Research findings show that the carotenoids found in dark green leafy vegetables such as kale can act as antioxidants and boost the body’s own antioxidant defenses. These defenses help stop free radicals from damaging DNA that can lead to cancer. The vitamin C in kale is also a powerful antioxidant, and helps to inhibit formation of carcinogens.
Interpreting the data
After a systematic review of the global scientific literature, AICR/WCRF analyzed how foods and their nutrients affect the risk of developing cancer.
“Convincing” or “probable” evidence 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
- Weight gain, overweight and obesity*
*This is important, because there is strong evidence that excess body fat increases the risk of at least 12 different cancers.
- There is probable evidence that non-starchy vegetables and fruit combined DECREASE the risk of:
- Aerodigestive cancers overall (such as mouth, pharynx and larynx; esophageal; lung; stomach and colorectal cancers)
“Limited suggestive” evidence means results are generally consistent in overall conclusions, but it’s rarely strong enough to justify recommendations to reduce risk of cancer.
- Limited evidence suggests that non-starchy vegetables may DECREASE the risk of:
- Estrogen receptor-negative (ER-) breast cancer
- Limited evidence suggests that non-starchy vegetables and fruit combined may DECREASE the risk of:
- Bladder cancer
- Limited evidence suggests that foods containing vitamin C may DECREASE the risk of:
- Lung cancer (in people who smoke) and colon cancer
- Limited evidence suggests that foods containing beta-carotene may DECREASE the risk of:
- Lung cancer
- Limited evidence suggests that foods containing carotenoids may DECREASE the risk of:
- Lung and estrogen receptor-negative (ER-) breast cancers.
Ongoing Areas of Investigation
- Laboratory Research
Carotenoids act as antioxidants themselves and stimulate the body’s own antioxidant defenses, decreasing free radical damage to DNA that can lead to cancer. Very high levels in cell studies, however, can have an opposite effect, promoting damage from oxidation.
Beta-carotene and lutein promote cell-to-cell communication that helps control cell growth. These carotenoids also increase carcinogen-metabolizing enzymes and stimulate the self-destruction of abnormal cells. The body uses beta-carotene to form vitamin A, which helps protect against cancer through the immune system and expression of genes that regulate cell growth.
Lutein and zeaxanthin are antioxidants that are especially concentrated in the eyes, brain and skin. Limited animal studies suggest that they may help protect against skin cancer related to sun exposure.
Vitamin C is a powerful antioxidant. In lab studies, it protects cells’ DNA by trapping free radicals, and it helps renew the antioxidant ability of Vitamin E. In cell studies, vitamin C also inhibits the formation of carcinogens and supports the immune system.
Glucosinolates in vegetables are broken down into isothiocyanates (such as sulforaphane) and indoles. In laboratory studies, these compounds decrease inflammation that could cause cell damage leading to cancer. They also inhibit enzymes that activate carcinogens and stimulate enzymes that de-activate carcinogens. These compounds turn on tumor suppressor genes, slow abnormal cell growth and stimulate self-destruction of abnormal cells.
- Indole compounds decrease the development of breast cancer in cell and animal studies. In some studies, indoles shift the active form of estrogen into a weaker form. (High amounts of estrogen are a risk factor for certain hormone-linked cancers).
Flavonols like kaempferol and quercetin influence gene expression and cell signaling in ways that increase antioxidant, anti-inflammatory and carcinogen-deactivating enzymes in cell and animal studies. They inhibit cancer cells’ growth and ability to spread, and activate signaling that leads to self-destruction of abnormal Flavonols dial down the expression of oncogenes (genes that have the potential to cause increased cell growth that can lead to cancer) and increase expression of tumor suppressor genes.
Folate helps maintain healthy DNA and keep cancer-promoting genes “turned off”. Animal studies, however, suggest that exceptionally high amounts or intervention after cancer cells have formed might promote development of cancer.
- Human Studies
Human studies related to kale and cancer risk compare groups of people who consume relatively high and low amounts of total vegetables, green vegetables, cruciferous vegetables and/or levels of dietary fiber, carotenoids and vitamin C. This effect is greater when comparing people with very low vitamin C consumption to people consuming moderate amounts than when comparing people with moderate dietary vitamin C to those consuming high amounts.
People who eat more vegetables and fruits have lower risk of a wide range of cancers. This probably reflects combined protection from many different nutrients and compounds they contain.
Greater consumption of green leafy vegetables was associated with lower risk of estrogen receptor-negative (ER-) breast cancer (but not ER+) in an analysis of 20 observational population studies.
Dietary Fiber: Observational population studies link high dietary fiber consumption with reduced risk of colorectal cancer. One meta-analysis of 16 prospective studies also link dietary fiber with a lower risk of breast cancer. However, analysis for the AICR/WCRF Third Expert Report considered the potential for an association of dietary fiber and this and several other cancers and found the evidence too limited to support a conclusion.
Carotenoids: In population studies, higher blood levels of total carotenoids and of beta-carotene are linked with lower risk of overall cancer. Blood levels may more accurately reflect the consumption of carotenoid-rich foods than diet questionnaires, and they include differences in how much is absorbed from food. However, it may be that the lower cancer risk is seen because blood levels of these compounds are recognized as signals of greater overall vegetable and fruit consumption.
- Lung cancer: Population studies link higher dietary and blood levels of beta-carotene or total carotenoids with a lower risk of lung cancer. Larger studies now show protection less clearly than earlier studies, and the AICR/WCRF Third Expert Report categorizes this link as Limited Suggestive. Additional research is needed.
- Breast cancer: Some population studies also link higher levels of diets to higher blood levels of carotenoids (including beta-carotene) in the diet or blood to lower the risk of breast cancer, mainly for estrogen receptor-negative (ER-) forms. The AICR/WCRF Third Expert Report categorized this link as Limited Suggestive. It is possible that an effect of carotenoids on ER-positive (ER+) tumors is simply masked by the hormonal influences that dominate the risk of ER+ breast cancer.
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 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 a lower risk of lung cancer among people who smoke tobacco, although not in those who used to smoke or who have never smoked. People with more vitamin C in their diet are also less likely to develop colon cancer. 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.
Cruciferous vegetables: An analysis published after the AICR/WCRF Third Expert Report that combined several population studies showed an association of cruciferous vegetables with reduced overall cancer risk, although there are inconsistencies between studies. Part of the inconsistent findings may stem from genetic differences that allow isothiocyanate compounds to remain in the body longer in some people than in others, as well as how differences in microbes that make up the gut microbiota can lead to differences compounds people absorb. Human studies are also complicated to interpret because people who eat the same amount of cruciferous vegetables may get different amounts of protective nutrients and compounds depending on how the vegetables are prepared.
- Prostate cancer: An analysis of 13 observational population studies reported higher cruciferous vegetable consumption associated with lower prostate cancer incidence. However, when looking only at studies less likely to be affected by bias (prospective cohort studies), no association was seen. In analysis for the AICR/WCRF Continuous Update Project, no significant association was seen for total prostate cancer or for advanced forms specifically.
- Breast cancer: Analysis from two large cohorts combined that was published after the WCRF/AICR report Third Expert Report found cruciferous vegetables associated with lower risk of breast cancer, which is consistent with the lower risk of postmenopausal breast cancer (but not pre-menopausal cancer) with high cruciferous vegetables in an earlier analysis that included some prospective cohort studies.32 In an analysis of 20 observational population studies, a greater consumption of cruciferous vegetables was associated with a lower risk of estrogen receptor-negative (ER-) breast cancer (but not ER+ cancer). More research is needed.
Flavonols: Higher levels of flavonols in the diet were linked with lower levels of oxidative stress in cross-sectional analysis of a large population study.
Folate: Research on folate and cancer is challenging to interpret, since effects may differ based on time in the cancer process, amount consumed and individual genetic differences. Levels of folate from food and in the blood that are too low are linked with greater risk of several forms of cancer in some population studies. However, excess folic acid from randomized controlled trials with supplements has increased the risk of some cancers. (Folic acid is the form of folate in supplements and fortified foods.) More research is needed to understand the amounts that are high enough to pose risk.
From the Blog
In the News
- Kim Y-I. Folate and cancer: a tale of Dr. Jekyll and Mr. Hyde? Am J Clin Nutr. 2018;107(2):139-142.
- Pieroth R, Paver S, Day S, Lammersfeld C. Folate and Its Impact on Cancer Risk. Current Nutrition Reports. 2018;7(3):70-84.
- 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.
- Bohn T. Carotenoids, Chronic Disease Prevention and Dietary Recommendations. International Journal for Vitamin and Nutrition Research. 2017;87(3-4):121-130.
- Kaulmann A, Bohn T. Carotenoids, inflammation, and oxidative stress–implications of cellular signaling pathways and relation to chronic disease prevention. Nutr Res. 2014;34(11):907-929.
- Bouayed J, Bohn T. Exogenous antioxidants – Double-edged swords in cellular redox state: Health beneficial effects at physiologic doses versus deleterious effects at high doses. Oxid Med Cell Longev. 2010;3(4):228-237.
- Buscemi S, Corleo D, Di Pace F, Petroni ML, Satriano A, Marchesini G. The Effect of Lutein on Eye and Extra-Eye Health. Nutrients. 2018;10(9):1321.
- Thomas SE, Johnson EJ. Xanthophylls. Advances in Nutrition. 2018;9(2):160-162.
- Moran NE, Mohn ES, Hason N, Erdman JW, Jr, Johnson EJ. Intrinsic and Extrinsic Factors Impacting Absorption, Metabolism, and Health Effects of Dietary Carotenoids. Advances in Nutrition. 2018;9(4):465-492.
- Balic A, Mokos M. Do We Utilize Our Knowledge of the Skin Protective Effects of Carotenoids Enough? Antioxidants (Basel). 2019;8(8):259.
- Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, D.C. : National Academies Press;2000.
- Lu JM, Lin PH, Yao Q, Chen C. Chemical and molecular mechanisms of antioxidants: experimental approaches and model systems. Journal of cellular and molecular medicine. 2010;14(4):840–860.
- Lachance JC, Radhakrishnan S, Madiwale G, Guerrier S, Vanamala JKP. Targeting hallmarks of cancer with a food-system–based approach. Nutrition. 2020;69:110563.
- 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.
- Gupta P, Kim B, Kim SH, Srivastava SK. Molecular targets of isothiocyanates in cancer: recent advances. Mol Nutr Food Res. 2014;58(8):1685-1707.
- Montgomery M, Srinivasan A. Epigenetic Gene Regulation by Dietary Compounds in Cancer Prevention. Advances in Nutrition. 2019;10(6):1012-1028.
- Bishop KS, Ferguson LR. The interaction between epigenetics, nutrition and the development of cancer. Nutrients. 2015;7(2):922-947.
- Thomson CA, Ho E, Strom MB. Chemopreventive properties of 3,3′-diindolylmethane in breast cancer: evidence from experimental and human studies. Nutr Rev. 2016;74(7):432-443.
- Gibellini L, Pinti M, Nasi M, et al. Quercetin and cancer chemoprevention. Evid Based Complement Alternat Med. 2011;2011:591356.
- 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.
- Jung S, Spiegelman D, Baglietto L, et al. Fruit and Vegetable Intake and Risk of Breast Cancer by Hormone Receptor Status. JNCI: Journal of the National Cancer Institute. 2013;105(3):219-236.
- 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.
- World Cancer Research Fund/American Institute of Cancer Research. Continuous Update Project Expert Report 2018. Other dietary exposures and the risk of cancer. Available at dietandcancerreport.com.
- Farvid MS, Chen WY, Rosner BA, Tamimi RM, Willett WC, Eliassen AH. Fruit and vegetable consumption and breast cancer incidence: Repeated measures over 30 years of follow-up. International Journal of Cancer. 2019;144:1496-1510.
- Aune D, Giovannucci E, Boffetta P, et al. Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality—a systematic review and dose-response meta-analysis of prospective studies. Int J Epidemiol. 2017;46(3):1029-1056.
- Gerhauser C. Impact of dietary gut microbial metabolites on the epigenome. Philosophical Transactions of the Royal Society B: Biological Sciences. 2018;373(1748):20170359.
- Liu B, Mao Q, Cao M, Xie L. Cruciferous vegetables intake and risk of prostate cancer: A meta-analysis. International Journal of Urology. 2012;19(2):134-141.
- Norat T, Vieira AR, Chan D, et al. The Associations Between Food, Nutrition and Physical Activity and the Risk of Prostate Cancer. WCRF/AICR Systematic Literature Review Continuous Update Project Report. London: World Cancer Research Fund / American Institute for Cancer Research;2014.
- Liu X, Lv K. Cruciferous vegetables intake is inversely associated with risk of breast cancer: A meta-analysis. The Breast. 2013;22(3):309-313.
- 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.
- Folate: Fact Sheet for Health Professionals. Office of Dietary Supplements, National Institutes of Health Available at: https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/Updated July 19, 2019. Accessed December 9, 2019.
- McKillop DJ, Pentieva K, Daly D, et al. The effect of different cooking methods on folate retention in various foods that are amongst the major contributors to folate intake in the UK diet. Br J Nutr. 2002;88(6):681-688.
- Nugrahedi PY, Verkerk R, Widianarko B, Dekker M. A Mechanistic Perspective on Process-Induced Changes in Glucosinolate Content in Brassica Vegetables: A Review. Crit Rev Food Sci Nutr. 2015;55(6):823-838.
- Song L, Thornalley PJ. Effect of storage, processing and cooking on glucosinolate content of Brassica vegetables. Food Chem Toxicol. 2007;45(2):216-224.
- McNaughton SA, Marks GC. Development of a food composition database for the estimation of dietary intakes of glucosinolates, the biologically active constituents of cruciferous vegetables. Br J Nutr. 2003;90(3):687-697.
- Cartea ME, Francisco M, Soengas P, Velasco P. Phenolic compounds in Brassica vegetables. Molecules. 2011;16(1):251-280.
- Rungapamestry V, Duncan AJ, Fuller Z, Ratcliffe B. Effect of cooking brassica vegetables on the subsequent hydrolysis and metabolic fate of glucosinolates. Proc Nutr Soc. 2007;66(1):69-81.