Glutathione from Wikipedia
"Glutathione: The Mother of All Antioxidants" from Huffpost Healthy Living
"In treating chronically ill patients with Functional Medicine for more than 10 years, I have discovered that glutathione deficiency is found in nearly all very ill patients. ... At first I thought that this was just a coincidental finding, but over the years I have come to realize that our ability to produce and maintain a high level of glutathione is critical to recovery from nearly all chronic illness -- and to preventing disease and maintaining optimal health and performance. The authors of those 76,000 medical articles on glutathione I mentioned earlier have found the same thing!"
"Impairment of intestinal glutathione synthesis in patients with inflammatory bowel disease" in Gut (1998)
"Decreased activity of key enzymes involved in GSH synthesis accompanied by a decreased availability of cyst(e)ine for GSH synthesis contribute to mucosal GSH deficiency in IBD. As the impaired mucosal antioxidative capacity may further promote oxidative damage, GSH deficiency might be a target for therapeutic intervention in IBD. "
Do you ever wonder what you really know about Crohn's Disease despite your experience and all the information out there? Do you find yourself unsettled, wondering why the pieces never seem to really fit together? Through simple questions linked to research evidence, this blog is a place where you can think quietly about Crohn's Disease, its cause, nature, and control. Join me in constructing a new view of Crohn's Disease. Your comments are gold.
Showing posts with label oxidative stress. Show all posts
Showing posts with label oxidative stress. Show all posts
10.5.12
4.5.12
Does L-carnitine improve Crohn's symptoms?
L-carnitine from Wikipedia
"L-carnitine and intestinal inflammation" in Vitamins and the immune system (2011) (pp. 353-366)
"The intestinal barrier is one of the most dynamic surfaces of the body. It is here where a single layer of epithelial cells mediates the intricate encounters that occur between the host's immune system and a multitude of potential threats present in the intestinal lumen. Several key factors play an important role in the final outcome of this interaction, including the state of oxidative stress, the level of activation of the immune cells, and the integrity of the epithelial barrier. This chapter describes the main evidence demonstrating the impact that L-carnitine has on each of these factors. These findings, combined with the demonstrated safety profile of L-carnitine, underscore the potential therapeutic value of L-carnitine supplementation in humans suffering from intestinal inflammation and highlight the functional data supporting an association between Crohn's disease and mutations in the L-carnitine transporter genes."
L-carnitine to Treat Fatigue Associated With Crohn's Disease, University of California, San Francisco
"L-carnitine and intestinal inflammation" in Vitamins and the immune system (2011) (pp. 353-366)
"The intestinal barrier is one of the most dynamic surfaces of the body. It is here where a single layer of epithelial cells mediates the intricate encounters that occur between the host's immune system and a multitude of potential threats present in the intestinal lumen. Several key factors play an important role in the final outcome of this interaction, including the state of oxidative stress, the level of activation of the immune cells, and the integrity of the epithelial barrier. This chapter describes the main evidence demonstrating the impact that L-carnitine has on each of these factors. These findings, combined with the demonstrated safety profile of L-carnitine, underscore the potential therapeutic value of L-carnitine supplementation in humans suffering from intestinal inflammation and highlight the functional data supporting an association between Crohn's disease and mutations in the L-carnitine transporter genes."
L-carnitine to Treat Fatigue Associated With Crohn's Disease, University of California, San Francisco
ClinicalTrials.gov identifier: NCT01523106
Estimated Enrollment: 200
Study Start Date: February 2012
Estimated Study Completion Date: February 2013
Active comparator: Patients will take 4 grams of L-carnitine (2 grams twice daily) for 3 months
"Role of carnitine in disease" in Nutrition and Metabolism (2010)
"Carnitine transporter mutations in Crohn's disease consists of missense mutation(s) in the gene coding plasma membrane transporter OCTN1 (SLC22A4) and/or mutation(s) in the promoter of the gene encoding OCTN2 (SLC22A5) [14,35]. Manifestation of these mutations results in disruption of a heat shock binding element decreasing the transport function (OCTN1), and reduced expression (through OCTN2 mutation) which both result in carnitine deficiency [14]. These mutations are in strong linkage disequilibrium, creating a two-allele risk haplotype and hence increasing the overall risk of this disease [14]."
"Identifying new therapeutic targets for treatment of Crohn's disease: The role of CD47 and L-carnitine in the pathogenesis and treatment of a murine model of intestinal inflammation", Geneviève Fortin
McGill University (2010)
"L-carnitine is an amino acid derivative normally present in meat and dairy products and is also available as an over-the-counter nutritional supplement. Since mutations in the L-carnitine transporters, OCTN1 and OCTN2, were found to be associated with CD, we sought to examine its role in the development of intestinal inflammation. Remarkably, L-carnitine displayed immunosuppressive properties both in vitro and in vivo, effectively suppressing both the innate and the adaptive arms of the immune response and resulting in a significant reduction in the development of intestinal inflammation."
"We have thus identified CD47 as an important regulator of SIRPα+ DC trafficking, and demonstrate that this DC subset is implicated in the development of intestinal inflammation. Additionally, we have identified two promising new therapeutic candidates, CD47-fc and L-carnitine, for the treatment of CD."
Estimated Enrollment: 200
Study Start Date: February 2012
Estimated Study Completion Date: February 2013
Active comparator: Patients will take 4 grams of L-carnitine (2 grams twice daily) for 3 months
"Role of carnitine in disease" in Nutrition and Metabolism (2010)
"Carnitine transporter mutations in Crohn's disease consists of missense mutation(s) in the gene coding plasma membrane transporter OCTN1 (SLC22A4) and/or mutation(s) in the promoter of the gene encoding OCTN2 (SLC22A5) [14,35]. Manifestation of these mutations results in disruption of a heat shock binding element decreasing the transport function (OCTN1), and reduced expression (through OCTN2 mutation) which both result in carnitine deficiency [14]. These mutations are in strong linkage disequilibrium, creating a two-allele risk haplotype and hence increasing the overall risk of this disease [14]."
"Identifying new therapeutic targets for treatment of Crohn's disease: The role of CD47 and L-carnitine in the pathogenesis and treatment of a murine model of intestinal inflammation", Geneviève Fortin
McGill University (2010)
"L-carnitine is an amino acid derivative normally present in meat and dairy products and is also available as an over-the-counter nutritional supplement. Since mutations in the L-carnitine transporters, OCTN1 and OCTN2, were found to be associated with CD, we sought to examine its role in the development of intestinal inflammation. Remarkably, L-carnitine displayed immunosuppressive properties both in vitro and in vivo, effectively suppressing both the innate and the adaptive arms of the immune response and resulting in a significant reduction in the development of intestinal inflammation."
"We have thus identified CD47 as an important regulator of SIRPα+ DC trafficking, and demonstrate that this DC subset is implicated in the development of intestinal inflammation. Additionally, we have identified two promising new therapeutic candidates, CD47-fc and L-carnitine, for the treatment of CD."
23.4.12
Does increasing choline improve Crohn's symptoms?
Choline - Wikipedia, the free encyclopedia
"Choline is a water-soluble essential nutrient.[1][2][3][4][5] It is usually grouped within the B-complex vitamins."
"There is some evidence to suggest that choline is anti-inflammatory. In the ATTICA study, higher dietary intake of choline was associated with lower levels of inflammatory markers.[27] A small study found that choline supplements reduced symptoms of allergic rhinitis."
"Choline or betaine supplements also may reducehomocysteine.[38]"
Choline from the world's healthiest foods
"Food sources of choline include soybeans, egg yolk, butter, peanuts, potatoes, cauliflower, lentils, oats, sesame seeds and flax seeds."
"Mild deficiency of choline has also been linked to fatigue, insomnia, poor ability of the kidneys to concentrate urine, problems with memory, and nerve-muscle imbalances. Choline deficiency can also cause deficiency of another B vitamin critically important for health, folic acid."
"In addition to poor dietary intake of choline itself, poor intake of other nutrients can result in choline deficiency. These nutrients include vitamins B-3, folic acid, and the amino acid methionine. The reason that these other nutrients can cause choline deficiency inolves the unusual chemical structure of choline as a "trimethylated" molecule."
"Dietary choline and betaine intakes in relation to concentrations of inflammatory markers in healthy adults: the ATTICA study." in Am J Clin Nutr (2008)
"Compared with the lowest tertile of choline intake (<250 mg/d), participants who consumed >310 mg/d had, on average, 22% lower concentrations of C-reactive protein (P < 0.05), 26% lower concentrations of interleukin-6 (P < 0.05), and 6% lower concentrations of tumor necrosis factor-alpha (P < 0.01). Similarly, participants who consumed >360 mg/d of betaine had, on average, 10% lower concentrations of homocysteine (P < 0.01), 19% lower concentrations of C-reactive protein (P < 0.1), and 12% lower concentrations of tumor necrosis factor-alpha (P < 0.05) than did those who consumed <260 mg/d. These findings were independent of various sociodemographic, lifestyle, and clinical characteristics of the participants."
"Is there a new component of the Mediterranean diet that reduces inflammation?" in Am J Clin Nutr (2008)
" It is possible that epigenetic mechanisms, via the methylation of promoter regions of genes involved in inflammation, are responsible for the observed association between dietary choline and betaine and inflammation (7). Choline-deficient humans overexpress genes in the immune-inflammatory response and lymphocyte differentiation-activation gene ontology groupings (14). Exposure to oxidative stress is a potent trigger for inflammation. Betaine is formed from choline within the mitochondria, and this oxidation contributes to mitochondrial redox status. Choline deficiency is associated with leaky mitochondria, leakage of free radicals, and damage to DNA (15-17). Thus, there are multiple potential mechanisms whereby diets lower in choline and betaine might result in increases in biomarkers of inflammation in healthy humans. If the association between choline and betaine and inflammation can be confirmed in studies of other populations, an interesting new dietary approach may be available for reducing chronic diseases associated with inflammation."
"Choline is a water-soluble essential nutrient.[1][2][3][4][5] It is usually grouped within the B-complex vitamins."
"There is some evidence to suggest that choline is anti-inflammatory. In the ATTICA study, higher dietary intake of choline was associated with lower levels of inflammatory markers.[27] A small study found that choline supplements reduced symptoms of allergic rhinitis."
"Choline or betaine supplements also may reducehomocysteine.[38]"
Choline from the world's healthiest foods
"Food sources of choline include soybeans, egg yolk, butter, peanuts, potatoes, cauliflower, lentils, oats, sesame seeds and flax seeds."
"Mild deficiency of choline has also been linked to fatigue, insomnia, poor ability of the kidneys to concentrate urine, problems with memory, and nerve-muscle imbalances. Choline deficiency can also cause deficiency of another B vitamin critically important for health, folic acid."
"In addition to poor dietary intake of choline itself, poor intake of other nutrients can result in choline deficiency. These nutrients include vitamins B-3, folic acid, and the amino acid methionine. The reason that these other nutrients can cause choline deficiency inolves the unusual chemical structure of choline as a "trimethylated" molecule."
"Dietary choline and betaine intakes in relation to concentrations of inflammatory markers in healthy adults: the ATTICA study." in Am J Clin Nutr (2008)
"Compared with the lowest tertile of choline intake (<250 mg/d), participants who consumed >310 mg/d had, on average, 22% lower concentrations of C-reactive protein (P < 0.05), 26% lower concentrations of interleukin-6 (P < 0.05), and 6% lower concentrations of tumor necrosis factor-alpha (P < 0.01). Similarly, participants who consumed >360 mg/d of betaine had, on average, 10% lower concentrations of homocysteine (P < 0.01), 19% lower concentrations of C-reactive protein (P < 0.1), and 12% lower concentrations of tumor necrosis factor-alpha (P < 0.05) than did those who consumed <260 mg/d. These findings were independent of various sociodemographic, lifestyle, and clinical characteristics of the participants."
"Is there a new component of the Mediterranean diet that reduces inflammation?" in Am J Clin Nutr (2008)
" It is possible that epigenetic mechanisms, via the methylation of promoter regions of genes involved in inflammation, are responsible for the observed association between dietary choline and betaine and inflammation (7). Choline-deficient humans overexpress genes in the immune-inflammatory response and lymphocyte differentiation-activation gene ontology groupings (14). Exposure to oxidative stress is a potent trigger for inflammation. Betaine is formed from choline within the mitochondria, and this oxidation contributes to mitochondrial redox status. Choline deficiency is associated with leaky mitochondria, leakage of free radicals, and damage to DNA (15-17). Thus, there are multiple potential mechanisms whereby diets lower in choline and betaine might result in increases in biomarkers of inflammation in healthy humans. If the association between choline and betaine and inflammation can be confirmed in studies of other populations, an interesting new dietary approach may be available for reducing chronic diseases associated with inflammation."
25.6.11
Can curcumin reduce Crohn's symptoms?

"Curcumin is the principal curcuminoid of the popular Indian spice turmeric, which is a member of the ginger family (Zingiberaceae). ... At present, these effects have not been confirmed in humans. However, as of 2008, numerous clinical trials in humans were underway, studying the effect of curcumin on various diseases, including multiple myeloma, pancreatic cancer, myelodysplastic syndromes, colon cancer, psoriasis, and Alzheimer's disease. In vitro and animal studies have suggested curcumin may have antitumor, antioxidant, antiarthritic, antiamyloid, anti-ischemic, and anti-inflammatory properties. ... Curcumin acts as a free radical scavenger and antioxidant, inhibiting lipid peroxidation[19] and oxidative DNA damage."
Tumeric from the world's healthiest foods
"A Potent, Yet Safe Anti-Inflammatory: The volatile oil fraction of turmeric has demonstrated significant anti-inflammatory activity in a variety of experimental models. Even more potent than its volatile oil is the yellow or orange pigment of turmeric, which is called curcumin. Curcumin is thought to be the primary pharmacological agent in turmeric. In numerous studies, curcumin's anti-inflammatory effects have been shown to be comparable to the potent drugs hydrocortisone and phenylbutazone as well as over-the-counter anti-inflammatory agents such as Motrin. Unlike the drugs, which are associated with significant toxic effects (ulcer formation, decreased white blood cell count, intestinal bleeding), curcumin produces no toxicity.An Effective Treatment for Inflammatory Bowel Disease: Curcumin may provide an inexpensive, well-tolerated, and effective treatment for inflammatory bowel disease (IBD) such as Crohn's and ulcerative colitis, recent research suggests. In this study, mice given an inflammatory agent that normally induces colitis were protected when curcumin was added to their diet five days beforehand. The mice receiving curcumin not only lost much less weight than the control animals, but when researchers checked their intestinal cell function, all the signs typical of colitis (mucosal ulceration, thickening of the intestinal wall, and the infiltration of inflammatory cells)were all much reduced. While the researchers are not yet sure exactly how curcumin achieves its protective effects, they think its benefits are the result of not only antioxidant activity, but also inhibition of a major cellular inflammatory agent called NF kappa-B. Plus, an important part of the good news reported in this study is the fact that although curcumin has been found to be safe at very large doses, this component of turmeric was effective at a concentration as low as 0.25 per cent&mash;an amount easily supplied by simply enjoying turmeric in flavorful curries.
Relief for Rheumatoid Arthritis: Clinical studies have substantiated that curcumin also exerts very powerful antioxidant effects. As an antioxidant, curcumin is able to neutralize free radicals, chemicals that can travel through the body and cause great amounts of damage to healthy cells and cell membranes. This is important in many diseases, such as arthritis, where free radicals are responsible for the painful joint inflammation and eventual damage to the joints. Turmeric's combination of antioxidant and anti-inflammatory effects explains why many people with joint disease find relief when they use the spice regularly. In a recent study of patients with rheumatoid arthritis, curcumin was compared to phenylbutazone and produced comparable improvements in shortened duration of morning stiffness, lengthened walking time, and reduced joint swelling."
For ideas on how to increase bioavailability, see "Make Mincemeat of Cancer Cells With This Breakthrough Spice" from Mercola.com
"One work-around is to use the curcumin powder and make a microemulsion of it by combining a tablespoon of the powder and mixing it into 1-2 egg yolks and a teaspoon or two of melted coconut oil. Then use a high speed hand blender to emulsify the powder.
Another strategy that can help increase absorption is to put one tablespoon of the curcumin powder into a quart of boiling water. It must be boiling when you add the powder as it will not work as well if you put it in room temperature water and heat the water and curcumin. After boiling it for ten minutes you will have created a 12 percent solution that you can drink once it has cooled down. It will have a woody taste. The curcumin will gradually fall out of solution however. In about six hours it will be a 6 percent solution, so it's best to drink the water within four hours. Dr. LaValley is also helping us beta test new curcumin preparations that will radically simplify this process."
"Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets" in Trends in Pharmcological Targets (2009)
"Extensive research within the past two decades has shown that curcumin mediates its anti-inflammatory effects through the downregulation of inflammatory transcription factors (such as nuclear factor κB), enzymes (such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6)."
"Dietary polyphenols can modulate the intestinal inflammatory response" in Nutrition Reviews (2009)
"Studies, conducted using in vivo and in vitro models, provide evidence that pure polyphenolic compounds and natural polyphenolic plant extracts can modulate intestinal inflammation."
"Anti-Inflammatory Effects of Resveratrol, Curcumin and Simvastatin in Acute Small Intestinal Inflammation " in PLoS ONE (2010)
"In a recent study, Curcumin has been shown to inhibit oxidative stress [36] that in turn has been associated with tight junction opening, thereby modifying intestinal permeability [37]. In the present study, bacterial translocation rates (due to compromised epithelial barrier function) into spleen and cardiac blood after treatment with either compound were lower as compared to the Placebo group. Therefore, Resveratrol, Simvastatin, and Curcumin might modulate tight junction protein expression and function." [See my post entitled "Does Resveratol lessen the symptoms of CD?"]"Curcumin: Getting Back to the Roots" by Shishodia et al., Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas
"Modern science has revealed that curcumin mediates its effects by modulation of several important molecular targets, including transcription factors (e.g., NF- B, AP-1, Egr-1, -catenin, and PPAR- ), enzymes (e.g., COX2, 5-LOX, iNOS, and hemeoxygenase-1), cell cycle proteins (e.g., cyclin D1 and p21), cytokines (e.g., TNF, IL-1, IL-6, and chemokines), receptors (e.g., EGFR and HER2), and cell surface adhesion molecules. Because it can modulate the expression of these targets, curcumin is now being used to treat cancer, arthritis, diabetes, Crohn’s disease, cardiovascular diseases, osteoporosis, Alzheimer’s disease, psoriasis, and other pathologies."
"Curcumin has Bright Prospects for the Treatment of Inflammatory Bowel Disease" in Current Pharmaceutical Design (2009)
"... [I]n recent years, a large number of research papers have reported intriguing pharmacologic effects associated with curcumin. These include inhibitory effects on cyclooxygenases 1, 2 (COX-1, COX-2), lipoxygenase (LOX), TNF-α, interferon γ (IFN-γ), inducible nitric oxide synthase (iNOS), and the transcriptional nuclear factor kappa B (NF-κB), in addition to a strong anti-oxidant effect. NF-κB is a key factor in the upregulation of inflammatory cytokines that have a high profile in inflammatory diseases, suggesting that curcumin could be a novel therapeutic agent for patients with IBD. Therefore, in recent years, the efficacy of curcumin has been investigated in several experimental models of IBD. The results indicate striking suppression of induced IBD colitis and changes in cytokine profiles, from the pro-inflammatory Th1 to the anti-inflammatory Th2 type. In human IBD, up to now, only one open study has achieved encouraging results. In this study, patients were given curcumin (360mg/dose) 3 or 4 times/day for three months. Further, curcumin significantly reduced clinical relapse in patients with quiescent IBD. The inhibitory effects of curcumin on major inflammatory mechanisms like COX-2, LOX, TNF-α, IFN-γ, NF-κB and its unrivalled safety profile suggest that it has bright prospects in the treatment of IBD. However, randomized controlled clinical investigations in large cohorts of patients are needed to fully evaluate the clinical potential of curcumin."
"Curcumin for inflammatory bowel disease: a review of human studies" in Alt Med Rev (2011)
"Although two small studies have shown promising results, all authors conclude that larger-scale, double-blind trials need to be conducted to establish a role for curcumin in the treatment of ulcerative colitis. In addition to improving results when used in conjunction with conventional medications for UC, curcumin may pose a less-expensive alternative."
"Novel formulation of solid lipid microparticles of curcumin for anti-angiogenic and anti-inflammatory activity for optimization of therapy of inflammatory bowel disease" in Journal of Pharmact and Pharmacology (2010)
"Objectives This project was undertaken with a view to optimize the treatment of inflammatory bowel disease through a novel drug delivery approach for localized treatment in the colon. Curcumin has poor aqueous solubility, poor stability in the gastrointestinal tract and poor bioavailability. The purpose of the study was to prepare and evaluate the anti-inflammatory activity of solid lipid microparticles (SLMs) of curcumin for the treatment of inflammatory bowel disease in a colitis-induced rat model by a colon-specific delivery approach. ...
Conclusions The degree of colitis caused by administration of DSS was significantly attenuated by colonic delivery of SLMs of curcumin. Being a nontoxic natural dietary product, curcumin could be useful in the therapeutic strategy for inflammatory bowel disease patients."
"Molecular Targets of Dietary Polyphenols with Anti-inflammatory Properties" in Yonsei Med J (2005)
"Studies using isolated bovine COX-1 and COX-2 enzymes showed that curcumin had significantly higher inhibitory effects on the peroxidase activity of COX-1 than that of COX-2"
"Bioavailability of curcumin" post on Margaret's Corner, section on "My Discovery of Curcumin" and her journey with Multiple Myeloma"Pre-, "Pro-, Synbiotics and Human Health"in Symbiotics and Human Health (2010)
"... eating substantial amounts of foods with documented anti-inflammatory effects such as turmeric/curcumin, molecules which might be included in future synbiotic compositions."
See my post "Can ginger reduce the symptoms of CD?"
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