The Cancer research
Carotenoids like those in spinach curb cancer development in laboratory studies, but it’s not clear whether their protection against breast cancer really is unique to ER-negative (ER-) tumors. Hormonal influences may simply mask protection against ER+ tumors.
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 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
- Limited evidence suggests that foods containing vitamin C may DECREASE the risk of:
- Lung cancer (in people who smoke) and colon cancer
Ongoing Areas of Investigation
- Laboratory Research
Laboratory research is extensive on spinach compounds such as beta-carotene and vitamin C.
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 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.
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 11,12 Flavonols 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.
- 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 the development of cancer.
- Human Studies
Human studies related to spinach and cancer risk compare groups of people who consume relatively high and low amounts of total vegetables, green vegetables, and/or levels of dietary fiber, carotenoids and vitamin C.
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 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.
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 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 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 carotenoids (including beta-carotene) in the diet or blood to lower 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 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 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.
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 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.
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