Talk:ME/CFS treatments

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Contents 1 Hydrocortisone 2 Lipid replacement therapy 2.1 Mitochondria enhancement 2.1.1 Enhancement using phospholipids 2.1.2 Enhancement using D-Ribose 3 CFS, diet and supplements 4 Thymic Protein 5 ref section for convenience, please keep on bottom of talk page

[edit] Hydrocortisone

There does need to be some discussion on the current Article and recent edit which I have corrected. As the reference which attached to this new comment was actually a combined treatment so conclusion on hydrocortisone treatment amounts used in this trial (when used alone) cannot be drawn from that study.

A review article not referenced previously I think gives a better comparision. I quote from the text of the free Article; The first, by McKenzie et al. (PMID 9757853), prescribed hydrocortisone in a pattern approximating the normal diurnal variation in cortisol [13 mg/m2 (about 20–30 mg) at 0800 and 3 mg/m2 (about 5 mg) at 1400, daily]. Seventy patients with CDC-defined CFS, many with comorbid psychiatric diagnoses, received either active or placebo treatment for 3 months. There was a moderate but significant benefit on a global health scale, although not on other more specific measures of fatigue or disability. However, there was significant adrenal suppression in 12 of 33 patients on hydrocortisone. A second study (PMID 9989716) used much lower doses of 5–10 mg, chosen to represent a dose likely to replace the observed reduction of approximately 30% in 24-h UFC seen in previous studies. Thirty-two subjects entered a cross-over study, with 28 d on each treatment. There was a clinically significant fall in fatigue scores in 34% on active treatment (28% returning to levels of fatigue at or below the population median score), compared with 13% (9%) on placebo. There were large reductions in self-rated disability scores in those whose fatigue improved. Furthermore, on this dose of hydrocortisone, there was no significant adrenal suppression, and there were no serious adverse effects. ------However, the second treatment study (PMID 9989716) was short term only, and the positive effects wore off rapidly on the switch to placebo; thus, routine use of this strategy as a treatment is not recommended without further evaluation. PMID 12700181

There are several problems with this review, firstly the author reviews his own study and secondly the use of co-morbid patients in the first study does not necessarily relate and give comparrision to all CFS groups, therefore the need to give more details in the Article.

There has been some study more recently by Cleare and co. (presumably using tertiary referral patients again) to try and show cortisol basis of patients. PMID 15922454 PMID 16439267 The selection basis of patients may explain the different trial findings? Jagra (talk) 05:14, 24 April 2008 (UTC)

I added more details in the Article of the co-morbid study to clarify matters. I do believe it is an important research and there are lots of extra details that need to be added to fully understand all his points in the review of all the previous articles, such as showing that long term use of low-dose HC does not induce bone-loss, adrenal suppression or immune suppression, as he shows in a long discussion. But in this encyclopedia article, I tried to make it as short as possible (though quite unsuccessfully). If you can make it even shorter without removing the reference it would be ok in my opinion. Regarding the review you mentioned feel free to add it but I feel this section is already too long and it's better to review only the latest articles. Mathityahu (talk) 13:18, 24 April 2008 (UTC)

The J of CFS is generally considered Wp:RS and that particular reveiw appears to have been comprohensive and well referenced, although it does not mention the adrenal suppression in the McKenzie trial so your comments on safety of HC use are his POV. To shorten to the basics and allow readers to inspect sources further is the aim.

I have removed the following from the text as it is unsourced "The study mentioned in the review had been a multi-faceted approach including a complex treatment protocol in which cortisol was only a part, was performed on over 4000 patients, and demonstrated that 85% of patients improved by the 4th visit. The author notes that "cortisol supplementation was shown to be a beneficial and safe therapeutic intervention with little or no risk." Much more detail would be needed to include this statement.Jagra (talk) 01:19, 25 April 2008 (UTC)

OK. As you said "To shorten to the basics and allow readers to inspect sources further is the aim." and I agree. Mathityahu (talk) 08:30, 25 April 2008 (UTC)

[edit] Lipid replacement therapy

This is actually Essential fatty acid treatment, which is covered lower in the Article. Also we have in past only included studies that are RCT's There are just too many pilot studies to take seriously. Please provide a link to the Article you referenced or PMID numbers on this page so that the details can be verified. Suggest you use Diberri's tool in future and it will automatically provide links. For any such as the J of CFS (referenced in hydrocortisone above) and not on pubmed it would be advisable to provide a link to the paper here also.Jagra (talk) 10:04, 24 April 2008 (UTC)

I added links to everything. I believe that including pilot studies showing good results is much better than the current state of the article, of including studies that are unknown in effectiveness. If you know of other pilot studies I'd be delighted to add them.

I believe the section of fatty acids treatment should be removed as it is unknown in effectiveness and treatment is different than that of that in the phospholipids section (omega-3 is not phospholipids). I added a section about mitochondria treatments with the latest results (also d-ribose treatment). I don't think there's a place for old articles with unknown effectiveness.

Mathityahu (talk) 13:19, 24 April 2008 (UTC)

I suggest you read the Talk page and Archives of the Main Article CFS for a better understanding of exactly what is and is not acceptable here. Yes the Essential fatty acid section can be improved but not with the edits you have provided for reasons given below. I have removed the following edit to this page for discussion and make comments below. Omega 3 efa's are incorporated naturally into phospholipids , suggest you do some reading, before pontificating further. Jagra (talk) 01:58, 25 April 2008 (UTC)

[edit] Mitochondria enhancement

[edit] Enhancement using phospholipids

A cell’s functional capacity can be measured, in part, by the fluidity of its membranes and its cell-to-cell communication capacity. One of the most common forms of cell damage is created by free radicals, which reduce membrane fluidity, cell communication, and cell to cell function. Protecting cell membrane integrity is thought to enhance cellular health, energy and efficient metabolism. Preventing loss of membrane integrity due to damaged components and the resultant loss of cellular energy may be accomplished, in part, by replacement of damaged lipids. It has been shown that a treatment with a dietary supplement rich in phospholipids lowers fatigue by an average of 33%, after 8 weeks. ^{[1] [2]}

[edit] Enhancement using D-Ribose

D-Ribose is a key molecule in the energy creation process in the mitochondria. In a place-controlled, double-blind study of supplementing D-ribose, 66% of patients have improved, energy levels have rised by 45% and there was an overall improvement of 30% in the patients. ^[3]

COMMENTS

Paper by Nicholson J of CFS on Lipid replacement: from the link provided,

- Appears to be not a reveiw but report on own trial only.

- No details on patient selection criteria given

- No mention of controls in trial

- No patient numbers or statistics

- No details of placebo, if any?

If you can provide these details by direct quotes from paper, and they are satisfactory, it will be considered further

J of CFS paper 2003;

- Trial is not with criteria defined CFS but with "fatigued aged'

- Not an RCT trial

- 20 only patients without controls cannot be statistically relevant

PMID 17109576 An uncontrolled pilot study, numbers unlikely to be statistically significant. Interesting but these referenced do not cut the Article grade.

This is a suitable page for discussion of recent trials and other users can read or comment further. Jagra (talk) 01:58, 25 April 2008 (UTC)

I cannot bring other studies, that's what I have. Although I do believe these sections are better than the other sections currently in the article, with the "unknown effectiveness". Mathityahu (talk) 08:30, 25 April 2008 (UTC)

You are correct it is not a right conclusion regarding EFA treatments, we have consensus on that, but we do not need uncontrolled studies to show this. There are RCT's that demonstrate reproducability for this treatment in certain CFS subgroups. It is unfortunate that certain reveiwers did not research the literature adequately before reaching their POV conclusion. It was also unfortunate that others selected a placebo that in their own paper they admitted was questionable. It is also questionable to compare trial results between different subgroups without mentioning that. It is necessary in order to show WP:NPOV that we bring this out, but in doing so we can only report what others have said, that is why the detail in studies and reveiws is important. I will address this in the near future. Jagra (talk) 10:46, 25 April 2008 (UTC)

[edit] CFS, diet and supplements

Thank you. I think that when addressing this issue of CFS treatments/diet, it would be helpful for the readers to separate those findings of articles that have been shown to improve patients clinically (that is, improve symptoms) and the articles that improve only the biochemical blood/urine/saliva testing. Also I think that "logical" suggestions of what to eat(even if well referenced) should be separated from those that have a proven clinical value (not only biochemical). Mathityahu (talk) 06:33, 27 April 2008 (UTC)

Well, An RCT trial is unlikely to be of value unless patients improve! Reason biochemical tests are sought is that patient reported improvement is a subjective test and objective tests are needed in CFS to both confirm trial results and for possible diagnostic use. A trial that has both is better than one without. When it comes to diet in CFS this is a very under researched aspect, see ME/CFS controversies regarding research funding issues. Frankly so is expecting supplements to have effect before adjusting basic diet parameters, just not scientific. For instance the calcium / magnesium ratio (Ca2+/Mg2+) is considered to be an important guide for signs of peripheral vasoconstriction and or spasm and possibly enhanced atherogenesis. Overall, the data point to important uses for IMg2+ in the diagnosis and treatment of disease states. PMID 7939386. However there are some supplements where RCT's have been conducted and I will address this in near future, Even a small RCT trial is a useful indicator of likely effectiveness, than uncontrolled studies, no matter how large. Jagra (talk) 03:42, 28 April 2008 (UTC)

Regarding Magnesium supplements:This article at present includes the words “magnesium treatments in dietary supplements having "unknown effectiveness”” This 2000 year review however does not compare different RCT’s but rather an RCT showing benefit with three papers showing no magnesium deficiency findings! In doing so it was selective in which findings it chose to quote and ignored other findings of lowered magnesium status in CFS including:

This review also in 2000 tabulates the findings of 9 studies to the same period with more balance and concludes; that overall they show marginal magnesium deficiency in CFS. Regarding the RCT treatment trials it says; ‘Perhaps the best clinical study to date involved patients with low erythrocyte magnesium levels who randomly received 100 mg magnesium IM or placebo each week for six weeks. “Twelve of the 15 patients who received magnesium felt better compared to only three of the 17 patients who received placebo. Moreover, erythrocyte magnesium levels returned to normal in all of the patients receiving magnesium, but in only one patient who received placebo. These findings are consistent with a report that CFS patients who were not magnesium-deficient failed to benefit from an injection of 580 mg magnesium, six times the dosage received by the group of magnesium deficient patients. PMID 1352002” That is one of the three ref’s used by Reid to discount the Cox study! It stands to reason those patients not magnesium deficient recorded no benefit from magnesium supplementation, but this does not indicate unknown effectiveness in patients with known deficiency, when an RCT indicates otherwise.

Since that time several studies have found lowered magnesium status in CFS; PMID 12745627 serum magnesium, PMID 10872900 found low magnesium in 47% and “Mg supplementation was followed by an improvement in Mg body stores,” One reveiw since PMID 12410623 concludes IV magnesium in a mixture is of value, other reveiws since like PMID 12030424, and PMID 12635882 consider that there is magnesium deficiency in CFS. There is also more recent evidence of altered magnesium metabolism in CFS, PMID 16405742. If we are to include reviews comparing RCT’s with only negative study findings then for NPOV we need to include other reveiws that compare same RCT's with findings. On balance it seems the Reid review is at best dated. Jagra (talk) 03:50, 29 April 2008 (UTC)

Regarding Carnitine; there have now been 3 RCT's finding benefit for this supplement in CFS. Werbach comments that Plioplys (author of first study) believes only one-third of CFS patients are carnitine responders. Of the responders, some improve so dramatically that, even if they were fully disabled initially, they return to normal functioning and remain well if they continue taking the supplement. Unfortunately, he found that pretesting of baseline serum levels of L-carnitine failed to predict who would respond. Possibly subgroup differences may effect responses? Response rates have been higher in the subsequent trials (50 to 60% on some parameters).Jagra (talk) 01:49, 30 April 2008 (UTC)

One RCT has been conducted on a polynutrient (multi-vitamin, mineral and enzyme) supplement in CDC defined patients, but no significant differences were found between the placebo and the treated group on any of the outcome measures used. The trial concludes that the findings do not support the use of a broad-spectrum nutritional supplement in treating CFS-related symptoms. PMID 12324640

However no testing was carried out either before or after the trial to assess deficiencies, marginal or otherwise and so conclusions cannot be drawn from this result on whether such low doses could correct deficiences in patients or whether or not correction of deficiences is of benefit in treatment of CFS. Jagra (talk) 07:19, 30 April 2008 (UTC)

[edit] Thymic Protein

Please see whether this thymic study article fits the criteria to be mentioned in wikipedia Mathityahu (talk) 06:43, 27 April 2008 (UTC)

1) The J of Nutrition and Environmental Medicine is not listed by the US National Library of Medicine and indicates it not likely a WP:RS reliable source.

2) Not a Controlled trial.

3) Paper alludes to Fukuda 1994 CFS definition but does not specifically say patients selected to this criteria, there is no seperate CFIDS criteria.

4) Abstract says 16 out of 23 patients improved, this is clearly misleading as 36 patients were enrolled in the study. 13 patients (36%) dropped out due to "unpleasant effects" but are not counted in results so statistics are skewed and would certainly alter the significance of results if included properly. How many improved due to placebo effect?

5) Papers conclusion that a RCT is needed to properly evaluate this treatment is correct, and we shall await a proper trial before considering inclusion.

Jagra (talk) 03:42, 28 April 2008 (UTC)

[edit] ref section for convenience, please keep on bottom of talk page

Jagra (talk) 10:56, 25 April 2008 (UTC)