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Dr Paul Marik's Sepsis/SIRS Protocol for ME/CFS? (Vit C / Hydrocortisone / Thiamine)

Jesse2233

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Southern California
Dr Paul Marik (of Sentara Norfolk General Hospital) has recently developed a novel treatment protocol for life threatening sepsis.

[Edit: full protocol]
  • IV Vitamin C (1.5 gm every 6 hours for 4 days)
    Infused over 30 to 60 minutes and mixed in 100ml normal saline / D5W in water

  • IV Thiamine (200 mg every 12 hours for 4 days)
    Infused over 30 minutes 50 ml of either normal saline / D5W following IV Vitamin C

  • IV Hydrocortisone (50 mg every 6 hours for 7 days followed w/ 3 day taper)
Thus far it has been quite successful;
The breakthrough came as Dr. Marik struggled to save a woman dying from overwhelming sepsis. He had recently read about vitamin C as a potential treatment for sepsis, and he recalled that steroids, a common treatment for sepsis, might work well in concert with the vitamin C.

Aware that both were safe and would not harm the patient, he gave her the vitamin C and steroid combination intravenously.

Within hours, his patient was recovering. Two days later she was well enough to leave the ICU.

Dr. Marik and is colleagues were astonished. “We said, ‘What just happened?’”

In the following days they used the combination therapy on two more patients seemingly destined to die of sepsis. Twice more the patients recovered. Dr. Marik and his team quickly adopted the combination therapy as standard practice.

http://www.evms.edu/about_evms/admi...ations/issue_9_4/has-sepsis-met-its-match.php

Given the latest research, I can't help but wonder if this might be an effective treatment for ME/CFS.

At the recent OMF Stanford Symposium Dr Wenzhong Xiao indicated that gene expression data matches ME/CFS more closely to SIRS than any other disease. Drs Jose Montoya and Kenny DeMeirleir have made similar statements. When I spoke to KDM earlier this year he told me ME is essentially a low grade chronic sepsis.

Obviously these treatments have been used individually in many ME patients, but Dr Marik has shown that the protocol's true benefit for SIRS comes from the unique combination.

To strengthen his case and to allay his own apprehensions that this was too good to be true, Dr. Marik worked with colleagues to study the interaction in a lab setting. Two separate biological tests proved that vitamin C and steroids were effective against sepsis — but only when used together.

My layman's guess at a mechanism of action...

Hydrocortisone lowers systemic inflammation, Vitamin C fights any underlying infection / acts as an antioxidant, Thiamine supercharges metabolism to fuel the process.

Has anyone tried this combo or heard of success with it? It seems reasonably safe and low cost

Of course SIRS is not ME, they are distinct in their presentation and prognosis, but the similarities are too close to ignore

Tagging
@Janet Dafoe (Rose49) and @JaimeS in case this is useful to Ron
 
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Jesse2233

Senior Member
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Location
Southern California
From Dr Marik's study
RESULTS: There were 47 patients in both treatment and control groups, with no significant differences in baseline characteristics between the two groups. The hospital mortality was 8.5% (4 of 47) in the treatment group compared with 40.4% (19 of 47) in the control group (P < .001). The propensity adjusted odds of mortality in the patients treated with the vitamin C protocol was 0.13 (95% CI, 0.04-0.48; P = .002). The Sepsis-Related Organ Failure Assessment score decreased in all patients in the treatment group, with none developing progressive organ failure. All patients in the treatment group were weaned off vasopressors, a mean of 18.3 ± 9.8 h after starting treatment with the vitamin C protocol. The mean duration of vasopressor use was 54.9 ± 28.4 h in the control group (P < .001).

https://www.ncbi.nlm.nih.gov/m/pubmed/27940189/
 

ljimbo423

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United States, New Hampshire
Those are very impressive treatment results in that study! I have hydrocortisone, thiamine and vitamin C all on hand. I might give it a shot and see how it goes. Although the last couple of times I tried hydrocortisone, I didn't fair so well.

When I spoke to KDM earlier this year he told me ME is essentially a low grade chronic sepsis.

Chris Armstrong seems to agree-

Well we all experience a bacteremia when we exercise. The type of bacteria that enter your bloodstream are usually quite controllable by your immune system but if your gut is further compromised they may release more bacteria into your blood or more pathogenic species or your immune system may already be depleted. This is the concept for the chronic sepsis or SIRS and this is what I think may be behind PEM.
LINK


Jim
http://forums.phoenixrising.me/inde...20-2016-metabolomics.47485/page-6#post-791828
 

Jesse2233

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1,942
Location
Southern California
Those are very impressive treatment results in that study! I have hydrocortisone, thiamine and vitamin C all on hand. I might give it a shot and see how it goes

If you do it, let us know how it goes!

I was just wondering if taken orally would work.

Going to some digging to find the exact protocol. It's very likely IV, but one might still see results if taken orally
 

Paralee

Senior Member
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571
Location
USA
@Jesse2233 , I'm sure in the hospital or a medical setting it would be IV. However, you can buy cortisone cream across the counter (not as strong) or if you had your own for adrenal problems you would probably up it to the point that I read people do for extra stress, etc. The vitamin C and Thiamine would be (according to article) increased considerably. Does sound interesting.
My DIL lost her mother a few months ago from sepsis that should not have happened in an ICU setting. It scares me to the point of wondering if I would go into a hospital to be treated.

Edit: Sorry, those were your words, I should have checked first. Anyway, still......
 

JES

Senior Member
Messages
1,320
I was just wondering if taken orally would work.

You might want to try liposomal Vitamin C. Liposomal achieves somewhat higher (about 30%) concentration in serum than normal vitamin C (article), although it's still far below what IV can achieve. But even the IV peak concentration only stays for a couple of hours.

I trialed liposomal vitamin C during the past summer. Even from a small dosage of liposomal vitamin C, I can feel the effect within an hour or so. It does intensify some of my immune system related symptoms, such as the small fiber neuropathy. Unfortunately, I couldn't carry on testing it for many weeks, as some of my symptoms worsened too much, which I think is due immune stimulation causing excessive inflammation, as it happens with other immune stimulating herbs as well.

Anyway, reading this was inspiring, so I plan to trial vitamin C again, this time in combination with some immune suppressing thing (not steroids, but bupropion for example), and see if I can tolerate it better that way, because I definitely felt it did something, and vitamin C is also active against herpesviruses at high dosage.
 

dannybex

Senior Member
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3,561
Location
Seattle
I went into what I would call a 75% remission with just 2-3 months of thiamine injections alone (and high-dose probiotics) back in 2003, which then lasted 2 years, until I ran out of $$. Then of course later completely forgot that I had done the thiamine injections...thanks brain fog.

Sepsis is one of the key things that interferes with the pyruvate dehydrogenase enzyme, let alone many other things. Just taxes the body overall.

It's worth noting though that some people have high cortisol during certain times of the day. I haven't read the study yet, but perhaps the cortisone was only given for a very short period at the beginning...?
 

JES

Senior Member
Messages
1,320
@JES , buproprion is an immune suppressant? That's Wellbutrin, right?

Yeah, it suppresses TNF-alpha and seems to help in Crohn's disease. I bet it would be used a lot more for immune disorders if it wasn't for the fact that it's a 30 year old antidepressant. Science is about to discover that many existing drugs have off-label potential to treat completely different diseases than what they were intended for, but sadly money still dictates and it's probably the reason why doctors ignore perfectly safe and often times helpful treatments like Wellbutrin or LDN.
 

Learner1

Senior Member
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6,305
Location
Pacific Northwest
I was getting high dose (50-75g) vitamin C IVs weekly for over 2 years + 4g day orally + B vitamin IVs with lots of B1 + 500-600mg B1 orally, with a lot more stuff.

I credit it for keeping me functioning as well as I do, I weight lift carefully, work 12-16 hours a week but am a patient the rest of the time...

Edit - while taking 25mg of hydrocortisone daily

So, I'd say it has merit, but is not a cure for everyone.
 
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Jesse2233

Senior Member
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1,942
Location
Southern California
Dr Marik's detailed treatment protocol for sepsis:
  • IV Vitamin C (1.5 gm every 6 hours for 4 days)
    Infused over 30 to 60 minutes and mixed in 100ml normal saline / D5W in water

  • IV Thiamine (200 mg every 12 hours for 4 days)
    Infused over 30 minutes 50 ml of either normal saline / D5W following IV Vitamin C

  • IV Hydrocortisone (50 mg every 6 hours for 7 days followed w/ 3 day taper)
Source: https://sci-hub.cc/https://www.ncbi.nlm.nih.gov/pubmed/27940189 / Page 9
 

Jesse2233

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Location
Southern California
@Learner1 as usual you are one step ahead :)

It seems like Dr Marik's protocol had more frequent and higher doses of hydrocortisone and likely higher doses of thiamine though your dose of vitamin C was much higher (albeit less frequent).

Might the magnitude of effect be dose and frequency dependent?
 

Jesse2233

Senior Member
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1,942
Location
Southern California
I went into what I would call a 75% remission with just 2-3 months of thiamine injections alone (and high-dose probiotics) back in 2003, which then lasted 2 years, until I ran out of $$. Then of course later completely forgot that I had done the thiamine injections...thanks brain fog.

Very interesting, do you recall how long it took you to see improvement from the thiamine and what dose you were taking?
 

Jesse2233

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Location
Southern California
The study's discussion of potential mechanism of action:
Experimental studies performed over the last 20 years have demonstrated that both vitamin C and hydrocortisone have multiple and overlapping beneficial pathophysiologic effects in sepsis. Vitamin C is a potent antioxidant which directly scavenges oxygen free radicals, restores other cellular antioxidants including tetrahydrobiopterin and α- tocopherol and is an essential co-factor for iron and copper containing enzymes. 70;71

Both drugs inhibit nuclear factor Ƙ-B (NF-ƘB) activation down regulating the production of proinflammatory mediators, increase tight junctions between endothelial and epithelial cells, preserve endothelial function and microcirculatory flow, and are required for the synthesis of catecholamines and increase vasopressor sensitivity.13-15;26;70-75

Vitamin C plays a major role in preserving endothelial function and microcirculatory flow.70;72 In addition, vitamin C activates the nuclear factor erythroid 2-like 2 (Nrf2)/ heme oxygenase (HO)-1 pathway which plays a critical role in anti-oxidant defences and enhances T cell and macrophage function. 76-78 The explanation as to why the combination of intravenous vitamin C, hydrocortisone and thiamine appeared to have a marked effect on the course of sepsis as compared to the myriad of designer molecules which have been evaluated in previous sepsis trials is likely related to the multiple and overlapping effects of all three agents as compared to drugs which target a single molecule or pathway.12

Furthermore, we believe that vitamin C and corticosteroids act synergistically. 79 Oxidation of cysteine thiol groups of the glucocorticoid receptor (GR) affects ligand and DNA binding reducing the efficacy of glucocorticoids. 80;81 Vitamin C has been demonstrated to reverse these changes and MANUSCRIPT ACCEPTED ACCEPTED MANUSCRIPT 17 | P a g e restore glucocorticoid function. 82 The transport of vitamin C into the cell is mediated by the sodium-vitamin C transporter -2 (SVCT2). 83

Proinflammatory cytokines have been demonstrated to decrease expression of SVCT2. 84 Glucocorticoids, however, have been shown to increase expression of SVCT2. 85 In an experimental model using cultured human lung vascular endothelial cells exposed to endotoxin we have demonstrated that incubation with the combination of vitamin C and hydrocortisone preserved endothelial integrity as compared to either agent alone which was no more effective than placebo.86

This finding is in keeping with recent clinical studies which suggest that hydrocortisone and vitamin C alone have little impact on the clinical outcome of patients with sepsis.16;54 The recently published “Hydrocortisone for Prevention of Septic Shock (HYPRESS)” study failed to demonstrate an outcome benefit from a hydrocortisone infusion in patients with sepsis.

While the dosing strategy for corticosteroids (hydrocortisone) in patients with severe sepsis and septic shock has been well studied,26;88 that for vitamin C is more uncertain. Critically ill patients have either very low or undetectable vitamin C levels (normal serum levels 40-60 umol/l).18;19 Due to the saturable intestinal transporter (sodium-vitamin C transporter-1), 20;83 oral administration of doses as high as 1500 mg cannot restore normal serum levels. 20 To achieve normal serum vitamin C levels in critically ill patients, a daily dose of more than 3 gm is required. 16;18;21 Based on pharmacokinetic data and preliminary dose response data we believe that a daily dose of 6gm combined with hydrocortisone is optimal.

When high dosages of vitamin C are given intravenously, metabolic conversion to oxalate increases.19 Oxalate is normally excreted by the kidney and serum levels will increase with renal impairment. In patients with renal impairment receiving mega-dose vitamin C, supersaturation of serum with oxalate may result in tissue deposition as well as crystallization in the kidney. 89;90 Worsening renal function is therefore a concern with mega-dose vitamin C. It is noteworthy that renal function improved in all our patients with AKI. Glyoxylate, a byproduct of intermediary metabolism, is either reduced to oxalate or oxidized to CO2 by the enzyme glyoxylate aminotransferase; thiamine pyrophosphate is a co-enzyme required for this reaction. 91 Thiamine deficiency increases the conversion of glyoxylate to oxalate. 92;93 Thiamine deficiency is common in septic patients and associated with an increased risk of death.64 For these reasons, thiamine was included in our vitamin C protocol.

Pgs 16-18
https://sci-hub.cc/https://www.ncbi.nlm.nih.gov/pubmed/27940189
 

Jesse2233

Senior Member
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1,942
Location
Southern California
To summarize the Marik protocol's rationale / mechanism of action:

Vitamin C

  • Direct antioxidant
  • Restores other antioxidants
  • Co-factor for iron and coper containing enzymes
  • Enhances T-cell and macrophage function

Vitamin C / Hydrocortisone
  • Inhibit NF-KB activation (down regulate proinflammatory mediators)
  • Increase tight junctions between endothelial and epithelial cells
  • Preserve endothelial function and microcirculatory flow
  • Fuel synthesis of catecholamines
  • Increase vasopressor sensitivity
Synergistic complements of Vitamin C & Hydrocortisone
  • Vitamin C reverses oxidation of cysteine thiol groups and improves efficacy of glucocorticoids
  • Synergistically preserves endothelial integrity

Thiamine
  • Protects kidney from increased oxalates caused by high dose Vitamin C
  • Restores thiamine deficiency found in sepsis

---------------------------

The authors don't discuss it, but I wonder if thiamine is also boosting the efficiency of pyruvate dehydrogenase

Also I wonder if the increase of tight junctions between endothelial and epithelial cells might repair intestinal permeability in ME/CFS

And I wonder if the effects on endothelial function, microcirculatory flow, and vassopressor sensitivity might ameliorate POTS/OI
 
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