Kasper's thoughts

[Kasper]

We have previously shown that physiological concentrations of zinc (7×10–6 M) inhibit the release of histamine from human basophil leukocytes.
Thus physiological concentrations of zinc inhibit the release of histamine from human basophils and lung mast cells, presumably by blocking Ca2+ uptake induced by anti-IgE activation.

histiminase ?
Complement component 3 ?

[overkees]

The sites you posted contain malware/virus, according to my virusscan.

[Kasper]

deleted them... weird..

[dime]

PDG2
http://synapse.koreamed.org/Synapse/Dat ... m-26-8.pdf
This study is REALLY interesting, if you want to understand PDG2.

Also this review: http://ai.jsaweb.jp/fulltext/057040307/ ... index.html
We can't know if it's good or bad, according to it:

PGD2 is abundantly present in the airways of asthmatics. However, its role in the pathophysiology of asthma remains mysterious because of its multi-dimensional activity, both pro- and anti-inflammatory.

[Kasper]

It probably is good and bad.
It activates Th2 cells, and indirectly deactivate Th1 cells.



But I think that PGD2 is overproduced in many people (everyone who sleeps more than 4/5 hours), and therefore there is an imbalance.
The sleep PGD2 connection is already long ago established. The more PGD2, the more sleepy you feel.
To many TH2/Th1 imbalance, which weaken the immune system, is another symptom.
Allergies, inflammation etc. also a symptom of PGD2 overproduction.

In other words, my hypothesis is that PGD2 in the right balance (which means less PGD2 in virtually all people), will give buteyko like effects.

[dime]

Sounds like something is wrong in your reasoning, that virtually everyone is defect in something doesn't make much sense.
PGD2 has been linked to hair loss in men -- shouldn't everyone be bald then?

I read that some people who sleep little and have problems with insomnia have tried to actually increase PGD2 with a niacin supplement, in order to get more sleep.
Which reminds me that supplements are a tricky business.. e.g. you take niacin and PGD2 goes up giving you that "niacin flush"

[panacea]

thinking that something inside our bodies is the cause of general illness or health problems is the way of thinking of orthodox medicine. Most is lack of oxygen in the tissues, but this isn't a cause it's an effect of the cause which is improper lifestyle habits which trickle down into labored breathing, which decreasing oxygen in tissues through co2 loss..

[RRM]

Trying to address health issues by increasing A or B does not take away the cause, indeed.
Candida, for example, is not caused by a lack of dietary biotin.
Also, increasing the level of A or B always has an effect on something inside the body.
Unless you have something like a parasite infection, (experimental) drugs (incl. pharmaceutical dosages of vitamins) do little to the cause.

[Kasper]

Sounds like something is wrong in your reasoning, that virtually everyone is defect in something doesn't make much sense.
PGD2 has been linked to hair loss in men -- shouldn't everyone be bald then?

In hair loss in man, PGD2 is overproduced locally (in the scalp).
14 times more PGD2 than in normal people if I remember correctly.
With asthma, PGD2 is overproduced locally in the lungs.
With an injury PGD2 is overproduced in that place.
With excessive omega-6, PGD2 is overproduced, because PGD2 is a product of AA.
All the inflammation diseases have this is in common PGD2.

And PGD2 is associated width sleep, and bad immune system.

I don't say that when you have much PGD2 in your system you get asthma and hair loss.
I think it is the other way around.
PGD2 overproduction by disease (asthma,allergy etc.) --> more PGD2 locally --> increase of PGD2 in your system --> more sleep, bad immune system

Trying to address health issues by increasing A or B does not take away the cause, indeed.
Candida, for example, is not caused by a lack of dietary biotin.
Also, increasing the level of A or B always has an effect on something inside the body.
Unless you have something like a parasite infection, (experimental) drugs (incl. pharmaceutical dosages of vitamins) do little to the cause.

I don't understand how this related to this topic ... I didn't talk about drugs, or increasing the level of A or B.
I'm talking about that PGD2 overproduction is associated with inflammation diseases. And maybe the cause of oversleeping, bad immune system.

btw, I still don't know what you think about the buteyko method. Have you tried out some of those exercises ?
I think you are able to make progress really quickly..
As you don't have candida, you have been in great health for many years, you have been an active person for many years etc., follow an optimal diet for buteyko purposes. (eating only when hungry, little protein, omega-3)
I think that within a couple of weeks, with very little effort, you could reach 60 MCP. In other words, feeling better during the day, sleeping less during the night (4/5 hours of sleep).
I guess you are not really looking for something like that, and content with the way you are now, but it would be an very interesting experiment (scientifically)! You can't deny that.

[panacea]

PGD2 may be associated with inflammation diseases as is many, many, many other internal things. You could find interconnections between all sorts of stuff but the error is that you are implying PGD2 is the cause of something whether it's oversleeping or bad immune system. This cannot be as PGD2 is not free of external factors - it can be located on the cause>effect chain but it's obvious that it isn't the source.

Let's just pretend you're on the right track though and that PGD2 is the body regulator for inflammation. First of all getting rid of inflammation is almost always a bad idea as it's a bodily response that is trying to help/protect/heal us, as is everything the body tends to do. Yes, sometimes this system has flaws, such as when you pinch a nerve and are in constant pain. Obviously the pain sensors in our body are meant to alert us to problems but constant pain is doing more harm than good, just as too much inflammation can do more harm than good. In these rare cases, maybe a drug or weird method to lower PGD2 and therefore inflammation would be a good idea, but you need a lot more than hunches or a few examples linking the two together etc. Obviously, if you have too much inflammation and need to sleep more because of it, there are lifestyle factors you need to fix in order to solve this problem, not short circuit your body's defense system (inflammatory response).

I believe there are cases when we need to outsmart our ancient bodies, such as that life extension is a desirable goal but if you eat abundantly there is strong evidence that your body goes into 'procreation mode' and forgets about longevity, so caloric restriction makes sense. Our brain is also outdated when it comes to the pleasure/pain system , it's far too easily addicted to substance abuse whether it be drugs, alcohol, cooked food, junk food, bad life style addictions like gambling playing too much video games or sex addictions. It's these areas we need to learn to outsmart and control, otherwise our body has our consciousness's best interest in mind. And also note that these problem areas can only be controlled through external measures so far. For example, I doubt there is actually a pill that makes it effortless to cease smoking, heroin use, eating junk food, or being lazy, despite the claims of linking A to B, so pill C fixes it if you buy from company D.

[dime]

well said, panacea

"Why We Get Sick: The New Science of Darwinian Medicine" is a very good book to read, it tries to explain diseases from an evolutionary point of view.

[Kasper]

In these rare cases, maybe a drug or weird method to lower PGD2 and therefore inflammation would be a good idea, but you need a lot more than hunches or a few examples linking the two together etc.

Hm.. I guess I didn't clarify myself good enough.
For some reasons you guys seem to think that I want to down-regulate PGD2 by drugs or something like that.

Obviously, if you have too much inflammation and need to sleep more because of it, there are lifestyle factors you need to fix in order to solve this problem, not short circuit your body's defense system (inflammatory response).

I think that people need to fix inflammation by lifestyle factors.
But what if some lifestyle factors just cause an overproduction of PGD2.
And other lifestyle factors cause a more balanced production of PGD2 where people immune system is functioning well, and sleep production is normal...

I'm not saying we to use medicines to down regulate PGD2, I'm just trying to figure out the biochemical interactions in our body, that makes us want to sleep more, and want to sleep less.
For now, I think PGD2 is the most important factor.
Also, I'm trying to figure out how lifestyle factors (such as buteyko exercises) could lower the overproduction of PGD2 in mast cells.
Just to understand it more.
I'm not thinking that PGD2 is necessarily bad, I think it is overproduced.

Well let's talk about another question than, how could you make sure PGD2 is not overproduced?

This article is really good: http://www.westonaprice.org/know-your-f ... n-pathways



PGD2 (or prostaglandin D2) is a (indirect) product of arachidonic acid. One reason a person might overproduce PGD2 is because there is imbalance of AA/EPA/DGLA.
All those three molecules compete for the same enzymes, cyclooxygenase-1 and cyclooxygenase-2.
If someone has a diet width an omega3:6 ratio which is very low, than this will cause (over)production of the serie-2 prostaglandins (including PGD2).

Displacement
Dietary ω-3 decreases tissue concentrations of AA. Animal studies show that increased dietary ω-3 results in decreased AA in brain and other tissue,.[11] Linolenic acid (18:3 ω-3) contributes to this by displacing linoleic acid (18:2 ω-6) from the elongase and desaturase enzymes that produce AA. EPA inhibits phospholipase A2's release of AA from cell membrane.[12] Other mechanisms involving the transport of EFAs may also play a role.
The reverse is also true – high dietary linoleic acid decreases the body's conversion of α-linolenic acid to EPA. However, the effect is not as strong; the desaturase has a higher affinity for α-linolenic acid than it has for linoleic acid,.[13]
Competitive Inhibition
DGLA and EPA compete with AA for access to the cyclooxygenase and lipoxygenase enzymes. So the presence of DGLA and EPA in tissues lowers the output of AA's eicosanoids. For example, dietary GLA increases tissue DGLA and lowers TXB2.[14][15] Likewise, EPA inhibits the production of series-2 PG and TX.[9] Although DGLA forms no LTs, a DGLA derivative blocks the transformation of AA to LTs.[16]
Counteraction
Some DGLA and EPA derived eicosanoids counteract their AA derived counterparts. For example, DGLA yields PGE1, which powerfully counteracts PGE2.[17] EPA yields the antiaggregatory prostacyclin PGI3 [18] It also yields the leuokotriene LTB5 which vitiates the action of the AA-derived LTB4.[19]
The paradox of dietary GLA
Dietary linoleic acid (LA, 18:2 ω-6) is inflammatory. In the body, LA is desaturated to form GLA (18:3 ω-6), yet dietary GLA is anti-inflammatory. Some observations partially explain this paradox: LA competes with α-linolenic acid, (ALA, 18:3 ω-3) for Δ6-desaturase, and thereby eventually inhibits formation of anti-inflammatory EPA (20:5 ω-3). In contrast, GLA does not compete for Δ6-desaturase. GLA's elongation product DGLA (20:3 ω-6) competes with 20:4 ω-3 for the Δ5-desaturase, and it might be expected that this would make GLA inflammatory, but it is not, perhaps because this step isn't rate-determining. Δ6-desaturase does appear to be the rate-limiting step; 20:4 ω-3 does not significantly accumulate in bodily lipids.
DGLA inhibits inflammation through both competitive inhibition and direct counteraction (see above.) Dietary GLA leads to sharply increased DGLA in the white blood cells' membranes, where LA does not. This may reflect white blood cells' lack of desaturase. Supplementing dietary GLA increases serum DGLA without increasing serum AA.[17][20]
It is likely that some dietary GLA eventually forms AA and contributes to inflammation. Animal studies indicate the effect is small.[15] The empirical observation of GLA's actual effects argues that DGLA's anti-inflammatory effects dominate.[21]

In general, if there is an imbalance in the polyunsaturated fatty acid someone consumes, this will cause an imbalance in prostanoids that are produced.
A good step in counteracting PGD2 overproduction is making sure the diet has a balance in omega3/omega6 fatty acids.
Since my omega3:6 ratio is 1:1 I notice much less inflammation in my feet.
Also less inflammation in my nose and I think my gut.

[dime]

AA is used by bodybuilders as supplement, it's considered anabolic as it increases PGF2 alpha: http://www.freepatentsonline.com/6841573.pdf
This patent has a bunch of info on it btw.
Where do you get too much AA besides a small amount from egg yolks? It's pretty scarce naturally as I know.

Here's a comment from the author of the patent, which sounds pretty reasonable, that AA itself would not cause inflammation, but if there's already some inflammation it may increase it:

What about all the stuff online that says AA causes inflamation , athritis, Joint Pain and the negative stuff surrounded by AA and that people on other forums said it did nothing for them?

AA is not "inflammatory", but can be used by the body to support the inflammatory process. This is important because the local response to training that dictates the level of anabolic response is rooted in the inflammatory process. It dictates things like local anabolic (igf-1, insulin, androgen) hormone sensitivity, for example. If your body has an inflammatory issue, it can use AA in other tissues to also heighten the process there. This is why if you have sore joints or an inflammatory disease we don't recommend taking AA. It can exacerbate symptoms. But again, it is very safe and would not be the cause of such conditions.

[Kasper]

First of all, this is some really intresting stuff dime. This might explain why some people are more muscled naturally.

Secondly, I'm not talking about consuming AA, but about the ratio of AA/DGLA/EPA in your blood.
Which is something (completely) different, as this image of the omega-3, omega-6 pathways shows.
For example, if you consume very much LA compared to LNA, your bodies production of ETA will get lower, and DGLA will get higher.
If your bodies blood level of ETA is low, compared to DGLA, this will cause less EPA production and more AA production.
If you consume much LA compared to LNA, your DGLA and AA blood level will raise, and EPA production gets (partly) inhibited.
If you consume much AA, only AA blood level will raise, but won't effect EPA production from LNA or DGLA production of LA.
So the AA/EPA/DGLA ratio in your blood does not only depend on how much AA,EPA,DGLA you consume.
But depends also heavily on LA,LNA,GLA,ETA,DHA etc.

But also on the trans fatty acids you consume:
One of the most common blocks in the prostaglandin chain involves delta-6 desaturase (D6D), the first step in the production of prostaglandins from essential fatty acids. When action of this enzyme is blocked, so is the entire pathway. This vital enzyme is inhibited first and foremost by trans fatty acids found in margarine, shortening and hydrogenated fats.

My hypothesis is that if you consume raw animal/fish fats (lamb and cow should be grass-fed), your AA/DGLA/EPA ratio will be balanced/optimal.
Coconut oil won't do much harm. Olive oil is more discutable. Not only because of the omega3:6 ratio, but more because it lowers COX-1/COX-2.
Oleocanthal, prevents the production COX-1 and COX-2 enzymes.
This is exactly how nonsteroidal anti-inflammatory drugs work (aspirin, ibuproven). So it could be regardes as a medicine, but it also causes an imbalance.
You are not only downregulating the inflammation, but it downregulates ALL the prostanoids created by AA,DGLA and EPA.

Here's a comment from the author of the patent, which sounds pretty reasonable, that AA itself would not cause inflammation, but if there's already some inflammation it may increase it.

I believe that is partly true. Without inflammatory stimuli much AA stays in the membrane phospholipids.
In response to inflammatory stimuli, AA is released from membrane phospholipids by phospholipase A2.

But in reality, inflammation, acute or chronic, is happening all the time, so it is really important that your body responds normally to such inflammatory stimuli.
This doesn't mean that AA is neccesarily a problem, because:
1. If you consume much AA, but your AA/DGLA/EPA ratio is normal, than you don't have a problem in that sense.
2. Besides that, I believe that even if your AA/DGLA/EPA is a mess, it doesn't neccesarily mean you get inflammation everywhere.
I think that if you have inflammation, you won't get an optimal reaction (too much serie-2 prostanoids). For people width chronic inflammation, this is really bad.
If you only have sometimes some accute inflammation, you will notice it less. But this is still not optimal, healthy wise, because prostonoids serie 1 and 3 are downregulated.
You might get some muscles made out of air, but you won't get an optimal functioning body.

I just wanted to convince you guys that PGD2 production has to do width lifestyle factors, we all agree are healthy. (a good omega3:6 ratio).
And this is also a lifestyle factor, artour says has really great impact on CP. And therefore also intresting in the buteyko context.

But regarding PGD2, it's not only about this ratio AA/DGLA/EPA ratio, I'm very aware of that.
AA is converted to PGH2 by COX's. An intersting question remains, how does the body decide which prostaglaninds are created from PGH2?



Those other prostaglandins are not regarded as critical in inflammation diseases as asthma and allergies.

If we look at for example AGA (male hair loss), PGE2 is downregulated and PGD2 is upregulated in the scalp (compared to people without AGA)
PGE2 has shown to promote hair growth, PGD2 promotes hair loss.
Both PGE2 and PGD2 are both products of PGH2 (AA).

If we look at asthma, you see the same, PGE2 is downregulated and PGD2 is upregulated (in the lungs).
PGE2 has shown to be beneficial for asthma, PGD2 is critical to the development of asthma.
http://www.hindawi.com/journals/mi/2012/645383/

Major cellular sources of PGE2 include epithelial cells, endothelial cells, airway smooth muscle, and monocytes/macrophages.
As far as I've read, only mast cells are able to produce PGD2.
But I still don't really understand how mast cells overproduce PGD2, and for which reason they do this. Histamine seems to play an important role.
It couls also be that some people just have to much mast cells ... ? And therefore overproducing PGD2.

I think this is the reason low-cortisol levels are preventing CP progress.
Cortisol clears up histamine by histimanse activity.

[Kasper]

Question to RRM (or anyone else who understand calcium better than me):
Do you know some some factors that cause an increase of intracellular calcium?
PTH? Or is this only increasing calcium in the blood ?

I ask this because this seems to be an important factor for releasing AA is from the membrane.

Another question:
Does EPA consumption correlates to EPA blood levels ? I can't find a good study.

Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression.
http://www.ncbi.nlm.nih.gov/pubmed/8729112