An observation on the inflammation story and suggested actions

[Guest guest]

As taken from _http://sarcinfo.com/phorum/read.php?f=1 & i=2340 & t=2340_

(http://sarcinfo.com/phorum/read.php?f=1 & i=2340 & t=2340)

Cod Liver Oil, 1 Tbs: 1,360 IU

Salmon, cooked, 3 1/2 oz: 360 IU

Mackerel, cooked, 3 1/2 oz: 345 IU

Sardines, canned in oil, drained, 3 1/2 oz: 270 IU

Milk, nonfat, reduced fat, and whole, vitamin D fortified, 1 c: 98 IU

Margarine, fortified, 1 Tbs: 60 IU

Pudding, 1/2 c prepared from mix and made with vitamin D fortified milk: 50

IU

Dry cereal, Vitamin D fortified w/10% of the recommended daily value, 3/4 c:

40-50 IU

(other cereals may be fortified with more or less vitamin D)

Liver, beef, cooked, 3 1/2 oz: 30 IU

Egg, 1 whole (vitamin D is present in the yolk): 25 IU

(Information provided by National Institutes of Health)

Remember, tuna is not good recommendation b/c it is often high in mercury.

As I posted last year, one of the lowest mercury is pilk salmon from Alaska,

but it does have Vit D in it.

In a message dated 8/2/2004 12:36:42 PM Eastern Daylight Time,

writes:

I have just checked at the USDA National Nutrient Database at:

http://www.nal.usda.gov/fnic/foodcomp/search/

and found:

cod liver oil, 1 tbsp (13.6 g) = 1360 IU

canned cod, 100 g = 84 IU

canned mackerel, 100 g = 252 IU

canned sardine, 100 g = 272 / 480 IU (in oil / in tomato sauce)

tuna = No data

salmon = No data

So, you might want to stick to tuna and salmon. (Not just because

the " no data " but because I remember reading that the richest fish

in vit. D were mackerel and sardine.)

[Guest guest]

,

It sounds as though we agree on a lot of things!

Your case does sound as though it has many parallels with

's. By the way, I wonder what ever happened to him. He sort

of faded out of that internet group, I think. One of the tough

things about the internet is that if someone stops posting for

whatever reason, you lose total track of them. A guy with CFS named

Harry Metsemakers, in the U.K., did that a few years ago, and I

later learned that he had died of a heart attack.

I like your military analogies to the immune system. At one time I

was a Captain in the Army Corps of Engineers, and I spent a fair

amount of time studying military science way back when. I am

continually struck with the parallels between the activities of the

immune system and military operations. I'm sure that someone (or

several someones) must have written some interesting dramas based on

this, probably to teach kids about the immune system. It really

lends itself to that.

I share your interest in inflammation. It seems to me that the

toughest aspects of CFS treatment have to do with infections (by

viruses, fungi, and bacteria, including the cell-wall-deficient or L-

form bacteria) and with the dysfunction of the HPA axis. In fact, I

think these two sticky areas are bound together by the effect that

cortisol has on the immune system. You need some to make it work

right, but too much causes immune suppression.

Rich

> >

> > As I may have said earlier, I think that prior to the onset of

> > CFS in many PWCs, cortisol is elevated because of some

combination

> > of long-term stress, be it physical, chemical, biological,

> > psychological or emotional. It is known that elevated cortisol

> > suppresses the immune system, including the Th1 immune response

as

> > well as the inflammation response (the latter being what

> > corticosteroid drugs such as prednisone are often used for). So

I

> > don't think that inflammation is a problem initially in CFS,

> because

> > the person is unable to generate an inflammatory response

> initially,

> > but rather the main problem is a suppression of the Th1 immune

> > response, as a result of elevated cortisol and depleted

> > glutathione.

>

> I could not agree more on the above, based on my personal case.

>

> One of the first contributions I saw from you (in 2003) was

> a " Response to 's Answers " that you wrote in alt.med.cfs in

> March 23, 2000. When I read it, I was struck by the analogy with

my

> case. Let me quote some bits:

>

> " It appears that you started out with an immune system that was

below

> average in its functioning, and it continued to be weak. I'm

basing

> this on your statement that you were " a fairly sickly kid with

lots

> of colds and tummy upset. "

>

> Well, that was quite my case. And I relate it to something I read

> in Barry Sears' 1999 book " The Anti-Aging Zone " ch 18 " Sex and the

> Zone for women " : " Infant milk formulae are deprived of these

> singular fatty acids (GLA, EPA and DHA), and that's why newborn

> babies have a greater risk of suffering direct eicosanoid

> defficiencies. Eicosanoids control the immune system. If when

> newborn you had lower levels of eicosanoids (especially of

> the " good " ones), you will also have a less efficient immune

> system. The new world to which you have just arrived is already

> tough enough without need to having to immunologically defend

> yourself with a hand tied to your back. " As you can suspect, I

was

> not breast-fed. And I wouldn't bet a cent for the fatty acid

profile

> of those 60's infant milk formulae.

>

> Differently from , I did not suffer depression, but long-

term

> psychological stress.

>

> Going back to 's case:

> " In the time leading up to the onset of CFIDS, you experienced some

> additional factors that are also known to deplete reduced

> glutathione: " many little tiny colds, one right after the other, "

> frequent use of antibiotics, and considerable emotional stress. "

>

> Again quite my case.

>

> " You didn't comment on your diet during this time, so I don't know

> whether it was a factor or not. "

>

> Mine was (in the sense of short of sulfur-containing aminoacids).

>

> So, as you say, before onset I probably was in a state of elevated

> cortisol because of some combination of long-term stress, (and

> depleted GSH too), and that elevated cortisol, compounded by the

> initial immunological handicap, brought about a supression of the

> immune system, including the Th1 immune response as well as the

> inflammation response. So I aggree with you that inflammation was

> not a problem initially, but rather the main problem was a

> suppression of the Th1 immune response, as a result of elevated

> cortisol and depleted GSH. Let's call that state " the background " .

>

> > I think this combination is what allows the endogenous

> > viruses (such as EBV and HHV-6) to come out of latency,

producing

> > the initial infection that robs the skeletal muscles of

cysteine,

> so

> > that they go low in glutathione and suffer partial blockades

from

> > peroxynitrite, producing the fatigue. I think it is very

possible

> > that there are factors that are elevating NO as well, as Marty

and

> > you have emphasized, making the production of peroxynitrite even

> > more severe. Perhaps bacterial infections get going during this

> > time, too, and because of the suppression of inflammation by the

> > elevated cortisol, the immune system doesn't respond to them

> yet.

>

> Again, wholly in agreement. It was a flu virus in my case. Quite

> strong and prolonged. It had never taken such a long time before

to

> recover from a flu. And as all of my flus had been followed up by

> an opportunistic bacterial infection, this was no exception. Let's

> call this " the triggering event " .

>

> So, using the proposed precise naming, we have not talked about

CFS

> yet. We have dealt with just " the background " (suppression of the

> Th1 immune response, as a result of elevated cortisol and depleted

> GSH, on top of an initial handicap) and " the triggering event "

(the

> flu and the subsequent bacterial infection).

>

> > I think there is therefore sort of a " one-two punch " that goes on

> > with infections and the immune system in CFS.

> > First the viruses produce infections, which the immune system

> > gets activated about but is unable to defeat,

> > and then later on the immune system produces inflammation to go

> after the bacteria, after the cortisol secretion has dropped.

>

> ... and then the inflammatory response keeps on even after the

> bacteria is gone because you crushed them with antibiotics.

>

> Now, THAT's what I call CFS: the condition that develops AFTER the

> poor weak immune system made an all-out effort to overcome the

> triggering infection. And the essence of that condition is

chronic

> inflammation.

>

> At this point, it might be useful to go back to the similarity

> between CFS and SIRS that I mentioned in my previous post. For CFS

> to develop you need a background and a triggering event. For SIRS

> you do not need a background because triggering events (such as

open-

> chest cardiac surgery) are so much more stressful than those

> involved in CFS. In CFS the patient develop a chronic

inflammatory

> condition, usually not life-threatening, which remains after the

> triggering infection is gone. In SIRS, quoting from the

> review, " the expression of (inflammatory) mediators is amplified

and

> runs out of control becoming independent of the originating cause " .

>

>

> > I think that Dr. Cheney has held the view for some time that you

> > expressed about it being pointless to try to figure out how a

case

> > of CFS started, once it has gotten going, and that one just

needs

> to

> > figure out how to treat it. I'm not quite in agreement with

that

> > position yet. I do think we need to focus on treatment, but I

> still

> > think it's important to figure out how a given case started,

> because

> > if that isn't resolved, I think it might be difficult to achieve

> > health, and difficult to maintain health once achieved.

>

> Sure. E.g., if the triggering event was exposure to chemicals,

the

> PWC might strive to be in a (relatively) " clean " enviroment

> thereafter.

>

> > it is very important to get the immune system back into

> > proper operation, because it has to be the day-in, day-out

> guardian

> > of our health. It's important to defeat infections by whatever

> > means will work, such as antivirals, antifungals, antibiotics

and

> > Benicar, but it is equally important to figure out why the

immune

> > system was not able to protect against them in the first place,

> and

> > to correct this problem.

>

> Sure. I'm NOT saying that you should focus ONLY on the chronic

> inflammation aspect. My point is that you should focus ALSO on it.

>

> Expanding your view, let's think of the immune system like an army

> guarding a city. The troop was a weak one, and after repealing a

> very stressful enemy attack they got mad. So now they are firing

> their guns at anything, though there is no enemy in sight. They

are

> killing their own fellow civilian citizens! What will happen if

you

> give those soldiers stronger weapons while they are still mad?

They

> will cause greater damage to the civilians! On the other hand,

what

> will happen if you just send the troop to sleep? The city will be

> defenseless in the possible event of an enemy attack. So, the

right

> approach is to calm down the troop AND make them strong. In CFS

> terms, cool down inflammation AND strengthen the immune system,

> particularly by building up GSH levels.

>

> So, the steps in my previous post are BY NO MEANS intended to

> replace those in your " strawman " protocol, but to add to them.

>

> BTW, right in line with this, I will make a separate post pointing

> out that if you have a high intake of EPA (thru fish or fish oils)

> then you MUST supplement with vitamin E in order not to decrease

you

> natural killer cell activity.

>

> >

> > I do agree that there are vicious circles in CFS, and that they

> are

> > hard to break. I don't think we know what all the vicious

circle

> > even are, yet.

> >

> > In the absence of a complete understanding of the vicious

circles,

> I

> > have also been advocating a " brute force, " " full court press "

type

> > of approach to treatment, as I think you are suggesting (check

the

> > archives for my " Suggested General Outline for Dealing with

Cases

> of

> > CFS. " ) I think Marty has advocated such an approach, too, as

have

> > quite a few of the CFS clinicians (Cheney, Teitelbaum, Corsello,

> > Conley and others), though they all include different

components.

> > Perhaps the combination of supplements you are suggesting will

do

> > the job for some PWCs. I'm still hopeful that eventually we

will

> be

> > able to put together the right combination of things to break

> these

> > vicious circles, but I don't think this has happened yet. One

of

> > the things that has been happening since you were last posting

> here

> > is that some doctors are now doing " fast I.V. pushes " of fairly

> > significant amounts of glutathione. I've also recently learned

> that

> > sublingual troches of 250 mg glutathione are available

(Lionville

> > Pharmacy, Lionville, PA, phone 1-877-363-7474). I think that

> > together with use undenatured whey protein products, such as

> > ImmunoPro Rx (www.immunesupport.com), these approaches have the

> > potential to build glutathione in a fairly aggressive way.

> Provided

> > a person can tolerate this, it might be a way to achieve

> a " critical

> > mass " and break the vicious circles holding down the glutathione

> > levels in CFS.

>

> Looks like a good, even necessary approach. However, it could

just

> not be sufficient to get rid of CFS (you would be

just " stregthening

> the army " ).

>

> And hey, the proposed anti-inflammatory actions in my previous

post

> are just healthy steps for ANY person, not just PWCs. You might

> want to look at the site http://www.stopinflammation.com/ by Jack

> Challem, or have a peek at what the folks at sci.life-extension

do.

> They are not PWCs, just normal folks who want to optimize their

> lifespan. Most of them supplement with ALA, biotin, ALC, gamma-T

> and vitamin C (some with a lot of other things). Most of them

have

> omega-3-rich fish, green tea, fruit, a low carb diet, and red wine

> if alcohol at all. So, the steps outlined might be conducive to

> optimal health for anyone. Just that while normal people can

still

> be in an acceptable condition without following them, PWCs cannot.

>

> Regards,

> .

[Guest guest]

Hi, .

Well, I still agree with you on all of that!

I do, however, think that the immune system in CFS suffers from both

the HPA axis problems (resulting usually in low cortisol at some

time after onset, and thus runaway inflammation) and from a

depletion of glutathione (and cysteine), which I think is what

accounts for the lack of perforin in the NK and cytotoxic T cells,

and hence the low NK activity and the continued activation of T

cells, but their inability to knock out the intracellular

infections. I think that both these factors must be fixed in order

to get the immune system operating properly again.

Rich

> > ,

> >

> > I share your interest in inflammation. It seems to me that the

> > toughest aspects of CFS treatment have to do with infections (by

> > viruses, fungi, and bacteria, including the cell-wall-deficient

or

> L-

> > form bacteria) and with the dysfunction of the HPA axis. In

fact,

> I

> > think these two sticky areas are bound together by the effect

that

> > cortisol has on the immune system. You need some to make it

work

> > right, but too much causes immune suppression.

> >

> > Rich

> >

> Well, there might at last be something we can start disagreeing

> upon: PWCs have too little cortisol, not too much. So, they have

> overactive immune systems.

>

> Again, I am talking AFTER CFS has set in. During the " background "

> stage, just the opposite happened. And it all makes sense. To see

> it clearly, let me make a couple of quotes. The first leaves no

> doubt that PWCs have low cortisol levels.

>

> <quote from http://www.lef.org/protocols/prtcl-033.shtml >

>

> " An article in the Journal of Affective Disorders described a study

> in which cortisol levels were measured in 10 patients with CFS, 15

> patients with major depression, and 25 healthy controls. Baseline

> circulating cortisol levels were highest in the depressed patients;

> lowest in the CFS patients; and intermediate between the two in the

> control group of 25 healthy individuals. Prolactin responses to the

> selective serotonin-releasing agent d-fenfluramine were lowest in

> the depressed patients, highest in the CFS patients, and

> intermediate between both in the healthy group. The authors

> concluded that depression is associated with hypercortisolemia and

> reduced central serotonin neurotransmission and suggest that CFS

may

> be associated with hypocortisolemia and increased 5-HT function

> (Cleare et al. 1995).

>

> 's disease results from hyposecretion of cortisol and is

> characterized by weakness, fatigue, and dizziness upon standing. As

> described below, CFS may be a mild form of 's disease.

> <snip>

>

> Adrenal Fatigue

>

> As noted, it has been proposed that CFS is a mild form of 's

> disease (referred to as adrenal insufficiency or hypoadrenalism).

> The following evidence has been presented (Jefferies 1994;

Baschetti

> 1999; Jeffcoate 1999; Baschetti 2000):

>

> Many of the symptoms of CFS overlap those of 's disease

> (adrenal failure).

> Improvement in CFS patients has occurred after supplementation with

> mineralocorticoids (fludrocortisone), low-dose hydrocortisone

> (cortisol), and licorice (an old herbal remedy for 's

> disease). "

>

> </quote>

>

> The second links logically the elevated cortisol levels during the

> background stage with the low levels once CFS has set in.

>

> <quote from Barry Sears " The Anti-Aging Zone " Ch.15 " Cortisol " ,

when

> it talks about 's disease>

>

> " However, the reduction in cortisol production can also be a

> consequence of an excess of adrenal cortex activity due to

continual

> exposure to a constant stress. The most usual experience of this

> excessive adrenal activity is a constant feeling of fatigue. That's

> the exhaustive phase described by Hans Seyle in his pioneer studies

> on stress, published first in 1937. In any case, you have exhausted

> your reserve capacity of cortisol, and then apparently small

> stressors can have devastating physiological consequences. "

>

> </quote>

>

> That's striking! It sounds as if he were talking specifically about

> CFS! (It should be noted that none of the studies Sears provides as

> references for that chapter is specifically about CFS.) So, an

> excess of cortisol production during the " background " stage and a

> subsequent deficient cortisol production during the CFS stage make

> perfect sense.

>

> So, it's no wonder that PWCs have a dysfunctional HPA axis. And

> since the HPA axis regulates the immune system, back to the

military

> analogy, that would mean the captain of the company got mad too,

and

> he's sending like orders to the soldiers.

>

> Now, I do not know to what extent can the damage to the HPA axis be

> reversed, how to do it, or how to do WITHOUT it. I just have a

> couple of hints:

>

> A) Alpha-Lipoic acid can cross the blood-brain barrier. And a

Pubmed

> search with arguments " alpha-lipoic hypothalamus " turned in this

> promising study:

>

> Ann N Y Acad Sci. 2004 Jun;1019:350-4.

> Alpha-lipoic acid increases Na+K+ATPase activity and reduces

> lipofuscin accumulation in discrete brain regions of aged rats.

>

> Arivazhagan P, Panneerselvam C.

>

> Department of Biochemistry, Dr. ALM Post Graduate Institute of

Basic

> Medical Sciences, University of Madras, Chennai, 600 113, India.

>

> A convincing link between oxidative stress and neurodegenerative

> diseases has been found with the knowledge that it actually damages

> neuronal cells in culture. We analyzed the effect of DL-alpha-

lipoic

> acid on lipofuscin and Na(+)K(+) ATPase in discrete brain regions

of

> young and aged rats. In aged rats, the level of lipofuscin was

> increased, and the activity of Na(+)K(+)ATPase was decreased.

> Intraperitoneal administration of lipoic acid to aged rats led to a

> duration-dependent reduction and elevation in lipofuscin and enzyme

> activity, respectively, in the cortex, cerebellum, striatum,

> hippocampus, and hypothalamus of the brain. These results suggest

> that lipoic acid, a natural metabolic antioxidant, should be useful

> as a therapeutic tool in preventing neuronal dysfunction in aged

> individuals.

>

> PMID: 15247042 [PubMed - in process]

>

> (There are other studies showing ALA's beneficial effect on

> hippocampus, which I snipped for not directly relevant after

> remembering that the H in HPA stands for hypothalamus.)

>

> Is the behaviour of the immune system FULLY determined by its

> regulation from the HPA axis? Or could it be cooled down to a

> significant extent even if the HPA axis keeps as dysfunctional as

> before? (In military terms, are the soldiers just like robots

> obeying the captain's orders, or do they act to a great extent

> according to their own degree of madness?) I suspect, hope, and BET

> that the latter is the actual case.

>

> .