8 replies to this topic

[lucid]

From Wiki

Histamine exerts its actions by combining with specific cellular receptors located on cells. The four histamine receptors that have been discovered are designated H1 through H4.

    * H1 histamine receptor - found on smooth muscle, endothelium, and central nervous system tissue; causes vasodilation, bronchoconstriction, smooth muscle activation, separation of endothelial cells (responsible for hives), and pain and itching due to insect stings; the primary receptors involved in allergic rhinitis symptoms and motion sickness.
    * H2 histamine receptor - located on parietal cells, which primarily regulate gastric acid secretion
    * H3 histamine receptor - decreased neurotransmitter release: histamine, acetylcholine, norepinephrine, serotonin
    * H4 histamine receptor - unknown physiological role. Found primarily in the thymus, small intestine, spleen, and colon. It is also found on basophils and in the bone marrow.

Histamine is released as a neurotransmitter. The cell bodies of neurons which release histamine are found in the posterior hypothalamus, in various tuberomammillary nuclei. From here, these histaminergic neurons project throughout the brain, to the cortex through the medial forebrain bundle. Histaminergic action is known to modulate sleep. Classically, antihistamines (H1 histamine receptor antagonists) produce sleep. Likewise, destruction of histamine releasing neurons, or inhibition of histamine synthesis leads to an inability to maintain vigilance. Finally, H3 receptor antagonists (which stimulate histamine release) increase wakefulness.

It has been shown that histaminergic cells have the most wakefulness-related firing pattern of any neuronal type thus far recorded. They fire rapidly during waking, fire more slowly during periods of relaxation/tiredness and completely stop firing during REM and non-REM sleep. Histaminergic cells can be recorded firing just before an animal shows signs of waking.

I have been taking niacin (not niacinamide) and I get a reasonably strong 15 minute histamine flush. I am taking it to help with my poor cholesterol levels. I was wondering what the effects of histamine flushes would be on my health so I did a little reading and found some interesting material in wiki (above). Anyone else have any other info?

[lucid]

Another wiki excerpt from senesence:

In higher organisms, aging is likely to be regulated in part through the insulin/IGF-1 pathway. Mutations that affect insulin-like signaling in worms, flies and mice are associated with extended lifespan. In yeast, Sir2 activity is regulated by the nicotinamidase PNC1. PNC1 is transcriptionally upregulated under stressful conditions such as caloric restriction, heat shock, and osmotic shock. By converting nicotinamide to niacin, it removes nicotinamide, which inhibits the activity of Sir2. A nicotinamidase found in humans, known as PBEF, may serve a similar function, and a secreted form of PBEF known as visfatin may help to regulate serum insulin levels. It is not known, however, whether these mechanisms also exist in humans since there are obvious differences in biology between humans and model organisms.

Nice. I am still unclear how taking niacin has the desired effect of reducing levels of niacinamide. This text above suggests that PNC1 or PBEF in humans may instead may critical to nicotinamide regulation. If nicotinamide gets converted to niacin, I don't see how supplementing niacin down regulates nicotinamide.

there is a patent on nocturnal niacin slo-niacin as more effective at reducing naughty cholesterol as naughty type cholesterol is a nocturally produced chemical

Taking niacin @ bedtime may hinder one's ability to sleep. I have been taking it before bed recently and I think that it has been keeping me up. I will test this theory over the next week.

[shamus]

Don't ANTI-histamines make you drowsy?



something to think about

[lucid]

I take niacin since I have low histamine levels. I disagree with niacin interfering with sleep. I have read that niacin (and the flush) can induce sleep. I take a dose before bed and it does not interfere with my sleep. Now, I have low histamine levels, so I know I need it. I think it may be possible that high histamine types may have a problem with it at bedtime.

I don't dispute the validitiy of that info from wikipedia, but I also know that they are asking for more info on that article on histamine. I don't consider wikipedia a good source for complementary medicine. The articles I have read have been biased, with only studies that are against a particular alternative medicine topic.
The flush is just your basophil and mast cells filling up with histamine. The dose it takes you to flush can help you determine your histamine levels. Low histamine types can take as much 250 mg. to get a flush on an empty stomach. High histamine types will get a flush from about 50 mg. But normal levels should flush at 100 mg.

Since my histamine levels have been balanced I don't like having the flush. I did a flush every single morning for almost two years and it never really phased me. Now, I don't enjoy the flush when I take too much niacin, histidine, beta alanine, or some other stuff.

Niacin does not in fact induce a histamine release (which would make one wakeful): it induces a prostaglandin release (which does indeed slightly make one drowsy). Niacin flush being a result of histamine release is misinformation that has been floating around the internet for a while (So I was misinformed when i made this thread).

Some abstracts:
Prostaglandin D2, a cerebral sleep-inducing substance in monkeys

ABSTRACT The sleep-inducing effect of prostaglandin D2 (PGD2) was studied in five conscious male rhesus monkeys (Macaca mulatta) maintained in a 12-hr light/dark cycle. PGD2 was infused into the lateral or the third ventricle of the cerebrum slowly and continuously for 6 hr in the light period. Infusion of PGD2 into the lateral ventricle at 15-2250 pmol/min induced natural sleep as identified by electroencephalogram, electromyogram, electrooculogram, body temperature, heart rate, and animal behavior. Although sensitivity to PGD2 was slightly different among individual animals, the amount of total sleep time increased maximally up to 3- to 4-fold over the control level. PGD2 infused into the third ventricle induced effects similar to those observed for the lateral ventricular route, but infusion into the third ventricle was about 1000 times more effective than infusion into the lateral ventricle. In three monkeys, PGD2 increased the amount of sleep in a dose-dependent manner. Bell-shaped dose-esponse curves were observed for the other two monkeys. Infusion of prostaglandin E2 or F2,, into the lateral ventricle caused sedation but slightly reduced the amount of slow-wave sleep and produced increases in heart rate and body temperature. These findings suggest that endogenous PGD2 may be involved in the regulation of sleep by acting on the brainstructures surrounding the third ventricle in the rhesus monkey.

http://www.pnas.org/.../85/11/4082.pdf


Release of markedly increased quantities of prostaglandin D2 in vivo in humans following the administration of nicotinic acid.

Author
Morrow JD; Parsons WG 3d; Roberts LJ 2d
Source
Prostaglandins, 1989 Aug, 38:2, 263-74
Nicotinic acid (niacin) is a B vitamin which is also a potent hypolipidemic agent. However, intense flushing occurs following ingestion of pharmacologic doses of niacin which greatly limits its usefulness in treating hyperlipidemias. Previous studies have demonstrated that niacin-induced flushing can be substantially attenuated by pre-treatment with cyclooxygenase inhibitors, suggesting that the vasodilation is mediated by a prostaglandin. However, the prostaglandin that presumably mediates the flush has not been conclusively determined. In this study we report the finding that ingestion of niacin evokes the release of markedly increased quantities of PGD2 in vivo in humans. PGD2 release was assessed by quantification of the PGD2 metabolite, 9 alpha, 11 beta-PGF2, in plasma by gas chromatography mass spectrometry. Following ingestion of 500 mg of niacin in three normal volunteers, intense flushing occurred and plasma levels of 9 alpha, 11 beta-PGF2 were found to increase dramatically by 800, 430, and 535-fold. Levels of 9 alpha, 11 beta-PGF2 reached a maximum between 12 and 45 min. after ingesting niacin and subsequently declined to near normal levels by 2-4 hours. Levels of 9 alpha, 11 beta-PGF2 in plasma correlated with the intensity and duration of flushing that occurred in the 3 volunteers. Release of PGD2 was not accompanied by a release of histamine which was assessed by quantification of plasma levels of the histamine metabolite, N tau-methylhistamine. This suggests that the origin of the PGD2 release is not the mast cell. Only a modest increase (approximately 2-fold) in the urinary excretion of the prostacyclin metabolite, 2,3-dinor-6-keto-PGF1 alpha, occurred following ingestion of niacin and no increase in the excretion of the major urinary metabolite of PGE2 was found. These results indicate that the major vasodilatory PG released following ingestion of niacin is PGD2. The fact that markedly increased quantities of PGD2 are released suggests that PGD2 is the mediator of niacin-induced vasodilation in humans.

I don't think I have read any studies directly correlating taking niacin to sleep induction, but some people here have given personal accounts of sleeping more.

Edited by lucid, 25 March 2008 - 03:10 PM.

[tarbtl]

Don't ANTI-histamines make you drowsy?



something to think about

Not all of them.

Zantec (Reactine here in Canada) is one of many excellent non-drowsy antihistamines available. Sorry - too lazy to google the active ingredient.

[chicha]

In light of this (new) information regarding PGD2 as the limiting factor in the flush response, how would one go about increasing the occurrence of this flush? I prefer the sensation associated with the flush, but am not always able to achieve it no matter how much niacin is taken.

I was just about to do a search for the foods with the highest amounts of histidine, thinking that those foods used in conjunction with B3 would promote the effect.

How does one increase PGD2, and would increasing its levels in the body facilitate the flush response when used with niacin?

[chicha]

In light of this (new) information regarding PGD2 as the limiting factor in the flush response, how would one go about increasing the occurrence of this flush? I prefer the sensation associated with the flush, but am not always able to achieve it no matter how much niacin is taken.

I was just about to do a search for the foods with the highest amounts of histidine, thinking that those foods used in conjunction with B3 would promote the effect.

How does one increase PGD2, and would increasing its levels in the body facilitate the flush response when used with niacin?

I found this information:
"Patients failing to flush with niacin showed significantly reduced levels of arachidonic and docosahexaenoic acids." So, maybe supplementation with the essential(?) fatty acids mentioned would be one approach.
http://www.heart-dis...a/studies/5.htm

[timhill88@outlook.com]

Does Niacinamide increase Histamine??