High dose, immediate release niacin has been a big hit in the world of plaque regression over the last decade. It has such superstars as Dr. William Davis solidly behind it, who regularly used it when he was still practicing. And usage is growing very rapidly. But is it safe over the long term? Let's look at a few of the Potential Dangers of High Dose Niacin. Note that the risks increase, at least in my opinion, as you descend the list. (Note that niacin has been positives and will likely help many men with their erectile dysfunction as I discuss on this page: Niacin and Erections.
1. Megadosing. In order a major change in lipids, which is niacin's mainstay, high dosages have to be taken. Patients typically take at least 1,000 mg per day and that is about 1,600% of the daily RDA!
2. Severe Flushing. One the guys on our site had a "bad trip" on niacin. Taking the high dosages above will almost always cause severe flushing. Check out this man's description:
"Something weird happened today as well. I am taking niacing for the last 3 weeks. It was a slow release niacin, and if I take it with meal - no effect. If it is on empty stomach, I feel skin tingling, and hands show red rash. It is itchy sometimes, but goes away after 30-60 minutes. This effect is well know with niacin. Today I took a different brand, 500 mg, NON-slow release, in the morning, on empty stomach. On the way to work I felt nuclear tingling, my face and hands went purple. I went to bathroom - turns out my whole body was red as if I had a massive sunburn. Then heart went into racing mode. In about 2 hrs it all subsided, but it was rather scary s__t." 
REBUTTAL: This can often be avoided by follow Dr. Gould's protocol mentioned on my page covering Niacin Dosages.
3. Liver Toxicity. Increased liver enzymes results in a small subset of patients.
REBUTTAL: These patients can simply lower the dosage or switch to a form (immediate release) that is less hard on the liver. Furthermore, when under a doctor's care, this appears to be a pretty rare issue:
"Although serious hepatic toxicity from niacin administration has been reported, it is largely confined to the use of slow-release formulations given as unregulated nutritional supplements." 
4. Fading Efficacy. Some commentators have written that niacin tends to fade in effectiveness, making it an undesireable option for many. For example, this doctor wrote that "my experience with niacin was pretty typical. There were modest reductions of both total cholesterol and LDL (~15%), but these changes weren t maintained over time. But I also experienced the major niacin side-effect, flushing. This irritation wasn t minor." 
5. A Rise in Uric Acid. Niacin occasionally causes an undesireable increase in uric acid. Potentially this could lead to gout, although I have never read of that being the case. One doctor treats this with allopurinol. 
6. Methylation. Niacin can lead to methylation issues in some men. For example, men with certain MTHFR variants are cautioned to "use extreme caution when supplementing with niacin, which can dampen methylation." 
7. Insulin Resistance. Thx to Torrential on the Peak Testosterone Forum for this one. I will quote from his post:
"I am bringing up this older thread to add another potential risk of long term niacin use. I have been taking 1,500mg Slo-Niacin daily for several months to help improve my lipid profile. It worked: Triglicerides way down, HDL up. I dropped down to 1,000mg daily and my Trig went up again; now back to 1,500mg daily. Liver enzymes fine btw. But my A1C level has been troublesome, creeping upward even as I clean up my act and take steps that should be driving it down. My new doc wants me on Metformin, which I will start soon."
"However, today I found this on examine.com:"
"'Current evidence suggests prolonged niacin supplementation increases insulin resistance because it hinders the ability of insulin to suppress glucose synthesis in the liver. This causes an increase in blood glucose levels, which leads to lowered insulin sensitivity over time, since the relevant receptor is eventually desensitized to the elevated glucose levels in the blood. http://examine.com/supplements/Vitamin+B3/'"
"The article discusses not only higher fasting blood glucose levels but higher insulin levels. Well, crap. Those things are worse than high triglycerides. Should I drop niacin?"
8. Possible Increased Risks of Infections, Gastrointestinal Disorders and Bleeding. Okay, I usually like to give "short and sweet" summaries of information, but I think in this case the long version is the one that is appropriate. The reason is that there are two recent studies of niacin that showed fairly similar adverse event profiles, i.e. increased risks of infections, GI and bleeding issues. Fans of niacin like to discuss only the first study, which was quite flawed, and ignore the second. Below I'll discuss both studies.
Study #1: Niacin + Laropiprant Study (2014). This study in my opinion was poorly designed and almost seems calculated to protect pharmaceutical interests. Let me start with some facts about growing niacin sales:
"The use of niacin in the US and Canada is increasing, with investigators reporting that nearly 700,000 prescriptions per month were being written in the US at the end of 2009, an increase of 191% from 2002 . In Canada, the use of niacin increased sevenfold, with nearly 14,000 prescriptions written at the end of 2009. In both the US and Canada, the increase in the use of niacin outpaced the use of statin therapy." 
Notice the incredible number of prescriptions for niacin and notice that it could be perceived as quickly gaining traction on the statin market. I am sure this did not go without notice, since statins are some of the most profitable pharmaceuticals to manufacture and sell. In 2011 they totaled over $30 billion in sales!
So what would you expect to happen if a relatively inexpensive vitamin begin to outperform and chip into sales of one of the most lucrative pharmaceutical lines of business? Well, if you are a bit jaded, you might expect that the following sequence of events would occur:
a) A study would be set up with the least effective, most commonly liver toxic form of high dose niacin. 
b) It would be coupled with a controversial and unsafe medication.
c) Non-ideal patients would be chosen for treatment, i.e. those that do not have very high LDL or triglycerides - the sweet spot for niacin. 
d) Niacin would be blamed for any issues even though two medications were involved.
Sounds far-fetched, right? Well, this is exactly what happened! So, in spite of the fact that slow-release niacin does not raise HDL as much and more often causes liver issues, this was the form chosen for the study. Furthermore, they added a weird medication called laropiprant into the mix to reduce the flushing from niacin, but laropiprant has the opposite effect on protasglandins that niacin does, so the drugs may have been fighting each other in certain pathways.
In spite of this poor design, the study seems to solely attach niacin and states that it does the following:
--Increases the risk of diabetes by 32%
--"There were also highly significant excesses of other recognized adverse effects of niacin, including gastrointestinal, musculoskeletal, and skin-related serious adverse events." 
--"The excess of gastrointestingal serious adverse events in the niacin-laropiprant group as compated with the placebo group (4.8% vs. 3.8%) included bleeding and peptic ulceration, as well as other problems in the the upper and lower gastrointestingal tracts (mostly dyspepsia and diarrhea, respectivey." 
The bottom line is that this study received significant criticism, the drug was pulled from the market and, because two medications were involved simultaneously, no definitive conclusions could be drawn. What was needed was a study with JUST niacin. It turns out that there was just such a study a few year prior:
Study #2. AIM-HIGH Study (2011 and 2014 Summary. It turns out that there was just the kind of study that we need just a few years prior to the NEJM to study #1. In the case of this study, they had a cohort with just time-release niacin and also carefully kept track of adverse events.  Perfect!
So what did this study find? Well, all you niacin-lovers out there would like to hear that niacin was a saint with almost no adverse events. Unfortunately, that did not prove to be the case. In fact, this better designed study found many of the same similar negative increases:
"There were significant between-group differences in the numbers of serious adverse events in the System Organ Class categories of gastrointestinal disorders (7.4% vs. 5.5%)."
--"...infections and infestations (8.1% vs. 5.8%). Although the full list of serious adverse events suggests certain similarities with the data from HPS2-THRIVE, particularly regarding serious adverse infectious events..."
--"..the nonsignificant numerical excess in adverse bleeding events with niacin cannot be considered definitive." 
If these sound familiar, it's because they are almost identical to those found in #1. Now, admittedly, statistical significance was not always achieved, but it is quite suspicious that increases were found in the exact same categories as the 2014 research.
Even worse, heart outcomes were just not there. They found NO improvement in cardiovascular outcomes from the niacin. And this is odd, because look at the positive changes in lipids:
--HDL rose from 35 to 42 mg/dl
--Triglcyerides dropped from 164 to 122 mg/dl
--LDL-C dropped from 74 to 62 mg/dl
Does this mean that niacin is worthless and ineffective? Let me give you several reasons why it would be hasty to jump to this conclusion:
a. Lipids Not That High. In the above study, the patients were already on a statin and another cholesterol-lowering medication. So their lipids had already been sigificantly lowered, which is obvious if you look at their starting point above. Again, as Dr. Gould pointed out with study #1, this is not really niacin's "sweet spot." Clearly, the incremental benefit of adding another medication on top of another is going to be less. This is generally with high blood pressure, diabetes and other classes of medications as well.
b. Improving Lipids Helps. Many, many studies have shown that improving lipids can improve cardiovascular mortality and events.
c. Triglcyerides Still High. With heart disease, you must improve ALL areas according to the work of the men I call The Plaque Regressing Doctors. If you'll notice, the triglycerides of these participants is still quite high. 122 is simply not that good. My guess is that the niacin helped slow down plaque buildup but did not stop it completely, because their triglcyeride levels were still too beefy. See my page on HDL, LDL and Triglyceride Targets to Reverse Arterial Plaque.
d, Niacin Meta-Analysis. There were recently a large meta-analysis done, which is a study of studies, that pooled together all the niacin research to date and concluded the following:
"Eleven eligible trials including 9,959 subjects were identified. Niacin use was associated with a significant reduction in the composite endpoints of any CVD event and major coronary heart disease event. No significant association was observed between niacin therapy and stroke incidence. The magnitude of on-treatment high-density lipoprotein cholesterol difference between treatment arms was not significantly associated with the magnitude of the effect of niacin on outcomes." 
Basically, the conclusion was that a) niacin helps signficantly heart disease except for stroke and b) HDL appears to have nothing to do with it.
MY CONCLUSION: Niacin has some very impressive meta-analysis cardiovascular results and heart disease is the number killer of men. That said, a case can be made that high dose niacin increases the risk of some rather serious side effects and adverse events. In my case, I am going to continue to try solve my issues using more natural means.
1) Medscape, "Niacin Use Increased Nearly 200% Over Seven-Year Period," Michael O'Riordan, June 10, 2013
3) Heal Your Heart, by Dr. K. Lance Gould, p. 176-177.
4) N Engl J Med, 2014 Jul 17, 371(3):203-12, "Effects of extended-release niacin with laropiprant in high-risk patients"
7) N Engl J Med 2011, Dec 15 2011, The AIM-HIGH Investigators, "Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy"
8) N Engl J Med, 2014, 371:288-290, "Safety Profile of Extended-Release Niacin in the AIM-HIGH Trial"
12) Am J Cardiol. 2007 Mar 19;99(6A):22C-31C, "Safety considerations with niacin therapy"