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Niacin Increases NAD+ Significantly in Human Trial

NiacinNiacin
 

Researchers have concluded a human trial using niacin, a very old vitamin discovered over 80 years ago, and have shown that it can increase the presence of an energy compound essential to cellular function.

Niacin and NAD+

Niacin is a form of water-soluble vitamin B3 and has been known since American biochemist Conrad Elvehjem identified it in 1937. Niacin was originally called nicotinic acid because it can be created by the oxidation of nicotine with nitric acid. However, people know nicotine to be the addictive chemical in tobacco, so the name niacin was adopted, which comes from the words NIcotinic ACid vitamIN.

There has been considerable interest in supplements that have the ability to increase NAD+ levels in recent years, and niacin is one such supplement that can do this. NAD+ biology plays an important role in energy metabolism, so before we dive into the results of a new human study that we want to spotlight today, we should discuss NAD+ and why it is important in the context of metabolism and aging.

Nicotinamide adenine dinucleotide (NAD) is a coenzyme found in all living cells. It is a dinucleotide, which means that it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine base, and the other contains nicotinamide.

In metabolism, NAD facilitates redox reactions, carrying electrons from one reaction to another. This means that NAD is found in two forms in the cell; NAD+ is an oxidizing agent that takes electrons from other molecules in order to become its reduced form, NADH. NADH can then become a reducing agent that donates the electrons it carries. The transfer of electrons is one of the main functions of NAD, though it also performs other cellular processes, including acting as a substrate for enzymes that add or remove chemical groups from proteins in post-translational modifications.

NAD+ is created from simple building blocks, such as the amino acid tryptophan, and it is created in a more complex way via the intake of food that contains nicotinic acid (niacin) or other NAD+ precursors. These different pathways ultimately feed into a salvage pathway, which recycles them back into the active NAD+ form.

An old compound given a new lease of life

The results of a new human trial using niacin shed new light on its role in NAD+ biology [1].

The trial participants were given a steadily increasing dose of niacin, starting at 250 mg/day to 750-1000 mg/day over a 4-month period, then a 10-month follow-up treatment period. The participants were organized into a study group of individuals with mitochondrial myopathy and a control group of healthy age-matched people consisting of two healthy people for each patient with mitochondrial myopathy. All the study participants were placed on the same niacin supplementation regimen.

The researchers report that niacin treatment increased muscle NAD+ levels by 1.3-fold at 4 months and 2.3-fold after 10 months in the study group. The control group saw no increase of NAD+, suggesting its levels are highly controlled in skeletal muscle tissue and will only increase in patients suffering from lower than normal levels of NAD+ experienced in conditions such as mitochondrial myopathy and potentially aging which also effects mitochondrial fuction. This is also important, as prior to this study, it was unknown if niacin supplementation improved NAD+ in muscle or if it is filtered out and simply elevated NAD+ in the liver.

The level of whole blood NAD+ was also increased by supplementation by 7.1-fold in the study group and 5.7 in the control group after 4 months compared to the participants’ baseline. At the 10-month mark, the increase was 8.2-fold compared to the baseline. This shows that niacin supplements are not simply filtered out by the liver; in fact, they reach the bloodstream in significant amounts to elevate NAD+ levels there.

Niacin supplementation also appears to improve body composition. Participants saw a decrease in whole-body fat percentage in controls and increased muscle mass in both the control and study group. After 10 months of niacin supplementation, the patients demonstrated improved muscle strength.

The researchers also observed that hepatic fat was halved and visceral fat was reduced by a quarter. These types of fat deposits are both linked to an increased risk of metabolic syndrome. So while the niacin had no effect on the surface fat around the body, it did impact significantly on the unhealthy fat surrounding the organs.

Finally, niacin has been linked to increasing blood glucose levels, a risk factor for developing conditions such as diabetes. The results of the study showed that niacin did increase fasting glucose levels in both study and control groups following 4 months of supplementation. However, glycosylated hemoglobin, which reflects long-term glucose levels, was not affected.

So, while niacin does appear to increase glucose levels according to the results of this study, the benefits appear to significantly outweigh any negatives that a slight elevation of glucose may have, as other studies support [2].

The other side effect of note following 4 months of niacin supplementation was that there was a slight decrease in hemoglobin concentration in the participants; however, this never fell below normal healthy ranges during the study.

NAD+ is a redox-active metabolite, the depletion of which has been proposed to promote aging and degenerative diseases in rodents. However, whether NAD+ depletion occurs in patients with degenerative disorders and whether NAD+ repletion improves their symptoms has remained open. Here, we report systemic NAD+ deficiency in adult-onset mitochondrial myopathy patients. We administered an increasing dose of NAD+-booster niacin, a vitamin B3 form (to 750-1,000 mg/day; clinicaltrials.gov NCT03973203) for patients and their matched controls for 10 or 4 months, respectively. Blood NAD+ increased in all subjects, up to 8-fold, and muscle NAD+ of patients reached the level of their controls. Some patients showed anemia tendency, while muscle strength and mitochondrial biogenesis increased in all subjects. In patients, muscle metabolome shifted toward controls and liver fat decreased even 50%. Our evidence indicates that blood analysis is useful in identifying NAD+ deficiency and points niacin to be an efficient NAD+ booster for treating mitochondrial myopathy.

Conclusion

These results give food for thought when we consider NAD+ biology in the context of metabolism and aging. The price of other precursor supplements that may increase NAD+ in humans, such as NR and NMN, are very high compared to niacin, which is cheap and readily available. These results show that niacin can elevate human NAD+ in muscle and blood and potentially in other tissues as well.

Needless to say, while these results are intriguing, we do not endorse supplement use or any product or supplement vendor, and all discussion here is for scientific interest.

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Literature

[1] Pirinen, E., Auranen, M., Khan, N. A., Brilhante, V., Urho, N., Pessia, A., … & Haimilahti, K. (2020). Niacin cures systemic NAD+ deficiency and improves muscle performance in adult-onset mitochondrial myopathy. Cell Metabolism.

[2] Goldberg, R. B., & Jacobson, T. A. (2008, April). Effects of niacin on glucose control in patients with dyslipidemia. In Mayo Clinic Proceedings (Vol. 83, No. 4, pp. 470-478). Elsevier.

Related Topics

About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 600 articles on the topic, interviewed over 100 of the leading researchers in the field, hosted livestream events focused on aging, as well as attending various medical industry conferences. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Swiss Monthly, Keep me Prime, and New Economy Magazine. Steve is one of three recipients of the 2020 H+ Innovator Award and shares this honour with Mirko Ranieri – Google AR and Dinorah Delfin – Immortalists Magazine. The H+ Innovator Award looks into our community and acknowledges ideas and projects that encourage social change, achieve scientific accomplishments, technological advances, philosophical and intellectual visions, author unique narratives, build fascinating artistic ventures, and develop products that bridge gaps and help us to achieve transhumanist goals. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project.
  1. ajkivela
    June 9, 2020

    I take it every day. You feel it instantly. Niacin is super important and most people dont really understand that well enough yet. You want very small doses at a time (follow the recommended daily amount – found at most any nutritional websites) and make sure you take it with food too. Pay attention now, Niacin may cause a hot flushing” – vasodilation effect. And boy let me tell you, when they say hot, they meant it Hot. If taken at high doses, it can definitely pack a whallop and you probably also will feel extremely thirsty and nauseous. But with that said, the loads of benefits it far outweighs any potential negatives to it. So again, I’d just take it right before you eat and drink, and you should avoid any negative side effects.

    ‘Last fun fact, Niacin plays an incredibly important in helping to ending hangovers quicker.’

    • David Birrell
      April 27, 2021

      That’s very funny re the hangovers.
      I started taking it a few months ago. Found physical performance increased a bit, but I wake up noticeably better after nights of drinking.

    • max91mb
      May 6, 2021

      Nicotinamide adenine dinucleotidecould help tabagic sevrage?

  2. mariemcintosh75
    June 9, 2020

    More than 60 yrs. ago Prevention magazine had an article about Niacin. It may help a stressed person who was losing patience , have better control over thoughts and actions. If my memory is correct.
    I took it including flushing side effect for awhile. I have thought it could benefit people contemplating suicide . Any thoughts on this??

    • crochetlady24
      June 9, 2020

      I can’t take it , it scares me that my face felt on fire and it’s takes along time for for feeling to go away. No i will eat more bread bc that’s what the ingredients say there’s is.

      • mikecottrill984
        June 29, 2020

        I felt the same flushing and it was highly disconcerting. However, I reduced the amount I was taking to 50 mg with food and I felt no flushing. My next step is to try 100 mg with food and see how that works.

    • dcalvente
      April 27, 2021

      I have been taking niacin for 9 months.
      It has changed my energy and vitality.
      I don’t feel tired. Before, I was physically exerting myself and I was so tired that I wanted to sleep.
      Now I go for a 2 hour walk and I come back perfectly.
      I do hard work and great.
      And finally, every morning I wake up with a huge erection like when I was 20 years old. I feel full energy.
      And have not experienced heat or flushing, no feeling of suffocation

  3. sdhey654
    June 9, 2020

    The main issue with niacin is not the flushing but the depletion of methyl donors. namely folate, choline, betaine/trimethylglycine, vit B12.

    • jonathanhadley9
      June 9, 2020

      For which is a concern if you have one of the MTHFR faulty genes So would there be a way of combating the effects?

      • etdj78ughf
        June 10, 2020

        Supplements is the easiest one or by eating foods rich with the above dietary methyl donors.

    • mamapatricia
      June 10, 2020

      What is a methyl donor ?

      • pelleter
        November 10, 2020

        choline, folate, b12, creatine

  4. michaeljohnirish
    June 9, 2020

    Some studies showed niacin increased homocysteine levels which is detrimental to health. And another study, below link, shows it reduces endurance performance.

    https://www.iat.uni-leipzig.de/datenbanken/iks/dtu-triathlon/Record/4001956

    • bogrunberger
      July 10, 2020

      Elevated homocysteine levels is often associated with depleted B12. Maybe it’s because Niacin depletes methyl in the liver and draining the body of B12. This suggests that you should combine Niacin intake with a good B multivitamin together with TMG.

  5. maquintanillaperez
    June 10, 2020

    I take niacin 500 mg. daily to help decrease colesterol and triglycerides levels. I have been taking this supplement for more than 4 years, because I prefer to take supplements than prescribed medication to avoid the secondary effects that are more damaging than good.

  6. venusk22
    June 10, 2020

    Niacin definitely increase blood glucose level CONSIDERABLY ! this is. Not insignificant. It is SIGNIFICANT

    • andrex0101aj
      June 10, 2020

      Only fasting blood sugar. HA1c levlels do not show a variation in studies.

    • Steve Hill
      June 10, 2020

      I addressed this in the article.

      The results of the study showed that niacin did increase fasting glucose levels in both study and control groups following 4 months of supplementation. However, glycosylated hemoglobin, which reflects long-term glucose levels, was not affected.

    • grosmec
      June 15, 2020

      “CONSIDERABLY” isn’t very helpful. How about a meta-analysis of the problem?

      Goldie, C., Taylor, A. J., Nguyen, P., McCoy, C., Zhao, X. Q., & Preiss, D. (2016). Niacin therapy and the risk of new-onset diabetes: a meta-analysis of randomised controlled trials. Heart, 102(3), 198-203.

      • thomaspinches
        February 14, 2021

        Conclusion of the study is “Niacin therapy is associated with a moderately increased risk of developing diabetes regardless of background statin or combination laropiprant therapy.” I imagine most people taking Niacin for longevity will also be doing some kind of intermittent fasting as this is the most beneficial intervention, which also reduces glucose intolerance.

  7. glennw100
    July 2, 2020

    Thanks for the great article. It is very helpful in guiding to an inexpensive supplement to support NAD in the body while aging.
    I have begun using niacinamide to avoid the flushing.
    Do these trial results apply for the niacinamide form of B3?
    I ask because the article discusses flushing.

    • pelleter
      November 25, 2020

      niacinamide apparently doesnt help increase NAD+ levels, it can actually be detrimental from what David Sinclair has said

  8. fmarchimede
    July 5, 2020

    This is a very good piece of paper. Congratatulations. Indeed, working at that key cellular level holds very good promises. We plan with my group to embark on this too end of this year or next.

  9. techadvisor2k8
    August 17, 2020

    I found this study very helpful and have done a bit of experimentation myself with Niacin. The study indicates a slow ramp up to 1000mg a day, and that is where I noticed a very surprising effect. because it increases blood flow, it makes things like creatine and other similar-use substances work better – which is why its included in most pre-workout formulas – albeit at much smaller doses. It has had a very tangible impact on my workouts and my overall mood frankly, and getting it to 1000mg was a force multiplier for me personally. Every person is different so too early to see if this is a panacea, but my results absolutely mirror the subjective effects denoted in the study re: muscle strength – I found it exceedingly difficult to get tired!

  10. matebugger
    September 13, 2020

    Thank you so much for a wonderful article. I took niacin years ago, and recently thought about restarting, since I received so many positive benefits. I guess I’m also the odd one who enjoys the flushing! I found your article, and I just ordered some from amazon. Thank you for giving me the push I needed!

    • Steve Hill
      September 14, 2020

      Hi Sheryl,

      Thanks for the kind words and you are not alone. I am one of the odd ones who also enjoys the flushing and I have met others in my travels, so you are not alone :)

  11. mevcit
    October 23, 2020

    The study uses a slow release form of niacin (nicotinic acid). This is written in the details of the methodology, but they don’t describe the form of slow release at all. That’s a pity. If they use the slowest sustained release niacin, then all of it goes through liver first-pass metabolism and gets converted to nicotinamide by the “high affinity-low capacity” pathway. Then, the liver converts it to NAD+ for its own use or releases nicotinamide into the bloodstream for other tissues. If they use intermediate release niacin, then some niacin passes into the bloodstream unchanged while some is converted into nicotinamide in the liver as I described above, and some is converted to nicotinuric acid (causes flushing) in the liver by the “low affinity-high capacity” pathway when the “high affinity-low capacity” pathway is saturated.

    Now, when we use immediate release niacin, the “high affinity-low capacity” pathway is very quickly saturated. Even the “low affinity-high capacity” pathway is saturated quickly. This ultimately means a large portion of niacin passes the liver unchanged. There is little conversion to nicotinamide in the liver. We know that unchanged niacin can be converted to NAD+ by some tissues including heart and kidneys via de novo pathway, but not all tissues have this capability. The good thing is niacin doesn’t inhibit sirtuins while large and immediate doses of nicotinamide do inhibit sirtuins (which is why it doesn’t improve the lipid profile) despite raising NAD+ levels.

    I’m wondering whether taking a slow release nicotinamide would produce the same effects as in the study because the study used a slow release form of niacin which predominantly and slowly provides nicotinamide to the body through conversion in the liver.

    I’m currently using immediate release niacin because I don’t want to take the risk of liver damage with the slow release forms of niacin. But I’m not sure how the immediate release niacin would perform compared to form used in the study. I think the form of niacin is very important. The study should have described this!

    • matebugger
      November 7, 2020

      Mevlut, I use immediate release as well, for the exact reason you mentioned. Informative response. Thank you.

  12. rtbphx
    November 21, 2020

    I used nicotinic acid some years back. I haven’t been taking it for a few years now because I was having a difficult time finding it after the brand I was using went to niacinamide. Now, I mostly see the sale of niacinamide, and the new thing seems to be NAD+ supplements. I came on to this article trying to find the answer to the difference between NAD+ and nicotinic acid. I must be missing something here as a bit of a novice. I understand that nicotinic acid is a precursor to NAD+. This means to me that you need nicotinic acid to form NAD+ in the body. Are NAD+ supplements legitimate? If NAD+ is a supplement you can take, does that then mean that nicotinic acid is no longer a necessary supplement? I also find it hard to find supplements without extra strange ingredients added like vegetable stearate.

    Grateful for a helpful response:)

    • pelleter
      November 25, 2020

      You can actually get an NAD+ IV, I’m not sure if it’s worth the price though since it’s expensive and not sure how well it’s absorbed. You could go with immediate release niacin, NMN and NR as NAD+ precursors with niacin being the cheapest. You will also need to supplement with ‘methyl donors’ I’m using choline bitartrate, not sure if it’s as good as TMG but it’s a hell of a lot cheaper as a choline supplement.

  13. December 3, 2020

    I was prescribed 1,000 mg of niacinamide daily by my skin cancer doctor after having a couple of skin cancers removed as it has been shown to significantly reduce the risk of BCCs and SCCs, so I’m disappointed to discover that it inhibit sirtuins. (I take resveratrol). I might cut back the dose and add niacin instead. I take NR, but perhaps the the niacin might substitute as it is expensive.

    I noticed that Dr. David Sinclair mentioned that oleic acid (from olive oil) has been shown to activate SIRT1 as well

    https://www.cell.com/molecular-cell/fulltext/S1097-2765(19)30894-9?rss=yes&utm_source=dlvr.it&utm_medium=twitter

  14. sally2
    September 23, 2021

    Such funny comments. I am 53. Been taking 1 to 3 grams of niacin for a little over 4 years now. I have a very clean diet and very athletic. I currently run 80 miles a week, every week. Plus other exercise. You dont notice the flush at all after awhile, and you learn to enjoy it if you do notice. Dont believe the silly studies, dont believe the methyl donor fear. Try for your self, slowly. It will take time to get past placebo feeling and gradually rise to a therapeutic dose. So you wont know a thing for a couple months. Get a good diet going and some exercise you enjoy, because without the basics you wont get anywhere. I find niacin much better than the crazy expensive niacin derivatives. Good luck. Nothing works for everyone, but if you really want to experiment with this kind of stuff, 2 months minimum or your just blowing smoke.

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