Georg Ivanovas From Autism to Humanism - systems theory in medicine

2. The medical paradigm and the anomalies of ‘Normal Medicine’

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2.6. The magic of reference values

Another example of an epistemological inconsistency is a phenomenon which I would like to call the magic of reference values.

In medicine we have a lot of individual measurements. Normally they are distributed according to a Gauss distribution. By calculating the standard deviation (SD) or by a different method certain limits are set. These limits do not concern ‘essential variables’. That is, a change beyond the defined limits does not change the behaviour of the organism (Ashby 1960: 36), nor does it endanger its existence (Ashby 1960: 41-43). Thus, the stability of the whole system cannot be assigned to any of these normal values.

In contrary, the vigorous activity of a certain variable might be meaningful for the organism and can result in a stable whole (Ashby, 1960: 56). Fixing this variable may be harmful (chap. 6.4; 6.7) and lead to a vigorous activity of other variables (Ashby, 1960: 67).

To make a clinical example: A value, often ‘altered’ and mostly treated is blood iron. Naturally there are studies supporting this view. Patients, mostly women, with a modest iron ‘deficiency’ did much worse on attention, memory and learning tests than those with enough iron in their blood (if we suppose it to be a relation and not only a correlation). “But women should not rush to take iron supplements as about one in 20 people of Anglo-Saxon origin carry a gene for "iron overload" or heredity haemochromatosis” (Bhattacharya 2004). That is, such a therapy might be harmful to a certain sensitive population

But reduced iron might also have a meaning. “Early in bacterial infection, iron becomes more tightly bound to protein, and is removed from circulation by the liver. From an adaptive point of view, the response is beneficial to the host because the bacteria need a plentiful supply of iron to thrive. Together with fever, low levels of iron help to fight the infection. And yet this 'deficiency' is often treated with dietary supplements, thus prolonging the disease process” (Lewin 1993).

A similar effect is seen in cancer which is mostly accompanied by anaemia. Epoetin ß ‘corrects’ anaemia but does not improve cancer control or survival. Disease control might even be impaired (Henke et al 2003). There is also some indication that iron reduction through regular phlebotomy is able to reduce cancer risk (Zacharski et al 2008).

Moreover, high dietarian iron was linked to Parkinson’s disease (Powers et al 2003), too much of intracerebral iron might be a cause for multiple sclerosis (Bakshi et al 2002) and higher iron stores are associated with an increased risk of type 2 diabetes (Jiang et al 2004).

What are physicians doing in prescribing supplementary iron in pregnancy, in early childhood and all along the way, just on the basis of low ferritin? Such a treatment of reference values might be rather harmful for the patient, although not immediately.

The reference values have to be seen in their context. What meaning has a haemoglobin of 11, 2 mg/dl for a female vegetarian, who exercises regularly? The Berlin vegetarian study (Rottka et al 1988; Rottka 1989) proved that, in fact, anaemia was quite common among vegetarians. But they were generally in a better health condition. Of course, vegetarian life facilitates anaemia, even with clinical signs. But other life-styles have other dangers. The subclincal anaemia found in many vegetarians might have no meaning for their health. It might be regarded as an accidental finding not as a state to be treated.

That is, it is not so easy to judge the meaning of all the measurements we are confronted with. This is especially true for all the new markers without established clinical importance yet (Manolio 2003).

The unreflected administration of substances like iron, minerals or vitamins just to provide a ‘necessary quantity’ or as a therapy comes lately under fire. More and more side effects are observed (Parker-Pope 2009). For example, vitamin A intake is correlated to more fractures (Lips 2003; Michaëlsson et al 2003) and beta carotene, vitamin A, and vitamin E may increase mortality (Bjelakovic et al 2008).

Around 1980 bilirubin concentrations in newborn over 14 mg/dl were treated with phototherapy, concentrations over 20mg/dl lead to exchange transfusions. “Unfortunately, the early 1980s was not a good time to be transfusing blood in San Francisco. Although we did not know it then, the blood supply was contaminated with HIV. We also did not know that most of these exchange transfusions were unnecessary.“ There was a ‘fear of twenty’ (vigintiphobia) for kernikterus (Newman 2003) (chap. 3.9). This fear led physicians to hold bilirubine levels low. However, bilirubine is a metabolite of biliverdin which is a potent cytoprotectant and might be of benefit for newborns (Barañano et al 2002).

Of course, this is an old story and we know better now. But we should be cautious. Comparably harmful treatments probably happen today, as well. They happened throughout all the history of medicine. For example, today’s intensive care in its attempt to control human physiology by drugs in order to promote a ‘better’ function might do more harm than good. If true, and there is strong evidence (Singer/Glynne 2005), this would be another example of how the overemphasis of certain reference values is not beneficial.

What has to be kept in mind is that all these limits are somehow arbitrary. They are helpful in judging the patient. Without doubt. But there is a danger to give them a signification (chap. 3.9), such that the description becomes a prescription, a point of intervention.

Just the way the police will fine someone who exceeds the speed limit, the physician then will fine a patient with a treatment if he exceeds the 2 SD limits of the standard deviation. But, in contrast to the police, the physician will sometimes intervene if the measurements only approach the limits (“your values are quite low” – that means ‘normal’).

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