A recent randomized, double-blind, placebo-controlled phase II presurgical trial has shed new light on the biological effects of curcumin and anthocyanin supplements in patients with colorectal adenomas. The study, published on September 7, 2023 in the journal Nutrients, aimed to explore how these natural compounds influence circulating biomarkers of inflammation and metabolism.
The trial, known as the MiRACol study, was conducted at the Department of Gastroenterology at Galliera Hospital in Genoa, Italy, between March 2014 and December 2017. Funding for the research was provided by Fondazione Umberto Veronesi and Indena SpA, with additional support from the Italian Ministry of Health.
The primary purpose of this study was to investigate the potential of curcumin and anthocyanins in impeding the progression of adenomatous polyps to colorectal cancer. These natural compounds have shown promise in preclinical models, but their effects in human subjects required further exploration.
The study included 35 patients with adenomatous polyps of the colon. To be eligible, participants had to be between 18 and 85 years old, have one or more adenomatous polyp in the colorectal tract with a diameter of at least 1 cm, and have an ECOG Performance Status ≤1. Exclusion criteria included hyperplastic polyps, flat serrated adenomas, cancer diagnosis, and recent use of experimental medications or supplements containing bilberry or curcumin.
Participants were randomly assigned to either the active treatment group or the placebo group. Those in the active group received a combination of 500 mg Mirtoselect® (standardized bilberry extract) and 500 mg Meriva® (curcumin-phosphatidylcholine complex) twice daily for 4-6 weeks before undergoing polypectomy. The placebo group received matching placebos on the same schedule.
Demographic data showed a relatively even distribution between the active and placebo groups in terms of gender, age, BMI, family history of colorectal cancer, and histological characteristics of the adenomas. The mean age of participants was around 69 years, with a slight male predominance.
The study's primary focus was on circulating biomarkers related to inflammation and metabolism. These included high-sensitivity C-reactive protein (hs-CRP), interleukin-10 (IL-10), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), adiponectin, leptin, insulin-like growth factor I (IGF-I), insulin-like growth factor-binding protein 3 (IGFBP-3), and 25-hydroxyvitamin D (25OHD).
Surprisingly, the results showed no significant differences in biomarker levels or changes between the treatment and placebo groups. However, the study did reveal several interesting correlations and trends:
1. Network analysis before treatment showed inverse correlations between adiponectin and both BMI and glycemia, as well as direct links between inflammatory biomarkers and between leptin and BMI.
2. After treatment, a considerable inverse relationship was detected between adiponectin and the grade of dysplasia (correlation coefficient = -0.45).
3. A significant increase in IL-6 levels was observed at the end of treatment in subjects with high-grade dysplasia (p = 0.02).
4. Subjects with a BMI ≤25 showed a greater increase in IL-10 compared to those with a BMI >25.
5. Individuals with low dietary anthocyanin intake exhibited a greater reduction in leptin levels.
6. Higher circulating levels of IGFBP-3 were found at the end of the trial in subjects with a family history of colorectal cancer.
The study had several limitations that should be considered when interpreting the results. The small sample size of 35 participants limited the statistical power to detect significant differences between groups. Additionally, the short duration of the intervention (4-6 weeks) may have been insufficient to observe more pronounced changes in biomarker levels.
Despite these limitations, the authors concluded that while the combined treatment of curcumin and anthocyanins did not directly modulate circulating biomarkers of inflammation and metabolism, the study revealed a complex interplay between these biomarkers in the context of colorectal adenomas. The inverse relationship between adiponectin and dysplasia grade, as well as the increase in IL-6 in subjects with high-grade dysplasia, warrant further investigation.
The potential clinical impacts of this study are multifaceted. While the results do not support the immediate use of curcumin and anthocyanin supplements for modulating biomarkers in patients with colorectal adenomas, they do provide valuable insights into the complex relationships between metabolic and inflammatory pathways in the development and progression of these precancerous lesions.
The findings suggest that adiponectin levels may be a potential marker for dysplasia severity, which could have implications for risk stratification and monitoring of patients with adenomatous polyps. The observed increase in IL-6 in high-grade dysplasia also highlights the potential role of inflammatory processes in the progression of these lesions.
Furthermore, the study underscores the importance of considering factors such as BMI, dietary habits, and family history when evaluating the risk and progression of colorectal adenomas. The differential responses observed based on these factors suggest that personalized approaches to prevention and treatment may be necessary.
In conclusion, while this study did not demonstrate a direct modulation of biomarkers by curcumin and anthocyanin supplementation, it has opened up new avenues for research into the complex interplay of metabolic and inflammatory pathways in colorectal carcinogenesis. Future studies with larger sample sizes, longer intervention periods, and more targeted approaches based on individual patient characteristics may help to further elucidate the potential role of these natural compounds in colorectal cancer prevention.
As research in this field continues, medical professionals should remain cautious about recommending curcumin and anthocyanin supplements for colorectal cancer prevention based solely on this study. However, they should be aware of the potential relationships between metabolic and inflammatory biomarkers and the progression of colorectal adenomas, as these insights may inform future diagnostic and therapeutic strategies.
References
Macis D, Briata IM, D'Ecclesiis O, et al. Inflammatory and Metabolic Biomarker Assessment in a Randomized Presurgical Trial of Curcumin and Anthocyanin Supplements in Patients with Colorectal Adenomas. Nutrients. 2023;15(18):3894. Published 2023 Sep 7. doi:10.3390/nu15183894
