Nicotinamide Riboside — Where’s the Beef?

NR is a supplement that affects energy generation in mitochondria and gene regulation through the same pathway as resveratrol and caloric restriction.  It has been promoted in recent months, and this month is featured in Life Extension Magazine.  But evidence for its life expectancy benefit is indirect.  There have been no positive results for fruit flies, let alone mice.  If it works in humans, benefits will likely be limited to people who are overweight.  And there are reasons to expect only limited benefits from the pathways through which NR works.

Reading about a new life extension supplement, I get excited when I see “we fed it to mice and they lived X% longer”, or better yet, “In preliminary human trials, mortality was found to be Y% lower.”  The articles about NR are full of biochemical pathways and chains of genes that promote other genes.  In my way of thinking, all the biochemistry is important for generating ideas, but the proof of the pudding is in life extension trials.  Lab experiments on live mice run hundreds of thousands of dollars to test a single compound.  We can’t be testing everything under the sun, so we rely on biochemistry for plausible candidates.  But jumping from biochemical theory to marketing of a supplement is a leap of faith that leaves me behind.

Worms and flies are much cheaper to breed than mice, and the experiments last weeks instead of years.  Furthermore, genetics of these lower animals is well-understood, and easy to manipulate.  Experiments with worms and flies provide an intermediate proving ground for ideas before the expensive life span trials with rodents.  The ultimate yield is low.  There are many interventions that work well to extend life in flies that don’t work in mammals.

 

NR and Resveratrol

Resveratrol, which works along similar biochemical pathways to NR, was all the rage from about 2003 to 2006.  First discovered in yeast, its mechanism of action was mapped out.  Len Guarente at MIT and others from his lab put the SIR gene on the  map, and coined the term “sirtuins” for substances that activate these genes.

Excitement mounted as resveratrol was shown to extend life span in worms, and then flies.  A young scientist in Italy launched his career by introducing a short-lived African fish to laboratory genetics.  Nothobranchius lives only a few months, one of the shortest life spans of any vertebrate.  For his PhD dissertation, Dario Ricardo Valenzano (2006) safaried to Africa to bring back samples of Nothobranchius, figured out how to breed them in the lab, and demonstrated they live 60% longer with resveratrol in their food.

Incidentally: Valenzano found best results for an intermediate dose of resveratrol, not the highest or the lowest dose.  This has been a recurrent theme in resveratrol research: a little is better than none, but a lot isn’t better than a little.

Soon after Valenzano’s fish, it was reported that resveratrol failed to extend life span in mice.  We were all disappointed.  The result came from the Harvard lab of David Sinclair, Guarente’s most famous student, who was highly motivated to get good results because he had commercial ambitions for resveratrol derivatives.  Sinclair reported that overweight mice that were fed a high-fat diet could be brought back to a normal life expectancy with resveratrol, but that normal-weight mouse received no life extension from the same treatment.

 

NR in experiments with lab animals

Almost all the literature on NR is about yeast cells.  I can’t find a single study on flies or fish.  I found one study of Alzheimer’s Disease in mice that did not look at life span, but the measured the plaques in the brain that are a symptom of AD.  These are mice that are genetically engineered to be vulnerable to AD, because normally AD is absent in mice.  They showed that feeding these mice NR slowed the progress of their mental decline, a good result that traces dietary cause all the way to behavioral effect, its ultimate benefit.  Another mouse study showed metabolic benefits for mice that were fed to obesity.  This was similar to the result for resveratrol, but not as strong because life extension for obese mice was recorded from resveratrol, but not from NR.  The only study in worms showed a 16% life extension.  This kind of performance would be impressive in mice, but there are many ways to double and triple the life span of worms that don’t work in mammals.  (the record is tenfold increase in a genetically modified worms).;

 

Biochemistry of NR and NAD+ / NADH

Biomolecules are a huge variety of different geometric structures, based mostly on covalent bonds between carbon and carbon or between carbon and hydrogen.  But the body’s energy metabolism is based on ionic bonds, because they store more energy in each bond.  Ionic bonds form between atoms that are very different from each other, like sodium and chlorine in table salt.  The standard biological energy repository is in phosphate bonds.

Every cell has hundreds of mitochondria, which are tiny energy factories that burn sugar and produce  phosphates for the cell’s use.  This energy generation process is an ancient biochemical trick called the Krebs Cycle, and is shared by all plants and animals today.  NAD+ has a role to play in the Krebs Cycle, where it absorbs an electron to become NADH, and then is recycled to NAD+ again.

As we age, we lose mitochondria, and the mitochondria we have become less active.  We have less of all the chemical intermediates of the Krebs Cycle, including CoQ10 and NADH.  CoQ10 is an important anti-oxidant, soaking up ROS and converting their energy to useful form.  CoQ10 has been found to improve heart health, but it has failed to extend life span in mice.

In addition to its role in the Krebs Cycle, NAD+ works through sirtuins.  These are high-level chemical signals that can close up DNA into tight balls (facultative heterochromatin) selectively in certain places to block expression of many genes at once.  NAD+ can turn on sirtuins in order to turn off a panoply of pro-aging genes.  This has been shown to work well to slow aging in obese lab animals, but not normal animals.  It works by some of the same pathways as caloric restriction, but without the restriction.

 

Saturation of the CR pathway

Life span is programmed in a flexible way, so as to respond to external mortality.  Famine is one of the deadliest dangers for populations in nature, and so evolution has provided extra ruggedness in the face of starvation.  Death from aging takes a vacation just when the death rate from starvation is highest, helping to level out the overall death rate and protect against extinction.

The fact that life span is extended by hunger was first discovered in the 1930s, and many years later, the genes and biochemical pathways associated with sensing food scarcity have proven to be the most accessible, the easiest to manipulate.

Underfeeding, and tricking the body into thinking it is underfed, are the simplest, most fertile, and most reliable strategies for extending life span.  On a percentage basis, these strategies work best in short-lived species.  With caloric restriction we can double the life span of worms, add 40% to the life span of mice, but only 15% to dogs and 5% or less in Rhesus monkey experiments reported last year.  So 3 to 5 years is an optimistic range for the available flexibility in humans via the caloric restriction pathway.

There are many ways to activate this pathway, either by eating less, exercising, or taking metformin or resveratrol, for example.  The benefit you get from each of these do not add together; rather you are getting the same 3 years over and over again.  So NR is likely to work best for people who are overweight and not taking metformin or resveratrol.

 

The bottom line

It may be that there have already been experiments feeding NR to mice or rats, but sometimes negative results don’t get published.  I am going to wait and see before jumping on the NR bandwagon.

150 thoughts on “Nicotinamide Riboside — Where’s the Beef?

  1. Dietary supplements of nicotinamide riboside, a derivative of vitamin B3, prevent the development of liver tumors and induce tumor regression in mice

    Liver cancer is one of the most frequent cancers in the world, and with the worst prognosis; according to the World Health Organisation (WHO), in 2012, 745,000 deaths were registered worldwide due to this cause, a figure only surpassed by lung cancer. The most aggressive and frequent form of liver cancer is hepato-cellular carcinoma (HCC); little is known about it and there are relatively few treatment options.

    Researchers from the Spanish National Cancer Research Centre (CNIO), have produced the first mouse model that faithfully reproduces the steps of human HCC development, from the appearance of the first lesions in the liver to the development of metastasis. The results, published in the prestigious journal Cancer Cell, indicate that diets rich in nicotinamide riboside, a derivative of vitamin B3, protect these mice from developing HCC in its most initial stage, when genotoxic stress is damaging cellular DNA. They also show a curative effect of the diet in those mice that had previously developed the disease.

    A MOUSE MODEL FOR HUMAN HEPATIC CANCER

    One obstacle to the study of human HCC is the absence of mouse models that replicate the disease, which could be used to investigate molecular pathways or new therapies. Given that human HCC is associated to alterations in hepatocytes survival, and that the URI oncogene plays a role in this process, the researchers genetically engineered mice that contained high levels of URI only in the liver, in a controlled manner over time.

    At 30 weeks, the mice with high levels of URI generated sporadic tumours in the liver and even metastasis when the induction lasted longer. The study details how deficiency in nicotinamide adenine dinucleotide (NAD+), a universal compound found in living organisms that is needed to burn calories via cell metabolism, orchestrates the development of the disease.

    “An increase in URI reduces cellular NAD+ and as a consequence produces genotoxic stress and DNA damage”, says Nabil Djouder, leader of the study and Head of the Growth Factors, Nutrients and Cancer Group in the BBVA Foundation-CNIO Cancer Cell Biology Programme. “It is still not totally clear, however, why the deficit in NAD+ causes these lesions,” he adds.

    ENERGY METABOLISM AND CANCER

    The appearance of DNA damage is the first link in the chain of events that activate the carcinogenic process in the liver, even before apoptosis or cell death, as has been described in the literature. “We normally say that oncogenes induce DNA damage. Now we may be able to say, more appropriately, that oncogenes induce NAD+ depletion [or deficits in NAD+] which causes DNA damage,” says Djouder.

    The inverse relationship between NAD+ and cancer awakened the curiosity of the researchers: could an increase in NAD+ have beneficial effects on the disease? When the scientists supplemented the diet in genetically modified mice with nicotinamide riboside, a derivative of vitamin B3 that increases intracellular levels of NAD+, they did not observe tumour development. Surprisingly, when they gave this diet to mice that had already developed the disease, the size of the tumours was reduced and they eventually disappeared.

    The results have been reproduced in other types of cancer such as pancreatic cancer. “We observed the same results in mice with pancreatic adenocarcinoma with regards to DNA damage, so we could conclude that this treatment is effective on tumours caused by oncogene-induced DNA damage and thus, deficit in NAD+,” says Krishna Tummala, first author of the study.

    In addition to working with the mouse model, the authors have collated the results of nearly a hundred human samples. “Those from patients with HCC contain URI levels that double those of healthy samples,” according to the article. The data, which also associates URI with a worse prognosis or evolution of the illness, suggests that the gene could be a possible new HCC marker, and nicotinamide riboside boosting NAD+ levels may have a human relevance.

    FUTURE RESEARCH

    Several epidemiological studies coincide in associating diets low in tryptophan [a NAD+ precursor] with an increased incidence of certain types of cancer. It has also been observed that daily supplements of vitamin B3 in populations with chronic nutritional deficiencies, reduces the incidence of some cancers including oesophageal cancer.

    Despite the results, the researchers underline that the efficiency of NAD+ enhancing nutritional supplements to protect healthy cells from chemotoxic stress as a combined therapy in oncology still needs to be demonstrated. Djouder’s team is collaborating with the CNIO Clinical Research Programme, lead by the oncologist Manuel Hidalgo to broaden these studies in mice and evaluate the possibility of carrying out clinical trials in humans in the future.

  2. Regards CR mimetics,
    Resveratrol has increased the lifespans of not just yeast, worms, fruit flies, fish, mice fed a high-calorie diet, but of genetically induced mitochnodrially dysfunctional mice, and in senescence accelerated SAMP8 and SAMR1 mice. It has also tripled human cell survival to a dose of gamma radiation.

    The dog experiment that yielded 16% was at 25% restriction not max 65% restriction We don’t know if igf1 levels in dogs are affected by protein intake as they are in primates which may have affected results

    The primate studies are not over yet and just this year it was said that big benefits are obtained contradicting earlier reports. Animals of off cr had triple the risk of death and animals who started cr in adulthood were already exceeding the max lifespan in captivity
    http://www.news.wisc.edu/22672

  3. “but only 15% to dogs and 5% or less in Rhesus monkey experiments reported last year. ”

    The 16% on dogs, was on 25% CR, iirc not maximal 65% CR. Human igff1 levels have been influenced by protein intake, which may also affect other long lived species igf1 which may affect longevity

    As for the primate study the earlier findings of small benefits were questioned this year. It seems that not only have several monkeys who started CR in adulthood exceeded the maximum lifespan in captivity of the species studied, but those not on CR experienced triple the risk of death
    http://www.news.wisc.edu/22672

    Regards resveratrol, it has not only extended the life of fish, worms, yeast, obese mice, but also mitochondrially dysfunctional mice and several types of senescent accelerated mice strains. It also tripled human cell survival upon exposure to gamma radiation. Why it failed on normal mice, is a good question…. the fact that their nad goes drastically down with age, iirc, could be a culprit as this might handicap sirtuin activity which necesitates it, iirc, even in the presence of sirtuin activity enhancing compounds such as resveratrol.

  4. *note on similarly worded replies. Since the first reply did not appear on site after a while, I thought it was lost and I did another reply and posted it just in case..

  5. Those responses, while interesting don’t negate Josh’s main point. We do not yet have anything close a complete model of how aging works so anything we discover about low level pathways is really only useful as a filter to decide where to direct further research efforts. Early excitement about almost every area of research from resveratrol to telomerase almost always gets tempered as research progresses to more complex organisms. And NR hasn’t progressed very far up that chain so a rational response is to acknowledge that at this stage the probability is still pretty low that its effects will be confirmed to extend life or even substantially improve the quality of life _for_most_people_. That assessment might improve with more research but that initial assessment of probability is based on the track record of other research in this area at this stage. So aggressive supplement marketing is most definitely selling hype not substance at this point in time.

  6. I know this is is not research but maybe the people here will find it interesting. I have suffered from low energy and fatigue for years. My best description is that my muscles feel like they are made of lead. Some days it was a challenge to go for simple walk with my wife and daughter. The only time I noticed and extreme change was about 12 to 16 hours into a fast. I would have a lot more energy and ease of movement. I always called it flow. I attributed it to something I wasn’t eating. I never thought it was because I wasn’t eating. I recently found out about NR and it’s affect on NAD+. I decided to try it out. It’s only been a week but I can say I have never experienced anything this dramatic before. I feel just like I did when i was fasting except it is all of the time. This whole week my energy has been through the roof and my movements are free and fluid. I feel like I am 20 again. I know more proof and studies are needed but for me, right now it’s as real as it gets. If I can keep this quality of life it’s well worth a buck fifty a day.

    • Joe: I also am no scientist yet do have Layman’s Knowledge on basic natural health. The energy level increases you sustain during fasting are typically due to your body using up the stored glycogen (usually 2 to 3 days) and shifting its caloric source to fat (from sugar, carbs, protein et al). I was taught that carbs and protein burn at a rate of about 4 calories per gram and fat burns at a rate of about 9 calories per gram.

      When your body reaches this level of ketosis (used up the glycogen and now burning fat), energy levels effectively double. CAREFUL though, without the carb intake, a crash is likely during “heavy” exercise.

      I conducted an experiment on myself (admittedly “non-scientific”) when I became a “diet consultant” and proceeded upon a strict eating protocol we dubbed “The Pancreatic Protocol.” Short explanation is that we altered our intake to “force” the body to burn fat (details available outside this forum (FB Richard Lee Eldridge). During the experiment, my energy levels shot through the roof and I tested sustainability by taking a brisk bicycle ride. My speed increased 4 to 7 mph over my standard (15 to 19)…. for about one (1) mile. I became so fatigued I walked my bike home. Doctors (participating in the Pancreatic Protocol) explained that my low carb intake would not allow heavy physical exercise — I became a believer! (BTW: I lost 36 pounds of pure fat and gained 11 pounds of muscle in 60 days of the experiment as measured and documented by medical doctors and their test equipment).

      I agree with previous comments that EXPERIENCING RESULTS is what counts. I hope the NR you’re using DOES help in the long-run. I am always looking for healthier and life-sustaining (even extending) natural processes… Shouldn’t we all? 🙂

        • Joe: You may contact me by FB message at the name listed above and we will find a convenient way to chat or talk.

          • Richard, I’d like more information on the diet as well. I’ve been struggling to lose weight. I have to lose it as my blood pressure is crazy high. I don’t know why but it was normal in October and then when I was checked in May it was way to high. My doctor told me to lose weight and quit my wine and she’ll retest me in July.

      • Richard: Thanks for the input. Unfortunately I never fasted for more than 24 hours and the increased energy I experienced usually happened within 12 to 16 hours. From what I understand that is not long enough to trigger ketosis. I also do not eat low carb before or after I fast. I tried that lifestyle in the past and it did not agree with me. For now NR is still working for me and I am very curious as to why it is so hit or miss for other people. I can only guess that it must work better for certain ailments than others, or maybe I am more sensitive than the average person. Hopefully science will eventually validate my experience with it.

        • The brand I use is Live Cell Research. If you get on their mailing list you can catch deals for as much as forty percent off. The bonus deals that pop up when you are ordering are pretty cheesy but I ignore them. I normally take the recommended dose in the morning. After a year of taking it I can say that it has not gotten rid of my grey hair, made me younger, helped my tinnitus, or cured my blood sugar issues but I still feel better when I take it than when I don’t. I also seem to sleep better. If you decide to try it let me know how it works for you.

    • I can second this. I am 49 years old and about 50 pounds overweight. Fasting is the only thing that gives me relief from feeling sluggish and totally lacking in energy. Exercising moderately (20 minutes on a treadmill every work day) has only had limited effects. I feel a little better but not much. Last summer I took NR and I can say that after a week and a half I felt great. I stopped taking it because of the expense and I went back to feeling crappy over the winter again. This week I have been taking it again and I feel great again. I think I’m going to shell out some $$$ for about three months supply. I agree it’s totally anecdotal but nevertheless.

  7. @ Joe – do you take Life Extension Foundation product
    Optimized Resveratrol with NAD+ Cell Regenerator™
    Nicotinamide Riboside
    or Biotivia’s product NAD+ MitoTrans?
    Also, if you do not mind to answer how old are you, since you compare your age with “20 years old”.
    I have the overall idea that some of these effects are more dramatic for older people, than younger people. It would be interesting to find a pattern/correlation.

    @Josh – I might have suggested this before, but would be more effective to organize your blog as a mind map. There are several Open Source mind-maps packages out there. That way logical connectors can be made between subjects, and who knows, discussions in this blog might help the overall progress/discoveries in age reversal.

    Thanks.

    • I have tried Doctor’s Best – Best Energy and HPN – N(R) so far. The Doctors best worked so well I ordered the HPN shortly afterwards since it was cheaper on a per gram basis. I didn’t see the need to go with anything else since there is currently only one manufacturer of NR. I am 43 years old, 6’1″ and 153 pounds. I can add that my wife saw my improvement and decided to try a half dose (75 mg) of the Doctor’s Best and said in three hours she noticed an amazing improvement in how she felt and in her energy level. She is the same age as me. Of course I can’t say much as far as life expectancy but I know NR is doing something. I want to add that I originally took NR to see if it would help with my tinnitus. I read an article that said it was able to protect mice from hearing loss after exposure to loud noise and it said it might help with tinnitus. So far I have not noticed any improvement in my tinnitus.

  8. Joe –
    thanks for reply!
    Took me a while to post again, as I got caught with other tasks.
    As age goes, we are pretty close (I’m going to be 45 soon), so I hope I can feel like “20 again” too!
    After you mentioned High Performance Nutrition N(R) Niagen NAD+ Booster, I was doing a Google search and I was looking at Live Cell Reasearch that have Niagen’s at a slightly lower price. I’ll do more research and see if it is a good buy, or I’ll buy LEF’s or HPN’s. Either way, once I start using it I’ll post my experience. Thanks again for your reply!

    • Adrian-
      Thanks for the heads up on the LCR brand being a bit cheaper. These days every dollar counts. I have a bit of an update concerning my experience with NR. I started taking it on 12/9. As of this post I am still experiencing increased energy levels along with a few other improvements. Both my tolerance for exercise and recovery (especially in between sets) are much better. My normal body aches and pains upon waking have mostly diminished. Lastly and most surprising to me is my knee. For at least 6 years I have had a dry thick patch of skin on my right knee. In the past I have tried using a pumice stone and moisturizers to get rid of it. Nothing worked. It would wax and wane but never go away. Over these past few weeks it has almost disappeared and I am starting to have feeling in that spot again. I am still extremely skeptical but very eager to see if it goes away permanently. That would be truly amazing. I found some interesting articles concerning NAD+ and autoimmune diseases. I posted a couple below. While I have never been diagnosed, maybe there is a link? I look forward to hearing your experience with NR and hope it is as positive as mine has been.

      Now, in a new study by researchers at Brigham and Women’s Hospital (BWH), a potential treatment maybe on the horizon. Researchers found that NAD+, a natural molecule found in living cells, plants and food protects against autoimmune diseases by altering the immune response and turning “destructive” cells into “protective” cells. The molecule is also able to reverse disease progression by restoring damaged tissue caused by the autoimmunity process.
      http://www.brighamandwomens.org/about_bwh/publicaffairs/news/pressreleases/PressRelease.aspx?PageID=%201889

      NAD+ protects against EAE by regulating CD4+ T-cell differentiation.
      http://www.ncbi.nlm.nih.gov/pubmed/25290058

      • These results sound truly wonderful. It would be nice if we could see that sort of result in many human patients taking this or any other supplement. We’d all be taking a supplement like that if it were as good as you describe!

        Also, some supplement advertisers might be out of a job! *smile*

  9. Joe –

    thanks for the update! Very interesting. Seems like at least for certain people, it is working on some aspects.

    Once I have start taking Niagen, and have some experience with it, I;ll post it here.
    I just wanted to mention that Live Cell Research offer a discount for Longecity community, and here is the link if you are interested:
    http://livecellresearch.com/longecity_special.php
    Again, I did not use it so far, so I cannot say anything about their product. But I do hope since they are using Chromadex’s Niagen, it is the same quality like others.

    Also, thanks for the links. Myself I do a lot in reading and researching scientific papers as I do believe reverse aging is possible and can be done in a foreseeable period of time.

    Recently I watched Leonard Guarente’s videos/interviews on youtube and other web places. Also watched a lot David Sinclair’s videos/interviews. And while everything they say there make sense, I do hope that certain aspects of aging can be reversed in humans too by replenishing NAD levels. Not that I do not want to save mice and other animals, but there is a lot of hype about “age reversal done in mice”, then after couple years, nothing happen in humans. I do think that research community needs to “wake up” and minimize the excitement around the initial results in mice/rats/flies/worms and then move quick and realistically in humans. I know that is not easy to do as saying – as first we need a clue from studies in mice/flies/etc. – but there is way too much buzz on initial studies that later on do not translate in humans. Let’s hope is not the case with NAD+.
    Also, from Guarente/Sinclair discussions, they hint at Resveratrol complementing NAD+. I guess that is why LEF and BioTivia pack their products with Resveratrol.

  10. I’m a 55 yr old male. When I started taking this product I had been working out almost daily, eating a very healthy diet, getting sufficient rest, yet I was still 30 pounds overweight, almost impotent, foggy thinking, wrinkles, ruddy complexion, thinning hair, agitated, hopeless and ready to hang it all up. My wife had run away with a young Tennessee Stud that she really liked to ride, and I was just a down trodden lonely fool.
    After a short while all that changed, well not all of it, she is still long gone with the stud, but I lost 35 pounds and am now solid and toned all over. My skin complexion is looking good, my hair grew back, my wrinkles are gone and I have the fires of life burning again.
    I look and feel like I did when I was 25. I’m dating a very attractive 26 year old gal, and she’s completely happy.
    Just joking, but I did order the product yesterday and I’m counting on all of the improvement part coming true even if I need to eat a bottle of the stuff for every single breakfast. Getting old just plain sucks, I hate it and it hates me. I’m gunna fight it until I kill it or it kills me. It’s kill or be killed.

  11. Something of interest to me is the potential impact on quality of life (or perhaps a higher chance to survive to theoretical maximum age) whether or not there is actual life extension.

  12. I have the Elysium Health product called Basic.

    The 250mg is for two capsules, and you’re looking at about $1.00 per capsule, so $2.00 a day.

    I am a fairly fit 40 year old individual but have had numerous health problems in the past year that have been unexplained. I wanted to start small so I’ve only been taking one capsule daily so far, and haven’t noticed a single change for the better or the worse. Strange to hear that only 75mg made someone’s day completely different within 3 hours (above). Wish that would happen for me! I may increase my dose however, as I was just diagnosed with a couple forms of skin cancer.

    I would also highly recommend people get their vitamin D levels up to 50-60 if you want to avoid all types of cancer.

    • I too have an AK that may need a biopsy. As its on my face, I am not eager for face knife interaction. I have been taking 500mg. NR (BASIS, 2 capsules per day) but just learned about vitamin K2. It works synergistically with vitamins A and D. So getting your Vitamin D level above 50 is good but you need to supplement with K2. I just started K2 yesterday. It is found naturally in Natto (fermented soy beans) apparently odorous and not tasty. It is also found in eggs and butter from animals fed in green pastures and in fish eggs. Google vitamin K2, it’s amazing stuff!

  13. I started taking Elysium Health Basis 3 and a half weeks ago for all the reasons listed above. What I did notice and never expected is that my rosacea improved quite a bit. I noticed it after 4 days and after 3 weeks it was better than it had been in 35 years. I never expected this and didn’t try the product with this in mind. What this means to any other part of my body I can’t guess but this is great news for me.

  14. Can I ask the difference between nicotinamide ribosine and another form of NADH as sold by Source Naturals? It’s a reduced form, and the highest milligrams sold are 20mg subliminal tabs. Can’t help but wonder what the difference is. Anyone know?

    • NADH is not absorbable through the digestive system, so there are two delivery strategies: (1) is the sublingual lozenge, which is supposed to be absorbed directly through the skin, and (2) is the precursor NR, which can be eaten, and the body converts it to NADH.

  15. Hi Josh,

    this is a good discussion. I agree with your points about not taking the natural excitement that researchers (and those who read the research) have when they have discovered something that logically may help with something like lifespan, and getting too carried away by it. Researchers try to be careful in their predictions for this very reason – but two factors also get balanced in: 1) researchers are people too, and they like to get excited about the implications of their findings, and 2) in an area such as life extension, getting excited and getting the public excited can help with getting funding agencies excited. The ultimate goal of this research has the promise to be very beneficial to potentially vast numbers of people. Given this, it is understandable that one might want to let the world know that we are getting closer and closer to compounds that may extend, if not life, then the amount of ones life that is spent in relatively good health. Even if these compounds do not prove to extend lifespan greatly in primates, there is already evidence that sirtuin activators and NAD+ precursors can revert mammalian cells and tissues from an aged phenotype to a youthful phenotype. This may explain the anecdotal effects that some of your bloggers have described. And the news, since you started this thread, is generally good. One Sirt1 activator SRT2104 that shows great promise in mice, appears from clinical trial results to be well tolerated in humans, and leads to improvements in their lipid profiles. A study run to determine if it improved insulin and glucose related parameters seems to indicate that pharmacologically, people respond differently to it, in terms of whether increasing dosage yields increases in circulating drug levels. This may mean that some people in the population metabolize it more quickly than others, or it may be related to absorption. So there is still quite a ways to go with this particular activator, like most drugs in their infancy. But a study in mice indicates that it does pass your increase lifespan in normal mice litmus test, mentioned in your first posting. Mercken et al reported in Aging Cell 2014, that mean lifespan of mice treated with this activator increased by 9.7%. Furthermore, and probably more importantly, the health of aging mice improved significantly. The abstract says it best:
    “Increased expression of SIRT1 extends the lifespan of lower
    organisms and delays the onset of age-related diseases in
    mammals. Here, we show that SRT2104, a synthetic small
    molecule activator of SIRT1, extends both mean and maximal
    lifespan of mice fed a standard diet. This is accompanied by
    improvements in health, including enhanced motor coordination,
    performance, bone mineral density, and insulin sensitivity associated
    with higher mitochondrial content and decreased inflammation.
    Short-term SRT2104 treatment preserves bone and
    muscle mass in an experimental model of atrophy. These results
    demonstrate it is possible to design a small molecule that can
    slow aging and delay multiple age-related diseases in mammals,
    supporting the therapeutic potential of SIRT1 activators in
    humans.”
    It’s a fascinating area. Once again, thanks for starting this discussion, and to everyone else for sharing your experiences with NR.

    Cheers,

    JWIV

  16. I just started taking Live Cell Research Niagen today. And will keep you informed on my findings.
    One thing to notice when purchasing NR isn’t the cost/dose but the amount of NR/dose.
    Notice some of the more expensive brands had less NR/Dose or cap and Live Cell Research has 250mg/dose.
    This is some in cases 3 time higher than other brands.

  17. I just turned 50. I purchased a bottle of the LCR Naigen and took 500mg/day for 2 weeks until I ran out. Was off Niagen for 3 days until new bottle arrived. Now back on as of today. My primary motivation was energy and focus. I’ve been slowing down for some time now and only just realized this was a part of age. I’m also about … was also about 40lbs overweight (5’9″ 199lbs two weeks ago).

    I’ve been dropping around a pound per day average since I started taking it. I’m now at 186 lbs. I have not exercised, but I haven’t been eating allot. I wouldn’t say dieting though. Weight loss started slower then accelerated. The last couple days before I ran out I lost about 1.5 lbs each.

    I have definitely noticed an increase in energy, mental clarity, focus and mood.

    It has effected my sleep. I just don’t sleep as much. At first this concerned me because I equated it with insomnia but I don’t seem to require as much sleep now. I’m still watching this closely because some of that aspect is on the extreme side. Even with 2.5 hours of sleep I am waking up with no grogginess or sluggishness. I don’t have mid-afternoon energy slumps.

    During the 3 days I was off Niagen I noticed my system beginning to return to what was normal. I started feeling a little groggy in the mornings, had less energy, mild slump in the afternoon. It wasn’t immediate though. It was gradual.

    I suspect if I took this when I was in my 30’s I wouldn’t have noticed anything significant. This feels like it’s fixing a slow metabolism and many of the side effects that go with it.

  18. Took one Niagen pill (250 mg) for three days and experienced stomach pains and constipation. I had none of those problems before. Coincidence? I’m afraid to keep using it. Will attempt to get my money refunded for 3 months worth of pills.

      • That is strange. I have been taking 2 Niagens per day for the last 2 years, and have had no trouble with them. They boost my jogging stamina. I suggest it may be a coincidence. Wait a month and try another pill. If you get Niagen working for you, it will boost your energy. It will be worth it.

        • I have been taking it for a year and a half now and have not had any issues either. I have more energy and I find that it helps me sleep better if I take one right before bed. I do think it is very possible that some people could have a sensitivity to it or maybe a filler being used in the capsule. We are all the same yet so very different.

        • Glad it works for you – I took one pill early in the am with water. Actually it worked great I experienced energy all day, mental clarity and I was in a great mood. Problem was I was awake all night and had a upset stomach, uncomfortable & very distended. The combination of lack of sleep and upset stomach really makes me hesitant to go another round with this stuff.

          • Hi Kim, Sorry to hear it is not working for you. I get my Niagen from HPN. It says take 2 capsules. Is mine the same as yours? Maybe you could try just half of a capsule?

  19. Can an obese diabetic taking Metformin, 2gm daily, reasonably expect to experience the benefits of nicatinamide riboside as indicated above and is there a dose dependence due to competitive binding with metformin for receptor sites?

  20. i received an analysis by a phd and have pasted below
    i would appreciate any comments from the people who are protagonists of NAD
    “My Review of the Clinical Trials that Have Been Conducted Using NAD
    According to the Niagen website, nicotinamide riboside (remember, this is the chemical that turns into NAD) was only recently discovered to have anti-aging properties in late 2013 by Harvard Medical School’s Dr. David Sinclair, during his clinical research performed on mice. After the study was complete, the researchers examined “muscle from two-year-old mice that had been given the NAD-producing compound for just one week, [and] looked for indicators of insulin resistance, inflammation and muscle wasting. In all three instances, tissue from the mice resembled that of six-month-old mice. In human years, this would be like a 60-year-old converting to a 20-year-old in these specific areas.”

    However, keep in mind that just because these benefits were shown to have occurred at a cellular level in mice, this doesn’t necessarily translate into any real-world benefits—whether for mice or for humans. In fact, of those NAD studies conducted on humans (such as for Parkinson’s disease), the benefits are murky, and even completely non-existent in some instances.

    On top of this, in the 2013 Harvard study noted above, mice were injected with 400mg of nicotinamide riboside, versus the 250mg found in each dose of Live Cell Research’s Niagen. In other words, these mice—which weigh much less than one pound—were given 400 mg of NR. In human with a body weight of 160 lbs this dose has to be 64,000 mg. A much higher dose than 250mg what you’ll receive in this supplement. No wonder the benefits are murky or non-existent.”

    • Do not agree at all, and frankly the logic of your PhD friend is fallacious.

      The only purpose of the nicotinamide riboside is to increase NAD+ levels.
      If you can get increased NAD+ with a small dosage (and live human trials show that is indeed the case), then that is all that is required. It would be pointless to increase the dosage when the small dosage has already produced the desired effect. A recent study showed:

      …single doses of NIAGEN® NR can elevate the co-enzyme NAD+ in the blood by as much as 2.7-fold. In the first-in-humans clinical trial which involved dosing twelve healthy adult subjects, the group showed that blood cell NAD+ increased with single 100 mg, 300 mg and 1 gram doses of NIAGEN® NR. Average maximal increases in blood NAD+ were approximately 30% at the 100 mg dose and approximately 50% at the higher doses. Increases in blood NAD+ tended to be sustained for longer times at higher doses

    • But one has to also keep the mouse/human metabolism ratio included so I think divide 64,000 by 12 = 5300mg injected a day. Elysium said in spring that they expect human trial results in fall — I hope soon.

      And I believe it was a Japanese researcher, not David Sinclair, who made the NAD / longevity connection and published in 2009. (He has published with Guarante.)

  21. I’ve been taking Niagen for over 9 months and my wife 3 months. We both have had positive results. When I started I noticed I felt better and my wife said that I looked younger. So she started taking it. After a month she noticed a difference in her face and also noticed that her heels that were once dry and callused were a lot softer and nearly normal. I’m going to stop for awhile to see if I notice a difference and will report back. I’m interested in knowing if there are other supplements that would enhance the use of the Niagen.

  22. niagen can probably be enhanced by liposomal resveratrol (way too expensive) or Pterostilbene (kind of similar molecule to resveratrol with better absorption and cheaper than liposomals)

    my feedback (47yo) on NR from the first day is:
    baseline, i use liposomal resveratrol, melatonin and some other very high quality supplements to slow aging but these last 2 years my vision has worsen so much i need glasses all the time for blurred vision.cannot wake up early and fresh (8 to 10 hrs sleep)

    incredible energy like when i was 20yo
    better sleep and short sleep 6-7hrs
    wake up fresh earlier
    glasses only to read now (shaving with glasses on was the most horrible thing) and after 2weeks i can start read pc and phone without glasses but still blurred
    ultra sharp mind
    walking superfast now

    i still have to see the differences if i swim, not swimming regularly since decades.i swim since 8-10yo so perfect technique and data to see any difference

    until now i used 100-200mg in the morning and 100mg before bed.now i ll try 200mg morning, 100mg during day and 200mg before bad to see if vision improvement can be pushed faster to throw away glasses

  23. dear josh, i m really getting big changes and i would like some feedback of what you think of it from your scientific point of view and ways to improve or fasten 47yo age regression:
    1 grey hair is going away, i have pics of before/after and friends and family consider that huge difference.
    2 face has changed very fast with cheekbones getting tighter and bigger, cheeks close to the nose a little tighter and fatter like there is some liquid retention.this could be thyroid too i have subclinical hypo antibody negative maybe upping t4/t3 meds without suppressing tsh can boost metabolism changes
    3 i have no wrinkles of a 47yo, i see some guys from 20 to 30yo having more face wrinkles than me but i have 3 wrinkles in the forahead.they had no change for now
    4 eyes view, about 7/10 of eye sight, dont know baseline but i could not read road signs without glasses now i can

    NR 500mg, liposomal resveratrol 100mg, selenium 400mcg plus some 3-4 brasilian nuts almost every day, 5,4g epa/dha from fish oil, zinc 50mg, ubiquinol 200mg, folate 1200mcg, b12900mcg,magnesium 500mg,b2 100mg,k2 mk7 200mcg, d3 15.000iu, pterostilbene 50mg, 10 mg lutein, 4 mg meso-zeaxantin & trans-zeaxantin, 6mg natural Astaxantin,C3G 2.2mg, melatonin 9mg.expert butterfly swimming 2 times a week to 5times a week

    what could be useful to add?milk thistle for telomerase?liposomal curcumin?pomegranate extract?
    what about canapa seeds, a friend told me about a friend of his looking incredibly younger after exercise plus canapa seeds that he could not recognize him, i saw studies about antinflamatory effect but little about antiage properties
    thanks

    • Hi Marco, sounds like you are real serious; and I like your attitude. However, I don’t know of anyone who ever died from wrinkles or grey hair. What is killing almost everyone are strokes and heart attacks, bad heart valves, and heart failure. All these deaths are just the final result of atherosclerosis, the deposits of cholesterol and Ca++ inside the arteries. It occurs where the arteries are stressed, like in bends and Y’s, and especially in the coronary arteries lining the heart. As the heart beats, these coronary arteries first fill with blood and then collapse flat. It is just like stepping on a garden hose; it does damage. The arteries are held together with collagen fibers. Collagen is a protein that contains 14% of the amino acid proline. This proline must be hydroxylated by an enzyme, in order for the collagen to form the strong triple helix fiber. In order for this enzyme to function, it needs the co-enzyme ascorbic acid (vitamin C). As you probably know humans, primates and guinea pigs don’t make vitamin C in their livers like other animals do. Humans have to get their vitamin C from their diet; otherwise they get atherosclerosis, a disease that starts at about age 20 and progresses until it kills at about age 40 to 90. The deposits of cholesterol and calcium are just secondary as the body tries to reinforce a damaged artery. The good news is that vitamin C can slowly reverse atherosclerosis; but it takes about a year to do so. A human needs at least 600 mgs of vitamin C each day. No one gets this much C unless they take supplements. I recommend timed release pills; since regular vitamin C pills cause diarrhea when taken in over 200 mgs per day. I know most people will call me an idiot; but all these facts have been known for the last 20 years. This information is available for free on the Internet in scientific reports by researches like Dr. Rath. Look it up, if you don’t believe me.

      • i understand that but i have no health issues appart mild subclinical antibody negative hypothyroid with normal free t4 and t3 even if i dont take t4/t3 drugs and no symptoms and low eys view.my area has the highest number of centenarios in the world and my grandad dyed between 90-100yo perfectly healthy, he was exposed to cold winter and got a pneumonia to kill him….so i can only see age regression from little grey hair and maybe not from wrinkles because the 3 ones in forehead are present since young usually.i eat organic and take the supplements for prevention but again no health issues for now

        • Hi Marco, Sounds like your are doing really good! I suggest you add at least 500 to 1000 mgs of timed release vitamin C to your daily supplement list; because being human, we don’t make our own vitamin C like animals do; and we don’t get enough vitamin C in our diet for optimum health. Keep up the good work! 🙂

        • Hi Marco, The other thing I would recommend is C60 (Buckyballs) in olive oil. It prevents cancer in rats and makes them live almost twice as long. I have been using it for my 60 kilo pet rat for the last 2 years, I am 75 and no cancer in my pet rat as yet! I get it from
          C60antiaging.com, $19 US per a 30 day supply. It comes from Czechoslovakia, and takes about a month to arrive, due to delays in Customs; but no custom fees are charged. Although C60 can prevent cancer, there is no evidence that it can cure an existing cancer.
          It has not been approved for human use by the FDA, but you can buy it for your pet rat. I expect the FDA to approve it in about the year 2090 or so, after we are all long gone.
          Instead of looking at various compounds for the percent increase in life expectancy in rats and mice, which produce their vitamin C in their livers and therefore are not human-like, we need to focus on what kills humans: That would be #1: Atherosclerosis, heart disease, and both kinds of strokes; all caused by a lack of sufficient vitamin C, of about 1000 mgs per day.
          #2 Cancer, the usual cause of death in our cousins, the rats and mice. Cancer is caused by improperly repaired double strand breaks in DNA. These breaks are caused by alpha particles. An alpha particle is an ionized helium atom released at high speed from a radioactive isotope such as strontium 90. The cancer rate has been climbing steadily, ever since the first A-bomb were exploded back in 1945, and the US and other countries continued testing nukes in the atmosphere for the next 10 years or more. Radioactive isotopes are now everywhere throughout the planet, and cannot be cleaned up. Our bodies are all radioactive. Radioactive bodies are not normal; so it takes someting not normal like C60 to stop alpha particles. So order your C60 today!
          Disclaimer: I have no financial interest in any supplements at all.

          • update

            metabolism has speed up like a teen, swimming 3-4 times a week with coach and other people (so i dont stop when i feel a little short breath) made me 65-66kg…as slim as when i was a teen, i ve been forced to eat double pasta, a lot of proteins and so on, i lost both all fat and muscles.i never had such an effect even swimming masters 2hrs per day every day

          • the very bad of this:
            my face got very very very thin/slim, not good at 47yo to lose weight like this
            but anyway no wrinkles at all, just big bags under the eyes and less cheeckbones.now i m trying dermaroll+vit c serum+mitoq cream+hialuronic acid to correct this.the second time i used dermaroll 0.5mm needles it worked for 2 days making a natural lifting of cheekbones but after 2 days got back to normal so working on gaining back some weight eating a lot, now at 69kg (i’m 1.76m tall)

          • i never had such an effect even swimming masters 2hrs per day every day, by the way this was when 30yo, so metabolism is for sure faster now than when 30yo

  24. forgot to add as baseline everybody says i still look in the 30-40yo range and my mother and my grandmother always looked much younger, so maybe i am getting more superfast results also for this reason

    • Hi Marco, I don’t know how C60 works; but from my knowledge of organic chemistry, I can tell C60 is an excellent free radical sponge; so if cancer involves free radicals, that may be the reason C60 prevents cancer in rats.

  25. At long last following the FDA’s decision in January 2016 to approve inclusion of NR on the GRAS register, it can now be added to foodstuffs and sold as a supplement. One fact that has not been mentioned in any of the posts above, is the case of purity levels. The majority of the few NR supplements that are being offered, are of comparatively low purity levels, say 84 – 87 %, and that does affect its impact on the body, as does the actual strength in mg per capsule or tablet taken on a daily basis. It is also best taken on an empty stomach. The problem is that the raw material at high purity is very expensive, and I mean expensive – up to $45,000 per Kg, and that defeats the object, as it would put tablets out of the price range for most people. However, there is at least one new supplier in the field in Europe (U.K in fact) that seriously wants to educate the general public about the benefits of NR, both scientifically and anecdotally, and is not only producing a website without a payment gateway, but will be offering NR at high purity at a far lesser price than hitherto. They feel that the general public deserve to try it for themselves and are shortly publishing a book independently about NR, with all the latest scientific data, including a high level fully funded University backed trial, with double blind protocols in place. This is all with humans, not mice or fruit flies or worms !!

  26. bought TA65 from TA sciences, very expensive but if it can prevent aging and stay like i am now for about 10 years it worths the price but only if it really stops aging
    any easy/cheap way to test telomers?

  27. what to inhibit telomerase?
    i was planning to stay on ta65 for a full month and see the effect combo with NR,PT and lipo resveratrol.open to suggestions since i just need to prevent aging and still looking in the 30-40yo range.i am also not so scared of cancer because i know all the research/researchers and used gcmaf (most potent macrophage activator) in the past.not a cancer cure for all cancer stages as monotherapy but a very potent cancer prevention tool for sure.

  28. mild macrophages activators like a gcmaf cream (mafactive.com) or the bravo probiotic itself could be a way to prevent cancer.now i have some mild infection so by using gcmaf cream i feel inflammatory state gets bad…mild interferon like state, worst eyes view.as the infection is totally cleared i ll try it again and see if these mild activation does not interfere with NR and TA65 effect.for all those scared about cancer have a look to gcmaf research on pubmed and saisei mirai clinics in japan.this thing is very potent infeact about 30 researchers/dcotors using it have been killed in US since june 2015, its not easy to get but it works for sure to prevent combo with vit d3

  29. 5 days on ta65 2 caps so 500iu and feeling few differences: mild cough i had 2 weeks and could not clear by high dose liposomal vitamin c as usual cleared the first day i took ta65, maybe coincidence but probably not

    eyes view:
    more vivid colors but when i read newspaper without glasses it is slightly better but so little that it cannot be said if it is NR or ta65.if i will discontinue reading glasses totally, well that would be ta65

    heavy sleeping problems:
    i already had a few going to bed not earlier than 1am but in any case i never went to bed before 10pm in my life but now i feel no sleepy at all going to bed at 3:30am, not good probably, but i wake up very fresh anyway at 10am

    swimming:
    i restarted swimming after a decade of no swimming, 20hrs from dec to now, so i should have gained nothing as breathing and muscle power, i ve always needed 2 hrs daily to go back to real power in swimming.despite this after a week of no swim monday i wanted to try 100m butterfly which is quite heavy without no previous gains and i did it without trouble just a little short breath after that, no muscles soreness.tuesday i did 40min of butterfly 50-75m continuous and then few min recovery.this is very unusual for me, i swim since very very young and i know my responses, i also wonder if this is usual for a 47yo

    confounding factor:
    nicotinamide riboside and liposomal resveratrol but i was already on this since jan, i dont think this gets boost all of a sudden exactly when i take ta65, anyway lets see what happens as weeks go by

    maybe i should use ta65 during day, is there any particular time when telomerase activation could be better, day or night?

    • Hi Marco, I would suspect your swimming endurance is due to nicotinamide riboside; since I got a large boost from it in my jogging. Since telemeres are a big factor during cellular division; and since the release of human growth hormone (HGH) mostly occurs during sleep, my guess would be to take your telemerase activator before you go to sleep. If you want to get to sleep faster and better, take a tablet of melatonin before bedtime. Cheers!

      • thanks sleeping is getting better now.

        any idea if resveratrol, curcumin and melatonin are telomerase inhibitors?and if it better to stay off those while on ta65?

        • Hi Marco,
          Yes, since resveratrol, and curcumin like calorie restriction work by reducing protein synthesis; while ta65 is up regulating the protein enzyme called telemerase, I can see a conflict. Best to cycle them.
          PS: I am a 75 year old test rat and doing well on Niagen for the last year, with my jogging and weight lifting, getting a little stronger each month. I have also been on C60 (buckyballs for a couple of years; because it prevents cancer in rats. Anyway, this old rat has no cancer so far, although my father died from cancer. Cheers

          • i discontinued melatonin but still taking resveratrol in afternoon and ta65 at night, do you suggest stopping resveratrol completely?

          • i tried stopping resveratrol, the effect looks more potent without it but just observations it can be just coincidence

  30. Hi Marco, Yes, stop resveratrol and curcumin until you complete your TA-65. You could cycle back and forth from month to month; but if TA-65 really worked and lengthened your telemeres, you could discontinue it for a long time while you took your resveratrol and curcumin. I have a similar problem: I am trying to build up my muscles, and diet restriction, resveratrol, curcumin, and aspirin interfere with it. So I have to discontinue them, until I complete my body building program. Cheers 🙂

  31. Hi everyone,
    I have just started taking HPN Niagen @ 250mg/day. The bottle recommends going three days without taking any after every thirty day bottle. Does anyone know why this is? I am asking because a friend has started taking a different brand that does not make that recommendation.
    Thanks

  32. I finally heard back from HPN regarding why they recommend three days off between bottles. Here is an excerpt from the email. “We found that customers who seek increased Cognitive support and health are recommended to take 3 days off of Niagen in order for your brain to rejuvenate itself and increase it’s efficient absorption of Niagen”. They go on to say that if I am taking it for anti aging etc to skip the three day wait. So now my new question to them is what if I am taking it for both?

    • Hi Ralph, Here is the thing: Nicotinamide riboside (Niagen) is naturally produced by the body as a step toward making NAD+. If you take Niagen, a feed-back mechanism will cause the body to reduce its own production of Niagen. The advantage of a few days off is that it causes the body to step up its own production of Nicotinamide riboside. If you are taking 2 pills per day, you are probably getting more Nicotinamide riboside than you body would normally produce; so I don’t think it is necessary to take time off, unless you find that the pills you are taking are no longer working for you. That is, if you find that Niagen no longer gives you extra energy, then take some time off, probably more than 3 days. As for myself, I have been taking it every day for the last year, and it is still working for me. I am 75 years old. Cheers!

      • Thanks Jerry, Are you basing this on your own experience or from research data? The reason I ask is that I have not heard that the body production of NAD+ decreases with NR supplements. Wouldn’t that mean that I would have to take even more to offset the decrease? Would you be willing to share your dose of NR and what you have noticed overall? This is all new to me but I really like what my own research on NR is finding. Thanks in advance.

        • Hi Ralph, Well, the production of almost every biochemical compound in the body is subject to feedback control; so that the body does not make too much of it and waste food and energy. A good example, is the caffeine in coffee. Caffeine slows the re-uptake of neurotransmitters in the synapses between nerves; so the nerve stays active a little bit longer, and keeps a person a little more alert. However, after awhile, the nerves get used to it; and so they down regulate the amount of neurotransmitters, and a person has to drink more coffee to get the same perkiness. Anyway, 3 years ago I was in the hospital for a month, and when I was released, I looked like a refugee from a WWII German concentration camp. I had lost about 50 pounds of my original 150 pounds, of mostly muscle and about 10 pounds of fat. I was sent to “physical therapy” which is nothing more than a very expensive exercise program. So rather than pay for that, I took up jogging and weightlifting. My jogging consisted of about 10 minutes, at which time I could go no further. Shortly thereafter I read about Niagen somewhere in someone’s comments here on Josh’s blog. So I ordered some. I take 2 tablets [er day that equals 250 mgs for 125 mgs per tab, if one reads the label carefully. Within the week, I suddenly found that I could easily run for an hour or more without getting exhausted and having to stop and rest. I know Niagen is still working for me; because I never run out of energy no matter how long I jog. I take several different supplements; but Niagen is the only supplement that I can tell really works for me. The rest of my supplements are just taken on faith in scientific research. However, Niagen did not make any noticeable difference in my weightlifting, even though I do keep careful records of the exercises, the weights, the sets and the repetitions that I do. I get a slow increase in my strength; but the rate of increase did not get any faster when I started taking Niagen. This is because weightlifting is anaerobic, whereas jogging and running are aerobic. Obviously one needs a good steady supply of energy in the form of ATP when running. Ultimately, Niagen speeds up the production of ATP, especially when combined with the supplement creatine. When weight-lifting, I stop and rest after each exercise, until my heart rate drops to normal, 2 or 3 minutes. So if you want to know if Niagen really works for you, just see how far you can run without stopping. Then take Niagen for a few days; go for another run and see the difference! Cheers (Disclaimer, I am retired and I have no financial interests in Niagen, nor any other supplement).

  33. Jerry, that is one heck of a reply and I thank you! I have been on 250mg/day for just a couple of weeks. I am very deep in my own research and have yet to find a downside other than the price. Even if I do not notice any significant boost etc I will continue on because of my “faith in scientific research”. Even with no noticeable improvements I still know that very good things are probably happening inside. Do you take both capsules at the same time or do you spread them over the course of a day? I take mine all at once first thing in the am but might spread it out because I am now sleeping “restless” and I don’t like that.This blog is a great place for me because when I try to explain NR to people they just roll their eyes and nod with no intention of even talking about it. People here at least show an interest and most are willing to try and share their findings. I do hike six miles daily and I have found that I am stronger the last 1/2 mile. My friend started NR at the exact same time as me and he also noticed the same thing at the end of his daily walk. That seems to be a common theme. Hats off to you and your regimen. You are obviously serious and I look forward to following your progress along with the others following this blog. At 61 years old I am hoping that NR can help me hang in a little longer and enjoy the ride along the way. I would love to hear from others regarding spreading out the capsules and any sleep issues / advice. Thanks again,
    Ralph

    • Hi Ralph, I must confess I take both Niagen pills at the same time, just because it is simpler. My guess is that they should be spread out. Yes, I would expect you to get a boost from Niagen in your daily walk. Walking, just like jogging requires a steady supply of ATP, and that is what Niagen does. I am surprised I don’t find more Niagen info from marathon runners, bicyclists, and long distance swimmers; but I can imagine they might want to keep their results quiet from competitors and they may be worried that the sports authorities would ban Niagen. When you get time, I suggest you extend your studies from Niagen on into vitamin C at
      www4.drrathfoundation.org/THE_FOUNDATION/About_Dr…/why_book.html
      This link was too big for one line; but you can put it all on one line on your browser. Cheers 🙂

      • Thanks Jerry, I can’t get the link to work for some reason. For what it’s worth I have been taking 4,000mg of vitamin C a day for a while now. I am interested in the link so when time permits please check it again and I will check it out. I love learning!

        • Hi Ralph, Yes, 4,000 mgs of C is good! Just google “Why animals don’t get heart attacks”. That will take you to the website.
          You also ought to check out the rat study. You should be able to find it by googling “rats bucky balls” or “rats C60”. Cheers! 🙂

  34. I am now closing in on three weeks of 250/mg of Niagen daily. I am feeling a “little” more energy and a slight but definite increase in focus and clarity. The only significant observation is a noticeable improvement in my skin. I started to rub my fingers last night and it felt as if I had been using hand lotion. Then it hit me that it was probably the Niagen. I went to the mirror and checked my face. I can see a marked improvement there. Skin is smoother and softer on my face, hands and feet. Being a man that does not mean a whole lot to me but the results sure do. Has anyone else had a similar experience? If yes how long did it take for you to notice?

  35. Being an old man I don’t much look in the mirror; so I had not noticed. I’ll ask my friends. However, you might want to market your own beauty cream for young women. 🙂

  36. I have a personal update to share. My neighbor and I are both up to our necks in NR research and just finished our first month of Niagen @ 250/mg/day. I did notice some more energy but not a lot and he reported the same. Both of us blindly commented without prior conversation that there was a definite improvement in our skin. We decided to step up to 500/mg/day. WOW! There is no comparison to the 250mg dose. The clarity and focus really jumped up and both of us noticed a huge increase in energy the same day. I just drove 45 miles at night on the freeway and I can honestly say that my night vision showed some nice improvement. I am four days @500mg and everyday is great. I know that it is pricey but the results, in my opinion, far outweigh the cost and are really promising.
    Another friend of mine just finished his third week. I casually asked him if he noticed anything and he responded not really except that his skin is softer and not dry. If that is what we feel on the outside I can only imagine the benefits happening inside!

    • did anybody try Nicotinamide Mononucleotide?does it have more power than nicotinamide riboside or can we combo both?
      i see supersmart has got it available although not sure if products on this website are real or just scam

      • I have been taking NMN for a few years but never really noticed any changes but continued as Jerry says above “just taken on faith in scientific research”. It is my understanding that NMN does not get into the cell as quickly or efficiently as NR. I treat NMN as yesterdays news but I still take it and NR. Here is a good article that shows the benefits of NR over NMN. http://blogs.scientificamerican.com/guest-blog/beyond-resveratrol-the-anti-aging-nad-fad/

      • Hi Marco, What we are trying to do is boost the production of NAD+; so basically either of these two compounds should work. In fact Tryptophan (Trp), nicotinic acid (Vit B3), nicotinamide (Nam), nicotinamide riboside (NR),and nicotinic acid riboside (NaR) are all utilized through distinct metabolic pathways to form NAD+. The nicotinamide mononucleotide (NMN) is the NR compound with a phosphate group (PO4) added to it, which makes it one step closer to NAD+. However, the real question is in absorption. It is my understanding that NR passes through the acid of the stomach safely and is absorbed in the intestines; but I don’t know whether or not NMN is absorbed as well. In any event, I think NMN is way too expensive. Cheers!

        • 46yo.did anybody also noticed some interference from telomerase activators on energy boost from NR?i started in may a combo NR 500mg, fish oil 5g, ta65 1 cap (2caps all may), solgar astragalus root extract 4caps, horany goats weed 5g (this made bigger muscles by few weeks use, thicker hair regrowth on temples/sideburns, clearer vision, oily skin), Ashwagandha 2 caps a day, carnosine 1500mg, liposomal resveratrol and liposomal curcumin.energy level has lowered compared to NR 500mg, fish oil, melatonin, liposomal resveratrol only combo.there s still a day by day improvement on youthful look, eyes vision but it is much less, slower and less energy now so i am thinking to cut all telomerase activators.did anybody experienced this effect?ordered also mito Q to try

          • there s still a day by day improvement on youthful look, eyes vision but it is much less, slower and less energy now…….actually i can t say this for sure because too personal and difficult to judge but definitely much less energy, very sure about this

        • also while not on telomerase activators:
          i had some insomnia, never felt tired, a little irritable , more cortisol after swimming and i gave me some accelerated heart beat, i could wake up early and fresh before adding telomerase activators.now i sleep more than 8hrs, still better than before all these antiage supplements but these telomerase activators look like interfering with NR effect

          • restarted telomerase activators, i had a crash with the little sleep and intense activity i was having by day 2 with little herpes on lips too.i had to go to bed midday and swim was heavier and i could not make fly more than 50m.telomerase supp clearly had an effect.i will try stop them again later on but slowly and see the difference if all this happens again.while off telomerase difficulty sleeping happened again like when i started NR.these supplements are very different than everything i tried in my life they seem to have an immediate impact on me

            so i resumed everything except ta65 for now

  37. I am a 58 year old male. I used 200mg of NR and 100mg of Pterostilbene for 3 weeks. I did not notice any changes. I then increased my NR from 200mg to 400mg daily for 5 days until I ran out. Again no effects noticed. I started off with my sleeping schedule badly fragmented, some insomnia, no energy, etc. If ever I needed the benefits claimed by other folks, this would be it. I suppose one reason may be that my NAD+ levels are already reasonably high? Most people assume I am in my early 40’s. Still, I certainly feel the effects of age when it comes to memory and stamina when learning new things and I was really hoping to see an improvement.

  38. Hi RJ, Well, different people have reported different results from Niagen. In my case I noticed a big increase in my jogging. I no longer get tired when I am jogging for an hour or more; but I used to have to quit after 10 or 15 minutes. In your case, I don’t know why you did not find any improvement. I notice that you mentioned 200 mg tabs; so I am wondering what brand you used; since my bottle from HPN comes in 250 mg tabs with a recommendation to take two each day.

    • Hi Jerry! I used the Basis product from Elysium Health as a guide to dosages – which I can’t get in Canada. So I bought my NR from ‘Life Extension’ which comes in 100mg capsules. I got it from Amazon. If I had seen any results from the 400mg dosage I took in the last 5 days, I probably would continue, but I don’t really want to just keep increasing when everything I’ve read suggests that around 300mg is probably as high as you’d want to go with no further improvement expected above that. So I have not continued since running out.

      One thing I did notice: I had not done a lower-body workout for awhile (a month or two) and when I finally got back to it during my NR experiment, experience tells me that a couple of days later I should have been really stiff and a bit painful to walk – but that didn’t happen. My muscle recovery was much quicker than expected. I wasn’t sure if it was the NR, or that I just hadn’t lost as much muscle mass as I expected, or maybe I just didn’t push myself as hard as I thought. But I did not notice any changes like skin improvements, better memory, more mental stamina and focus, better sleep, etc, like so many others have reported.

      • Hi RJ, Well, there is some evidence to suggest NR is only effective in a larger dose. The theory being that digestive enzymes convert it to nicotinamide (NAM); but in a larger dose the digestive enzymes are overwhelmed and at least half of the NR get absorbed before it is digested. This would indicate it is best to take the daily dose all at once in the morning (since less energy is needed at night when asleep). The best way to see if it is working is to go jogging. If you find you can jog without getting tired, it is working; because jogging uses up energy fast. I know it is expensive, though. Cheers!

    • Hey Jerry, I get mine from HPN also but mine only come in 125mg capsules and the bottle says to take two (2×125=250mg). I can not find anywhere on the HPN website that shows 250mg capsules available. Maybe you are only taking 250mg/day or I am not looking in the right place.

      • That’s encouraging for me to hear – I’m 58. 3 weeks at 200mg and 5 days at 400mg didn’t do anything for me. I just ordered more NR from a different supplier (HPN instead of Life Extension) in case there was a quality issue, and I intend trying 500mg when I get it. I’ll have enough for a 1.5 month experiment at that dosage.

        • Good luck RJ! I am one of the lucky people that is feeling all of the benefits that NR is supposed to provide. I truly hope that your next try works for you. I just got some in from HPN and the date of manufacture is June 2016. Please keep us posted.

          • Apologies for not following up sooner. I did receive the NR from HPN and tried up to 750mg/day with no effect. Here were my dosages over 4 weeks:
            week 1 and 2:
            500mg – split into 250mg twice daily
            no effect
            week 3:
            500mg – once a day
            no effect
            week 4:
            750mg – split into 375mg twice daily
            no effect

            However, I just saw the posting by ProudDaddy of the 1gm trial. I have enough pills left over for around a 1 wk trial at 1gm. I may give that a try soon.

  39. Babu G. Ranganathan*
    (B.A. Bible/Biology)

    NATURAL LIMITS TO EVOLUTION: Only micro-evolution, or evolution within biological “kinds,” is genetically possible (such as the varieties of dogs, cats, horses, cows, etc.), but not macro-evolution, or evolution across biological “kinds,” (such as from sea sponge to human). All real evolution in nature is simply the expression, over time, of already existing genes or variations of already existing genes. For example, we have breeds of dogs today that we didn’t have a few hundred years ago. The genes for these breeds had always existed in the dog population but never had opportunity before to be expressed. Only limited evolution or adaptation, variations of already existing genes and traits, is possible.

    WHAT ABOUT THE GENETIC AND BIOLOGICAL SIMILARITIES BETWEEN SPECIES? Genetic information, like other forms of information, cannot happen by chance, so it is more logical to believe that genetic and biological similarities between all forms of life are due to a common Designer who designed similar functions for similar purposes. It doesn’t mean all forms of life are biologically related! Only genetic similarities within a natural species proves relationship because it’s only within a natural species that members can interbreed and reproduce.

    HOW COULD SPECIES have survived if their vital tissues, organs, reproductive systems, etc. were still evolving? A partially evolved trait or organ that is not complete and fully functioning from the start would be a liability to a species, not a survival asset. Plants and animals in the process of macro-evolution would be unfit for survival. For example, “if a leg of a reptile were to evolve (over supposedly millions of years) into a wing of a bird, it would become a bad leg long before it became a good wing” (Dr. Walt Brown, scientist and creationist). Survival of the fittest actually would have prevented evolution across biological kinds!

    Many people have wrong ideas of how evolution is supposed to work. Physical traits and characteristics are determined and passed on by genes – not by what happens to our body parts. For example, if a woman were to lose her finger this wouldn’t affect how many fingers her baby will have. Changing the color and texture of your hair will not affect the color and texture of your children’s hair. So, even if an ape or ape-like creature’s muscles and bones changed so that it could walk upright it still would not be able to pass on this trait to its offspring. Only changes or mutations that occur in the genetic code of reproductive cells (i.e. sperm and egg) can be passed on to offspring.

    What about the new science of epigenetics? Epigenetics involves inheritable environmental factors that can turn genes (in our DNA) on or off, but epigenetics does not alter or change the DNA code itself. Epigenetics cannot produce evolutionary change.

    Modern evolutionists believe and hope that over, supposedly, millions of years, random mutations in the genetic code of reproductive cells caused by environmental radiation will generate entirely new genes. This is total blind and irrational faith on the part of evolutionists. It’s much like believing that randomly changing the sequence of letters in a romance novel, over millions of years, will turn it into a book on astronomy! That’s the kind of blind faith macro-evolutionists have.

    Some evolutionists teach that evolution occurred across biological kinds suddenly due to massive environmental radiation so that, for example, a reptile suddenly changed into a bird. This, too, is nothing more than blind faith.

    Most biological variations are from new combinations of already existing genes, not mutations. Mutations are accidents in the genetic code, are mostly harmful, and have no capability of producing greater complexity in the code. Even if a good accident occurred, for every good one there would be hundreds of harmful ones with the net result, over time, being harmful, even lethal, to the species. At best, mutations only produce further variations within a natural species.

    What about natural selection? Natural selection doesn’t produce biological traits or variations. It can only “select” from biological variations that are possible and which have survival value. The real issue is what biological variations are possible, not natural selection. Nature is not a genetic engineer and has no mind or ability to invent and program entirely new genes for entirely new traits. Only variations of already existing genes and traits are possible!

    All species of plants and animals in the fossil record are found complete, fully-formed, and fully functional. This is powerful evidence that species did not come into existence gradually by any macro-evolutionary process but, rather, came into existence as complete and ready-to-go from the very beginning, which is possible only by special creation.

    All the fossils that have been used to support human evolution have been found to be either hoaxes, non-human, or human, but not non-human and human (i.e. Neanderthal Man was discovered later to be fully human). Textbooks and museums still continue to display examples and illustrations supporting human evolution which most evolutionists have rejected and no longer support. Many diagrams of ape-man like creatures over the years were reconstructed according to evolutionary interpretations from disputable bones that have now been discredited even by many evolutionists but still being taught in school textbooks.

    There has never been unanimous agreement among evolutionary scientists on ANY fossil evidence that has been used to support human evolution over the many years, including LUCY.

    Apes are quite comfortable in how they walk just as humans are quite comfortable in how they walk. Even a slight change in the position of a tendon, muscle, bone, or cartilage, for either, would be excruciatingly painful and would not be an advantage for survival. There’s no hard evidence that humans evolved from ape-like creatures anymore than there’s hard evidence that apes evolved from four-legged creatures. All the fossils that have been used to support human evolution have been found to be either hoaxes, non-human, or human, but not non-human and human (i.e. Neanderthal Man was discovered later to be fully human). Textbooks and museums still continue to display examples and illustrations supporting human evolution which most evolutionists have rejected and no longer support. Many diagrams of ape-man creatures over the years were reconstructed according to evolutionary interpretations from disputable bones that have now been discredited but still being taught in school textbooks.

    What about the chimp-human DNA similarity? The actual similarity is between 70-87% not 99.8% as commonly believed. The original research stating 99.8% similarity was based on ignoring contradicting evidence. Only a certain segment of DNA between apes and humans was compared, not the entire DNA genome.

    In some cases evolutionists use similarities of features between species as an argument for a “transitional link”. But in all such cases the features are complete and fully functioning. And, evolutionists are not consistent when using this argument. For example, the duck-billed platypus has features belonging to birds and mammals, but even evolutionists wouldn’t classify the platypus as a transitional link.

    Also, so-called “Junk DNA” isn’t junk. Although these “non-coding” segments of DNA don’t code for proteins, they have recently been found to be vital in regulating gene expression (i.e. when, where, and how genes are expressed, so they’re not “junk”).

    Read my Internet article, ARE FOSSILS REALLY MILLIONS OF YEARS OLD?

    Visit my latest Internet site: THE SCIENCE SUPPORTING CREATION

    Author of popular Internet article, TRADITIONAL DOCTRINE OF HELL EVOLVED FROM GREEK ROOTS

    *I have given successful lectures (with question and answer period afterwards) defending creation before evolutionist science faculty and students at various colleges and universities. I’ve been privileged to be recognized in the 24th edition of Marquis “Who’s Who in The East” for my writings on religion and science.

    • Note: I recognize many problems with the way evolution is currently understood, some of them deep and seeming to point to the need for a new paradigm. However, I think that just saying, “that means that a Creator did it” is to give up on the scientific method while there is still much territory to explore.
      – JJM

  40. I am no where near the quality biochemist the Noble Winners are.. but from what little I could see. I “think” Leonard Guarente was getting at NR being a precursor to NAD, which the NAD was fueling the actions of the SIRT1 to switch-off adverse gene expression. [Why?] NAD was falling was never discovered and a complete mystery.. it could be for multiple reasons.. or different for each person.

    The benefits of restoring NAD levels were attributed to restoring SIRT1 activity, switching off gene expressions which led to various degenerative expressions.. again.. different for each person.

    NAD was also used as a general purpose fuel to propel other cellular activity.. so it wasn’t so much that it “did anything” as it fueled “preventing” further damage via the SIRT1 activity. at best its a temporary bandaid for a serious problem that is probably not general.. and will probably continue as a chronic condition.. until we actually understand whats causing falling NAD and the random adverse gene expressions.

    Its very far from a coherent understanding of whats going on.. this simple bandaid however is somehwat better than nothing.

    That it might buy more time in a slightly incremental way also seems reasonable if meagerly supported by recent research.. but the actual method of driving death into the victim is still out there and left unaddressed.

    One method of research is to slowly tease out cause and effect and derive theories and prove of disprove them.

    It might be just as interesting however to build up a canidate cell starting with a model.. adding one gene at a time.. until we re-originate “Aging and Death” of a similar nature.. if it even is a gene expression that is causing the aging and eventual death.. it could be an emergent combination of expressions.. in which case it could be a very long time before we actually understand what it going on.. or come up with a method of dealing with the problem.

    • One caution is that playing with the body’s ROS metabolism has generated counter-intuitive results in the past. It seems that ROS plays a dual role as an agent of damage and a signal promoting longevity.
      -JJM

  41. k here are my notes two weeks into taking this stuff
    been researching; NAD+ and read most things here and top 30 google hits on topic: listened to the harvard guy and the mit guy: (hate driving in cambridge)

    im going with gnc niagen product:
    take four with empty stomach when i get up at four and go back to sleep: then two tablets on empty stomach at three pm with lots of water.

    on days i drink more water i feel it absorbs better: if i dont drink enough water it doesnt work: if i drink alkaline water i dont think it works as well as neutral pH water; i think it binds to lots of stuff and needs a very empty stomach and my feel is the crash is related to gastric uptake issues; if i eat too soon or take it too soon after a meal i think it just doesnt absorb.

    would be curious on pharmockinesics on this stuff? what happens when it flows through liver?

    nails and hair growing faster
    motivation to excercise and finish work outs
    self motivation to not over eat seems to be better (food addiction is something ive battled with and binge eating) and it seems to be in line with what the addiction people are saying about this stuff.

    grey is same with series selfies
    wrinkles a little better (qualitiative)
    muscle soreness post work out seems to recover post work out from previous 48 to 52 hours to no sorness at 18 hours
    mood happier: able to turn a joke around faster
    cope better with stress and seem to be able to turn out work like i did 10 years ago and getting to productivity i havent seen in myself in a while.

  42. Some human results have finally been published. Looks like one gram a day of NR will double the NAD+ of middle-agers, about the same effect as a the NMN used in Sinclair’s mice. Whether that will turn us elderly into studs remains to be tested.

    • The only thing I have noticed is that on 2 pills of Niagen each day, I can jog as long as I want without getting tired and having to stop to rest. I was hoping it would improve my weightlifting, but I don’t think it does; because weightlifting is anaerobic, whereas jogging is aerobic. I am 75 years old.

  43. At 64 I feel , well not really like a stud, but after taking 300 to 400 mgs/day of NAD+Cell Regenerator since April 2014 I think it gives me the extra energy to exercise. In my case the big gain is in resistance training. I gained muscle and look a lot more trim.People comment on how young I look for my age. However , taking NR has not prevented me from getting cataracts.
    Jerry, following the latest trends on the main NR discussion website you should consider to take about 500 mgs per day if possible. I would like to do the same but costs are prohibiting.
    http://www.longecity.org/forum/topic/82770-nicotinamide-riboside-curated/page-51#entry794458

    • This is about month four

      -feel great working out more regularly
      -nails and hair still growing
      – no improvement in eyesite- maybe worse
      But it’s age related
      -sexual drive increased
      – able to fight food addictions and weight has dropped from 312 to 268
      – food cravings and ability to do a bullet proof coffee in am and salmon dinner at night w some vegetables and walnuts- able to calorie restrict and my feel if I do t take the niagen I get food cravings and feel food addiction feelings- not taking niagen if I run out I tend to binge on those days and gain weight real fast
      – less bloating and my feel a fatty liver is Better w less fluid retention
      – able to memorize seven digit phone numbers and I never could before
      – gradual but steady increase in muscle but it’s the motivation and improvement in mood and depression
      – feel like dancing sometimes. Just better mood
      – better sleep and more dreams- my feel better sleep architecture
      – people can’t believe I’m 48 even though I have a grey beard- I do think I look younger
      – just energy and focus- I have high stress job and focus more
      – I do yoga and meditate last two years as well so don’t know how to filter out signal from noise but both signals result in better overall health
      – being able to control Appetite and thoughts about food is key to my wellbeing and was on my way to a fatty liver and Diabetes
      – neuropathy in feel is better

      • Ditto. I feel my overall wellbeing is so much better and has helped kicked all other possible crutches except a little gin occasionally 😉

    • Hi Peter, Thanks for the update. Niagen does not improve my weightlifting; but YK-11 (aj SARM) does; so I suspect your improvement in strength may be due to the Cell Regenerator. It is too expensive; but I may try NR for just a month to see what it does; so thanks for the suggestion.

  44. I feel it is more about the quality of life while living as much as extending it. I do feel more aware, energetic, with better metabolism and overall a happier person on it.

    • Mark –
      I’ve been taking it for 8 months or so, with no noticeable change in the way I feel – but then, I didn’t expect any. Its benefits are supposed to be long-term. Recently, my doctor suggested I stop because she thinks it has elevated my ALT and AST in blood tests, giving a false positive for liver damage, and she wants to check.
      – Josh

      • Hi Josh Mitteldorf,

        Please update us when you know. It is my second month but definitely do not want to damage my liver!

        Cheers!

  45. I am a 60 year old male and have been taking 250 mg of HPN Niagen for 3 months, with some changes in the way I feel – mainly more energy and memory clarity. Don’t workout anymore due to serious neck and knee surgeries so I can only walk – the same distance to and from work 5 days a week – and my walk times have decreased per my fitbit. Drink a lot of beer twice a week and hangovers are mostly gone which is different from pre-niagen. Started taking a low dose of a statin a year ago but stopped because of side effects so I am curious to see niagen’s impact on my cholesterol levels (and my liver enzyme levels per Josh above), if any. I am not overweight but would like to lose 10-15 pounds to get back to where I was before marriage and my wonderful desk job of 30 years. Also have been taking 100 mgs of ubiquinol a day for 2 years before I started taking niagen and continue to take it with the niagen.

  46. Please note – I did not say that NR is damaging my liver, or that it “might be” damaging my liver. There is no suspicion of that. My doctor’s hypothesis is that NR was raising blood markers (ALT and AST) that in other circumstances would be a warning of possible liver damage, but in this case they are a “false positive”.

  47. I have a vague understanding of how Nicotinamide Riboside works, but I can’t seem to find an answer to my dilemma anywhere, so I thought I would ask here, in hopes that someone would know. I’m a 45 year old female and I have been taking Live Cell Research Niagen for 8 months. I have taken several breaks, usually due to finances. At first, it was a wonder supplement, giving me energy and helping my workouts. I’ve read about people taking 1 gram a day and more, and anytime I’ve tried to go up to 750mg a day, I crash- passing out napping in the afternoon. it happens every. single. time. So I have stuck with 500mg/day. This last run of my Niagen supplementation lasted 4 months- 500 mg a day. Suddenly in the 4th month, I started getting extremely drowsy in the afternoons, like uncontrollable napping (even though I sleep 8 hours a night). I stopped the Niagen and felt great. I stopped for a week, went back to it today at 250mg and crashed again, sleeping for 2 hours in the afternoon. Why is the niagen doing this to me? Have I built up a tolerance? Historically and currently I am low in D3 ( i take 10,000 iu a day), B12 (i inject weekly for several months out of the year) and Ferritin ( i take supplemental iron as well).

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