INTRODUCTION

The latest research articles & scientific papers on NMN (nicotinamide mononucleotide) and NAD (nicotinamide adenine dinucleotide).

WHAT IS NMN (NICOTINAMIDE MONONUCLEOTIDE)?

NMN is a nucleotide derived from ribose and nicotinamide.

NMN is a derivative of niacin - a form of vitamin B3, an essential human nutrient.

People have enzymes that can use NMN to produce NAD.

RESEARCH SUMMARY

  1. NMN enters cells via newly discovered pathway
  2. Rewinding the clock with NMN
  3. NMN: impairment of and endothelial NAD+ - H2S signaling is a reversible cause of vascular aging
  4. NMN: improves blood flow similar to exercise - by promoting sirtuins
  5. Long-term administration of NMN mitigates age-associated physiological decline in mice
  6. NMN inhibits JNK activation to reverse Alzheimer disease
  7. NMN reduces signs of aging in healthy mice
  8. Cardioprotection by NMN: involvement of glycolysis and acidic PH
  9. NMN, a key NAD+ intermediate, treats the pathophysiology of diet – and age – induced diabetes in mice
 

1)  NMN enters cells via newly discovered pathway

ABSTRACT

A scientific study (Nature Metabolism 9 Jan 2019) showing how NMN enters the cell becoming NAD+ without converting into NR.

The NAD+ coenzyme is fundamental to combat age-related diseases

NAD+ naturally declines with age in animals and humans.

This decline contributes to many age-related diseases and metabolic conditions.

leafscience.org/nad-transporter-identified/

 

2)  NMN:  rewinding the clock

ABSTRACT

NMN can restore 

  • Blood vessel growth
  • Muscle vitality
  • Can boost exercise endurance in aging animals

 

Harvard Medical School discovered

NMN restored blood vessel growth in mice   

“If we are as old as our arteries…
 Could reversing the aging of blood vessels
 be the key to restoring youthful vitality?”

harvard.edu/news/rewinding-clock

 

3)  NMN: impairment of endothelial NAD+ - H2S signaling is a reversible cause of vascular aging

NMN prevents the decline of physical endurance and muscle strength.

NMN: EXPERIMENT ON AGING MICE

The natural decline in capillary density and blood flow causes mortality and morbidity. 

cell.com/cell/fulltext/S0092-8674(18)30152-1

David Sinclair - senior author and co-director of the Paul F. Glenn center for the biology of aging at Harvard Medical School - states:

 

“Loss of blood flow seems to be one of the early things that leads to diseases of aging(..)
As organs like the brain and muscles lose their [blood] perfusion,
they no longer function effectively.”

 

Mice were given NMN to stimulate the formation of tiny blood vessels in cells that form the muscle.

As a result, the mice given NMN were:

  • FASTER ON THEIR TREADMILL RUN BY 60% compared to the other animals who did not get the molecule.
  • HAD DOUBLE THE EXERCISE ENDURANCE AND STRENGTH.

cell.com/cell/fulltext/S0092-8674(18)30152-1

 

4)  NMN: Improves blood flow similar to exercise - by promoting Sirtuins:

“Here we have the potential of having
a pill which gives the benefits of running 10 miles a day
without having to do that(..)
It’s not just about trying to replace exercise when you are middle-aged,
but giving you the benefits of exercise when you are too old to be able to do it.”

 – Dr David Sinclair

ncbi.nlm.nih.gov/pmc/articles/PMC6359187

 

IMPROVING BLOOD FLOW IS IMPORTANT TO PREVENT AGING OF TISSUES AND ORGANS.

 

In aging mice NMN effectively improved:

  • Weight gain
  • Energy metabolism
  • Physical activity
  • Insulin sensitivity
  • Plasma lipid profile
  • Eye function

 

5)  Long-term administration of NMN mitigates age-associated physiological decline in mice

NMN has been shown to enhance NAD+ biosynthesis and ameliorate various pathologies in mouse disease models.

NMN synthesized NAD+ in tissues.

NMN was able to mitigate age-associated physiological decline in mice.

NMN has been shown to:

  • Suppress age-associated body weight gain
  • Boost energy metabolism
  • Promote physical activity
  • Improve insulin sensitivity and plasma lipid profile
  • Ameliorate eye function and other pathophysiologies
  • Prevent age-associated gene expression changes
  • Enhance mitochondrial oxidative metabolism

These results suggest the preventive and therapeutic potential of NAD+ intermediates as anti-aging interventions in people.
sciencedirect.com/science/article/pii/S1550413116304958     

                 

6)  NMN inhibits JNK activation to reverse Alzheimer disease

A study in mice, showed that NAD+ is related to the decline of amyloid-β (Aβ) oligomers, which have been accepted as major neurotoxic agents in the therapy of Alzheimer's disease (AD).

This study investigated the potential therapeutic effect of NMN in behavioral measures of cognitive impairments compared to control AD-Tg mice.

NMN effectively controlled JNK activation, potently progressed nonamyloidogenic amyloid precursor protein (APP) and suppressed amyloidogenic APP by mediating the expression of APP cleavage secretase in AD-Tg mice.

This study suggests that NMN substantially decreases multiple AD-associated pathological characteristics at least partially by the inhibition of JNK activation.

ncbi.nlm.nih.gov/pubmed/28330719

 

7)  NMN reduces signs of aging in healthy mice

Our body cells’ ability to produce energy declines with age.

Suggesting that the loss of efficiency in the body’s energy supply chain is a key driver of the aging process.

This study showed that supplementing healthy mice with NMN can compensate for the loss of energy production, reducing signs of aging, such as weight gain, loss of insulin sensitivity and declines in physical activity.

When NMN was dissolved in drinking water and given to mice, it appeared in the bloodstream in less than three minutes.

It was also found that NMN in the blood is quickly converted to NAD+ in multiple tissues.

Researchers found a variety of beneficial effects of NMN supplementation in older mice including in:

  • Skeletal muscle
  • Liver function
  • Bone density
  • Eye function
  • Insulin sensitivity
  • Immune function
  • Body weight and physical activity levels.

 sciencedaily.com/releases/2016/10/161027122047.htm

 

8)  Cardioprotection by NMN: involvement of glycolysis and acidic PH

In this study in mice, researchers hypothesized that NMN may confer cardiovascular protection in part via direct stimulation of cardiac glycolysis.

It found that NMN was cardioprotective when delivered acutely at reperfusion (recovery 39±8%).

In conclusion, acute cardioprotective benefits of NMN are mediated in part via glycolytic stimulation, with the downstream protective mechanism involving enhanced ATP synthesis during ischemia and/or enhanced acidosis during reperfusion.

ncbi.nlm.nih.gov/pmc/articles/PMC6103815/

 

9)  NMN, a key NAD+ intermediate, treats the pathophysiology of diet – and age – induced diabetes in mice

This study found that injecting NMN into mice with type 2 diabetes improved their disease.

NMN also improved glucose tolerance on male mice with age-related diabetes.

NMN was given by injection at a dose of 500mg/kg bodyweight to the mice for 7-10 consecutive days.

The researchers investigated how NMN influences insulin sensitivity in the liver, specifically in female mice, and what enzymes and genes might be important in this process.

They also investigated the effect of NMN would be in mice that developed diabetes naturally in old age.

In female mice, the researchers found that administering NMN restored NAD+ levels to normal and also completely restored their glucose tolerance to normal levels (glucose intolerance is the main characteristic of diabetes).

They found the female mice were also more sensitive to insulin (one of the main hormones responsible for regulating glucose levels in the body) after receiving NMN.

In diabetic male mice NMN also restored NAD+ levels and improved glucose tolerance, but the effects were not as great. In a further gender difference, insulin tolerance remained unchanged in males after NMN treatment.

Researchers also suggest that a key enzyme, SIRT1, was important in how NMN acted to increase insulin sensitivity in the liver.

In conclusion, this study demonstrated the importance of NMN in reversing type 2 diabetes and proposed a partial biological explanation for how it works. This will help guide future research to fully explore the processes involved.

cell.com/cell-metabolism/fulltext/S1550-4131(11)00346-9

 

NMN DELIVERY OPTIONS

Oral NMN capsules are common place, but sublingual delivery is strongly recommended

  • It allows the compound to be absorbed into the blood vessels underneath the tongue
  • Enabling NMN to avoid digestion in the gastrointestinal tract and faster delivery to the bloodstream.

fightaging.org/2018/03/results-from-a-preliminary-human-trial-of-nicotinamide-riboside