Niacin or niacinamide supplementation – good or bad idea?

It was disturbing to some readers when I characterized niacinamide as a pro-aging substance in the March 24 blog post  SIRT1, mTOR, NF-kappaB and resveratrol, as it was disturbing to me when I first came to that realization years ago.  In response to several blog comments I promised some readers to further research niacinamide and niacin for both health benefits and possible pro-aging hazards, and this blog post reports on that research. I will report on a number of research studies and finally I will give my opinions on how it all comes together and I will even disclose my past secret affair with niacin.

Niacin and Niacinimide

Nicotinamide, also known as niacinamide and nicotinic acid amide, is the amide of nicotinic acid (vitamin B3/ niacin). Nicotinamide is a water-soluble vitamin and is part of the vitamin B group. Nicotinic acid, also known as niacin, is converted to nicotinamide in vivo, and though the two are identical in their vitamin functions, nicotinamide does not have the same pharmacologic and toxic effects of niacin, which occur incidental to niacin’s conversion. Thus nicotinamide does not reduce cholesterol or cause flushing,[1] although nicotinamide may be toxic to the liver at doses exceeding 3 g/day for adults.[2] In cells, niacin is incorporated into nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), although the pathways for nicotinamide and nicotinic acid are very similar. NAD+ and NADP+ are coenzymes in a wide variety of enzymatic oxidation-reduction reactions.[3] (ref)” 

Continuing, “Nicotinamide adenine dinucleotide (NAD) and its relative nicotinamide adenine dinucleotide phosphate (NADP) are two of the most important coenzymes in the cell. NADP is simply NAD with a third phosphate group attached – (ref).  NAD plays several key roles in metabolism.  It “participates in many redox reactions in cells, including in glycolysis and most of those in the citric acid cycle of cellular respiration(ref).”  And, as I have discussed previously, SIRT1 requires NAD for its actions(ref)(ref). 

General information on dietary sources of niacin/niacinamide and problems associated with deficiency of vitamin B3 can be found here and here.   Niacin can be found in nuts, dairy products, lean meats, poultry, fish, and eggs. Some niacin is also supplied by legumes and enriched breads and cereals. The best dietary sources of vitamin B3 are found in beets, brewer’s yeast, beef liver, beef kidney, pork, turkey, chicken, veal, fish, salmon, swordfish, tuna, sunflower seeds, and peanuts. The body can synthesize niacin from the essential amino acid tryptophan, but the synthesis is extremely slow; 60 mg of tryptophan are required to make one milligram of niacin. For this reason, eating lots of tryptophan is not an adequate substitute for consuming niacin. As serotonin synthesis is reliant on tryptophan availability, inadequate dietary intake of vitamin B3 may also therefore lead to depression. The liver is the main storage area for this vitamin and absorption of vitamin B3 takes place in the intestines(ref).”  

Further,  “Niacin works closely with vitamin B1, vitamin B2, vitamin B6, pantothenic acid, and biotin to break the carbohydrates, fats, and proteins in food .  — Vitamin B3 is essential in the metabolism of carbohydrates (to produce energy), fats, and proteins. It also aids in the production of hydrochloric acid, needed for proper digestion. Additionally, vitamin B3 facilitates the body’s ability to eliminate toxins.” —  Vitamin B3 is required by the body for digestive processes, activating enzymes which nourish the brain, regulating blood pressure and regulating cholesterol levels.”  “Niacin is a water-soluble vitamin that participates in more than 50 metabolic functions, all of which are important in the release of energy from carbohydrates. Because of its pivotal role in so many metabolic functions, niacin is vital in supplying energy to, and maintaining the integrity of, all body cells. Niacin also assists in antioxidant and detoxification functions, and the production of sex and adrenal hormones. Vitamin B3 (niacin, niacinamide, nicotinic acid) lowers cholesterol by preventing its buildup in the liver and arteries. Niacin moves fat from tissues for fat metabolism, burning it for energy. It promotes healthy skin, the health of the myelin sheath (the protective covering of the spinal nerves), and good digestion, where it is also vital for the production of hydrochloric (stomach) acid. It is an aid in protecting the pancreas, and is necessary for the health of all tissue cells(ref).”

The government-recommended daily allowance (RDA) for niacin/niacinamide is 16 mg a day for men, 14 mg for women.  The 95th percentile intake for both food and supplements is estimated to be 40-70 mg for both food and supplements(ref).  Pharmacological doses of either form of B3 can range from 500mg to 2gm daily.  There is a possibility of liver endangerment at the level of 3gms or more daily.

The case for niacinamide promoting health and longevity

B3 has been used now for over 40 years, often in large doses as a drug(ref).  A major application has been control blood cholesterol levels.  According to a 1986 publication: “The Coronary Drug Project was conducted between 1966 and 1975 to assess the long-term efficacy and safety of five lipid-influencing drugs in 8,341 men aged 30 to 64 years with electrocardiogram-documented previous myocardial infarction. The two estrogen regimens and dextrothyroxine were discontinued early because of adverse effects. No evidence of efficacy was found for the clofibrate treatment. Niacin treatment showed modest benefit in decreasing definite nonfatal recurrent myocardial infarction but did not decrease total mortality. With a mean follow-up of 15 years, nearly 9 years after termination of the trial, mortality from all causes in each of the drug groups, except for niacin, was similar to that in the placebo group. Mortality in the niacin group was 11% lower than in the placebo group (52.0 versus 58.2%; p = 0.0004). This late benefit of niacin, occurring after discontinuation of the drug, may be a result of a translation into a mortality benefit over subsequent years of the early favorable effect of niacin in decreasing nonfatal reinfarction or a result of the cholesterol-lowering effect of niacin, or both.”  Later it has become popular to combine niacin with a statin to control blood lipids.  A 2009 study concludes: “ Combined use of extended-release niacin with atorvastatin was superior to atorvastatin monotherapy alone in lipid profile regulation. Combination therapy with niacin ER and atorvastatin was well tolerated and safe in patients with coronary artery disease.” 

Several researchers think that pathways activated by niacin/niacinamide could offer hope for development of new drug treatments for several diseases, diabetes being prime among them,  but further understanding of the complex metabolic pathways involved is a prerequisite.   

The 2008 review article NAD+ and vitamin B3: from metabolism to therapies espouses this viewpoint.  The 2008 publication Triple play: promoting neurovascular longevity with nicotinamide, WNT, and erythropoietin in diabetes mellitus, states “Here we discuss the novel application of nicotinamide, Wnt signaling, and erythropoietin that modulate cellular oxidative stress and offer significant promise for the prevention of diabetic complications in the nervous and vascular systems. Essential to this process is the precise focus upon diverse as well as common cellular pathways governed by nicotinamide.” 

The 2010 publication Diabetes Mellitus: Channeling Care through Cellular Discovery comes to essentially the same conclusion “For these reasons, innovative strategies are necessary for the implementation of new treatments for DM that are generated through the further understanding of cellular pathways that govern the pathological consequences of DM. In particular, both the precursor for the coenzyme beta-nicotinamide adenine dinucleotide (NAD(+)), nicotinamide, and the growth factor erythropoietin offer novel platforms for drug discovery that involve cellular metabolic homeostasis and inflammatory cell control.” 

Health and potential life-extending properties of niacin/niacinamide 

“More recently, the health benefits of niacin have been shown to be far more extensive than previously appreciated — Numerous reports indicate niacin might help prevent atherosclerosis, diabetes and hypercholesterolemia. Niacin is effective in assisting burn-wound recovery, and in the prevention of cataracts and skin cancer. Unfortunately, the molecular basis for most of these health benefits remains unclear(ref).”

The 2006 e-publication Nicotinamide extends replicative lifespan of human cells reports “We found that an ongoing application of nicotinamide to normal human fibroblasts not only attenuated expression of the aging phenotype but also increased their replicative lifespan, causing a greater than 1.6-fold increase in the number of population doublings. Although nicotinamide by itself does not act as an antioxidant, the cells cultured in the presence of nicotinamide exhibited reduced levels of reactive oxygen species (ROS) and oxidative damage products associated with cellular senescence, and a decelerated telomere shortening rate without a detectable increase in telomerase activity. Furthermore, in the treated cells growing beyond the original Hayflick limit, the levels of p53, p21WAF1, and phospho-Rb proteins were similar to those in actively proliferating cells. The nicotinamide treatment caused a decrease in ATP levels, which was stably maintained until the delayed senescence point. Nicotinamide-treated cells also maintained high mitochondrial membrane potential but a lower respiration rate and superoxide anion level. Taken together, in contrast to its demonstrated pro-aging effect in yeast, nicotinamide extends the lifespan of human fibroblasts, possibly through reduction in mitochondrial activity and ROS production. 

Another possible longevity contribution of nicotinamide is via autophagy as related in the 2009 publication Nicotinamide enhances mitochondria quality through autophagy activation in human cells.  Nicotinamide (NAM) treatment causes a decrease in mitochondrial respiration and reactive oxygen species production in primary human fibroblasts and extends their replicative lifespan. In the current study, it is reported that NAM treatment induces a decrease in mitochondrial mass and an increase in membrane potential (DeltaPsim) by accelerating autophagic degradation of mitochondria.”  

I note that these two studies as well as some others commenting on possible longevity benefits of niacin/niacinamide supplementation are in-vitro and the results may or may not apply in human bodies because of the many complex biochemical feedback loops involved.

The darker side of niacin/niacinamide supplementation

Turning now to the darker side, there is unquestionable evidence that niacinamide inhibits the expression of SIRT1 and its multiple health and longevity benefits discussed in three recent blog posts ( SIRT1, mTOR, NF-kappaB and resveratrol, Visit with Leonard Guarante, and  SIRT1, the hypoxic response, autophagy and hormesis).   

The 2002 publication Inhibition of Silencing and Accelerated Aging by Nicotinamide, a Putative Negative Regulator of Yeast Sir2 and Human SIRT1 reported that in yeast at least nicotinamide inhibited Sir2 and decreased lifespan.  “We show here that nicotinamide strongly inhibits yeast silencing, increases rDNA recombination, and shortens replicative life span to that of asir2 mutant.”

The 2005 treatise Vitamin B3 and sirtuin function is among the documents that makes the point  via a comprehensive analysis:  “Most notable with respect to the cellular regulation of sirtuins is their dramatic inhibition by nicotinamide.” —  “Sirtuins are NADC-dependent protein deacetylases that are involved in transcriptional regulation, metabolism, apoptosis, differentiation and ageing. These unique enzymes are inhibited by nicotinamide, which is a form of vitamin B3.  Recent studies have uncovered the molecular basis for nicotinamide inhibition, and provided the framework to understand the physiological processes mediated by sirtuins — .”  SIR2 and its human counterpart SIRT1 produce many of their health and longevity processes via deacetylation reactions. “ SIRT1 targets transcription factors that are dynamically regulated by reversible acetylation.” — “Deacetylation by Sir2 requires NADC and yields the additional products nicotinamide and O-acetyl-ADP-ribose (OAADPr). Nicotinamide is a potent inhibitor of the reaction, but can be recycled back to NADC via a NADC-salvage pathway(ref).” – “Most notable with respect to the cellular regulation of sirtuins is their dramatic inhibition by nicotinamide. First analyzed in several kinetic studies [15–17] and recently by X-ray crystallographic analysis [18], nicotinamide and several of its derivatives are powerful mechanism-based inhibitors. The inhibition constants vary between homologs, but usually fall within the 20–200-mM range, which makes nicotinamide the most potent general inhibitor described to date. Accordingly, nicotinamide has been used to inhibit cellular sirtuins in a wide variety of experiments in yeast and mammalian cells.”  The paper goes into the detailed biochemistry of the inhibition process.

An interesting point is that the acid form of niacin, nicotinic acid “displays almost negligible binding to and inhibition of sirtuins(ref).”  The point is fairly moot in terms of what goes on in us mammals, however, since “Niacin is converted to nicotinamide and then to NAD and NADP in vivo. — “It is important to mention that, although only nicotinamide inhibits sirtuins, both nicotinic acid and nicotinamide lead to increased cellular NADC production. To help clarify these issues, a complete understanding of NADC metabolism with quantification of relevant metabolites and intermediates, and how these impinge on sirtuin-mediated pathways will be essential(ref).”

 Going back to fruit flies, the 2008 study, Life span extension and neuronal cell protection by Drosophila nicotinamidase says that in Drosophila fruit flies, overexpression of nicotinamidase, D-NAAM significantly increases median and maximal fly life span.  Nicotinamidase is an enzyme that promotes the breakdown of nicotinamide

The unknown effects of niacin/nicotinamide

After 50 or more years of use, researchers are starting to wonder exactly what large doses of niacin/ nicotinamide do in terms of activating cellular pathways.  The 2009 publication The vitamin nicotinamide: translating nutrition into clinical care  reports “Nicotinamide, the amide form of vitamin B3 (niacin), is changed to its mononucleotide compound with the enzyme nicotinic acid/nicotinamide adenylyltransferase, and participates in the cellular energy metabolism that directly impacts normal physiology. However, nicotinamide also influences oxidative stress and modulates multiple pathways tied to both cellular survival and death. During disorders that include immune system dysfunction, diabetes, and aging-related diseases, nicotinamide is a robust cytoprotectant that blocks cellular inflammatory cell activation, early apoptotic phosphatidylserine exposure, and late nuclear DNA degradation. Nicotinamide relies upon unique cellular pathways that involve forkhead transcription factors, sirtuins, protein kinase B (Akt), Bad, caspases, and poly (ADP-ribose) polymerase that may offer a fine line with determining cellular longevity, cell survival, and unwanted cancer progression. If one is cognizant of the these considerations, it becomes evident that nicotinamide holds great potential for multiple disease entities, but the development of new therapeutic strategies rests heavily upon the elucidation of the novel cellular pathways that nicotinamide closely governs.”  I summarize this as “It is very interesting and potentially very useful stuff but we don’t know enough yet to be able to say exactly what it does.”

The same wondering tone is found in the 2009 publication Niacin status impacts chromatin structure, “Niacin is required to form NAD and NADP, which are involved in many essential redox reactions in cellular metabolism. In addition, NAD+ acts as a substrate for a variety of ADP-ribosylation reactions, including poly- and mono-ADP-ribosylation of proteins, formation of cyclic ADP-ribose, and the generation of O-acetyl-ADP-ribose in deacetylation reactions. These nonredox reactions are critical in the regulation of cellular metabolism, and they are sensitive to dietary niacin status. There are 4 known mechanisms by which ADP-ribosylation reactions directly regulate chromatin structure. These include the covalent modification of histones with poly(ADP-ribose), the extraction of histones from chromatin by noncovalent binding to poly(ADP-ribose) on poly(ADP-ribose) polymerase-1, poly ADP-ribosylation of telomeric repeat-binding factor-1 within telomeres, and deacetylation of histones by the sirtuins. These reactions produce a variety of localized effects in chromatin structure, and altered function in response to changes in niacin status may have dramatic effects on genomic stability, cell division and differentiation, and apoptosis.”  Yes indeed they may.  But do they, and if so what exactly are the dramatic effects?

The March 2010 e-publication Widespread effects of nicotinic acid on gene expression in insulin-sensitive tissues: implications for unwanted effects of nicotinic acid treatment summarizes the paradoxical effects of niacin supplementation.  In mice, an infusion of niacin was shown to affect the expression of a great many genes.  Some of the changes in gene expression produce wanted effects, others produce unwanted effects. “Nicotinic acid (NA; or niacin) has been used as a hypolipidemic agent for more than 4 decades. However, the mechanisms underlying the effects of NA treatment (wanted and unwanted) are still poorly understood. In the present study, we discovered that NA infusion in rats resulted in dephosphorylation (i.e., activation) of the forkhead transcription factor FOXO1 in insulin-sensitive tissues such as skeletal and cardiac muscles, liver, and adipose tissue. These NA effects were opposite to the effects of insulin to increase FOXO1 phosphorylation. Nicotinic acid had widespread effects on gene expression in all of the tissues studied, and the number of genes affected by NA greatly exceeded that of genes affected by insulin. — Some of the NA-induced changes in gene expression are discussed as potential mechanisms underlying wanted and unwanted effects of NA treatment.”

The literature suggests that either too little or too much (“pharmacological quantities”) of niacin/niacinamide can produce multiple, strange, and possibly unwanted effects.  According to the 2009 publication Niacin status, NAD distribution and ADP-ribose metabolism, “Dietary niacin deficiency, and pharmacological excesses of nicotinic acid or nicotinamide, have dramatic effects on cellular NAD pools, ADP-ribose metabolism, tissue function and health. ADP-ribose metabolism is providing new targets for pharmacological intervention, and it is important to consider how the supply of vitamin B3 may directly influence ADP-ribosylation reactions, or create interactions with other drugs designed to influence these pathways. — A wide range of metabolic changes can take place following pharmacological supplementation of nicotinic acid or nicotinamide. As niacin status decreases towards a deficient state, the function of other types of pharmaceutical agents may be modified, including those that target ADP-ribosylation reactions, apoptosis and inflammation.”

There is a body of literature I am not covering here on the cosmetic use of nicotinamide in skin creams with purported anti-aging results.  I might dig into this in another blog entry later. 

How does it all come together? 

Observation 1:  The body absolutely needs to have an adequate supply of niacin or niacinamide available to make the amounts of NAD and NADP required for health.  Further, this must come from dietary sources, foods or supplements. 

Observation 2:  The research literature related to therapeutic use of niacin/niacinamide is at first confusing expressing different viewpoints that have emerged during different periods of time and representing different ways of looking at the effects of substance. Some articles cite reasons why large doses of niacin may promote longevity, and other articles cite reasons why such use may shorten life.

Observation 3:  For about 40 years large doses of niacin have been used for several therapeutic purposes.  Many physicians currently prescribe large doses of niacin for lipid control and other purposes. Mild benefits seem to exist in some areas like raising HDL cholesterol.  The long-term consequences of repeatedly taking large doses are unknown.

Observation 4:  Large scale niacin dosage profoundly affects multiple genes through multiple pathways producing both wanted and unwanted results.  While many researchers are excited by the possibilities of niacin-related therapies for a variety of conditions, the one thing they agree on is a need for further understanding of the pathways involved.

Observation 5:  The sirtuin-related pathways involving the niacin metabolites NAD and NADP are among those related to niacin most intensely studied in recent years.  Large doses of niacin/niacinamide inhibit the expression of SIRT1 and therefore prevent the health and longevity benefits associated with expression of SIRT1.   

Niacin and my personal regimen I have been taking niacin included in a B-complex “B-50” pill taken twice daily, for a total of 100 mg daily.  And added to this is niacin/niacinamide included in my breakfast cereals and other food, perhaps another 40mg.  So, with food I have probably been ingesting  140 mg a day of B3.  This is considerably over the minimum USRDA of 16mg and is possibly excessive for my optimal health.  I am changing my personal regimen and my suggested anti-aging Supplement Regimen to include only one B-50 a day and am looking into different B-complex supplements.  And  clearly, I do not plan to take larger doses of either niacin or niacinamide.

Personal note on my affair with niacin

In the spirit of disclosure, I need to own up to the fact that I once had a torrid affair with niacin.   And I really mean torrid because the stuff gives you hot flushes.  In the late 1970s there were some psychiatric and medical practitioners prescribing megadoses of niacin for all kinds of conditions, including chronic hypoglycemia and what later has come to be called bipolar disease.  It was a period where megavitamin therapy and orthomolecular medicine seemed to be the latest and best things for health.  Proponents of this approach like Dr. Allan Cott were respected people to be paid attention to.   I came under the influence of a New Hampshire medical practitioner who tested me and several of my sons for hypoglycemia, “evaluated” our mental states, and soon the whole bunch of us were taking megadoses of niacin, 1,000-1,500 mg a day.  This at first may have actually benefitted one of my sons who had been having problems with his schoolwork.  Reading some of the orthomolecular medicine literature of the day, I thought niacin was wonderful stuff.  After about three years, however, two things happened that resulted in the affair with niacin ending.  The first is that the son mentioned started taking larger and larger doses after he entered college, hoping it would help him cope with harder and harder schoolwork.  He ended up being seriously ill with a very inflamed liver and had to be hospitalized.  The diagnosis was overdose on Niacin.  The second thing is that we learned that the New Hampshire practitioner was not really a medical doctor as he had represented himself to be.  He was a fake.  We stopped taking megadoses of niacin.  In essence looking back, I think the spirit and intent of orthomolecular medicine was and continues to be a good thing, but that the scientific knowledge required to allow effective orthomolecular therapy to become a systematic practice is only now emerging.

Please see the medical disclaimer for this blog.

About Vince Giuliano

Being a follower, connoisseur, and interpreter of longevity research is my latest career, since 2007. I believe I am unique among the researchers and writers in the aging sciences community in one critical respect. That is, I personally practice the anti-aging interventions that I preach and that has kept me healthy, young, active and highly involved at my age, now 93. I am as productive as I was at age 45. I don’t know of anybody else active in that community in my age bracket. In particular, I have focused on the importance of controlling chronic inflammation for healthy aging, and have written a number of articles on that subject in this blog. In 2014, I created a dietary supplement to further this objective. In 2019, two family colleagues and I started up Synergy Bioherbals, a dietary supplement company that is now selling this product. In earlier reincarnations of my career. I was Founding Dean of a graduate school and a full University Professor at the State University of New York, a senior consultant working in a variety of fields at Arthur D. Little, Inc., Chief Scientist and C00 of Mirror Systems, a software company, and an international Internet consultant. I got off the ground with one of the earliest PhD's from Harvard in a field later to become known as computer science. Because there was no academic field of computer science at the time, to get through I had to qualify myself in hard sciences, so my studies focused heavily on quantum physics. In various ways I contributed to the Computer Revolution starting in the 1950s and the Internet Revolution starting in the late 1980s. I am now engaged in doing the same for The Longevity Revolution. I have published something like 200 books and papers as well as over 430 substantive.entries in this blog, and have enjoyed various periods of notoriety. If you do a Google search on Vincent E. Giuliano, most if not all of the entries on the first few pages that come up will be ones relating to me. I have a general writings site at www.vincegiuliano.com and an extensive site of my art at www.giulianoart.com. Please note that I have recently changed my mailbox to vegiuliano@agingsciences.com.
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34 Responses to Niacin or niacinamide supplementation – good or bad idea?

  1. Frank says:

    Thanks Vince. As always your detailed search and interpretations are greatly appreciated. I am tapering off on my niacin use and over about a week or so plan to be down to around 20-30 mg (I started at more than 500 mg). I will get my HDL tested and see if this affects it much. My guess is that it will not change all that much.

    I’m not sure if it makes any difference, but I am thinking I will take my main reduced amount of niacin at least six or seven hours after my resveratrol since the half-life of resveratrol is reportedly around 9 hours in the body. Do you think this will make any difference?

    Again, thanks for the info and analysis.

    Frank

  2. admin says:

    Hi Frank

    I don’t know of any applicable studies but my guess is that at the levels of 20-30mg it probably does not terribly interfere with the resveratrol. But again, this is just a guess. And I thank you again for your positive feedback. I am sitting here thinking about what my next blog entry should be about.

    Vince

  3. MachineGhost says:

    In theory, a large dose of niacinamide taken orally could benefit the skin, not just when applied topically. However, when I tried taking a 500mg capsule I always wound up with a most debilitating and nauseating migraine about 12 hours later. It is far worse than MSG-induced migraines, which I thought was the mother of all headaches.

  4. admin says:

    Hi MachineGhost

    The thing I remember most back from my niacin-dropping days is the hot flushes that would come a couple of minutes after taking them. I remember once in a diner I asked a good friend, back in the drugie days of the early 70s, “Want to try something really hot?” When he said yes I gave him a 500mg niacin and he got an incredible red burning itchy flush all over. Still my closest friend, this is something he will never forget.

    Vince

  5. Jai says:

    Hi Vince, I’ve just recently stumbled on to your site and am finding it of great use! thanks. I’ve been on anti-aging regime since 2002.

    I’ve had trouble managing my cholesterol and tried statins.
    Here are past results:

    No Statins Serum Cholesterol : 5.2 HDL: 1.58 LDL: 3.4 Trig: 0.58 chol/hdl ratio: 3.3

    Simvastatin 20mg Serum Cholesterol : 3.8 HDL: 1.44 LDL: 2.1 Trig: 0.5 chol/hdl ratio: 2.6

    Rosuvastatin 5mg Serum Cholesterol : 3.7 HDL: 1.49 LDL: 2.0 Trig: 0.54 chol/hdl ratio: 1.5

    Statins alone as above shows reduced LDL levels but never really raised HDL levels, infact they too were reduced.

    I then Included in my regime is Niacin (500mg daily) and Rosuvastatin (5mg) for managing my cholesterol. I also introduced Rev-Genetics Nitro-250 Resveratrol 250mg x 2 & Omega 3 (4gms EPA 300mg and DHA 200mg, twice than before). I’ve managed to alter my lipid profile to folowing:

    Serum Cholesterol:3.6, HDL: 1.79, LDL: 1.6 Trig: 0.4

    As you can see there’s been a dramatic change. My HDL is now infact higher than the my LDL.
    I’ve now reduced my rosuvastin 5mg Mon, Wed & Fri only as research indicates that it has a half life of 17hrs and good results are still achievable on a every other day regime.

    Reading this posting now has made me now think of cutting out Niacin all together. But what about Rosuvastin? Is that pro aging in any way?

    Who knows maybe my new results may be more or some in part to the resveratrol. Please take a look at the following study: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1857339/

    What are your thoughts on all this?

    Jai

  6. admin says:

    Thanks for your contribution. I hesitate to respond to your particular clinical situation because I cannot in this blog even come close to suggesting medical advice lest I be burned at the stake.

    As to Rousvastin, I don’t know that its actions differ significantly than those of other statins. I do make some general remarks on cholesterol scores and statins as related to cardiovascular risk in my treatise here Susceptibility to Cardiovascular Disease Firewall http://www.vincegiuliano.name/Antiagingfirewalls.htm#Susceptibilit toCardiovasculaDiseas Firewall

    As to the 2006 publication you cite, there might indeed be something to combining resveratrol and a statin, although I don’t know if the approach has ever progressed to human trials. could well be. The rate of what we don’t know seems to expand as an exponential function of what we do know

    Vince

  7. Jai says:

    Thanks Vince, Just checked out your link. In it you advise Omega 3 caps 1500mg of EPA and 1000mg of DHA twice a day. Thats a lot more than i’m on now, which is 400mg DHA and 600mg EPA twice a day. Where do you get you Omega 3 from?

    I’ve dropped the Niacin altogether now. Lets hope i can still get a good profile on my next blood test.

    Another Issue with Astral C cycloastragenoll, i’ve combined my 10mg with 1000mg Astragalus (root)which also has 700mg polsaccharides. Thought it would give the cycloastragenoll a little boost. Wise decision?

    Thanks again Vince. Your Blog enlightening to say the least!

  8. Jim Green says:

    Dear Vince,
    I take 4 Spring Valley Super B-complex
    vitamin pills every day, thinking to inhibit
    atherosclerotic plaque formation by interfering
    with homocysteine. However, I also get from that
    100 mg of nicotinamide, which might help me
    according to Kang. I am not sure what an optimal
    dose would be according to his research. Thanks for
    communicating the 3 mg upper limit and the many
    insights into niacinamide.
    Years ago I tried a big niacin pill and came down
    with a nasty case of Niacin Flush that was miserable.

  9. admin says:

    Hi Jim

    Again, thanks for your contribution. Years ago, I would trick my friends by sneaking niacinamide pills into their coffee and then asking them embarrassing questions and watching them flush and blush. That was not nice, pranks of my youth. But I was into megadoses of the stuff for myself for a while back in the early 70s when I thought I (and everybody else in my family) had hypoglycemia.

    Vince

  10. admin says:

    Jai:

    Interesting, with respect to Astral Ccycloastragenoll, am taking the same amount and combining it with astragalus root just as you are. I have another 2 month supply on hand and am not sure what I will do when that is gone.

    I used to order my Omega 3 supplements from Vitacost and still have a large bottle on hand. I have discontinued shopping with them because repeatedly I have ordered supplements listed “usually ships the same day,” paid for fast shipping and then received an e-mail 5 days later saying that some substance was out of stock, and did not get my order completed for 3 or more weeks. I do not know where I will be getting the Omega 3 in the future.

    I still like the vitacost product line, but am fed up with the delivery unreliability.

    Vince
    Vince

  11. Jai says:

    Hi Vince,
    They’re getting new stock in on July according to the website, 3rd gen. You may still be ok. What about this mastergene p16? worth a shot?

    Omega3 for 180caps 1000mg is about $18 with free delivery here in the UK.

    Vitamins and other goods sold from Crown dependancies like Guernsey & Jersey are not technically part of the UK and so are tax free.

    About Guernsey, I drink Organic non-homogenized Guernsey cattle Milk. What are your views on milk especially A2 milk like Guernsey.

  12. admin says:

    Hi Jai

    As to the new Astral Fruit supplement, I don’t think Revgenetics has let on what it consists of, I know it will be expensive – I seem to remember $84 a bottle, but I am not sure what it will be, I await the information.

    As to Mastergene P16, I don’t qhite understand the logic behind the supplement. I think it is supposed to promote expression of the P16 gene, a pro-apoptosis gene. Fine, but P16/Ink4a levels build up with age inhibiting the differentiation of stem cells and this in itself is thought possibly to be a major cause of aging. I have written about this both in my treatise and in this blog. So, it would seem to me that further promoting of P16 is the opposite of what one would want to do if the concern is about aging.

    As to non-homogenized Guernsey cattle milk, I don’t especially have any views on that.

    Vince

  13. Jai says:

    Hi Vince,
    Your right about the new astral fruit. What exactly is new about it. I’ll be talking to them.

    Before introducing Astral Ccycloastragenoll & astragalus root 6hrs and 4 hrs before, I used to have an additional dosage of Vitamin C or Rosehip extract. Is combing Vitamin C or rosehip with the Astral Ccycloastragenoll & astragalus root doses a bad idea. I’m confilicted about this, as i’m aware the bodies vitamin c absorbtion is better when doses are spread throughout the day. Right now i’m on 2g absorbic acid vit C plus 1g rosehip extract, once in the morning and once at night.

    Oh yes i’m also take lypo-spheric vit c too.

    • Hi Jai

      With respect to your 5 July comment, as a personal decision I have recently cut back on my Vitamin C dosage to 1gm a day. And of course I gave up on Cycloastragenol long long ago. My reasons for cutting back on Vit C is explained in my recent blogs on Nrf2 and on hormesis, namely putting me in the sweet spot of the hermetic response curve for Nrf2 activation. I am not at all sure that 1gm does this though. We need better biomarkers for Nrf2 activation.

      Vince

  14. Niacinamide says:

    Niacinamide:

    Niacinamide and Niacin are two different forms of vitamin B-3. Niacinamide does not cause a niacin flush. Niacinamide (B-3) is an essential member of the B-vitamin family. Niacinamide on discount at NutroVita.com.

    For more details please visit:
    http://www.nutrovita.com/23644/now-foods/niacinamide.htm

  15. Tom says:

    Wow…disheartening stuff. I will now stop taking niacin. HOWEVER, I hda been tjaking 1500 mg for 5 months as my triglycerides were over the range, my LDL was high and my HDL was low. The LDL/HDL ratio was about 3:1 respectively, not at all life threatening but not ideal. My LDL particle sizes were strongly weighted towards the small end as well. After 5 months of niacin my LDL/HDL ratio was nearly 1:1!
    My triglycerides went from 162 to 79. My lipid panel was better than perfect. No ill effect. I for one happen to enjoy the flush effect.

    Bummer on the sirt1 thing. Goodbye niacin!

  16. brandon says:

    This blog is misleading. Guys and gals, please don’t go off a protocol including niacin just because of this one blog. That’s not too bright.

    The sirt1 gene is normally inhibited! The only ways I know of activating it are severe caloric restriction and huge doses of extracts of reservatol. Taking niacin isn’t a pro-aging substance, it simply won’t allow you to have the benefits of caloric restriction or taking supplements which activate sirt1. So what?

    Dr Abram Hoffer took niacin for 57 years and lived to the age of 92. Two time Nobel prize winner Linus Pauling took niacin for over 40 years and lived to age 93. It’s also of importance to note that both his parents died in their 40’s. The second oldest Canadian started taking niacin in her 70’s and as of last year was 111 years old. I’m honestly not sure if she’s still kicking or not.

    I’m nearly 28, have been taking niacin for over two years, and plan on taking 3 grams inositol-hexanicotinate and 3 grams ascorbic acid with bioflavinoids until the day I die. My father had heart surgery to open up a 90% blocked main artery and put in stints last year at age 52. His father double bypass heart surgery at age 52. I don’t plan on having surgery at all. I eat healthy, take adaptogens, exercise, and take nutritional supplements.

    Think for yourself. Take in many sources and make up your own mind.

    Peace.

  17. admin says:

    This is in response to Brandon’s comment.

    I don’t agree with Brandon that this blog is misleading and also don’t at this point want to engage further about the benefits or disadvantages of niacin supplementation, But I do agree with him on one basic point in his last sentence which is to think for yourself, investigate multiple sources and make up your own minds about what is so. I remind you that the purpose of my blog is not to give personal or medical advice but to report on and discuss research findings From time to time I include the following medicl disclaimer at the end of blog posts: MEDICAL DISCLAIMER

    FROM TIME TO TIME, THIS BLOG DISCUSSES DISEASE PROCESSES. THE INTENTION OF THOSE DISCUSSIONS IS TO CONVEY CURRENT RESEARCH FINDINGS AND OPINIONS, NOT TO GIVE MEDICAL ADVICE. THE INFORMATION IN POSTS IN THIS BLOG IS NOT A SUBSTITUTE FOR A LICENSED PHYSICIAN’S MEDICAL ADVICE. IF ANY ADVICE, OPINIONS, OR INSTRUCTIONS HEREIN CONFLICT WITH THAT OF A TREATING LICENSED PHYSICIAN, DEFER TO THE OPINION OF THE PHYSICIAN. THIS INFORMATION IS INTENDED FOR PEOPLE IN GOOD HEALTH. IT IS THE READER’S RESPONSIBILITY TO KNOW HIS OR HER MEDICAL HISTORY AND ENSURE THAT ACTIONS OR SUPPLEMENTS HE OR SHE TAKES DO NOT CREATE AN ADVERSE REACTION.

  18. Max says:

    What I gather from this blog is that nicotinic acid (niacin, the kind that makes you flush) does NOT inhibit (or at least inhibits negligibly) the SIRT1 gene, and niacinamide (or niacinimide, the non-flushing kind found in most supplements) DOES inhibit SIRT1. Is this correct?

    If I’m right, I’ve always thought that the flush of nicotnic acid is a great transport system to increase bioavailability and distribution of resveratrol (a SIRT1 activator w/ anti-aging properties) to deep tissue and skin, etc.

  19. admin says:

    Max
    No, what you gather is not correct. Niacin is converted to nicotinamide in-vivo so no matter what you take you end up internally with nicotinamide which does, according to the cited research, inhibit SIRT1,

    Vince

  20. Roderick Beck says:

    Experimental results have only shown benefits from niacinamide,, including reversal of Alzheimers in rats and improving human longevity. It is a power anti-inflammatory. David Sinclair, the famous resveratrol research, has noted that it is rash to categorize niacinamide as promoting aging:

    “One must be careful when calling nicotinamide an “inhibitor” in this experiment. While it is true that our lab showed that nicotinamide is a direct inhibitor of SIRT1 enzyme, it is also a precursor of NAD+, and NAD+ is a co-substrate (i.e., activator) of SIRT1.

    In vivo, there is an abundant enzyme called Nampt in cells and serum that initiates the conversion of nicotinamide to NAD+. Therefore we should entertain the possibility that nicotinamide is activating SIRT1 in vivo, not inhibiting it. This would fit with other papers showing that SIRT1 is neuroprotective.”

    It is very likely that niacinamide never reaches the sirtuins because Nampt converts into life promoting NAD+.

    Your article doesn’t sufficiently distinguish between nicotinic acid and niacinamide. Both prevent B3 deficiency, but they are very different otherwise. Nicotinic acid lowers LDL and raised HDL, but not niacinamide. And niacinamde has anti-inflammatory effects that appear absent in nicotonic acid.

    It is probably smartest to take resveratrol, nicotinic acid and niacinamide.

  21. admin says:

    Roderick Beck:

    Thanks for your comment pointing to the David Sinclair quote and the role of Nampt in converting nicotinamide to NAD+ and consequent possible activation of SIRT1. The actions of Nampt appear to be interesting, complex and have a controversial history. Quoting a 2009 article Nicotinamide phosphoribosyltransferase (Nampt): a link between NAD biology, metabolism, and diseases at http://www.ncbi.nlm.nih.gov/pubmed/19149599, “Among them, nicotinamide phosphoribosyltransferase (Nampt) has drawn much attention in several different fields, including NAD biology, metabolism, and immunomodulatory response. The research history of this protein is peculiar and controversial, and its physiological function has been a matter of debate. Nampt has both intra- and extracellular forms in mammals. Intracellular Nampt (iNampt) is an essential enzyme in the NAD biosynthetic pathway starting from nicotinamide. On the other hand, an extracellular form of this protein has been reported to act as a cytokine named PBEF, an insulin-mimetic hormone named visfatin, or an extracellular NAD biosynthetic enzyme named eNampt. This review article summarizes the research history and reported functions of this unique protein and discusses the pathophysiological significance of Nampt as an NAD biosynthetic enzyme vs. a potential inflammatory cytokine in diverse biological contexts.”

    Starting to look into the literature related to nicotinamide and Nampt, I have found a wealth of recent publications relating Nampt to SIRT1, circadian gene expression and possibly to the regulation of aging. I want to study this literature further and possibly generate a blog entry on the topic. At present I certainly take resveratrol but I do not now have a sufficiently clear understanding of the multiple biological actions of nicotinamide, Nampt and niacinamide to justify my taking these substances. I remain always open to learning however and there appears to be much new research on these substances to be digested. I do appreciate your putting me on this track.

    Vince

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  23. electhor says:

    It’s now October 2012 – I only recently found this site and enjoy it very much. Recently there have been reports of nicotinamide killing superbugs in anaimal trials and in labroratry tests on human blood. Mega doses were used to kill MRSA. No articles I have found have stated exact dosages. Assume they will think people will start self medicating in a dangerous fashion. The multi-national drug companies won’t like this too much – they can’t patent vitamin B3.
    http://oregonstate.edu/ua/ncs/archives/2012/aug/vitamin-b3-may-offer-new-tool-fight-against-staph-infections-%E2%80%9Csuperbugs%E2%80%9D
    **Hope it is not out of line to add to this post, so long after it was written.**

    • Electhor:

      No problem with late comments, and as you can see this reply is much later yet. Possibly megadoses of B3 interferes with quorum sensing in MRSA – at least that is my suspicion. Back in the early 70’s my family and I were into megadoses of Niacin for mental/emotional stability – back when that was popular among alternative practitioners. Until one of my sons took an OD dose and had to be hospitalized. So large doses should be coupled with regular liver function tests.

      Vince

  24. jeff says:

    I wouldnt close the door on Niacinamide:

    “In some of the publications claiming that resveratrol increases lifespan, it was reported that niacinamide had the opposite effect, suppressing Sir2, the longevity gene, and shortening the organism’s lifespan. To put their claims into context, it’s helpful to look at a variety of experiments involving treatment with niacinamide.

    It protects nerves, vascular cells, insulin-producing cells in the pancreas, and a variety of other types of cell from cell death produced by lack of oxygen, excitotoxicity, endotoxin, and a variety of stressors and toxins. (Niacinamide acts in many ways as a negation of resveratrol; for example, resveratrol interferes with the ability of the beta cells to secrete insulin [Szkudelski, 2007]).

    Niacinamide protects mitochondrial respiration from many of the age-related factors that can damage mitochondria and decrease energy production. Lipopolysaccharide, the bacterial endotoxin, increases the production of the free radical nitric oxide, leading to the secretion of inflammatory mediators and the suppression of energy production by the mitochondria. These effects are blocked by niacinamide (Fukuzawa, et al., 1997). Calorie restriction also protects mitochondrial respiration, in yeasts (Lin, et al., 2002) and rats (Broderick, et al., 2002)

    The “replicative lifespan” of human cells in vitro is extended by treatment with niacinamide (Kang, et al., 2006).

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  26. timar says:

    You may have already read it. Niacinamide may play a crucial role in Sirtuin mediated mitohormesis:

    http://www.nature.com/nchembio/journal/v9/n11/full/nchembio.1352.html

  27. Jim says:

    Hello Vince,
    Your credentials and understanding on Niacin and Niacinamide is very authoritative and broad. With the recent work at University of NSW in Australia on nicotinamide mononucleotide (NMN) as mentioned in the story which was very poorly written at http://www.news.com.au/lifestyle/health/university-of-nsw-research-finds-compound-that-can-reverse-ageing/story-fneuzlbd-1226786877989 this raises some interesting questions.
    If they can turn back the ageing clock in mice with these massive doses on Niacinamide and turn an equivalent 60 year old mouse into a 20 year old mouse in one week, what can be learned from this as it relates to humans – from your experience?
    Niacin and Niacinamide and particularly nicotinamide mononucleotide are not the same and act differently, i.e. Niacinamide doesn’t have the same benefits of Niacin for diabetics and digestive health; while nicotinamide has been used for anxiety and is purported for cell repair and anti-aging qualities, and also doesn’t cause the flushing of Niacin. What is the specific nature of nicotinamide mononucleotide that distinguishes it from the other two and how does this relate to the above benefits?
    What are your thoughts on the massive doses applied to mice and how will this relate to human trials?
    What form of nicotinamide and/or combination with niacin is useful for cell repair and anti-aging as a supplement, until the human trials show definitive results?

    I believe you currently ingest approximately 100mg of Niacin a day, without mention of nicotinamide. Does this remain your personal recommendation? (I’m 58 yrs old).

    Thanks in advance for your considered response… …Jim

  28. Hey Jeff and Jim

    First of all, thanks for sharing your insights. These blog comments are often important guideposts for where I should focus my research efforts.

    Personally I don’t close the door on Niacinamide. As a matter of fact, I just reopened that door after slamming it shut on it for personal use about 40 years ago. That was after a son ODd on excessive doses of it and had to be hospitalized. Prior to that time, knowing blessedly little at the time but being health innovator, several members of my family and I were megadosing on niacin as was fashionable at the time. I reopened the door a crack a few days ago when I read the latest David Sinclair et al article on age reversal in mouse muscles due to NAD+ enhancement based on nicotinamide mononucleotide. A further reason for turning off on niacin/micotinamide about 7 years ago was learning that they inhibit expression of telomerase. At the time, I was a great believer in the telomere length theory of aging. Since I now see telomerase expression and telomere lengths as downstream non-determinative events when it comes to aging, that argument against nicotimamide no longer has any force. I may add it back into my personal regimen.

    Jim, you asked “If they can turn back the ageing clock in mice with these massive doses on Niacinamide and turn an equivalent 60 year old mouse into a 20 year old mouse in one week, what can be learned from this as it relates to humans – from your experience?”

    The basic message I get from this and other research in 2013 is that many, probably most, of the markers areof aging that apply in the lifespan range of up to over a 100 years are probably reversible. The recent discovery of GDF11 is another indicator of this progress. this means that in a few years we will have enough knowledge to keep most people going to 100 IF they can and do apply that knowledge. It is not clear, however that we have any interventions now that will allow us to break the 122 agespan limit for humans.

    As to the questions you ask at the end of your e-mails, they are good ones and I don’t know the answers to some. I expect to get back to you on them.

    Vince

    The following is from an Australian news report. The Australian scientist David Sinclair is of course the same as our Harvard buddy. During the 10-15 years of product development,clinical trials, etc., if we want to upgrade our personal NAD, how about plain old B-3, Niacin? cost per day, less than 35 cents, not $35,000. Takes me back 40 years to when my family was megadosing on niacin.

  29. michelemmm says:

    After reading some research, this blog and comments I’ve decided on a bio available form of a B complex. There aren’t many but I’ve found one. I’m diabetic and in my mid fifties, my husband who is the same age has MS. I do believe most of the B vitamins are beneficial to us. I take Benfotiamne as well. My question is; There is 130 mg as niacinamide and 10 mg of niacin in this supplement for a daily total of 140 mg. Is this amount ok or is it too much to be taken long term based on all of your research and personal opinion?

  30. Physics Student says:

    Hello Vince,

    1. As argued in your post in this blog, low level of either nicotinamide or nicotinic acid in vivo is a cause of aging due to depleted NAD+ level, but high level of either of them is also a cause of aging due to Sirt1 inhibition.
    Then,
    Have you ever found any references(any journals like pubmed) mentioning about the threshold or the proper amount that need to be taken for NAD+ deficiency?

    In the below web-site, niacinamide(or nicotinic acid in vivo) has two properties of not only inhibiting PARP, leading to Sirt activation, but also inhibiting Sirt 1 inhibition.
    What I am now confused is that which one of effect between these two outweighs the other. Do you have any idea?
    http://www.alzforum.org/papers/nicotinamide-restores-cognition-alzheimers-disease-transgenic-mice-mechanism-involving

    Thanks.

  31. mtcg says:

    I had some interest in anti-aging supplements and stumbled upon this article in my niacin research back in late 2014.

    My first niacin supplement was taken shortly thereafter. Within an hour I remember experiencing the “niacin flush” response to the dose –though I don’t recall how many of the niacin pills I’d ingested (no more than a couple a day). After a few days, I stopped taking the pills altogether.

    Two months later, I started noticing regular, random muscle twitching throughout my body, particularly in the calves and feet. At 45 years of age, I’d never experienced such twitching before.

    My life endured an emotional roller coaster soon after, as neurologists began testing me for ALS. They found neurogenic nerve damage in an arm and in my legs. They called it chronic, but not “active,” which is the hallmark of ALS. So, it seemed the disease could be ruled out.

    Two years later, my muscles still randomly twitch and I’m still trying to understand why. The only causal link I have, something that varied from my normal routine, was my brief, high-dose niacin intake. I seem to recall an article that linked niacin supplements as a possible ALS trigger and a trigger for other neurological disorders. Alas, I can no longer find that article. Perhaps someone will visit here in the future armed with that information.

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