Question: Thank you for your response to my last question about the use of Prozac in Down’s syndrome. One of the changes that I have noted is that my son is no longer constipated. Dr. [Lawrence] Leichtman [clinic located in Virginia Beach, Virginia] has told me that this phenomenon is common. He thinks that Down’s children may not be suffering from Hirschsprungs’s disease, but from a serotonin deficiency. ——TR

Answer: Constipation can be caused by a lack of peristalsis (rhythmic contractions of intestinal smooth muscles). Peristalsis is under the influence of the cholinergic and serotoninergic nervous systems. Cholinergic neurons use acetylcholine as a neurotransmitter, which is why choline, DMAE and vitamin B-5 increase peristalsis and stimulate bowel movements. Although I have suggested cholinergic stimulation to mothers with constipated children, it has not seemed to work as well in children with Down’s syndrome as it does in the general population. It is possible that the constipation problem in Down’s syndrome is due to serotoninergic deficit, rather than a cholinergic deficit as I had first assumed. In retrospect, it makes perfect sense.

If true, then you might want to investigate the effects of 5-hydroxytryptophan (5-HTP) on peristalsis and constipation. Unlike tryptophan, whose conversion to serotonin in the gut is limited by feedback control mechanisms (see step 1 in Figures 2 and 3), 5-HTP bypasses the bottleneck (step 2) and can raise serotonin activity beyond the level established by the body’s normal feedback control. Indeed, the most common side effect from 5-HTP is gastrointestinal motility (i.e., gut-muscle stimulation) from the conversion of 5-HTP into serotonin in the lining of the intestine, where 5-HTP is first absorbed. It seems likely that 5-HTP supplementation would achieve the same serotoninergic effect in the gut as Prozac. In addition, the 5-HTP that escapes gut metabolism can be absorbed by the brain and converted into serotonin producing central behavioral effects similar to Prozac (refer to the answer in the last issue for more explanation).

Although tryptophan supplementation can increase serotonin in the central nervous system when it is taken without protein and/or with carbohydrate, it does not raise serotonin very effectively in the peripheral nervous system that controls intestinal smooth muscles. The conversion of tryptophan to serotonin is strongly regulated in the gut. The conversion of 5-HTP to serotonin is not.

5-HTP is about ten times more potent than tryptophan, gram for gram, at increasing brain serotonin. I can’t say I have much idea about how efficient 5-HTP may be in stimulating peristalsis in serotoninergically deprived Down’s syndrome children. Some experimentation may be needed. The Fiona study of piracetam and 5-HTP [see SDN v5n9], used 5-HTP doses of 1 mg/kg body weight. But you might want to start with only 5 mg and see if there is any effect for a few days before going to 10, 25 or maybe even 50 mg doses. Currently, 5-HTP is sold most commonly in 25, 50 and 100 mg sizes. These larger sizes are likely to be too large for young children. However, they can be divided up into smaller doses and mixed into beverages or solid foods.

To maximize the brain’s absorption of 5-HTP, it is best to take 5-HTP on an empty stomach (i.e., without protein-containing foods). However, for maximizing gastrointestinal stimulation, I think it might be better to take it with food. Plus, giving 5-HTP with meals is probably much more convenient for parents with young children and busy schedules.

LifeLink mentioned to me that they have just produced a mint flavored 25 mg 5-HTP losenge that might be a convenient strategy for giving 5-HTP to children, especially between meals. Interested readers can call LifeLink at 1-888-433-5266. ——SWF