Whats the TRUTH about Nicotinamide Riboside (NIAGEN)

As we age, our levels of the Co-enzyme Nicotinamide Adenine Dinucleotide NAD+ drop significantly in multiple organs in mice and humans  (5,8,10).

NAD+ decrease is described as a trigger in age-associated decline(23), and perhaps even the key factor in why we age (5).

In 2013, research published by Dr David Sinclair demonstrated that short term supplementation with Nicotinamide MonoNucleotide (NMN) replenished NAD+ and reversed many aspects of aging, making the cells of old mice resemble those of much younger mice, and greatly improving their health (8).

The quotes below are directly from that research:

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”

Since Dr Sinclairs landmark 2013 study, dozens of others have been published investigating the efficacy of supplementation with NMN and Nicotinamide Riboside (NR) in treatment and prevention of a wide range of disease including cancer, cardiovascular disease, diabetes, Alzheimers, Parkinsons, and more (5,6,7,9,10,11,13,14,15,16).

According to Dr Sinclair:

“enhancing NAD+ biosynthesis by using NAD+ intermediates, such as NMN and NR, is expected to ameliorate age-associated physiological decline”

NAD+ METABOLISM IN HUMANS

NAD+ can be synthesized in humans from several different molecules (precursors), thru 2 distinct pathways:
De Novo Pathway

• Tryptophan
• Nicotinic Acid (NA)

Salvage Pathway

• NAM – Nicotinamide
• NR – Nicotinamide Riboside
• NMN – Nicotinamide MonoNucleotide

The NAD+ supply is constantly being consumed and replenished through the Salvage Pathway, with approximately 3g of NAM metabolized to NMN and then to NAD 2-4 times per day (14).

WHAT IS NR

NMN is the immediate precursor to NAD+ in the salvage pathway that constantly recycles NAD+.

Nicotinamide Riboside (NR) is a NAD+ intermediate that is used inside our cells to metabolize NMN and NAD. It is found in natural food sources and broken down in our bodies digestive system to NAM, NMN and other NAD metabolites.

In 2004 Dr Charles Brenner published a paper showing that the enzyme Nrk1 can catalyze NR directly to NMN (100) which can make it a more effective precursor to NAD+ than the previously known NAM, NA, or Tryptophan.

Although NR is unstable by itself, Dartmouth University has patented production methods that combine it with Chloride which makes it stable.

Chromadex has licensed this technology and has been selling NR commercially since 2014 under the brand name “Niagen”.

Tru Niagen is the brand name used by Dr Brenner’s company ProHealthSpan to market their Niagen product.

ALL PRECURSORS BOOST NAD+ SIGNIFICANTLY IN LIVER

NAM, NA, NMN, NR, and Tryptophan ALL elevate levels of NAD+ significantly in the liver, which has many benefits for metabolic health.

This chart from the Trammell thesis shows the impact on liver NAD+ for mice given NR, NAM, and NA by oral gavage 0.25, 1, 2, 4, 6, 8 and 12 hours before testing.

Charts showing NMN impact on NAD+ levels in the liver are further down the page.

NMN

• “NMN makes its way through the liver, into muscle, and is metabolized to NAD+ in 30 minutes” (R)

NR

• Is much slower, taking 8 hours to reach peak NAD+ in humans (R)

NAM

• Has very similar NAD+ profile to NR, taking 8 hours to reach peak NAD+ in humans (R)
• Has been shown to increase NAD+ level in liver (47%), but was weaker in kidney (2%), heart (20%), blood (43%) or lungs (17%) (R)

NA (Niacin)

• Elevates NAD+ to peak levels in liver in 15 minutes (R)
• raised NAD+ in liver (47%), and impressively raised kidney (88%), heart (62%), blood (43%) and lungs (11%) (R)

TRYPTOPHAN

• In the liver  tryptophan is the preferable substrate for NAD+ production (R)
• Administration of tryptophan, NA, or NAM to rats showed that tryptophan resulted in the highest hepatic NAD+ concentrations(R)

ONLY NMN BYPASSES THE NAMPT BOTTLENECK IN TISSUES THROUGHOUT THE BODY

Restoring NAD+ to youthful levels in ALL CELLS throughout the body is the goal.

However, many tissues cannot utilize NAD+ directly from the blood as NAD+ cannot readily pass through the cellular membrane.

Muscle tissue, for example, depends on cells internal recycling of NAD+ through the salvage pathway which is controlled by Nampt.

To restore depleted NAD+ levels in such cells, a precursor must:

• Be available in the bloodstream
• Once inside a cell, be able to bypass the Nampt bottleneck

NAM is abundant in the blood and easily carried into such cells throughout the body, but  depends on Nampt, which is the rate limiting enzyme in the salvage pathway.

NR can bypass the Nampt bottleneck, but is not normally available in the bloodstream (see below)

After oral NMN supplementation, levels of NMN in the bloodstream are quickly elevated and remain high longer than NAM, NA, or NR (18,22,97,98,99)

Oral NMN supplements:

• Make their way intact thru the digestive system (22)
• Quickly elevates levels of NMN in the bloodstream for use throughout the body (22)
• Quickly elevates levels of  NMN in tissues throughout the body (22)
• Quickly raises levels of NAD+ in blood, liver and tissues  through the body (22,23)
• Remain elevated longer than NAM, NA, or NR (18)

MOST NR IS FIRST METABOLIZED TO NAM

When taken orally as a supplement, most NR does not make it through the digestive system intact, but is broken down to NAM (97,98,99).

Quotes from some studies are below:

“This evidence indicates that NR is converted to NAM before absorption occurs and that this reaction is the rate-limiting step ” (98)

“NR has been shown be converted to Nam before being absorbed or reaching tissues” (99)

“oral NR dosing increased circulating NAM ~40-fold while NMN remained unchanged” (97)

“we were surprised to find that NR exerts only a subtle influence on the steady state concentration of NAD in muscles. Our tracer studies suggest that this is largely attributable to breakdown of orally delivered NR into NAM prior to reaching the muscle. ” (97)

For more info on how NR is converted to NAM in the body.

ORAL NR SUPPLEMENTS NOT DETECTABLE IN BLOODSTREAM

In both mice and humans, studies repeatedly failed to find any NR in the bloodstream at any time, even after very high dosages of NR (97,98,99).

Finally, this 2017 study did find a trace of NR in the bloodstream briefly, 100 minutes after oral gavage of 200mg/kg.

The Trammell thesis shows that the liver quickly processes any NR to other metabolites such as NAAD, NAM, NaAd, but also failed to find any trace of NR in the bloodstream.

Here are some quotes in the discussion section from the Trammell thesis:

“NR has not been detected in the blood cell fraction nor in plasma”

“NR varied and displayed no response to NR administration … but was detected after IP of double labeled NR in liver (Figure 5.7) and muscle (Figure 5.9), revealing NR does circulate”

This research found  that:

• NR is found in small quantities in the liver
• NR is normally not detectable in bloodstream
• Oral supplementation with NR did not show any increase in NR in the body
• Injection (IP) of NR does result in a detectable increase of NR in muscle and Liver
• Oral NR does not result in increased NAD+ levels in organs beyond the liver

Any NR supplements that do make it to the blood are quickly cleared by the liver so it is very rarely detected in the bloodstream, and then only at trace levels.

ORAL NR IS NOT AVAILABLE  TO TISSUES BEYOND THE LIVER

The charts below are from this 2016 study which used mice that have had the gene for Nampt “knocked out” in quadricep muscle, so are unable to process NAM. As a result, the NAD+ levels drop to 15% of normal.

These mice were fed 200mg/kg bodyweight of double labelled NR to track the movement of the NR through the body.

Any NR that makes it through digestion intact would be incorporated as double labelled NAD (M+2). NR that has been metabolized to NAM loses 1 heavy tracking molecule and would be found as M+1.

Chart D shows both single and double labelled NAD+ (green and red) are abundant in roughly equal amounts in the liver.

Chart C shows quite a lot of single labelled NAD+ in the muscle.

This is from labelled NR that has been metabolized to NAM and then NMN (likely in the liver) then traveled through the bloodstream to the muscle where it is incorporated to single labeled NAD+

We know this NAD+ was metabolized as NAM and then NMN because these mice lacked Nampt, so can not process NAM.

At the same time, there is only a tiny fraction of double labelled NAD+ in the muscle.

This demonstrates that NMN, but not NR was readily available for use in the Salvage Pathway inside the muscle.

ORAL NMN IS READILY AVAILABLE THROUGHOUT THE BODY

The chart at right shows levels of a double labeled NAD+ (C13-d-nad+) in liver and soleus muscle at 10 and 30 minutes after oral administration of double labeled NMN.

This clearly shows that NMN makes it way through the liver intact, through the bloodstream, into muscle, and is metabolized to NAD+ in 30 minutes (22) .

This quote below is directly from that study.

Orally administered NMN is quickly absorbed, efficiently transported into blood circulation, and immediately converted to NAD+in major metabolic tissues (22).

NMN QUICKLY RAISES NAD+ IN LIVER AND BLOOD

In this 2016 study, mice were given a single dose of  NMN in water.

NMN  levels in blood showed it is quickly absorbed from the gut into blood circulation within 2–3 min and then cleared from blood circulation into tissues within 15 min

 

 

 

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 SUPPLEMENTATION WITH NMN

In a long-term experiment documented in the 2016 study (22) , mice were given 2 different doses of NMN over 12 months.

Testing revealed that NMN  prevents some aspects of  physiological decline in mice, noting these changes:

• Decreased body weight and fat
• Increased lean muscle mass
• Increased energy and mobility
• Improved visual acuity
• Improved bone density
• Is well-tolerated with no obvious bad side effects
• Increased oxygen consumption and respiratory capacity
• Improved insulin sensitivity and blood plasma lipid profile

Here are some quotes from  the  study:

NMN suppressed age-associated body weight gain, enhanced energy metabolism, promoted physical activity, improved insulin sensitivity and plasma lipid profile, and ameliorated eye function and other pathophysiologies

NMN-administered mice switched their main energy source from glucose to fatty acids

These results strongly suggest that NMN has significant preventive effects against age-associated impairment in energy metabolism

NMN effectively mitigates age-associated physiological decline in mice

LOWER FAT AND INCREASED LEAN MUSCLE MASS

Researchers found that NMN administration suppressed body weight gain by 4% and 9% in the 100 and 300 mg/kg/day groups.

Analyses of  blood chemistry panels and urine did not detect any sign of toxicity from NMN.

Although health span was clearly improved, there was no difference in maximum lifespan observed.

These results suggest that NMN administration can significantly suppress body weight gain without side effects

INCREASED OXYGEN CONSUMPTION AND RESPIRATORY CAPACITY

Oxygen consumption significantly increased in both 100 and 300 mg/kg/day groups during both light and dark periods (Figure 3A).

Energy expenditure also showed significant increases  (Figure 3B).

Respiratory quotient significantly decreased in both groups during both light and dark periods (Figure 3C),

This suggests that NMN-administered mice switched their main energy source from glucose to fatty acids.

The mice that had been receiving NMN for 12 months exhibited energy levels, food and water consumption equivalent to the mice in the control group that were 6 months younger.

NMN administration has significant preventive effects against age associated physical impairment

HUMAN STUDIES – LONG TERM SUPPLEMENTATION WITH NMN

The first clinical trial of NMN in humans is currently underway by an international collaborative team between Keio University School of Medicine in Tokyo and Washington University School of Medicine (33).

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 125mg capsules of 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 parameter 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.

SUMMMARY

NAD+ levels decrease throughout the body as we age, contributing to disease and aging.

Restoring NAD+ levels can ameliorate many age released health issues.

All the NAD+ precursors are effective at raising NAD+ levels in the liver.

Raising NAD+ in the liver has many benefits, but is not effective in tissues and organs that cannot access NAD+ directly from the bloodstream and so depend on internal cellular NAD+ recycling.

For these tissues, utilizing each cells internal Salvage Pathway is necessary to restore NAD+ levels.

NR is not stable in the body and not normally found in the bloodstream, so is not readily available as NR to many tissues. Once metabolized to NAD+ it cannot enter cells. If metabolized to NAM it cannot bypass the Nampt bottleneck.

NMN is the only precursor that is stable and available to cells through the bloodstream, and can bypass the Nampt bottleneck to quickly restore NAD+ throughout the body.

NMN IS THE WHOLE BODY NAD+ BOOSTER

 

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)

 

 

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