PUFA Triggers Histamine Release

[haidut]

It seems that PUFA is also behind abnormal histamine release. This was observed during the course of "normal" PUFA metabolism, the kind that Mary Enig claimed is different (and harmless) from the rancidity suggested by Peat. So, nothing "harmless" about it after all.

http://www.ncbi.nlm.nih.gov/pubmed/1690007

"...The release of mast cell histamine by activated PUFA has a long time-course and the electron microscopical features are consistent with an exocytotic secretion in the case of arachidonic acid and cell lysis in the case of linoleic acid. The phenomenon is associated with a significant increase in malonyldialdehyde (MDA) and conjugated diene generation, suggesting a relationship between histamine release and membrane lipid peroxidation. The secretion of histamine was inhibited by anti-free radical interventions such as D-mannitol, reduced glutathione and alpha-tocopherol. Some cyclooxygenase and lipoxygenase inhibitors, cimetidine and carnitine derivatives, are differentially active in the inhibition of mast cell histamine release by activated arachidonic acid. These results suggest that free radical derivatives of PUFA, generated by metabolic activation, trigger mast cell histamine release."

 

[PakPik]

Thanks, Haidut. This effect of PUFAs on mast cells reminds me of what I found I few months ago; it seems certain PUFAs peroxides in the membrane (called PAF-like species) stimulate the Platelet-Activating Factor Receptor (PAF-R) in Mast Cells, and this stimulation in turn releases histamine. This process finally leads to tremendous systemic immunossuppression Mast Cell-derived Histamine Is Necessary For Platelet-activating Factor Mediated Systemic Immunosupp

 

[Arugula]

Thanks for posting this info, @haidut.

I have mast cell activation syndrome, among many other health problems, which developed after long-term VLC/ketosis. At one point the reactions to foods became so extreme that I could no longer eat anything without throat swelling, itching, hypotension and other allergic symptoms. After a few months of forced near-starvation, I decided to go on a high carb low fat (HCLF) near zero PUFA diet. A vast array of problems began to clear up almost immediately. It has been a very slow, gradual process and I'm nowhere near cured, but I'm noticing continued improvements, with more and more foods becoming tolerable as months go by. I can eat a ton of different foods from the plant kingdom without reaction now, as long as I stay HCLF and abstain from animal products, vegetable oils, nuts, seeds etc. I do appreciate that this is an unpopular view around here but saturated fat causes me as much difficulty as PUFA.

 

[haidut]

Thanks, Haidut. This effect of PUFAs on mast cells reminds me of what I found I few months ago; it seems certain PUFAs peroxides in the membrane (called PAF-like species) stimulate the Platelet-Activating Factor Receptor (PAF-R) in Mast Cells, and this stimulation in turn releases histamine. This process finally leads to tremendous systemic immunossuppression Mast Cell-derived Histamine Is Necessary For Platelet-activating Factor Mediated Systemic Immunosupp

Thanks for that link!
When I said on Danny's show that PUFA is a known and commercially / medically used immunosuppressor, I got so many angry calls and emails from doctors that I stopped counting. Now I am just going to point them to your study. I think getting a "career" in any discipline nowadays is very traumatic. You get trained to fight every bit of information that may threaten that career in any way. Oh well.

 

[Blossom]

I got so many angry calls and emails from doctors that I stopped counting.

Wow, I figured you'd have to be pretty open minded to begin with be listening to Danny's show! It makes me wonder if we are going to make the Quackwatch list soon.

 

[thebigpeatowski]

These results suggest that free radical derivatives of PUFA, generated by metabolic activation, trigger mast cell histamine release."

Could burning through body fat stores through increased metabolism trigger this?

This process finally leads to tremendous systemic immunossuppression Mast Cell-derived Histamine Is Necessary For Platelet-activating Factor Mediated Systemic Immunosupp

I've had 4 or 5 outbreaks of cold sores on my mouth over the last 6 months, after going for nearly two years with practically NONE.

Pushing on my metabolism seems to trigger the whole brain meltdown/cold sore outbreak in a BIG way.

I'm wondering if loading up on anti-oxidants to quell the free radicals would help my brain and keep my immune system strong enough to hold the cold sore virus suppressed......just guessing out loud here, any thoughts???

 

[Koveras]

Could burning through body fat stores through increased metabolism trigger this?



I've had 4 or 5 outbreaks of cold sores on my mouth over the last 6 months, after going for nearly two years with practically NONE.

Pushing on my metabolism seems to trigger the whole brain meltdown/cold sore outbreak in a BIG way.

I'm wondering if loading up on anti-oxidants to quell the free radicals would help my brain and keep my immune system strong enough to hold the cold sore virus suppressed......just guessing out loud here, any thoughts???

Maybe some supplemental Lysine to lower inflammatory NO?

 

[thebigpeatowski]

I have Lysine powder and have used it in the past. I guess I should be taking it daily, preemptively....Thanks Koveras.

 

[PakPik]

I've had 4 or 5 outbreaks of cold sores on my mouth over the last 6 months, after going for nearly two years with practically NONE.

Pushing on my metabolism seems to trigger the whole brain meltdown/cold sore outbreak in a BIG way.

I'm wondering if loading up on anti-oxidants to quell the free radicals would help my brain and keep my immune system strong enough to hold the cold sore virus suppressed......just guessing out loud here, any thoughts???

Hi @thebigpeatowski
If you're heavily burning through your fat stores and if they contain lots of PUFAs, it is very plausible you're producing tons of immunosuppressive peroxides. Antagonizing histamine might help that effect. Also, lots of Reactive oxygen species come from the normal metabolism (beta oxidation) of these fats, which by itself may increase oxidative stress significantly and therefore result in immunosuppression.

Finally, acetylcholine seems to be immunosuppressive to the brain as well -not sure if you're taking AChe inhibiors-. If so, that may have to do with your brain issues (good brain function requires a well regulated brain immune system, i.e not too much inflammation, not too much immunosuppression, but a happy medium)
"the inhibition of acetyl-cholinesterase (AChE) activity in the CNS resulted in the suppression of the immune response. It seems that ACh in the brain plays an immunoinhibitory role... It is suggested that a functional connection is present in the ACh of the brain and the immune system." Immunoregulatory role of neurotransmitters. - PubMed - NCBI

 

[thebigpeatowski]

Finally, acetylcholine seems to be immunosuppressive to the brain as well -not sure if you're taking AChe inhibiors-. If so, that may have to do with your brain issues (good brain function requires a well regulated brain immune system, i.e not too much inflammation, not too much immunosuppression, but a happy medium)
"the inhibition of acetyl-cholinesterase (AChE) activity in the CNS resulted in the suppression of the immune response. It seems that ACh in the brain plays an immunoinhibitory role... It is suggested that a functional connection is present in the ACh of the brain and the immune system." Immunoregulatory role of neurotransmitters. - PubMed - NCBI

Thanks for your insightful reply....I quit all dairy for a couple weeks, that seemed to help. I've recently added back goat milk and goat cheese, so far so good...

I don't take anything with anticholinestrase activity very often....often less than once per month and only when I'm having such an attack as described above as it makes me feel better very quickly. I do crave eggs almost daily....not sure what all of this means just yet.

I think I need more anti-oxidants.

 

[PakPik]

Thanks for your insightful reply....I quit all dairy for a couple weeks, that seemed to help. I've recently added back goat milk and goat cheese, so far so good...

I don't take anything with anticholinestrase activity very often....often less than once per month and only when I'm having such an attack as described above as it makes me feel better very quickly. I do crave eggs almost daily....not sure what all of this means just yet.

I think I need more anti-oxidants.

Well, this is wild speculation, but nonetheless a pretty interesting potential connection: there's a difference between cow's milk vs. goat milk. Goat's milk has a considerable amount of the enzyme PAF-AH (platelet-activating factor acetylhydrolase). Cow's milk does NOT contain it. Why does this matter? This enzyme destroys platelet-activating factor type of lipids, which, from what we discussed in the initial posts, PUFAs peroxides are basically "the" main generator of these immunosuppressive+tissue damaging molecules.

"PAF-AH has been found in the milk obtained from rat, pig, goat, or human at any postpartum period.... A higher activity was found in the colostrum of the pig (16). Surprisingly little, if any, PAF-AH activity was found in bovine colostrum or milk obtained at any time postpartum..." Platelet-activating factor-induced ischemic bowel necrosis: the effect of platelet-activating factor acetylhydrolase. - PubMed - NCBI

 

[KellyP]

Hi @thebigpeatowski
If you're heavily burning through your fat stores and if they contain lots of PUFAs, it is very plausible you're producing tons of immunosuppressive peroxides. Antagonizing histamine might help that effect. Also, lots of Reactive oxygen species come from the normal metabolism (beta oxidation) of these fats, which by itself may increase oxidative stress significantly and therefore result in immunosuppression.

Finally, acetylcholine seems to be immunosuppressive to the brain as well -not sure if you're taking AChe inhibiors-. If so, that may have to do with your brain issues (good brain function requires a well regulated brain immune system, i.e not too much inflammation, not too much immunosuppression, but a happy medium)
"the inhibition of acetyl-cholinesterase (AChE) activity in the CNS resulted in the suppression of the immune response. It seems that ACh in the brain plays an immunoinhibitory role... It is suggested that a functional connection is present in the ACh of the brain and the immune system." Immunoregulatory role of neurotransmitters. - PubMed - NCBI

I've been doing a low-fat diet with restricted calories for about 5 weeks now and have been losing what I believe is a lot of fat, mostly PUFA. This week especially my allergies/sinuses were bothering me and I've been fighting off an outbreak of cold sores/fever blisters! I haven't dealt with that much at all in the last several weeks (but has always been a problem for me off and on). This morning my stress hormones were high as well and eating sugar, salt, progesterone didn't help (like it has with any other stress reactions so far).

I had an idea after reading this thread and took a Norel (antihistamine I have) and in 20 minutes my lips are only tingly instead of red and on fire (about to erupt with cold sores). Does this seem related to PUFA/histamine response? I can't even pretend to understand all the science that the rest of you are discussing upthread. I'm reading but don't understand very much yet.

 

[schultz]

It seems that PUFA is also behind abnormal histamine release. This was observed during the course of "normal" PUFA metabolism, the kind that Mary Enig claimed is different (and harmless) from the rancidity suggested by Peat. So, nothing "harmless" about it after all.

Histamine release from rat mast cells induced by metabolic activation of polyunsaturated fatty acids into free radicals. - PubMed - NCBI

"...The release of mast cell histamine by activated PUFA has a long time-course and the electron microscopical features are consistent with an exocytotic secretion in the case of arachidonic acid and cell lysis in the case of linoleic acid. The phenomenon is associated with a significant increase in malonyldialdehyde (MDA) and conjugated diene generation, suggesting a relationship between histamine release and membrane lipid peroxidation. The secretion of histamine was inhibited by anti-free radical interventions such as D-mannitol, reduced glutathione and alpha-tocopherol. Some cyclooxygenase and lipoxygenase inhibitors, cimetidine and carnitine derivatives, are differentially active in the inhibition of mast cell histamine release by activated arachidonic acid. These results suggest that free radical derivatives of PUFA, generated by metabolic activation, trigger mast cell histamine release."

@haidut Is this apart from the effect that PGE2 has on mast cells and histamine? Prostaglandin E2–EP3 Signaling Induces Inflammatory Swelling by Mast Cell Activation

 

[haidut]

@haidut Is this apart from the effect that PGE2 has on mast cells and histamine? Prostaglandin E2–EP3 Signaling Induces Inflammatory Swelling by Mast Cell Activation

Yes, it is separate from the effects of prostaglandins. This activation of histamine release occurred during the course of normal lipid metabolism through the beta oxidation cycle.

 

[schultz]

Yes, it is separate from the effects of prostaglandins. This activation of histamine release occurred during the course of normal lipid metabolism through the beta oxidation cycle.

So it's quite effective at raising histamine I guess. Apparently histamine can increase the expression of COX-2 and PGE2 and also amplify the effect that endotoxin has on COX-2 expression and production of PGE2 and PGI2. Are we going in circles?

Histamine directly and synergistically with lipopolysaccharide stimulates cyclooxygenase-2 expression and prostaglandin I(2) and E(2) production in... - PubMed - NCBI

 

[PakPik]

I've been doing a low-fat diet with restricted calories for about 5 weeks now and have been losing what I believe is a lot of fat, mostly PUFA. This week especially my allergies/sinuses were bothering me and I've been fighting off an outbreak of cold sores/fever blisters! I haven't dealt with that much at all in the last several weeks (but has always been a problem for me off and on). This morning my stress hormones were high as well and eating sugar, salt, progesterone didn't help (like it has with any other stress reactions so far).

I had an idea after reading this thread and took a Norel (antihistamine I have) and in 20 minutes my lips are only tingly instead of red and on fire (about to erupt with cold sores). Does this seem related to PUFA/histamine response? I can't even pretend to understand all the science that the rest of you are discussing upthread. I'm reading but don't understand very much yet.

Hello KellyP,

I can't say for sure, but in light of the research discussed and from what lots of us experience when going ultra low fat and oxidizing PUFA stores, sure, your immune system may have been lowered through the PUFA->histamine pathway and the PUFA->Prostagladin pathway. So infections can get reactivated.

Glad you got that remedy work for you! I also found that upping up the calories (an adequate calorie intake) was way better for health and recovery when doing ultra low fat. Low calorie sure lowers immunity.

 

[PakPik]

So it's quite effective at raising histamine I guess. Apparently histamine can increase the expression of COX-2 and PGE2 and also amplify the effect that endotoxin has on COX-2 expression and production of PGE2 and PGI2. Are we going in circles?

Histamine directly and synergistically with lipopolysaccharide stimulates cyclooxygenase-2 expression and prostaglandin I(2) and E(2) production in... - PubMed - NCBI

Thanks for sharing, schultz, it's interesting to learn about the vicious cycles!

 

[ecstatichamster]

this may be why many of us feel so shitty on ultra low fat diets, that probably release PUFAs into our bloodstream...

 

[KellyP]

Hello KellyP,

I can't say for sure, but in light of the research discussed and from what lots of us experience when going ultra low fat and oxidizing PUFA stores, sure, your immune system may have been lowered through the PUFA->histamine pathway and the PUFA->Prostagladin pathway. So infections can get reactivated.

Glad you got that remedy work for you! I also found that upping up the calories (an adequate calorie intake) was way better for health and recovery when doing ultra low fat. Low calorie sure lowers immunity.

Thanks @PakPik. Yes, after reading this thread I decided to up my calories for the day and symptoms were relieved, inflammation decreased. I don't know if it was the calories or the fat (had over 80g that day) but it shut it down just as well as the antihistamine I took. I need to do a lot more research!