The Cancer Research
Research is investigating effects of proanthocyanidin compounds from grape seeds and skins. Laboratory studies suggest that they, or compounds gut microbes produce from them, may influence expression of genes related to cancer development. Much work is needed to understand whether this has practical applications in eating habits to reduce cancer risk.
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 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 fruit may DECREASE the risk of:
- Lung cancer (in people who smoke or used to smoke tobacco) and squamous cell esophageal cancer
- Limited evidence suggests that non-starchy vegetables and fruit combined may DECREASE the risk of:
- Bladder cancer
Ongoing Areas of Investigation
- Laboratory Research
Resveratrol is the focus of much of the research related to grapes in eating habits to reduce cancer risk, since grapes are one of a few major food sources. In cell culture studies, resveratrol inhibits all stages of development and progression of various cancers: skin, colorectal, breast, prostate, liver, lung and others. In isolated cells, resveratrol is a powerful antioxidant, directly scavenging free radicals that could damage DNA and stimulating cells’ own antioxidant enzymes. Limited studies in mice and rats show some effects reducing inflammation and cancer development and metastasis, though less consistently.
Anthocyanins influence 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 cells.
Phenolic acids increase cells’ antioxidant and anti-inflammatory defenses against damage that could lead to cancer in cell and animal studies. 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.
Flavonols and flavan-3-ols 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 and flavan-3-ols dial down expression of oncogenes (genes that have potential to cause increased cell growth that can lead to cancer) and increase expression of tumor suppressor genes.
Proanthocyanidins are complex compounds that are mostly unabsorbed. Microbes in the gut break them down to form phenolic acids and 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.
- Human Studies
People who eat more fruit have lower risk of a wide range of cancers. This probably reflects combined protection from many different nutrients and compounds they contain, and how they support overall healthful eating patterns.
Human clinical trials of resveratrol are very limited. Interpretation of results is complicated, because some studies used grape extracts without noting resveratrol concentrations. And once absorbed, resveratrol is quickly metabolized to other compounds, and excreted. Overall, the absorption and effects of resveratrol seem to vary with the amount consumed, the composition of foods eaten at the same time, and individual differences in the gut microbiota.
Human studies of how grapes might influence cancer risk are extremely limited. One small, short-term trial showed daily grape juice can decrease free radicals and DNA damage. Women in two case-control studies who consumed the most grapes or resveratrol from grapes had less breast cancer; however, resveratrol from wine was not protective. In a small pilot study, giving colon cancer patients grape powder reduced expression of a tumor-promoting gene in normal colon cells; levels in colon cancer cells did not change, however.
In an observational (prospective cohort) study of older adults, higher urinary levels of compounds formed from resveratrol — a marker of higher resveratrol consumption – showed no association with markers of inflammation, cancer risk, or longevity after 9 years of follow-up. It’s possible that amounts of resveratrol from dietary habits were not high enough to make a difference. It may also be important that in this study, conducted in a major wine production area of Italy, higher urinary levels of resveratrol-related compounds were strongly linked with greater alcohol consumption.
Amounts of resveratrol that show potential protective effects in laboratory studies seem to translate to grape consumption beyond amounts likely to be reached through food choices. Benefits are more likely, therefore, to come from overall effects of multiple compounds in grapes and those of many other plant foods.
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