Mast Cells Travel To The Brain

[BigYellowLemon]

Interesting thread, I have high histamine and have been curious for some time whether this is a good or bad thing.

On one hand I see all the potential inflammatory downsides.

But when I used cetirizine, racemic or levo, I experienced only negative effects. I don't want to make a broad conclusion about histamine in general based only on my experience with cetirizine.

Histamine seems to be one of the variables in intelligence. I really think it increases intelligence to an extent. The people I've met with allergies are often at the very least sharp.

Instead of an anti-histamine, I will try to remove the downstream problems it causes instead.

Somewhat related, anti-muscarinics show promise in increasing myelination. Old Drug May Wield New Power | Multiple Sclerosis Discovery Forum

The problem is that they destroy the ability to think.

 

[General Orange]

Asiaticoside Mitigates the Allergic Inflammation by Abrogating the Degranulation of Mast Cells
https://pubs.acs.org/doi/abs/10.1021/acs.jafc.7b01590?src=recsys&journalCode=jafcau

Centella asiatica

 

[Travis]

Interesting thread, I have high histamine and have been curious for some time whether this is a good or bad thing.

On one hand I see all the potential inflammatory downsides.

But when I used cetirizine, racemic or levo, I experienced only negative effects. I don't want to make a broad conclusion about histamine in general based only on my experience with cetirizine.

Histamine seems to be one of the variables in intelligence. I really think it increases intelligence to an extent. The people I've met with allergies are often at the very least sharp.

Instead of an anti-histamine, I will try to remove the downstream problems it causes instead.

Somewhat related, anti-muscarinics show promise in increasing myelination. Old Drug May Wield New Power | Multiple Sclerosis Discovery Forum

The problem is that they destroy the ability to think.

But does peripheral histamine enter the brain?

Mast cells could perhaps enter the brain in response to persorbed starch granules, shown by Volkheimer to end-up in nearly every organ after oral ingestion. (This is only a problem with dry starch particles, and starch heated in water becomes gelatinized. Although never tested, I think native starch—such that found in carrots—is probably fine.) Amyloid deposists in the brain were at one time thought to be starch, but later had officially become 'misfolded glycogen.'

Immune cells in the brain doesn't sound good, but this of course depends on the cell type. I admit that the brain mast cell would be the safer than the neutrophil or the eosinophil, but mast cells also synthesize and release prostaglandins and leukotrienes.

Mast cell migration could perhaps be reduced by avoiding dry starch particles and the ω−6 fatty acids. The enzyme 5-lipoxygenase transforms arachidonic acid into leukotriene B₄, the most powerful lipid chemoattractant known. Leukotriene B₄ had been discovered based on its ability to attract neutrophils, yet the direct analogues made from other membrane lipids are far less powerful in this regard.

Leukotriene B₅ is formed by 5-lipoxygenase acting on eicosapentaenoic acid, an membrane lipid derived from ω−3 α-linolenic acid. Leukotriene B₅ has been shown to recruit neutrophils at ¹⁄₅₀₀ the potency of leukotriene B₄, making this the least immunogenic leukotriene.

Leukotriene B₃ is formed from Mead acid and it (synthetic) is about four times less potent than leukotriene B₄. But as it turns out, this molecule (as commonly depicted and systematically-named) not even produced in the body. The structure of leukotriene B₃ had been predicted beforehand based on the assumed Mead acid leukotriene product—extrapolated known structures of leukotriene B₄ & B₅. However, experiments show that a related molecule—the all-cis isomer—is actually produced from Mead acid having ¹⁄₁₀ the chemotactic potency of leukotriene B₄.

Besides the leukotrienes, 13-hydroxylinolenic is also a powerful chemoattractant. This molecule is formed from 15-lipoxygenase and has about ²⁄₃ the potency of leukotriene B₄. This means that even simple oxides of linoleic acid, those which even be formed through cooking, are even more powerful immunologically than endogenous hormones produced for this express purpose—very embarrassing for Wesson and related vegetable oil companies. Molecules derived from Mead acid appear to be our natural leukocyte chemoattractants*, and the ω−3 fatty acids appear to be delegated exclusively for the role of biological membrane lipids.

What is interesting about histamine and histadine is that they quench singlet oxygen fluorescence at the 440·nm region, the same wavelength in which tryptophan fluoresces. This could have relevance for people who ascribe to Förster resonance energy transfer models of nerve conduction and consciousness.

[*] Leukotriene B₄ is the most powerful lipid chemoattractant (there are also peptide chemoattractants). ​

 

[artist]

Very interesting. Histamine intolerance and high histamine symptoms dominate my proverbial medical chart. My personality tends to be very very speedy, racing thoughts, talking and thinking a mile a minute (@BigYellowLemon mentioned intelligence, the speed of thought could be something there). At the same time my memory is very shoddy and alarms people at times when I forget recent things ever happened at all. I lack the capacity for contemplation, silence, stillness. I also struggle to learn from mistakes, always lose things, make the same errors over and over. My life started to derail when I hit puberty (estrogen's synergistic effects?). Milk and high unrefined starch diets give me symptoms that in the past I have compared to schizophrenia. The more I get of either, the more mentally ill I get, including paranoia, suicidal depression, obsessive compulsion (I was anorexic for a number of years and was especially fond of the rituals surrounding it). Fermented milk gives me much milder symptoms, perhaps the predigestion of casein is the reason. Still not good though. I'm also very sensitive to orange juice because it is such a massive histamine liberator. Histamine has trapped me diet wise - the only truly safe food I've found is meat - but this thread is encouraging. I have noticed that white rice really doesn't seem to give me issues. I may experiment with restricting dairy further (butter only? ghee only?) and truly limiting starch to white rice and see how it goes. I've also noticed mental benefits from niacinamide.

I wonder if the sodium acetate that is working so well for me is somehow acting on brain histamine. Much of what I describe above has been resolved in the past 2 weeks as a result of taking this. I need to update my thread on the subject to mention that I was on niacinamide early in the trial and since going off some of the benefits have subsided - they seem to synergize. (The glycogen depletion is rough though)

My dad has terrible allergies and a similar keyed up, manic personality to me - he wound up with full blown multiple sclerosis about 10 years back.

 

[General Orange]

IDO expression in the brain: a double-edged sword.
...In the brain, IDO can be induced in microglia by interferon-gamma-producing T helper (Th) 1 cells, thereby initiating a negative feedback loop which downmodulates neuroinflammation in experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). This protective effect could to be counteracted by the production of neurotoxic metabolites of the kynurenine pathway such as quinolinic acid, which are produced upon IDO induction. Some metabolites of the kynurenine pathway can pass the blood-brain barrier and thus could act as neurotoxins, e.g., during systemic infection.
In this paper, we give a brief overview on established immune regulatory functions of IDO, review recent data on IDO expression in the brain, and propose that autoimmune neuroinflammation and the increasingly appreciated neuronal damage in MS are linked by Th1-mediated IDO induction through subsequent synthesis of toxic metabolites of tryptophan.
IDO expression in the brain: a double-edged sword. - PubMed - NCBI
...
We found that chronic pain in rats induced depressive behavior and IDO1 upregulation in the bilateral hippocampus. Upregulation of IDO1 resulted in the increased kynurenine/tryptophan ratio and decreased serotonin/tryptophan ratio in the bilateral hippocampus. We observed elevated plasma IDO activity in patients with both pain and depression, as well as in rats with anhedonia induced by chronic social stress.
Brain indoleamine 2,3-dioxygenase contributes to the comorbidity of pain and depression
Brain indoleamine 2,3-dioxygenase contributes to the comorbidity of pain and depression

...Th2-type cell activation leads to IL-4, IL-5 and IL-13 cytokine expression. These cytokines lead to the accumulation of a high number of eosinophils and mast cells, thus boosting systemic inflammation, as these cells again start to produce large numbers of cytokines, chemotactic factors or free radicals, which ultimately leads to enhanced vascular permeability and persistent inflammation [48, 49]. Furthermore, these cytokines can interact with their receptors to stimulate allergen-specific IgE production. High levels of IgE circulate in the blood and bind to the high-affinity IgE receptors (FcεRI) of mast cells or basophiles to activate histamine release, which is the main inductor of an allergic disease [50].
...
Frequent treatment with aspirin, anti-inflammatory agents or antibiotics can inhibit Th1-type immune response and strengthen the development of Th2-type responses and cause allergic symptoms [58, 59]. Interestingly, exposure of PBMCs to aspirin or salicylic acid had a suppressive effect on neopterin production and tryptophan breakdown similar to that of Th2-type cytokines [58].

Tryptophan Metabolism in Allergic Disorders
Tryptophan Metabolism in Allergic Disorders

Asiaticoside Mitigates the Allergic Inflammation by Abrogating the Degranulation of Mast Cells
The effects of asiaticoside (AS) on allergic responses mediated by mast cells were investigated. ...
AS reduced the intracellular calcium in RPMCs and deprived the histamine release and degranulation. AS also decreased the generation of antigen-induced tumor necrosis factor α, interleukin (IL)-4, IL-8, and IL-1β in RBL-2H3 cells sensitized by IgE. The suppression of AS on pro-inflammatory cytokines was related with the activation of the intracellular FcεRI and the inhibition of the nuclear factor-κB signaling pathway. ...
In summary, we demonstrate that AS suppresses the allergic inflammation mediated by mast cells and this effect might be mediated by FcεRI-dependent signaling pathways.
https://pubs.acs.org/doi/abs/10.1021/acs.jafc.7b01590?src=recsys&journalCode=jafcau

 

[lvysaur]

Are you eating any immunogenic proteins, such as those found in wheat and oats? These can release interferon-γ and interferon-6 shown to induce phospholipase A₂ and cyclooxygenase‐2, respectively. These two enzymes, when working in tandem, powerfully increase all prostaglandins.

Are these unique to wheat and oats?

What about rice?

 

[Travis]

Are these unique to wheat and oats?

What about rice?

I think this is unique to wheat because only wheat has a δ-exorphin. Although opiates are generally seen through a paradigm of pain management, δ- and κ-opioid receptors are actually found on immune cells. Obviously these receptors don't do anything for 'pain' since they are not connected to nerves, so you have to assume that their natural ligands—i.e. dynorphin and the enkephalins—are involved in the immune response. This is in fact what has been observed by researchers, who often drag opiate peptides into their reaction schemes for describing how cytokines are released (cytokine release is often inhibited by naloxone). While it's highly plausible that our immune cells create & release opioid peptides to control pain, it also appears that they use them for signalling purposes. I think the most likely explanation for how immune cells release γ-interferon after wheat ingestion is through gluten exorphin B4 & B5 acting on their δ-opioid receptors as a enkephalin mimetic.

 

[Travis]

Very interesting. Histamine intolerance and high histamine symptoms dominate my proverbial medical chart. My personality tends to be very very speedy, racing thoughts, talking and thinking a mile a minute (@BigYellowLemon mentioned intelligence, the speed of thought could be something there). At the same time my memory is very shoddy and alarms people at times when I forget recent things ever happened at all. I lack the capacity for contemplation, silence, stillness. I also struggle to learn from mistakes, always lose things, make the same errors over and over. My life started to derail when I hit puberty (estrogen's synergistic effects?). Milk and high unrefined starch diets give me symptoms that in the past I have compared to schizophrenia. The more I get of either, the more mentally ill I get, including paranoia, suicidal depression, obsessive compulsion (I was anorexic for a number of years and was especially fond of the rituals surrounding it). Fermented milk gives me much milder symptoms, perhaps the predigestion of casein is the reason. Still not good though. I'm also very sensitive to orange juice because it is such a massive histamine liberator. Histamine has trapped me diet wise - the only truly safe food I've found is meat - but this thread is encouraging. I have noticed that white rice really doesn't seem to give me issues. I may experiment with restricting dairy further (butter only? ghee only?) and truly limiting starch to white rice and see how it goes. I've also noticed mental benefits from niacinamide.

I wonder if the sodium acetate that is working so well for me is somehow acting on brain histamine. Much of what I describe above has been resolved in the past 2 weeks as a result of taking this. I need to update my thread on the subject to mention that I was on niacinamide early in the trial and since going off some of the benefits have subsided - they seem to synergize. (The glycogen depletion is rough though)

My dad has terrible allergies and a similar keyed up, manic personality to me - he wound up with full blown multiple sclerosis about 10 years back.

Perhaps initially during the course of evolution histamine had been used to chelate zinc, then perhaps came its protective function against superoxide released from neutrophils—formed and released towards pathogens, among other products such as proteases. Later on: peripheral cells could have evolved histamine receptors that control more sophisticated functions such as capillary dilation, leuokocyte signalling, the 'histamine flush,' and the 'histamine itch.' Histamine also seems to signal goblet cells to produce mucus, upregulating epithelial defenses against pathogens while also flushing-away those already there. The brain seems to have evolved to view histamine as an signal of real or presumed pathogen attack, or as an alarm system for unfavourable immunological circumstances. The catecholamine system, on the other hand, seems to be more of a signal for physical attack. Perhaps coincidentally, and then perhaps not, epinephrine's oxidation product—adrenochrome—is also used to explain schizophrenia (Hoffer & Osmond, 1967).

Schizophrenia is a psychological disorder with no officially recognized biological cause. As such, this condition is diagnosed rather subjectively. In the absence of any formal chemical definition there is no reason to assume that one molecule is responsible for all diagnosed cases; there could be the relatively mild histamine subtype, and also the more severe adrenochrome subtype. Dementia is a perfect example of multiple etiologies: dementia can be formed by amyloid deposits (persorbed starch granules), sulfate depletion via acetominophen, aluminum, and low docosahexaenoic acid.

Although Hoffer & Osmond concentrated on adrenochrome as the cause for schizophrenia, they are more well known for the treatment they'd found most effective. Niacin is similar to histamine on a few levels: the two are molecularly similar and they both will cause a skin 'flush.' I don't think this is a coincidence and think that niacin could perhaps inhibit brain transport of histidine, the only precursor for histamine. Niacin also increases indoles by inhibiting tryptophan breakdown in the liver leading to higher brain melatonin & serotonin levels, two molecules known for having a calming or anti-psychotic effect.

 

[BigYellowLemon]

But does peripheral histamine enter the brain?

Mast cells could perhaps enter the brain in response to persorbed starch granules, shown by Volkheimer to end-up in nearly every organ after oral ingestion. (This is only a problem with dry starch particles, and starch heated in water becomes gelatinized. Although never tested, I think native starch—such that found in carrots—is probably fine.) Amyloid deposists in the brain were at one time thought to be starch, but later had officially become 'misfolded glycogen.'

Immune cells in the brain doesn't sound good, but this of course depends on the cell type. I admit that the brain mast cell would be the safer than the neutrophil or the eosinophil, but mast cells also synthesize and release prostaglandins and leukotrienes.

Mast cell migration could perhaps be reduced by avoiding dry starch particles and the ω−6 fatty acids. The enzyme 5-lipoxygenase transforms arachidonic acid into leukotriene B₄, the most powerful lipid chemoattractant known. Leukotriene B₄ had been discovered based on its ability to attract neutrophils, yet the direct analogues made from other membrane lipids are far less powerful in this regard.

Leukotriene B₅ is formed by 5-lipoxygenase acting on eicosapentaenoic acid, an membrane lipid derived from ω−3 α-linolenic acid. Leukotriene B₅ has been shown to recruit neutrophils at ¹⁄₅₀₀ the potency of leukotriene B₄, making this the least immunogenic leukotriene.

Leukotriene B₃ is formed from Mead acid and it (synthetic) is about four times less potent than leukotriene B₄. But as it turns out, this molecule (as commonly depicted and systematically-named) not even produced in the body. The structure of leukotriene B₃ had been predicted beforehand based on the assumed Mead acid leukotriene product—extrapolated known structures of leukotriene B₄ & B₅. However, experiments show that a related molecule—the all-cis isomer—is actually produced from Mead acid having ¹⁄₁₀ the chemotactic potency of leukotriene B₄.

Besides the leukotrienes, 13-hydroxylinolenic is also a powerful chemoattractant. This molecule is formed from 15-lipoxygenase and has about ²⁄₃ the potency of leukotriene B₄. This means that even simple oxides of linoleic acid, those which even be formed through cooking, are even more powerful immunologically than endogenous hormones produced for this express purpose—very embarrassing for Wesson and related vegetable oil companies. Molecules derived from Mead acid appear to be our natural leukocyte chemoattractants*, and the ω−3 fatty acids appear to be delegated exclusively for the role of biological membrane lipids.

What is interesting about histamine and histadine is that they quench singlet oxygen fluorescence at the 440·nm region, the same wavelength in which tryptophan fluoresces. This could have relevance for people who ascribe to Förster resonance energy transfer models of nerve conduction and consciousness.

[*] Leukotriene B₄ is the most powerful lipid chemoattractant (there are also peptide chemoattractants). ​

I had a thought while reading what you said about starch granules ending up in the brain: why is cellulose not as or more toxic?

From what I understand, the reason ungelatinized starch is so toxic is because the bonds between the glucose units isn't hydrated, there is no or little H2O present, and thus the enzymes cannot reach these bonds and clip them.

So shouldn't cellulose be the same? The reason cellulose cannot be broken down by any animal at all is because the bond, due to the angle and resulting spatial conformation, is unhydrated. Cellulose is dry and hydrophobic and the bond cannot be broken because no water, and thus no enzymes (of animal origin) can reach it.

So shouldn't that make cellulose even more toxic then ungelatinized starch? Ungelatinized starch will eventually hydrate, though I'm not sure if that'd change anything if it's already in the brain (would the cells there be able to sense the starch and produce amylase and break it down?). But cellulose would be stuck in these areas until it was physically pushed out, never able to be broken down. Really it seems every glucose polymer should be capable of being absorbed hole and transported to areas where it shouldn't be, where it then causes damage. Damage like hairloss (where the particle would block the capillaries and shutdown or outright kill follicles). Glucose polymers being absorbed like this may be a significant cause of hairloss.

But perhaps only ungelatinized starch is capable of this, because it's stored in amyloplasts as granules, while the other glucose polymers make up cell walls. But it really does seem to me that glucose polymers smaller than starch granules could easily enter the blood and get stuck in areas they shouldn't be.

The "misfolded glycogen" could imo be any of these glucose polymers. The scientists studying this course could never admit starchs and vegetables result in toxic foreign matter entering the body and causing disease.

Why do you think native starch, like say in carrots or other low starch vegetables, is safe? Eating starchs like cereal grains or potatoes raw is sure as hell not safe at all. And I doubt carrots store the starch in a different way then potatoes.

It could be that the reason raw carrots seem to cause little problems when compared to raw potatoes is because they contain so little starch that it's not a problem, or that when eaten raw the structure is so strong that only the starch on the surface oftbe pieces are even felt by the body while the rest on the inside is unavailable. Carrots are definitely fermented in the gut though.

The main issue I'm seeing with omega-3's is the fragility of them. They would definitely have a strong anti-inflammatory effect for the average person. But DHA membrane levels is definitely the main factor in aging for the majority of animals studied, we don't know for sure in humans but it likely is a factor for us as well. Aspirin and other COX inhibitors are likely good, same with leukotriene inhibitors like those in boswellia (which in my experience feels good, and has steroidal chems that look cool).

Personally I think I've found the key that solves the PUFA free problem. Obviouslyif you want to eat a diet of real food that is nutritious, PUFAs are gonna be present. So what I'm gonna do is take high levels of orlistat, which is OTC in the US, to inhibit ALL of my lipase enzymes. At the same time I will eat a diet with no oils/fats (besides MCT oil which of course doesn't require lipase to be absorbed), and also eat a diet with low fat levels. So the side effect of orlistat fat in stool will be eliminated. For fat soluble vitamins I will use them topically as well as use bile salts like TUDCA. I've also been thinking of buying either pure oleic acid, or fractionating high oleic sunflower oil, and then using lipase on them to make the oleic acid free, and then consuming like 10g with meals + tocopherols/MK-4/retinol. If you know how chylomicrons, you'll understand this possibly solves the fat soluble vitamin problem (only other issue would fat soluble vitamins getting caught in un-lipased triglycerides that were already present in food).

So yeah, just solved the PUFA problem. I'll then test my blood after 6 months of this to see mead acid levels, possibly getting a biopsy and seeing what my tissue fat composition is.

I think this is the way. The ultimate solution.

Can you explain how the resonance theory works mechanically? That would be appreciated.

 

[TreasureVibe]

Famotidine was shown in multiple studies to mess with the electricity of the heart:

Complete Atrioventricular Block and Cardiac Arrest following Intravenous Famotidine Administration | Anesthesiology | ASA Publications

Ranitidine also messes with the electricity of the heart:

H2-blocker modulates heart rate variability. - PubMed - NCBI

What would be a safe anti-histamine?

 

[tara]

So shouldn't cellulose be the same? The reason cellulose cannot be broken down by any animal at all is because the bond, due to the angle and resulting spatial conformation, is unhydrated. Cellulose is dry and hydrophobic and the bond cannot be broken because no water, and thus no enzymes (of animal origin) can reach it.

So shouldn't that make cellulose even more toxic then ungelatinized starch? Ungelatinized starch will eventually hydrate, ...

I wouldn't be quick to eat powdered cellulose, either. Microcrystaline cellulose as an excipient in tablets etc looks like a bad idea to me.

I think starch granules have to be wet at higher temperatures than they find in the body to gelatinise.

 

[Waynish]

So what I'm gonna do is take high levels of orlistat, which is OTC in the US, to inhibit ALL of my lipase enzymes. At the same time I will eat a diet with no oils/fats (besides MCT oil which of course doesn't require lipase to be absorbed), and also eat a diet with low fat levels. So the side effect of orlistat fat in stool will be eliminated. For fat soluble vitamins I will use them topically as well as use bile salts like TUDCA. I've also been thinking of buying either pure oleic acid, or fractionating high oleic sunflower oil, and then using lipase on them to make the oleic acid free, and then consuming like 10g with meals + tocopherols/MK-4/retinol. If you know how chylomicrons, you'll understand this possibly solves the fat soluble vitamin problem (only other issue would fat soluble vitamins getting caught in un-lipased triglycerides that were already present in food).

So yeah, just solved the PUFA problem. I'll then test my blood after 6 months of this to see mead acid levels, possibly getting a biopsy and seeing what my tissue fat composition is.

I think this is the way. The ultimate solution.

Can you explain how the resonance theory works mechanically? That would be appreciated.

How did your experiment go? :)

 

[BigYellowLemon]

How did your experiment go? :)

No money nor means to do such a thing until this exact day actually, so I now will be doing it. Will be experimenting, I will be buying some Alli (orlistat) the next time I go to a chain store with a pharmacy, probably this weekend if I have time.

Only concern I have is that orlistat might inhibit lipase functions beyond the hydrolysis of a triglyceride. What if it blocks the hydrolysis of phospholipids (it does)? It could do all sorts of things beyond the main mechanism.

Orlistat might be a very dirty drug.

Idk if I've mentioned this, but to get pass the fact that orlistat will block the absorption of chylomicron dependent vitamins (A, E, K2, and other fat solubles), raw fatty acids could be eaten, which are guaranteed absorption. They could easily be made at home, take fully hydrogenated & bleached coconut oil and mixed with lye. This is the basics of soap making, and chemically hydrolyses the triglyceride into fatty acid salts and glycerin. Then add appropriate amount of acid to neutralize the basic lye, extract fatty acids or drink whole.

Fatty acids 14-18 carbons long are best for chylomicron production, fully hydrogenated coconut oil would be 10% palmitic (16c), 12% stearic (18c), as well as 16% myristic (14c), which is more than enough for production of chylomicrons and absorption of fat soluble vitamins. You could take 10g worth and get zero PUFA, along with fully saturated long chain fats plus some MCTs.

 

[Evandrojr]

I think some of the risks around cimetidine related to it's ability to increase prolactin

• Rojdmark, S. (1983). Prolactin release in man: influence of cimetidine, thyrotrophin-releasing hormone and acute hypercalcaemia. Acta Endocrinol (Copenh), 102(4), 481-485.

Also interesting to note that cimetidine inhibits diamine oxidase (DAO, aka. histaminase) which is partly responsible for the metabolism and inactivation of histamine

• Finazzi-Agro, A., Floris, G., Fadda, M. B., & Crifo, C. (1979). Inhibition of diamine oxidase by antihistaminic agents and related drugs. Agents Actions, 9(3), 244-247.
• Wantke, F., Hemmer, W., Focke, M., Stackl, W., Gotz, M., & Jarisch, R. (2001). Are adverse effects of sildenafil also caused by inhibition of diamine oxidase? Urol Int, 67(1), 59-61. doi:10.1159/000050946

“Histamine intolerance results from a disequilibrium of accumulated histamine and the capacity for histamine degradation.”

“The main enzyme for metabolism of ingested histamine is diamine oxidase (DAO).”​

View attachment 7715

And decreased DAO and subsequently increased histamine being related to a number of intestinal issues

“An impaired histamine degradation based on a reduced DAO activity and the resulting excess of histamine may cause numerous symptoms mimicking an allergic reaction. “

“Ingestion of histamine-rich food, alcohol, or drugs that release histamine or block DAO may provoke diarrhea, headache, congestion of the nose, asthmatoid wheezing, hypotension, arrhythmia, urticaria, pruritus, flushing, and other conditions in these patients.”​

• Enko, D., Kriegshauser, G., Halwachs-Baumann, G., Mangge, H., & Schnedl, W. J. (2017). Serum diamine oxidase activity is associated with lactose malabsorption phenotypic variation. Clin Biochem, 50(1-2), 50-53. doi:10.1016/j.clinbiochem.2016.08.019
• Enko, D., Meinitzer, A., Mangge, H., Kriegshauser, G., Halwachs-Baumann, G., Reininghaus, E. Z., . . . Schnedl, W. J. (2016). Concomitant Prevalence of Low Serum Diamine Oxidase Activity and Carbohydrate Malabsorption. Can J Gastroenterol Hepatol, 2016, 4893501. doi:10.1155/2016/4893501
• Hoffmann, K. M., Gruber, E., Deutschmann, A., Jahnel, J., & Hauer, A. C. (2013). Histamine intolerance in children with chronic abdominal pain. Arch Dis Child, 98(10), 832-833. doi:10.1136/archdischild-2013-305024
• Jarisch, R., & Wantke, F. (1996). Wine and headache. Int Arch Allergy Immunol, 110(1), 7-12.
• Ji, Y., Sakata, Y., & Tso, P. (2011). Nutrient-induced inflammation in the intestine. Curr Opin Clin Nutr Metab Care, 14(4), 315-321. doi:10.1097/MCO.0b013e3283476e74
• Kovacova-Hanuskova, E., Buday, T., Gavliakova, S., & Plevkova, J. (2015). Histamine, histamine intoxication and intolerance. Allergol Immunopathol (Madr), 43(5), 498-506. doi:10.1016/j.aller.2015.05.001
• Maintz, L., & Novak, N. (2007). Histamine and histamine intolerance. Am J Clin Nutr, 85(5), 1185-1196.
• Manzotti, G., Breda, D., Di Gioacchino, M., & Burastero, S. E. (2016). Serum diamine oxidase activity in patients with histamine intolerance. Int J Immunopathol Pharmacol, 29(1), 105-111. doi:10.1177/0394632015617170
• Music, E., Korosec, P., Silar, M., Adamic, K., Kosnik, M., & Rijavec, M. (2013). Serum diamine oxidase activity as a diagnostic test for histamine intolerance. Wien Klin Wochenschr, 125(9-10), 239-243. doi:10.1007/s00508-013-0354-y
• Reilly, M. A., & Schayer, R. W. (1970). In vivo studies on histamine catabolism and its inhibition. Br J Pharmacol, 38(3), 478-489.
• Rosell-Camps, A., Zibetti, S., Perez-Esteban, G., Vila-Vidal, M., Ferres-Ramis, L., & Garcia-Teresa-Garcia, E. (2013). Histamine intolerance as a cause of chronic digestive complaints in pediatric patients. Rev Esp Enferm Dig, 105(4), 201-206.

Some other points of interest:

• Serotonin inhibits DAO and thus may increase histamine levels
• Histamine increases the synthesis of estrogen (participating in a loop where estrogen increases the synthesis of serotonin).
• Estrogen can also augment the action of histamine, possibly through serotonin as mentioned above and also potentially through the augmentation of nitric oxide signalling
• Long chain fats, such as polyunsaturated fats, activate mast cells and increase the secretion of histamine (and likely serotonin as well)
• Part of this effect may be due to the role fats have on increasing the absorption of endotoxin
• Endotoxin activates the enzyme histamine decarboxylase, which increases the formation of histamine
• The formation and degranulation of mast cells is increased in hypoxia, and hypoxia in intestinal cells may be brought about partially by effects of endotoxin and serotonin on energy metabolism

“A further matter of interest is the competitive inhibition of diamine oxidase by serotonine and tryptamine, typical substrates of mitochondrial monoamine oxidase. “

“Various drugs were tested as inhibitors of diamine oxidase on the basis of chemical relationships to the enzyme substrates. It was found that serotonine tryptamine and phenformin are good competitive inhibitors while cimetidine and pheniprazine are non-competitive inhibitors. “

“Histamine has been shown to stimulate, in a dose- dependent manner, the synthesis of estradiol via H1R “

“Thus, histamine may augment dysmenorrhea by increasing estrogen concentrations. And, in reverse, estrogen can influence histamine action. A significant increase in weal and flare size in response to histamine has been observed to correspond to ovulation and peak estrogen concentrations. In pregnancy, DAO is produced at very high concentrations by the placenta, and its concentration may become 500 times that when the woman is not pregnant. This increased DAO production in pregnant women may be the reason why, in women with food intolerance, remissions frequently occur during pregnancy”

“The gut microbiota affects intestinal permeability and mucosal mast cell (MMCs) responses. Activation of MMCs has been associated with absorption of dietary fat.”

“The intestinal microbiota appears to activate MMCs following the ingestion of fat in rats—this contributes to fat-induced intestinal permeability.”

“There is increasing evidence linking gut local inflammatory events with the intake of nutrients. Our recent studies, using the conscious lymph fistula rat model, demonstrate that fat absorption activates the intestinal mucosal mast cells. This is accompanied by a dramatic increase in the lymphatic release of mast cell mediators including histamine, rat mucosal mast cell protease II (RMCPII), as well as the lipid mediator prostaglandin D2 (PGD2).”

“Studies in our laboratory have shown that DAO secretion into intestinal lymph significantly increases during active fat absorption. Lymphatic histamine and DAO both peak at the same time during fat absorption, suggesting a close relationship between the two. It is tempting to speculate that DAO is released during fat absorption to safeguard against the deleterious effect of the excessive histamine secretion during fat absorption. The increased release of histamine and DAO is specific to fat feeding and is not shared by carbohydrate or protein feeding.“

“Pretreatment of mice with endotoxin or with Freund's adjuvant, irritants known to cause activation of histidine decarboxylase, failed to affect histamine catabolism”

“Tissue hypoxia occurs when local oxygen demand exceeds oxygen supply. In chronic inflammatory conditions such as IBD, the increased oxygen demand by resident and gut-infiltrating immune cells coupled with vascular dysfunction brings about a marked reduction in mucosal oxygen concentrations.”

“During active inflammation, resident macrophages and dendritic cells (DCs) become activated and produce proinflammatory cytokines and chemokines that trigger Tcell differentiation and the recruitment of inflammatory cells from the peripheral blood into the mucosa. The infiltrated immune cells consume a large amount of the local oxygen in the mucosa and submucosa. At the same time, the oxygen supply from the bloodstream is decreased during inflammation as a result of microvascular occlusion and thrombosis. The resulting imbalance between oxygen consumption and supply renders the inflamed intestinal mucosa severely hypoxic.”​

DAO requires several nutritional cofactors such as Vitamin B6, Vitamin C, and copper

“Diamine oxidase (E.C. 1.4.3.6) is a copper enzyme “

“In addition, histamine degradation can be supported by the administration of vitamin C and vitamin B-6, which leads to an increase in DAO activity.”​

Dear @Koveras and @Travis , in your opinion, what would a diet that aims to reduce histamine production look like (aside from avoiding high histamine foods of course)? Or perhaps a more appropriate question, what do you dieta looks like? Btw, thanks for all the amazing information in this thread!

 

[Logan-]

I wouldn't be quick to eat powdered cellulose, either. Microcrystaline cellulose as an excipient in tablets etc looks like a bad idea to me.

I think starch granules have to be wet at higher temperatures than they find in the body to gelatinise.

Does modified cellulose used for making vegetable capsules have the same issue?

I have this product in mind: https://www.amazon.com/Doctors-Best-Vitamin-Quali-C-Scotland/dp/B005CD3J4O

 

[energyandstruct]

In human studies it raises prolactin and also causes pneumonia in hospital patients for some reason.

is this true of all h2 blockers? would you say the safest drugs for mcas problems = ketotifen, cromolyn, cypro? does cypro have less anticholinergic activity than other old generation antihistamines, and thus maybe safer long term?

 

[haidut]

is this true of all h2 blockers? would you say the safest drugs for mcas problems = ketotifen, cromolyn, cypro? does cypro have less anticholinergic activity than other old generation antihistamines, and thus maybe safer long term?

I think all of them have similar problems except famotidine.

 

[Logan-]

I think all of them have similar problems except famotidine.

Haidut, you mean cypro increases prolactin in doses effective against mcas; but not in smaller doses (0.5 mg - 1.5 mg)?

 

[haidut]

Haidut, you mean cypro increases prolactin in doses effective against mcas; but not in smaller doses (0.5 mg - 1.5 mg)?

No, my answer was about other H2 antagonists of which famotidine is one. Cypro is H1 antagonist.