Flavonoids are a class (or subtype) of plant-derived polyphenolic compounds that represent a larger class of nearly 8000 phytochemicals/phytonutrients. These chemical compounds are responsible for protecting plants from threats, like insects and animals. In humans, flavonoids have been shown to have multiple beneficial health effects on metabolic disorders. Based on their chemical structure, flavonoids are grouped into six primary subclasses: anthocyanins, flavonols, flavan-3-ols, flavanones, flavones, and isoflavones. They are most concentrated in the skins and seeds of the plant, which is why consuming both are recommended to receive their antioxidant and anti-inflammatory properties.
A recent study found that regularly consuming a diet rich in flavonoids protects against cancer and heart disease. According to the cohort study which assessed diets of over 50,000 people for 23 years, participants who consumed moderate to high amounts (at least 500g total per day) of flavonoid-rich foods had the lowest risk of cardiovascular disease-related and cancer-related mortality. Their findings suggest that flavonoid consumption in populations at a higher risk of developing these chronic diseases, such as heavy alcohol users and cigarette smokers, showed stronger and more linear protective effects than in those who do not engage in such lifestyle habits.
Another review published recently from Oxidative Medicine and Cellular Longevity provides evidence that suggests flavonoids derived from citrus fruits protect against “oxidative stress, inflammation, diabetes, endothelial dysfunction, and atherosclerosis”. All of these playing major pathogenic roles in the development of metabolic dysfunction and disease. The most notable and well-known flavonoid compounds present in citrus fruits are hesperidin, rutin, and quercetin among several others. By their direct abilities to quench free radicals (caused by everyday toxins, stressors, poor dietary and lifestyle choices), citrus flavonoids can prevent cellular damage, thus lowering the risk of metabolic-related diseases such as cardiovascular disease (CVD), diabetes mellitus, obesity, liver diseases, especially due to flavonoids’ ability to attenuate myocardial damage.
A review from the journal Biomolecules demonstrates how naturally-occurring flavonoids are able to prevent diabetes and its complications. Flavonoids target certain molecules involved in regulating pathways that support beta-cell proliferation, promote insulin signaling and secretion, reduce apoptosis, regulate the metabolism of glucose in the liver, improve carbohydrate digestion, glucose uptake, and lipid deposition. For example, in a meta-analysis, quercetin (the most abundant dietary flavonoid in human nutrition) was shown to stimulate GLUT 4 translocation in mitochondria and decrease serum glucose, with similar mechanisms as the drug metformin.
A study in Nutrition & Metabolism summarizing the role of flavonoids in metabolic diseases found that they are able to elevate the energy system by activating the sympathetic nervous system and increasing epinephrine and thyroid hormone release, stimulating thermogenesis and induces browning of white adipose tissue (WAT). Browning of WAT and up-regulating brown adipose tissue (BAT) activity increases energy expenditure and improves the metabolism of glucose and lipids as there are substantially more mitochondria in BAT versus WAT. Flavonoids do this by stimulating AMPK-PGC-1𝛼, Sirt1, and PPAR𝛼 signaling pathways, critical pathways involved in the prevention of obesity and metabolic derangement due to their role in energy metabolism.
In a previous article, we showcased a study on how blueberries - a rich source of flavonoids - may help improve brain function in older adults and have protective effects against developing neurocognitive disorders like Alzheimer’s and other dementias. Anthocyanins were responsible for improving cognitive function and working memory of those who participated in the clinical study. However, blueberries (although popular) are not the only dietary source of flavonoids available.
Flavonoids have been shown to target astrocytes, the star-shaped glial cells of the central nervous system (CNS). Healthy astrocytes are crucial for functional control of the CNS; they are the main cells responsible for neurotrophic growth, synaptic plasticity, neurogenesis, cell migration and differentiation. Glial cell dysfunction and overactivation, however, are associated with the pathogenesis of brain diseases and cancers, hence flavonoid therapy may be a safe treatment of brain pathologies. Moreover, quercetin supplementation in animal models significantly reduced cytotoxic lipopolysaccharide-induced inflammatory markers in the hippocampus and cortex preventing neuroinflammation.
Luckily, flavonoids are easily attainable through eating plant-based foods and beverages such as vegetables and fruits, tea, dark chocolate, and red wine. The phrase “eat the rainbow” takes on a whole new meaning when referring to colorful foods with deep red, purple, orange, yellow, green, blue and black hues, all of which are rich in flavonoids. Though it is often recommended to avoid white foods that are void of nutrients like refined breads, pasta, and sugar, there is a variety of white/tan-colored foods that offer a variety of oxidant-fighting potentials, like garlic, cauliflower, mushrooms, ginger, onions, and parsnips just to name a few!
Providing a full spectrum list, such as The Institute for Functional Medicine’s Phytonutrient Spectrum Comprehensive Guide is an excellent tool and resource to offer patients for consuming more flavonoid-rich foods. Unfortunately, many grocery stores have a limited variety of produce on the shelves, thus if possible, shopping at local farmer’s markets is a great way to find more varieties. Encouraging patients to be more adventurous with foods, for example, trying at least one new vegetable and/or fruit each week is an excellent way to diversify phytochemical intake into their diets. As a reminder, patients should aim for 9 to 12 servings of vegetables and fruits daily (around 3-4 servings per meal). For enhanced benefits, combine multiple flavonoid-rich foods in each meal to maximize their effects.