Posted by Jaqui (UK)
on August 28, 2000 at 08:59:09:
In Reply to: Re: Cod Liver Oil posted by Jaqui (UK) on August 28, 2000 at 08:55:17:
As with secretin, I listened to the story and rationale and then did my own reality testing on some patients to see about Mary Megson's Cod Liver Oil / Bethanecol idea. My early impression is quite positive, and I think this needs to be passed along to other clinicians who may want to look at this in parallel to our work under the IRB. Bethanecol is an oral parasympathetic agonist, very similar to endogenous acetylcholine, but more resistant to inactivation by endogenous acetylcholinesterase and therefore much longer acting. It has a good safety record, at least in the adult, non-autistic population.
We have a pretty good idea from Stephen Davies' work and by inference that many of our kids are hypochlorhydric, and this must diminish the secretion of pancreatic digestive enzymes and peptide messengers like secretin with receptors outside the gut. Bethanecol is a strong pancreatic stimulant. It has a ubiquitous positive effect on gastric acid secretion. Happily, this increased parietal cell acitivity isn't usually associated with increased gastro-esophageal reflux. Rather, there is a very long clinical tradition using Bethanecol expressly for symptoms of G.E.-reflux.
In healthy adult males, Bethanecol increased gastric-residence time by 64%, but did not affect mouth-to-cecum time. (Pharmacotherapy 9 226-231, 1989). Increased volume of stomach acid and increased time of exposure to it in the stomach would seem beneficial to digestion and absorption. In spite of its parasympathetic qualities, Bethanecol does not appear to cause problems with hypermotility, and my very first Bethanecol patient had his first-ever formed stool the following day. Improved digestion and more ordered peristalsis may explain the firmed stool.
I have observed truly marked language and social gains within 40 minutes of the first dose of Bethanecol, as if a switch had been flipped. Bethanecol could have such an immediate effect either as a strong pancreatic stimulant physiologically upstream to Secretin or through its own effect at numerous known CNS binding cites (Biochemical Pharmacology 38: 837-50, 1989, Mar 1). My early impression, by the way, is that the children who have demonstrated a response to secretin may fall within the group of likely Bethanecol-responders.
I am very happy to add to this discussion some recent literature research from Teresa Binstock and Linda Carlton. Experimentally, Bethanecol stimulates secretion of numerous antimicrobial peptides (defensins) by the small intestine (Infect Immunol 64:5161-5 Dec 1996. These defensins may have a wide spectrum, including antiviral. One child with damaged intestinal ganglia and pseodo-obstruction associated with active Epstein Barr was treated successfully with Bethanecol. (Am J Gastroenterol 95:280-4 Jan 2000) Dysbiosis control could be an important mechanism.
The official literature suggests contraindication in asthma, seizures, hyperthyroidism and peptic ulcer, though one clinician reports a definite pattern of improvement with Bethanecol in numerous patients with seizure activity, and I have used it effectively in one child with quiescent reactive airway disease. At the low doses being used, no significant abdominal pain or other clinical suggestion of ulcer activation is being seen. I strongly advise observation of the first dose in the office for one hour with injectable Atropine handy in the unlikely case of respiratory difficulties.
The thin, scored 10 mg Bethanecol tablets are easily halved or quartered for starting doses of 2.5-5.0 mg. For the tablet-averse, Bethanecol has been shown stable in water solution for at least thirty days (Ann. of Pharmacotherapy 31 Mar p 294-6 1997). There may be a preference for the generic Bethanecol over the proprietary ("Urecholine") in order to avoid the dyes. It is inexpensive.
Some adults have been on Bethanecol for many years for heartburn or urinary retention, but we must advise parents that safety in children over long periods has not been established. If a significant part of its mechanism is improved digestion and assimilation of nutrients, then perhaps the need for the Bethanecol will lessen over time.
I would emphasize that we don't think that the Bethanecol is effective unless you prime for about two months prior with cod liver oil. Kirkman is the first supplier to tell me that their cod liver oil is 100% natural, unspiked with any A-palmitate.
Pre-treat for a few days pior to CLO (and continue):
Vitamin E 200-400 IU/day plus Vitamin C 250-1000 mg bid
Dose Cod (Salmon) Liver Oil according to Vitamin A content:
2-5 years--2500 IU Vitamin A
5-10 years--3750 IU Vitamin A
>10 years--5000 IU Vitamin A
Minimize A-Palmitate (blocks Retinol G-Protein Signalling Protein)
Try to keep total supplementation with pre-formed Vitamin A (Carotene sources
do not count towards this maximum) not greater than double the amount provided
with the CLO over the long term to stay well below potential toxic doses of Vit A.
Begin Bethanecol after child has been on CLO for 2 months, continuing the CLO:
< 5 years of age--start with 2.5 mg of Bethanecol PO
5-8 years--start 5.0-7.5 mg
Older--start 10 mg
Adjust dosages upward to observe effect (arbitrary current maximum is 12.5mg)
Pupillary size (get smaller) may help guide dosing (anyone else
seeing a tendency to relatively dilated pupils in our kids, by the way?)
A second dose in the afternoon is often desirable.
I would certainly like to hear any feedback if you choose to try this. Best wishes for this last year of the second millenium. (Sometimes I prefer to think of it this way so it seems like we have more time left to help these kids.)