Creatine Supplementation for Patients with Inflammatory Bowl Diseases: A Scientific Rationale for a Clinical Trial

Based on theoretical considerations, experimental data with cells in vitro, animal studies in vivo, as well as a single case pilot study with one colitis patient, a consolidated hypothesis can be put forward, stating that “oral supplementation with creatine monohydrate (Cr), a pleiotropic cellular energy precursor, is likely to be effective in inducing a favorable response and/or remission in patients with inflammatory bowel diseases (IBD), like ulcerative colitis and/or Crohn’s disease”. A current pilot clinical trial that incorporates the use of oral Cr at a dose of 2 × 7 g per day, over an initial period of 2 months in conjunction with ongoing therapies (NCT02463305) will be informative for the proposed larger, more long-term Cr supplementation study of 2 × 3–5 g of Cr per day for a time of 3–6 months. This strategy should be insightful to the potential for Cr in reducing or alleviating the symptoms of IBD. Supplementation with chemically pure Cr, a natural nutritional supplement, is well tolerated not only by healthy subjects, but also by patients with diverse neuromuscular diseases. If the outcome of such a clinical pilot study with Cr as monotherapy or in conjunction with metformin were positive, oral Cr supplementation could then be used in the future as potentially useful adjuvant therapeutic intervention for patients with IBD, preferably together with standard medication used for treating patients with chronic ulcerative colitis and/or Crohn’s disease.

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Differences in Visceral Fat and Fat Bacterial Colonization between Ulcerative Colitis and Crohn’s Disease. An In Vivo and In Vitro Study

PLoS ONE ◽

10.1371/journal.pone.0078495 ◽

2013 ◽

Vol 8 (10) ◽

pp. e78495 ◽

Cited By ~ 30

Author(s):

Alessandra Zulian ◽

Raffaella Cancello ◽

Chiara Ruocco ◽

Davide Gentilini ◽

Anna Maria Di Blasio ◽

...

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Visceral Fat ◽

Bacterial Colonization ◽

In Vitro Study ◽

Vitro Study

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Sonographic features of colonic Crohn's disease: Comparison of in vivo and in vitro studies

Journal of Clinical Ultrasound ◽

10.1002/jcu.1870180304 ◽

1990 ◽

Vol 18 (3) ◽

pp. 161-166 ◽

Cited By ~ 20

Author(s):

Bernd Limberg

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

In Vitro Studies

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Mesenchymal Stromal Cell Therapy in Crohn's Disease

Digestive Diseases ◽

10.1159/000449091 ◽

2017 ◽

Vol 35 (1-2) ◽

pp. 115-122 ◽

Cited By ~ 15

Author(s):

Geoffrey M. Forbes

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Adult Stem Cells ◽

Hla Class I ◽

Haematopoietic Stem Cell ◽

Dose Frequency ◽

Serious Adverse Events ◽

Considerable Work

Background: Mesenchymal stromal cells (MSC) are multipotent adult stem cells with immunomodulatory properties. They uniquely express HLA class I antigen at a low level, and do not express HLA class II. Hence, for allogeneic administration, donor to recipient matching is not required; yet a prolonged chimeric state does not occur. Contrary to haematopoietic stem cell transplantation, cytotoxic drug therapy is not required to harvest, or administer, cells. Key Messages: MSC are obtained from marrow, adipose tissue or placenta. In our centre, MSC are isolated from a 10 ml donor marrow aspirate, by virtue of their adherence to plastic. They are expanded in culture, cryopreserved, and subjected to strict quality controls before release for intravenous administration. These activities occur in a dedicated, nationally accredited, laboratory. Initial observations of allogeneic MSC efficacy were in graft-versus-host disease. Both autologous and allogeneic MSC have since been evaluated in biologic refractory luminal and fistulising Crohn's disease (CD). Data from early-phase studies have suggested efficacy for luminal disease when allogeneic MSC were given intravenously and also suggested efficacy for fistulising disease when either allogeneic or autologous MSC were administered into fistulas. MSC treatment is not reported to have caused serious adverse events. Although in vitro criteria for defining MSC exist, a major challenge lies in how to define MSC for clinical use. MSC function in vivo is likely to be dependent upon donor immunological characteristics, and widely varying manufacturing processes between laboratories. MSC dose, frequency of administration, stage of disease, and presence of concomitant immunosuppression also require to be defined. Conclusions: MSC therapy may have future utility in CD, but considerable work is first required to determine appropriate phenotypic and functional characteristics of administered cells.

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Peripheral Blood Based Discrimination of Ulcerative Colitis and Crohn’s Disease from Non-IBD Colitis by Genome-Wide Gene Expression Profiling

Disease Markers ◽

10.1155/2011/756290 ◽

2011 ◽

Vol 30 (1) ◽

pp. 1-17 ◽

Cited By ~ 17

Author(s):

Ferenc Sipos ◽

Orsolya Galamb ◽

Barnabás Wichmann ◽

Tibor Krenács ◽

Kinga Tóth ◽

...

Keyword(s):

Gene Expression ◽

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Peripheral Blood ◽

Independent Set ◽

Molecular Diagnostic ◽

Blood Samples ◽

Specificity And Sensitivity

A molecular diagnostic assay using easily accessible peripheral blood would greatly assist in the screening and diagnosis of ulcerative colitis (UC) and Crohn’s disease (CD). Transcriptional profiles in blood/biopsy samples from 12 UC (6/12), 9 CD (5/9), 6 non-inflammatory bowel disease (non-IBD) colitis (6/0), and 11 healthy (11/11) patients were assessed by Affymetrix HGU133Plus2.0 microarrays. Prediction analysis of microarrays, discriminant and ROC analyses were performed, the results were validated by RT-PCR and immunohistochemistry using also an independent set of samples (15 blood samples, 45 biopsies). A set of 13 transcripts was differentially expressed in IBD, non-IBD controls and healthy blood samples (100% specificity and sensitivity). Validated difference was found in 16 transcripts between UC, non-IBD and normal blood, and 4 transcripts between CD, non-IBD and normal samples. UC and CD blood cases could be also distinguished by 5 genes with 100% specificity and sensitivity. Some disease associated alterations in blood transcripts were also detected in colonic tissue. IBD subtypes may be discriminated from non-IBD (diverticulitis, infective and ischemic colitis)in vitrofrom peripheral blood by screening for differential gene expression revealed in this study. Transcriptional profile alterations in peripheral blood can be located in diseased colon.

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The effect of marine oil-derived n-3 fatty acids on transepithelial calcium transport in Caco-2 cell models of healthy and inflamed intestines

British Journal Of Nutrition ◽

10.1017/s0007114507201758 ◽

2007 ◽

Vol 97 (2) ◽

pp. 281-288 ◽

Cited By ~ 4

Author(s):

Jennifer Gilman ◽

Kevin D. Cashman

Keyword(s):

Fatty Acids ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Human Subjects ◽

Healthy Human ◽

Marine Oil ◽

Ca Transport ◽

Tnf Α

Marine oil-derived n-3 fatty acids have been shown to stimulate intestinal Ca absorption in animal studies, but the effects of such fatty acids on Ca absorption in human subjects are relatively unknown. In particular, n-3 fatty acids may be of therapeutic value for some Crohn's disease patients who experience Ca malabsorption. Therefore, the aim of the present study was to investigate the effect of 20 : 5n-3 and 22 : 6n-3 on transepithelial Ca transport across monolayers of healthy Caco-2 cells as well as of TNF-α-treated Caco-2 cells (an in vitro model of Crohn's disease). Caco-2 cells were seeded onto permeable filter supports and allowed to differentiate into monolayers, which were treated with 80 μm-20 : 5n-3, 80 μm-22 : 6n-3, or 40 μm-20 : 5n-3+40 μm-22 : 6n-3 for 6 or 8 d, with or without co-treatment with TNF-α (10 ng/ml) (n 11–15 monolayers per treatment). On day 16, transepithelial and transcellular transport of 45Ca and fluorescein transport (a marker of paracellular diffusion) were measured. Treatment of healthy and inflamed Caco-2 cells with 20 : 5n-3, 22 : 6n-3 and both fatty acids combined for 8 d significantly (P < 0·005–0·01) increased total transepithelial Ca transport compared with that in control, effects which were mediated by an enhanced rate of transcellular Ca transport. The effects of n-3 fatty acids on Ca absorption after 6 d were less clear-cut. In conclusion, the present in vitro findings highlight the need to investigate the effect of marine oil-based n-3 fatty acids on Ca absorption in vivo in studies of healthy human subjects as well as of Crohn's disease patients.

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