Are Low Doses of Niacin Dangerous?

In Food Fortification: A Risky Experiment?, Mar 23, 2012, we began looking at the possibility that fortification of food, especially the enriched flours used in commercial baked goods, with niacin, iron, and folic acid may have contributed to the obesity and diabetes epidemics.

As this plot shows, fortification caused intake of per capita niacin intake in the United States to rise from about 20 mg/day to about 32 mg/day:

Multivitamins typically contain about 20 mg niacin, so (a) a typical American taking a multivitamin is getting 52 mg/day niacin, and (b) if the increase of 12 mg/day due to fortification is dangerous, then taking a multivitamin would be problematic too.

There wasn’t evidence of niacin deficiency at 20 mg/day. The RDA was set at 16 mg/day for men and 14 mg/day, levels that equalize intake with urinary excretion of niacin metabolites [source: Dietary Reference Intakes]. Fortification of grains with niacin was designed to make refined white wheat have the same niacin content as whole wheat, not to rectify any demonstrated deficiency of niacin.

B-vitamins are normally considered to have low risk for toxicity, since they are water soluble and easily excreted. But recently, scientists from Dalian University in China proposed that niacin fortification may have contributed to the obesity and diabetes epidemics. [1] [2]

Niacin, Oxidative Stress, and Glucose Regulation

The Chinese researchers note that niacin affects both appetite and glucose metabolism:

[N]iacin is a potent stimulator of appetite and niacin deficiency may lead to appetite loss [10]. Moreover, large doses of niacin have long been known to impair glucose tolerance [23,24], induce insulin resistance and enhance insulin release [25,26].

They propose that niacin’s putative negative effects may be mediated by oxidative stress, perhaps compounded by poor niacin metabolism:

Our recent study found that oxidative stress may mediate excess nicotinamide-induced insulin resistance, and that type 2 diabetic subjects have a slow detoxification of nicotinamide. These observations suggested that type 2 diabetes may be the outcome of the association of high niacin intake and the relative low detoxification of niacin of the body [27].

The effect of niacin on glucose metabolism is visible in this experiment. Subjects were given an oral glucose tolerance test of 75 g glucose with or without 300 mg nicotinamide. [1, figure source]

Dark circles are from the OGTT with niacinamide, open circles without. Plasma hydrogen peroxide levels, a marker of oxidative stress, and insulin levels were higher in the niacinamide group. Serum glucose was initially slightly higher in the niacinamide group, but by 3 hr had dropped significantly, to the point of hypoglycemia in two subjects:

Two of the five subjects in NM-OGTT had reactive hypoglycemia symptoms (i.e. sweating, dizziness, faintness, palpitation and intense hunger) with blood glucose levels below 3.6 mmol/L [64 mg/dl]. In contrast, no subjects had reactive hypoglycemic symptoms during C-OGTT. [1]

Of course 300 mg is a ten-fold higher niacinamide dose than most people obtain from food, but perhaps chronic intake of 32 mg/day (52 mg/day with a multivitamin) daily over a period of years have similar cumulative effects on glucose tolerance as a one-time dose of 300 mg.

Is There a Correlation with Obesity?

OK. Is there an observable relationship between niacin intake and obesity or diabetes?

There may be, but only with a substantial lag. Here is a figure that illustrates the possible connection [2, figure source]:

Niacin intake maps onto obesity rates with a 10-year lag. After niacin intake rose, obesity rates rose 10 years later. Note the scaling: a 60% increase in niacin intake was associated with a doubling of obesity rates 10 years later.

Obesity leads diabetes by about 15 years, so we could also get a strong correlation between niacin intake and diabetes incidence 25 years later. The scaling in this case would be a 35% increase in niacin associated with a 140% increase in diabetes prevalence after a lag of 25 years.

How seriously should we take this? As evidence, it’s extremely weak. There was a one-time increase in niacin intake at the time of fortification. A long time later, there was an increase in obesity, and long after that, an increase in diabetes. So we really have only 3 events, and given the long lag times between them, the association between the events is highly likely to be attributable to chance.

It was to emphasize the potential for false correlations that I put the stork post up on April 1 (Theory of the Stork: New Evidence, April 1, 2012). Just because two data series can be made to line up, with appropriate scaling of the vertical axis and lagging of the horizontal axis, doesn’t mean there is causation involved.

Is There Counter-Evidence?

Yes.

If niacin from wheat fortification is sufficient to cause obesity or diabetes, with an average intake of 12 mg/day, then presumably the 20 mg of niacin in multivitamins would also cause obesity or diabetes.

So we should expect obesity and diabetes incidence to be higher in long-time users of multivitamins or B-complex vitamins.

But in fact, people who take multivitamins or B-complex vitamins have a lower subsequent incidence of obesity and diabetes.

One place we can see this is in the Iowa Women’s Health Study, discussed in a previous post (Around the Web; The Case of the Killer Vitamins, Oct 15, 2011). In that post I looked at a study analysis which was highly biased against vitamin supplements; the authors chose to do 11-factor and 16-factor adjustments designed to make supplements look bad. The worst part of the analysis, from my point of view, was using obesity and diabetes as adjustment factors in the regression analysis. As you can see in the table below, multivariable adjustment including obesity and diabetes significantly raises the mortality associated with consumption of multivitamins or B-complex supplements:

This increase in hazard ratios (“HR”) with adjustment for obesity and diabetes almost certainly indicates that the supplements reduce the incidence of these diseases.

Multivitamins are protective in other studies too. The relation between multivitamin use and subsequent incidence of obesity was specifically analyzed in the Quebec Family Study, which found that “nonconsumption of multivitamin and dietary supplements … [was] significantly associated with overweight and obesity in the cross-sectional sample.” [3]

Does this exculpate niacin supplementation? I don’t think so. In general, improved nutrition should reduce appetite, since the point of eating is to obtain nutrients. So it’s no surprise that multivitamin use reduces obesity incidence. But multivitamins contain many nutrients, and it could be that benefits from the other nutrients are concealing long-term harms from the niacin.

Conclusion

At this point I think the evidence against niacin is too weak to convict in a court of law.

Nevertheless, we do have:

  • Clear evidence that high-dose (300 mg) niacinamide causes oxidative stress and impaired glucose tolerance. If niacinamide can raise levels of peroxide in the blood, what is it doing at mitochondria?
  • No clear evidence for benefits from niacin fortification or supplementation.

Personally I see no clear evidence that niacin supplementation, even at the doses in a multivitamin, is likely to be beneficial. Along with other and stronger considerations, this is pushing me away from multivitamin use and toward supplementation of specific individual micronutrients whose healthfulness is better attested.

I also think that food fortification was a risky experiment with the American people, and stands as yet another reason to avoid eating grains and grain products. (And to rinse white rice before cooking, to remove the enrichment mixture.)

References

[1] Li D et al. Chronic niacin overload may be involved in the increased prevalence of obesity in US children. World J Gastroenterol. 2010 May 21;16(19):2378-87. http://pmid.us/20480523.

[2] Zhou SS et al. B-vitamin consumption and the prevalence of diabetes and obesity among the US adults: population based ecological study. BMC Public Health. 2010 Dec 2;10:746. http://pmid.us/21126339.

[3] Chaput JP et al. Risk factors for adult overweight and obesity in the Quebec Family Study: have we been barking up the wrong tree? Obesity (Silver Spring). 2009 Oct;17(10):1964-70. http://pmid.us/19360005.

Leave a comment ?

105 Comments.

  1. @Tess

    100-130 g carb per day sounds like it would be enough for a 125 pound woman. Why are you trying to add carbs?

    You can get up to half of cals from fat, if they’re the right kinds. The healthy sources of dietary fat for humans are animal (organic, because the pollution’s in the fat), nut (peanut is not a nut, but a little is ok), and fruit (olive, coconut, avocado). Get all three.

    Before I saw Paul’s response, before I even finished your post, I was already thinking “Has she done a round of pro-biotics?” You did some serious nutritional self-abuse on that vegan kick. Acidophilus first, then bifidus. Also, look into “fructo-oligo-saccharide” (FOS); it’s called “pre-biotic” because it specifically feeds the good gut bacteria, and helps them thrive.

  2. George Henderson

    Interestingly I got that tired, drugged unfocussed feeling after resuming carbs for a while; think I will drop back to 50g and only eat more when I have symptoms that suggest more is needed.

    FOS can feed dysbiosis, and there would be lots of it in a vegan diet:
    http://www.archevore.com/panu-weblog/2011/2/5/fodmaps.html

  3. Hi Tess,

    I think you should eat enough carbs to get rid of the dry eyes and low energy, but stay near the minimum until you fix your gut problems.

  4. Just wanted to add my two cents: These dates also correspond to when iodine was replaced with bromides as the primary dough conditioner in commercial bakeries, which happened sometime in the mid to late 60’s.

  5. comments on blogpost critical of niacin (cobcon)

    the comments on this post remind of people that criticize the us post office. we take it for granted all of our lives/even generations and then criticize them with the first problem. in fact, we have all been taking niacin in our bread all of our lives and thank you god.

    niacin is in fact one of the greatest successes in the history of modern medicine. deficiencies of niacin were the most devastating nutritional disease ever observed in the history of man. there are only about 5 different vitamins that were deemed so important that the us government felt compelled to make it a law that the refined foods (most dramatically preceding the pellagra epidemics; the introduction of white flour, white rice, and white bread) was niacin.

    it could even be argued that the insane world wars that took place, all occurred just prior to discoveries or at least enrichment of grains. niacin was discovered for example in 1939 and mandatory enrichment took place starting roughly in 1942.

    some of the concerns here are with respect to niacin at high doses. niacin at 40mg vs 20mg as an association with obesity, are you kidding me?! niacin has been used to treat people with high cholesterol for over 50 years! i could find stock charts with much better correlations with the increase in obesity. obviously however, the best correlations will involve increases in sugar intakes, not niacin.

    any normal healthy individual will experience a flush response to niacin at dosages over a range but starting from typically 150mg or higher. the flush is a wonderful thing to many people, myself included. however, it can be very uncomfortable if you are not ready for it. particularly post-menopausal women and light weighted people in general may find the flush particularly intense. however, the flush response is specifically associated with niacin’s particularly fantastic benefits to dyslipidemia. it has also been proven to assist in speeding up metabolism of drugs and toxins. its benefits remain to be discovered by the inquisitive individual. our bodies are designed to use it and we need more during times of stress. at high levels the flush response occurs and while we do not fully understand why this occurs at a normal functioning level, but from a drug standpoint it is unparalleled in its ability to help prevent cardiovascular disease (strokes, heart attacks, etc… )

    niacin is in fact phenomenal. it is involved with over 450 different proteins we now know (i just published the textbook chapter and this is only recently understood in some respects; i.e. we only recently sequenced the entire human genome and so with everything annotated we can begin to carefully determine these numbers). this number represents a greater number than any other vitamin-derived molecule.

    the oral glucose tolerance test is of no to little concern with respect to niacin. in fact in clinical trials focused on cardiovascular disease there were some patients that had problems with diabetes that subsequently obtained benefits from there niacin treatments.

    the recent aim-high trials include patients for whom their niacin medication was stopped for a full month before they experienced subsequent pathology. they concluded that these patients were hurt by niacin. that does not make sense to me. it could also be included that by stopping for a whole month this led to the pathology happening again.

    here is a small list all of which are >500mg niacin a day:
    coronary drug project, >8000 people, 27% reduction in myocardial infarctions and 24% reduction cerebrovascular events… 15 years later and 11% reduction in total mortality
    stockholm study… similar results as above, but ~600 patients
    aim-high.. no difference in cardiovascular endpoints (this study involved combinations with statins)
    arbiter studies … several hundred patients… significant decreases in carotid intimal artery thickness…

    again… over the years thousands of people take high doses of niacin… no particular increase in diabetes or risk to diabetics at all. if anything, it benefits diabetics, but a person should be aware of niacin’s effects. i.e. be ready for some degree of fluctuation in glucose levels as with eating anything especially for brittle diabetics. its just a case of be prepared with some candy or what you need just in case for diabetes.

    regarding the individual in this list that gets angry after taking niacin. this is curious and quite unique in my opinion. i know myself and others i know who take niacin, will immediately become very focused on what they are doing shortly after taking niacin. at this point, if you are interrupted, you may feel a little disturbed. for me this is not a panicky anger response. it is instead just a realization that i am being interrupted, where previously such an interruption may instead be perceived without as much response.

    in the ny times bestselling book called 8 weeks to a cure to heart disease, the author -a self described heart attack waiting to happen- describes in chapter 8 that if he had to pick one thing that helped him more than anything, it would be niacin.

    high doses of niacin (you can get just about any immediate release niacin; get the one that warns, may cause a flush response) cause a person to:
    1) decrease their high cholesterol
    2) reduce their really bad cholesterol (VLDL)
    3) raise their good cholesterol (HDL; and this has the highest correlation with CVD of all these)
    4) reduce triglycerides

    in fact the benefits of high doses of niacin save people’s lives all of the time.

    cardiovascular disease is tough though. we have miles of plumbing inside our body and anywhere there are calicifications/plaques etc… there is eventually potential for problems. for some people we don’t know to do and then it just happens. however, niacin is one of the most effective pharmacologic agents known for dealing with all this.

    no other molecule does this as well.
    how can one molecule push all 4 of these in the correct direction?
    this is the eternal question in niacin research and the pathways are interesting.

    niacin becomes NAD in the cell and NAD participates as NAD, NADH, NADP, or NADPH in hundreds of redox reactions, many of which are involved in metabolizing all kinds of lipds in the cells. Ultimately high doses of niacin keeps these cofactors at high enough levels so that they are never the limiting step in much of your cellular chemistry.

    NAD is rapidly depleted with all kinds of stresses. Niacin repletes this phenomena.

    Sincerely,
    W. Todd Penberthy

  6. Hi Paul,

    sorry about the off-topic, but here’s an interesting article about a rather unusual researcher in one of your fields of interest:
    http://www.psychologytoday.com/articles/201204/the-mysterious-case-the-vanishing-genius

  7. Thanks for the link, Michael. That’s a great story and yes, an area of interest for us.

  8. Paul, was I totally off with my reasoning or why didn’t you respond?

  9. Hi Primordial,

    It was an excellent comment. (For those wondering what we’re talking about, the comment is here: http://perfecthealthdiet.com/?p=5866&cpage=1#comment-75359.)

    I haven’t had time to read the papers you cited, but here’s my off-hand reaction:

    Hypoglycemia is dangerous and low liver glycogen shouldn’t be enough to push someone into hypoglycemia. So whether the mechanism is via excessive inhibition of lipolysis or some other pathway, the niacin clearly created a dangerous situation in some people.

    It is a good point that the study subjects had metabolic syndrome. It may be that healthy people would tolerate niacin much better.

    The Kang et al and Oh et al studies seem contradictory in that one shows niacin inhibiting lipolysis and one shows niacin promoting it.

    I don’t follow the argument that peroxidation of polyunsaturated fats can account for the rise in hydrogen peroxide. Peroxidation of fats should destroy hydrogen peroxide. It seems more logical that the increased hydrogen peroxide is due to an increase in glucose metabolism.

    Best, Paul

  10. George Henderson

    @ Todd,

    great comment except for

    “its just a case of be prepared with some candy or what you need just in case for diabetes.”

    which will go down like a cup of cold sick here.

    In defense of Paul, these “niacin causes obesity” theories are out there on PubMed therefore worth analysing. Someone is paying for them.

  11. Thanks for your answer, I will contemplate about it.

  12. thank you george for the comments.

    i do agree that the effects of niacin on glucose levels is definitely worthy of investigation, but practicality and physiological significance must be taken into consideration. these “high” doses of niacin (40mg) … ridiculous concern. i take about 1500mg over 3x 500mg a day for over 10 years. many people do.

    i respectfully disagree regarding pubmed and getting paid. we all know that getting paid does not mean something is worth anything to the 3rd person observer (us). pubmed is of course full of negative data or trivial data.

    i’ve seen brittle diabetics come back from zombie state with drops of orange juice. the practical diabetic knows that value of one m&m in some situations.

    without niacin in the flour/white rice we had over 100,000 people die in the first 2 decades of the 20th century united states alone. entire mental health hospitals were full of pellagrans. the epidemic started just after we developed milling technologies that enabled the common man to have white rice and flour. today, thank goodness.. .nearly all cakes, bread, flour etc.. is fortified to prevent so much suffering. we’re all ignorant when we are young and don’t know better until someone tells us or prevents us from these bad things.

    most respectfully yours,
    todd

  13. George Henderson

    My point was that someone is funding research into niacin-obesity research even though the premise seems ridiculous and the evidence is underwhelming.

    I was being flippant about the candy-diabetes line. The idea that insulin needs to be “covered” with extra carbs, instead of being calibrated properly with a lower carb diet, and the low-carb response to that, is what I was satirising. The use of boiled lollies (which are made from glucose mainly, not fructose) in hyperinsulinemia is not controversial.

    Flour and rice were fortified to protect populations that couldn’t afford to eat meat and milk every day. Pellagra was a major killer during the WW1 blockades and the depression.
    And it’s not farfetched to see the connection with WW2, which was started by one blockaded nation (germany) and one white-rice dependent society (Japan) both of which had also been through more recent economic hardship.
    This was an important public health measure, but it

  14. George Henderson

    can always be reviewed in better times.

    Funny article on the news last night about how
    gluten-free diets can cause B vitamin deficiency.
    Because of the fortification of flour being a major source of Bs. But surely US rice would suffice.
    It just goes to show that gluten-free grain products are no substitute for a grain-free diet…

  15. Thank you for the history lesson and perspective (deaths in depression) George. I did not realize Germany was blockaded and that Japan was a white-rice dependent society (real interesting to my way of thinking… so frequently we especially in America know little about international history). Much appreciated.

  16. George Henderson

    In fact, the malnutrition produced by blockade of the Central Powers (which lasted well after the war) allowed the first human experiments on vitamin supplementation in deficiency to be carried out in Vienna.
    http://jn.nutrition.org/content/132/7/1805.full

  17. What about MSG? I understand that MSG makes people “addicted” to food and could be a major source of obesity. Further, I’ve read that the only way to produce obese mice for studies is to inject them with MSG.

  18. Great question Ann.
    I too have heard this and look forwards to the responses.
    All I know is that glutamate is also excitotoxic to neurons at least when it is injected.
    Todd

  19. George Henderson

    Acrylamide is also worth looking at as a potential obesigenic food neurotoxin. It is found in the fattening starchy foods; fried starches, bread, biscuits, pastry and the like.

    Another beneficial function of niacin: nitric oxide production. ADMA (asymetrical dimethyl-arginine blocks conversion of l-arginine to NO*.

    Endothelial dysfunction reflects an imbalance between release
    of vasodilator and vasoconstrictor endothelium-derived factors.
    A decrease in the bioavailability of NO involves either a
    decrease in NO synthesis or inactivation of NO due to
    increased endothelial production of reactive oxygen species
    (ROS).8 With increased oxidative stress, tetrahydrobiopterin
    (BH4), a cofactor that tightly regulates NO production, is oxidized
    resulting in the uncoupling of eNOS and reduced NO
    production.9 Elevated levels of asymmetric dimethylarginine
    (ADMA), an endogenous inhibitor of eNOS through competition
    with L-arginine, may further reduce NO production.7 This
    perpetuates a cycle of vascular oxidative stress through the
    transfer of electrons to molecular oxygen, forming oxidant
    species such as superoxide and peroxynitrite, which further
    consumes NO and increases oxidative stress (figure 1).9,10
    https://www.google.com/url?url=http://scholar.google.com/scholar_url%3Fhl%3Den%26q%3Dhttp://www.dvdres.com/content/4/2/89.full.pdf%26sa%3DX%26scisig%3DAAGBfm2iqyv-87vt5xwxZVXnB4s25LD_eA%26oi%3Dscholarr&rct=j&sa=X&ei=_BmwT5vME4qkiQfupbXeCA&sqi=2&ved=0CBsQgAMoADAA&q=asymmetrical+dimethylarganine+nicotinic+acid+nicotinamide&usg=AFQjCNEl1SwGve35eWAJ3nNHV7Kpze-74A

    This shows how high nicotinamide intakes interaqct with homocysteine; this is the same effect that can lower ADMA.

    http://www.nature.com/hr/journal/v35/n2/full/hr2011151a.html

  20. Beyond absurd, especially given other more well established factors like excess of refined carbs and micronutrient deficincies. That small amount of added Niacin can’t even prevent deficiency in some people which have higher needs then stated by RDA, the ridiculous hard-coded value that is supposed to reflect adequate level of nutrients for humanity (Hemilä, 1984, Nutritional Need Versus Optimal Intake)

    First, niacin may be behind nicotine’s well known weight reducing effect.

    Second, for all we know its anti-inflamatory, anti-infective and anti-CVD effects are all helpful in obesity. Infections can lead to obesity via different mechanisms – by replacing beneficial flora, by stealing nutrients and so on…

    Niacin rises adiponectin which is found to be decreased in obesity.

    Via its well known protective effects on central nervous system it could also be speculated that it is of benefit in obesity.

    It is also found that it reduces MI equally in patients with and without metabolic syndrome (PMID: 16461040) which would not be so if it actually agravitates MS.

    On a negative side, it is PPAR& agonist which looks like a fattening thing (well known from diabetes synthetic agonists, PMID: 16386710, how much does it relates to vitamin can not be said).

    Also, theoretically, via its effect on GPR109A on adipose tissue which activation reduces TG lipolysis we could expect promotion of obesity.

    All those potential negatives are by far exceeded by “proven” positives of high dose niacin for various problems, ranging from migraine to cholesterol problems, and its remarkable safety (apart from transaminase elevation with questionable sustained release formulas) is well known (there are cases of schizophrenics ingesting 60 and 100g at once without any serious side effects, for instance)

  21. George Henderson

    If niacin is PPAR-alpha agonist this is just the ketone receptor effect. We can predict that niacin will fit better with a low-carb diet and be effective at lower doses, if it is not struggling against carbohydrate inducing an opposite state.

    Not everyone is overweight.
    The appetite limiting effect of nicotine is possibly linked to methylation and catecholamine levels, and may well be paralled by niacin.
    Pyridine is a powerful methyl acceptor in chemistry.

  22. Hi Paul,

    I was wondering if you had any thoughts on the niacin/sauna detox, in which a person takes 5,000 mg of regular niacin and then goes into a sauna. They’re supposed to do this daily for a month. Supposedly the niacin will cause lipolysis, which will liberate toxins stored in fat cells. Does this sound dangerous to you?

  23. The 5g of niacin and a sauna sounds extremely intense to me. I have been taking 500mg spread out over roughly 4x a day and when I have taken 1g it it typically a little more than I prefer.

    5g will feel terribly uncomfortable for some people, but it definitely doesn’t kill people. It may be a little bit dangerous for someone with a seriously compromised liver, but there was one individual just for example that took 12g at once a couple of years ago to try to treat his schizophrenia and he basically suffered from low blood pressure for a day or so, but completely recovered just fine after than.

    The idea that niacin detoxifies is correct. The cytochrome P450 enzymes metabolize drugs, pollutants, and toxins as well as being central to all endogenous metabolism involving sterols/vitamin D/steroids, retinoids, prostaglandins, and more. The P450 enzymes require NAD for activity and niacin becomes NAD in your body. So plenty of NAD helps to assist to make sure these enzymes are ready to help with all of this chemistry and besides at a more practical level, this has been shown before, that niacin really does help to metabolize and clear drugs, which is essential to helping to prevent adverse drug reactions which occur with the slow metabolizer phenotype.

    Todd

  24. @Todd:

    Hoffer described cases of acute ingestion of 60 and 100g without any serious effects.

  25. Isn’t that amazing. That has got to be about the size of a niacin potato.
    I don’t know what the LD50 is for niacin to mice as compared to other toxins, but it would be interesting to know.
    Todd

  26. If 100 mice are given the drug and half die that dose is the LD50; for niacin it is very high, about 4.5 grams per kilogram. This is equivalent to 225 grams (nearly half a pound) for a 110 pound female and 360 grams for a 176 pound male, or approximately 100 times as much as is normally recommended. At autopsy the animals showed elevated fatty acids in the liver.

    http://www.orthomolecularvitamincentre.com/vitaminb3.php
    http://www.sciencelab.com/msds.php?msdsId=9926207

  27. Thank you for the heads up Majkinetor. It looks like the LD50 is even higher for rats – the MSDS lists 7g/kg. I would have to eat 600g to reach that point. One hundredth of that is recommended by the scientologists with sweat-detox therapy and I personally take 1/1000th of that (500mg) with much pleasure throughout the day several times for over 10 years now. I guess 1/1000th of predicted LD50 is likely to be fine.

  28. Is it dangerous to take 5grams of L-Arganine and 1500 mg of flush Nacine. I am doing this to improve my circulation as I suspect that I have Periferal vascular disease. I have numbing of of my feet at night, no hair on my ankles or toes which I used to have. Dr Oz says this is a warning sign. I also have broken my right ankle 4 times and have varicous viens and a enlarged right calf.
    I also have sleep Apnea and use a c-pap machine. I am 53 6ft 1 245 pounds. I carry my extra weight in my stomack all my Dr ever says to me is your to fat lose weight which I am. I really don’t want to have a heart attack or stroke and have been increasing my exercise routine. Going to my Dr is not a option as he thinks I’m a life extension nut. Any opinion(advice) will be greatly appreciated. Thanks Drew

    • Hi Drew,

      1.5 g niacin can certainly cause liver toxicity. Amino acids like arginine are usually best taken in balance with other amino acids, as in food.

      Are you eating our diet?

  29. Hi Drew,

    I think you are on the right track with 1.5g of nicotinic acid / the flush niacin. You should take it though several times a day, hopefully experiencing a slight flush several times. I personally take 500mg 3-5x a day. There are no real concerns at all for toxicity at these levels. Niacin has been used for over 50 years in clinical medicine at higher dosages. The problems come with sustained release niacin. The plain ole cheap flush causing niacin works best. You can get it at GNC for about 15$.

    The thing is you, pee this stuff out in a couple of hours. So, I like to take it in the morn, whenever I feel like a want to jump in the day, and before I go to bed (a time for lots of cellular regeneration). All of this helps.

    Regarding arginine, that should be fine. I just published my own evaluation of high doses of arginine for consideration for the treatment of schizophrenia last year. From examining the literature, you might try 3-10g of arginine 3x a day.

    You may also want to consider 250 mg of magnesium, which is amazing for so many reasons and so many people as well. Particularly if you don’t eat much green food, you may want to get this pill.

    This is only what I would do for myself if I had similar symptoms and does not constitute medical advice or diagnosis.

    Best,
    Todd

  30. You can also use no-flush niacin (inositol bound), I’ve seen someone with peripheral circulation problems get benefits with that. It’s pretty safe.
    i’d also suggest rutin or similar bioflavinoids.

    • Yes, Drew mentioned he/she had varicose veins which are also related to ‘venous insufficiency’, so the most prudent thing to do would be to address that with rutin, or pycnogenol or other flavonoids that have been proven in studies to be effective.

      And venous insufficiency is connected to insulin resistance/pre-diabetes and diabetes, so would taking niacin be wise considering that connection?

  31. you seem to list a lot of reasons to go against some things that the CDC claims as top 10 public health achievements. couldn’t fluoride be added to this list as well, the replacement of iodide in bread with bromide for conditioning the dough, etc.? I know these are controversial topics and I do believe, as you do, that the dose makes the cure. perhaps that’s the only problem with these public health achievements is that they cannot control the dose and therein lies the problem with fortification of water, foods, etc. but in a different population that truly was malnourished they did have an effect and were very useful. do you agree that perhaps it’s an anachronism?

    • Hi Lynh,

      I do think replacing iodine with bromine in bread was a bad idea. Fluoridated water — I think it would be better to have unfluoridated water and fluoridated toothpaste.

      I also agree that fortification can benefit certain malnourished persons. Still, I think they are fortifying with the wrong things, as a rule.

  32. Dr Jaminet – I appreciate your work and am finding my health much improved on your diet, however I was just diagnosed with oesteoarthritis and have quite a bit of pain so have been doing some additional research. I have been reading about Dr Kaufman’s niacinamide protocol which both he and his wife used for 55 years with no adverse side effects – please see this site for information on Dr Kaufman http://www.doctoryourself.com/biblio_kaufman.html. As a scientifically challenged layperson I’m having difficulty reconciling his work with what I’m reading here. I would appreciate any illumination you can provide. Also wondering if you are aware of the study UC Irvine is doing on niacinamide and Altzheimers?

  33. Hi Paul,
    what’s your opinion on supplementing with chromium Polynicotinate ? 200mcg a day. (it does have a bit of niacin as far as I know)
    I’ve been dealing with reactive hypoglycemia and though a paleo diet improved it, it didn’t solved it. I’ve heard this type of chromium is what some doctors recommend to overcome RH.
    Before I used to supplement with chromium picolinate (100mcg) but I didn’t see any benefits from it.
    Thank you.

  34. Thank you Paul. I suppose you don’t consider the niacin in chromium polynicotinate to be dangerous. It’s only 1mg. I plan on supplement just for 3 months tops… I used to take a multivitamin (centrum) every single day for 5 months. I’m plannig on stop for a while. The only supplement I take now is Magnesium and sometimes Omega 3.
    Also I want to let you know that after 2 years on VLC and having problems from it your recommedations and diet are helping me alot. I feel alot better physically and mentally.

    • Hi Thomas,

      Well, those are pharmacological doses of niacin and a superphysiological response of growth hormone. Growth hormone has negative as well as positive effects. I would say we don’t really know the health effects of taking that much niacin, and I wouldn’t recommend it for most people.

  35. I saw this article today which discusses niacin and gut health.

    http://www.sciencedaily.com/releases/2014/01/140116113510.htm

    As someone who has Ulcerative Colitis maybe I will keep some niacin on hand for when I feel a flare starting. It will be just another n=1 experiment added to my list.

  36. Could it be that there is an accidental addiction happening? If modern wheat causes digestive distress in many people and impairs the absorption of niacin, if that wheat is then fortified with niacin, first it will induce deficiency and then will induce craving to eat more wheat. In other words, the more wheat you eat, the less you are able to digest niacin, and the more you crave the niacin-fortified wheat.

  37. I have just been through a lot of test and am deficient in a number of areas and B3 is one of them. I am a paleo eater so I don’t consume things out of boxes and only eat pretty close to paleo.

    I have read some research that says in order to fix a deficiency in this area you need to take on board 1000+ mg daily?

    I believe Paul and PHD says to not supplement Niacin as it is everywhere. Maybe no one told my body that so it is looking in the wrong places

  38. Actually, fortification of foods with thiamin and iron has been implicated in the obesity epidemic too. See this article.

    And if you read the comments in that link, iron when unopposed by Manganese has links to obesity. Manganese is a blood sugar regulating mineral. Most flours are fortified with iron but not Manganese. It’s as if some governments want their citizens to be obese.

    Note the comments about how this explains the French paradox, as the French have very low obesity, eat twice as much wheat as Americans, but do not fortify their flour.

  39. Niacinamide not the same as nicotinamide. Often opposite effects between the two.

  40. I meant Niacin and Niacinamide/nicotinamide.
    Do you still think it is dangerous to supplement any of these forms?

    • Indeed I was scrolling through the comments thinking, “Who is going to point out to Mr. Jaminet that niacinamide aka nicotinamide does not equal niacin aka nicotinic acid?”

  41. While there maybe a chance of encountering side effects while using Niacin (the flush etc) but from what I gather the benefits far outweigh any negatives.

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