People want to learn as much as possible from the PACE trial for chronic fatigue syndrome

By 1975 I was experiencing many health problems which my doctor was unable to explain or treat effectively, so I decided to study them myself. 
I began by purchasing a small Reader’s Digest book which presented the range of diseases in an A-Z format, where I found that my symptoms were only consistent with one ailment which was called Da Costa’s syndrome. 
I later decided to try treating those problems by exercising so I enrolled in an exercise program at a fitness research institute.

While I was training my aerobic capacity was being scientifically measured at the start and at twelve weekly intervals and was found to be abnormally low, and to improve in the first period, and then even out below normal levels. 
I later asked one of the research staff to tell me the formal name of the ailment, and he said that it was “neurocirculatory asthenia”.

I then began using Index Medicus at the Adelaide University library to study research papers on that topic. 
In 1982 the head of that institute invited me to design and co-ordinate a research project for that condition. It revealed that other patients also had a lower aerobic capacity than normal, which explained the fatigue, and established scientific evidence of a physical cause.

A few more years went by when I heard a radio report about a supposedly new illness called “The chronic fatigue syndrome”, but it was just another label for the same ailment.


Since then I have found that it had been given more than 100 different labels during the past 140 years. 
For example, effort syndrome referred to the abnormal response to exertion, anxiety neurosis and anxiety state referred to the ideas of psychological cause, and post-viral syndrome referred to the possibility of a virus being the cause etc. 
When a researcher suggests a new label a lot of old Ideas and evidence are discarded and forgotten, especially if they involve obscure terminology which the average person can’t pronounce or remember. 
However, the new definition then comes under the same sort of criticism where contradiction and confusion continues.


Nevertheless, my symptoms have not changed except for the fact that I have gradually determined what aggravates them and how to control them so that, apart from my limitations, they are no longer a problem. 
I will therefore present a definition which is clear and consistent. If anyone wishes to provide a different one, it won’t change, but will relate to a variation of the ailment, or an entirely different condition.

The Banfield Definition of CFS . . .


The word “chronic” refers to anything which exists and or recurs for a long time, and fatigue has two meanings.

First, tiredness, and second, the exhaustion associated with physical exertion. The word syndrome refers to any ailment which has a set of symptoms, rather than just one. Hence the chronic fatigue syndrome refers to a long term illness which involves several symptoms where abnormal fatigue is the main one.


They include . . .

1 . . . Lower left-sided chest pain which is generally described as a stabbing or lancinating sensation.

It feels as if as if a sewing needle has been stabbed into the left side of the chest between the lower ribs, and proceeds to a depth of about four centimetres and darts out again, all in a fraction of a second. Similar pains can sometimes occur on the opposite side, and in other parts of the chest wall, and occur occasionally, for example, once every few months. There have also been reports of a small area of tenderness at the same location on the left side.


2 . . . Palpitations. This is a more forceful beating of the heart than usual, and occurs occasionally.


3 . . . Breathlessness.This is a very distinct form of breathlessness which involves a sensation of difficulty breathing inwards, as if against an obstruction at the end of inhalation. It can occasionally occur at rest, but becomes more frequent during exercise and as the level of exercise increases. It is associated with an abnormal spasm of the diaphragm which is the main breathing muscle.


4 . . . Abnormal fatigue which includes two types . . .

(a) The first type is related to tiredness, and involves waking several times during the night, waking up tired in the morning, and being tired several times throughout the day. It is probably due to inefficient blood flow to the brain, and is associated with occasional difficulty concentrating.

 (b) The second type of fatigue relates to exertion. Severe cases may involve abnormal responses to low levels of exertion. However, in most cases, if the individual is at rest or exerting at basic levels they may not experience any symptoms, or may only have occasional mild problems.

Nevertheless, as the level of exercise increases the physiological responses increase out of proportion to that increase. The symptoms involve an abnormal pulse rate and a periodic sense of breathlessness with relatively moderate levels of exertion, and more so with higher levels such as sprinting or running.

There may also be limits to aerobic capacity where the symptoms associated with exceeding those limits impels the person to stop and rest, and may result in the after effect of exhaustion accompanied by alertness and delayed recovery. The sense of alertness is comparable to that which occurs after drinking too much coffee. The fatigue also relates to various aspects of lifestyle.


5 . . . Faintness and, or dizziness which occasionally occurs when moving from the laying to the standing position, and when exercising at too high a level, again due to inefficient blood flow.


6 . . . Upper abdominal pain in an area the size of a 20 cent piece just below the tip of the sternum, which is aggravated by mild pressure applied by a finger or knuckle.

Addendum

Other symptoms may include a tendency to sore throats, coughs, and colds, and neck and back aches, headaches, and kidney aches etc.

Furthermore, some individuals report muscular aches and pains, and may have a variation of the ailment, or an entirely different condition, particularly those whose more general responses to physical exertion are normal.


Also, if the individual only has one or two symptoms such as chest pains and palpitations, they may not necessarily have the chronic fatigue syndrome. 
However, if there is a combination of the typical breathlessness, occasional faintness when moving from the laying to the standing position, abnormal tiredness, reduced aerobics capacity, and an abnormal response to exertion, then they probably do, as they are the core aspects which are essential to identifying the ailment, and distinguishing it from others.

When I was a teenager I played a lot of sport, and ran in athletic events such as the hurdles, the mile, and the cross country. I also learnt to swim, and I was involved in gymnastics where a wide range of activities included somersaulting from mats, springboards, or trampolines. I was also an instructor where I needed to take into account the varying abilities of younger gymnasts in relation to their age and experience. I didn’t know anything about medicine, but did occasionally suggest modifying exercise for those who were overweight or had asthma etc. I generally recommended that such individuals do what they could, but not be too concerned about keeping up with other members of the group.

However, by the age of 25 I had gradually become more easily fatigued by relatively minor exercise for other reasons.

My doctor was unable to diagnose the cause, and none of the medications were relieving the symptoms, so I decided to study the problem myself.

I considered the possibility that gradually improving my fitness might improve my health, and about a year later, in 1976, I heard about a medically based fitness research organisation called the South Australian Institute for Fitness Research and Training, so I enrolled in one of their courses.

As part of the training each person was medically examined to determine their aerobic capacity at the start, and at 12 weekly intervals.

The measurement was made by having each person ride a stationary cycle while their pulse rate was being recorded as the brake pressure on the wheel was increased at intervals of three minutes of riding and resting. A graph of load over pulse was then drawn to give the level.
I later found that my initial reading was zero, but when I enquired about how that could be so, I was told that normal measurements were made with straight line graphs, and that a curve would be needed at the low end of the graph, in which case my actual reading would be between zero and 100.

I then trained twice a week for 12 weeks, with each session involving 20 minutes of light exercise, 20 minutes of walking or jogging, and 20 minutes of light games.
I found that when I just walked I had a minimum of symptoms, but when I began to increase my pace I would have to take from one to three extra deep breaths about ever 30 or more yards. Sometimes I could keep walking, but at other times I would actually have to stop and take the extra deep breaths, and then start again. I therefore walked slowly, or briskly, or jogged, and stopped and started my way around a 400 yard track. I was running last, and by the time I was two thirds around the track every other runner had out-lapped me.

My aerobic capacity was measured again after 12 weeks and it was 350 kps.

I therefore increased the frequency of my training to 3 or 4 times per week at the institute venues, and, or local ovals, and was training at a slightly faster pace, but after 24 weeks my aerobic capacity was still 350 kps.

Nevertheless, I continued to train and increased the frequency to 5-7 times per week, until, in the tenth month, I injured my knee and had to stop.

When I discussed the training with others I found that athletes had capacities of 1200-1400 kps, weekend sportsmen who trained for 2 hours on Wednesday and played for 2 hours on Saturday had a capacity of about 900 kps, and a sedentary worker who did no exercise would be 700 kps.

In other words, despite regular training, my capacity was half that of healthy individuals.
I therefore concluded that if I exercised within my limits I would be relatively free of symptoms, and if I reached my limit I would have some trouble with my breathing, and if I exceeded those limits the problem would just get worse. I therefore developed the general policy of exercising within my limits. I also applied that principle to any other aspect of health, by doing things casually instead of hurrying etc.

I also concluded that aerobic testing could be a way of diagnosing the problem, and measuring it’s severity, and that regular exercise could be used as a treatment in some cases.
I continued to study the problem by reading medical books and journals, and some years later found that international researchers were not able to get data on the effects of exercise because the patients could not, or would not train.

I knew that it would be due to the standard exercise programs requiring gradual increases in training to gain improvement, and that as soon as the patients exceeded their limit they would get problems and drop out of the course.

I also found that, in 1980, Russian researchers had measured the aerobic capacity of such patients and found that they were generally below average. In the U.S.A. one of the main names for the ailment was neurocirculatory asthenia. The Russian researchers called it neurocirculatory dystony and placed it in 3 levels for mild, moderate, and severe cases.

Several years later a friend of mine introduced me to the head of the research institute where I had trained.

When I explained how his researchers could solve some of the research problems, he asked them if they would do such a study, but they were busy on other projects, so he asked me to design and co-ordinate a project myself.

I arranged for other patients with similar problems to train in the same manner that I had, and was able to verify that most of them had lower aerobic capacity than normal, and that improvement occurred in the first 12 weeks and began to level out, indicating that they had a limit to their capacity.

The success of the project was reported in newspapers throughout Australia between 1982 and 1983, and although I prepared a research paper and sent it to two medical journals it wasn’t published, so I put it in my filing cabinet where it stayed until recently, when I sent it to BMJ and it was accepted.

References for these comments can be seen in my other responses to the topic in this section of BMJ.

The adverse effects of exercise in patients with Chronic Fatigue Syndrome (CFS) are due to the potentially diagnosable and treatable biochemical abnormalities found in the condition. Unfortunately the best tests, including an analysis of red blood cell magnesium levels, are not widely available.

In 1989 John McLaren-Howard demonstrated that a myothermogram reveals smooth muscle contractions when red cell magnesium levels are normal but large irregular spikes in marked magnesium deficiency signalling muscle damage.1

John McLaren-Howard later discovered that about 98% of the CFS patients who have adenosine triphosphate (ATP) profiles have low levels of ATP-related magnesium. Most ATP functions work as complexes with magnesium. Low levels of ATP in CFS indicate the need for specific treatment which he has found is almost always helpful.

A low whole-cell ATP is not exclusive to CFS patients as almost all non-haematological causes of fatigue usually involve lowered ATP levels.

About 40 % of the CFS people with low ATP have some degree of blocking of the translocator sites in the mitochondrial membranes. This has to be addressed as well as trying to improve ATP availability. When ADP to ATP translocation is blocked at the translocator site there is, in effect, a double block because ATP provision to the cytoplasm will also be reduced. The same translocator takes ADP into mitochondria and delivers reformed or de novo synthesised ATP back to the cytoplasm.

Very low magnesium levels can occur without CFS. I know that hard exercise--for example, running five miles every day--may contribute to low red cell magnesium levels. Low cell magnesium cannot only damage muscles but also can affect sperm quality and motility. Repletion of red cell magnesium status is an important part of preconception care for both men and women.

Fatigue, like headache, migraine, or flushing, is a warning symptom which signals perturbations in cell chemistry which can benefit from state of the art investigations. Exercise is easy for those with healthy bodies.

1 Howard J. Muscle action, trace elements and related elements: the myothermogram. In Chazot Gea; ed. Current Trends in Trace Element Research. Smith-Gordon, 1989

2 Myhill S, Booth NE, McLaren-Howard J. Chronic fatigue syndrome and mitochondrial dysfunction. Int J Clin Exp Med. 2009;2:1-16.

3 Booth NE, Myhill S, McLaren-Howard J. Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Int J Clin Exp Med. 2012;5(3):208-20.

4 Myhill S, Booth NE, McLaren-Howard J.
Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) - a clinical audit. Int J Clin Exp Med. 2013;6:1-15.

I would like to thank the editors of BMJ for publishing my comments about my 1982 research project on chronic fatigue and exercise on their website on 4th October 2013.

I have only recently found that item on 5th December 2013, and would like to add a further response to the letter of Ellen C.G. Grant who asked why anyone would expect to learn anything of scientific importance from the recent five million pound PACE trial. Grant also reports on the importance of studies into mitochondrial dysfunction.

First of all, in 1975 I had been offered many different treatments, mainly medications, for my own ailments, but none of them had any beneficial effects, so I decided to try and find my own solutions.
One of the main symptoms was an abnormal physiological response to exertion.

I began with the objective of joining an exercise class, and gradually improving my fitness until I returned to normal health.

At that time I heard a radio report about an organisation called the South Australian Institute for Fitness Research and Training which invited members of the public to enrol, so I did on the grounds that research doctors might know more than my local GP and specialists.

The institute, as I understand, had some specific studies, and, or, classes for people with such ailments as asthma, high blood pressure, and arthritis, and for those who were overweight, or cigarette smokers etc, but it did not have anything for those who had chronic fatigue.

Consequently, I was placed in a standard group where all kinds of people trained, including sportsmen, and those who were recovering from injuries, and those who just wanted to get fit.
At the outset I was encouraged to ignore my symptoms and try to keep up with the group, but that level of activity was making the symptoms worse instead of better, so I had two choices.

The first was to stop training, and the second was to continue, which I did, by walking or jogging at my own pace.

I started training twice per week, and increased it to six or seven times per week over a period of ten months before injuring my knee, when I had to stop, and during that time my health did improve, although not to the extent that I was aiming for.

I therefore began investigating other aspects and found that international researchers were unable to get scientific information on the effects of regular exercise because patients were not able to complete their training programs for 12 weeks.

Seven years later I had a discussion with Tony Sedgewick who was in charge of the Institute, and I explained how to solve that problem.

However, because his researchers were too busy on other projects he asked me to organise one specifically for fatigue patients.

My objectives were to make it safe for all participants, and to see if the those who trained the same way as I had could continue for twelve weeks or more, and nine did. None of them became significantly worse, three stayed the same or slightly less, and six improved their aerobic capacity, and of the total, five kept training for 24 weeks or more, with one of them apparently on his way back to full recovery, and who, about a year after starting, was still training, and participated in a six mile run.

Consequently, the reason that the project was important, was because I had developed a reliable way of having patients train regularly for 12 weeks or more for the first time, and since then researchers who use that method have been able to get scientific data about any aspect of exercise which they studied.

The exercise method is also important because for some patients it may be the only effective way of improving health when other methods don’t.

Also, since then the name chronic fatigue syndrome has been introduced into official lists of diagnosis, the abnormal physiological response to exertion has become the identifying aspect in the definition, and the method of treatment which I developed has been widely used, and been given the name of PACING.

However, some researchers apparently haven’t been as successful For example, the recent five year study of 650 patients called the PACE trials has been criticised by patients where 51% report that they were worse after, than when they started.

Nevertheless, exercise training can be useful, and should be studied further, to reduce the adverse effects and improve the outcomes.

As for other forms of treatment, I have considered every possibility, and found that at least 100 different labels have reached prominence at some time in the past 150 years, and they all need to be considered in the context that they all have their proponents and potential to help patients.

The concept of mitochondrial dysfunction, as mentioned by Grant, is one of those, and I would encourage the people concerned to pursue that area of study.

However, as I said, it isn’t necessary to discard the exercise methods which have already proven helpful to some patients, and should continue to be available as an option in the future.

Max Banfield

References . . .
1974: J.W. Hurst, The Heart, 3rd edition, McGraw Hill, New York, p.1554 . . . (a quote from a section about the abnormal physiological responses in neurocirculatory asthenia which is often described as having symptoms similar to those of heart disease occurring in the absence of heart disease) . . . ”Attempts by Cohen and his associates to alter these abnormalities by physical training were unsuccessful since the patients could not or would not follow the prescribed training programme” (end of quote).
1982: August, M.A.Banfield - The Australasian Nurses Journal, letter to the editor, p.15 (an invitation for people with the relevant symptoms to enrol in a fitness training course)
1982: August 5th, Fitness helps in therapy, The News (Adelaide) p.5.
1982: December 20th, SA study matches Russian Results, The News (Adelaide) p.18.
1983: August 11th, Study lifts fitness levels, The News (Adelaide) p.13.
1983: August 20th Researchers solve mystery, The Courier Mail (Brisbane, Queensland newspaper) p.14.