The Science Behind CurQD®

The CurQD® Compounds

Gut-Directed Curcumin

Curcumin is the active compound extracted from the turmeric rhizome. The golden polyphenic is rich in anti-inflammatory and antioxidant properties and has been used in Ayurvedic medicine for thousands of years.

Traditionally used to treat blood and liver disorders, as well as digestive disorders, curcumin has come under considerable clinical interest as a therapy for ulcerative colitis and Crohn’s disease. This is due to the many mechanisms through which curcumin effectively targets inflammation, covering a broader spectrum than conventional medicine.

Curcumin has been found in a large number of studies to quickly induce remission in IBD patients, and promote long-lasting remission maintenance.

Oxidative Stress

Curcumin not only fights oxidative stress (one of the leading causes of chronic inflammation) but appears to enhance the body’s own natural antioxidant defense system. The compound has been found to neutralize the activity of reactive oxygen species (ROS), inhibiting ROS-generating enzymes such as LOX, COX, and xanthine oxidase.¹ Curcumin additionally boosts Glutathione (GSH) levels, an antioxidant produced within the body. This further fortifies the body’s own antioxidant defense. Studies recently found that curcumin can also inhibit lipid peroxidation, meaning the spontaneous chain reaction of oxidation resulting from the attack of free radicals.²

Inflammatory Signals & Cytokines

Curcumin targets inflammation through several mechanisms. The compound inhibits pro-inflammatory cytokines by blocking the NF-kB signaling pathways, when overactivated, can cause harmful immune dysregulation that leads to severe inflammation and tissue damage.^3,4 Studies show that curcumin also suppresses the activity of interleukin-1 (IL-1β), and TNFα, rendering the compound a safe and less hazardous option before patients are administered biologic therapy.^5,6

Gut Dysbiosis

The latest research on the human gut microbiome shows that curcumin has a direct, regulatory effect on gut microbiota.⁷ The compound appears to be able to shift the composition of healthy and pathogenic bacteria, promoting balance and homeostasis across the entire system. This is exceptionally important for IBD patients, who are statistically prone to an imbalance of gut bacteria (known as “dysbiosis”). A review of the literature found that patients taking curcumin had less pro-inflammatory bacteria (e.g. prevotellaceae, coriobacteriaceae, enterobacteria, and enterococci) and higher levels of the anti-inflammatory bifidobacteria and lactobacilli.

Curcumin for UC Induction

Curcumin has been shown by a number of studies to quickly induce remission in patients with mild-to-moderate ulcerative colitis. Most notably, a multi-center randomized control trial in Israel testing curcumin in combination with mesalamine for inducing remission in UC patients who were all shown to be non-responsive to mesalamine therapy, conducted by Lang et al.⁸ After 4 weeks of treatment, 53.8% of patients in the curcumin group achieved clinical remission, which was not achieved by any in the placebo group. 65.3% of patients in the curcumin group showed clinical response and 38% achieved endoscopic remission. The combined use of curcumin and mesalamine was shown to be significantly more effective than mesalamine alone. It was the first trial to investigate ‘gut-directed’ curcumin and the first to test curcumin for treatment-resistant patients.

A later study tested add-on curcumin in combination with mesalamine for mild to moderate UC, assessing patients at 6 weeks, at 3 months, and again 6-12 months to assess remission maintenance. At six weeks, 44.1% of patients achieved clinical remission and 35% achieved endoscopic remission, compared to none in the placebo group. Clinical response was also significantly higher in the curcumin group. The 6-month follow-up showed that 95% of responders to curcumin maintained clinical remission, showing that curcumin as an add-on therapy can induce sustained remission for patients with mild-to-moderate UC.⁹

Curcumin for UC Remission Maintenance

Several studies show that curcumin can effectively improve the chances of maintaining remission in UC, as seen in a 2006 study conducted by Hanai et al.¹⁰ Researchers tested curcumin for remission maintenance for six months, after which the curcumin group showed a significant reduction in relapse compared to the placebo group. The six-month follow-up showed higher rates of relapse after the discontinuation of curcumin. In 2021, Banerjee et al assessed UC patients on curcumin alongside mesalamine for 3 months, with a 6-12 month follow-up to observe long-term maintenance of remission. At 6 weeks, 44.1% of patients in the curcumin group showed clinical remission, with 35% achieving endoscopic remission compared to zero in the
placebo group.¹¹ In the 6-month follow-up, 95% of those who had responded well to curcumin were able to maintain clinical remission. The results of these trials clearly show that curcumin used alongside mesalamine is a more effective therapy than mesalamine alone in inducing remission.

Curcumin for Crohn’s Disease

While there are relatively more studies on curcumin for UC than for Crohn’s disease, a meta-analysis from a database of trials on both types of IBD found that curcumin can significantly increase the rate of clinical remission and endoscopic remission, and improve clinical symptoms. Improved quality of life was also shown compared to control groups.¹²  One notable study for Crohn’s disease tested curcumin as an add-on treatment alongside Remicade. Remicade reduces IL-1 and CRP levels of inflammation in patients, inhibits TNF-a, and significantly reduces the Crohn’s disease Activity Index, but many patients lose response to the therapy. As curcumin targets IL1, the authors recommend the complimentary use of curcumin alongside Remicade to reduce loss of response.¹³

Indigo (QD)

Indigo, or Qing Dai (QD), is a unique compound extracted from the pigments of plants such as Indigofera tinctoria, Strobilanbthes cusia, O Kuntze, and Polygnonum tinctoium Lour. Once a treasured dye for fabrics, Qing Dai traversed the Silk Road to China, where it fell into the hands of ancient Chinese physicians and became a staple treatment in Traditional Chinese Medicine. Today, Qing Dai is still used in China to treat infectious diseases, tumors, and IBD. Due to the limited nature of conventional therapies for IBD, there has been rising clinical interest in Qing Dai as it shows considerable promise as an effective and safe anti-inflammatory therapy for IBD. Mounting evidence indicates that Qing Dai may be an effective short-term treatment for UC patients who are nonresponsive to conventional therapy.

How Indigo (Qing Dai) Targets Inflammation

Qing Dai contains potent anti-inflammatory, antioxidant, antibacterial, antiviral, and immunomodulatory properties, showing “good clinical effect” on psoriasis, leukemia, and ulcerative colitis.¹⁴ A recent study found that Indirubin, an active component of Qing Dai, “markedly inhibits” NF-κB signals, resulting in the relief of severe inflammation in UC cases.¹⁵ QD also activates the AhR pathway, further suppressing the production of proinflammatory cytokines such as TNF-α, IL-1, and IL-6, to name a few.¹⁶ Qing Dai also reduces serum MCP-1 levels and inhibits myeloperoxidase (MPO) activity, which is involved in oxidative stress leading to chronic inflammation.¹⁷ Qing Dai additionally contains ligands for the aryl hydrocarbon receptor and induces the production of interleukin 22, promoting the regeneration of the mucosa.¹⁸ Please note that Qing Dai should only be taken in strictly recommended doses, for specific conditions, and with thorough follow-ups. It is not a long-term treatment, but can effectively reduce severe intestinal inflammation and induce quick remission in many patients, especially those with ulcerative colitis.

Indigo (Qing Dai) for Induction

Researchers in Japan were the first to conduct trials on Indigo for UC. One of the earliest studies took place in 2013 when researchers observed patients with active ulcerative colitis who had been administered conventional, pharmaceutical medications and were interested in taking Qing Dai as an alternative medication. At 4 months, the CAI score decreased significantly, and patients on prednisolone at the start of treatment were able to discontinue the corticosteroid. The trial concluded that QD has significant clinical and endoscopic efficacy in patients who have failed to respond to conventional medications.¹⁹ Two years later, researchers at the Keio University Hospital investigated oral Qing Dai for inducing remission in moderate ulcerative colitis.

At week 8, 72% of participants showed clinical response, with 33% achieving clinical remission, and 61% achieving mucosal healing. There was a significant improvement in clinical and endoscopic scores, CRP levels, and fecal occult blood results.²⁰

The trial was followed by several similar studies finding Qing Dai to be a safe and effective therapy for inducing remission in UC patients, as shown by Yoshimatsu et al and Urushikubo et al.^21,22 A study published in 2019 analyzed the data from a multicenter, double-blind clinical trial investigating the efficacy and safety of QD for inducing clinical response in patients with active UC. The rate of clinical response was 77.8% in patients with steroid-dependent disease, 77.5% in patients with previous use of anti–TNF-α, and 76.7% in patients with a Mayo endoscopic score of 9-11. The QD group showed a significantly higher rate of mucosal healing than the placebo group for patients with steroid-dependent disease.²³

With mounting evidence of Qing Dai as an effective therapy for UC, researchers analyzed data from medical records of both UC and Crohn’s disease patients who had undertaken Qing Dai (QD) therapy at Kyushu University Hospital. After 8 weeks of treatment, 94.1% of participants showed clinical response, with remission rates at 88.2% in UC patients. 37.5% of the Crohn’s disease patients showed clinical response and 25% achieved remission. The study concluded that Qing Dai (QD) showed ‘favorable’ therapeutic efficacy for UC and ‘modest’ efficacy for Crohn’s Disease.²⁴ 

The CurQD® Strategy

Considering the promising results of the above trials, researchers and gastroenterologists in Israel began using a carefully calculated combination of both curcumin and Qing Dai on patients in local clinics and hospitals, with exceptional results. Over the years, they’ve developed a strategy that evolved from their clinical experience and various trials, including the initial 2015 trial on gut-directed curcumin alongside mesalamine for UC.

Due to the fact that some patients experienced side effects from Qing Dai, the researchers began tapering patients off after induction of remission, administering a higher ratio of curcumin. The combined use of compounds eliminated adverse events, and the researchers were able to further refine the strategy, pinpointing the most effective dosages and treatment timeline for achieving and maintaining remission. The strategy also ensures a careful transition from induction to maintenance, a phase sorely lacking in most treatments for IBD. They’ve since completed the first trial on the combined use of curcumin and Qing Dai for UC for all phases of recovery, with results showing unprecedented rates of remission and improvement due to this tailored strategy.