What are Flavonoids?
Flavonoids are plant-made chemicals (phytochemicals) in the “polyphenol” family of molecules. They are widely found in fruits, vegetables, cereals, herbs, spices, stems and flowers, teas, red wine, beer, beans, cocoa, and many other botanical foods and beverages. They represent one one of the most diverse group of compounds which play an important role in human health. In terms of their anti-cancer activity, flavonoids possess numerous antioxidant, anti-tumor, anti-inflammatory, immune supporting and hormonal modulating activities.
The flavonoid compounds have been divided into the following subclasses based on their unique chemical structures:
- anthocyanidins (i.e. cyanidin, delphinidin)
- found in: berries and grapes
- flavanols (i.e. catechin, epigallocatechin gallate, theaflavins, proanthocyanidins)
- found in: green and white teas, chocolate, grapes, berries, apples
- flavanones (i.e. hesperetin, naringenin)
- found in: citrus fruits
- flavonols (i.e. quercetin, kaempferol)
- found in: yellow onions, scallions, kale, broccoli, apples, berries, teas
- flavones (i.e. apigenin, luteolin)
- found in: parsley, thyme, celery, hot peppers
- isoflavones (i.e. daidzein, genistein)
- found in: soybeans, legumes
Anti-Cancer Qualities of Flavonoids:
Consuming a diet rich in a wide-variety of flavonoid phytonutrients has the potential to help us prevent and fight cancer through a multi-targeted approach (Read our blog entry on “Food as Chemo”.)
These are just some of the anti-cancer mechanisms influenced by flavonoids:
- Antioxidant (reducing DNA damage)
- Inhibiting growth factor receptors (slowing cell growth and proliferation)
- Promoting the excretion of carcinogenic compounds (reducing DNA damage)
- Promoting DNA repair in cells with damaged DNA
- Inducing apoptosis (cell death) in cancer cells
- Inhibiting tumor cell invasion into surrounding tissues
- Inhibiting the formation of tumor blood vessels
- Decreasing inflammation by reducing free radical stimulation/activation of inflammatory pathways (reducing “oxidative stress”)
Where’s the Proof That Consuming Flavonoids Reduces Cancer Risks?
Animal studies have shown that flavonoids have anti-cancer activity in reducing the risk of various cancers (lung, head and neck, gastrointestinal, skin, prostate and breast). Unfortunately, we don’t have definitive evidence (in humans) to tell us whether consuming more flavonoid-rich foods will reduce the risk of cancer development, progression or recurrence.
There are numerous “case-control” studies that either support or show no effect for the anti-cancer activity of various flavonoids in reducing cancer risks. This type of study design asks patients with a cancer diagnosis to recall what they ate over the months-to-years prior to their diagnosis. Patients may say they ate more or less of a certain food, based on their recollections. I don’t know about everyone else, but I can’t remember what I ate yesterday… let alone months-to-years ago. A patient with a cancer diagnosis may say they didn’t eat lots of flavonoid-rich foods, when in fact they might have eaten more than they recall. This is called “recall bias,” and is one of the potential flaws of these types of studies. Nevertheless, these studies suggest that there may be anti-cancer activity with quercitin, kaempferol, catechins and total flavonoid intake.
Nutrition researchers place more credibility on a different type of study, called a “prospective cohort study.” In this study design, individuals without a cancer diagnosis have their dietary intake assessed repeatedly, over time (typically using food questionnaires or interviews), and followed to determine their risk of eventually developing a cancer. Unfortunately, the results from these studies have also been inconsistent, with some showing no effect and others showing an anti-cancer effect (i.e. lung, prostate, ovarian, gastrointestinal) with higher consumption of flavonoid-rich foods and beverages.
Population-based nutrition studies are incredibly difficult to analyze due to the complexity of variables that need to be accounted for (i.e. characteristics of the participants, selected assessment tools, foods assessed, variation in phytonutrient content in foods, etc.) The only way to know for sure whether a specific type of food has an anticancer effect is to sequester study participants in a room, feed them a controlled diet, continuously assess blood and tissue levels of the active compounds and monitor them for years to see what happens. Never going to happen. So, the best we can do for now is piece together the bits of data we have and draw our best educated conclusions. To be safe and have the greatest potential for benefit, I recommend consuming a very wide variety of phytonutrient-rich, whole foods versus supplement versions. After all, we know even less about the efficacy, long-term risks, pharmacology and nutrient-nutrient/drug-nutrient interactions with the consumption of high-dose, synthetic phytonutrient supplements.
Potential Adverse Drug Interactions:
It is important to recognize and avoid or limit your consumption of certain phytonutrient supplements (and possibly, whole food sources rich in these phytonutrients) while taking specific medications. I recommend discussing the details of potential drug-nutrient interactions with your physicians. Researchers have reported in-vitro studies in which the flavonoids naringenin and quercitin inhibit the liver enzyme CYP34A. This can increase the toxicity of many drugs that are metabolized by that enzyme:
- cholesterol lowering medications (“statins”)
- blood pressure medications (“calcium channel blockers”)
- anti-arrhythmia medications (i.e. amiodarone)
- HIV medications (“protease inhibitors”)
- immunosuppressants (i.e. cyclosporin)
- antihistamines (i.e. terfenadine)
- benzodiazepines (i.e. diazepam, midazolam)
- anti-seizure medications (i.e. carbamazepine)
- anti-anxiety medications (i.e. buspirone)
- anti-depressant medications (“SSRIs”, i.e. sertraline)
- erectile dysfunction medications (i.e. sildenafil)
**avoid drinking grapefruit juice with these medications, as the effect on CYP34A inhibition is even more pronounced**
Another potentially adverse interaction has been identified with the flavonoids, quercetin, naringenin and epigallocatechin gallate (from green tea.) These compounds have been shown, in-vitro, to inhibit a cell membrane drug transporter, called P-glycoprotein. When P-glycoprotein is inhibited, the concentration of certain drugs build up in cells, which potentially can lead to drug toxicity. The drugs that are regulated by P-glycoprotein are numerous: anti-arrhythmia medications, blood pressure medications, chemotherapy drugs (i.e. taxanes, anthracyclines, epipodophyllotoxins, camptothecins and vinca alkaloids), antifungal medications, HIV medications, immunosuppresive medications, etc.
**One area of research that is getting a lot of attention is in the study of reducing chemotherapy drug resistance. Cancer cells often become resistant to chemotherapy drugs by increasing the activity of their P-glycoprotein drug transporters. Compounds that inhibit the P-glycoprotein are being investigated as a way to combat this, thereby allowing the anti-cancer drugs to stay in these cancer cells longer. So, on the one hand these inhibitor compounds might increase drug toxicity, on the other hand they might be useful in combating drug resistance.**
An increased risk of bleeding may potentially occur when consuming large amounts of flavonoid-rich foods or flavonoid supplements while taking certain blood-thinning medications (i.e. warfarin, clopidogrel, aspirin, non-steroidal anti-inflammatory drugs.)
What’s the Bottom Line on Flavonoids and Cancer?
We simply do not know for sure whether consumption of flavonoid-rich foods will reduce your risk of cancer development, progression or recurrence. It is possible that at the end of the day, the anti-cancer activity of flavonoid-rich foods may turn out to not be related to this class of phytonutrients and instead could be influenced to a greater degree from the other components within these foods. Alternatively, the potent anti-cancer benefits may simply be eluding us at the low-dose levels typically consumed in the standard Western diet.
If I was a betting man (I do live in Vegas… although I don’t bet), I would put my money on the likelihood that we will eventually discover that those individuals who consume whole foods rich in flavonoids (and other phytonutrients) will have a significantly lower rate of cancer risk outcomes. In the meantime, I’ll continue to enjoy my 3-4 cups of green tea a day while I await the answers to these questions.
