Highlights
Different studies indicate that flavonoids have a range of health benefits including antioxidant, anti-inflammatory and cancer fighting properties and are found in a variety of foods including fruits (such as cranberries, blueberries, blackberries, bilberries, fiber rich apples etc), vegetables and beverages. Hence, including flavonoid rich foods as part of our daily diet will be beneficial. However, before taking any flavonoid supplements, cancer patients should always discuss with their healthcare professionals.
What are flavonoids?
Flavonoids are a group of bioactive phenolic compounds and a subset of phytonutrients found abundantly in different plant foods. Flavonoids are present in different types of fruits, vegetables, nuts, seeds, spices, grains, bark, roots, stems, flowers and other plant foods as well as beverages such as tea and wine. With the increasing use of flavonoids by taking fruits and vegetable-rich diets, different studies have been carried out across the world to evaluate their potential health benefits and cancer fighting properties.
Different Classes of Flavonoids and Food Sources
Based on the chemical structure of the flavonoids, they are classified into the following subclasses.
- Anthocyanins
- Chalcones
- Flavanones
- Flavones
- Flavonols
- Flavan-3-ols
- Isoflavones
Anthocyanins – The Flavonoid Subclass & Food Sources
Anthocyanins are the pigments responsible for providing colours to the flowers and fruits of the plants. They are known to have strong antioxidant properties. The flavonoid Anthocyanins are widely used in the food industry due to its health benefits and stability.
Some of the examples of anthocyanins are:
- Delphinidin
- Cyanidin
- Pelargonidin
- Malvidin
- Peonidin and
- Petunidin
Food Sources of Anthocyanin flavonoids : Anthocyanins are abundantly found in the outer skin of variety of fruits/berries and berry products including:
- Red grapes
- Merlot grapes
- Red wine
- Cranberries
- Black currants
- Raspberries
- Strawberries
- Blueberries
- Bilberries and
- Blackberries
Chalcones – The Flavonoid Subclass & Food Sources
Chalcones are another subclass of flavonoids. They are also known as open-chain flavonoids. Chalcones and their derivatives have many nutritional and biological benefits. Dietary chalcones seem to have activity against cancer cells, suggesting that they may have anti-cancer properties. Chalcones are known to have antioxidative, antibacterial, anti-inflammatory, anticancer, cytotoxic, and immunosuppressive properties.
Some of the examples of chalcones are :
- Arbutin
- Phloridzin
- Phloretin and
- Chalconaringenin
The flavonoids, Chalcones, are commonly found in a variety of foods such as :
- Garden tomatoes
- Shallots
- Bean sprouts
- Pears
- Strawberries
- Bearberries
- Licorice and
- certain wheat products
Flavanones – The Flavonoid Subclass & Food Sources
Flavanones, also known as dihydroflavones, are another important subclass of flavonoids with strong antioxidant and free radical-scavenging properties. Flavanones give the bitter taste to the peel and juice of citrus fruits. These citrus flavonoids also exhibit anti-inflammatory properties and also act as blood lipid-lowering and cholesterol-lowering agents.
Some of the examples of flavanones are:
- Eriodictyol
- Hesperetin and
- Naringenin
The flavonoids, Flavanones, are mostly found in foods such as all citrus fruits including:
- Oranges
- Limes
- Lemons and
- Grapefruits
Flavones- The Flavonoid Subclass & Food Sources
Flavones are a subclass of flavonoids which are widely present in leaves, flowers and fruits as glucosides. They are the pigments in blue and white flowering plants. Flavones also work as natural pesticides in plants, providing protection against insects and fungal diseases. Flavones are known to have strong antioxidant and anti-inflammatory properties.
Some of the examples of flavones are :
- Apigenin
- Luteolin
- Baicalein
- Chrysin
- Tangeritin
- Nobiletin
- Sinensetin
The flavonoids, Flavones, are mostly present in foods such as:
- celery
- parsley
- red peppers
- chamomile
- Peppermint
- ginkgo biloba
Flavonols – The Flavonoid Subclass & Food Sources
Flavonols, another subclass of flavonoids and the building blocks of proanthocyanins, are found in a variety of fruits and vegetables. Flavonols are known to have many health benefits including antioxidant potential and reduced risk of vascular disease.
Some of the examples of flavonols include :
- Fisetin
- Quercetin
- Myricetin
- Rutin
- Kaempferol
- Isorhamnetin
The flavonoids, Flavonols, are mostly present in foods such as:
- Onions
- Kale
- Tomatoes
- Apples
- Grapes
- Berries
- Tea
- Red wine
Flavan-3-ols – The Flavonoid Subclass & Food Sources
Flavan-3-ols are the major tea flavonoids with a wide range of health benefits. Flavan-3-ols are known to have antioxidant, anti-inflammatory and anti-cancer properties.
Some of the examples of flavan-3-ols include :
- Catechins and their gallate derivatives : (+)-Catechin, (-)-Epicatechin, (-)-Epigallocatechin, (+)-Gallocatechin
- Theaflavins, Thearubigins
- Proanthocyanidins
The flavonoids, Flavan-3-ols, are mostly present in foods such as:
- black tea
- green tea
- White tea
- oolong tea
- Apples
- cocoa based products
- purple grapes
- red grapes
- Red wine
- blueberries
- strawberries
Isoflavones – The Flavonoid Subclass & Food Sources
Isoflavonoids are another subgroup of flavonoids and some of their derivatives are sometimes referred to as phytoestrogens due to their estrogenic activity. Isoflavones are associated with medicinal properties including anticancer, antioxidant, and cardioprotective properties due to the estrogen receptor inhibition functionality.
Some of the examples of isoflavones are :
- Genistein
- Daidzein
- Glycitein
- Biochanin A
- Formononetin
Among these, isoflavones such as genistein and daidzein are the most popular phytoestrogens.
The flavonoids, isoflavones, are mostly present in foods such as:
- Soybeans
- Soy foods and products
- Leguminous plants
Some isoflavonoids may also be present in microbes.
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Cancer Fighting Properties of Flavonoids present in Fruits, Vegetables & Beverages
Flavonoids are known to have many health benefits due to its antioxidant and anti-inflammatory properties. Some of the health benefits of flavonoid rich foods are listed below.
- Including flavonoids in our diet may help to manage high blood pressure.
- Flavonoids may help in reducing the incidence of heart attack or stroke.
- Flavonoids may also help in reducing the risk of diabetes.
- Some studies have reported that flavonoids can enhance bone formation and inhibit bone resorption.
- Flavonoids may improve cognition in older adults.
Along with all the aforementioned health benefits, flavonoids commonly found in foods such as fruits, vegetables and beverages are also known to have cancer fighting properties. Flavonoids can scavenge free radicals which can damage macromolecules such as DNA. These can also help in DNA repair and also inhibit angiogenesis and tumor invasion.
We will now zoom into some of the studies carried out to evaluate the cancer fighting properties of few flavonoids/ flavonoid rich foods including fruits, vegetables and beverages. Let us see what these studies say!
Use of Soy Isoflavone Genistein along with Chemotherapy in Metastatic Colorectal Cancer
Metastatic Colorectal Cancer has poor prognosis with a 2-year survival less than 40% and a 5-year survival less than 10%, despite the very aggressive combination chemotherapy treatment options (AJCC Cancer Staging Handbook, 8th Edn). Different studies have shown that east Asian populations who consume a Soy-rich diet are associated with a lower risk of colorectal cancers. Many preclinical experimental studies also demonstrated the anti-cancer properties of the soy isoflavone Genistein, and its ability to reduce chemotherapy resistance in cancer cells.
Researchers at the Icahn School of Medicine at Mount Sinai, in New York, evaluated the safety and efficacy of consuming isoflavone Genistein along with the standard of care combination chemotherapy in a prospective clinical study in metastatic Colorectal Cancer patients (NCT01985763) (Pintova S et al, Cancer Chemotherapy & Pharmacol., 2019). The study included 13 patients with metastatic colorectal cancer with no prior treatment, with 10 patients treated with a combination of FOLFOX chemotherapy and Genistein and 3 patients treated with FOLFOX + Bevacizumab and Genistein. Combining Genistein with these chemotherapies was found to be safe and tolerable.
There was an improvement in best overall response (BOR) in these metastatic colorectal cancer patients taking the chemotherapy along with Genistein, when compared to those reported for the chemotherapy treatment alone in earlier studies. BOR was 61.5% in this study compared to 38-49% in previous studies with the same chemotherapy treatments. (Saltz LB et al, J Clin Oncol, 2008) Even the progression free survival metric, which indicates the amount of time that the tumor has not progressed with the treatment, was a median of 11.5 months with Genistein combination in this study compared to 8 months for chemotherapy alone based on a prior study. (Saltz LB et al, J Clin Oncol., 2008)
The study indicates that it may be safe to use the soy isoflavone Genistein supplement along with the combination chemotherapy FOLFOX for the treatment of metastatic colorectal cancer. Combining Genistein with chemotherapy has the potential for improving the treatment outcomes. However, these findings, although promising, will need to be assessed in larger clinical studies.
Use of flavonol Fisetin in Colorectal Cancer
The flavonol – Fisetin is a coloring agent that is naturally found in many plants and vegetables including strawberries, fiber rich apples and grapes. It is known to have diverse health benefits such as neuroprotective, anti-inflammatory, and anti-carcinogenic effects. Different studies have been carried out to evaluate the effect of Fisetin on the chemotherapy outcomes in colorectal cancer patients.
A clinical study was carried out in 2018 by the researchers from Iran to study the effects of fisetin supplementation on factors related to inflammation and cancer spread (metastasis), in Colorectal Cancer patients receiving adjuvant chemotherapy (Farsad-Naeimi A et al, Food Funct. 2018). The study included 37 patients aged 55 ± 15 years old, who were admitted to the Oncology Department of Tabriz University of Medical Sciences, Iran, with stage II or III colorectal cancer, with a life expectancy of more than 3 months. Oxaliplatin and capecitabine were the chemotherapy treatment regimen. Out of 37 patients, 18 patients also received 100 mg of fisetin for 7 consecutive weeks.
The study found that the group using fisetin supplement had a significant reduction of the pro-cancer inflammatory factor IL-8 as compared to the control group. The study also showed that Fisetin supplementation also reduced the levels of some of the other inflammation and metastasis factors such as hs-CRP and MMP-7.
This small clinical trial indicates the potential benefit of fisetin in reducing pro-cancer inflammatory markers in colorectal cancer patients when given along with their adjuvant chemotherapy.
Use of Flavan-3-ol Epigallocatechin-3-gallate (EGCG) in Esophageal Cancer Patients treated with Radiation Therapy
Epigallocatechin-3-gallate (EGCG) is a flavonoid/flavan-3-ol with strong antioxidant and anti-inflammatory properties. It is also used for reducing the risk of specific cancers and for alleviating certain chemotherapy side effects. It is one of the most abundant ingredients found in green tea and is also found in white, oolong, and black teas.
In a phase II clinical study conducted by the Shandong Cancer Hospital and Institute in China, data from a total of 51 patients were included,out of which 22 patients received concurrent chemoradiation therapy (14 patients were treated with docetaxel + cisplatin followed by radiotherapy and 8 with fluorouracil + cisplatin followed by radiotherapy) and 29 patients received radiation therapy. The patients were monitored weekly for acute radiation induced esophagitis (ARIE).(Xiaoling Li et al, Journal of Medicinal Food, 2019).
The study found that EGCG supplementation reduced esophagitis/swallowing difficulties in esophageal cancer patients treated with radiation therapy without negatively impacting the efficacy of radiation therapy.
Cancer Fighting Properties of Apigenin
Apigenin is found naturally in a wide variety of herbs, vegetables and fruits including celery, onions, grapefruit, grapes, apples, chamomile, spearmint, basil, oregano. Apigenin has antioxidant properties along with anti-inflammatory and antibacterial properties. Different pre-clinical studies done on a wide-variety of cancer cell lines and animal models using Apigenin have also demonstrated its anti-cancer effects. Flavonoids like Apigenin helps in cancer-preventative measures to decrease the potential future risk of developing a tumor but it is also able to work synergistically with some chemotherapies to enhance the efficacy of the drug (Yan et al, Cell Biosci., 2017).
In different studies using cell culture and animal models, Apigenin enhanced the efficacy of gemcitabine chemotherapy in otherwise hard to treat pancreatic cancer (Lee SH et al, Cancer Lett., 2008; Strouch MJ et al, Pancreas, 2009). In another study with prostate cancer cells, Apigenin when combined with chemotherapy drug Cisplatin significantly enhanced its cytotoxic effect. (Erdogan S et al, Biomed Pharmacother., 2017). These studies suggest that Apigenin found in different fruits, vegetables and herbs have the potential to fight cancer.
Cancer Fighting Properties of Flavonoid and Fiber rich Apples
Apples are rich in a variety of antioxidants, including flavonoids such as quercetin and catechin. Apples are also rich in fiber, vitamins, and minerals, all of which benefit health. The antioxidant properties of these phytochemicals and fiber in apples may protect DNA from oxidative damage. Different studies were carried out to evaluate the effect of these flavonoid/vitamin/fiber rich apple consumption on the risk of cancer.
A meta-analysis of different observational studies identified by literature search in PubMed, Web of Science and Embase databases found that a high consumption of flavonoid/vitamin/fiber rich apple was associated with a reduced risk of lung cancer.(Roberto Fabiani et al, Public Health Nutr., 2016) Few of the case-control studies also found a reduced risk of colorectal, breast and overall digestive tract cancers with increased consumption of apples. The anti-cancer properties of apples, however, cannot be attributed to flavonoids alone, as it may also be due to nutrients like vitamins, minerals and fibers. The dietary fibers (which are also found in apples) are known to reduce the risk of colon cancers.(Yu Ma et al, Medicine (Baltimore), 2018)
Health benefits of Flavonoid rich Cranberries
Cranberries are a good source of bioactive constituents including flavonoids such as anthocyanins, vitamins and antioxidants and have a variety of health benefits. One of the major health benefits of Cranberry extract powders is that it reduces urinary tract infections (UTIs). The health benefits of Proanthocyanidin found in cranberries include inhibiting the growth of bacteria that causes plaque formation, cavities and initial stages of gum disease.Many preclinical studies and a few human studies were also conducted to assess if cranberry fruit also has an additional health benefit of cancer fighting properties.
In a double blind placebo controlled study, the researchers investigated the health benefits of cranberries by assessing the effects of cranberry consumption on prostate specific antigen (PSA) values and other markers in men with prostate cancer before radical prostatectomy.(Vladimir Student et al, Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub., 2016) The study found that daily consumption of a powdered cranberry fruit reduced serum PSA in patients with prostate cancer by 22.5%. The researchers concluded that this health benefit is possibly due to the properties of the bioactive ingredients of cranberries that regulate the expression of androgen-responsive genes, which play a critical role in the development and progression of prostate cancer.
Conclusion
Different studies indicate that flavonoids have a range of health benefits including cancer fighting properties and are found in a variety of foods including fruits (such as fiber rich apples, grapes, cranberries, blueberries), vegetables (such as tomatoes, leguminous plants) and beverages (such as tea and red wines). Taking flavonoid rich foods as part of our daily diet will be beneficial. However, before randomly including any flavonoid supplements or concentrates as part of the cancer patient’s diet, one should discuss it with the healthcare professionals .
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