What if a stellar treatment for Crohn’s disease has been sitting under doctors’ noses for even longer than they’ve known about the disease? What if patients could supplement their diets with a natural compound which could control their intestinal inflammation? In light of an abundance of research investigating the therapeutic value of the turmeric plant, these hypotheticals may be more likely previously realized.
Presenting as a fine orange powder, the turmeric plant has caught the attention of scientists for its potential as an anti-inflammatory agent. Long-standing informal research by pastoral healers into the therapeutic value of turmeric, however, has a significant head start on current scientific efforts; traditional Ayurvedic medicine and Indian cuisine have made use of the rhizome of the turmeric plant for thousands of years, in part due to its medicinal properties. Today, the scientific consensus on turmeric is still evolving because turmeric itself contains a handful of components, each of which needs to be investigated individually before turmeric itself can find its niche in treating patients. The potentially useful compounds in turmeric are called curcuminoids and these are the compounds on which scientists have primarily focused their inquiry. Curcuminoids are a diverse group, however.
Of the curcuminoids, the most deeply investigated molecule is that which the entire class of chemicals is named after: curcumin. Curcumin has been proven to interact with a plethora of critical physiological molecules, including those associated with inflammation. These interactions with pro-inflammatory molecules serve as the primary basis for the potential of turmeric supplementation to treat Crohn’s disease, preventing the runaway inflammatory episodes characteristic of the condition. Patients who are seeking a complement to their current therapies for more complete symptom relief would therefore do well to learn more about curcumin and carefully follow research into its anti-inflammatory effects.
Curcumin’s Anti-Inflammatory Potential In Crohn’s
Though the evidence supporting the use of curcumin in Crohn’s is still forming, researchers have already identified how it impacts human cells and reduces their ability to cause inflammation. Critically, curcumin can hypothetically suppress proinflammatory transcription factors like NF-kB, STATs, and beta-catenin in the gut. Of these transcription factors, NF-kB is responsible for the self-sustaining chain reaction that occurs in inflammation. Inhibiting NF-kB therefore means that runaway inflammatory flare-ups would be heavily suppressed, though low levels of inflammation could still occur. Given that inflammation is one of the core symptoms of Crohn’s, curcumin could thus reduce occurences of flare-up and provide significant symptom relief. The evidence to support its use is mixed, however.
One pilot study found that curcumin supplementation lowered symptom severity scores significantly in four out of the five study participants with Crohn’s disease. Unfortunately, larger studies have failed to replicate the pilot study’s findings regarding symptom severity in Crohn’s disease. Nonetheless, in a review of several pieces of literature examining curcumin’s impact in Crohn’s, researchers found that patients who were administered curcumin alongside their normal therapeutic regimen experienced a 55-point reduction of their Crohn’s Disease Activity Index (CDAI) on average. A 55-point reduction in CDAI could be the difference between a moderate flare-up and remission.
Additional investigations suggest that if remission does occur, it is likely to be significant in duration. A large, placebo-controlled study found that only 4.7% of the study’s ulcerative colitis patients who were treated with curcumin in addition to traditional treatment relapsed after stopping traditional treatment in comparison with 20.5% of patients who were treated with placebo in addition to traditional treatment. The researchers, however, could not propose a mechanism responsible for the medium-term effects of the curcumin supplement, as nearly all other research indicates that curcumin should not be biologically active after a few hours. The most likely explanation for these effects is that curcumin altered the regulatory regions of certain genes, inhibiting or activating those genes for periods that extend beyond the presence of curcumin itself.
The High Tolerability of Curcumin
Due to its rapid metabolism, turmeric supplementation rarely has many negative side effects, making it inviting for patients who want to try alternative treatments for Crohn’s. Mild diarrhea is the most common side effect reported, which means that it would be tolerable for Crohn’s patients in the midst of an inflammatory episode who can’t shoulder more serious side effects. Overall, most patients find curcumin supplementation to be highly tolerable and experience side effects only with high doses. This makes curcumin a low-risk intervention, especially if patients are concerned about disrupting their compromised gastrointestinal tract. Nonetheless, there are many questions about curcumin which still require answers.
The Trouble With Curcumin
While there is strong evidence curcumin may be useful in the treatment of Crohn’s disease, bioavailability is a major obstacle to becoming therapeutically useful. Drs. Kathryn Nelson, Jayme Dahlin, and Jonathan Bisson compiled a review of literature on curcumin’s bioactivity, finding that:
Curcumin is best typified as a missile that continually blows up on the launch pad, never reaching the atmosphere or its intended target(s). These results have given curcumin the label of pharmacodynamically fierce (hits many targets) yet pharmacokinetically feeble (does not get to its targets).
The ability to reach physiological targets refers to a chemical’s absorption and metabolic properties, otherwise known as its bioavailability. Having a low or inconsistent bioavailability is an obstacle for using a given chemical to treat a patient. With some chemicals, the workaround is to increase the quantity that the patient consumes, but this doesn’t always work in the context of Crohn’s disease; in Crohn’s, intestinal cells can’t absorb chemicals as effectively thanks to the compromised state of their tissue structure.
Unfortunately, the typically low bioavailability of curcumin hampers researchers’ efforts to examine its efficacy in the body, potentially explaining the inconsistency of research results. However, it is a solvable issue. With the help of advanced drug delivery systems or alternative routes of administration, researchers have been able to overcome low bioavailability of drug molecules in the past. Such experiments with highly bioavailable curcumin have usually centered around formulations that include fat emulsions, plant matter complexes, and cellulose capsules which degrade upon contact with specific molecules common to the gastrointestinal tract. More advanced bioavailable formulations may include nanospheres which interface with white blood cells to disburse their payload.
According to research, this improved bioavailability makes a difference. In a study designed to test the efficacy of curcumin in mouse models of inflammatory bowel disease published in Gastroenterology, researchers found that highly bioavailable curcumin supplements were able to regulate the T-helper cells in the gut, reducing inflammation and promoting healthy microbiota. Attending to the health of the microbiome is critical in Crohn’s disease because patients often have microbiota which are markedly aberrant compared to healthy controls. While it’s unclear whether this is a cause or an effect of Crohn’s disease, unhealthy microbiota make for worse nutrient absorption and may contribute to inflammation. By formulating curcumin to be highly bioavailable, the researchers were able to observe clear results regarding its impact in the gut. However, their unique formulation makes their study nearly impossible to compare with others and so far, such formulations are nearly unrepresented in the literature.
The larger problem with curcumin is that it’s very difficult to work with in the laboratory. Curcumin is unstable, which means that it can degrade mid-experiment as a result of environmental conditions. Nelson, Dahlin, and Bisson’s review laments curcumin’s poor stability, noting that “both its in vitro and in vivo stabilities are abysmal relative to commercial drugs.” Even more troublesome than its instability is its propensity to react with all biological molecules around it; this is the property that the review called “pharmacodynamically fierce.” By reacting promiscuously, scientists are hard-pressed to determine curcumin’s biological impact because their typical tools like antibodies and fluorescent tags can’t be used. Attempts to measure curcumin’s binding to other physiologic molecules result in endless numbers of false positives simply because curcumin disrupts the measuring methodology.
This disruptive effect may be part of the reason that, despite a number of studies strongly supporting its use, curcumin has not been definitively found to be helpful for any disease despite its investigation in over 120 different controlled trials. The studies which report positive effects may similarly be mistaken due to curcumin causing false positives in the experiment. Despite these issues, other compounds derived from turmeric are still under active investigation.
The Promise Of Tetrahydrocurcumin
As the research community continues to explore the potential of turmeric in the treatment of Crohn’s disease, some are expanding the scope of their investigations beyond curcumin in order to overcome the barriers presented by the molecule and expand the potential for symptom relief in patients. Of particular interest in the curcuminoid tetrahydrocurcumin, which was highlighted in Nelson, Dahlin, and Bisson’s review as a turmeric-derived compound with a wide number of potential applications.
Tetrahydrocurcumin is a metabolite of curcumin and shares many of the same properties as curcumin, including protecting against certain kinds of DNA damage, scavenging free radicals, and controlling inflammation. Tetrahydrocurcumin, however, is naturally more bioavailable, increasing the possibility of therapeutic benefit. Additionally, it provides a higher level of antioxidant activity, which may provide an additional and significant avenue toward creating relief of Crohn’s symptoms; because tetrahydrocurcumin is a stronger antioxidant than other curcuminoids, it could be administered to patients in smaller doses while exhibiting superior therapeutic effects.
Antioxidants are potentially beneficial in the treatment of Crohn’s—as well as a plethora of other conditions—because they capture reactive oxygen species generated as byproducts of normal metabolism. If left to run amok, reactive oxygen species can react with DNA, enzymes, and other cellular components, interfering with their function. In the event that a nearby antioxidant “scavenges” a circulating reactive oxygen species, it can’t hurt important cellular machinery.
While the review finds these antioxidant properties have the most potential for use in treating Alzheimer’s disease thanks to the proven relationship between Alzheimer’s and oxidative damage, it’s also possible that tetrahydrocurcumin could help to prevent oxidative damage to the intestine resulting from acute inflammatory episodes in patients with Crohn’s disease. By reducing oxidative damage, tetrahydrocurcumin could benefit white blood cells in the GI tract by removing reactive oxygen species which might interfere with their functions by damaging key enzymes. This therapeutic avenue is currently being investigated. While scientists are improving their ability to experiment with tetrahydrocurcumin to ensure the validity of results, tetrahydrocurcumin supplements are already entering the market, giving Crohn’s patients more opportunities to experience the benefits of turmeric.
The Future Of Turmeric Therapies
As turmeric and its associated compounds become better understood, there many possibilities for its future uses. Turmeric may soon prove useful for treating disease in randomized controlled clinical trials, but it’s hard to predict exactly which disease will benefit most. Currently, turmeric is under investigation in the contexts of Crohn’s disease, Alzheimer’s disease, HIV, various cancers, and many others. It’s also possible that turmeric may be used in more general research; scientists may find the compounds within turmeric to be advantageous as experimental tools because of the very properties they currently find inconvenient.
No matter the application of turmeric, researchers are heavily invested in learning more in hope of harnessing its power to help a broad spectrum of patients. For patients with Crohn’s disease, the anti-inflammatory and antioxidant effects of turmeric make for a promising supplemental therapy which carries few risks and significant therapeutic potential. Should patients with Crohn’s seek to increase their periods of remission and guard against flare-ups, turmeric compounds, particularly tetrahydrocurcumin, may be a viable place to start.
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Nelson KM, Dahlin JL, Bisson J, Graham J, Pauli GF et al. 2017. The essential medicinal chemistry of curcumin. Journal of Medicinal Chemistry. 60:1620–1637. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346970/
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