Background

In 1986 the use of antibiotics in animal feed was banned in Sweden, as one of the first countries in the world. The ban was due to an escalating antibiotic resistance developing in animals, similar to that seen in human antibiotic use. Antibiotics in animal feed are used to prevent for instance post-weaning diarrhoea in piglets. The ban resulted in an increased prevalence of diarrhoea. The suffering this caused and the increased number of deaths due to stress and infectious disease epidemics was disastrous and caused noticeable profit loss.

To come to terms with the problem and possibly find an alternative feed, a joint scientific project was initiated, combining the expertise from veterinary medicine, microbiology, infectious disease and immunology.

Since the 1980's Stefan Lange and Ivar Lönnroth at the Department of Clinical Bacteriology at the Sahlgrenska University Hospital in Gothenburg, Sweden had been studying mice and cholera disease. They were searching for a substance that immunized mice and rats to diarrhoea caused by cholera toxin. It is well known that survivors of cholera, both rats and humans, develop resistance for a long time. Lange and Lönnroth discovered an endogenous system that reacted faster than the immune system, probably an endogenous substance prone to different types of stimulation. The resistance can be triggered by the addition of enterotoxins or by a combination of amino acids and sugars in defined proportions.

Through further research they discovered that a substance produced in the pituitary gland gave resistance to cholera toxin. The protein was named Antisecretory Factor, in short AF (Lange and Lönnroth 1984; Lange et al 1987). This regulatory protein affects the intestinal fluid and electrolyte balance in cell membranes in different organs. AF normalises intestinal fluid secretion, an important factor in the treatment of diarrhoeal disease.


AF-Feed

Immediate results from novel AF-pig feed

The knowledge gained from the rat toxin studies and the discovery of AF protein was applied in the search for a novel feed aimed at post-weaning diarrhoea in piglets. At first, feed with added amino acids and sugars was given to piglets to stimulate their own AF production. Urine samples showed that there was a correlation between the AF-level and diarrhoea. Samples from pigs without diarrhoea had a high level of AF whereas samples from pigs with diarrhoea had low levels of AF. The use of this specialised feed gave immediate effect, resulting in substantially lowered prevalence of diarrhoea and significantly fewer deaths in piglets.

From this point research began to develop a feed that in itself contained the proper amounts of amino acids and sugars, without the need for additives. A production process was created and in 1991 a feed intended for piglets and sows was introduced under the brand name of Trygge® . A large number of Swedish pigs are weaned today on a feed that induces AF, thus reducing the effects of both invisible (subclinical) and visible (clinical) diarrhoea. 

 


Initial test on humans

Since the mechanisms involved in AF are of general physiological nature and similar to all mammals, transferring experiences learned about AF from animals and applying it to humans was not as complicated as one could expect. The concept of AF-feed had also proved effective in calf, horse, dog and cat. 

The researchers began to test the cereal based piglet feed on themselves, preparing it as a porridge and baking bread. Also the gastroenterologists at the Sahlgrenska University Hospital became interested and began tests on patients with ulcerative colitis. All patients treated showed favourable results and responded with a significant increase of AF in the blood. This effect remained measurable for up to four weeks after the intake of piglet feed. These results showed that the same principle that had worked in animals was also applicable to humans. 


Europe’s first medical food 

Encouraged by the positive results seen on man the desire became to produce food based on AF protein. At this time EU was discussing the introduction of new dietary Foods for Special Medical Purposes (not to be confused with Functional Foods). The Commission Directive 1999/21/EC on dietary Foods for Special Medical Purposes (FSMP) was ratified in May 2000. The MagiForm® product range was the first to be approved according to the new legislation. The product range includes muesli, rusks and biscuits with AF stimulating effects. The range expanded to also include more potent stimulators in the form of SPC-Flakes®  and Salovum® a product based on Egg yolk powder B221®, a vehicle for exogenous administration of high dose AF protein.


The Reasercher

The development of  protein AF (Antisekretorisk Faktor)were made of Professor Stefan Lange and  Ass.Professor Ivar Lönnroth at Sahlgrenska Universitetssjukhuset in Gothenburg.