31 for 21: N-acetyl-cysteine & concerns in it's use

There is concern about N-acetyl-cysteine (NAC) and it's use in individuals with DS. It's an extremely beneficial supplement if you are trying to raise Glutathione levels. But, from what I have seen, it looks like it is something that should not be used in individuals with DS, and likely even autism.

There is concern that it increases oxidative stress in individuals with DS. We know they don't need anymore of that in their bodies!

Plus, it also appears that it can cause leaky gut syndrome, another thing which is not good to have in DS. And in DS, there is already a tendency towards gut problems. I know of one mother whose son was diagnosed with leaky gut syndrome just one month after starting NAC, interestingly.

Susan Owens, is a well known researcher in the autism world and Kay Ness shared some information that she had written regarding this concern a few years back. I'll quote a couple things from her email and share some research studies she shared.

"I found something I should have thought about a long time ago when I learned that N-acetylcysteine is the experimental and therapeutic best choice as an agent to break apart mucus. Somehow, back then, I didn't think about how this would effect the gut, but others have thought about it and conducted experiments to see what happened. Apparently, taking N-acetylcysteine breaks down the mucus that protects the brush border and the villi in the intestines and it thus increases intestinal permeability.

Perhaps finding out that NAC can increase intestinal permeability could explain why some do not do well on it."

The studies Susan included in her email:

JPEN J Parenter Enteral Nutr. 1996 Mar-Apr;20(2):98-104.

Adhesive mucous gel layer and mucus release as intestinal barrier in rats.

Iiboshi Y, Nezu R, Cui L, Chen K, Khan J, Yoshida H, Sando K, Kamata S, Takagi Y, Okada A.

Department of Pediatric Surgery, Osaka University Medical School, Japan.

BACKGROUND: Although it has been reported that total parenteral nutrition induces an increased intestinal permeability and a decreased mucous gel layer covering the intestinal epithelium, the role of mucous gel on intestinal permeability has not been well understood. We examined the in vivo effects of N-acetyl cysteine

(NAC) as mucolytic agent and colchicine as suppressant of the mucus production on the intestinal transmission of fluorescein isothiocyanate dextran 70,000 (FITC-dextran). METHODS: Rats were divided into four groups. In each group, FITC-dextran (750 mg/kg) with or without NAC (3000 mg/kg) was injected into the small intestinal lumen 3 hours after intraperitoneal injection of saline or colchicine (Col, 10 mg/kg). Thirty minutes after injection of FITC-dextran, blood samples were taken from portal vein to analyze plasma fluorescein concentration by fluorescence spectrometry. Samples of small intestine were sectioned in a cryostat for fluorescence microscopy, and the identical sections were stained by periodic acid-Schiff reaction. RESULTS: Plasma FITC-dextran level in NAC group was higher than that in control group (p < .01), that in Col + NAC group was higher than that in Col group (p < .01) and that in Col + NAC group was higher than that in NAC group (p < .05). The spaces between villi were filled with mucous gel in the control and Col groups, whereas those were not entirely filled with mucous gel in NAC and Col + NAC groups. FITC-dextran and mucous gel showed complementary distribution in all rats. The villous interstitial edema was recognized in NAC group and the villi were disrupted in Col + NAC group.

CONCLUSIONS: These results suggest that intestinal permeability is possibly affected not only by the mucous gel covering the intestinal epithelium but also by mucus release from goblet cells of the small intestine.

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 8676540 [Pubmed - indexed for MEDLINE]

1: Comp Biochem Physiol A Mol Integr Physiol. 2000 Jun;126(2):203-12.

Decreased colonic mucus in rats with loperamide-induced constipation.

Shimotoyodome A, Meguro S, Hase T, Tokimitsu I, Sakata T.

Biological Science Laboratories, Kao Corporation, 2606 Akabane, 321-3497 Ichikai-machi, Haga-gun, Tochigi, Japan.

Constipation is a risk factor of colorectal cancer. Mucin is a major component of lumenal mucus, which protects the colorectal mucosa against mechanical and chemical damage. The aim of this study was to evaluate mucus production and to quantitate lumen mucus in a rat model of spastic constipation. We induced constipation with loperamide (1.5 mg/kg), and histochemically evaluated mucus production and the thickness of the mucus layer at the fecal surface. We quantitated the mucus attached to the mucosal surface using colonic perfusion with N-acetylcysteine. While more feces remained in the colon, there was less fecal excretion and lower fecal water content in loperamide-administered rats than in control rats. Crypt epithelial cells contained less mucus in constipated rats than in control rats. The mucus layer at the fecal surface was thinner and less mucus was recovered from the mucosal surface in constipated rats than in control rats. Mucus production of crypt epithelial cells and mucus at the fecal and mucosal surface were reduced by loperamide-induced constipation.

PMID: 10936760 [Pubmed - indexed for MEDLINE]

2: JPEN J Parenter Enteral Nutr. 1999 Jan-Feb;23(1):19-23.

Role of intestinal mucus on the uptake of latex beads by Peyer's patches and on their transport to mesenteric lymph nodes in rats.

Khan J, Iiboshi Y, Cui L, Wasa M, Okada A.

Department of Pediatric Surgery, Osaka University Medical School, Japan.

BACKGROUND: The effects of N-acetylcysteine (NAC) as a mucolytic agent on the uptake of fluorescent polystyrene microparticles by Peyer's patches, on intestinal permeability, and on subsequent transport to mesenteric lymph nodes (MLNs) were investigated to establish the role of mucus gel layer in this process. METHODS: Twenty rats were divided into two groups: control (n =

10) and NAC (n = 10). Fluorescent polystyrene latex beads of 3.2+/-0.2 microm in diameter were used as a probe for measuring the previously mentioned parameters. The solution of latex beads (0.1 mL) was injected into a 2-cm length of ileal loop containing Peyer's patches, with 0.1 mL of saline (control group) or with 0.1 mL of NAC solution (NAC group) within 10 cm proximal from the ileocaecal valve.Intestinal loops, portal blood, and neighboring MLNs were taken within 1 hour of injection. Intestinal sections were stained by periodic acid-Schiff reagent. Peyer's patches and MLNs were analyzed for the count of particles by image analysis using a confocal laser scanning microscope. RESULTS: Morphologically, periodic acid-Schiff positive uniform mucus gel was present in front of Peyer's patches of the control group, and mucus gel layer was disrupted and noncontinuous in the NAC group. The number of particles within Peyer's patches and MLNs in the NAC group was significantly higher than that in the control group (p<.001). Intestinal permeability of latex beads in the NAC group was significantly higher than that in the control group (p<.001). CONCLUSIONS: These data suggest that the mucus gel layer located in front of Peyer's patches is one of the important factors for the uptake of noxious macromolecules, and this in turn plays a major role on small intestinal permeability and subsequent translocation to MLNs.

PMID: 9888413 [Pubmed - indexed for MEDLINE]

3: JPEN J Parenter Enteral Nutr. 1996 Nov-Dec;20(6):406-11.

Developmental changes in distribution of the mucous gel layer and intestinal permeability in rat small intestine.

Iiboshi Y, Nezu R, Khan J, Chen K, Cui L, Yoshida H, Wasa M, Fukuzawa M, Kamata S, Takagi Y, Okada A.

Department of Pediatric Surgery, Osaka University Medical School, Japan.

BACKGROUND: From the developmental aspects, the distribution of fluorescein isothiocyanate dextran 70,000 (FTTC-dextran) and mucous gel across the lumen of small intestine was observed as an investigation into the role of mucous gel on intestinal permeability. Furthermore, the effect of N-acetyl cysteine (NAC), a mucolytic agent, on intestinal permeability was examined. METHODS: In suckling and weaned rats, FTTC-dextran (750 mg/kg body wt) was gavage-fed. After 3 hours, blood samples were taken by cardiac puncture to analyze plasma FTTC-dextran by fluorescence spectrometry. Samples of small intestine with luminal contents were frozen and sectioned in a cryostat for fluorescence microscopy; the same sections were placed in a 0.2% celloidin solution to preserve mucous gel and were stained by periodic acid-Schiff reaction for light microscopy. In weaned rats, intestinal permeability was examined with different concentrations of intraluminally instilled NAC. RESULTS: The plasma level of FTTC-dextran showed a significant increase (p < .01) in suckling rats compared with the weaned rats. Morphologic findings were similar in both the jejunum and ileum: The spaces between villi were not entirely filled with mucus but filled with FTTC-dextran in suckling rats, whereas the spaces were filled with mucus and not filled with FTTC-dextran in weaned rats. Intestinal permeability in groups with NAC were significantly higher (p < .01) than that in group without NAC. CONCLUSIONS: These results suggest that an increase in the mucous gel layer that coats the epithelial lining according to the maturation of the gastrointestinal tract is one of the most important factors for a restriction in intestinal permeability.

Publication Types:

Research Support, Non-U.S. Gov't

PMID: 8950741 [Pubmed - indexed for MEDLINE]

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