Can Nicotinamide Mononucleotide (NMN) really reverse aging?

This POST has been redirected to a PAGE – is only here to show in recent posts and such widgets.

NAD+ DECLINES WITH AGE

As we age, our bodies produce less NAD+ and the communication between the Mitochondria and cell nucleus is impaired. (5,8,10).

Over time,  decreasing NAD+ impairs the cell’s ability to make energy, which leads to aging and disease (8, 5) and perhaps even the key factor in why we age (5).

Read more about NAD+

NAD+ METABOLISM IN HUMANS

NAD+ can be synthesized in humans from several different molecules (precursors), thru  the De Novo  and Salvage Pathways.

The salvage pathway sustains 85% or more of our NAD+ (14), with approximately 3g of NAM metabolized to NMN and then to NAD 2-4 times per day (14).

Nampt is the rate-limiting step in the salvage process (97).

NMN IS QUICKLY METABOLIZED IN TISSUES THROUGHOUT THE BODY

This 2016 study found NMN is rapidly metabolized to NAD+ in tissues throughout the body.

The red line in chart to right shows NMN quickly absorbed into blood circulation within 2–3 min, and then into tissues within 15 minutes.

The blue line shows NAD+ levels begin to increase significantly in tissue within 15 minutes.

This chart at left from the same study shows levels of a double labeled NAD+ in liver and soleus muscle at 10 and 30 minutes after oral administration of double labeled NMN.

This clearly shows the NMN makes its way through the liver and into muscle in 30 minutes.

NMN INCREASES NAD+ and SIRT1 DRAMATICALLY IN ORGANS

In this 2017 study, NMN supplementation for 4 days significantly elevated NAD+ and SIRT1, which protected the mice from Kidney damage.

NAD+ and SIRT1 levels were HIGHER in OLD Mice than in YOUNG Mice that did not receive NMN.

LONG TERM STUDY ON NMN

This 12 month long study designed to evaluate the long-term effects of oral supplementation of NMN in mice published in Oct 2016.

Mice were feed 100 or 300Mg/Kg of NMN per day by oral garage. The 100 Mg dosage showed more improvement in some metabolic parameters, which 300 Mg per kg a day was more effective at others.

Using the FDA guidelines on conversion, the 100 Mg dosage equates to 560 mg per day in a 70 kg human.

•  better glucose control
• increased energy
• less weight gain
• better mobility
• better overall health
• immune function

Below are some quotes from that study.

“NMN was able to mitigate most age-associated physiological declines in mice”

“treatment of old mice with NMN reversed all of these biochemical aspects of aging”

HUMAN STUDIES – LONG TERM SUPPLEMENTATION WITH NMN

There are at least 2 clinical trials of NMN in humans currently underway.

The first was started in late 2016 by Keio University School of Medicine in Tokyo (R).

The second was begun in the summer of 2017,by Washington University School of Medicine (R).

The Washington University study appears to be much larger and investigates more health parameters.In that study, participants are 50 healthy women between 55 and 70 years of age with slightly high blood glucose,BMI and triglyceride levels.

Using a dose of 2 capsules of 125mg NMN per day over a period of 8 weeks, researchers are testing for:

• change in insulin sensitivity
• change in beta-cell function
• works to control blood sugar
• blood vessels dilate
• effects of NMN on blood lipids
• effects of NMN on body fat
• markers of cardiovascular and metabolic health

According to the study:

“Data from studies conducted in rodents have shown that NMN supplementation has beneficial effects on cardiovascular and metabolic health, but this has not yet been studied in people”

Testing of metabolic parameters will continue for 2 years after supplementation has ended, so final results will not be published for some time yet, but preliminary results are expected to be announced in early 2018.

Aging

Head to Head Comparison of Short-Term Treatment with the NAD(+) Precursor Nicotinamide Mononucleotide (NMN) and 6 Weeks of Exercise in Obese Female Mice (Uddin, 2016)

NAD(+) levels were increased significantly both in muscle and liver by NMN
NMN-supplementation can induce similar reversal of the glucose intolerance
NMN intervention is likely to be increased catabolism of fats
NMN-supplementation does mimic exercise

DNA Damage

A conserved NAD+ binding pocket that regulates protein-protein interactions during aging (Sinclair, 2017)

This study showed supplementation with NMN was able to repair the DNA in cells damaged by radiation.

the cells of old mice were indistinguishable from young mice after just one week of treatment.”

Diabetes & Metabolic disease

Nicotinamide Mononucleotide, a Key NAD+ Intermediate, Treats the Pathophysiology of Diet- and Age-Induced Diabetes in Mice (Yoshino, 2011)

NMN was immediately utilized and converted to NAD+ within 15 min, resulting in significant increases in NAD+ levels over 60 min

administering NMN, a key NAD+ intermediate, can be an effective intervention to treat the pathophysiology of diet- and age-induced T2D

Surprisingly, just one dose of NMN normalized impaired glucose tolerance

Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging (Gomes, Sinclair,2013)

raising NAD+ levels in old mice restores mitochondrial function to that of a young mouse

treatment of old mice with NMN reversed all of these biochemical aspects of aging

restore the mitochondrial homeostasis and key biochemical markers of muscle health in a 22-month-old mouse to levels similar to a 6-month-old mouse

CardioVascular Disease

Nicotinamide mononucleotide, an intermediate of NAD+ synthesis, protects the heart from ischemia and repercussion (Yamamoto, 2014)

NMN significantly increased the level of NAD+ in the heart

NMN protected the heart from I/R injury

Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice (de Picciotto, 2016)

NMN reduces vascular oxidative stress
NMN treatment normalizes aortic stiffness in old mice
NMN represents a novel strategy for combating arterial aging

Short-term administration of Nicotinamide Mononucleotide preserves cardiac mitochondrial homeostasis and prevents heart failure (Zhang, 2017)

NMN can reduce myocardial inflammation

NMN thus can cut off the initial inflammatory signal, leading to reduced myocardial inflammation

Nicotinamide mononucleotide requires SIRT3 to improve cardiac function and bioenergetics in a Friedreich’s ataxia cardiomyopathy model

Remarkably, NMN administered to FXN-KO mice restores cardiac function to near-normal levels.

restoration of cardiac function and energy metabolism upon NMN supplementation
remarkable decrease in whole-body EE and cardiac energy wasting

Neurological Injury

Nicotinamide mononucleotide attenuates brain injury after intracerebral hemorrhage by activating Nrf2/HO-1 signaling pathway (Wei, 2017)

NMN treats brain injury in ICH by suppressing neuroinflammation/oxidative stress

NMN treatment protects against cICH-induced acute brain injury
NMN treatment reduces brain cell death and oxidative stress
These results further support the neuroprotection of NMN/NAD+

Alzheimers

Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer’s disease-relevant murine model (Long, 2015)

We now demonstrate that mitochondrial respiratory function was restored

Nicotinamide mononucleotide protects against β-amyloid oligomer-induced cognitive impairment and neuronal death (Wang, 2016)

NMN could restore cognition in AD model rats.
The beneficial effect of NMN is produced by ameliorating neuron survival, improving energy metabolism and reducing ROS accumulation.
These results suggest that NMN may become a promising therapeutic drug for AD

Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer disease(Yao, 2017)

NMN Treatment Rescues Cognitive impairments
NMN Treatment Improves Inflammatory Responses

Kidney Disease
Nicotinamide Mononucleotide, an NAD+ Precursor, Rescues Age-Associated Susceptibility to AKI in a Sirtuin 1-Dependent Manner (Guan, 2017)

Supplementation with NMN restored kidney SIRT1 and NAD+ content in 20-month-old mice and protected both young and old mice from acute kidney injury.

References:

1. Detection and pharmacological modulation of nicotinamide mononucleotide (NMN) in vitro and in vivo (Formentini, 2009)
2. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity (Cato, 2009)
3. A possibility of nutriceuticals as an anti-aging intervention: activation of sirtuins by promoting mammalian NAD biosynthesis (Imai, 2010)
4. NAD blocks high glucose induced mesangial hypertrophy via activation of the sirtuins-AMPK-mTOR pathway (Zhuo, 2011)
5. Nicotinamide Mononucleotide, a Key NAD+ Intermediate, Treats the Pathophysiology of Diet- and Age-Induced Diabetes in Mice (Yoshino, 2011)
6. The NAD (+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity(Canto, 2012 )
7. NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice. (Zhang, 2016)
8. Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging (Gomes, Sinclair,2013)
9. Nicotinamide mononucleotide, an intermediate of NAD+ synthesis, protects the heart from ischemia and repercussion (Yamamoto, 2014)
10. NAD+ and sirtuins in aging and disease (Imai, 2014)
11. Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3 (Khan, 2014)
12. Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer’s disease-relevant murine model (Long, 2015)
13. NAD+ metabolism and the control of energy homeostasis – a balancing act between mitochondria and the nucleus (Canto, 2015)
14. NAD+ metabolism: Bioenergetics, signaling and manipulation for therapy (Yang, 2016)
15. NAD+ replenishment improves lifespan and healthspan in ataxia telangiectasia models via mitophagy and DNA repair( Fang, 2016 )
16. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans(Trammell, 2016a )
17. Nicotinamide riboside opposes type 2 diabetes and neuropathy in mice(Trammell, 2016b )
18. β-Nicotinamide Mononucleotide, an Anti-Aging Candidate Compound, Is Retained in the Body for Longer than Nicotinamide in Rats (Kawamura, 2016)
19. The first human clinical study for NMN has started in Japan (Tsubota, 2016)
20. Nicotinamide mononucleotide protects against β-amyloid oligomer-induced cognitive impairment and neuronal death (Wang, 2016)
21. Head to Head Comparison of Short-Term Treatment with the NAD(+) Precursor Nicotinamide Mononucleotide (NMN) and 6 Weeks of Exercise in Obese Female Mice (Uddin, 2016)
22. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice (Mills, 2016)
23. Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice (de Picciotto, 2016)
24. Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer disease (Yao, 2017)
25. Nicotinamide mononucleotide requires SIRT3 to improve cardiac function and bioenergetics in a Friedreich’s ataxia cardiomyopathy model (Martin, 2017)
26. Nicotinamide Mononucleotide, an NAD+ Precursor, Rescues Age-Associated Susceptibility to AKI in a Sirtuin 1-Dependent Manner (Guan, 2017)
27. Nicotinamide mononucleotide attenuates brain injury after intracerebral hemorrhage by activating Nrf2/HO-1 signaling pathway (Wei, 2017)
28. Short-term administration of Nicotinamide Mononucleotide preserves cardiac mitochondrial homeostasis and prevents heart failure (Zhang, 2017)
29. Modulating NAD+ metabolism, from bench to bedside (Auwerx, 2017)
30. Aspects of Tryptophan and Nicotinamide Adenine Dinucleotide in Immunity: A New Twist in an Old Tale. (Rodriguez, 2017)
31. Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice (Williams, 2017)
32. NAMPT-mediated NAD biosynthesis as the internal timing mechanism: In NAD+ World, time is running in its own way (Poljsak, 2017)
33. Effect of “Nicotinamide Mononucleotide” (NMN) on Cardiometabolic Function (NMN)
34. The dynamic regulation of NAD metabolism in mitochondria (Stein, 2012)
35. Novel NAD+ metabolomic technologies and their applications to Nicotinamide Riboside interventions (Trammel, 2016)
36. Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans (Meydayni, 2016)
37. A high-fat, ketogenic diet induces a unique metabolic state in mice. (Kennedy, 2007)
38. Ketone body metabolism and cardiovascular disease.(Cotter, 2013)
39. Ketone bodies as signaling metabolites(Newman, 2014)
40. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease(Youm, 2015)
41. The effect of the Spanish Ketogenic Mediterranean Diet on nonalcoholic fatty liver disease: a pilot study.(Guisado, 2011)
42. β-Hydroxybutyrate: A Signaling Metabolite in starvation response(Morales, 2016)
43. Physiological roles of ketone bodies as substrates and signals in mammalian tissues(Robinson, 1980)
44. Ketone bodies mimic the life span extending properties of caloric restriction (Veech, 2017)
45. Novel ketone diet enhances physical and cognitive performance(Murray, 2016)
46. Mitochondrial biogenesis and increased uncoupling protein 1 in brown adipose tissue of mice fed a ketone ester diet.
47. Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes(Cox, 2013)
48. Neuroendocrine Factors in the Regulation of Inflammation: Excessive Adiposity and Calorie Restriction (Fontana, 2009)
49. Beta-adrenergic receptors are critical for weight loss but not for other metabolic adaptations to the consumption of a ketogenic diet in male mice(August, 2017)
50. A randomized trial of a low-carbohydrate diet for obesity(Foster, 2003)
51. β-Hydroxybutyrate suppresses inflammasome formation by ameliorating endoplasmic reticulum stress via AMPK activation(Bae, 2016)
52. The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. (Maalouf, 2009)
53. AMPK activation protects cells from oxidative stress‐induced senescence via autophagic flux restoration and intracellular NAD + elevation (Han, 2016)
54. Regulation of AMP-activated protein kinase by natural and synthetic activators (Hardie, 2015)
55. Effects of Exhaustive Aerobic Exercise on Tryptophan-Kynurenine Metabolism in Trained Athletes (Strasser, 2016)
56. PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation(Bai, 2011)
57. Carbohydrate restriction regulates the adaptive response to fasting (Klein, 1992)
58. Interventions to Slow Aging in Humans: Are We Ready? (longo, 2015)
59. Extending healthy life span–from yeast to humans (longo, 2010)
60. Dietary restriction with and without caloric restriction for healthy aging (Lee, 2016)
61. A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan (Longo, 2015)
62. Diet mimicking fasting promotes regeneration and reduces autoimmunity and multiple sclerosis symptoms (Longo, 2016
63. Resistance Exercise Training Alters Mitochondrial Function in Human Skeletal Muscle (Porter, 2015)
64. Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice (Newman, 2017)
65. The NAD(+)/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling.  (Mouchiroud, 2013)
66. NAMPT- mediated NAD(+) biosynthesis is essential for vision in mice  (Lin, 2016)
67. NAD+ replenishment improves lifespan and healthspan in ataxia telangiectasia models via mitophagy and DNA repair( Fang, 2016 )
68. Inhibiting poly ADP-ribosylation increases fatty acid oxidation and protects against fatty liver disease (Gariani, 2017 )
69. Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle(Canto, 2010)
70. The NAD (+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity(Canto, 2012 )
71. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans(Trammell, 2016a )
72. Nicotinamide riboside opposes type 2 diabetes and neuropathy in mice(Trammell, 2016b )
73. Dietary leucine stimulates SIRT1 signaling through activation of AMPK (Hongliang, 2012)
74. Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3 (Khan, 2014)
75. NAD blocks high glucose induced mesangial hypertrophy via activation of the sirtuins-AMPK-mTOR pathway (Zhuo, 2011)
76. The effect of different exercise regimens on mitochondrial biogenesis and performance (Philander, 2014)
77. Dietary proanthocyanidins boost hepatic NAD+ metabolism and SIRT1 expression and activity in a dose-dependent manner in healthy rats (Aragon’s, 2016)
78. NAD+ Deficits in Age-Related Diseases and Cancer (Garrido, 2017)
79. Anti-diabetic and anti-lipidemic effects of chlorogenic acid are mediated by ampk activation (Ong, 2013)
80. Chlorogenic Acid Improves Late Diabetes through Adiponectin Receptor Signaling Pathways in db/db Mice (Chang, 2015)
81. Adenosine Monophosphate (AMP)-Activated Protein Kinase: A New Target for Nutraceutical Compounds (Marin-Aguilar, 2017)
82. The Effects of Ramadan Fasting on Body Composition, Blood Pressure, Glucose Metabolism, and Markers of Inflammation in NAFLD Patients: An Observational Trial (Mazidi, 2014)
83. Comparative effects of carbohydrate versus fat restriction on metabolic profiles, biomarkers of inflammation and oxidative stress in overweight patients with Type 2 diabetic and coronary heart disease: A randomized clinical trial. (Raygan, 2016)
84. Normal fasting plasma glucose and risk of type 2 diabetes diagnosis (Nichols, 2008)
85. Are We All Pre-Diabetic? (Stokel,2016)
86. Hepatic NAD⁺ deficiency as a therapeutic target for non-alcoholic fatty liver disease in aging (Zhou, 2016)
87. Effect of exercise intensity on post-exercise oxygen consumption and heart rate recovery (Mann,2014)
88. A 45-minute vigorous exercise bout increases metabolic rate for 14 hours (Knab,2011)
89. Effects of high-intensity resistance training on untrained older men. II. Muscle fiber characteristics and nuclei-cytoplasmic relationships (Gerontol, 2000)
90. Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice (Newman, 2017)
91. A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice (Roberts, 2017)
92. NK cells link obesity-induced adipose stress to inflammation and insulin resistance (Wensveen, 2015)
93. The “Big Bang” in obese fat: Events initiating obesity-induced adipose tissue inflammation (Wensveen, 2015)
94. The impact of the Standard American Diet in rats: Effects on behavior, physiology and recovery from inflammatory injury(Totsch, 2017)
95. Bioenergetic state regulates innate inflammatory responses through the transcriptional co-repressor CtBP (Shen, 2017)
96. The Ketogenic Diet as a Treatment Paradigm for Diverse Neurological Disorders (Stafstrom, 2012)
97. Loss of NAD Homeostasis Leads to Progressive and Reversible Degeneration of Skeletal Muscle (Fredrick 2016)
98. Digestion and absorption of NAD by the small intestine of the rat (Henderson, 1983)
99. Effects of a wide range of dietary nicotinamide riboside (NR) concentrations on metabolic flexibility and white adipose tissue (WAT) of mice fed a mildly obesogenic diet(Shi, 2017)
100. Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans (Brenner, 2004)
101. Nampt Expression Decreases Age-Related Senescence in Rat Bone Marrow Mesenchymal Stem Cells by Targeting Sirt1 (Ma, 2017)

The post Can Nicotinamide Mononucleotide (NMN) really reverse aging? appeared first on Alivebynature - Evidence Based Reviews.