Crohn's Disease - Thorne Research

ReviewCrohn’s Diseasenormal and deranged endogenous responses. Astudy examined mucosal tissue SOD levels andfound manganese-dependent SOD (Mn-SOD) wassignificantly higher in IBD patients, includingthose with CD – 1.6-fold higher in non-inflamedtissue and almost 3-fold higher in inflamed tissue.230 These same researchers, in a follow-upstudy, found metallothionein levels were significantlylower in inflamed mucosa from CD patientscompared to non-inflamed mucosa and normalcontrols. Catalase activity was increased 1.5-foldin non-inflamed and 2.5-fold in inflamed mucosa;glutathione peroxidase activity was increased inboth inflamed and non-inflamed mucosa; andmyeloperoxidase levels were increased 1.5-foldin non-inflamed and 2.3-fold in inflamed mucosa.The researchers hypothesize an increase in theratio of step 1 of endogenous free-radical quenchingactivity in relation to step 2 (Figure 1), resultingin an over-abundance of hydrogen peroxide,hypochlorous acid, and hydroxyl radicals in inflammatorybowel disease. 231 Exogenous antioxidantsin the form of supplementation may helprelieve the burden.A study using synthetic antioxidants (e.g.,BHA; butylated hydroxyanisole) in tissue culturefound antioxidants decreased inflammatorycytokine production, although the effects weremore dramatic in tissue from UC patients than CDpatients. 232GlutathioneReduced glutathione (GSH), an endogenousquencher of hydrogen peroxide, may be of benefitas an exogenous supplement. GSH was deficient andoxidized glutathione (GSSG) elevated in tissuesamples from 12 CD patients – demonstrating increasedoxidative stress in patients compared to sevencontrols. Another arm of the study examined the effectof oral supplementation of glutathione to ratsand found 1.3-fold and 3.5-fold increases in tissueGSH after 0.4 mM/kg and 4.0 mM/kg, respectively. 233Nutrients that enhance glutathione levels, either asco-factors for glutathione reductase (e.g., riboflavinand niacin) or because they spare glutathione or contributeto its synthesis (e.g., N-acetylcysteine, lipoicacid), may prove of benefit in CD as well.Vitamins C and EIn a study of 57 CD patients in remissionbut demonstrating oxidative stress, subjects wererandomly assigned to receive 800 IU vitamin Eand 1,000 mg vitamin C or double placebo for fourweeks. Oxidative stress significantly decreased inthe supplemented group as measured by breathpentaneand -ethane and plasma F2-isoprostane.Disease activity remained low in both groups duringthe one-month study. 234Vitamin ABecause vitamin A enhances epithelial celldifferentiation and CD is characterized by disruptionsin intestinal epithelium, supplementation wastried in a CD patient at a dose of 50,000 IU threetimes daily along with vitamin E 100 mg threetimes daily for two weeks. Diarrhea she had beenexperiencing disappeared. After experimentingwith each of the vitamins alone, it was concludedvitamin A was responsible for the improvementin bowel movements. 235 Based on this case reporta small pilot study examined clinical and laboratoryparameters in eight patients with severe CDwho were supplemented with 50,000 IU vitaminA three times daily for two weeks. No changes inbowel habits, abdominal pain, or gut permeabilitywere noted. 236 Although it may have been sufficienttime to note clinical improvement, structuralimprovements in gut permeability wouldlikely take longer than two weeks.A more extensive study involving 86 CDpatients examined the effect of 50,000 IU vitaminA acetate twice daily or placebo for an average of14.1 months. All patients had been in remissionfor at least three months prior to study onset. Nodifferences were noted between the two groupsregarding disease activity, rate of relapse, or laboratoryparameters. Serum levels of vitamin A werenot significantly higher than the placebo groupuntil the fifth month of the trial. Discontinuationof vitamin A at the end of the trial did not result inclinical deterioration. 237Alternative Medicine Review ◆ Volume 9, Number 4 ◆ 2004 Page 383Copyright©2004 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission