Flavonoid

Flavanoid: What is it?

• Other names: Polyphenols.

  • Subcategories: Flavones, Flavonols, Flavanones, Flavanonols, Chalcones, Catechins, Anthocyanins.

  
  

Description:

Flavonoids are a large group of natural substances found in numerous fruits, vegetables, grains, bark, roots, stems, flowers, and teas.

Mechanism of action:

Generally, their health benefits are attributed to their antioxidative, anti-inflammatory, and anti-carcinogenic properties. Flavonoids are understood to contain these properties via numerous mechanisms of action. Each flavonoid exerts its health effects via varying use of different mechanisms. Some well understood and studied mechanisms of action are listed below:

1. Anticholinesterase activity via Inhibition of Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE)

2. Anti-inflammatory activity via inhibition of COX-2

3. Antioxidant via free radical scavenging

Common indications/uses:

Flavonoids are used to either prevent or treat a wide array of disease processes. Ongoing investigation in their efficacy has led to a growing list of potential indications. A list of common and well-studied indications are listed below:

1. Hypertension prevention and management

2. Lipid management

3. Chronic venous disease management

4. Hemorrhoids

Dosing:

In many studies, flavonoid consumption is marked as products high in flavonoid content. There is a lack of data regarding precise dosing.

Chronic venous disease management

Micronized Purified Flavonoid Fraction (MPFF): Two 500 mg tablets daily

Evidence:

Mechanisms

Anticholinesterase activity: In vitro inhibitory studies performed showed that quercetin and macluraxanthone possess concentration-dependent inhibition against AChE and Butyrylcholinesterase (BChE).

Macluraxanthone was found to inhibit both enzymes with 50% inhibitory concentration (IC50) values of 8.47 and 29.8 µm, respectively.

Anti-inflammatory activity: Studies observing binding modes of flavonoids, demonstrated that some flavonols and flavones contain a 2,3-double bound which acts as a preferential inhibitor of COX-2. This discovery led to the creation selective COX-2 inhibitors.

Antioxidant activity: Flavonoids are oxidized by free radicals resulting in a more stable, less reactive radical. Research by Hanasaki found that some flavonoids can directly scavenge superoxides while other flavonoids can scavenge high reactive oxygen-derived radicals.

Indications and efficacy

Hypertension: A Cochrane meta-analysis revealed that ingestion of flavanol-rich cocoa products significantly reduced both systolic and diastolic pressure compared with low flavonol containing cocoa powder or flavonol-free interventions (1.8/1.8 mmHg).

Chronic venous disease: a meta-analysis comparing micronized purified flavonoid fraction (MPFF) to placebo revealed a significant reduction in pain, heaviness, cramps, paresthesias, leg circumference, leg redness, and improvement in skin changes and quality of life. Seven trials examining MPFF and ulcer healing revealed that MPFF significantly improved the rate of ulcer healing at 6 months (61.3% versus 47.6%) as well as time to healing (16 versus 21 weeks).

Lipid: A trial of 200 men examining virgin olive oil (high in polyphenols) versus refined olive oil (low in polyphenols) on serum lipids revealed a dose-response effect of virgin olive oil on both LDL- and HDL-cholesterol; raising HDL- and lowering LDL-cholesterol.

Hemorrhoids: Flavonoids such as hydroxyethylrutoside function as phlebotonics which improve venous tone, microvascular permeability, lymphatic activity, and microcirculatory nutritive flow. Studies have shown its utility in reducing acute and recurrent hemorrhoidal attacks, as well as useful in bridging patients to surgery.

Safety concerns:

No adverse effects have been associated with high dietary intake of flavonoids from plant-based food. This is thought to be related to its low bioavailability, rapid metabolism, and elimination of most flavonoids.

Adverse reactions:

Drug-induced liver injury: Flavocoxid, a blend of two flavonoids (baicalin and catechins) has been used to treat osteoarthritis. The FDA has recommended it be discontinued due to drug-induced liver injury. One study revealed an incidence of 0.4%.

Drug interactions:

Many anthocyanins and anthocyanidins have been described as inhibitors of BRCP-mediated transport thus theoretically affecting anticancer drugs such as mitoxantrone, topotecan, tyrosine kinase inhibitor, fluoroquinolones, prazosin, and sulfasalazine.

High intake of flavonoids from grape juice and dark chocolate has been found to inhibit platelet aggregation and thus can theoretically increase the risk of bleeding when also taken with anticoagulant and antiplatelet drugs.

Consumption of flavonoid-rich grapefruit inhibits cytochrome P450 and increase the bioavailability and the risk of toxicity of more than 85 drugs.