The Cancer Research
Blueberries contain many phytochemicals and nutrients which show potential anti-cancer effects in laboratory studies.
Several studies found that eating blueberries increases antioxidant activity in the blood as well as showing potential to prevent DNA damage. Studies are limited and results vary so more research is needed to understand blueberries’ role in these areas.
Interpreting the data
After a systematic review of the global scientific literature, AICR/WCRF analyzed how fruits and their nutrients affect the risk of developing cancer.
- Evidence categorized as “convincing” or “probable” means there is strong research showing a causal relationship to cancer—either decreasing or increasing the risk. The research must include quality human studies that meet specific criteria and biological explanations for the findings.
- A convincing or probable judgement is strong enough to justify recommendations.
- There is probable evidence that foods with dietary fiber DECREASE the risk of:
- colorectal cancer
- There is probable evidence that fruit and non-starchy vegetables combined DECREASE the risk of:
- cancers of the aerodigestive tract (mouth, pharynx, nasopharynx, esophagus, lung, stomach, and colorectal cancers)
- Evidence categorized as “limited suggestive” means results are generally consistent in overall conclusions, but it’s rarely strong enough to justify recommendations to reduce the risk of cancer.
- Limited evidence suggests that foods containing vitamin C may DECREASE the risk of:
- lung cancer (in people who smoke) and squamous cell esophageal cancer
- colon cancer
Ongoing Areas of Investigation
- Laboratory Research
- In cell and animal studies, anthocyanins influence cell signaling in ways that increase antioxidant, anti-inflammatory and carcinogen-deactivating enzymes. They inhibit cancer cells’ growth and ability to spread, and activate signaling that leads to self-destruction of abnormal cells.
- In cell and animal studies, phenolic acids increase cells’ antioxidant and anti-inflammatory defenses against damage that could lead to cancer. Emerging evidence in animal studies suggests they may also improve glucose metabolism and decrease insulin resistance, and alter the gut microbiota (microbes living in the colon), creating an environment in the body less likely to support cancer.
- In cell and animal studies, flavonols and flavan-3-ols influence gene expression and cell signaling in ways that increase antioxidant, anti-inflammatory and carcinogen-deactivating enzymes. They inhibit cancer cells’ growth and ability to spread, and activate signaling that leads to self-destruction of abnormal. Flavonols and flavan-3-ols dial down the expression of oncogenes (genes that have potential to cause increased cell growth that can lead to cancer) and increase expression of tumor suppressor genes.
- In cell and animal studies, flavones influence gene expression and cell signaling in ways that increase antioxidant, anti-inflammatory and carcinogen-deactivating enzymes. They inhibit cancer cells’ growth and ability to spread, and activate signaling that leads to self-destruction of abnormal cells. They reduce expression of oncogenes (genes that have potential to cause increased cell growth that can lead to cancer) and increase expression of tumor suppressor genes.
- Tannins such as ellagitannins and proanthocyanidins are complex compounds that are mostly unabsorbed. Microbes in the gut break them down to form other phytochemicals.
- In cell studies, proanthocyanidins are antioxidants that seem to influence gene expression to decrease growth of cancer cells and increase their self-destruction. However, this may not reflect effects when they are consumed in food, especially in parts of the body other than the gut.
- Ellagitannins are broken down in the digestive system to ellagic acid and then to urolithins, which are the compounds that can be absorbed into the body. In cell and animal studies, ellagic acid and the urolithins that form from it increase antioxidant enzymes, decreasing free radical damage to DNA that can lead to cancer. By influencing gene expression, they decrease growth and stimulate self-destruction of several types of cancer cells.
- In some cell studies, urolithins inhibit the aromatase enzyme that produces estrogen and inhibit the growth of estrogen-responsive breast cancer cells.
- Animal studies show decreased inflammation in the colon with ellagitannins and the compounds that form from them at levels that could be reached by people eating a healthful diet.
In animal studies, blueberries decrease inflammatory cytokines, esophageal cancer and pre-cancerous changes in the colon, although impact on colon cancer is less clear. In other animal studies, blueberries decreased estrogen-induced mammary cancer and DNA damage.
- Human Studies
Human studies related to blueberries and cancer risk compare groups of people who consume relatively high and low amounts of total fruit, dietary fiber, berries, or blueberries specifically.
People who eat more fruits have a lower risk of a wide range of cancers. This probably reflects combined protection from many different nutrients and compounds they contain.
Dietary Fiber: Observational population studies link high dietary fiber consumption with reduced risk of colorectal cancer. One meta-analysis of 16 prospective studies also links dietary fiber with lower risk of breast cancer. However, analysis for the AICR/WCRF Third Expert Report considered potential for an association of dietary fiber and this and several other cancers, and found the evidence too limited to support a conclusion.
Vitamin C: Population studies comparing people with higher and lower levels of vitamin C in their diets, and especially levels circulating in their blood, link higher amounts with lower overall risk of cancer. This effect is larger when comparing people with very low levels to moderately increased levels than comparing people with moderate and much higher levels. Higher levels of vitamin C from foods are linked with lower risk of lung cancer among people who smoke tobacco, although not in those who used to smoke or who have never smoked. That’s even after adjusting for other risk factors for colon cancer, such as alcohol, red meat and tobacco. Evidence for both lung and colon cancer is rated as Limited Suggestive in the AICR/WCRF Third Expert Report, and more research is needed.
Ellagitannins and urolithins: Bacteria in the colon convert ellagitannins from blueberries and other berries to ellagic acid and then to urolithins that can be absorbed. People differ dramatically in the amount and types of urolithins they produce from ellagic acid, which could cause differences in the benefits people get from these foods.
Flavonoids found in blueberries: Higher levels of anthocyanins in the diet were strongly associated with lower levels of markers of inflammation, and flavonols and flavan-3-ols were linked with lower levels of oxidative stress in cross-sectional analysis of a large population study.
Several studies show that eating blueberries increases antioxidant activity in people’s blood and potential to prevent DNA damage. But studies are limited and results vary, so more research is needed.
- AICR-Supported Studies
- Tips for Selection, Storage and Preparation
- Choose firm, plump, dry blueberries with dusty blue color. Avoid berries that are soft, shriveled or with any sign of mold.
- Buy frozen blueberries too. These also are high in nutrients and antioxidant phytochemicals.
- Treat yourself to wild blueberries with even more antioxidant power than the more common cultivated blueberries.
- Refrigerate blueberries for up to 10 days.
- Wait to wash until ready to eat.
- Whirl blueberries alone or with other fruits into a smoothie or fruit freeze drink.
- Top cereal or yogurt with fresh or dried blueberries.
- Add blueberries to a green salad.
- Blueberries play well with other fruits! Alone or in combinations, enjoy them in muffins, pancakes, and fruit crumble or crisp desserts.
- Be creative with blueberries: try a blueberry quesadilla with wild blueberry sauce.
- Kalt W, Cassidy A, Howard LR, et al. Recent Research on the Health Benefits of Blueberries and Their Anthocyanins. Advances in Nutrition. 2019.
- Duthie SJ. Berry phytochemicals, genomic stability and cancer: Evidence for chemoprotection at several stages in the carcinogenic process. Mol Nutr Food Res. 2007;51(6):665-674.
- de Sousa Moraes LF, Sun X, Peluzio MdCG, Zhu M-J. Anthocyanins/anthocyanidins and colorectal cancer: What is behind the scenes? Crit Rev Food Sci Nutr. 2019;59(1):59-71.
- Del Rio D, Rodriguez-Mateos A, Spencer JP, Tognolini M, Borges G, Crozier A. Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases. Antioxid Redox Signal. 2013;18(14):1818-1892.
- Tajik N, Tajik M, Mack I, Enck P. The potential effects of chlorogenic acid, the main phenolic components in coffee, on health: a comprehensive review of the literature. Eur J Nutr. 2017;56(7):2215-2244.
- Villa-Rodriguez JA, Ifie I, Gonzalez-Aguilar GA, Roopchand DE. The Gastrointestinal Tract as Prime Site for Cardiometabolic Protection by Dietary Polyphenols. Advances in Nutrition. 2019;10(6):999-1011.
- Gibellini L, Pinti M, Nasi M, et al. Quercetin and cancer chemoprevention. Evid Based Complement Alternat Med. 2011;2011:591356.
- Montgomery M, Srinivasan A. Epigenetic Gene Regulation by Dietary Compounds in Cancer Prevention. Advances in Nutrition. 2019;10(6):1012-1028.
- Li W, Guo Y, Zhang C, et al. Dietary Phytochemicals and Cancer Chemoprevention: A Perspective on Oxidative Stress, Inflammation, and Epigenetics. Chem Res Toxicol. 2016;29(12):2071-2095.
- Yang CS, Chen JX, Wang H, Lim J. Lessons Learned from Cancer Prevention Studies with Nutrients and Non-Nutritive Dietary Constituents. Mol Nutr Food Res. 2016;60(6):1239-1250.
- Yang CS, Wang X. Green tea and cancer prevention. Nutr Cancer. 2010;62(7):931-937.
- Yang CS, Wang X, Lu G, Picinich SC. Cancer prevention by tea: animal studies, molecular mechanisms and human relevance. Nat Rev Cancer. 2009;9(6):429-439.
- Lachance JC, Radhakrishnan S, Madiwale G, Guerrier S, Vanamala JKP. Targeting hallmarks of cancer with a food-system–based approach. Nutrition. 2020;69:110563.
- de Melo FHM, Oliveira JS, Sartorelli VOB, Montor WR. Cancer Chemoprevention: Classic and Epigenetic Mechanisms Inhibiting Tumorigenesis. What Have We Learned So Far? Frontiers in oncology. 2018;8:644-644.
- Casey SC, Amedei A, Aquilano K, et al. Cancer prevention and therapy through the modulation of the tumor microenvironment. Semin Cancer Biol. 2015;35:S199-S223.
- Imran M, Rauf A, Abu-Izneid T, et al. Luteolin, a flavonoid, as an anticancer agent: A review. Biomedicine & Pharmacotherapy. 2019;112:108612.
- George VC, Dellaire G, Rupasinghe HPV. Plant flavonoids in cancer chemoprevention: role in genome stability. J Nutr Biochem. 2017;45:1-14.
- Smeriglio A, Barreca D, Bellocco E, Trombetta D. Proanthocyanidins and hydrolysable tannins: occurrence, dietary intake and pharmacological effects. Br J Pharmacol. 2017;174(11):1244-1262.
- Ismail T, Calcabrini C, Diaz AR, et al. Ellagitannins in Cancer Chemoprevention and Therapy. Toxins. 2016;8(5):151.
- Boateng J, Verghese M, Shackelford L, et al. Selected fruits reduce azoxymethane (AOM)-induced aberrant crypt foci (ACF) in Fisher 344 male rats. Food Chem Toxicol. 2007;45(5):725-732.
- Simmen FA, Frank JA, Wu X, Xiao R, Hennings LJ, Prior RL. Lack of efficacy of blueberry in nutritional prevention of azoxymethane-initiated cancers of rat small intestine and colon. BMC Gastroenterol. 2009;9:67.
- Stoner GD, Wang LS, Seguin C, et al. Multiple berry types prevent N-nitrosomethylbenzylamine-induced esophageal cancer in rats. Pharm Res. 2010;27(6):1138-1145.
- Wang LS, Hecht S, Carmella S, et al. Berry ellagitannins may not be sufficient for prevention of tumors in the rodent esophagus. J Agric Food Chem. 2010;58(7):3992-3995.
- Aiyer HS, Gupta RC. Berries and ellagic acid prevent estrogen-induced mammary tumorigenesis by modulating enzymes of estrogen metabolism. Cancer Prev Res (Phila). 2010;3(6):727-737.
- Aiyer HS, Kichambare S, Gupta RC. Prevention of oxidative DNA damage by bioactive berry components. Nutr Cancer. 2008;60 Suppl 1:36-42.
- World Cancer Research Fund / American Institute for Cancer Research. Continuous Update Project Expert Report 2018. Wholegrains, vegetables and fruit and the risk of cancer. Available at: dietandcancerreport.org.
- Aune D. Plant Foods, Antioxidant Biomarkers, and the Risk of Cardiovascular Disease, Cancer, and Mortality: A Review of the Evidence. Advances in Nutrition. 2019;10(Supplement_4):S404-S421.
- Ma Y, Hu M, Zhou L, et al. Dietary fiber intake and risks of proximal and distal colon cancers: A meta-analysis. Medicine. 2018;97(36):e11678.
- World Cancer Research Fund / American Institute for Cancer Research. Continuous Update Project Expert Report 2018. Diet, nutrition, physical activity and colorectal cancer. Available at: dietandcancerreport.org.
- Aune D, Chan DS, Greenwood DC, et al. Dietary fiber and breast cancer risk: a systematic review and meta-analysis of prospective studies. Ann Oncol. 2012;23(6):1394-1402.
- Aune D, Keum N, Giovannucci E, et al. Dietary intake and blood concentrations of antioxidants and the risk of cardiovascular disease, total cancer, and all-cause mortality: a systematic review and dose-response meta-analysis of prospective studies. Am J Clin Nutr. 2018;108(5):1069-1091.
- Burton-Freeman BM, Sandhu AK, Edirisinghe I. Red Raspberries and Their Bioactive Polyphenols: Cardiometabolic and Neuronal Health Links. Advances in Nutrition. 2016;7(1):44-65.
- Kang I, Buckner T, Shay NF, Gu L, Chung S. Improvements in Metabolic Health with Consumption of Ellagic Acid and Subsequent Conversion into Urolithins: Evidence and Mechanisms. Advances in Nutrition. 2016;7(5):961-972.
- Afrin S, Giampieri F, Gasparrini M, et al. Chemopreventive and Therapeutic Effects of Edible Berries: A Focus on Colon Cancer Prevention and Treatment. Molecules. 2016;21(2):169.
- Cassidy A, Rogers G, Peterson JJ, Dwyer JT, Lin H, Jacques PF. Higher dietary anthocyanin and flavonol intakes are associated with anti-inflammatory effects in a population of US adults1. Am J Clin Nutr. 2015;102(1):172-181.
- Prior RL, Gu L, Wu X, et al. Plasma antioxidant capacity changes following a meal as a measure of the ability of a food to alter in vivo antioxidant status. J Am Coll Nutr. 2007;26(2):170-181.
- Johnson SA, Arjmandi BH. Evidence for Anti-Cancer Properties of Blueberries: A Mini-Review. Anti-Cancer Agents in Medicinal Chemistry- Anti-Cancer Agents). 2013;13(8):1142-1148.