Showing posts with label bioavailability. Show all posts
Showing posts with label bioavailability. Show all posts

29.7.11

Do probiotics lessen Crohn's symptoms?

Probiotic on Wikipedia
" ... live microorganisms thought to be beneficial to the host organism. ...Lactic acid bacteria (LAB) and bifidobacteria are the most common types of microbes used as probiotics; but certain yeasts and bacilli may also be helpful. Probiotics are commonly consumed as part of fermented foods with specially added active live cultures; such as in yogurt, soy yogurt, or as dietary supplements."

"What are some of the best food sources for probiotics and prebiotics?" from the world's healthiest foods
"Cultured dairy foods such as yogurt and kefir can be great sources of "healthy" or "friendly" bacteria. ... In most prepackaged, processed foods, however, it is unlikely to find any sizable quantities of live bacteria ("probiotics") due to the use of heat and chemicals in food processing. ...  it's important to select cultured dairy products that indicate "contains live cultures" or "contains active cultures" on the packaging. Some manufactures will actually report the amounts of live culture contained in the product.
Live bacterial cultures can be added to other foods besides dairy foods. Sauerkraut-another name for fermented cabbage-is an example of a cultured vegetable. An Asian version of fermented cabbage, particularly popular in Korea, is called kim chee. A basic fermentation process is used to culture the cabbage in kim chee, and chili pepper, garlic, and salt are typically added to give this cultured vegetable its pungent character. As with cultured yogurts and kefirs, these fermented vegetables may or may not contain active bacterial cultures. Once again, the manufacturers who are sensitive to these issues will often indicate the presence of live bacteria cultures (if they are present) on the packaging. Miso, a thick paste often made from soybeans, is another example of a cultured food that can contain live bacterial populations."


"Pre-, Pro-, Synbiotics and Human Health" in Synbiotics and Human Health (2010)
"The reason why attempts to reduce inflammation with the use of probiotics sometimes failed in the past might be that the pro-inflammatory pressure is simply too high due to the underlying disease, but also due to the consumption of too much of pro-inflammatory foods and prescription drugs, all with inflammation-enhancing abilities. It is likely that under certain conditions, additional measures are needed in order to achieve successful treatment with  probiotics. Measures such as reduced supply of pro-inflammatory foods, restriction in the use of pharmaceuticals and increased intake of plant foods rich in anti-inflammatory vitamins and antioxidants, especially various polyphenols, might well be needed.
...
Thousands of factors are important to maintain health and to cure disease. This might explain why single drug
pharmacy fails both to prevent a disease and to cure it, especially when chronic. Human innate immunity for a proper function much depends on continuous access to bacteria and plants. Using probiotics in combination with plants and their active ingredients remains an attractive approach for prevention and treatment of various acute and chronic diseases."

"Colon-specific delivery of a probiotic-derived soluble protein ameliorates intestinal inflammation in mice through an EGFR-dependent mechanism " in J Clin Invest (2011)
"... The effects of probiotics on the clinical course of Crohn disease are controversial.

Recently, three distinct and complementary cellular mechanisms for the actions of probiotics were proposed (11). First, probiotics block pathogenic bacterial effects by producing bacteriocidal substances and competing with pathogens and toxins for adherence to the intestinal epithelium. Second, probiotics regulate immune responses by enhancing innate immunity and modulating pathogen-induced inflammation via Toll-like receptor–regulated signaling pathways. Third, probiotics regulate intestinal epithelial homeostasis by promoting intestinal epithelial cell survival, barrier function, and protective responses through several signaling pathways.

The clinical application of probiotics has at least two limitations: bioavailability and biosafety. For example, bacteremia associated with probiotic therapy has been reported in very young (12) and immunocompromised patients (13). One potential approach to address these concerns may be development of probiotic bacteria–derived proteins as novel therapeutic agents. Thus, identification of probiotic-derived soluble factors that exert effects similar to those of probiotics offers not only insight into the mechanisms of probiotic action, but also significant potential for clinical application. ...

In the present study, we demonstrate that the LGG-derived soluble protein p40 activates EGFR in vivo and in vitro in colon epithelial cells. Activation of EGFR by p40 is required for inhibition of cytokine-induced apoptosis and disruption of barrier integrity in intestinal epithelial cells in vitro and ex vivo. Importantly, p40 prevents and treats DSS-induced colon epithelial injury and inflammation and ameliorates oxazolone-induced colitis, and it mediates reductions of intestinal epithelial apoptosis and disruption of barrier function in these two mouse models, in an EGFR activation-dependent manner. Therefore, our findings provide a rationale for conducting new hypothesis-driven studies to define the clinical efficacy of probiotic-derived proteins in preventive, adjunctive, or alternative treatments for intestinal inflammatory disorders. ...

A number of disorders of the gastrointestinal tract, including IBD, are characterized by elevated cytokine production and increased apoptosis, which disrupt the integrity of the protective epithelial monolayer. Therefore, strategies that promote maintenance of intestinal epithelial integrity may serve as effective approaches for treatment of IBD and other cytokine-mediated intestinal disorders. ...

However, it should be noted that aberrant EGFR activation due to overexpression and/or mutation of EGFR and autocrine growth factor loops have been related to hyperproliferative diseases such as cancer. Thus, one concern regarding probiotic therapy in IBD is an increased risk of cancer. ...

We are focusing on determining the mechanisms by which p40 regulates innate immunity. It has been reported that LGG-conditioned cell culture media decreases TNF production in macrophages, indicating that soluble molecules derived from LGG exert this immunoregulatory role (20). Therefore, we hypothesize that p40 may have direct effects on macrophages and/or lymphocytes to regulate immune responses during inflammation. This hypothesis is being tested in our laboratory. ...

Although both p40 and p75 are able to prevent cytokine-induced apoptosis, p40 appears more potent than p75 (our unpublished observations). It is likely that additional factors secreted by LGG and other probiotic bacteria may have cytoprotective or immunological effects in the gastro­intestinal tract or other tissues, and thus this field represents an important area for further investigation. ...

This is the first report to our knowledge showing delivery of probiotic-derived soluble proteins to the colon to protect mice from colitis. This effect is mediated through activation of EGFR and supports development of probiotic-derived proteins as novel reagents for preventing and/or treating ulcerative intestinal inflammatory disorders." [Emphases mine.]


Does magnesium supplementation improve Crohn's symptoms?

The Magnesium Website Online Library

Magnesium in biology from Wikipedia

Dietary Supplement Fact Sheet

Micronutrient Information CenterMagnesium from the Linus Pauling Institute

Magnesium from the world's healthiest foods
excellent sources: Swiss boiled chard, spinach
very good:  kelp, summer squash, turnip greens, mustard greens, raw pumpkin seeds, black strap molasses, steamed broccoli, baked/boiled halibut

Common Conditions That May Result from Low Magnesium Levels




25.6.11

Can curcumin reduce Crohn's symptoms?

Curcumin on Wikipedia
"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."

"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?"

11.6.11

How can bioavailability be improved in Crohn's?

Premeal drink of a fatty acid mixed in a nutritional supplement
Inflammatory bowel disease: from bench to bedside, Targon et al. (2005)
"We have shown recently that abnormally rapid transit contributes to poor bioavailability of an oral drug in IBD patients with chronic diarrhea, and that drug bioavailability can be readily and safely increased with the fatty acid-based therapy." (
"... this therapy is directed specifically at slowing gastro-intestinal transit, an important beneficial side-effect of this therpy is increased contact time of the luminal contents with digestive enzymes and absorptive surfaces.  In addition to improving diarrhea, this therapy is likely to improve nutrition by increasing digestion and absorption of a meal. ... the end products of fat digestion are the most potent nutrient triggers of the intestinal brake system" (p. 597)