Secretin
Secretin
A controlled clinical trial of secretin in children with autism or PDD reports that secretin has no more effect than a placebo.
Breaking news – Two new articles about Secretin research from the Associated Press and the New England Journal of medicine. (Credit= Autism Society of Alabama )
A new double-blind clinical trial also finds no different effect from the placebo. By Owley, et al. (Credit= Autism Society of Alabama )
A controlled clinical trial of secretin in children with autism or PDD reports that secretin has no more effect than a placebo. By Sandler, et al. (Credit= Autism Society of Alabama )
Autism Biomed Network – has a paper discussing the function of secretin and analysing the Horvath study. (Credit= Autism Society of Alabama )
Secretin-Cysteine – A new paper from a team of researchers discusses the implications of the fact that one of the stabilizers in the Secretin preparation, cysteine hydrochloride, crosses the blood-brain barrier. This site has the paper, as well as a letter listing potential side effects of Secretin, and reports of severe negative side-effects from the use of secretin or oral cysteine. (Credit= Autism Society of Alabama )
This article on Secretin and Autism was written for us by Kevin McShane, a medical writer and the father of a six-year-old son with autism. It reflects the state of public knowledge on the subject in December, 1998. (Credit= Autism Society of Alabama )
Victoria Beck, the mother who popularized Secretin, has licensed the pharmaceutical company Repligen to develop Secretin as a treatment for autism. Repligen will attempt to produce synthetic human secretin for use in FDA-approved clinical trials. You can get on an email list for news of upcoming trials. (Credit= Autism Society of Alabama )
A DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF SYNTHETIC HUMAN SECRETIN IN THE TREATMENT OF AUTISM AND PERVASIVE DEVELOPMENTAL DISORDER (PDD) (Credit= Autism Society of Alabama )
Disclaimer: This website was created in response to media attention surrounding the use of secretin as an intervention for autism. The authors stress that any information contained on this site does not at this time constitute a recommendation for the use of secretin.
- Homoeopathic Secretin
- Responses to Secretin
- The Use of Secretin for the treatment of Autism
- What is Secretin ?
- Background information from Paul Shattock, Autism Research Unit.
- Some caveats.
- Conclusion
- References
- Retardation of gastric emptying of solid food by secretin
Homoeopathic Secretin
The story of Secretin appears to be gathering pace as more parents respond to the success of Billy Tommey and other children treated with the injection of the pancreatic derivative.
However, the practical difficulties in both obtaining Secretin and having the injection administered are proving the largest barrier to most parents. One suggestion has been put forward that may provide an answer to the current situation. That is to administer a homoeopathic preparation of Secretin. Ainsworths have prepared this and it is now available for those who wish to try it. We would however make the following comments about this approach.
Firstly that there is no guarantee that the remedy will work.
We would stress that this has not been tested clinically for use in Autism. This is no different to the conventional Secretin injection. Homoeopathic remedies are by nature less harmful than conventional drugs and side effects are less of an issue compared to the problem of generating any effect in this case.
Secondly the effect may build up slowly rather than very suddenly (with the injection) since the dose is smaller. This would require the daily dosage of pills that are dissolved in the mouth for at least two weeks at a time.
We cannot be sure how much if any help can be obtained by pursuing this direction. We can only make it available for those who want to explore this approach. For those interested a course of 100 pills is available with a suggested dose of one tablet twice a day. The cost including postage being £?. If pills are problematic drops are available at £? for 10ml, or £? for 30ml. They are available from Ainsworths Homoeopathic Pharmacy, 36 New Cavendish Street, London W1M 7LH. Telephone 0171-935 5330, fax 0171-486 4313. E-mail Ainshom@msn.com
Update: We have received some feedback from parents using homoeopathic secretin for at least two weeks. All report that their child is more voluble, in some instances this has included speech. In addition small but noticeable behavioural improvements have been observed, and teachers have noticed improvements in interaction with both adults and children. In one case a mother noticed that her boy would now respect requests to pick up a toy he has discarded.
These are obviously early reports but we hope that more parents will share their experiences so that we can feedback the extent to which the remedy can help in autism and hyperactivity.
Responses to Secretin
Please can you help? I’ve been giving my daughter a liquid form of your homeopathic Secretin for just over a week now. It’s been a bit of a roller coaster ride as she’s been ill during this time too, however I’d like to know if you’ve had any feedback from other parents giving this form of Secretin to their Autistic children & if so, what results have they seen. It’s still early days yet, but I think her eye contact is much improved & she’s more willing to use language. I’ll keep you posted about any other ‘adventures’ along the way, but I’d be interested in hearing any other results you’ve had so far.
Dear Sir/Madam,
We have been giving our autistic 4 and a half year old son 2 tablets a day as recommended of secretin for the past 13 days. How long should we be giving him the tablets ? We have noticed a slight improvement in his condition, namely
* he is more affectionate and kisses us properly at the first request
* he is now shaking his head to mean “No”
* he is more vocal and has said a couple of words at school
* his attention span has improved at school as has his willingness to interact with others in PE and during circle time
* he seems to understand our comments a little better
Reprinted by kind permission: Paul Shattuck, Autism Research Unit
The Use of Secretin for the treatment of Autism
What is Secretin ?
Secretin is a polypeptide hormone involved in the regulation of gastric function. It is prepared from the duodenal mucosa of pigs. Following administration by intravenous injection, it causes an increase in the secretion of the pancreas of water and bicarbonate into the duodenum. It is used alone or in conjunction with pancreozymin or cholecystokinetic agents as a test for exocrine pancreatic function, and in the diagnosis of biliary-tract disorders.
Background information from Paul Shattock, Autism Research Unit.
Readers of the “Observer” and/or “Mail” and listeners to Radio will be aware that there has been interest in the potential use of a hormone “Secretin” for the treatment of autism.
Perhaps a bit more background information would be useful.
Secretin has been known for at least 20 years and it has a variety of functions but not much in the way of medical uses. One thing it has been used for is to test pancreatic function in other words to see if the pancreas is functioning correctly. A small amount is injected and the amount of “bicarbonate” which appears in the bloodstream is measured a short time afterwards. The bicarbonate secretion is required in order to neutralise the acid from the stomach and allow the enzymes in the duodenum to function.
As well as secreting bicarbonate, the pancreas secretes many other enzymes including lipases and especially peptidases. These peptidases will break down the peptides which, according to proponents of the opioid excess theories of autism, may be responsible for the problems. One way to diminish the problems caused by these potentially harmful peptides is the remove them from the diet. That is why people experiment with gluten and casein free diets.
Since secretin will stimulate the pancreas to produce these enzymes it could ameliorate the symptoms by this mechanism. It could, also or alternatively, be acting in the brain itself or in the intestinal wall (if it acts at all).
There are numerous anecdotal reports (a hundred or so) of the benefits of this form of therapy from parents whom I have met and others with whom I have “talked” on the net. I have also discussed the effects with 5 physicians in the US all of whom are enthusiastic about what they have seen.
Some caveats.
There have been no proper trials to prove efficacy although there has been a brief report published by Karoly Horvath.
The drug is not licenced for this purpose so it would take a fairly daring physician top prescribe this medication, in the UK, for this purpose and at this time.
The drug without side effects does not exist. Secretin has not been used over periods of time so we don’t know what will happen when it is. With products as complex as this we should expect them to occur. The benefits/advantages ratio will have to be taken into account.
There are some children with whom no effects are seen anyway.
This could be a significant contribution or it could turn out to be yet another gross disappointment. We will have to wait and see on this one.
There is an element of disagreement about who should be credited with the “discovery” of the potential of this material. The “Observer” contacted Mrs Victoria Beck who appears to have interpreted the events surrounding the discovery in a way that those physicians treating her child fail to recognise. I don’t want to get involved in that argument – it has little relevance to the main plot anyway.
Conclusion
There is no doubt that this is an interesting development but we will have to see if it pans out. There is a biomedical plausibility about the mechanism and results seem promising. Since the material is not readily available and it is not licenced for this particular use at the moment anyway, we have little alternative than to monitor progress with interest and some cautious optimism.
Paul Shattock
Karoly Horvath, M.D., Ph.D. Associate Professor of Paediatrics Paediatric Gastroenterology and Nutrition 22 S Greene Street, N5W70, Box 140 Baltimore, Maryland 21201-1595
References
Improved Social and Language Skills After Secretin Administration in Patients with Autistic Spectrums Disorders
Karoly Horvath, MD, PhD, Gerry Stefatos, DPhil, Kenneth N. Sokolski, MD, Renee Wachtel, MD, Laura Nabors, PhD, and J. Tyson Tildon, PhD.
Autistic Behavior and Secretin. Journal of the Association for Academic Minority Physicians. January, 1998. Vol. 9, No.1. pp.9-15.
Abstract: We report three children with autistic spectrum disoreder who underwent upper gastrointestinal endoscopy and intravenous administration of secretin to stimulate pancreaticobiliary secretion. All three had an increased pancreaticobiliary secretory response when compared with nonautistic patients (7.5 to 10 mL/min versus 1 to 2 mL/min). Within 5 weeks of the secretin infusion, a significant amelioration of the children’s gastrointestinal symptoms was observed, as was a dramatic improvement in their behavior, manifested by improved eye contact, alertness, and expansion of expressive language. These clinical observations suggest an association between gastrointestinal and brain function in patients with autistic behavior.
Additional References
Regulation of tyrosine hydroxylase activity in rat PC12 cells by neuropeptides of the secretin family.
Roskoski R Jr, White L, Knowlton R, Roskoski LM
Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, New Orleans.
Tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, is subject to regulation by the cAMP as well as the calcium and cGMP second messenger systems. Treatment of intact rat PC12 cells with neuropeptides including secretin and vasoactive intestinal polypeptide (VIP) stimulated tyrosine hydroxylase activity 2 to 3-fold in vitro. Secretin (EC50 = 10 nM) was about 3 orders of magnitude more potent than VIP (EC50 = 3 microM). A combination of several protease inhibitors failed to enhance the potency of either peptide. Other members of the secretin family including glucagon and peptide histidine isoleucine (PHI) stimulated tyrosine hydroxylase activity to a lesser extent. Somatostatin, which is not homologous to secretin, was ineffective. The maximal response of tyrosine hydroxylase activation to 1 microM secretin occurred within 6-15 sec. Secretin, VIP, and forskolin also enhanced tyrosine hydroxylase activity (3,4-dihydroxyphenylalanine production) in intact cells, as determined by high performance liquid chromatography and electrochemical detection. Secretin, VIP, PHI, and glucagon increased the levels of cAMP in PC12 cells more than 10-fold, as determined by radioimmunoassay. We also demonstrated that cAMP is released from the cells into the incubation medium following secretin treatment. Secretin and VIP treatment also enhanced the activity of cAMP-dependent protein kinase in a concentration-dependent fashion, as measured subsequently in vitro. Based on the greater potency of secretin in comparison with VIP, PHI, and glucagon, we suggest that the PC12 cells contain a secretin-preferring receptor that increases cAMP levels and brings about an activation of tyrosine hydroxylase activity through the stimulation of cAMP-dependent protein kinase.
Retardation of gastric emptying of solid food by secretin
JH Kleibeuker, H Beekhuis, DA Piers and OB Schaffalitzky de Muckadell Department of Gastroenterology, University Hospital, Groningen, the Netherlands.
The effect of secretin at nearly physiologic plasma concentrations on the gastric emptying rate of solid food was studied in 12 healthy men. A 99mTc colloid-labeled pancake was used as the test meal. The gastric emptying rate was measured during 1 h using a dual-headed gamma-camera, and was expressed as the half-time of the emptying curve. To prevent endogenous secretin release, 400 mg of cimetidine was given before the meal. Subjects were studied under three conditions: (1) during infusion of saline; (2) during continuous infusion of secretin, 6.6 pmol/kg.h; and (3) during three intermittent 10-min periods of secretin infusion, 7.6 pmol/kg.h during each period. Both continuous and intermittent infusion of secretin increased half-emptying time, by 133% and 55%, respectively. The plasma secretin concentration in condition 1 was 0.8 pM; plateau concentration in condition 2 was 9.8 pM; and integrated mean concentration in condition 3 was 4.8 pM. It is concluded that secretin at approximately physiologic plasma concentrations retards gastric emptying of solid food in humans.
Cholecystokinin- and secretin-releasing peptides in the intestine–a new regulatory interendocrine mechanism in the gastrointestinal tract.
Herzig KH
Regul Pept 1998 Feb 2;73(2):89-94
Department of Internal Medicine, Christian-Albrects-Universitat, Kiel, Germany. kherzig@1med.uni-kiel.de
Maintenance of homeostasis in the upper small bowel is a vital process for the body and therefore highly controlled. The enteric nervous system and the endocrine system are the regulators in this process influencing each other. The endocrine system in the gut consists of the classical hormones [cholecystokinin (CCK) secretin] to evoke motility or secretion. They are under control of releasing factors which are probably influenced by the enteric nervous system. Diazepam binding inhibitor and luminal CCK-releasing factor are likely candidates for CCK-releasing peptides in the negative feedback process in the absence of pancreatic juice. Experimental evidence suggests a secretin-releasing peptide. Further studies will be needed to determine the physiological role of each of these peptides. Monitor peptide in the pancreatic juice seems to function as a specific positive enhancement for CCK release. All these peptides are inactivated by the proteolytic enzymes during the interdigestive period. The discovery of additional releasing peptides and factors is very likely.
[Effectiveness of cimetidine, pirenzepine and synthetic secretin on stimulated gastric acid secretion].
[Article in German]
Gastroenterol 1980 Jun;18(6):306-313
Londong W, Londong V, Prechtl R, Schwanner A
Two possibilities of an inhibition of gastric acid secretion are compared in regard to effectiveness and side effects. Combined i.v. bolus injection of 0.3 mg/kg cimetidine caused almost complete inhibition of peptone-stimulated acid secretion in normal volunteers and duodenal ulcer patients-radomized and double blind investigated-to the same extent as high dose secretin (3 CU/kg/h i.v. infusion) in normal volunteers. Postprandial gastrin was unchanged by combined drug application, but was suppressed by secretin. Temporary blurred vision, dry mouth, and signifiant increase of serum prolactin were side effects of the drug combination, whereas secretin caused dose-dependent diarrhoea, increaded diuresis and elecvation of serum lipase, trypsin, and sodium. Inhibition of acid secretion by combination of the antimuscarinic drug pirenzepine with the H2-receptor blocking substances cimetidine was almost complete, i.e. more effective than the combination of classic anticholinergics with H2-blockers tested so far. Inhibition of acid secretion by secretin was dose-dependent; the dosage clinically applied so far (10 CU/kg s.c. and 0.5 CU/kg/h i.v.) had the smallest effect. In spite of first favourable results with secretin in bleeding mucosal lesions, the observed side effects cast doubt on its broad clinical applicability. A controlled clinical trial of the combination of cimetidine plus pirenzepine as prophylaxis of bleeding from mucosal lesions in risk patients seems to be indicated.
Some comments by clinicians using secretin
“Two patients unexpectedly received oral antibiotics the day after I.V. Secretin and had no observed benefit from the Secretin. Later, second doses of Secretin were administered with significant positive response. A third child received I.V. Secretin and full relief of chronic diarrhea for 36 hours, but diarrhea re-occurred with a vengeance when the child was given generous amounts of a juice known to precipitate diarrhea in the past as well as simultaneous first-time oral Magnesium. These may suggest that the thresholds in the gut affected by Secretin may be very sensitive and intertwined, and that we especially should consider optimization of other controllable factors in the gut—strict dietary avoidance of irritating foods and solute loads, administration of probiotics and supporting nutrients, suppression of overgrowths–for best results with Secretin”.
“Most of you know that Secretin is a hormone native to the human body which stimulates secretion of bicarbonate from the pancreas. Secretin injections have been used for a long time for diagnostic purposes (determining levels of pancreatic function) and is incredibly safe. The secretin used today has a pork source and differs only slightly from native human secretin. The results that I have experienced have been overwhelmingly good, with 85 – 90% of patients responding positively. Positive responses range from mild (which I have compared to a very good response to yeast/dysbiosis treatment or to nutritional measures) to dramatic, where the parents describe remarkable changes in a short period of time. I have had 5-6 dramatic responses, about 20 mild responses, and the rest falling somewhere in-between. There have been no negative responses and no untoward side effects. Repeat doses seem to create a cumulative effect. Age does not seem to be a factor in response. The patients that seem to respond the best are the children characterized by gut problems, dysbiosis, yeast overgrowth, and food allergies”.
