Friday, May 7, 2010

Niacin and its effects on growth hormone, glucagon, cortisol, blood lipids, mental disorders, and fasting glucose levels

Niacin is a very interesting vitamin. It is also known as vitamin B3, or nicotinic acid. It is an essential vitamin whose deficiency leads to a dreadful disease known as pellagra. In large doses of 1 to 3 g per day it has several effects on blood lipids, including these: it increases HDL cholesterol, decreases triglycerides, and decreases Lp(a). Given that this is essentially a reversal of the metabolic syndrome, for those who are on their way to developing it, niacin must really do something good for our body. Niacin is also a powerful antioxidant.

The lipid modification effects of niacin are so consistent across a broad spectrum of the population that some companies that commercialize niacin-based products guarantee some measure of those effects. The graphs below (click to enlarge) are from Arizona Pharmaceuticals, a company that commercializes an instant-release niacin formulation called Nialor (see: The graphs show the peak effects on HDL cholesterol and triglycerides at the recommended dose, which is 1.5 g per day. The company guarantees effects; not the peak effects shown, but effects that are large enough to have clinical significance.

Niacin also has been used in the treatment of various mental disorders, including schizophrenia. Its effectiveness in this domain (mental disease) is still under debate. Yet many people, including reputable mental health researchers, swear by it. Empirical research suggests beyond much doubt that niacin helps in the treatment of depression and bipolar disorder.

Abram Hoffer, a Canadian psychiatrist who died in 2009, at the age of 91, has discussed at length the many beneficial health effects of niacin. He was also a niacin user. He argued that it can even make people live longer, and be generally healthier and more active. The effect on longevity may sound far-fetched, but there is empirical data supporting this hypothesis as well. (For more, see this book.)

By the way, moderate niacin supplementation seems to increase the milk output of cows, without any effect on milk composition.

Most people dislike the sensation that is caused by niacin, the “niacin flush”. This is a temporary sensation similar to that of sunburn covering one’s full torso and face. It goes away after a few minutes. This is niacin’s main undesirable side effect at doses up to 3 g per day. Higher doses are not recommended, and can be toxic to the liver.

Nobody seems to understand very well how niacin works. This leads to some confusion. Many people think that niacin inhibits the production of VLDL, free fatty acids, and ketones; preventing the use of fat as an energy source. And it does!

So it makes you fat, right?

No, because these effects are temporary, and are followed, often after 3 to 5 hours, by a large increase in circulating growth hormone, cortisol and glucagon. These hormones are associated with (maybe they cause, maybe are caused by) a large increase in free fatty acids and ketones in circulation, but not with an increase in VLDL secretion by the liver. So ketosis is at first inhibited by niacin, and then comes in full force after a few hours.

The decreased VLDL secretion is no surprise, because VLDL is not really needed in large quantities if muscle tissues (including the heart) are being fed what they really like: free fatty acids and ketones. When VLDL particles are secreted by the liver in small numbers, they tend to be large. As they shrink in size after delivering their lipid content to muscle tissues, they become large LDL particles; too large to cross the endothelial gaps and cause plaque formation.

It is as if niacin held you back for a few hours, in terms of fat burning, and then released you with a strong push.

Since niacin does not seem to suppress the secretion of chylomicrons by the intestines, it should be taken with meals. The meals do not necessarily have to have any carbohydrates in them. If you take niacin while fasting, you may feel “funny” and somewhat weak, because of the decrease in VLDL, free fatty acids, and ketones in circulation. These, particularly the free fatty acids and ketones, are important sources of energy in the fasted state.

Given niacin’s delayed effects, it does not seem to make much sense to take slow release niacin of any kind. In fact, the form of niacin that seems to work best is the instant-release one, the one that gives you the flush. It may be a good idea to wait until 3 to 5 hours after you take it to do heavy exercise. You may feel a surge of energy 3 to 5 hours after taking it, when the delayed effects kick in.

The delayed effects of niacin on growth hormone, cortisol and glucagon are probably the reasons why people taking niacin frequently see a small increase in fasting glucose levels. This increase is usually of a few percentage points, but can be a bit higher in some people. Growth hormone, cortisol and particularly glucagon increase blood glucose levels; and the blood levels of these hormones naturally rise in the morning to get you ready for the day ahead. Niacin seems to boost that. Hence the increase in fasting blood glucose levels. This appears to be a benign effect, easily counterbalanced by niacin’s many benefits.

In spite of a possible increase in fasting glucose levels, there is no evidence that niacin increases average blood glucose levels. If it did, that would not be a good thing. In fact, it has been argued that niacin intake can be part of an effective approach to treating diabetes; Robert C. Atkins discussed this in his Vita-Nutrient Solution book.

Niacin’s effects on lipids are somewhat similar to those of low carbohydrate dieting. For example, both lead to a decrease in fasting triglycerides and an increase in HDL cholesterol. But the mechanisms by which those effects are achieved appear to be rather different.


Quabbe, H.J., Trompke, M., & Luyckx, A.S. (1983). Influence of ketone body infusion on plasma growth hormone and glucagon in man. J. Clin Endocrinol Metab., 57(3):613-8.

Quabbe, H.J., Luyckx, A.S., L'age M., & Schwarz, C. (1983). Growth hormone, cortisol, and glucagon concentrations during plasma free fatty acid depression: different effects of nicotinic acid and an adenosine derivative (BM 11.189). J. Clin Endocrinol Metab., 57(2):410-4.

Schade, D.S., Woodside, W., & Eaton, R.P. (1979). The role of glucagon in the regulation of plasma lipids. Metabolism, 28(8):874-86.


Venkat said...

Hi Ned,

Thanks for this post.

Do you consume/recommend any particular brand of niacin for these benefits?


~ Venkat

Gretchen said...

Of possible interest:

Ned Kock said...


I started a while back when my doctor suggested statins, and I opted for niacin. After some research, I decided to use Nialor:

Nialor is instant-release. It gives me the flush, so I know I am taking the real thing.

The flush does not bother me in the least. I often don't notice it, unless I try to pay attention. I've had the flush while in class, teaching in front of 50 people; nobody noticed.

I don't take it for the lipids, as those are pretty good now. I take it for the other benefits.

It is a good idea to talk to a doctor that knows about niacin, and have her/him monitor your health. Make sure you have your liver enzymes tested after taking, just to be sure.

Ned Kock said...


Thanks. I like that journal - Medical Hypotheses.

ET said...

I've been taking immediate-release niacin since 2003, and every time I switch from twice a day dosing to thrice daily, my liver enzymes become elevated.

I was also curious about its effect on blood glucose, so I measured mine around the clock for a week and I saw no effect of niacin on blood glucose. However, my glucose went up significantly after short bouts of intense weight training, more so when doing squats than anything else.

By itself, niacin elevated my HDL by 35%. Moving to a lower carb, higher fat diet boosted it by 60%. Together, the increase has been over 100%.

The flushing effect does improve over time. If I take it after eating, I'm often unaware of any flush. On an empty stomach, I still turn noticeably red in the face. I take niacin capsules for my daytime does, but at bedtime, I take EP Products niacin because it's more a delayed-release which is handy because I go to bed with an empty stomach, and the flush usually doesn't occur until after I'm alseep.

The last time I saw my cardiologist, he was adamant about putting me on a statin. I told him I preferred niacin because of its effect on multiple parameters. He was unconvinced and said a statin was preferable because my LDL was too high at 80!

Ned Kock said...


Flushing intensity has gone down with time for me too.

The transitory increase in blood glucose induced by weight training is interesting.

Weight training produces lactic acid in high quantities, and also induces ketosis, which is associated with gluconeogenesis.

And, lactic acid fuels gluconeogenesis.

You end up with a fair amount of glucose being produced based on lactic acid, and physiological insulin resistance (induced by ketosis). Blood glucose goes up.

By the way, your cardiologist is really persistent!

Jim said...

Ned, another good and useful post: thanks.

I had been taking the brand SloNiacin to reduce flush for a year or so, but since going from low-carb to low-carb plus higher fat, I have dropped it. The flush was unpredictable and often very uncomfortable.

I may now go back to a 500mg dose following a morning meal on days when I am going to work out using the super-slow reps Body By Science protocol in order to stimulate GH. It's hard to build any muscle tissue at 69yoa.

Should one be concerned about added cortisol release?

Sounds like ET needs to fire his cardiologist, unless the dude gets with the primal program.

Ned Kock said...

Hi Jim.

I don't think the temporary cortisol increase induced by niacin is something to be too concerned about. It happens together with growth hormone increase; similar to the early morning elevation.

Cortisol has a bad rep, but I think it somewhat undeserved. This hormone is involved in so many health-promoting processes, and also in memorization and learning.

What one does not want is to have chronically elevated cortisol levels, in the same way that chronically elevated adrenaline and insulin levels are undesirable.

How is the slow reps routine working for you? Does it help build muscle?

Venkat said...

Thanks for your reply Ned.



Anonymous said...

While you are touching upon the subject, at what time do people prefer taking their niacin? AM/PM? Lunch?

Ned Kock said...

A lot of people seem to take it three times per day. From a lipid modification standpoint, this may work fine, as suppression of VLDL secretion would happen throughout the day.

If you are trying to maximize endogenous growth hormone release, my guess is that twice a day, with at least 8 hours in between, would be better.

Anonymous said...

Great info, thanks to all. I was all set to try Sloniacin until I looked further into its fat blocking aspects. I tried regular immed. release niacin, but after a month I could never adjust to the flush. It was intense every time. I was interested in raising my HDL a bit from 49 to help offset my LDL of 199. I'm semi new to this. I think I will go a bit more low carb and add oat bran. Once again, great info here.

Jim said...

Sorry for the delayed answer, Ned.

Yes, the slow reps to failure in 60-120 seconds is working very well for compound-muscle movements, like the Big Five. It's hard to not work out more frequently than every 5-7 days, but necessary for the recovery. Strength is increasing steadily, as well as body conformation. No 'bodybuilding' interest.


Aaron Blaisdell said...

Hi Ned,

It seems like niacin is percolating up into internet consciousness. I prefer getting as many of my beneficial nutrients from natural, whole-food sources as possible. I do take D3 (Carlsons drops) and sometimes K2 (Thorne), but everything else comes from real food. I count the high-vitamin fermented cod liver oil (Blue Ice) and high vitamin butter oil (both influences of Weston Price's book) as real food rather than supplements, since they are minimally and only traditionally processed. Sorry for the long lead in, but I do have a question. What sources of real food are highest in niacin. To put it another way, how would our hunter-gatherer ancestors have procured their needed amount of niacin?


Ned Kock said...

Hi Aaron. Fish, certain organ meats (e.g., liver), beef, poultry, pork, and peanuts are among the best natural sources.

The levels that are needed for the effects discussed in this post (1-3 g) are completely unnatural. No surprise that, at those levels, niacin is called a "drug".

One would have to eat approx. 10 lbs of beef liver (a toxic amount) to get 1 g of niacin.

Aaron Blaisdell said...

Well, I love all of those foods, though I can't eat peanuts because they give me fierce gas. I avoid grains and legumes for this and other reasons.

Since I don't appear to have any symptoms of niacin deficiency I guess I'll stick to getting the proper amount for me from whole foods. It's good to know that megadoses can help a lot of folk, however.

Jim said...

Hi Ned,
Since you mentioned peanuts, which I am crazy about, what is your informed opinion about having them as a cheat component of a mostly paleo diet?

Ned Kock said...

Hi Jim.

From a macro- and micro-nutrient perspective, peanuts look great. Good sources of protein, antioxidants etc. They are even a significant source of the anti-aging substance resveratrol.

But there is research suggesting that they contain lectins that induce digestive tract problems. Foods that induce allergic reactions in some people tend to also cause low-grade problems in others. Those often go undetected for many years.

Also, peanuts can be contaminated with aflatoxin, a carcinogenic substance produced by fungi.

All in all, if you eat them in small amounts, perhaps the benefits will offset the costs. I don't know. Many foods have some health costs. And our body has mechanisms to deal with the health costs of natural foods.

Of course, between eating peanuts and white bread or table sugar, the health costs of peanuts are probably not even in the same universe.

Kindke said...

Correct me if im wrong, but after reading a few times, it appears that ketones surpress the delayed GH response by about 50% ( 9.3 ng/ml ).

Am I to believe that the delayed GH response for someone on a ketogenic diet is therefore only 50% since the niacin will surpress FFA's in the blood but not the ketones?

Ned Kock said...

Hi Kindke.

I don't think ketosis would have any effect on the GH response induced by niacin. These folks (in the post below) were on a high fat diet, and thus very likely in ketosis, and the GH response that Quabbe and colleagues found was unaffected:

One thing to bear in mind regarding the Quabbe and colleagues study is that ketones (beta-hydroxybutyrate) were injected into the participants.

That is bound to have a completely different effect from elevation of ketones via ketosis, where ketones are produced by the liver as a byproduct of fatty acid breakdown.

It is quite possible that injection of ketones sends a signal to the liver that ketone production is not needed. That suppresses the GH response, possibly because a GH rise induces ketosis. This makes sense, since blood ketone concentration during exercise is highly correlated with blood GH concentration.

Anonymous said...

Hi sir. I have a question. I suffer from chronic fatigue. I have tried B3
in the past and it gives very intense flushing at 50mg.

First hour or so I feel very energetic, but then I start feeling very tired and need to pee a lot. As if the increased energy from niacin has depleted something else. Does niacin use any other vitamins/minerals to do it's job?


Alexey said...

Niacin and ketone act on the same receptor hense similar and synergistic effect

Alexey said...

Niacin and ketone act on the same receptor hense similar and synergistic effect

Robert said...

Niacin raises cortisol, so if one takes it every day, one would have 'chronically elevated cortisol'. Also niacin increases insulin resistance, thus worsening pre-diabetic or diabetic conditions.