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101 Storie Zen
101 Storie Zen
The AF protein
A clinical innovation of
endogenous origin
Twenty years of Swedish research has led to the
discovery of the Antisecretory Factor (AF), an
endogenous protein with significance in secretory
and inflammatory disease. The research has already
resulted in medical foods with clinical use.
CLINICAL STUDIES AND CASE REPORTS
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The AF protein – a Swedish discovery
Pioneering research Europe’s first medical food
In 1986 the use of antibiotics in animal feed was Encouraged by the positive results seen on man the
banned in Sweden, as one of the first countries in the desire became to produce food based on AF protein.
world. The ban resulted in increased diarrhoea and Since 1999 it is possible to approve dietary foods for
mortality in piglets. special medical purposes within the EU. The
Since the 1980’s Stefan Lange and Ivar Lönnroth MagiForm® product range was the first to be
at the Department of Clinical Bacteriology at the approved according to the new legislation. The
Sahlgrenska University Hospital in Gothenburg, product range includes muesli, rusks and biscuits with
Sweden had been studying mice and cholera disease. AF stimulating effects. The range expanded to also
They were searching for a substance that immunized include more potent stimulators in the form of pure
mice and rats to diarrhoea caused by cholera toxin. SPC and Egg yolk powder B221®, a vehicle for
Lange and Lönnroth discovered an endogenous exogenous administration of high dose AF protein.
system that reacted faster than the immune system,
probably an endogenous substance prone to different Regulates fluid transport
types of stimulation. The resistance could be triggered The AF-protein is of medium size, 41 kDa,
by the addition of enterotoxins or by a combination comprised of 380 amino acids with the active
of amino acids and sugars in defined proportions. The region located as a peptide of 8-38 amino acid
protein was named Antisecretory Factor, in short AF. length in the terminal N-region of the protein.
This regulatory protein affects the intestinal fluid and It is possible to produce highly purified protein
electrolyte balance in cell membranes in different through microbiological methods as well as chemical
organs. It is the most potent anti-diarrhoeal substance synthesis.
identified. AF normalises intestinal fluid secretion, an The protein has its own pharmacological effect
important factor in the treatment of diarrhoeal and initiates production of endogenous defence
disease. mechanisms against secretion and inflammation.
An AF-stimulating feed was developed through a Within a couple of hours the plasma level of AF
patented process involving hydrothermal treatment. rises quickly following exposure to diarrhoea
The cereals, oats and wheat, are first soaked in water, stimulation by e.g. bacterial toxins. An elevated
then heated. No additives are needed in the process. synthesis of AF can also be achieved by the ingestion
This enzymatically activated specially processed cereal of AF-inducing specially processed cereals (SPC). It
(SPC) stimulates the endogenous production of AF has effect in regulating fluid transport over the
protein. In 1991 an AF-feed intended for piglets and intestinal wall in e.g. Crohn’s disease and fluid
sows was introduced and has become the dominating pressure in the inner ear in Ménière’s disease. Aside
feed on the Swedish market. from the highly potent antisecretory activity, AF
The encouraging results from the animal research protein also has important anti-inflammatory effects
led the researchers to look beyond and widen their which have proven clinically important in e.g.
scope and produce a drug based on a synthetic AF ulcerative colitis, Mb Crohn, rheumatoid arthritis
peptide as well as medical food for human use. and mastitis.
The researchers began to test the piglet feed on With immunohistochemistry techniques it has
themselves, preparing it as a porridge and baking been shown that AF is present in most tissues in the
bread. Also the gastroenterologists at Sahlgrenska body. Eva Jennische, at Gothenburg University, has
University Hospital became interested and began tests shown that AF protein is located in three cell types;
on patients with ulcerative colitis. All patients treated epithelial cells, lymphatic cells and nervous cells.
showed favourable results and responded with a Research is ongoing to identify a true classical
significant increase of AF in the blood. This effect receptor for AF and to develop an analytical method
remained measurable for four weeks after the intake for blood measurement of AF in man.
of piglet feed.
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THE AF PROTEIN AND ITS ANTISECRETORY EFFECTS
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THE AF PROTEIN AND ITS ANTISECRETORY EFFECTS
plasma prior to treatment to 1,28 ± 0,23 AF units/ as a complement to the patients’ ongoing medical
ml plasma after the two week treatment period therapy.
(p<0,05). Elevated levels of AF (1,28 ± 0,39) were Eight critically ill patients were included. Six
maintained during at least four weeks after intake of patients with the midgut carcinoid syndrome and
the SPC diet. two with metastasizing medullary thyroid carcinoma
In the patients baseline values were low (0,04 ± (MTC) participated. In an initial open part of the
0,07), rising during the treatment period to a mean study all patients received Egg yolk powder B221®
of 0,66 ± 0,45 units. The two patients with the for 4 weeks. This was followed by randomisation
longest remaining small intestine, 300 and 400 cm, to a double-blind crossover period with SPC and
achieved elevated AF levels comparable to healthy control cereals (CCs) without AF inducing ability
subjects, i.e. over 1 unit/ml plasma. These patients for 6 weeks in a dose of 1 g/kg bodyweight divided
also lowered the number of daily bowel movements. into four doses daily.
Analysis showed that there was a significant Treatment with SPC and Egg yolk powder B221®
correlation between the length of the remaining resulted in a significant reduction of daily bowel
small intestine and AF concentration (r=0.94, movements (Table 1) and several patients reported
p<0.01). firmer stools.
The study showed that AF activity is strongly All patients had low levels of AF-activity in serum
associated with remaining length of intestines. A at baseline. During treatment with Egg yolk powder
small intestine length of at least 1 metre is needed to B221®, the mean level increased slightly. AF-activity
induce AF and to maintain the elevated levels after was also significantly higher after SPC diet. In four
the treatment with AF-inducing diet. of five patients, the AF concentration reached above
a level which in other studies correlated well with
Lange, Bosaeus, Jennische, Johansson, Lundgren and
Lönnroth, Food-induced antisecretory factor activity is correlated positive effects of diarrhoea treatment.
with small bowel length in patients with intestinal resection, Although these patients had been given optimal
APMIS, 2003; 111:985-988
medical therapy, an added positive effect could
be seen with the addition of the AF-treatment.
Treatment with Egg yolk powder B221® was well
Secretory diarrhoea due to tolerated by all patients. The two patients with
carcinoid tumours MTC and fully intact intestines responded best to
To test if AF primarily influences the secretory SPC-diet with the highest AF levels.
component of the diarrhoea, a study was performed The positive response to Egg yolk powder B221®
on patients with endocrine tumours. Patients indicates that AF protein has a local effect in the
with neuroendocrine tumours may suffer from intestine, directly interacting with the receptors
severe diarrhoea, that may be both difficult to and its binding proteins in mucosal cells. Therapy
treat, treatment resistant and persistent despite an with Egg yolk powder B221® may hence be the
otherwise optimal treatment regime. most suitable treatment alternative for patients with
The aim of the study was to investigate if specially difficulties ingesting large amounts of cereals.
processed cereals (SPC) and Egg yolk powder Laurenius, Wängberg, Lange, Jennische, Lundgren and
B221® could induce AF-activity and if AF-therapy Bosaeus, Antisecretory factor counteracts secretory diarrhoea of
could reduce the number of bowel movements. endocrine origin, Clinical Nutrition, 2003; 22(6):549-552
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THE AF PROTEIN AND ITS ANTISECRETORY EFFECTS
Ménière’s disease
“A little SPC at breakfast relieves
me of my dizziness!”
10 years ago, Elisabeth woke up and found the
room spinning causing her to vomit. One week
later she had a spell of dizziness while out for a
walk. After another severe spell lasting an entire
week she was diagnosed with Ménière’s disease.
Elisabeth was offered several treatments – diuretics,
antihypertensive drugs and even pills for motion
sickness – but nothing seemed to help. The spells
continued for a year with a few attacks a week.
Finally she hardly dared leave the house in fear
that she would not make it home before an attack
hit her. She became socially handicapped and her
mental health deteriorated.
In the spring of 1998 she came in contact with
Per Hanner at the Sahlgrenska University Hospital
and was asked to enter a study with specially
processed cereals (SPC). As she had nothing to loose
she agreed. Immediately after she began treatment
with SPC her symptoms disappeared and Elisabeth
felt as she had got a new lease of life. She has since
gradually been able to lower the dose of SPC that
she takes with her yoghurt in the morning. one side and she still has tinnitus, but she is now
The disease has made Elisabeth almost deaf on relieved from the troubling attacks of dizziness.
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THE AF PROTEIN AND ITS ANTISECRETORY EFFECTS
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THE AF PROTEIN AND ITS ANTI-INFLAMMATORY EFFECTS
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THE AF PROTEIN AND ITS ANTI-INFLAMMATORY EFFECTS
ulcerative colitis
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A study was performed to see if AF inducing
cereals could promote endogenous AF production
in patients with ulcerative colitis and Crohn’s ���
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disease, and to determine if an elevated AF level
was correlated to clinical improvement of intestinal
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function.
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The experimental group consisted of 26 patients
given AF inducing cereals as muesli, bread and/
or pasta in addition to their regular diet during
30 days. A control group of 24 received a similar ���
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THE AF PROTEIN AND ITS ANTI-INFLAMMATORY EFFECTS
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THE AF PROTEIN AND ITS ANTI-INFLAMMATORY EFFECTS
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THE AF PROTEIN AND ITS ANTI-INFLAMMATORY EFFECTS
Mastitis
“Imagine if I could have prevented it with SPC”
Karin, aged 31, has just had her first child. Two
weeks after giving birth to their daughter, Karin
does not feel so well after returning home from an
afternoon walk with her husband. One of her breasts
feels sore and she can feel a plum-sized mass on one
side. Karin lies down to rest but after a few hours
she feels febrile. The stiffness has spread and almost
half her breast is now affected. She has a temperature
of 40° C. When her husband calls the doctor she
is recommended to continue breastfeeding, take
antipyretic medication and get plenty of rest. The
doctor believes it is simply an inflammatory mastitis
since Karin does not have any other symptoms
or sores on her nipples. If on the other hand the
symptoms do not gradually improve then it may
be infected and need treatment with antibiotics, in
which case they should contact the doctor again. The next day the swelling has subsided and
Karin continues to breastfeed although her Karin has been able to breastfeed during the night.
daughter finds it more difficult due to the stiff She spends the weekend in bed and is tired due
nipple. The milk doesn’t come as easily as before and to the high fever, but the swelling continues to go
her daughter is unsettled. Karin finds breastfeeding down and by the end of the week she is completely
painful and her breast is red and warm. recovered and feeling well.
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THE AF PROTEIN AND ITS ANTI-INFLAMMATORY EFFECTS
AF-inducing cereals (SPC) can probably increase AF-levels in breast milk, thereby preventing sub-clinical mastitis. This
condition increases the risk of transferring virus from an HIV-infected mother to her child.
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THE AF PROTEIN AND ITS ANTI-INFLAMMATORY EFFECTS
Rheumatoid arthritis
“SPC improved AF treatment of rheumatoid arthritis
As earlier studies had shown that AF-inducing
my situation” cereals had a positive effect on symptoms and disease
processes in diseases of inflammatory nature, it
Ian, a man in his fifties, became diagnosed with
became of interest to study what effect AF-inducing
rheumatic arthritis seven years ago. He couldn’t
cereals (SPC) may have on the activity of rheuma-
continue his work as a car mechanic and had
toid arthritis.
to find another occupation. The disease came
In a randomised, double-blind, placebo con-
gradually and finally he was not able to handle
trolled study patients with active rheumatoid
his tools. Eventually he could hardly walk and
arthritis were allocated to either SPC or control
the medication he received was causing him
cereals. The cereals were given at a daily dose of 0,5
gastrointestinal problems.
g/ kg bodyweight, divided into three doses daily, for
He was offered a chance to try treatment
12 weeks. This dosage is lower compared to normal
with specially processed cereals (SPC). Soon he
dosage (1g/kg bw). Prior medication remained
noticed an improvement of the gastrointestinal
unchanged (methotrexate and salazopyrin) and no
problems and the inflammation was reduced.
patients were currently on cortisones. CRP, DAS
The study showed that there is a correlation
28 (Daily Activity Score measured in 28 joints)
between inflammation in the gastrointestinal
and HAQ (Health Assessment Questionnaire) was
areas and in the joints. However, no improvement
recorded at baseline, and after 4 and 12 weeks of
of his arthritis was seen during the three-month
treatment. 16 patients in the treatment group and
treatment period.
18 in the control group followed through.
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THE AF PROTEIN AND ITS ANTI-INFLAMMATORY EFFECTS
The results show a significant increase of AF- 4±12% in the active treatment group (p<0,05). No
levels in the SPC treated group (Table 2). difference between groups could, however, be seen in
Baseline comparisons and after 12 weeks status and symptoms of the joints.
treatment showed a significant difference in CRP
Mörck, Ek, Jennische, Laurenius, Tarkowski och Lange, Anti-
between groups. CRP was increased by 66±29% inflammatorisk effekt av kosttillskott med specialprocessade
in the control group, whereas it was reduced by cerealier vid reumatoid artrit – en dubbel-blind pilotstudie,
Posterpresentation vid Riksstämman, 2003
15
Treatment
Dosage Expected treatment outcome
SPC: Normal dosage of AF-inducing cereals (SPC) is A positive therapeutic response can normally be
1 g/kg bodyweight daily, divided into 2-3 occasions. seen after 10-15 days of SPC treatment and within
When treating children the dose may need to be hours after ingestion of Egg yolk powder B221®.
increased and when treating elderly it may need to After termination of the treatment levels will decline
be reduced. The dosage should be introduced step by again after a few weeks. If treatment is resumed, AF
step and reach full dosage after 4-6 days. The cereals levels will rise within a matter of days, indicating a
can be eaten with yoghurt or boiled to a porridge. biological memory for AF production.
Egg yolk powder B221®: Normal dosage is 2g
5 times daily. The powder is blended with a cold Side effects, interactions and
liquid, e.g. water or juice, preferably using a whisk
precautions
or a blender.
Egg yolk powder B221® is the recommended AF products have been eaten by tens of thousands of
AF treatment for patients who have difficulties individuals and no side effects of medical nature
eating large amounts of specially processed cereals. have been reported. A few patients have experienced
Studies also indicate that patients not responding to occasional constipation, but this discomfort can be
treatment with AF inducing cereals may respond to reduced by a step-by-step introduction of the treat-
Egg yolk powder B221®. ment.
To stimulate the endogenous production of AF There are no reported interactions with
is has been favourable to introduce AF inducing concomitant medications. This is of importance as
cereals (SPC) during treatment with, or as a follow- the patients should continue with their regular
up treatment towards the end to, Egg yolk powder medical treatment. Neither SPC nor Egg yolk
B221®. powder B221® should replace or change the
For seriously ill patients or in patients with patients’ current medication. Persons with celiac
suspected low AF-levels, treatment with Egg yolk disease or gluten intolerance should not be treated
powder B221® quickly raises AF-levels directly in with AF inducing cereals and persons with allergy
the intestine. Most often the patients initially treated to eggs should not be treated with Egg yolk powder
with Egg yolk powder B221® for 5-10 days can B221®.
thereafter be transferred to the AF-inducing SPC, in
order to stimulate the body’s own production of AF.
20 g of SPC is equally potent to 2 g Egg yolk
powder B221®. Revised by Stefan Lange, M.D., PhD
Vitality, Stockholm, August 2004
Box 30192, SE-104 25 Stockholm, Sweden. Phone 0046-8-657 42 70. [email protected] www.as-faktor.se