For thousands of years, turmeric has been renowned for both its culinary uses and a multitude of potential health benefits, ranging from decongestion to wound-healing to the treatment of chicken pox. In recent years, the scientific community has increasingly recognized the therapeutic potential of turmeric as well, leading to the development of sophisticated nutraceuticals formulated with curcumin, the active metabolite in turmeric. By combining advanced medical technologies with traditional medicine to create more effective turmeric supplements, new opportunities are opening up for preventing, managing, and treating a wide range of health conditions.
When it comes to gastrointestinal disorders, biochemical research indicates that the benefits of turmeric derive from its anti-inflammatory and antioxidant activities. Due to the naturally low bioavailability of curcumin, the clinical evidence is still mixed. However, the latest research suggests that a relatively new turmeric-based supplement—tetrahydrocurcumin—may be more effective for addressing gastrointestinal symptoms, particularly when delivered in highly bioavailable forms. There is already one noted tetrahydrocurcumin therapy on the market and with its promise, we expect to see more over time.
The Anti-Inflammatory and Antioxidant Effects of Curcumin in Turmeric Supplements
Inflammation in the gastrointestinal tract is associated with many of the functional bowel problems that commonly characterize conditions like ulcerative colitis, irritable bowel syndrome (IBS), and even autism spectrum disorder (ASD). At the biochemical level, the effectiveness of curcumin for fighting inflammation is largely the result of its ability to interact with multiple molecular targets and thereby modulate a wide range of inflammation-related signaling pathways. Specifically, curcumin can contribute to the following anti-inflammatory processes:
- Inhibition of inflammatory cytokines. Cytokines are small proteins released by cells that function in both the innate and adaptive immune systems. They play a key role in cell signaling, acting as messengers to other parts of the cell to mount a full-scale immune response. Thus, the activity of curcumin may reduce cytokine activity in chronic inflammatory bowel conditions, like ulcerative colitis.
- Down-regulation of two types of MAP and JAK kinases. Proteins in the kinase family play a key role in the mounting of the immune response, binding to transmembrane proteins that initiate changes in the cell that promote inflammation. By reducing the activities of these proteins, curcumin may reduce inflammation in the GI tract.
- Down-regulation of three enzymes that promote inflammation (COX-2, lipoxygenase, and inducible nitric oxide synthase). COX-2, a common target for over-the-counter and prescription NSAIDs, can not only reduce inflammation in the GI tract but can also serve as a useful alternative to standard anti-inflammatory drugs that threaten long-term GI health.
In recent years, researchers seeking to understand the mechanistic intricacies of inflammatory bowel disease have identified connections between NF-kappa-B inflammatory cytokines and a specific kinase-associated signaling pathway—and curcumin plays a key role in both pathways. As a result, more researchers and clinicians are posing turmeric supplements as possible therapies for patients with bowel inflammation.
Similarly, recent biochemical research has highlighted the molecular mechanisms through which curcumin may act as an antioxidant. At the most basic level, reactive oxygen species (ROS) can be generated by various aspects of the immune response, so curcumin can act as an antioxidant simply through its anti-inflammatory activities. In addition, curcumin has been shown to regulate the expression of Nrf2, a protein that turns certain genes on to produce proteins. These genes code for enzymes that degrade ROS or stop them from being produced unnecessarily. Therefore, when Nrf2 activity is high, the levels of ROS-fighting proteins are also high. In this way, the activity of curcumin indirectly reduces cellular levels of ROS.
Enhancing the Anti-Inflammatory and Antioxidant Effects of Curcumin
Although there is solid in vitro evidence biochemistry behind the anti-inflammatory and antioxidant activities of curcumin, the clinical results are less convincing. For instance, in a 2017 review of clinical studies in which curcumin was used to treat functional and inflammatory bowel disorders, the results were promising, but not definitive. The authors noted a number of studies indicating potential efficacy:
- A randomized, blinded (but not placebo-controlled) study in which 207 IBS patients were treated with curcumin for 8 weeks and showed improvements for multiple symptoms, including diarrhea, constipation, and abdominal pain.
- Two randomized, double-blinded, placebo-controlled studies in which a combination of curcumin and mesalamine (a common medication for inflammatory bowel disorders) was shown to be more effective than mesalamine alone.
- Two small-scale, open studies in which both pediatric and adult patients with ulcerative colitis or Crohn’s disease reported “marginal benefits” after taking a curcumin supplement.
However, other studies have failed to establish the statistically significant therapeutic effects one would expect based on in vitro findings
One of the reasons curcumin has proven to be more effective in the lab than in the clinic is its low bioavailability level, which has long been recognized by researchers. In a study in 1978, researchers found that in rats that took in curcumin supplements (1g/kg of body weight), 75% was excreted in the feces. More recently, a 2001 study showed that significant quantities of curcumin were also present in the fecal samples of a group of 15 patients who were taking between 36mg and 180mg of curcumin per day. This indicates that a considerable proportion of the curcumin the patients took in was being excreted without being absorbed.
Due to these decades-old concerns about bioavailability, researchers have been examining the potential efficacy of tetrahyrdocurcumin, an active metabolite of curcumin that can be much more readily metabolized when taken in supplement form than the curcumin in traditional turmeric supplements. In a 2014 paper out of the Department of Experimental Therapeutics at UT Austin, the authors highlighted both in vitro and animal studies demonstrating that the efficacy of tetrahydrocurcumin as an antioxidant is significantly higher than that of curcumin. Not only does this metabolite show improved efficacy for quenching free radicals, but it also induces key antioxidant enzymes, including GSH peroxidase, glutathione-S-transferase, quinone reductase, and NADPH.
It is important to note that the differences in the activity of curcumin and tetrahydrocurcumin are not only derived from their different bioavailability levels but also because they have different molecular targets. While it is true that a tetrahydrocurcumin does not bind to some of the targets involved in the anti-inflammatory response, it also limits some of the mild pro-inflammatory activities of curcumin, which may contribute its effectiveness on the clinical level.
There is also preliminary evidence suggesting that certain delivery systems can improve the bioavailability of different types of curcumin supplements, including both curcumin and tetrahydrocurcumin. In one randomized, double-blind study, researchers at the University of Tampa found that serum levels of curcumin were 45.9 times higher in patients who took a formulation of curcumin that included a hydrophilic carrier, cellulosic derivatives, and natural antioxidants, as compared to those who took an unformulated supplement. In the same study, researchers also reported a 7.9-fold increase in absorption of curcumin in patients who took a phytosome formulation and a 1.3-fold increase in those who took a formulation with volatile oils of turmeric rhizome. These results indicate that the delivery system can make an important difference in the bioavailability of curcumin.
Choices for Clinicians and Patients: Yes or No to Turmeric Supplements?
Based on the strong biochemical evidence, recommendations for turmeric supplements are becoming increasingly common. While more research is needed to confirm clinical efficacy on a broad scale, these nutraceuticals present intriguing possibilities for clinicians and patients who want to look beyond conventional gastrointestinal treatments for more complete and tolerable symptom relief. For those who wish to integrate curcumin and tetrahydrocurcumin in their treatment plans, seeking out supplements formulated for optimal bioavailability can be critical to achieving the best outcomes.
Aggarwal BB, Deb L, Prasad S. 2014. Curcumin differs from tetrahydrocurcumin for molecular targets, signaling pathways and cellular responses. Molecules. 20(1):185-205. https://www.ncbi.nlm.nih.gov/pubmed/25547723
Dulbecco P, Savarino V. 2013. Therapeutic potential of curcumin in digestive diseases. World of Gastroenterology. 19(48):9256-70. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3882399
Hilsden RJ, Verhoef MJ, Rasmussen H, Porcino A, DeBruyn JC. 2011. Use of complementary and alternative medicine by patients with inflammatory bowel disease. Inflammatory Bowel Diseases. 17(2):655-62. https://www.ncbi.nlm.nih.gov/pubmed/20848543
Jager R, Lowery RP, Calvanese AV, Joy JM, Purpura M, Wilson JM. 2014. Comparative absorption of curcumin formulations. Nutrition Journal. 13:11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918227
Soetikno V, Sari FR, Lakshmanan AP, Armugam S, Harima M, Suzuki K, Kawachi H, Watanabe K. 2013. Curcumin alleviates oxidative stress, inflammation, and renal fibrosis in remnant kidney through the Nrf2-keap1 pathway. Molecular Nutrition & Food Research. 57(9):1649-59. https://www.ncbi.nlm.nih.gov/pubmed/23174956
Yuksel I. 2017. Antioxidant supplements and gastrointestinal diseases. Medical Principles and Practice. 26(4): 397. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768106/