Anthocyanin

What Is It?

Anthocyanins are a group of water-soluble plant-derived pigments belonging to the flavonoid family$^{1,2}$.  They are responsible for the distinctive red, blue, and purple coloration of many fruits and vegetables such as elderberries, strawberries and blackberries$^{2}$. Unlike most micronutrients, anthocyanins are absorbed in both the stomach and small intestine via the help of active transporters$^{1}$. These compounds have been shown to possess potent antioxidant activity, thus underscoring their potential in alleviating numerous chronic conditions where oxidative damage is an underlying factor, such as cardiovascular disease, metabolic disorders, and cancer$^{1}$.  Anthocyanin vs Anthocyanidins Anthocyanin and anthocyanidins are related compounds belonging to the same plant pigment family. Anthocyanin is said to be the glycosylated derivative of anthocyanidin as the main difference between the two compounds is the presence of sugar moieties on the former$^{3}$. The presence of these sugar groups also confers water solubility to these compounds, which thus necessitates the help of active transporters to facilitate their absorption in the body$^{1}$. 

What Are Its Other Names?

Anthocyanin is sometimes referred to as flavylium or enocyanin$^{4}$. The IUPAC name for this compound is 2-phenylchromenylium$^{4}$.

What Foods Have It?

Anthocyanin is found in several different fruits and vegetables that have a characteristic red, blue, or purple pigmentation, with berries containing the highest amount of anthocyanin. The following table highlights the different types of raw fruits and vegetables as well as their anthocyanin content.

It is crucial to note that the anthocyanin content of most produce is presented as a range as the anthocyanin content can differ significantly depending on a variety of conditions such as season, light exposure, time of harvest, and method of processing$^{5}$.

What Are Its Main Benefits?

Benefits for Cancer Prevention Several studies have demonstrated anthocyanin’s potential in fighting a variety of cancer types. However, the correlation between anthocyanin supplementation and gastrointestinal cancer prevention in humans is best characterised$^{6,7}$.  In one trial involving 25 colon cancer patients, it was reported that the consumption of anthocyanin-enriched extracts not only led to a reduction in the rate of tumour proliferation, but it also enhanced apoptosis in colon tumours$^{6}$. Interestingly, anthocyanin had no effect on normal growths$^{6}$. This therefore underscores the cancer-specific fighting potential of anthocyanins. Similarly, in a separate in vitro study, anthocyanin supplementation inhibited the growth of human HT-29 colon cancer cells and increased the expression of tumour suppression genes (p21WAF1 and p27KIp1), but it had no effect on normal colon tissue$^{8}$. Additionally, studies in mice have shown that the consumption of anthocyanin extracts resulted in the reduction of aberrant crypt foci, which are lesions that form in the lining of the colon that are precursors to colon cancer$^{8,9}$.  In addition to colorectal cancer, anthocyanin consumption has also been shown to be protective against pancreatic cancer and cancers in general. In the context of pancreatic cancer, a clinical study with 35 healthy subjects reported that anthocyanin supplementation impaired pancreatic cancer cell migration, thus hindering the ability of these cancer cells to spread$^{10}$. Furthermore, several other clinical trials also demonstrated that the consumption of anthocyanin-rich foods enhanced the body’s natural anti-cancer defence systems, thus equipping it with the tools necessary to defend against an array of cancers, irrespective of the specific cancer type$^{11,12}$.  Several in vitro studies have also demonstrated the cancer-fighting properties of anthocyanin in breast cancer. In one study, it was reported that anthocyanin either inhibited the growth of breast cancer cells, or it induced apoptosis altogether$^{13}$. Furthermore, anthocyanin supplementation was also reported to reduce angiogenesis, a major hallmark of cancer by disrupting the expression of pro-angiogenic factors (see ‘What Are its Mechanisms of Action’ for more details)$^{8,14}$. However, it is important to note that while the results obtained from these studies are promising, these studies were conducted using in vitro and in vivo models, therefore the effects of anthocyanin against breast cancer in humans still requires further investigation.  Benefits for Side-Effects of Cancer Treatment  In addition, anthocyanin has also demonstrated potential in mitigating the side effects of cancer treatment, specifically in the context of radiation therapy$^{15}$. Radiation therapy can sometimes lead to inflammation at the irradiated site which can manifest as peeling and itching, leading to a dry red and sometimes swollen appearance$^{16}$. In a randomized controlled trial involving 32 breast cancer patients undergoing radiation therapy, it was reported that a specific gel known as RayGel, which contains anthocyanins among other nutrients, was effective in reducing these radiation-induced skin reactions$^{15}$. Although these results are promising, due to the presence of other nutrients in addition to anthocyanins, these effects cannot be solely attributed to anthocyanin alone, thus warranting further investigation.  Benefits for Inflammatory Disease Prevention  Beyond cancer, anthocyanin may also prevent diseases where inflammation is an underlying factor, such as colitis (inflammation of the colon), and postprandial inflammatory response (meal-induced inflammation)$^{7,17,18}$. Anthocyanin supplementation has been shown to downregulate the expression of pro-inflammatory factors, namely COX-2 and PGE-2$^{18}$. COX-2 plays a crucial role in stimulating the inflammatory response as it is responsible for mediating the production of pro-inflammatory prostaglandins (PGE-2) from arachidonic acid and polyunsaturated fatty acids$^{19}$. Therefore, the inhibition of COX-2 through the consumption of anthocyanin can dampen the inflammatory response.  

What Are Its Main Drawbacks?

Low Bioavailability  Bioavailability is the extent to which a drug or metabolite can enter the systemic circulation in its unchanged form$^{20}$. One significant drawback of anthocyanins is its low bioavailability. Anthocyanins are protonated in the stomach’s acidic environment, and thus become ionized (charged)$^{20}$. This consequently prevents anthocyanins from crossing the stomach lining and entering the systemic circulation, thus lowering its bioavailability$^{20}$.  High Reactivity  Anthocyanins are considered highly reactive compounds$^{20}$. They are sensitive to a range of factors such as oxygen concentration, light and pH$^{20}$. Resultantly, this means that anthocyanins are highly susceptible to degradation as they travel through the gastrointestinal tract upon consumption$^{20}$.

What Are Its Mechanisms of Action?

1. Reduction of Oxidative Damage: Oxidative stress is caused by an imbalance between the production of reactive oxygen species (ROS) and antioxidants in cells$^{21}$. ROS refers to byproducts of metabolism – including superoxide radicals, hydrogen peroxide, hydroxyl radicals, and singlet oxygen – that have the potential to induce cellular and DNA damage$^{21}$. Anthocyanins have been hailed as an effective antioxidant due to their chemical structures, allowing this micronutrient to scavenge free radicals in the body$^{22}$. Additionally, clinical studies have revealed that anthocyanin consumption is linked with increased levels of antioxidant enzymes like superoxide dismutase$^{23}$. Besides that, this nutrient can also reduce oxidative damage through the Keap1-Nrf2 pathway which normally acts on the antioxidant response element (ARE) to activate the expression of antioxidant enzymes$^{22}$.
2. Inhibition of Cancer Cell Migration: Invasion and metastasis govern an important hallmark of cancer, and a major contributing factor lies in the ability of cancer cells to migrate$^{14}$. Research has shown that epithelial-to-mesenchymal transition (EMT) relies on the loss of a protein known as E-cadherin$^{24}$. In one randomized clinical trial, it was reported that anthocyanin supplementation resulted in a downregulation of the NF-kB pathway, consequently impairing its ability to inhibit E-cadherin$^{24,25}$. As a result, this highlighted how anthocyanin is able to disrupt the migratory abilities of cancer cells. 
3. Reduction of Chronic Inflammation: Chronic inflammation is associated with cell transformation and proliferation, which may help to build a tumour microenvironment that is conducive to the growth of cancer$^{26}$. As discussed in the above ‘What Are Its Main Benefits’ section, anthocyanins have been shown to decrease the expression of COX-2 and the production of PGE-2, which are both heavily implicated in the inflammatory response$^{22}$. Besides that, anthocyanins are also able to modulate the NF-kB pathway which normally plays a huge role in initiating inflammation$^{22}$.
4. Inhibition of Angiogenesis: The induction of angiogenesis has classically been known to be a significant hallmark of cancer, and it refers to the process by which cancer cells drive the formation of new blood vessels to fuel the growth of a tumour$^{14}$. In an in vitro study involving breast cancer cells, anthocyanin was reported to downregulate the expression of pro-angiogenetic factors, namely matrix metallopeptidase-9, matrix metallopeptidase-2, and urokinase plasminogen activator, thus inhibiting angiogenesis$^{13}$. In a separate study in human skin cells, anthocyanins were shown to inhibit the expression of vascular endothelial growth factor (VEGF) (a potent inducer of angiogenesis), and thus suppress the induction of angiogenesis$^{8}$.

What Are Typical Doses and Durations?

Clinical studies investigating the cancer-fighting properties of anthocyanin consumption employed a range of treatment doses. Across these studies, oral intake was the sole mode of administration. Studies examining the anticancer effects of anthocyanin supplements used doses ranging from 375mg/day to 1g/day$^{27,28}$. Meanwhile, there were also studies that opted to provide anthocyanin in the form of anthocyanin-rich foods, such as juices and fruits. The treatment doses for these studies ranged from 240mL twice a day to 750mL once a day$^{11,23}$. The studies that assessed the effects of anthocyanin in cancer prevention were relatively short-term studies, lasting over a period of a few weeks$^{11,23,28}$. There were some studies that examined the effectiveness of anthocyanin in improving the side effects of cancer treatment, in which case the study lasted over the duration of the cancer treatment, which was typically a few weeks$^{15,27}$. 

Summary of Data

Summary of clinical trials that administered anthocyanin as a supplement. A total of 1 study that fit this criteria was found using the PubMed database.

📄 Detailed Anthocyanin (as a supplement) human clinical trial study notes analyzed by Anticancer.ca

Summary of clinical trials that administered anthocyanin from anthocyanin-rich food sources. A total of 5 studies that fit this criteria were found using the PubMed database.

📄 Detailed Anthocyanin (from anthocyanin-rich foods) human clinical trial study notes analyzed by Anticancer.ca

Summary of clinical trials that investigated the effects of anthocyanin in improving the side effects of cancer treatment. A total of 2 studies that fit this criteria were found using the PubMed database.

📄 Detailed Anthocyanin (for side effects of cancer therapy) human clinical trial study notes analyzed by Anticancer.ca

References

1. Smeriglio, A., Barreca, D., Bellocco, E. & Trombetta, D. Chemistry, pharmacology and health benefits of anthocyanins. Phytotherapy Research 30, 1265–1286 (2016).
2. Mattioli, R., Francioso, A., Mosca, L. & Silva, P. Anthocyanins: A comprehensive review of their chemical properties and health effects on cardiovascular and Neurodegenerative Diseases. Molecules 25, 3809 (2020).
3. Higdon, J., Drake, V. J., Delage, B. & Crozier, A. Flavonoids. Linus Pauling Institute (2016). Available at: https://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/flavonoids#subclasses. (Accessed: 15th January 2024)
4. Flavylium. National Center for Biotechnology Information. PubChem Compound Database Available at: https://pubchem.ncbi.nlm.nih.gov/compound/Anthocyanin. (Accessed: 16th January 2024)
5. Petre, A. Anthocyanin: Foods, benefits, side effects, and supplements. Healthline (2023). Available at: https://www.healthline.com/nutrition/anthocyanin. (Accessed: 15th January 2024)
6. Kocic, B., Filipovic, S., Nikolic, M & Petrovic, B. Effects of anthocyanins and anthocyanin-rich extracts on the risk for cancers of the gastrointestinal tract.J BUON.16, 602-8 (2011).
7. Li, D., Wang, P., Luo, Y., Zhao, M. & Chen, F. Health benefits of anthocyanins and molecular mechanisms: Update from recent decade. Critical Reviews in Food Science and Nutrition 57, 1729–1741 (2015).
8. Khoo, H. E., Azlan, A., Tang, S. T. & Lim, S. M. Anthocyanidins and anthocyanins: Colored pigments as food, pharmaceutical ingredients, and the potential health benefits. Food & Nutrition Research 61, 1361779 (2017).
9. Alrawi, S. J. et al. Aberrant crypt foci. Anticancer Res 26, 107–119 (2006).
10. Mostafa, H. et al. Plasma anthocyanins and their metabolites reduce in vitro migration of pancreatic cancer cells, PANC-1, in a FAK- and NF-KB dependent manner: Results from the attach-study a randomized, controlled, crossover trial in healthy subjects. Biomedicine & Pharmacotherapy 158, 114076 (2023).
11. Bakuradze, T. et al. Antioxidative activity and health benefits of anthocyanin-rich fruit juice in healthy volunteers. Free Radical Research 53, 1045–1055 (2019).
12. McAnulty, L. S. et al. Six weeks daily ingestion of whole blueberry powder increases natural killer cell counts and reduces arterial stiffness in sedentary males and females. Nutrition Research 34, 577–584 (2014).
13. Hui, C. et al. Anticancer activities of an anthocyanin-rich extract from black rice against breast cancer cells in vitro and in vivo. Nutrition and Cancer 62, 1128–1136 (2010).
14. Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: The next generation. Cell 144, 646–674 (2011).
15. Miko Enomoto, T. et al. Combination glutathione and Anthocyanins as an alternative for skin care during external-beam radiation. The American Journal of Surgery 189, 627–631 (2005).
16. Skin and nail changes and cancer treatment - side effects. National Cancer Institute Available at: https://www.cancer.gov/about-cancer/treatment/side-effects/skin-nail-changes (2022). (Accessed: 29th March 2024)
17. Colitis: Symptoms, what it is, types & treatment. Cleveland Clinic Available at: https://my.clevelandclinic.org/health/diseases/23384-colitis. (Accessed: 16th February 2024)
18. Akiyama, S., Nesumi, A., Maeda‐Yamamoto, M., Uehara, M. & Murakami, A. Effects of anthocyanin‐rich tea “Sunrouge” on dextran sodium sulfate‐induced colitis in mice. BioFactors 38, 226–233 (2012).
19. Chen, C. Cox-2’s new role in inflammation. Nature Chemical Biology 6, 401–402 (2010).
20. Fernandes, I., Faria, A., Calhau, C., de Freitas, V. & Mateus, N. Bioavailability of anthocyanins and derivatives. Journal of Functional Foods 7, 54–66 (2014).
21. Pizzino, G. et al. Oxidative stress: Harms and benefits for human health. Oxidative Medicine and Cellular Longevity2017, 1–13 (2017).
22. Lin, B., Gong, C., Song, H. & Cui, Y. Effects of anthocyanins on the prevention and treatment of cancer. British Journal of Pharmacology 174, 1226–1243 (2016).
23. Traustadóttir, T. et al. Tart cherry juice decreases oxidative stress in healthy older men and women , ,. The Journal of Nutrition 139, 1896–1900 (2009).
24. Wu, Y. & Zhou, B. P. TNF-α/NF-ΚB/snail pathway in cancer cell migration and invasion. British Journal of Cancer 102,639–644 (2010).
25. Mostafa, H. et al. Plasma anthocyanins and their metabolites reduce in vitro migration of pancreatic cancer cells, PANC-1, in a FAK- and NF-KB dependent manner: Results from the attach-study a randomized, controlled, crossover trial in healthy subjects. Biomedicine & Pharmacotherapy 158, 114076 (2023).
26. Singh, N. et al. Inflammation and cancer. Annals of African Medicine 18, 121 (2019).
27. Macis, D. et al. Inflammatory and metabolic biomarker assessment in a randomized presurgical trial of curcumin and anthocyanin supplements in patients with colorectal adenomas. Nutrients 15, 3894 (2023).
28. Bracone, F. et al. Skin toxicity following radiotherapy in patients with breast carcinoma: Is anthocyanin supplementation beneficial? Clinical Nutrition 40, 2068–2077 (2021).

About This Article

Disclaimer

The content on Anticancer.ca is intended for educational and informational purposes only and does not serve as a substitute for professional medical advice or services. Consult a licensed physician for personalized medical advice or questions about your health. Do not disregard professional advice or delay seeking help based on information found on our website. In case of a medical emergency, call 911 or visit the nearest emergency room immediately.

Anticancer.ca strives to provide accurate and reliable information but cannot guarantee its error-free or comprehensive nature. We are not responsible for the quality or endorsement of information, services, products, treatments, or therapies provided by third parties mentioned on our website. Always consult a qualified healthcare professional before making medical decisions.

• Anthocyanin
• What Is It?
• What Are Its Other Names?
• What Foods Have It?
• What Are Its Main Benefits?
• What Are Its Main Drawbacks?
• What Are Its Mechanisms of Action?
• What Are Typical Doses and Durations?
• Summary of Data
• References
• About This Article
• Disclaimer