Sunday, July 28, 2013
One of the major herbal remedies recommended for topical irritation is an extract from the aloe vera plant. It has been used since the first century CE as a treatment for multiple skin conditions, ranging for sunburn to psoriasis. The efficacy of aloe vera for skin treatments isn’t covered here, but it oral use has been proposed to treat ulcerative colitis, based on the principal that it would have similar “topical” healing effects on the colon. There is a current clinical trial to use aloe vera (1) as a treatment for mild UC, and there have been previous studies looking at its effects for UC patients. We’ll take a look at the current research in this posting.
The initial research done on treating UC in humans was published in 2004 and was based on a double blind, placebo controlled study. An earlier study in rats provided little support for its use as a treatment - though there was potentially a small preventative affect(2), but the 2004 study was the first widely available controlled study to look at the impact through objective measures.(3)
The 2004 study was well designed, and contained the appropriate controls and measures. It looked at 44 patients with 14 controls (given placebo) and 30 given aloe vera gel liquid. Six of the aloe vera patients withdrew and 3 of the controls prior to the end of the study, resulting in 38 in the treatment group and 11 controls.(3)
The study looked at the outcomes on a variety of measures – blood results, sigmoidoscopy results, SCCAI scores and IBDQ scores. The authors concluded that there were a larger number of individuals who achieved SCCAI scores in the remission category than the placebo category, but a close look shows the average SCCAI score dropped further in the placebo group. The sigmoidoscopy and blood test scores were not statistically different between groups (there was a greater drop in blood test numbers on the active group, but the end average and spread were the same as placebo). The IBDIQ scores rose in both groups, with a higher rise in the placebo group, but neither was statistically significant.(3)
The above study found no significant side effects in either group. A broader study of general side effects of Aloe Vera found, however, that oral ingestion can cause diarrhea, electrolyte imbalance, kidney dysfunction, and conventional drug interactions.(4)
There is no compelling evidence to use aloe vera to treat UC at this time. There may be positive result from future studies, but there are side effect of taking it that can be detrimental to those with UC that are known today with no statistically significant efficacy shown in any controlled, large trial.
The European Evidence-Based Consensus on the Treatment of UC concluded:
ECCO Statement 13E
There is insufficient evidence for the use of acupuncture, Boswellia serrata gum, germinated barley, aloe vera gel and other herbal medicines in the treatment of UC. (5)
- Several companies market aloe vera-based products to treat ulcerative colitis.
- There is no statistically significant evidence to recommend UC patients take aloe vera supplements
- There are known side effects, including diarrhea and electrolyte imbalance, that can exacerbate problems for UC patients.
2. Korkina, Ludmila, Maxim Suprun, Anna Petrova, Elena Mikhal'Chik, Antonio Luci, and Chiara De Luca. "The protective and healing effects of a natural antioxidant formulation based on ubiquinol and Aloe vera against dextran sulfate-induced ulcerative colitis in rats." Biofactors 18, no. 1 (2003): 255-264.
3. Langmead, L., R. M. Feakins, S. Goldthorpe, H. Holt, E. Tsironi, A. De Silva, D. P. Jewell, and D. S. Rampton. "Randomized, double‐blind, placebo‐controlled trial of oral aloe vera gel for active ulcerative colitis." Alimentary pharmacology & therapeutics 19, no. 7 (2004): 739-747.
4. Boudreau, Mary D., and Frederick A. Beland. "An evaluation of the biological and toxicological properties of Aloe barbadensis (miller), Aloe vera." Journal of Environmental Science and Health Part C 24, no. 1 (2006): 103-154.
5. Travis, S. P. L., E. F. Stange, M. L mann, T. resland, W. A. Bemelman, Y. Chowers, J. F. Colombel et al. "European evidence-based consensus on the management of ulcerative colitis: current management." Journal of Crohn's and Colitis 2, no. 1 (2008): 24-62.
Posted by Martin Bishop at 2:58 PM
Sunday, July 21, 2013
Medical Marijuana and IBD
The great pot debate has been raging for several years. While possessing marijuana is still a federal offense, many state governments have chosen to create medical marijuana exceptions to laws at a state level. At a federal level, resource limitations and other priorities have limited any federal enforcement of medical marijuana providers at a state level.
Medical marijuana has been proposed as a treatment for many conditions, ranging from glaucoma relief to its use as an anti-emetic by cancer patients. This post focuses on the use of marijuana and cannabinoids on inflammatory bowel disease from a medical perspective, and does not address other uses of the drug or its legal status.
Marijuana has been shown to have a modulation effect on the cannabinoid receptors CB1 and CB2 in rat studies. Because CB1 and CB2 are related to enteric and immune modulation, marijuana has the potential for impacting Crohn’s and Ulcerative Colitis patients (though positively or negatively is not known).(1) There has been some human genetic research showing that CNR1, a human cannabinoid receptor, has a modulation effect on the susceptibility of an individual to Crohn’s and UC.(2) There is even some evidence in mouse models of colitis that cannabidiol (not the psychotropic THC), an ingredient of marijuana, has a positive impact on intestinal protection.(3)
Marijuana has been postulated to have a positive effect on both Crohn’s disease and Ulcerative Colitis, however the evidence for it doing so is sparse. The most cited study looking at the effects showed a positive increase in the health of individuals who used marijuana and had Crohn’s disease. Unfortunately, the study only included 30 patients and was a retrospective (and uncontrolled) study.(4) A smaller study, consisting of 21 patients, showed a positive change in CDAI scores vs. placebo in a prospective look. This study used cigarettes with THC for the active and with the THC removed for the control, so the study was likely not blind to the users.(5) To date, there have been no large-scale, well-controlled studies showing the efficacy of marijuana for IBD.
Marijuana consumption through smoking has many of the same associated negatives as nicotine-based smoking, though some to a lesser degree, including the impact on the lungs and the psychotropic effects (which can also be a positive in some circumstances). Additionally, smoking marijuana has an impact on gastric motility, slowing down digestive function, which may be dangerous for individuals with structuring disease.(6)
If a particular cannabinoid can be isolated and taken orally to interact positively with the CB1 and CB2 receptors, it may open up a new treatment path for IBD. Right now, smoking marijuana has known negative side effects (and the cannabinoid ratios are not well controlled), and has not shown efficacy in quality evidence-based studies for the treatment of Crohn’s and Ulcerative Colitis. That said, preliminary studies show areas of promise, and cannabinoid extracts may prove an effective treatment with substantial testing and research (though more likely through oral administration than inhalation).
· Smoking marijuana to treat Crohn’s and Ulcerative Colitis has no solid proof of efficacy.
· There are known negative side effects to smoking marijuana, and unless better evidence is uncovered, its use by those with IBD is not warranted.
1. Tsou, K., S. Brown, M. C. Sanudo-Pena, K. Mackie, and J. M. Walker. "Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system." Neuroscience 83, no. 2 (1997): 393-411.
2. Storr, Martin, Dominik Emmerdinger, Julia Diegelmann, Simone Pfennig, Thomas Ochsenkühn, Burkhard Göke, Peter Lohse, and Stephan Brand. "The cannabinoid 1 receptor (CNR1) 1359 G/A polymorphism modulates susceptibility to ulcerative colitis and the phenotype in Crohn's disease." PLoS One 5, no. 2 (2010): e9453.
3. Borrelli, Francesca, Gabriella Aviello, Barbara Romano, Pierangelo Orlando, Raffaele Capasso, Francesco Maiello, Federico Guadagno et al. "Cannabidiol, a safe and non-psychotropic ingredient of the marijuana plant Cannabis sativa, is protective in a murine model of colitis." Journal of molecular medicine 87, no. 11 (2009): 1111-1121.
4. Naftali, T., L. Bar Lev, D. Yablecovitch, E. Half, and F. M. Konikoff. "Treatment of Crohn's disease with cannabis: an observational study." The Israel Medical Association journal: IMAJ 13, no. 8 (2011): 455.
5. Naftali, Timna, Lihi Bar Lev, Iris Dotan, Ephraim Philip Lansky, Benjaminov Fabiana Sklerovsky, and Fred Meir Konikoff. "Cannabis Induces a Clinical Response in Patients with Crohn’s Disease: a Prospective Placebo-Controlled Study." Clinical Gastroenterology and Hepatology (2013).
6. Aviello, G., B. Romano, and A. A. Izzo. "Cannabinoids and gastrointestinal motility: animal and human studies." Eur Rev Med Pharmacol Sci 12, no. Suppl 1 (2008): 81-93.
Posted by Martin Bishop at 2:55 PM
Sunday, July 14, 2013
Flares and IBD
What constitutes a flare in Crohn’s Disease and Ulcerative Colitis? We use the term to mean any active state of the disease in which we are feeling less than optimal. It is generally characterized by increased diarrhea, abdominal pain, and similar states of distress. Because we are looking at evidence-based medicine, is there a clinical definition of a flare that we can use? The best clinical definition is disease that is not in a state of remission. Unfortunately, that simply shifts the need to accurately define remission. There have been several attempts to quantify remission, with the most common being the Crohn’s Disease Activity Index (CDAI).
The CDAI was put forth in 1976 as a mechanism for quantifying the state of an individual’s disease. By quantifying the disease through a rating of symptoms, the progression can be tracked and the efficacy of medication can be judged. The CDAI provided a mix of both quantifiable, objective measures with subjective (though still quantified) evaluations. The primary areas of the CDAI are as follows:
2 points for each liquid or soft stool from the past week.
5 points for level of severity (0-3) of abdominal pain each day for the past week
7 points for each level of general malaise (0-4) each day for the past week
20 points each for:
· Eye inflammation
· Ulcerations of the mouth, lips, or gums
· Perianal disease
· Fever during the past week
30 points for taking Lomotil or an opiate to control diarrhea
10 points for each level of abdominal mass present (0-5)
6 points for a Hematocrit of <0.47 in men and <0.42 in women
1 points for every percentage point above/below expected weight
Any score about 150 for the CDAI is considered to be active disease, or a “flare”.(1) The CDAI is still in use, but has several criticisms, a few of which include:
· It does not include other blood tests, like CRP, that are associated with inflammation
· The results of a colonoscopy, sigmoidoscopy, or endoscopy are not included (or any other imaging)
· Some of the general well-being evaluations are overly subjective, and don’t include things like fatigue or depression
· There are multiple ways to control diarrhea, and the presence or absence of taking a particular drug may be a poor measure
· It is primarily focused on Crohn’s disease vice Ulcerative Colitis (though there is a correlation to UC scores and health)
As an alternative (or complement) to CDAI, the Inflammatory Bowel Disease Questionnaire (IBDQ) was developed. The IBDQ is a copyrighted, 32 question assessment used to look at the quality of life issues impacting those with IBD. Each question is provided a 1-7 scale, with one being the worst score and 7 being the best. While not specific to detecting remission, the IBDQ is helpful in tracking patient quality of life over the course of time. A short version of the IBDQ is available for patient self-use at http://www.remicade.com/remicade/assets/SIBDQ_PDF.pdf, and there are multiple variants to the original IBDQ that have been proposed and are available in the research literature.(2) Other IBD measures, such as the Simple Index of Crohn’s Disease Activity, are used in multiple research areas, generally for large patient population evaluations.(3)
There is still room for improvement in creating special-purpose tools to identify flares. The indices can quantify the state of the disease in an individual, but don’t take into account the “normal” baseline, making the identification of “flare” points difficult. Because general IBD health is a gradient and not a binary status, no measure is likely to be perfect. Hence the term “flare” has a fairly arbitrary usage as a non-clinical term meaning a currently poor state of health due to active disease.
· Flares are an active state of Crohn’s or Ulcerative Colitis where the patient is no longer in remission.
· Tools such as the CDAI, SICDA, and IBDQ allow for objective tracking of disease progress over time.
· There is room for improvement in most of the indices, and as new markers and correlations are identified they can be expected to be further modified to reflect the new research.
1. Best, William R., Jack M. Becktel, John W. Singleton, and F. Kern Jr. "Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study." Gastroenterology 70, no. 3 (1976): 439.
2. Guyatt, Gordon, Alba Mitchell, E. Jan Irvine, J. Singer, N. Williams, R. Goodacre, and C. Tompkins. "A new measure of health status for clinical trials in inflammatory bowel disease." Gastroenterology 96, no. 3 (1989): 804.
3. Harvey, R. F., and J. M. Bradshaw. "A simple index of Crohn's-disease activity." Lancet 1, no. 8167 (1980): 514.
Posted by Martin Bishop at 3:59 PM
Sunday, July 7, 2013
Other IBD Blogs
This isn’t really evidence-based, but it is a tribute to some others who run excellent blogs related to Crohn’s Disease and Ulcerative Colitis. These are blogs whose posts and comments help me determine topics to cover (generally based on what’s popular in new treatments or trends). The list is by no means exhaustive, but represents a sampling of the information available on IBD in the blogosphere. I’ve tried to only include blogs that are current and are updated regularly (unfortunately, because no one pays us to blog, some excellent blogs drop off a bit - I’m personally waiting for http://www.ibeafoodie.com/ to start back up with their recipes).
Ali on the Run (http://www.aliontherunblog.com/)
This is a great blog for those who like to exercise with Crohn’s and Ulcerative Colitis. Many of Ali’s posts resonate with IBD sufferers who try to exercise as much as possible, even during flares. I generally don’t read “My Story” blogs, but this one is special in that it is well written, updated regularly, and inspirational without moving into the glurge category.
Jenni’s Guts (http://jennisguts.blogspot.com)
The “Don’t Say This” section is one of my favorite links to provide folks who make dumb comments to any of us that have IBD. Here at Evidence Based IBD we very much appreciate wisdom like “I don't want to try your weird diet because contrary to popular belief it will NOT cure me. But thanks for trying and I'm glad it works for you.” What put this blog over the top, though, is the new Twitter feed of Ally’s Law Breakers, a list of establishments that refused people with IBD the use of their restrooms.
Mind Your Body (http://opbmed.blogspot.com/)
While not directed at IBD specifically, this wonderful covers the mental health aspects of chronic illness. The posters keep up-to-date with the latest research results in mental health, and post fantastic summaries. Maybe because one of the professionals writing the blog suffers from IBD, many of the posts resonate well.
Caring For Crohns (http://caringforcrohns.com/)
My site covers evidence-based treatments for IBD (primarily, except for diversions like this post!) This blog covers a niche that doesn’t often get the attention it deserves – how to care for someone you love who has IBD. The author (and guest authors) have some great tips and it is a good place to look for information on understanding from the caregiver perspective.
Science Based Medicine (http://www.sciencebasedmedicine.org/)
SBD is my single favorite blog site. While it isn’t IBD specific, all of the posters are professionals and they post tons of topics related to quack medicine in the same well-researched style as sites like Quack Watch (http://www.quackwatch.com/). Science based medicine is the gold standard for treatments (my blog covers evidence based medicine – a lesser standard but it allows the freedom to look at unproven but “keep-watching-it” research). If you are a fan of the site, I also highly recommend the Skeptics Guide to the Universe podcast (http://www.theskepticsguide.org/).
The sites listed above are my favorites, but I peruse many other wonderful blogs related to IBD. If anyone else has a favorite (you can plug your own – go ahead) please post it in the comments section, as long as it isn’t a commercial site (if you sell a few IBD awareness items as a sideline or have ad-based revenue that’s fine), which I will remove.
Posted by Martin Bishop at 10:01 AM