Niacin is a B vitamin that is cheap and highly effective at raising HDL and lowering LDL. HDL and LDL were previously called good and bad cholesterol, resp., but since the data from numerous studies show that they don’t have a big impact on health, it is probably easier to just call them heavy and light reflecting less and more lipid content. If you still want to adjust your blood lipids, then niacin is more effective than the costly statins. Unfortunately, niacin also causes an uncomfortable (itchy and hot) flush.
The niacin flush is part of the inflammatory process that includes the classic tetrad of symptoms: rubor (redness), calor (increased heat), tumor (swelling), dolor (pain). Flushing in response to niacin shows that the immune cells in the skin respond to ingested niacin that is flowing through the capillaries. Mast cells in the skin have receptors that bind niacin and the cells secrete inflammatory prostaglandins. The prostaglandins act on the capillaries to cause dilation and flushing. Mast cells have secretory granules that fuse to the cytoplasmic membrane and release their contents outside. The granules contain histamine, heparin and tryptase. The histamine stimulates histamine receptors on pain/itch nerves and the tryptase stimulates receptors on a second set of pain/itch nerves.
Prostaglandins are produced by membrane bound enzymes on the surface of mast cells. When the mast cells are stimulated, additional enzymes are added to the surface through fusion of the secretory granules. The combined enzyme complex produces prostaglandins by releasing arachidonic acid (ARA) from phospholipids of the membrane (phospholipase A2, PLA2), converting the ARA to an epoxide prostaglandin (cyclooxygenase, COX-1) and stepwise producing additional prostaglandins. These prostaglandins cause the dilation of capillaries that is seen as flushing.
Niacin also binds to receptors on fat cells, adipocytes, and blocks release of fatty acids from the triglycerides stored in these cells. It is this action that is responsible for the increase in HDL and the lowering of LDL in blood serum.
An extension of the niacin skin flushing reaction is the use of this response to demonstrate the presence of arachidonic acid and a functional immune system in the skin. A recent study used topical application of niacin and skin reddening to test the idea that schizophrenia exhausts ARA as a result of inflammatory processes in the brain. Tests showed a tendency for schizophrenic episodes to be accompanied by a diminished flushing response to niacin. This result also suggests that a lowered system-wide ARA level should show up in a predisposition to gut problems.
It would be very interesting to test the interplay between inflammatory provocations, e.g. infection, serum omega-6/omega-3 fatty acids, and measures of inflammation, e.g. C-reactive protein on niacin flushing. Inflammatory depletion of ARA may be important in the decline in the integrity of tissues that is observed in inflammatory diseases of the gut (Helicobacter-based ulcers, IBD, Crohn’s disease, celiac), autoimmune diseases (arthritis, atherosclerosis), skin diseases (vitiligo), etc. It would also be interesting to test the impact of helminth infections to reverse ARA depletion.
reference:
Benyó Z, Gille A, Kero J, Csiky M, Suchánková MC, Nüsing RM, Moers A, Pfeffer K, Offermanns S. 2005. GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing. J Clin Invest. 2005 Dec;115(12):3634-40.
Saturday, December 6, 2008
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14 comments:
Fantastic post! Doc can I ask you about the inflammation caused by grains, seeds and potatoes? i.e. Lectins?
Please also do have a peekaboo at my blog. Its health in bite size articles. Thanks
That's a pretty broad question. The quick answer is that lectins are only a problem in legume seeds. Soybeans, for example, are cooked and curded to eliminate the activity of the soy lectin and remove the trypsin inhibitor that remains soluble after heating. I don't think that lectins, carbohydrate-specific proteins, are of any consequence in grains and potatoes. The problem with those is the high starch; hyperglycemia is inflammatory. Eat small portions of starch and take a walk. The big problem with grains and other seeds is the fatty acid composition. They are very high in omega-6 fatty acids and should be avoided. Skip corn, soy, cottonseed, safflower oils and only eat olive oil. For most people, saturated fats are safer. The HDL, LDL ideas were all wrong and are only used to support statin sales. There is no research support for any of it. The whole point is that inflammation leads to disease and some statins are marginally good at lowering inflammation. Lowering LDL does not change disease risk. That's the way it looks to me. I also covered some of these subjects in my other 90 articles. I hope this helps. If you have some suggestions for articles, just ask. I enjoy your blog.
Good luck.
Hi Dr Ayers, many thanks for the thorough information. I've been into the whole blog scene just under a month now and yours is one of the best I've come across. I'll be spending some quality time studying your articles.
May I suggest an article on sugar, cholesterol and inflammation? Thanks
Rosso
hmmm.
Sugar is a broad topic, because it should include sucrose, starch, fructose and artificial sweeteners.
Cholesterol synthesis, ingestion, LDL/HDL, etc. wouldn't be so bad, but it would lean toward a discussion of the cell receptors that transport the lipid carriers, because that involves heparin.
Then, how are sugar and cholesterol involved in inflammation is a big question. I will work on some responses.
Rosso note the paleolithic article.
DR. Ayers,
I'm so glad Chris found your blog! I LOVE LOVE LOVE it. You do a wonderful job reviewing MOA and pharmacodynamics of drugs and... FOOD!
I've never heard that schizophrenic patients have niacin-flush resistance. We use a lot of niacin (SLO niacin to be precise) at Track Your Plaque -- a unique heart dz reversal program. Did you know that many of the benefits of Niacin are derived from the PG derivatives which not only cause the flush but also bind PPAR, one of the most potent inflammation shut-off switches?
EPA DHA, SCSFA butyrate (from fiber fermented by gut flora/probiotics or BUTTER), MCSFA MCT oil, and coconut oil indeed also bind PPAR. Leucine and I suspect other amino acids also activate it via indirect routes.
I can't locate the article now but I believe ketone bodies (b-oh-butyrate) do as well...
It is SO NICE to find a geek like you. Would love to hear your BRILLIANT thoughts on PPAR, esp PPAR-delta which I am quite fond of. Like you, I am really into astaxanthin (and krill oil) as well -- which is one of the top 3 most potent carotenoids so far elucidated (out of hundreds still not characterized). RXR/RAR heterodimer with vitamin D nuclear receptors for very potent synergistic anti-inflammatory actions in every chronic/acute disease state.
Thank you in advance.
Kindly, G
Dr. B G,
Let me start by saying that I know little about PPAR. Unfortunately that doesn't keep me from communicating my prejudices and molecular stereotypes.
PPARs are transcription factors and they are like the steroid hormone receptors, i.e. they have a ligand binding domain loosely connected to a DNA-binding domain. Ligands, as you indicated, are diverse.
Ligand binding is a problem for me, because the specificity is questionable and interaction between the ligand and PPAR is problematical. The ligands can't get around any easier than testosterone/estrogen/vitamin D, so carriers outside and inside the cell are required. Presumably the carriers pass the ligands eventually to the cytoplasmic form of the PPAR, binding exposes nuclear localization signals and the PPAR/ligand complex appears in the nucleus ready for action. The rest is transcription.
Lack of specificity means that the pharmaceuticals that alter PPAR are going to be problematical. They will appear to alter PPAR activity, but they will also interact with lots of other proteins and have many other side effects. I would also expect many plant products, e.g. curcumin, berberine, aspirin, etc., to also impact PPAR.
PPAR appears to provide a link between glucose metabolism, fat metabolism and inflammation.
I tried to stay outside the cell and stick to heparin sulfate interactions, but then I got drug into NFkappaB/inflammation signaling and now I am stuck in the transcription factor morass. Whoa is me.
Thanks for being interested in cellular details.
Art
Could it be that the just-halted government drug study using niacin to boost HDl, which found that heart attack risk did not decrease, missed the point, i.e., niacin DID boost HDL but was not applied in such a way to DECREASE blood vessel inflammation?
How might docs better use niacin in treating high cholesterol? Combine with Omega 3?
--AHG
AHG,,
I think that you are correct. Lowering LDL with statins has no impact on heart disease and raising HDL with niacin has no impact on heart disease. The point is that cholesterol levels and the tests for cholesterol are of no importance in heart disease compared to overall inflammation, which is best controlled by diet.
I would guess that lowering LDL in most people actually increases risks.
Regarding the last two posts - the study found that a combination of a statin and niacin had no positive effect on heart disease. It did not show anything about niacin's benefits on its own, since the statin was a confounding factor. Are there other studies showing that niacin by itself is useless for controlling heart disease?
Hello,
I am trying to find out if my lab results which were 10 for CRP might be a result of the Niacin Flush reaction I had the day before. Severe reaction including tingling, itching, burning, rash, etc.
thank you
Dr. Ayers,
I'm curious, so is your article saying that a niacin flush causes inflammation, or reduces inflammation, or causes some of it temporarily (reducing it when flush is over), or....?
So if I have for example may have inflammation under the skin at a given moment, would taking niacin be helpful? harmful? Just a guess as a general ballpark here, not a specific, since I understand you don't have specifics in my case.
Thanks a ton for all your hard work here on the blog,
PJ
Dear Doc,
What are the effects of Niacin on Vitiligo? Does it cause / increase Vitiligo of helps to cure it?
Regards
Loyora
Dear Doc,
What are the effects of Niacin on Vitiligo? Does it cause / increase Vitiligo or does it help to cure it?
Regards
Loyora
Thanks so much for the detailed write-up doc, everywhere I look gives the same oversimplified symptomatic explanations with none of the bio-mechanisms.
I may be wrong but the way I understand is that Vitiligo is an autoimmune disorder, reversing it is more about avoiding inflammation from dietary intolerance like gluten, eggs, peanuts, etc. depending on your personal reactions. I think that the doctor's point in the article is that it would be interesting to study the effects of Niacin on vitiligo, suggesting at the time of the blog post he did not know.
Here are some other articles that mention reversing vitiligo and have several followers that have had success doing so. http://robbwolf.com/2012/08/21/oils-episode-146/ or https://chriskresser.com/the-gut-skin-connection-how-altered-gut-function-affects-the-skin/
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