New Study finds Nicotinamide Riboside safe at typical dosages

safetyA clinical study was published January 2016 on the safety and side effects  of Nicotinamide Riboside in the HET Journal (Human and Experimental Toxicology), an international peer reviewed journal.

Although naturally occurring in trace amounts in some foods such as milk and beer, Nicotinamide riboside (NR) is a recently discovered form of vitamin B3.

It is being studied along with Nicotinamide Mono-Nucleotide  for a wide range of potential health benefits due to it’s ability to increase NAD+ levels in human and animal testing.

NAD+ is a co-enzyme found in all animals that enable the mitochondria to perform their role in powering the basic functioning of every cell in our bodies. NAD+ levels naturally drop as we age and is thought to be a key driver in many age related diseases and health problems.

Prior research has shown that increased NAD+ levels in older mice results in improved energy and muscle performance similar to that of young animals.

This study was performed using Niagen, which is the only commercially available brand of Nicotinamide Riboside (NR). They also compared the effects of NR with that of similar dosage of Nicotinamide (also referred to as niacinamide) , a more common and better studied form of B3 vitamin with a long record of safe usage.

In the first phase of the study, mice that were fed 5000 mg per kg of bodyweight exhibited no mortality.

The second phase was a 90 day assessment comparing dosages of 300, 1000, and 3000 mg/kg of bodyweight per day.

Researchers compared the effects on liver, kidneys, ovaries, and testes and found no toxicity at any of the dosages tested.

Their was no adverse effects noted at the 300 mg level. Minor effects at 1000 and 3000 mg levels were similar to that of Nicotinamide.

There are  guidelines used by the FDA to translate the dosages used in mice to the equivalent dosage for the Human Equivalent Dose (HED).

The 300 mg/kg dosage equals 48mg/kg HED, which would be approximately 2880 mg a day for a 132 lb human, which is well over the dosage recommended. However, the FDA requires a 10x safety factor which would result in a dosage of 288 mg, which is at the lower end of recommended dosage.

Comparing results on animals given NR vs Niacinamide, the researchers concluded that NR has a similar toxicity to niaciniamide.

Niacinamide has a long track record of safe use in humans, and is rated as LIKELY SAFE at normal dosages. At dosages above 3 grams per day, Niacinamide can result in serious side effects including liver problems, gout, vision, elevated blood sugar, and other serious problems.

3 grams of Niacinamide per day equals roughly 7 grams per day of Nicotinamide Riboside.

Based partly on the results of this study, Chromadex was able to obtain GRAS status for Niagen.

Niagen (Nicotinamide Riboside) recognized as GRAS (Generally Recognized as Safe)

The company called ChromaDex Corporation, an innovator of nutritional and health ingredients, announced that an independent scientific panel of experts determined that NIAGEN , a patented formula of Nicotinamide Riboside (NR) is Generally Recognized As Safe (GRAS). 

Generally recognized as safe (GRAS) is an American Food and Drug Administration (FDA) designation that a chemical or substance added to food is considered safe by experts, and so is exempted from the usual Federal Food, Drug, and Cosmetic Act (FFDCA) food additive tolerance requirements.

It is a very strong testimony that Nicotinamide Riboside supplementation is safe without side effect. It should be noted here that the GRAS status was only given to Chromadex’s commercially available form of nicotinamide riboside (NR) called Niagen. This formula is protected by five patents issued and several pending and so far it appears this is the only NR form that is known to be commercially available. Hence when buying NR it seems prudent to ensure oneself of the source to avoid buying false formula’s.

Frank Jaksch Jr., founder and CEO of ChromaDex, commented, “Receiving GRAS status immediately allows NIAGEN to be included as an ingredient in both food and beverages –applications that we believe presents a very substantial opportunity for ChromaDex. Coupled with the recent NDI status, we believe the stage is set for widespread commercialization of NIAGEN as an innovative and compelling ingredient across a myriad of consumer products.”

You can find the press release here.

Nicotinamide Riboside supplements aid metabolic health in Mice

cells artResearchers at the Wageningen University in the Netherlands took a different approach to understand the effect of NAD+ pre-cursers and their influence on health. They presented a poster publication during the “10th World Congress on Polyphenols Applications” about an experiment  to test the effects of marginal dietary supplementation with Nicotinamide Riboside (NR) on metabolic flexibility and anti-oxidant response in mice exposed to a high fat diet. This is in particular interesting because most studies with NR have been done at higher therapeutic levels as opposed to levels more typical for daily supplementation with an aim to maintain health.

The researchers fed two groups of adult male mice with a high fat diet containing dosing of 5 or 30 mg NR/kg. They measured body weight, lean mass, fat mass and feed intake weekly. After 14 weeks the metabolic flexibility was assessed with a fasting and re-feeding challenge using indirect calorimetry. With indirect calorimetry a measurement of respiratory exchanges takes place. Oxidation of the energetic substrates by the body is associated with oxygen consumption, carbon dioxide production, and heat release specific to the nature of the energetic substrates being oxidized. In the following week (so at 15 weeks) the researchers determined the anti-oxidant response in epididymal white adipose tissue.

The results showed that in the fasting and re-feeding challenge, the delta respiratory exchange ratio (ΔRER) was higher when comparing 30 to 5 mg/kg NR dosing thus indicating an increase in metabolic flexibility. In addition the expression levels of anti-oxidant genes were enhanced in the 30 mg/kg group compared to the 5 mg/kg group. The body physiological parameters were not affected by the dietary NR.

nr nad namFrom these results it is still not possible to conclude what is the minimum level at which NR supplementation impacts the body as there are no intermediate dose test results between 5mg and 30mg / kg but it seems reasonable to conclude that NR supplementation does impact at a dosing level of  30mg / kg in mice.

Using FDA specified guidelines  we can calculate the Human Equivalent Dose (HED) for the NR diet given to the mice. Using this guideline 30mg/kg dosing in mice translates into a HED of approx. 2.4mg/kg. Or into approximately 170mg daily nicotinamide riboside dosing for a person weighing 70kg.  This is below the limit wrt to side effects and safety and less than the typical serving sizes of 250mg of supplements on the market. The result supports the view that NR supplementation may help maintain health as we age.

Here the updated overview of Nicotinamide Riboside dosing in various studies.

You can find the poster presentation summary here.

Is Basis by Elysium Health a Hoax?

As we age, levels of the co-enzyme Nicotinamide Adenine Dinucleotide NAD+ drop significantly in multiple organs, which disrupts our bodies ability to fight inflammation, disease, and physiological decline  (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 Sinclair  of Harvard stunned researchers by showing that short term supplementation with Nicotinamide MonoNucleotide (NMN)  reversed many aspects of aging, making the cells of old mice resemble those of much younger mice, and greatly improving their health.

Since then, dozens of other studies have been published investigating the efficacy of supplementation with NAD+ precursors such as NMN and Nicotinamide Riboside (NR) in treatment and prevention of a wide range of disease including cancer, cardiovascular disease, diabetes, Alzheimers, Parkinsons, and more (5,6,7,9,10,11,13,14,15,16,23).


NR and NMN are precursors that are used by our bodies to replenish NAD+ levels.

In 2004 Dr Charles Brenner published a paper showing that the enzyme Nrk1 can catalyze NR directly to NMN (100) which might make it a much more effective precursor to NAD+.  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”.

Basis is the brand name used by Elysium Health to market their Nicotinamide Riboside product.


NR benefits chartNAD+ is a key co-enzyme that the mitochondria in every cell of our bodies depend on to fuel all basic functions. (3,4)

NAD+ play a key role in communicating between our cells nucleus and the Mitochondria that power all activity in our cells (5,6,7)


NAD+ levels decreaseAs 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).


NAD+ is synthesized in humans by several different molecules (precursors), thru 2 different pathways:
De Novo Pathway

  • Tryptophan
  • Nicotinic Acid (NA)

Salvage Pathway

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

The NAD+ supply is not stagnant – it is constantly being consumed and replenished, with the entire NAD+ pool being turned over 2-4 times per day (14).

This recycling is through the salvage pathway, where the enzyme Nampt catalyzes NAM to NMN, which is then metabolized to NAD+.

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

Many studies have confirmed the importance of Nampt in maintaining sufficient NAD+ levels, such as the quote below from a 2016 study that used mice lacking Nampt in muscle fiber:

“NAD content of muscle was decreased by ~85% confirmed the prevailing view that the salvage route of NAD synthesis from NAM sustains the vast majority of the NAD” (97)

These mice exhibited normal muscle strength and endurance while young, but deteriorated rapidly as they aged which confirmed Nampt is critical to maintaining NAD+ levels.

As we age, Nampt enzyme activity is lower, resulting in less NAM recycling, less NAD+, more disease and aging (97,101).


NR had been known for decades, but was not thought to be that important until 2004 when Dr. Charles Brenner discovered the enzyme NRK1 can phosphorylate NR directly to NMN, bypassing the Nampt “bottleneck” (100).

This newly discovered “shortcut” in the NAD+ salvage pathway found that NR can be metabolized directly to NMN to boost NAD+ levels more effectively than 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).

Even when taken at very high dosages, NR has not been detected in the bloodstream in any research (97,98,99).

“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)

“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)

Note:NAM does elevate NAD+, but is on the “wrong” side of the Nampt bottleneck, which limits it’s effectiveness


[post-content id=59982]


1000s of articles have teased us with the possibility that taking Niagen could halt or maybe even actually reverse some of the signs of aging. Of course there is a lot of skepticism with such claims.

Chromadex has been producing the only commercially available form of Niagen and supplies it to 20 or more different companies that put their own brand name on the bottle and sell to customers.

Elysium Health is only one of these sellers, although they have fairly deep pockets and extensive connections among top researchers in the field.

They have also enlisted 6 Nobel Laurete scientists to serve as advisors to the company, which lends a great deal of credibility.

However, these scientists have had no significant role in researching,creating or testing Basis or either of the ingredients used.


Elysium Health makes a change to the formula for Basis

Basis contracted to buy Nicotinamide Riboside Chloride (often referred to as NR, or the brand name Niagen), and combine it with another off the shelf product from Chromadex, Pterostilbene.

But in June 2016, Elysium got into a contract dispute with Chromadex and later sued Chromadex for abusing the patent process.

Their goal seems to be to invalidate Chromadex patent(s) so they could produce their own version, which appears to be what they are doing now.

Elysium has changed the product information on their website to list “Nicotinamide Riboside”, without the Chloride.  A key patent Chromadex has licensed the rights to involves adding the Chloride to make it more stable.

This new ingredient used by Basis likely has the same effects in the human body, but we don’t really know for sure.

It seems Elysium Health plans to go forward with this revised formula for now, and continue to use previous test results obtained with their prior  formula that used Chromadex Nicotinamide Riboside Chloride.  It will be interesting to see how that strategy holds up going forward.

Elysium Health has some very slick Marketing people

So now they have changed their product to use a slightly different ingredient, but want to smooth it over and not cause customers to worry about it.

Their answer is to portray the change as something they did on purpose – to MAKE THE PRODUCT BETTER.

When a customer questioned the change, this is how they answered on their Facebook page:

Hi Anne–

Thank you for reaching out to us with your questions. I’d be happy to provide additional information for you here!

From the start, Elysium has always been committed to bringing superior, high-quality supplements to market. As part of that effort, we have established a new supply chain, located in the United States, that utilizes a proprietary process to produce Nicotinamide Riboside — the first of its kind for the production of Basis, and this does fully meet the GMP standard as outlined by the FDA. We believe our vertically integrated supply chain benefits our customers as it enables us to better manage manufacturing, packaging, shipment and eventually the expansion of our new product line.
While the specific Basis formulation and the amount of each ingredient have not changed, this new production process has allowed us to take an exceptional product and make it even purer. This reflects our ongoing commitment to being a trusted source for our customers by continually exceeding the highest standards in the industry.

In regard to your question about GMO’s, this does not apply to Basis as we don’t have food products in our ingredients eligible for genetic modification. Basis is produced by nature identical synthesis, meaning that the active molecules are constructed to be nature identical. This process is preferable to attempting to distill down the ingredients from food as the final product is purer than what the bi-product would be via distillation.
If you have other questions or if there is anything we can do to help, my team can be reached directly here or by email at or phone at 888-220-6436.

Pretty slick, I thought. No, they didn’t substitute something they just threw together to get around the patent and supply problem – they made something more pure and trustworthy.

I don’t know who is going to with the legal battles between Chromadex and Elysium Health, but I see Elysium as way ahead in the marketing department even if I don’t really trust their honesty.


Why Logo White red You’ll find very little mention of Niagen in the sales and marketing literature about Basis.

Elysium would like you to think that Basis is some exclusive formula created by their founders.

In fact, they purchase Niagen from Chromadex like several other brands.

The research and testing that has generated so much excitement has been done with Nicotinamide Riboside from Chromadex.

There has been no research published to show that Pterostibene makes Niagen work any better.

[box]Conclusion: ALL Niagen comes from Chromadex, there is no proof that Basis is any more effective than other brands of Niagen.[/box]


dollar sign moneybagBasis is available only thru their website for $60 a bottle, which would last for one month if taking 2 pills per day (250mg of Niagen).

Recent research indicates that the optimum dosage for maximum increase in NAD+ levels is at least 250mg per day, or more.

In fact, the best evidence on recommended dosage will hopefully soon be available from a recently completed study sponsored by Elysium Health themselves.

This study of 120 elderly patients tested blood NAD+ levels of 250mg and 500mg of Elysium Health Basis vs placebo.

Once this study is published we’ll have a lot better idea if one bottle per month is sufficient


If you know that Basis is Niagen + Pterostilbene, and start searching for “Niagen”, you quickly realize you can get the same thing for 1/2 the cost or less elsewhere.

Screenshot 2016-01-25 15.21.18

[box]Conclusion: Since ALL Niagen comes from Chromadex, there is no difference in the quality among brands[/box]

What does Basis do?

The field of Anti-Aging supplements is littered with scams and hoax products that are supposed to miraculously stop the aging process.

It is for that exact reason that Elysium Health DOES NOT market Basis specifically as an anti-aging pill.

Rather, they focus on some specific areas that their pill may help with such as:

— DNA repair
— Energy production
— Cellular detoxification
— Protein function

Basis – Conclusion

  • Niagen plus Pterostilbene (similar to Resveratrol)
  • Pre-eminent antiaging researcher as cofounder of company
  • 6 Nobel laureate scientists on advisory board
  • By far the most expensive Niagen on the market
  • One bottle a month may not be enough for optimum results



[post-content id=59982]


[post-content id=55017]

Nicotinamide Riboside fights aging liver disease in Mice

NR liver disease5Increasing evidence about the importance NAD+ levels in the body continuous to emerge.

This week reseachers in China released a report indicating a link between the onset of nonalcoholic fatty liver disease (NAFLD) and the aging associated decline in NAD+ level.

Further more they found that supplementation with nicotinamide riboside in a NAD+ deficient mice model completely corrected these NAFLD onset symptoms.

Aging is known to be an important risk factor of nonalcoholic fatty liver disease (NAFLD). The researchers wanted to know whether the whether the deficiency of nicotinamide adenine dinucleotide (NAD+) that develops with aging may be the cause or part of the cause.

They setup an experiment that firstly compared NAD+ concentration, together with the protein levels of nicotinamide phosphoribosyltransferase (NAMPT) and several other critical enzymes regulating NAD+ biosynthesis, between middle-aged and aged mice or human patients.

NR liver diseaseIn addition the influences of NAD+ decline on the steatosis (infiltration of liver cells with fat) and steatohepatitis (type of liver disease, characterized by inflammation of the liver with fat accumulation in liver) was evaluated in wild-type (WT) and H247A dominant-negative enzymatic-dead NAMPT transgenic mice (DN-NAMPT) under normal and high-fat diet (HFD).

The found that hepatic NAD+ level (NAD+ level in the liver) decreased in aged mice and also people. NAMPT-controlled NAD+ salvage, but not de novo biosynthesis pathway, was compromised in the liver of elderly mice and human.


NR liver disease3The experiment also revealed that under normal diet, middle-age DN-NAMPT mice displayed systemic NAD+ reduction, and had moderate NAFLD phenotypes, like lipid accumulation, enhanced oxidative stress, triggered inflammation and impaired insulin sensitivity in liver.

A high fat diet worsened these NAFLD sympthoms.


A diet that contained nicotinamide riboside however, a natural NAD+ precursor, completely corrected these NAFLD onset sympthoms that were induced by NAD+ deficiency alone or the high fat diet.

From an experiment to evaluate whereas an adenovirus-mediated SIRT1 overexpression would reverse NAFLD phenotypes also it was found that this only partially corrected the disease sympthoms.

NR liver disease2Overall this contributes further to the evidence that aging-associated NAD+ deficiency is a critical risk factor for aging related diseases.

In this study it was shown that supplementation of nicotinamide riboside may be a promising therapeutic strategy to prevent and treat NAFLD.

This article will in the future be updated with dosing related information once that comes available so we can calculate the human equivalent dose.

You can find the article here.

Nicotinamide Riboside helps alleviate problems from diabetes in Mice

NR diabetes1 In a study that perhaps more serves as proof that NAD+ deficiency plays a role in diabetes researchers used high levels of nicotinamide riboside supplementation to demonstrate it protects mice from diabetes complications.

There is an association between prediabetic polyneuropathy (PDPN)1 and obesity, about half of individuals with diabetes will also suffer from diabetic peripheral neuropathy (DPN)2, which makes them insensitive to heat and touch.

This condition can progress to foot ulcers and amputations. Unfortunately there are few treatments that are effective for obesity while there are no known treatments for DPN. Best available care is tight glycemic control, lifestyle changes centered on dietary improvement and exercise, and pain medication when DPN is painful.

The researchers noted that in prior research there are indications that supplementation with nicotinamide riboside (NR), a NAD+ precursor vitamin can improve metabolic health in overfed mice. They also noted that research indicates that NR has an ability to protect damaged neurons.

Because of this dual potential the researchers hypothized that NR may improve prediabetic (PD) and diabetic glucose and lipid metabolism while simulatanuously treating the neuropathic complications that come with DPN. The researchers tested the potential positive effect of NR in mouse models.

NR diabetes2A large cohort of mice was used in the experiment and several comparison groups created, increasing its relevance.

Out of a group of 60 mice 40 were transferred to a HFD and 20 mice stayed on normal diet. Of the 40 mice 20 were given 20 STZ, a chemical that induces type 2 diabetes (T2D). Finally of each group 10 mice were given NR supplementation at a dosing level of 3g/Kg/day. The groups were then studied for various disease indicators.

The study found that NR improved glucose tolerance, reduced weight gain, liver damage and the development of hepatic steatosis in prediabetic mice while protecting against sensory neuropathy.

In type 2 diabetes mice the results showed that NR strongly reduced non-fasting and fasting blood glucose, weight gain and hepatic steatosis while protecting against diabetic neuropathy. The researchers concluded that the neuroprotective effect of NR could not be explained by glycemic control alone.

They therefore used corneal confocal microscopy to analyse deeper. This revealed a protective effect of NR on small nerve structures in living mice. It was established that hepatic NADP+ and NADPH levels were significantly degraded in prediabetes and type 2 diabetes but were largely protected when mice were supplemented with NR.

The dosing, as mentioned earlier, was very high at 3g/Kg/day. Using FDA specified guidelines  we can calculate the Human Equivalent Dose (HED) for the NR diet given to the mice. Using this guideline 3g/kg dosing in mice translates into a HED of approx. 240mg/kg.

Or into approximately 17 gram daily nicotinamide riboside dose for a person weighing 70kg. Typical supplements on the market have serving sizes of 250mg. It should be noted that this dose is well over the limit wrt to side effects and safety.

NR diabetes4Nevertheless the data calls for further investigation e.g. repetition at lower dosing and possibly testing of NR in human models of obesity, type 2 diabetes and associated neuropathies.

Given the current dosing ranges it appears likely that a therapeutic approach will need to be done under medical supervision. It should be noted that there are also alternative supplements that hold promise for treatment of diabetes.

You can find the study here.

Nicotinamide Riboside Reprograms Aging Stem Cells


By Mickey Johnston

A study published in the leading academic journal Science in April 2016 showed that supplementation of aged mice with nicotinamide riboside, a form of vitamin B3, resulted in both increased lifespan and enhanced healthspan.1

Scientists found that nicotinamide riboside has the ability to reprogram dysfunctional stem cells to function as they did in youth.(1)

Although this study was done on mice, it suggests enormous promise for nicotinamide riboside to halt and reverse human aging factors.

Nicotinamide riboside functions to boost cell levels of the energy-factor NAD+.

In this article, we will review the implications of this research for human longevity. We’ll also review the beneficial impact of nicotinamide riboside on obesity, fatty liver disease, and cognitive impairment.

Landmark Study

Landmark Study

An international group of researchers investigated the impact of nicotinamide riboside on life-span and functions related to overall health.1 The results, published in mid-2016, were remarkable.

Aged mice (24 months old) treated with nicotinamide riboside for 6 weeks survived, on average, 5% longer than control mice.(1)

While this may seem to be a fairly modest increase, consider two points.

First, the supplementation began when these mice were already fairly advanced in age.

Second, the average human life expectancy today is about 78.8 years.2 A 5% increase in this figure would add nearly 4 years, a significant increase if those years are healthy and rewarding ones.

Perhaps most importantly, this study suggests that the supplemented animals were healthier overall compared with controls.

Here are the highlights of those findings:(1)

  • Aged mice supplemented with nicotinamide riboside demonstrated increases in maximal running times and distances, and in grip strength.
  • Chemically damaged muscle tissue from supplemented mice was regenerated faster, and regenerated muscle was bulkier than in mice fed the control diet.
  • Supplemented mice showed increased proliferation and development of new brain cells, especially in the memory-intensive hippocampus region of the brain, compared with control animals.

Reprogramming Dysfunctional Stem Cells

With aging, adult stem cell function declines (stem cell senescence), causing a loss in tissue homeostasis and regeneration.(1)

Researchers found that nicotinamide riboside increased strength, endurance, and recovery times in aged mice because it increased the number and function of muscle stem cells, providing the mice greater resources for maintaining strong, healthy muscles.(1)

This study showed that supplementation with nicotinamide riboside led to significant improvements in lifespan and factors influencing health. The fact that these changes occurred in aged mice gives hope to older individuals who are looking for viable ways to live longer, healthier lives.

How it Works

How it Works

The reason why nicotinamide riboside is such a potent promoter of healthspan and lifespan is because once it enters the body, it converts to one of the most essential factors in energy production in cells, nicotinamide adenine dinucleotide(NAD+).

NAD+ has two key functions in the body that help combat aging. First, it enhances cellular energy by boosting the function of mitochondria, the body’s cellular “power plants” that convert the food we eat into energy our bodies can use.3 While age-related mitochondrial dysfunction can result in tissue and organ failure, studies show that restoring mitochondrial function slows aging and extends longevity.1

Second, NAD+ activates enzymes called sirtuins that control gene expression. SIRT enzymes “turn off” certain genes that promote aging, such as those involved in inflammation,4,5 in fat synthesis and storage, and in blood-sugar management.6,7

By boosting the body’s levels of NAD+, nicotinamide riboside helps protect the body against some of the most potent age-accelerating processes that threaten longevity. Three of these disorders include obesity, nonalcoholic fatty liver disease, and cognitive decline.

Let’s look at nicotinamide riboside’s impact on each one:

  • Obesity: A 2012 paper showed that nicotinamide riboside supplementation in both cultured cells and tissues activates sirtuins, which boost fat-burning and prevent some of the metabolic changes induced by obesity.8
  • Nonalcoholic fatty liver disease: NAFLD is the most common chronic liver disorder in industrialized nations and one closely related to our obesity epidemic.9 Nicotinamide riboside was found to prevent—and even reverse—NAFLD in mice on a high-fat, high-sugar diet. This effect was due to its ability to increase sirtuin activity, which resulted in sharp increases in mitochondrial fat burning as well as increases in the energy storage molecule ATP, which all cells require to perform their functions.9
  • Alzheimer’s disease: Mitochondrial dysfunction and poor energy management in brain cells are closely associated with the development of Alzheimer’s disease.10 Nicotinamide riboside helps combat both of these factors. A recent study of a mouse model of Alzheimer’s showed that supplementation with nicotinamide riboside for three months significantly slowed cognitive deterioration.10 As expected, these results appeared to arise from the supplement’s ability to improve energy production in brain cells.


The concept of radical life extension is steadily moving from science fiction to science reality

The concept of radical life extension is steadily moving from science fiction to science reality.

Nicotinamide riboside shows evidence of enhancing the healthspan as well. This is vital, because added years of low-quality life do not represent, for most people, much of a gain.

This landmark study indicates that supplementing with nicotinamide riboside could help one live longer and healthier. More research is urgently needed to corroborate these remarkable findings.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.


  1. Zhang H, Ryu D, Wu Y, et al. NAD(+) repletion improves mitochondrial and stem cell function and enhances life span in mice. Science. 2016;352(6292):1436-43.
  2. Available at: Accessed December 21, 2016.
  3. Guarente L. CELL METABOLISM. The resurgence of NAD(+). Science. 2016;352(6292):1396-7.
  4. Kotas ME, Gorecki MC, Gillum MP. Sirtuin-1 is a nutrient-dependent modulator of inflammation. Adipocyte. 2013;2(2):113-8.
  5. Galli M, Van Gool F, Leo O. Sirtuins and inflammation: Friends or foes? Biochem Pharmacol. 2011;81(5):569-76.
  6. Li X, Kazgan N. Mammalian sirtuins and energy metabolism. Int J Biol Sci. 2011;7(5):575-87.
  7. Chang HC, Guarente L. SIRT1 and other sirtuins in metabolism. Trends Endocrinol Metab. 2014;25(3):138-45.
  8. Canto C, Houtkooper RH, Pirinen E, et al. The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab. 2012;15(6):838-47.
  9. Gariani K, Menzies KJ, Ryu D, et al. Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice. Hepatology. 2016;63(4):1190-204.
  10. Gong B, Pan Y, Vempati P, et al. Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-gamma coactivator 1alpha regulated beta-secretase 1 degradation and mitochondrial gene expression in Alzheimer’s mouse models. Neurobiol Aging. 2013;34(6):1581-8.

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+ 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).

  • The salvage pathway sustains 85% or more of our NAD+ (14)
  • Nampt is the rate-limiting step in the salvage process (97).
  • As we age, Nampt enzyme activity is lower, resulting in less NAM recycling, less NAD+, more disease and aging (97,101).


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.


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.

* Note:  These charts are somewhat deceptive. It shows NAM (green bar) elevated NAD+ nearly as much as NR (black bar)

However if they used equal mg of each supplement, which is how people actually purchase and use them, it would show NA about equal with NR and NAM far effective than NR at elevating NAD+ in the liver.

Mice in these experiments didn’t receive equal WEIGHTS of each precursor. Instead researchers chose to use quantity of molecules, which makes NR look “better” by comparison.

In this case, “185 mg kg−1 of NR or the mole equivalent doses of Nam and NA”(16).

Molecular weight for NR is 255 grams, NAM is 122 grams, and NA 123 grams.  So this chart used a ratio of  255 grams of NR to 122 and 123 grams of NAM and NA.


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


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


  • 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)


  • 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)


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)

Only NMN is readily available in the bloodstream to all tissues, and bypasses the Nampt bottleneck in the Salvage pathway


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.


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.


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.


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).


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





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.



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


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


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


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.


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.


[post-content id=59982]



[post-content id=55017]


Research shows Nicotinamide Riboside may prevent Liver Disease


Nonalcoholic fatty liver disease (NAFLD) is the underlying problem being most liver disease in the US and other western countries due to the prevalence of obesity.

It can result in total liver failure and death. With nearly 37%  of adults in the US now classified as Obese, and projected to be 60% in the next 10 years, the problem is only going to get worse.

Although there are many contributing factors, insulin resistance plays a key role in the deterioration of the livers ability to process the fat.

Mitochondria dysfunction also contributes to inflammation and fibrosis further impacting the liver function.

This study  demonstrates that boosting NAD+ can  protects  against many age and diet related chronic diseases such as chronic liver failure.

The results confirm prior studies on the role NAD+   plays in supporting sirtuinsi to repair cellular damage, and in particular protecting from NAFLD.

The research shows that a diet high in  fat and sugar contributes to NAFLD, and that adding Nicotinamide Riboside to the diet boosts NAD+ levels which improves Mitochondria unfolded protein response (UPRMT) to help prevent and reverse NAFLD.

For the study,  SIRT Knockout Mice were fed a high-fat, high-sucrose diet, or normal chow diet.   1/2 the mice were also fed  500 mg/kg Nicotinamide Riboside pellets for 18 weeks.

From the data, the researchers postulated that boosting NAD+ levels increases sirtuin-mediated UPRmt activation and mitochondrial biogenesis, while also reducing UPRer stress response.

In agreement, they found nicotinamide riboside attenuated the severe mitochondrial dysfunction, typified by reduced mitochondrial content and function, present in fatty livers of mice fed a long-term high-fat high-sucrose diet.

These robust effects of NR on mitochondrial function were reliant on the NAD+-mediated SIRT1 and SIRT3 induction of mitonuclear protein imbalance, triggering the UPRmt.

Similar to previous reports linking the beneficial effects of NMN and NR to the UPRmt activation of UPRmt in livers of these NR-treated animals maintained optimal mitochondrial function despite a chronic FA overload.

Overall the data shows that boosting of depleted liver NAD+ stores in mouse models of NAFLD, by administration of Nicotinamide Riboside supplements, recovers liver NAD+-dependent SIRT1 and SIRT3 signaling to counteract the development of NAFLD.

And that the beneficial effects of NR are largely mediated by the cell-autonomous effect of SIRT1 activation in the liver.

Using the FDA guidelines for converting the dosage tested to humans, the 500 mg/kg results in a daily dosage of around 2,200 mg for a person weight 160 lbs.  This is in the range used for other testing with mice for therapeutic purposes.

Note that this is much higher than the dosage used in recent testing for safety.  It is also nearly 4x the  recommended by most brands, and more than double the amount used in recent testing to measure NR’s ability to raise NAD+ levels.

Chromadex is currently performing tests with humans at various dosage levels to determine optimum and safe dosage levels.


Niagen Brands and Pricing

chromadex niagenNiagen is the brand name of the only commercially available brand of Nicotinamide Riboside, a recently discovered B3 Vitamin that is proving to have astounding anti-aging and health benefits.

Chromadex is the manufacturer, and owns 5 patents granted for its production which allows them to control the market for Nicotinamide Riboside.

They license several companies to bottle and distribute Niagen, and tightly regulate the retail pricing, so there is very little difference in Nicotinamide Riboside products.

There are minor differences as manufacturers use different capsule sizes, and some add fillers to aid in the bottling process and/or preservatives to extend shelf life.


HPN and LiveCellResearch were the first brands to market online.

As Niagen becomes mainstream, many big brands are now coming to market such as Thorne Research who have a reputation for producing some of the most innovative and top quality products.

The lowest advertised pricing online is below. They use different capsule sizes, and different number of capsules per bottle, so we do the math for you to figure the cost per milligram to make it easier to compare the prices.

[table id=2 /]

[box]These are the minimum allowable prices, which are strictly enforced by manufacturers.
Click Here to receive notice of special offers, group buys, or recent news.[/box]

HPN- High Performance Nutrition has options for 3 bottles, and also a 6 bottle package which further cut the cost a little closer to what Thorne Research cost.

LiveCellResearch This company does the most advertising all over the internet. They have good price for single bottle purchase, but they don’t offer quantity deals like HPN does. Also, many people aren’t too thrilled by the constant stream of emails they send marketing other products.

Thorne Research manufactures the highest quality products and sells through their networks of Doctors, clinics and other health professionals, without the added markup of going through distributors and vitamin stores, so often have the best prices as with their Nicotinamide Riboside products.


Most of these brands use pure Niagen, so there is no real difference in the product, only in the cost.

An exception is Basis, which adds pterostilbene, a kind of resveratrol, that supposedly increases the effectiveness. They certainly do have a very impressive list of 7 nobel laureate scientists backing this product which aids them in their marketing efforts and allows them to charge a LOT more than competitors for their fancy version of Niagen. Read the full review on Elysium Health.

  • Basis $60 for 60 125 mg capsules make this by far the most expensive Niagen on the market. If you don’t care about cost, this may be a good choice.
  • Doctors Best Good Brand, but expensive, and 75mg capsules too small
  • F1rst Available soon at GNC stores. $49 for 60 (100mg) capsules.
  • Enerdrex (Not yet Available) soon to be in Walgreens, Costco, Publix, Kroger
  • Proctor and Gamble (Not yet Available) to be included with other products
  • NR Age defense  (Not yet Available) – CVS stores Nationwide

[product_category category=”nicotinamide-riboside” columns=”3″ per_page=”9″ orderby=”date” order=”desc”]

Nicotinamide Riboside Benefits and Side Effects

Senior hispanic man working on a white backgroundNicotinamide Riboside is said to repair functioning of the mitochondria which power energy generation in every cell in our bodies.

This is supposed to “turn back the clock” and make us younger, and repair many (not all) of the ravages of aging.

There have been several research studies  with NR and NMN that do show great promise, but also leave some questions to be answered by other studies that are currently underway

In this article we examine the research to date on Nicotinamide Riboside.


NR has been shown to increase NAD+ levels in humans.

This results  in speculation that NR might be useful in treating many age related health conditions such as:

  • alzheimers
  • parkinsons
  • metabolic syndrome
  • erectile dysfunction
  • rheumatoid arthritis
  • depression
  • thyroid
  • prostate cancer
  • hearing loss
  • acne
  • appetite suppression

Testing is currently underway to evaluate Nicotinamide Riboside  for treating many of these symptoms.

Research studies  with mice have demonstrated that supplementation with NR:

  • Improves cognition in mice with Alzheimers (32) 2013
  • Lowered cholesterol, improved hepatic inflammation in tumors (33) 2015

To date the only completed testing with human subjects for treatment of specific conditions is:

  • Protects against hearing loss caused by noise exposure (34) 2014

Many studies are currently ongoing such as an obesity study underway by  the Novo Nordisk Foundation Center for Basic Metabolic Research.

[box]Conclusion: Nicotinamid Riboside has proven effective in treating several degenerative conditions. Much more testing is needed and currently underway. [/box]


Decreased NAD+ levels are implicated in many age related disease and disabilities.

NR does raise NAD+ levels in human tests lasting 1 week. Long term testing is not yet complete.

NR has been shown to improve or protect against some age related problems, and shows potential for much more.

In addition to protecting various organs such as liver and kidney, heart, lungs, and neuro-protection, NR is marketed as a potential anti-aging therapy. It may yet prove to be of some benefit in slowing some aspects of the aging process, but as yet there is no definitive proof.

[product_category category=”nicotinamide-riboside” columns=”3″ per_page=”9″ orderby=”date” order=”desc”]