Updated on February 2, 2023
- Turmeric’s potential to enhance the body’s natural inflammatory response and its high tolerability make it an ideal candidate for addressing Crohn’s disease.
- While curcumin is the most studied compound derived from turmeric, bioavailability challenges can impede the therapeutic impact of curcumin-based supplements.
- Research suggests that a tetrahydrocurcumin supplement is the best option for patients seeking to benefit from turmeric due to its naturally higher bioavailability and stronger antioxidant effects.
What if a stellar therapeutic benefit 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 that could could help maintain a normal inflammatory response in their gut? In light of an abundance of research investigating the therapeutic value of derivatives of the turmeric plant, these hypotheticals are more likely than previously realized.
Derived as a fine orange powder, the turmeric plant has caught the attention of scientists for its potential to support the body’s natural inflammatory response. Longstanding informal research by pastoral healers into the therapeutic value of turmeric, however, has a significant headstart 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 contains a handful of components, each of which needs to be investigated individually before one of these components can find its niche in addressing Crohn’s disease. 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 the body’s inflammatory response. These interactions with pro-inflammatory molecules serve as the primary basis for the potential of using a turmeric supplement for the nutritional support of Crohn’s disease by down-regulating the inflammatory episodes characteristic of the condition. Patients who are seeking a complementary therapy to their current traditional therapies for more robust symptom relief would therefore do well to learn more about curcumin supplements, in particular, the potentially more effective tetrahydrocurcumin.
The Potential of Curcumin for Crohn’s
Although the evidence supporting the supplemental use of curcumin in Crohn’s is still forming, researchers have already identified how curcumin impacts human cells and limits their ability to down-regulate the inflammatory response. It is believed that curcumin does this by suppressing pro-inflammatory 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 during inflammatory response. Inhibiting NF-kB therefore means that inflammatory flare-ups would be beneficially down-regulated, although low levels of inflammation would still occur. Given that inflammation is one of the core symptoms of Crohn’s, curcumin could thus promote a reduction of flare-ups and their accompanying symptoms. The evidence to support its use is mixed, however.
One pilot study found that curcumin supplementation benefited symptom severity scores significantly in four of five study participants with Crohn’s disease. Unfortunately, larger studies have failed to replicate the pilot study’s findings regarding symptom severity. Nonetheless, in a review of several pieces of literature examining curcumin’s impact in Crohn’s, researchers found that patients who were administered curcumin in conjunction with their normal therapeutic regimen experienced an average 55-point reduction of their Crohn’s Disease Activity Index (CDAI). A 55-point reduction in CDAI would have a significant beneficial impact on moderate flare-ups.
Additional investigations suggest that when benefits do occur, they are likely to be significant in duration. A large, placebo-controlled study found that the study’s ulcerative colitis patients who were administered curcumin in addition to traditional therapies achieved better results than patients who were treated with placebo in addition to traditional therapies. The researchers, however, could not propose the mechanism responsible for the medium-term effects of the curcumin supplement, because nearly all other research indicates that curcumin is not biologically active after several hours. The most likely explanation for these beneficial effects is that curcumin alters 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 supplements for Crohn’s rarely have negative side effects, making it inviting for patients who want to try alternative therapies. Mild diarrhea is the most common side effect reported, which means it would be tolerable for Crohn’s patients in the midst of an inflammatory episode who can’t tolerate more serious side effects. Overall, most patients find curcumin supplementation to be highly tolerable and experience side effects only with doses higher than suggested uses. This makes curcumin a low-risk intervention, especially when patients are concerned about disrupting their compromised gastrointestinal tract. Nonetheless, there are many questions about curcumin which still require answers.
The Issue With Curcumin
Although there is strong evidence that curcumin is useful in addressing the symptoms of Crohn’s disease, curcumin’s bioavailability is a major obstacle to becoming therapeutically useful. Drs. Kathryn Nelson, Jayme Dahlin, and Jonathan Bisson compiled a review of the 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 substance’s absorption and metabolic properties, otherwise known as its bioavailability. Having a low or inconsistent bioavailability is an obstacle for using a given substance to address a patient’s symptoms. With some substances, the workaround is to increase the quantity the patient consumes, although this doesn’t always work in the context of Crohn’s disease; in Crohn’s, intestinal cells can’t absorb chemicals as effectively because of 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 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 that degrade on contact with specific molecules common to the gastrointestinal tract. More advanced bioavailable formulations include nanospheres that interface with white blood cells to disburse their payload.
According to research, enhanced bioavailability does make 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 support the activities of the T-helper cells in the gut, down-regulating the inflammatory response and promoting healthy microbiota. Attending to the health of the microbiome is critical in Crohn’s disease because patients often have microbiota that are markedly aberrant compared to healthy controls. Although it is unclear whether this is a cause or an effect of Crohn’s disease, unhealthy microbiota make for worse nutrient absorption and likely contribute to inflammation. By formulating curcumin to be highly bioavailable, the researchers were able to observe clear results regarding curcumin’s 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 issue with curcumin is that it’s very difficult to work with in the laboratory. Curcumin is unstable, which means 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 curcumin’s instability is its propensity to react with all biological molecules around it; this is the property 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 is likely part of the reason why, 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 more than 120 different controlled trials. The studies that report positive effects might 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 using a turmeric supplement for Crohn’s disease, some are expanding the scope of their investigations beyond curcumin 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 modulating inflammatory response. Tetrahydrocurcumin, however, is naturally more bioavailable, increasing the possibility of therapeutic benefit. Additionally, it provides a higher level of antioxidant activity, which might provide an additional and significant avenue toward creating therapeutic applications for Crohn’s symptoms; because tetrahydrocurcumin is a stronger antioxidant than other curcuminoids, it can be administered to patients in smaller doses while exhibiting superior therapeutic effects.
Antioxidants are potentially beneficial for 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 adversely 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 addressing issues related to Alzheimer’s disease thanks to the proven relationship between Alzheimer’s and oxidative damage, it’s also possible that tetrahydrocurcumin could help to limit 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 that 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 and Crohn’s
As turmeric and its associated curcuminoids become better understood, there are many possibilities for their future uses. Turmeric might soon prove useful for addressing health conditions in randomized controlled clinical trials, although it is difficult to predict exactly which health condition 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 might find the compounds within turmeric to be advantageous as experimental tools because of the very properties they currently find inconvenient.
No matter the application, researchers are heavily invested in learning more in hope of harnessing turmeric’s power to help a broad spectrum of patients. For patients with Crohn’s disease, turmeric makes for a promising supplemental therapy that carries few risks and significant therapeutic potential. Should a patient with Crohn’s seek to enhance their traditional medication regimen with a safe and efficacious natural alternative turmeric compounds, particularly tetrahydrocurcumin, would be a viable place to start.
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Works Cited
Holt PR, Katz S, Kirshoff R. 2005. Digestive Diseases and Sciences. 50:2191–2193.
Nelson KM, Dahlin JL, Bisson J, Graham J, Pauli GF et al. 2017. Journal of Medicinal Chemistry. 60:1620–1637.
Ohno M, Nishida A, Sakai S, Nishino K, Fujii M, et al. 2017. Gastroenterology. 152.
Schneider A, Hossain I, Vandermolen J, Nicol K. 2017. Complementary Therapies in Medicine. 33:32–38.
Taylor R, Leonard M. American College for Advancement in Medicine (ACAM).
