Corticosteroids such as prednisone given during an acute viral infection may trigger ME/CFS

[datadragon]

Dr John Chia has noted that corticosteroids when given during an acute viral infection seems to be a "recipe" that can often precipitate ME/CFS. That is to say, quite often: acute infection + corticosteroids = ME/CFS

I think the cause is below. ongoing stress = ME/CFS which can lead to all the symptoms, including viral reactivation from supression of TH1 immune system by the stress.

Cortisol from ongoing stress depletes the Magnesium and Dhea, B Vitamins, Zinc etc. Cortisol prevents cells from losing sodium and accelerates the rate of potassium excretion as well. And stressors are not just the mental/emotional life stress. Mercury from seafood and dental amalgams (and wifi/radiofrequencies from cell phones double the mercury release of amalgam mercury and also deplete mag as well even without amalgams), copper in excess (coppertoxic.com), alcohol, caffeine, blood sugar issues, body tissue inflammation and more are all treated like you were being chased by a tiger, activating the body's same fight or flight response with release of cortisol and adrenaline same as any stressor. The normal reaction of the body to stress is to produce greater quantities of both cortisol and DHEA. When the stress is gone, the body reduces its output of cortisol and DHEA to resting levels and everything is fine. This is what happens with short episodes of stress which is how our bodies work best. However, when the stress is prolonged which as you can see is quite common, the body prefers to make increasingly greater amounts of cortisol and less DHEA in order to be already ready to handle the expected stress, bypassing things like pregnenolone to make more of the downstream things - cortisol.

One study showed that after just 28 days of ongoing stress, cortisol levels had climbed to 240 percent of starting values and DHEA had dropped to 15 percent of initial levels! What's even worse is that even after the stress is removed, the body sometimes does not recover and bring these hormones back to normal levels, but instead, remains in the stress response mode with high cortisol and low DHEA output. No matter which of these types of stress are present, the body's response is always the same: initially both cortisol and DHEA increase, and with prolonged stress, the DHEA drops heavily. Zinc loss from stress causes copper to accumulate faster putting more stress on them. Eventually however the body runs out of these resources it uses to deal with the ongoing stress, the adrenal glands become exhausted, and you will see a reduction of cortisol below normal levels when not using stimulants/cortisol, with DHEA coming back up to normal range.

The consequences of elevated cortisol and reduced DHEA levels are devastating: The immune system is compromised with increased risk to infections, certain cancers, allergies and autoimmune diseases. Glucose utilization and insulin function are altered with resultant higher blood sugar levels. Salt and water are retained and higher potassium excreted, producing tendency toward high blood pressure (low in later exhaustion). Blood cholesterol and triglycerides increase and predispose to heart disease. Thyroid function becomes impaired due to lower potassium and higher calcium, resulting in decreased metabolism, lowered body temperature, and reduced vitality. The body stores fat, especially around the midsection. Depression/Anxiety from loss of minerals as well as insomnia, hunger, and PMS result. Reproductive function falters with resultant infertility and cessation of the menstrual cycle. The body becomes more susceptible to the accumulation of toxins and heavy metals such as mercury and copper. Stomach ulcers form. Memory and learning become impaired. Brain Fog. The combination of reduced R.E.M. (rapid eye movement) sleep depletes melatonin and lowered growth hormone release at night diminish mental and physical regeneration, which results in acceleration of the aging process. Protein synthesis is reduced and protein breakdown is increased, leading to bone loss, skin wrinkles, arthritis, muscle loss and weakness, and all the protein supplements in the world won't make a difference.
http://www.naturalhealthresearch.or...evices-release-mercury-from-amalgam-fillings/
http://www.drdebe.com/articles/dhea-the-real-story

https://www.selfhacked.com/blog/homing-fundamenal-cause-epstein-barr-reactivation/
The Th1 immune system is supressed by chronic stress as well. Th1 of the immune system protects us from viral reactivation. When TH1 is supressed, viral infections can then reactivate, including Epstein Barr Virus, Herpes, and a host of other viruses. When a viral infection becomes active it “hijacks” what’s known as the “mevalonate pathway.” Viruses use this pathway to make their protective outer coats. In response, your body makes interferon, which suppresses the mevalonate pathway, which in turn suppresses the virus. However, inhibiting this pathway leads to a reduction in synthesis of pregnenolone and CoQ10. Acute infections respond well to this, as the interferon production is helpful in the short term. But in the long term, this can lead to starving your body of CoQ10 and key hormones. This appears to be part of what happens in CFS.

Magnesium which is depleted by the stress is essential to create 'energy' in the body by facilitating the production of ATP (adenosine triphosphate) in the mitochondria (the power stations) of the cell. ATP is the main source of energy in cells, and must be bound to a magnesium ion in order to be biologically active. What is called ATP is often actually Mg-ATP. The process of moving sodium and potassium ions across the cell membrane is mostly an active transport process involving the hydrolysis of ATP (ATP + Water) to provide the necessary energy. This energy is used to drive the sodium/potasssium pumps that sit inside the cell membrane pumping two potassium ions into the cell and three sodium ions out of the cell. Magnesium is needed in the serotonin/melatonin pathway as well. Potassium as part of this process has a RDA of 4,700 mg a day, and cortisol depletes it while retaining sodium. The lack of Mag/Potassium/B6 are big factors in energy. Boron 3-6mg/day seems to be required for proper absorption of magnesium and calcium.

http://www.mgwater.com/dur09.shtml (chloride is involved, as is some calcium)
The Na-K-Cl cotransport system moves sodium, potassium and chloride ions across the cell membrane. Movement is electroneutral: the number of chloride ions moved equals the sum of the number of sodium and potassium ions. In most cells, the ratio of ions moved is 1Na:1K:2Cl. This system is activated by cell shrinkage and is important in regulating cell volume and potassium content. K-Cl cotransport is the electroneutral movement of one K+ ion with one Cl- ion across the cell membrane K-Cl cotransport is usually measured as the flux of K+ which depends on the presence of Cl-

https://webcache.googleusercontent.com/search?q=cache:AW38gsGff80J:www.resultsrna.com/pdf/journal/issue_4/treat_magnesium_deficiency_by_removing_mercury.pdf+&cd=2&hl=en&ct=clnk&gl=us https://www.ncbi.nlm.nih.gov/pubmed/1317120
Mercury blocks Na-K-ATP, it competes with Magnesium. The mercury antidote 2,3-dimercapto-1-propanesulfonic acid (DMPS) was able to reactivate approximately 70% of the blocked enzyme. I used pectaclear which is pectasol c and sodium algimate to detox mercury without chelating essential minerals as can methods like cutler and why they need breaks.

 

[Hip]

When a viral infection becomes active it “hijacks” what’s known as the “mevalonate pathway.” Viruses use this pathway to make their protective outer coats. In response, your body makes interferon, which suppresses the mevalonate pathway, which in turn suppresses the virus. However, inhibiting this pathway leads to a reduction in synthesis of pregnenolone and CoQ10. Acute infections respond well to this, as the interferon production is helpful in the short term. But in the long term, this can lead to starving your body of CoQ10 and key hormones.

Interesting, I did not know that.

Magnesium which is depleted by the stress is essential to create 'energy' in the body by facilitating the production of ATP (adenosine triphosphate) in the mitochondria (the power stations) of the cell. ATP is the main source of energy in cells, and must be bound to a magnesium ion in order to be biologically active. What is called ATP is often actually Mg-ATP.

But the psychological stress which may have helped trigger ME/CFS during the time when the virus was first caught may be long gone after the patient has had ME/CFS for several years. So this would not explain why ME/CFS patients continue to have energy shortages.

By the way, according to the ME/CFS energy metabolism studies of Myhill, Booth and McLaren-Howard, lack of intracellular magnesium needed to make Mg-ATP is one of the energy blockages found in ME/CFS, but there are others too, such as a blockage in Oxidative Phosphorylation, and a blockage on the translocator protein.

Note that Myhill et al use the term "translocator protein" to refer to the adenine nucleotide translocator (ANT).



It's not really clear to me why elevated cortisol or corticosteroids during the acute phase of the viral infection is a recipe for creating ME/CFS, but a simple explanation might be because cortisol or corticosteroids weakens the antiviral Th1 immune response, this allows the acute viral infection to enter tissues such as the brain. Then once inside the brain, it leads to a chronic infection, and ME/CFS ensues.

 

[datadragon]

It's not really clear to me why elevated cortisol or corticosteroids during the acute phase of the viral infection is a recipe for creating ME/CFS, but a simple explanation might be because cortisol or corticosteroids weakens the antiviral Th1 immune response, this allows the acute viral infection to enter tissues such as the brain. Then once inside the brain, it leads to a chronic infection, and ME/CFS ensues.

Hi Hip, You may have missed it in the post as it was long. chronic stress supresses TH1 and TH1 is what protects us from viral reactivation of a past exposure. When Th1 is supressed, viral infections can then reactivate, including epstein barr virus, herpes, and a host of other viruses. A current exposure would likely be the same of course. More here:
https://www.selfhacked.com/blog/homing-fundamenal-cause-epstein-barr-reactivation/

But the psychological stress which may have helped trigger ME/CFS during the time when the virus was first caught may be long gone after the patient has had ME/CFS for several years. So this would not explain why ME/CFS patients continue to have energy shortages.

Any prolonged stress can cause reactivation of a virus from TH1 supression, It can also be a past virus exposure and a current stress situation that sets it off. The energy shortages even to the point of being bedridden however doesnt need virus involvement which is another part some have, its just the stress itself depleting resources and ultimately cortisol itself all leading to the energy shortages. I've explained how it happens in that post, its generally called adrenal fatigue or general adaptation syndrome but I posted in more detail to help explain it. Eventually you lack magnesium, potassium, zinc, b vitamins, dhea etc from being used up to counter cortisol, and then cortisol itself is below normal when resources are low.

By the way, according to the ME/CFS energy metabolism studies of Myhill, Booth and McLaren-Howard, lack of intracellular magnesium needed to make Mg-ATP is one of the energy blockages found in ME/CFS, but there are others too, such as a blockage in Oxidative Phosphorylation, and a blockage on the translocator protein (adenine nucleotide translocator).

Havent looked into the others other then Mg-ATP , but magnesium seems to be required and would be lacking. Magnesium is a cofactor in more than 300 enzyme systems that regulate diverse biochemical reactions in the body
http://www.pnas.org/content/pnas/111/43/E4560.full.pdf

Excess copper is sometimes one additional cause of the stress on the adrenals and is one of the main causes of adrenal fatigue. Mercury from amalgams and fish combined with wifi exposure is another one. With zinc going lower from any stressor, copper accumulates further regardless of the stressor and can lead to the using up of the resources and burnout.
https://coppertoxic.com/adrenals

 

[Hip]

chronic stress supresses TH1 and TH1 is what protects us from viral reactivation of a past exposure. When Th1 is supressed, viral infections can then reactivate, including epstein barr virus, herpes, and a host of other viruses.

Yes, I can appreciate that, but there is no evidence for chronic stress in ME/CFS. It is only in the year prior to onset of ME/CFS that studies have shown patients may be exposed to psychological stress (such as from major stressors like divorce, bereavement or loss of job and financial security).

The question here is why do corticosteroids drugs given during the acute stage of a viral infection greatly increase the risk of developing ME/CFS? What are the specific mechanisms that allow corticosteroids given during acute infection to trigger ME/CFS?

The energy shortages even to the point of being bedridden however doesnt need virus involvement which is another part some have, its just the stress itself depleting resources and ultimately cortisol itself all leading to the energy shortages. I've explained how it happens in that post, its generally called adrenal fatigue

Saying "stress itself depleting resources and ultimately cortisol itself all leading to the energy shortages" is not really a scientific explanation of the disease mechanism of ME/CFS or the energy shortfall studies have found in ME/CFS (except perhaps for the depletion of intracellular magnesium by stress, which might explain some of the energy shortages).

But cortisol tends to be slightly low in ME/CFS, not elevated. And corticosteroids often improve ME/CFS symptoms rather than worsen them.

Adrenal fatigue is not a medically recognized condition, by the way.

 

[Hip]

You may like the Cortene peptide thread if you are interested in the stress connection to ME/CFS, @datadragon. The hypothesis is that an upregulation of a stress-related receptor called the corticotropin-releasing hormone receptor 2 (CRF2) in the brain can explain the symptoms of ME/CFS.

 

[pamojja]

Cortisol from ongoing stress depletes the Magnesium and Dhea, B Vitamins, Zinc etc...

Amazed how that summarizes my deficiencies very well. With onset of disease 10 years ago very fast developed very painful muscle cramps (despite getting 630 mg from diet and supplementing upto 2.4 g/d of elemental Mg; 1.6 g/d in average these 10 years), which I finally only completely got rid of with Mg-Sulfate IVs since Nov. last year. Dhea and male hormones deficient most of the time. With Zinc now at 70 mg/g supplemented in my decade long attempts to bring serum levels up. Which also didn't bring Cu down yet. Needed 1.5 g/d of sodium and potassium to keep levels in range. Also need at least 160 mg/d of Ubiquinone (half of that if Ubiquinol) to avoid very debilitating angina-like chest pains.

AM cortisol always been at high end of normal, and out of 4 24hrs cortisol excretion tests, 2 have been above normal. 2 years before onset had a very stressful job (along with infections: myopericartitis and schistosomiasis) which I ironically quit just before got a diagnosis of PAD with a 60% walking disability.

Yes, I can appreciate that, but there is no evidence for chronic stress in ME/CFS. It is only in the year prior to onset of ME/CFS that studies have shown patients may be exposed to psychological stress (such as from major stressors like divorce, bereavement or loss of job and financial security)....

Saying "stress itself depleting resources and ultimately cortisol itself all leading to the energy shortages" is not really a scientific explanation of the disease mechanism of ME/CFS or the energy shortfall studies have found in ME/CFS (except perhaps for the depletion of intracellular magnesium by stress, which might explain some of the energy shortages).

Though I never had a drop in cortisol yet, some years ago tested HRV which still showed very low. And I admit, I can't fathom how such a ongoing debilitating disease without easy solution in sight could ever cease to stress.

 

[datadragon]

The question here is why do corticosteroids drugs given during the acute stage of a viral infection greatly increase the risk of developing ME/CFS? What are the specific mechanisms that allow corticosteroids given during acute infection to trigger ME/CFS?

Yes, I can appreciate that, but there is no evidence for chronic stress in ME/CFS. It is only in the year prior to onset of ME/CFS that studies have shown patients may be exposed to psychological stress (such as from major stressors like divorce, bereavement or loss of job and financial security).

A deficiency for any reason in zinc lowers the immune system and opens us to viruses and infections, including reactivation of a past virus. Viruses and infections are stressors to the body with the same release of cortisol and adrenaline. Corticosteroids add more cortisol especially if your body isnt actually low on cortisol and given incorrectly, as would those with dental amalgams (especially those exposed to wifi and radiofrequencies which are everywhere), excess copper exposure which is everywhere, life stressors which arent just bad events.

Alcohol depletes zinc since its used in its metabolism. Caffeine, Carbs/Sugar, Blood Sugar issues or inflammation, its all stressors putting a demand on the adrenals for cortisol as outlined. So to answer your question, in some people the lack of zinc can occur first even just from low intake and be the starting point and lead to the virus along with any of those things including coricosteroids that increase demand and start the process before all the other symptoms which would come later in those specific cases.

https://web.archive.org/web/2018030...thalamic-pituitary-adrenal-axis/#.WxW4mUgvzIV
Cortisol’s weakening effects on the immune response have also been well documented. T-lymphocyte cells are an essential component of cell-mediated immunity. T-cells respond to cytokine molecules called interleukins via a signaling pathway. Cortisol blocks T-cells from proliferating by preventing some T-cells from recognizing interleukin signals. It also stifles inflammation due to inhibition of histamine secretion. Cortisol’s ability to prevent the promulgation of the immune response can render individuals suffering from chronic stress highly vulnerable to infection.

A role for cortisol in memory has also been demonstrated. The hippocampus, the region of the brain where memories are processed and stored, contains many cortisol receptors. While normal cortisol levels have no adverse effects on the hippocampus, excess cortisol overwhelms the hippocampus and actually causes atrophy. Studies of the elderly have indicated that those with elevated cortisol levels display significant memory loss resulting from hippocampus damage, but the exact age range at risk is unclear. There is a reprieve, however, for the chronically stressed: the damage incurred is usually reversible

https://coppertoxic.com/flowchart - Click it then zoom buttons on bottom right. This explains a bit of the process of a stressor to the body, in this example, just excess copper exposure by itself.

The mitochondia requires copper for completing the electron transport where our energy is produced. Copper is however required to be attached to ceruloplasmin to be usable at all by the body. It no longer will be attached well to ceruloplasmin once adrenals become too weak from stressors making you low or deficient in copper even though copper is still being taken in (can have normal or high serum copper but ceruloplasmin (usable) would then be low in later phase of ME/CFS progression.

In the meanwhile, magnesium, zinc, and b vitamins are being depleted from stressors.

Magnesium which is depleted by the stressors to the body is essential to create 'energy' in the body by facilitating the production of ATP (adenosine triphosphate) in the mitochondria (the power stations) of the cell. ATP is the main source of energy in cells, and must be bound to a magnesium ion in order to be biologically active. What is called ATP is often actually Mg-ATP. The process of moving sodium and potassium ions across the cell membrane is mostly an active transport process involving the hydrolysis of ATP (ATP + Water) to provide the necessary energy. This energy is used to drive the sodium/potasssium pumps that sit inside the cell membrane pumping two potassium ions into the cell and three sodium ions out of the cell and also requires chloride, calcium, and copper.
Magnesium and zinc and B2 are needed for of the conversion of B6 to the active form, which is another problem with energy when B6 is lacking. Mag, Zinc, B6 are involved in the serotonin/melatonin pathway. Magnesium alone is involved in over 300 enzymes/conversions in the body. A few of the additional mag deficiency symptoms http://www.magnesiumeducation.com/mg-deficiencies. Zinc deficiency lowers the immune system and opens us to viruses and infections, including reactivation of a past virus.

It is the lack of resouces that stops the ability to produce energy. And then metals like copper and mercury can accumulate from the lowering of zinc, and this further puts demand on the adrenals until it cant keep up. This is when ceruloplasmin (usable copper) drops and we go into adrenal exhaustion. Those with ApoE4 also cant detox metals as well so they build faster then other people. The effects are outlined throughout the threads.

http://www.mgwater.com/dur09.shtml (chloride)
The Na-K-Cl cotransport system moves sodium, potassium and chloride ions across the cell membrane. Movement is electroneutral: the number of chloride ions moved equals the sum of the number of sodium and potassium ions. In most cells, the ratio of ions moved is 1Na:1K:2Cl. This system is activated by cell shrinkage and is important in regulating cell volume and potassium content. K-Cl cotransport is the electroneutral movement of one K+ ion with one Cl- ion across the cell membrane K-Cl cotransport is usually measured as the flux of K+ which depends on the presence of Cl-. When zinc and mag fall, so will potassium which is required as well as leading to lowering of stomach acid which can create even more deficiencies.

https://forums.phoenixrising.me/ind...ses-me-cfs-not-germs.60072/page-2#post-980595

 

[Hip]

So to answer your question,

Your post does not answer the question; and there is absolutely no evidence to support your idea that ME/CFS is caused by zinc deficiency.

In many of the posts you've made since joining this forum, you appear to want to explain medical illnesses in terms of simple nutrient deficiency. Biochemistry has almost infinitely more complexity that just magnesium, zinc, etc.

 

[datadragon]

Going back to the original question. IFN-γ induction of IDO is potentiated by the synthetic glucocorticoid dexamethasone, which exerts no effect by itself. (A corticosteroid)

The kynurenine pathway, which is often systemically up-regulated when the immune response is activated. IFN-y, which is induced by intense exercise, strongly induces IDO1 expression TRP breakdown was significantly induced by intense exercise as indicated by a decline in TRP levels by 12% (p<0.001) and an increase of KYN levels by 6% (p<0.02), accompanied by an elevation of KYN/TRP by 20% IFN-y is the most important stimulus of indoleamine 2,3-dioxygenase-1 (IDO1) activity although other mainly pro-inflammatory stimuli can do the same. IFN-γ is able to induce both the gene expression and enzymatic activity of IDO-1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849644/figure/pone.0153617.g002/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849644/

This one mentions neutralization of IL-1α inhibits the antiviral activity of IFN-γ by 90%, whereas no inhibition of type I IFN activity was observed. Indeed, the antiviral activity of IFN-γ depends largely on the basal level of NF-κB, which is maintained by constitutively expressed IL-1α https://www.sciencedirect.com/science/article/pii/S1568997221000227#s0070

This article confirms IL-1 can induce production and release of more IL-1, a process described as an autoinflammatory loop. Anakinra is a bio-engineered form of the naturally occurring interleukin-1 receptor antagonist (IL-1ra) that blocks the action of interleukin-1. It is routinely used in patients with autoimmune and inflammatory disorders and MAS. Within the IL-1 family of cytokines, several inhibitory mechanisms are in place to prevent runaway inflammation induced by IL-1α or IL-1β. The main mechanism is the IL-1 receptor antagonist (IL-1Ra), which blocks the IL-1R1 and prevents binding of IL-1α and IL-1β. In contrast to JAKinibs, anakinra will not directly block the IFN-STAT1/STAT2 pathway critical for host defense against viral infections. Third, in contrast to tocilizumab (an IL-6 inhibitor), it targets and inhibits the core mechanism in the pathogenesis of MAS, namely the hyperactive inflammasome loop https://ccforum.biomedcentral.com/articles/10.1186/s13054-020-03166-0