A preliminary survey of 49 UK patients with CFIDS - 27 th march 2000

Patients
This survey consists of the records of all 49 patients to date in the UK who undertook the 'PETROVIC PROPRIETARY REGIMEN' of antioxidants and vitamin and mineral supplements. Owing to different starting times for different patients not all the patients have finished the course as yet. A final study will be done when all have finished. However the results are already conclusive.

PART I:- CONFIRMATION OF THE REGIMEN AS AN EFFECTIVE TREATMENT FOR CFIDS

The purpose of the survey was to confirm previous findings that the regimen was effective, and to see whether the results were affected by extraneous factors. In addition, a revised, more stringent, criterion was used to define recovery. In previous studies, recovery was defined as the time taken for the patient to feel very much better than before the treatment. This was found to be unsatisfactory, since many patients tended to stop further treatment as soon as they felt relatively better. The result was that these patients never fully recovered to a state of normalcy, and tended to relapse as soon as they started to overdo their energy expenditure. It is advised that the full 9 months course should be slavishly followed by all patients to ensure complete recovery to a normal state. In addition it is essential that NO other ingredients be added to the protocol during this period. As experience has shown that these all have a detrimental effect on the regimen..

In this survey only the effect of antidepressants on the recovery was considered, and the data examined statistically. In future other factors will be investigated as well.

The following additional factors need to be considered:

RESULTS

Considering all 49 patients we get the following results:

Gender.
There were 24 male and 25 female patients. This was different from previous surveys where there was a preponderance of females. From the statistics, it is suspected that one patient out of the 49 was mis-diagnosed and was not suffering from CFIDS at all. She was nevertheless included in the statistical study, in absence of proof of the conjecture.

Ages.
These ranged from 18 to 73 years. Average = 38.6 and s.d. = 13.6

Years of Suffering
This time is recorded as the time since the patient was diagnosed by an independent medical practitioner. The times ranged from 1 to 36 years. (Obviously the latter was from hindsight because the disease was not officially recognized before 1993 as a disease entity, but was considered a psychosomatic malady.) Average = 8.8 S.D. = 7.7 s.e.m.= 1.1

It is important to note that the disease has been recognized as such since at least 1993. However, many medical practitioners still regard it as largely psychosomatic and treat it as such. The Australians however, have shown it to be a set of at least seven different organic diseases, which can be differentiated by different excretory patterns of mainly organic acids in the urine. They have also diagnosed at least seven different disorders all called CFIDS by a study of lipids in blood and also lipids excreted in faeces. They have not yet shown a correlation between the urinary profiles and the lipid profiles so it is not yet known if there are only seven types or more. This state of affairs makes it very difficult to design a cure for the syndrome since it can be expected that each disease would require a different treatment. Nevertheless a very effective treatment appears to have been devised by Dr Petrovic in South Africa which has been tried on a very large number of patients all over the world with phenomenal success.

The UK patients show that a double blind trial would not prove anything new because the psychosomatic effect has already been eliminated , in that the patients previously had great faith in their doctors when first starting conventional treatments and the `so called` placebo effect of the Petrovic regimen would have been eliminated by the failure of conventional treatments, so that the patients, almost without exception , approached the Petrovic regimen with a great deal of scepticism because of their previous experience with treatment. They could not believe that anything could do them any good since everything they had previously tried was a failure. They expected this regimen to fail also and hence from a psychological point of view, the regimen was at a disadvantage.

COMPLIANCE

The recommended length of the course is 9 months; 2months of initial treatment followed by 7 months of follow-up. However for various reasons many patients failed to take the full course. (See below). Forty eight of the 49 patients took more than 2 months of the full treatment and 45 of them (93.8%)showed an initial response after an average of 2.3 months, (range 0.25 to 9 months). Only 22 patients have been completely cured to date after an average of (7.1 months, range is 4 to 14 months ) with 12 others who started later still continuing the treatment( after 2 to 7 months, average 4.8 months) and improving steadily. Thirteen patients stopped the treatment prematurely (average 3.7 months Range 1 to 6 months), presumably mainly because of impatience with the slowness of their full recovery, although 2 patients admitted financial difficulties.

TIME FOR INITIAL RESPONSE

The initial response time was defined as the time to THE FIRST MAJOR IMPROVEMENT noted. This is very subjective and each patient has his/her own criteria for determining this time. However, there is a remarkable uniformity in the results among the patients with no extraneous problems (this being defined as either having intercurrent maladies or taking antidepressants), with a standard deviation for individual assessments of only 0.7 month, and a range of 0.5 to 2 months. The 99% confidence limits of the average of 1.25 months are from 0.6 to 1.9 months. This means that if we were to measure a large number averages on groups of12 0r more patients 99% of the averages would fall between these limits.

Out of the 49 patients who embarked on the regimen, 48 had two months of full treatment and 13 stopped before completing the full nine months specified, and hence failed to recover even though 45 (93.8%) of them had shown an INITIAL RESPONSE after an average of only 2.3 months. This is a remarkable response rate in spite of ignoring information gleaned later from the results concerning the effects of antidepressants. This indicates that the regimen is very beneficial against the malady, in agreement with previous findings on South African patients. The failure of patients to persist with the treatment is attributed to a misunderstanding on the part of patients who expected to be cured in a few days whereas the previous studies had only shown that a marked improvement was noted in the South African patients after about 9 days. This was then (in the 1996 report) called a recovery which was interpreted as a cure by patients and hence their disappointment, which led to abandonment of the treatment prematurely. This reaction of patients reinforces the concept that the regimen was viewed with scepticism by the UK patients.

RECOVERY RATE OF ALL PATIENTS

Of the 49 patients who took the protocol, only 22 finished the course. There were various reasons for this problem, but it was impossible to include the ones who dropped out in the statistical survey since that is mathematically incorrect. In order to test a procedure, the patients must comply exactly with the procedure. Hence an analysis was done on the 22 patients who completed the course. Fourteen other patients who started later , are still taking the course and are recovering normally. The latter were not included in the calculations at this stage.

Analysis of the relevant 22 patients showed that all of them recovered fully (100%). The average time to recovery was 6.8 months (Range = 4 to 14 months). In the light of later analyses, this recovery time was corrected, by eliminating the effects of the antidepressants to yield a recovery time of normal CFIDS patients of 5.3 months (range = 4 to 8 months),(see below). The 95% confidence limits of this average are 4.8 to 5.8 months and the standard deviation of the average is 0.5 months which means that 95% of patients will recover between 4.4 and 9.7 months if there are no extraneous problems.

CONCLUSION

The Petrovic protocol is an effective cure for CFIDS

PART II:- EFFECT OF ANTIDEPRESSANTS ON RECOVERY TIME
TIME FOR COMPLETE RECOVERY

On consideration of all these patients, it was found that only 24 (49%) of them had no extraneous problems, and only 13 patients (54%) of this group completed the course and all of them (100%) were cured in an average of 5.3 months There were 14 (28.6%) of the 49 who had used or were using antidepressants. Of these 7 completed the course and completely recovered. One of the 14 was addicted to amitriptyline and suffered psychological crises on trying to stop the use ( withdrawal symptoms). She was advised by her `carer' to continue on the amitriptyline and abandon the treatment after 5 months. From the results on the other patients, this seems to have been bad advice, on hindsight, and she would probably have done better to first get rid of the amitriptyline and then finish the treatment. There is a great probability that she then would have been completely cured within 1 year, in spite of her previous use of the antidepressant.

The two groups who finished the regimen, even though they might or might not have been using antidepressants, were compared using the unpaired t-test. The results were:

a) 13 patients who finished the course and had no extraneous problems compared with
b) 7 patients who finished the course but were using, or had been using, antidepressants
For a), the average time to partial recovery = 1 month s.d. = 0.7 month range 0.25 to 2 months
.for b), the average time to partial recovery = 5.1 months s.d. = 4.0 months range = 0.3 to 10 months.
For a) the average time for full recovery = 5.3 moths s.d. = 1 months range = 4 to 8 months.
For b) the average time for full recovery = 10.1 months s.d. = 2.3 months range = 7 to 14 months

Unpaired t-test for partial recovery gives P = 0.0017 (18 degrees of freedom*)which is highly significant.
Unpaired t-test for full recovery gives P < 0.00005 (18 degrees of freedom*) which is conclusive.
* Note on significance

In comparing averages, a measure , t, is used which represents the ratio of the differences between the averages to the standard deviation of the difference. Student, in his classic paper of 1908 (Biometrika, IV, 1-25 ) who first revealed the properties of this measure together with a table showing the chances that various limiting values of t would be exceeded if both sets came from the same source, i.e. if the averages were actually not different from each other , taking into account the natural errors of measurement. "Before Student, only limiting values of t for infinite sets were known and this accounts for the early insistence on 'large samples' for the application of statistical procedures . When the degrees of freedom are a dozen or more. The critical values are not seriously larger than those which hold for infinite sets". (See Youden- Statistical methods for Chemists 1951 pp25,27. John Wiley and Sons, Inc. Canada)

Hence it is possible to get reliable comparisons if each average is from a set of only 7 or more observations giving 12 or more degrees of freedom.

The value of P given is the probability that the two averages actually are identical, with a value of 1 meaning that they are certainly the same and a value of 0 meaning they are certainly different.

CONCLUSION
Hence we conclude that patients who were taking or had taken anti-depressants shortly before or during the Petrovic regimen, { the anti-depressants include both Prozac and Amitriptyline.} experience a very long delay in their recovery (nearly double the time) which is conclusively adverse. It is therefore recommended that any patient who is taking these anti- depressants before treatment should first stop all use of these drugs and get over the withdrawal symptoms if they exist, before embarking on the Petrovic Regimen. If the patient is unable to comply with this requirement owing to dependancy on the drug, it is advised that the patient reduce the usage as much as possible before embarking on the protocol. He/she should then expect that the time before a complete cure is achieved will be greatly increased, even extending as long as 16 or more months. If during the treatment the patient succeeds in stopping the use of the drug or reducing use significantly, the rate of cure will correspondingly increase. This requirement should not discourage patients from taking the regimen because there is no other cure yet known, and no patient should be willing to remain in the grip of this disease any longer than necessary while trying out other useless methods which have not shown any hope of a permanent cure.

Other factors which affect the recovery will be studied in another survey.

The ability of the Petrovic protocol to affect a cure for CFIDS has been confirmed and a partial explanation for the variability of results with different patients has emerged, in the very large effect of anti-depressants..

PART III:- COMPARISON OF THE PETROVIC REGIMEN WITH OTHER TREATMENTS

Conventional treatments
The fact that patients on these, had been suffering despite treatment for an average of 8.8years, indicates that there has been no real accepted cure for the syndrome to date. If there had been one known, then medical practitioners would have used it to cure patients. The treatments used were actually only palliative, and many of the patients have actually paid a lot of money for nothing. The use of antidepressants appears now to be without benefit to patients except perhaps psychologically.

Ampligen Treatment
The NCF report (national CFIDS Foundation/ USA) may be viewed on the internet on:
http//www.abcjb.com/news/ncf reports on ampligen.htm The effectiveness of this treatment against CFIDS is very dubious. Although synthetic RNA derivatives have hypothetical anti-viral effects, there is no conclusive proof that CFIDS is always of viral origin. Where the CFIDS might have been of viral origin, there is no proof that Ampligen can reverse the damage, even though it may kill the virus. Patients using Ampligen report very limited benefits and almost 90% of the patients reported relapsing and the disappearance of the temporary limited benefits as soon as they discontinued the Ampligen treatment, according to the report by Dr Cheney.

Costs of treatments.
The current cost of the Ampligen treatment is 5000 pounds sterling for a 5 month treatment plus doctor's fees . By comparison, the Petrovic regimen costs 1450 pounds sterling (or 1350 for patients on disability) for the first five months plus 1300(1200 for those on disability) pounds sterling for the next six follow -up months total of 2750(or 2550) pounds sterling for the whole 11 months of the course. Normally it is not necessary to continue for more than 9 months. The price also includes the one hundred pound courier service for transport of the protocol and free doctor's advice and encouragement throughout the course. This is a highly competitive price in the light of the fact that the Petrovic protocol is the only known curative procedure for CFIDS with the potential to save the economy of a country millions of pounds as a result of preventing lost man-hours of work in the normally economically active population, especially since it is estimated that as much as 10% of this population suffers from the malady.

Conjecture on Mechanism of the Protocol

The protocol was designed on the hypothesis that CFIDS is caused by an excess of free radicals which may be mainly in the liver as a result of xenobiotic (strange to the body) substances (including various medicinal substances or poisons such as insecticides, or cleaning materials, e.g. carbon tetrachloride, or even excess alcohol consumption which are all oxidized and generate these free radicals. The danger of free radicals is that they set up a chain reaction of oxidations which attack the membranes of the cells and disrupt their proper functioning. The hypothesis is partly corroborated by the change in excretory products observed by the Australian team in their three bioscreen tests. What is then required, is that these membranes should be restored.. The protocol is designed to do just that. However, unless the cell is almost completely restored, it still cannot function properly and presumably, the CFIDS will persist. Theoretically, the full list of 92 substances required for cell synthesis ( Dr Wallach) should be supplied simultaneously in the right proportions, else the supplements will be excreted without doing their job properly.
The interference, by anti-depressants, with the recovery process, as proved in this article, may be explained by the fact that extra stress is being put on the liver during the body's attempt to rebuild the cells and this could lead to a delay in recovery. In some cases it could prevent recovery altogether. This hypothesis leads to the conjecture that there are many more substances which could cause the same effects, and hence the intention to investigate this in future research, as mentioned in the introduction.

Normally, the body is able to process a limited amount of xenobiotic substances by destroying the free radicals produced before they cause any damage. But if the system is overloaded for any reason, CFIDS may develop. The overload may result from many causes but probably does not have a single cause as is manifest from the many different aetiologies seen in patients.

Abstract

Of the 48 patients who took up to 3 months of the full treatment, 45(93.8%) responded to the regimen after an average of 2.3 months.
Patients tended to stop the regimen after this initial response, apparently because of a mistaken idea that they were fully recovered or they would not recover further. There were 24 patients who had no extraneous problems such as intercurrent diseases but only 13 of these patients completed the course. All of these 13, who had not taken antidepressants and also had no other complications recovered fully (100%). Average time to recovery was 5.3 months. On the other hand there were 14 patients who were using or had used antidepressants and only 7 of these fully recovered ( 50%).

At this stage there are still 12 patients not taking antidepressants, continuing to take the regimen after an average of 4.8 months (4-7), and are recovering normally. They only started later than the others. A further 3 patients are still using antidepressants and are continuing the regimen after an average of 8 months. The latter patients should be advised to stop all antidepressants, which would speed up their recovery.
It is still too early to determine the permanence of the recovery from the figures gleaned from this survey,( one patient, E.M., has now been stable for 2 and a half years being very active without any relapse, and from experience with the South African patients, it is probable that the other UK patients will experience the same results as those from South Africa where there have been no relapses yet after as long as 5 years from the end of treatment.

Of the UK patients one (C.D) experienced a slight relapse when she was treated with large doses of corticosteroids for her endometriosis before full recovery from CFIDS. However, as soon as the corticosteroids were stopped , the patient went on to a full recovery from CFIDS.
We conclude that both Prozac and Amitriptyline (antidepressants) as well as possibly corticosteroids, taken during the regimen, drastically delay recovery from CFIDS .

T.A.Kilroe-Smith
Medical Scientist No. 0006688; March 27, 2000
email address kilroe@hotmail.com
Postal address:
P.O.Box 266
Bromhof,
2154
Republic of South Africa

Comments on the Petrovic protocol for treatment of CFIDS

This protocol has been used, starting in South Africa in 1993, all over the world including USA, UK, Canada, and Australia.. It has met with constant opposition from all sorts of sources because it was difficult to believe that such a protocol could be unique in healing the malady. However, with at least 250 successfully treated patients, it is difficult to gainsay the effectiveness of the treatment. Other practitioners have also devised protocols of anti-oxidants and supplements but have had lesser success rates compared to the Petrovic result of over 90%. In my latest analysis of the protocol used on UK patients a very important result has surfaced showing why the success rate is not always 100%. It appears that the protocol is very carefully balanced, and the addition of other factors to the protocol can adversely affect the results. Even non-compliance with the laid down procedure in not taking the supplements in the quantities specified can lead to a complete failure to recover.

Dr Petrovic has devised the protocol by several years of careful observation of patients coupled with wide reading of the literature and logical deductions in the light of known biochemistry. The exact quantities seem to be important since patients who do not follow the protocol as laid down, do not recover so readily. Obviously, further factors may come to light which may lead to a modification of the protocol in future, especially in the light of bioscreening to determine from which type of CFIDS the patient suffers. However since there is no better treatment now available patients will have to make do with what is available.

There should be no objection to this, since recovery is mostly complete and the patients are able to lead normal lives again after recovery.

Although Dr Petrovic is not willing, for obvious reasons, to divulge the exact composition of his protocol to the world in general, nevertheless, I have found that his research results are not to be questioned. I have examined his stock-room of ingredients and have found nothing other than what he says is in the protocol. There is no substance/s present in amounts which could produce adverse toxic effects. This is only to be expected since Dr Petrovic is a medical doctor(MD.) who has taken the Hippocratic oath. In fact, experience with the patients whom I have interviewed in South Africa shows that all of them have experienced only beneficial effects from the protocol.

I have not heard of any other protocol which claims and has proved the same beneficial effects on CFIDS patients.

Signed: T.A.Kilroe-Smith

T.A.Kilroe-Smith
Medical Scientist No. 0006688; March 27, 2000
email address kilroe@hotmail.com
Postal address:
P.O.Box 266
Bromhof,
2154
Republic of South Africa