Wagner83

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I tried one serving of tocovit yesterday with a meal (stuff tastes like crap), it did get some mucus moving around, I 'll repeat the experiment. I also became a furnace as I started walking, similar to when I used K2 in dmso + caffeine .
 

Peata

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I had a bad attack set off by climbing up a steep hill on Monday.

Then yesterday evening, I realized I hadn't had to use my albuterol inhaler since early that morning. I hadn't coughed much all day, was able to forget about it, which was so nice. It also gave my sore rib a break. I cut my Singulair in half last night, but I was too afraid it would set things off again. In the past, before the Vitamin E, I would try to take half Singulair and would wake up coughing and gasping. Last night I was afraid I'd push my luck too much, so I took the other half before I fell asleep. Had another good night. I'll see how today goes. If it's as good as yesterday, I may try half a Singulair.

So, overall things have improved a lot. Still get acute attacks (such as getting hot when exercising). I'm not quite two weeks into the experiment.
 

Peata

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Had a bit of coughing spell yesterday evening after I sneezed a couple times. Used the inhaler. But...haven't had to use it since then.

Even this morning, I thought I'd need the abluterol it to "clear things out" to get the day going like usual, but no. I even did some mild exercise (trying not to get too hot and out of breath) and did not have a problem. I may get brave enough to do half a Singulair tonight. I'd like to come off prescriptions if I can.
 
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Vinero

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This study contradicts other studies about Vitamin E and lung function. Most studies find alpha tocopherol beneficial for lung function and gamma tocopherol worsens lung function.

http://www.atsjournals.org/doi/full/10.1164/rccm.201303-0503ED

"We have demonstrated that the isoform α-tocopherol is antiinflammatory and blocks airway hyperreactivity and that the isoform γ-tocopherol is proinflammatory and increases airway hyperreactivity during eosinophilic allergic lung inflammation in mice"

"We recently demonstrated that γ-tocopherol increases allergic lung inflammation in mice"

"Interestingly, γ-tocopherol negated the antiinflammatory benefit of α-tocopherol (8, 28). In these mice, α-tocopherol blocked and γ-tocopherol increased airway hyperresponsiveness (8). Furthermore, α-tocopherol plus γ-tocopherol resulted in an intermediate phenotype for airway responsiveness similar to that of the vehicle control–treated allergic mice, suggesting that these two tocopherols have competing opposing functions"

"The prevalence rate of asthma is higher in the United States, Netherlands, and Scotland than several European and Asian countries (Figure 1B). Interestingly, countries with the highest prevalence rate for asthma also tend to have high average human plasma levels of γ-tocopherol"
 
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LeeLemonoil

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This study contradicts other studies about Vitamin E and lung function. Most studies find alpha tocopherol beneficial for lung function and gamma tocopherol worsens lung function.

http://www.atsjournals.org/doi/full/10.1164/rccm.201303-0503ED

"We have demonstrated that the isoform α-tocopherol is antiinflammatory and blocks airway hyperreactivity and that the isoform γ-tocopherol is proinflammatory and increases airway hyperreactivity during eosinophilic allergic lung inflammation in mice"

"We recently demonstrated that γ-tocopherol increases allergic lung inflammation in mice"

"Interestingly, γ-tocopherol negated the antiinflammatory benefit of α-tocopherol (8, 28). In these mice, α-tocopherol blocked and γ-tocopherol increased airway hyperresponsiveness (8). Furthermore, α-tocopherol plus γ-tocopherol resulted in an intermediate phenotype for airway responsiveness similar to that of the vehicle control–treated allergic mice, suggesting that these two tocopherols have competing opposing functions"

"The prevalence rate of asthma is higher in the United States, Netherlands, and Scotland than several European and Asian countries (Figure 1B). Interestingly, countries with the highest prevalence rate for asthma also tend to have high average human plasma levels of γ-tocopherol"

@Vinero

Yes, I've seen these studies on the different Tocos and their effects on several lung-pathologies too. It needs to really read the mechanisms they describe to extrapolate why, when and how much of the Tocos are use- or harmful.
At the moment after a very superficial look into these stuides I tend to be wary about Gamma-E and their effects on lungs. But making sense of these findings will help understad the ole of the Es in general. Would be interesting for further Peat-knowledge as well, especially regardin the fatty acids. As it is, Alpah-Toc occus predominantly in MUFA-mediums and Gamma in PUFA-rich oils and so forth.
Maybe @Travis @Amazoniac or @Westside PUFAs can shed some ideas?

I'm also not so skeptical about the Tocotrienols like Peat seems to be. The unsaturated nature doesn't make him discard Retinol either.
 

Travis

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@Vinero
Yes, I've seen these studies on the different Tocos and their effects on several lung-pathologies too. It needs to really read the mechanisms they describe to extrapolate why, when and how much of the Tocos are use- or harmful.
At the moment after a very superficial look into these stuides I tend to be wary about Gamma-E and their effects on lungs. But making sense of these findings will help understad the ole of the Es in general. Would be interesting for further Peat-knowledge as well, especially regardin the fatty acids. As it is, Alpah-Toc occus predominantly in MUFA-mediums and Gamma in PUFA-rich oils and so forth.
Maybe @Travis @Amazoniac or @Westside PUFAs can shed some ideas?

I'm also not so skeptical about the Tocotrienols like Peat seems to be. The unsaturated nature doesn't make him discard Retinol either.
Inflammation is understood in common language as redness or swelling, but this same word has been commandeered by biochemists to describe altogether different things. Inflammation is now defined biochemically on the basis of: enzymes such as cyclooxygenase‐2, inducible nitric oxide synthase, and phospholipase A₂; cytokines such as interleukin‐1, interferon‐γ, and tumor necrosis factor; and small molecules such as nitric oxide, histidine, and the prostaglandins. In practically no instance is redness or swelling ever looked for. In modern scientific articles, these molecules serve more than a proxy for inflammation as they should; the language now indicates that these molecules themselves have become the very definition of inflammation.

Before considering mechanisms, keep in mind that these scientists were using unphysiological amounts of γ‐tocopherol—amounts so high as to be considered absolutely impossible to achieve by diet or oral supplement. The tissues selectively enrich the cell membrane with α‐tocopherol at a ratio of about 9:1 (to γ‐tocopherol). The only way these experimenters could actually invert this chemical ratio was through the use of γ‐tocopherol injections—bypassing the liver and intestines.

So for the sake of argument: Do supraphysiological levels of γ‐tocopherol cause inflammation? Considering the experimental Cook–Mills article, it depends on your definition of the word inflammation. Both supplemental α‐ and γ‐tocopherol lowered cytokines in nearly every instance so they could perhaps both be seen as anti‐inflammatory:

cytokines.png click to embiggen (chemokines and antibodies ommited for brevity)

Exceptional seems to be interleukin‐10, and this one deserves special mention. Through being labeled an 'interleukin' might give one the the impression that IL‐10 signals inflammation like most cytokines in that class, but the opposite is mostly true. Interleukin‐10 can rightly be considered 'anti‐inflammatory,' since it works to transcribe genes in the cell's nucleus responsible for the formation of interleukin‐1 receptor antagonist. Interleukin‐1 is one of the most dangerous cytokines, as it powerfully‐upregulates phospholipase A₂ leading to increased arachidonic acid release and subsequent increased prostaglandin flux. Interleukin‐1 receptor antagonist binds nonfunctionally in the receptor for interleukin‐1, and its antagonist naturally exists in amounts rivaling the cytokine itself. The systemic alarm level of the interleukin‐1 system is significantly determined through its receptor antagonist; interleukin‐10 upregulates this antagonist. Interleukin‐4 is also considered one of the anti‐inflamatory cytokines.

Since the more inflammatory cytokines were decreased in number, and they had not even measured prostaglandins, what exactly had these researchers meant when they had used the term inflammation? What these researchers had meant by the word inflammation was merely the presence of white blood cells in lung tissue, determined 24 hours after an immune challenge. The immune challenges were either an injection of chicken albumin (review on anaphylactic sensitization found here), or an Aspergillus lung gavage. In the Cook–Mills article, you can consider the word inflammation—as it's usedto be essentaily synonymous with white blood cell intrusion.

But γ‐tocopherol had actually lowered inflammation, by their own definition, resulting from two of the three assays employed: the Aspergillus lung gavage, and the in vitro cell migration.

cytokine2.png


'Nevertheless, in vivo, highly elevated levels of γ‐tocopherol increased accumulation of leukocytes in the tissue but decreased lung lavage inflammation at 24 h after the third Ag challenge.' ―Cook–Mills
So even if you were, for whatever reason, to take white blood cell intrusion to be synonymous with inflammation—despite no consistent changes in cytokine or prostaglandin levels—you'd be forced to admit that γ‐tocopherol actually lowers thus‐defined inflammation in response to Aspergillus in the lungs. However: this effect is reversed, paradoxically, in response to chicken albumin (egg white) injection. But just as a reminder, both of these effects are dependent on a concentration of γ‐tocopherol in the lungs impossible to achieve even through dedicated oral supplementation.

cytokine3.png


Moreover, γ‐tocopherol had been demonstrated by these very same researchers to reduces leukocyte transendothelial migration—meaning that it lowers the velocity in which white blood cells travel along endothelial cells. You could perhaps consider this effect the tie‐break between the paradoxical and conflicting results of the two other experiments performed.

Considering the results of one of her own studies I am left wondering why Cook–Mills considers γ‐tocopherol more 'inflammatory' than α‐tocopherol, in general. What Cook–Mills, and crew, had done seems like biased selection of evidence—a type of intra‐experimental cherry picking.

Is there any way to realistically explain these effects of γ‐tocopherol? Yes, I think there is. The most canonical, real effect is the undeniable ability of γ‐tocopherol to intercept nitrogen dioxide—precursor to nitric oxide. Alpha‐tocopherol cannot do this because it has a methyl group where γ‐tocopherol has none.

'In contrast, γ‐tocopherol lacks a methyl group in position 5 and hence might be anticipated to experience nitration in vivo.' ―Hensley

These are real effects, undeniable chemical observations. The nitration of phenolic rings, such a tyrosine, are known to occur in vivo; these are considered biomarkers of nitrate production, and it wouldn't surprise me if nitrate users have higher blood levels of 5‐nitro‐γ‐tocopherol. Smokers do have higher levels of both nitric oxide and 5‐nitro‐γ‐tocopherol, see below:

tocopherol3.png


This is the only way, as far as seems realistically feasible, in which the small differences—the 5‐methyl group—between α-tocopherol and γ‐tocopherol could possibly be physiologically‐relevant. Inducible nitric oxide synthase (iNOS) is considered part of the immune system. And like the prostaglandin‐forming enzymes, inducible nitric oxide synthase can be activated by cytokines—a fact which basically defines it as such.

'Unlike endothelium NOS and brain NOS, iNOS is constitutively active and less well regulated. iNOS seems to function as part of the mammalian armamentarium against invading pathogens and also as part of the autoimmune defense against neoplasia.' ―Hensley

Cook–Mills makes no mention of nitric oxide in either of the two studies I had read. I think this is is absurd, since the ability to detoxify nitric oxide is what is considered the definable trait of γ‐tocopherol—something α‐tocopherol cannot do.

'Moreover, in rats fed a high γ‐T diet (33 mg/kg chow) and subjected to carrageenan-induced inflammation, PGE₂ and leukotriene B₄ synthesis were decreased by 46% and 70%, respectively [20].' ―Leonard

And as a gas you'd could certainly expect a much higher nitric oxide flux in the lungs than in other tissues, demonstrating why the differential effects between α‐ and γ‐tocopherol appear most pronounced in this organ.

I think any slight changes in cytokines produced by supraphysiological concentrations of γ‐tocopherol in the lungs in response to chicken egg albumin in anaphylactically‐sensitized rats could simply be do to γ‐tocopherol's ability to remove nitric oxide from the bloodstream. As a vasodilator, small changes in arterial diameter caused by NO reduction could mitigate white blood cell intrusion rates as seen by Cook–Mills in the Aspergillus experiments. The reduced nitric oxide caused by the presence of γ‐tocopherol would also be expected to reduce the chemokines CCL11 and CCL24, also noted by Cook–Mills (Figure 8).

So this would explain the Aspergillus lavage and the in vitro migration assay, but what about the other experiment? How to make sense of the paradoxical results of the converse effect upon chicken egg albumin injection?

cytokine6.png


The lungs are the only place, really, in which exists a nitric oxide flux derived non‐locally; gasses from the entire body pass through this organ. The massive flux of nitric oxide through the lungs in the other groups—the control groups and the α-tocopherol groups—might lower neutrophil formation, because neutrophils actually synthesize nitric oxide. Assuming a feedback system—high nitric oxide lowers the need for neutrophils, and vice versa—you would expect γ‐tocopherol mice to have more neutrophils although it's probably better to see it in a different but equivalent way: All the other study groups would have had lowered neutrophils due to the higher nitric oxide.

Consider these:
Ma, Xin Liang. "Diminished basal nitric oxide release after myocardial ischemia and reperfusion promotes neutrophil adherence to coronary endothelium." Circulation Research (1993)
McCall, Therese B. "
Synthesis of nitric oxide from L-arginine by neutrophils. Release and interaction with superoxide anion." Biochemical Journal (1989)

I think understanding the role of γ‐tocopherol in the immune system is understanding nitric oxide, and I don't understand why Cook–Mills fails to even mention nitric oxide. I am also uncertain how she could frame language in a way which maligns γ‐tocopherol based ostensibly on the selective acceptance of paradoxical findings. And I'm shocked—
shocked!—to read how one could use the word 'inflammation' in such a strange manner, essentially synonymous with changes in white blood cell density.

The Aspergillus assay involved a local immune response; Aspergillus directly on the lungs induced the formation of nitric oxide. The higher levels of γ‐tocopherol in those study groups would lower this nitric oxide through the formation of 5‐γ‐tocopherol, causing reduced white blood cell intrusion consequent of relative vasoconstriction. The egg albumin injection would obviously provide a much greater nitric oxide flux through the lungs, as it comes from everywhere, far too much for γ‐tocopherol to completely deal with. Sensing extremely high levels of nitric oxide, lung cells reduced the rate of new neutrophil synthesis as they'd been assumed redundant. This would occur, of course, a bit more in the control and α-tocopherol groups, explaining how the γ‐tocopherol groups could have more neutrophils.

McCary, Christine A. "Supplemental and highly elevated tocopherol doses differentially regulate allergic inflammation: Reversibility of α-tocopherol and γ-tocopherol’s effects." The Journal of Immunology (2011)
Hensley, Kenneth. "Measurement of 3-nitrotyrosine and 5-nitro-γ-tocopherol by high-performance liquid chromatography with electrochemical detection." Free Radical Biology and Medicine (2000)
Cooney, Robert V. "Gamma-tocopherol detoxification of nitrogen dioxide: superiority to alpha-tocopherol." Proceedings of the National Academy of Sciences (1993)
Leonard, Scott W. "
5-nitro-γ-tocopherol increases in human plasma exposed to cigarette smoke in vitro and in vivo." Free Radical Biology and Medicine (2003)
Cook-Mills, Joan M. "
Two faces of vitamin E in the lung." American journal of respiratory and critical care medicine (2013)

 
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LeeLemonoil

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@Travis

Sincere thanks for your elaboration, very appreciated.
One is tempted to submit this to the journal that published the study ;)

Your posts are always extremely insightful, much to learn every time!
 

Peata

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Been 3 weeks now and still doing fine. Don't think I can stop or even cut the Singulair in half though. I still have coughing after some exercise, change in air outside/inside, etc. But it's so nice to sleep through the night without waking up gasping. It's nice that my bruised/cracked? rib from all that coughing is feeling better. Albuterol use down to 1 - 3 x day instead of 8. A day or two I've been able to skip it entirely. I'd say I'm doing better than last winter, and that was when I was using Advair too (along with Singulair and albuterol as needed like I'm doing now). I have a lot less stress than last winter, so that's probably helping too.
 

Wagner83

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Been 3 weeks now and still doing fine. Don't think I can stop or even cut the Singulair in half though. I still have coughing after some exercise, change in air outside/inside, etc. But it's so nice to sleep through the night without waking up gasping. It's nice that my bruised/cracked? rib from all that coughing is feeling better. Albuterol use down to 1 - 3 x day instead of 8. A day or two I've been able to skip it entirely. I'd say I'm doing better than last winter, and that was when I was using Advair too (along with Singulair and albuterol as needed like I'm doing now). I have a lot less stress than last winter, so that's probably helping too.
Are you going to try the broth?
 

berk

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@Peata Did you ever have test yourself on sulphite/sulfite intolerance?
Most Asthma patients have a sulphite/sulfite intolerance and they are also sensitive for sulfur (body convert sulfur to sulphites)
 

Aad

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I'm taking 2 of this one, btw: Swanson Ultra Maximum Gamma Tocopherol.
Hello lads, where can i find a stand-alone gamma tocopherol product WITHOUT soy?

Thank you in advance people
 

Motif

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@Peata Did you ever have test yourself on sulphite/sulfite intolerance?
Most Asthma patients have a sulphite/sulfite intolerance and they are also sensitive for sulfur (body convert sulfur to sulphites)
What can be done for that?
 

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