Safety and tolerance

Regarding safety and side effects, NR has also proven to be the leading contender. When presented in any other form, including NA and NAM, these NAD+ precursors can cause painful flushing sensations, dizziness, or hypotension at therapeutic doses.50

NR has been confirmed across several studies as being well-tolerated, up to 2 g of a daily dose, and was not found to be associated with flushing or any such side effects 45, 51.

Bioavailability and stability of nicotinamide riboside

Compared to all other NAD+ precursors, NR is the best nutrient available in terms of bioavailability, safety, and ability to raise NAD+ levels. In addition, unlike other forms of vitamin B3, NR does not require any metabolic conversions to enter the cell, which could partially explain the high level of bioavailability.

However, while there are numerous human studies demonstrating that NR supplementation raises blood levels of NAD+, it has also been shown that NR is very unstable in circulation. This instability has been consistently observed by researchers and has resulted in wide fluctuations in body levels of NR across numerous studies. 43 - 45

Another contributing factor that may further explain the blood level variability of NR is its strong affinity for water. Unlike fat-soluble nutrients, such as vitamins A, D, E and K, which can enter the intestinal cells by simple diffusion, the hydrophilic nature of NR means it requires more complex transportation mechanisms that vary from individual to individual.45
It has also been proposed that NR can be degraded in the gut which might further explain low bioavailability in other tissues.46

Liposomal nicotinamide riboside for rapid and efficient absorption

Given that NR is unstable in blood and susceptible to degradation and poor absorption in the gut, the ideal form of this nutrient is one that provides rapid and efficient absorption and remains stable in circulation.

In recognition of these challenges, researchers developed a version of NR that is not only protected from the harsh environment of the digestive system but also rapidly enters the bloodstream in a form recognised by cells to ensure optimal bioavailability.

Liposomes are composed of a double layer of phospholipids, which are the same material that makes up our cells. And, just like our cells, they can self-organise into microscopic spheres. 47

These phospholipids have a water-loving head and a water-repellent tail, which allow them to safely transport both fat-soluble and water-soluble nutrients through the gut wall, into the bloodstream and then release them directly into cells where they are needed. 47

This form of encapsulation ensures that NR is protected from degradation and destruction in the gut and creates a stable delivery system with enhanced absorption.48

And because they are made up of the same phospholipid components as our cells, once a liposome has been passively absorbed into the bloodstream, it then fuses with cell membranes and delivers NR directly into the cell.49

The Bottom Line

There are several factors that contribute to the ageing process. One of these is the body’s decline in the production of NAD+, a critical cofactor responsible for energy metabolism and DNA repair.

Nicotinamide riboside (NR), when taken in liposomal form, can overcome issues associated with absorption and degradation, to boost NAD+ levels, which may reverse several signs of ageing.

 

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References:

 

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