page 26 CFS > ALLOPATHIC MEDICINES > STEROIDS > CORTICOSTEROIDS PEM

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Corticosteroids as Potent PEM Shielders
https://forums.phoenixrising.me/threads/supplements-and-drugs-that-reduce-or-prevent-pem-post-exertional-malaise.48438

 

Corticosteroids such as prednisone, prednisolone and hydrocortisone are reported to be potent PEM shielders. When normal doses of these corticosteroids are taken around one or two hours before any physical or mental exertion, they can totally prevent any PEM from later appearing.

 

But these drugs were found to be useless if taken after the exertion. That is, they do not help if you are already experiencing PEM from a previous period of exertion.

 

Note that it is normal doses of corticosteroids (eg, prednisolone 20 mg, or hydrocortisone 80 mg) that can prevent PEM, not the low doses (eg, prednisolone 5 mg, or hydrocortisone 20 mg) that some ME/CFS patients take daily.

 

And note that normal doses of corticosteroids should only be used occasionally in ME/CFS, perhaps as a maximum of once a week. If normal doses are used every day on a long term basis, this can lead to worsening of ME/CFS (possibly because the corticosteroid Th1 immune suppression may allow any underlying viral infections to proliferate).

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CHRONIC FATIGUE SYNDROME: A TREATMENT GUIDE, 2nd Edition (open in new window or download)

 

HYDROCORTISONE/CORTEF

 

DESCRIPTION. Hydrocortisone is the pharmaceutical name for cortisol, a glucocorticoid hormone excreted by the adrenal cortex in response to stress, inflammation, and low blood sugar levels.

 

BACKGROUND. Cortisol is produced in the outer layer of the adrenal gland, known as the adrenal cortex. The release of cortisol is controlled by the hypothalamus, which secretes corticotropin-releasing hormone (CRH) to the pituitary gland, which in turn releases adrenocorticotropic hormone (ACTH). ACTH is carried by the bloodstream to the adrenal glands, where cortisol is then released.

 

Cortisol has numerous effects on body functions, including reduction of inflammation, maintenance of sodium and potassium balance, and regulation of blood sugar. Cortisol also has profound effects on protein and carbohydrate metabolism. Because cortisol can suppress the immune system (specifically the proliferation on T cells), hydrocortisone is used medically to treat inflammatory conditions such as rheumatoid arthritis, lupus, and allergies.

 

USES IN CFS/ME. Whether hydrocortisone should be used to treat CFS/ME is a topic of much debate among CFS/ME clinicians. Studies performed by Dr. Mark Demitrack and colleagues showing endocrine system deficiency along the CFS Treatment Guide Verrillo/408

 

hypothalamic-pituitary-adrenal axis (HPA axis) seem to indicate that there is a chronic adrenal insufficiency in patients with CFS/ME (Journal of Clinical Endocrinology and Metabolism, 1991). The low levels of cortisol found in some CFS/ME patients, combined with increased or new inflammatory responses, such as allergies, irritable bowel syndrome, and rheumatic conditions, also seem to point to the use of cortisol as a potentially effective treatment.

 

Several studies have confirmed that treatment with low-dose hydrocortisone increases energy levels and stamina in CFS/ME patients. In 1999 Cleare et al found that in a group of 32 CFS/ME patients treated with 5-10 mg of cortisol daily for a month, energy levels were significantly improved. In a subsequent study published in 2001, Cleare also found that low-dose cortisol restored normal adrenal responses to CRH in CFS/ME patients.

 

A number of prominent CFS/ME doctors include low-dose hydrocortisone as part of their CFS/ME protocols. In a 2008 study of 500 patients, Dr. Holtorf found that 5-15 mg a day of time-release hydrocortisone resulted in an overall improvement in 94% of his patients. Moreover, Dr. Holtorf states that “physiologic [low] doses of cortisol have been shown to improve cellular and hormonal immunity, including natural killer cell activity” both of which are problems with CFS/ME patients.

 

However, not all clinicians agree that treatment with hydrocortisone is beneficial. Cortisol can be an immune system suppressant and, in cases in which the immune system is already compromised, its effects could be disastrous. Clinicians who are critical of hydrocortisone's usefulness as a CFS/ME treatment point out that glucocorticoids are best used as a short-term treatment for severe allergic reactions. Long-term use may exacerbate the disease process.

 

PROTOCOL. Hydrocortisone (cortisone, cortisol) may be given as a single injection to treat severe allergic response or in acute cases of CFS/ME when immediate intervention is required. It may also be administered in pill form (Cortef) in low doses (5 to 15 mg) on a daily basis.

 

PROS. Many patients report a significant increase in energy and stamina from hydrocortisone. For some patients hydrocortisone makes the difference between having to lie in bed all day and being able to get up, which can make all the difference in the world for the severely ill. Single ("pulse") administrations of cortisol can be lifesaving for patients with severe allergic reactions or acute-onset CFS/ME.

 

CONS. Cortisol is a naturally occurring chemical. However, its use on a long-term basis, carries significant risks. When the body registers the presence of hydrocortisone, the adrenal glands decrease production. Although proponents of low-dose hydrocortisone claim that the risks are minimal, when taken over a long period of time the adrenal glands may fail to produce glucocorticoids altogether, making the patient entirely dependent on a drug source for this essential hormone.

 

In addition to the risk of dependency, the dosage must not be excessive or Cushing's syndrome may eventually develop, with tendencies for obesity, hypertension, osteoporosis, and mental disturbances. Side effects of even small doses of cortisol include headache, gastrointestinal disturbances, insomnia, and weakness. Hydrocortisone is strongly contraindicated for people with fungal infections.

 

AVAILABILITY AND COST. Hydrocortisone is available by prescription, in generic and brand-name formulations. The cost of brand (Cortef) or generic is similar, ranging from $15 to $30 a month, depending on the dosage. It is usually covered by insurance.

 

BOOKS

Jeffries, William. Safe Uses of Cortisol. Charles C Thomas Pub Ltd , 3rd edition. 2004. (Originally published in 1970, this is the “bible” for physicians who prescribe hydrocortisone for CFS/ME and FM.)

 

FURTHER INFORMATION

Excellent discussion of low-dose hydrocortisone by a CFS/ME patient detailing the dosage and effects:
www.revolutionhealth.com/groups/me-chronic-fatigue-syndrome-support/discussions/topic/c433312d-35c5-41b1-a2b2-7be3aecc6987

 

Pro-health's patient thread on low-dose hydrocortisone

http://www.prohealth.com/fibromyalgia/blog/boardDetail.cfm?id=1058069&b1=CHWEBO#1058069

 

A review of the literature concerning low-dose hydrocortisone treatment in CFS/ME and FM:

http://www.endfatigue.com/health_articles_f-n/Hormones-adrenal_problems_in_cfs.html

 

Discussion of low-dose hydrocortisone in CFS/ME
http://enotes.tripod.com/fatigue2.htm

 

Dr. Teitelbaum's excellent review of HPA axis dysfunction and low-dose hydrocortisone treatment in CFS/ME patients:
http://www.endfatigue.com/health_articles_f-n/Hormones-adrenal_problems_in_cfs.html

 

Dr. Holtorf's review of HPA axis dysfunction and study of 500 patients receiving low-dose hydrocortisone:
http://www.holtorfmed.com/dr-pdf/Diagnosis%20Treatment%20CFS%20FM.pdf

 

Dr. Baschetti discusses the benefits of low-dose cortisol and makes a comparison of 36 shared features between Addison's disease and CFS/ME
http://jcem.endojournals.org/content/84/6/2263-a.full

 

PATIENT REVIEWS

CFS/ME patient reviews of Cortef (hydrocortisone)
http://www.revolutionhealth.com/drugs-treatments/rating/cortef-for-chronic-fatigue-syndrome-cfs-cfids-me

 

RESEARCH

Cleare AJ, Heap E, Malhi GS, Wessely S, O'Keane V, Miell J. “Low-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial.” CFS Treatment Guide Verrillo/410

 

Lancet 1999 Feb 6;353(9151):455-8.
http://www.ncbi.nlm.nih.gov/pubmed/9989716 (Abstract)

 

Cleare AJ, Miell J, Heap E, Sookdeo S, Young L, Malhi GS, O'Keane V. “Hypothalamo-pituitary-adrenal axis dysfunction in chronic fatigue syndrome, and the effects of low-dose hydrocortisone therapy.” J Clin Endocrinol Metab. 2001 Aug;86(8):3545-54.
http://jcem.endojournals.org/content/86/8/3545.full

 

Demitrack, Mark A, Dale, Janet K, Straus, Stephen E, Laue, Louisa, Listwak, Sam J, Dreusi, Markus JP, Chrousos, George P, and Gold, Philip W. “Evidence for Impaired Activation of the Hypothalamic-Pituitary-Adrenal Axis in Patients With Chronic Fatigue Syndrome.” Journal of Clinical Endocrinology and Metabolism. 73:1224-1234

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                        Examples of ME/CFS patients using corticosteroids to prevent PEM                        (click to open) User Patrick found that prednisone at a dose of 20 mg taken a just before a mentally exerting event (such as socializing) was effective at relieving ME/CFS symptoms. Sometimes he would take another 20 mg later in the day. Other ME/CFS patients have vouched this works effectively and reliably (though others report ill effects from this corticosteroid drug). Note that this dosing is only used as a one-off, not regularly every day. User hamsterman found hydrocortisone at a one-off dose of 80 mg (or alternatively and equivalently prednisolone 20 mg) taken 30 minutes before a mentally or physically exerting event very effective for preventing PEM due to physical and mental exertionhamsterman said: "I tested it hydrocortisone with 80 mgs (equiv. to 20 mgs prednisone), and used it 30 minutes prior to 4 different situations which always cause PEM 1) Doctors visit, 2) engaging chat with friend 3) cardio workout 4) another chat with a different friend. Each time, no PEM. Just as with prednisone, its useless if taken after the exertion, it does nothing if you are already experiencing PEM, is not meant to be taken daily, But unlike prednisone, it hydrocortisone doesnt stay in the system for very long, so after a couple hours or so, it is no longer active. But this can be an advantage, since it can be used more strategically... and more often.... potentially multiple times per week,Correction: hamsterman told me he was actually using prednisolone and not prednisone as he stated in the quote above. The former takes effect faster. Note that hamsterman said he has the autoimmune disease Crohn's, which causes has extreme fatigue, though thinks he may have ME/CFS as well. User gregh286 found prednisone will block PEM from appearing. How long for the corticosteroid PEM shield to kick in? Prednisone takes around 2.6 hours for the drug to reach peak levels in the bloodstream, whereas prednisolone is faster, taking only around 1.3 hours. Hydrocortisone takes around 1 to 2 hours. Ref: 1 So when taking any of these corticosteroids in advance to prevent PEM from a physical or mental exertion you are about to perform, give these drugs enough time to kick in before starting the exertion, else your PEM shield will not be in place. CAUTION: note that there are also timed release versions of prednisone, which only slowly release the drug into your system over several hours, so it might be best to avoid these. What is the dose equivalence of different corticosteroids? Difference corticosteroid drugs have different strengths: hydrocortisone 80 mg = prednisone 20 mg = prednisolone 20 mg = methylprednisolone 16 mg = triamcinolone 16 mg = dexamethasone 3 mg = betamethasone 2.4 mg. Source: here. How long does the corticosteroid PEM shield last? In terms of how long the "PEM shield" lasts, the plasma half-life of prednisone and prednisolone is 3 to 4 hours, and the plasma half-life of hydrocortisone is 2 hours. So once your "PEM shield" is active it will last for say one or two half-lives, ie, your PEM shield may last about 4 to 8 hours for prednisone and prednisolone, and last around 2 to 4 hours for hydrocortisone. When taking prednisone 20 mg, hamsterman found its PEM protection lasted for as long as 8 hours; but when he tried exercising 13 hours after his prednisone, then he crashed. So for a single 20 mg dose of prednisone, around 8 hours would seem the limit of its protective effects. Of course you could take a second 20 mg dose at the 8 hour point, and get another 8 hours of protection. Efficacy of the corticosteroid PEM shield. This is how effective hamsterman found a one-off dose of prednisolone 20 mg to be at completely eliminating PEM from a major physical workout at the gym hamsterman said: "Just as a side note, I've been using Prednisone once a week for about a year, and I've found its absolutely impossible to induce PEM while Im on these corticosteroids. I've really taken this to the limit.... doing crazy cardio... things that would normally cause severe multi-week PEM... and each time... nothing. I've also accidentally done a 'double-blind' test, when I accidentally took the wrong medication, and had severe PEM afterwards." Note that hamsterman was using prednisolone and not prednisone as he stated in the quote above. Interestingly enough, after doing this intense cardiovascular exercise once weekly for a year, courtesy of the PEM shielding provided by corticosteroids, hamsterman was able to completely cure his POTS (see here). But his ME/CFS has not improved through exercise. POTS is known to responds well to exercise, whereas ME/CFS does not. Corticosteroids may lead to major problems if taken daily for weeks in a row. If corticosteroids are used every day on a long term basis of weeks, this can lead to worsening of ME/CFS, perhaps because the immune suppression from the corticosteroids may allow any underlying infections to proliferate (corticosteroids reduce the antiviral Th1 response, reduce T-cell function, and increase the antibacterial Th2 response). See the warning in this post, which cautions against using prednisone for any extended period of time, and warns that the PEM protective effects do not work for the whole day, they seem to wear off after about 6 to 8 hours. Prednisone is a strong drug, and has sometimes caused adverse events in ME/CFS patients. Dr Chia says two ME/CFS patients who took prednisone daily for two weeks remarkably improved; but when they tapered off they got much worse, and ended up in the hospital. He believes it such extended use of corticosteroids allows enterovirus to proliferate. The mechanism by which corticosteroids provide a potent PEM shield may relate to their effects on energy metabolism and mitochondrial oxidative phosphorylation. Mitochondria possess a glucocorticoid receptor, and that receptor regulates oxidative phosphorylation. Refs: 1 2 Interestingly, the over-the-counter drug theophylline greatly potentiates the anti-inflammatory effects of corticosteroids. Ref: 1 In this study of adding theophylline to the corticosteroid regimen of asthma patients, they used a dose of 250 mg of theophylline daily. Theophylline also has a vasoconstriction effect, and is thus useful for POTS, to reduce blood pooling in the legs on standing. Whether theophylline would help ME/CFS patients get the same anti-PEM effects from lower doses of corticosteroids remains to be seenLow Dose Hydrocortisone: Flare Buster for Fibromyalgia and Chronic Fatigue Syndrome https://www.healthrising.org/blog/2021/02/15/low-dose-hydrocortisone-fibromyalgia-chronic-fatigue-syndrome Cortisol, our body’s main stress hormone, has an amazing reach. Given the effects it has on our metabolism, inflammation, blood pressure, blood sugar, energy production and even the sleep-wake cycle, it’s no surprise that researchers early on latched onto signs of cortisol problems in chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM). Even after concluding that low cortisol levels (hypocortisolism) are common (but not universal) in ME/CFS and FM, they have never let go of the subject. Decades after low cortisol levels were first found in the disease, they’re still investigating the role cortisol plays in ME/CFS and FM. A large, but flawed, recent study “General theory of inflammation: patient self-administration of hydrocortisone safely achieves superior control of hydrocortisone-responding disorders by matching dosage with symptom intensity” brought cortisol and hydrocortisone (Cortef – the drug used to boost cortisol levels) to the fore. The results suggested that using low-dose hydrocortisone to reduce flares was safe and effective in both diseases and  provided an opportunity to dig a bit deeper and check out what past studies have found and what some ME/CFS experts have said. The StudySternberg, the senior author of the paper, reported that when activated by stress, the HPA axis creates a time-delayed, 6-fold+ increased surge of hydrocortisone (cortisol) surge in the blood, which in about 4 hours terminates the inflammatory bout. As the HPA axis weakens and cortisol production declines, though, because of age, injury, and/or heredity, a short- term, beneficial inflammatory response can turn into chronic inflammation. Sternberg asserted that hydrocortisone is the only substance produced by the body which can effectively terminate chronic states of inflammation. When given in too large of amounts for extended periods of time, though, hydrocortisone administration could produce adverse effects. The authors repeatedly cited a 1957 paper, “Diagnosis, treatment and prevention of chronic hypercortisonism in patients with rheumatoid arthritis. (psu.edu)“, which stated that too much hydrocortisone produces symptoms such as “excessive appetite, weight gain, euphoria, insomnia, increased nervous tension and irritability, facial rounding, increase of fat pads, fluid retention, edema, irregular menses, acne and excessive hair growth. First the participants were given a food sensitivity test (not identified) and they monitored their symptoms for a week to establish a baseline. They also eliminated foods the laboratory test suggested were giving them problems. The study reported that a high percentage of FM patients improved while on low-dose hydrocortisone. I’s methods, though, left something to be desired. Next came a 2-4 week induction period in which daily doses of hydrocortisone tablets sufficient to achieve a “minimum symptom” state (75% reduction in symptoms) were taken once a day from 7-9 am. The authors reported that the participants ingested an average of 12 mg hydrocortisone per day – which is less, the authors asserted, than the 15 mg/day  which produces adverse effects in the most sensitive adults. The 15 mg/day dose rate was based on the 1957 study. The authors did not state, though, whether the 12 mgs/day occurred during the flare period or if it was an average of the doses taken during the induction and flare periods. Dose During Induction PeriodBody mass Week 1 Week 2 Week 3<68 kg 60 mg/day 40 mg/day 20 mg/day68 to 114 kg 80 60 40>114 kg 100 80 60 The doses provided in the 3-week induction phase were extremely high – up to five times higher, in fact, than the doses (25-35 mg/day) which produced adrenal suppression in a several month long ME/CFS study. (See below). These appear to be types of doses typically used to treat inflammation. Adrenal suppression occurs when the adrenal glands fail to produce normal amounts of cortisol often after a patient has been on higher levels of steroids. It is a serious matter and needs to be dealt with carefully. Since the authors did not determine if adrenal suppression had occurred we don’t know if 37 mg/day (<68 kg), or 48 mg.day (68-114kg), or 77 mg/day (!) (>114 kg) induced adrenal suppression over a shorter period of time (three weeks). While the authors reported that no symptoms suggestive of overdosing or adrenal suppression occurred the British Medical Journal Best Practices states that it can occur within 3 weeks. Approximately 15% of the participants failed to receive any significant benefits and were eliminated from the study.Those participants who failed to achieve a 75% reduction in symptoms, but did improve otherwise, repeated the induction period and were given a broad spectrum antibiotic called doxycycline for approximately six weeks. Stress management techniques (not identified) were provided to reduce symptoms flares. Flare reductionAfter the induction period, the hydrocortisone protocol was discontinued until a flare hit at which point the participants went on a 5-day “flare-quenching regimen” which consisted of taking a hydrocortisone tablet immediately and then from 7-9 am for the next four days at the following dosesDose for the 5-day flare-quenching regimenBody mass Day 1 Day 2 Day 3 Day 4 Day 5<68 kg 30 mg 20 mg 20 mg 20 mg 10 mg68 – 114 kg 40 30 20 20 10>114 kg 50 40 30 20 10 The patients were told to limit their “hydrocortisone booster use” to four times a month. This apparently meant 4 5-day flare-quenching hydrocortisone regimens a month – leaving, at the very least, 8-11 hydrocortisone holidays – which the authors asserted was enough avoid adrenal suppression. Those 8-11 days were enough “exercise” they felt for the adrenal gland to maintain health and keep producing cortisol. Patients who had trouble judging the beginning of a flare could, they felt, take hydrocortisone during the week and not on the weekends. The authors apparently feel that any flare must be hit hard as the recommended doses are quite high – and could easily lead to adrenal suppression if taken for very long.  If someone from 68-114kg. took the flare reducing dose five days a week for the entire month (as they recommend for some people) they would average 16 mg/day. Someone >114 kg would average 20 mg/day and possibly be flirting with adrenal suppression. It appears that most people, though, limited their hydrocortisone usage to lower amounts. If the patients experienced significant symptom improvements “during days in which no hydrocortisone was ingested (that is, when they were on a “hydrocortisone holiday”), a hydrocortisone blood test was done. If their blood hydrocortisone levels were “significantly below average” (no levels provided) they were given extra hydrocortisone. If evidence of too much hydrocortisone appeared (moon face and a hyper state), the patient’s dosage was assessed and the “appropriate action” was taken. The patients rated their symptoms using a 0-10 scale (not defined). ResultsNo less than 2,428 participants with over 30 diseases enrolled in the study. Eighty-one physicians from 20 states participated. With 601 participants in the trial, fibromyalgia was the most common disease assessed. Twenty-five people with ME/CFS also participated. Arthritis and chronic pain diseases were common. A mishmash of other diseases ranging from Parkinson’s to dementia, to multiple sclerosis, and asthma, were also included. Seventeen percent (n=413) of the participants did not improve, and 2,015 participants completed the study. For those who completed the trial, the authors reported an average symptom improvement rate of 76%. The authors reported that the fibromyalgia and chronic fatigue syndrome patients had a 77% and 78% symptom improvement rate, respectively.Remarkably – give the size of the study – no significant adverse reactions (weight gain, hypertension, gastrointestinal symptoms, insomnia, muscle pain or spasms, and hyperglycemia) were reported. Past StudiesA 3-month, 56-person, 1998 randomized, placebo-controlled, double-blinded CFS trial used hydrocortisone (13 mg/m2 of body surface area every morning and 3 mg/m2 every afternoon (approx. 25-35 mg/day). Although Wellness scores significantly improved in those taking the drug relative to placebo, about 20% of the participants showed signs of adrenal suppression.A 1-month, 32-person, 1999 randomized, crossover hydrocortisone trial found that low doses (5-10 mg) moderately reduced fatigue and resulted in almost 30% of the participants meeting normal fatigue scores. The authors concluded: “In some patients with chronic fatigue syndrome, low-dose hydrocortisone reduces fatigue levels in the short term.” Another 1-month, 32-person, 2001 double-blind, placebo-controlled crossover hydrocortisone trial produced the expected increase in urinary cortisol output. In most patients, the increase in cortisol did not impact symptoms, but in about a quarter, it produced a reduction in fatigue “to normal population levels“. Giving cortisol to those patients also resolved “a blunted response to a corticotropin-releasing hormone (CRH) challenge. The authors concluded that the low dose did not result in adrenal suppression. Dr. Myhill pointed out that the results were complicated by the fact that baseline cortisol levels did not predict who benefitted from the treatment, and that baseline levels were within normal reference ranges. The studies suggest that a subset of people with ME/CFS do respond well to a short-term (1 month) trial of low-dose hydrocortisone. The over-the-counter drug theophylline greatly potentiates the anti-inflammatory effects of corticosteroids ('Theophylline New Perspectives for an Old Drug' https://www.atsjournals.org/doi/full/10.1164/rccm.200210-1142PP) So possibly taking theophylline with corticosteroids may allow you to get the same anti-PEM effects at a lower corticosteroid dose. In this study where they added theophylline to the corticosteroid regimen of asthma patients, they used a dose of 250 mg of theophylline daily. Theophylline also has a vasoconstriction effect, and is thus useful for POTS, to reduce blood pooling in the legs on standing Note long term use may entail major side effects such as bone loss and diabetes (taken from 'Oral corticosteroids'
https://www.hse.ie/eng/health/az/c/corticosteroids/effects-of-corticosteroids.html Side effects of oral corticosteroids that are used on a short-term basis include:

• an increase in appetite,
• weight gain,
• insomnia,
• fluid retention, and
• mood changes, such as feeling irritable, or anxious.

 Side effects of oral corticosteroids used on a long-term basis (longer than three months) include:

• osteoporosis (fragile bones),
• hypertension (high blood pressure),
• diabetes,
• weight gain,
• increased vulnerability to infection,
• cataracts and glaucoma (eye disorders),
• thinning of the skin,
• bruising easily, and
• muscle weakness.

 Although such side effects are mostly observed with daily use, and in patients taking more than needed. For instance, Addison's patient don't necessary see all these side effects. Nor do thyroid patients who need hydrocortisone for adrenal fatigue. The latter patients find the right physiologic amount, not the high pharmacological amounts which can cause those side effects

 

 

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