What are Bioflavonoids?

Amy Bigus, Deanna Massengill, and Christy Walker

Thanks to the University of North Carolina School of Pharmacy for the use of this article.

Bioflavonoids

• Once known as "Vitamin P" and semi-essential nutrients
• 4000 flavonoid compounds have been characterized and classified
• Group of plant pigments that are largely responsible for colors of many fruits and flowers
• Useful in treatment and prevention of many health conditions

Four categories:

• PCO (Proanthocyanidins)

• most potent PCOs are those bound to other PCOs
• exist in many plants and red wine
• commercially available sources are from grape seeds and bark from the maritime pine
  

• Quercetin

• serves as backbone for other flavonoids such as citrus flavonoids: rutin, quercitrin, hesperidin
• these derivatives have sugar molecules attached to the backbone
• most active of the flavonoids
  

• Citrus bioflavonoids

• include rutin, quercitrin, hesperidin, naringin
• standardized mixture of rutinosides known as hydroxyethylrutosides (HER)
• clinical results have been obtained in treatment of capillary permeability, easy bruising, hemorrhoids, and varicose veins
  

• Green Tea Polyphenols

• derived from tea plant camellia sinensis
• produced by steaming the fresh cut leaf
• polyphenol indicates presence of phenolic ring in the chemical structure
• polyphenols = flavonoids
• polyphenols in green tea: catechin, epicatechin, epicatechin gallate, epigallocatechin gallate, and proanthocyanidins
• epigallocatechin gallate = most significant active compound

Dietary Sources

• Citrus fruits
• Berries
• Onions
• Parsley
• Legumes
• Green Tea
• Red Wine

Average Daily Intake = 150-200 mg

Beneficial Effects

• referred to as "nature's biological response modifiers" - modify body's reaction to compounds such as allergens, viruses, and carcinogens
• powerful antioxidants by giving protection versus oxidative and free radical damage
• prevents formation of oxidized cholesterol through antioxidant effects
• greater antioxidant effects than Vitamins C, E, Selenium, and Zinc

PCOs

• increase intracellular Vitamin C levels
• decrease capillary permeability and fragility
• scavenge oxidants and free radicals
• inhibit destruction of collagen

• crosslinks collagen fibers to reinforce the natural crosslinking
• prevents free radical damage

• inhibits enzymatic cleavage of collagen by enzymes secreted by leukocytes in inflammation and microbes in infections
• prevents release and synthesis and compounds that promote inflammation and allergies (histamines, prostaglandins, leukotrienes)
• antioxidant effects are beneficial in:

• aging process
• chronic degenerative diseases (heart disease, arthritis, and cancer)
• fat and cholesterol oxidation

• antioxidants are produced by:

• inhibiting xanthine oxidase noncompetitively(oxygen free radicals)
• on the cellular level: PCOs are incorporated into the cell membranes along with the antioxidant effects offer great protection to cells against free radical damage.

Quercetin

• anti-inflammatory activity due to inhibition of initial processes of inflammation

• inhibits manufacture and release of histamine

• potent antioxidant activity and Vitamin C sparing action
• beneficial effects for diabetics

• helps prevent diabetic cataracts, and retinopathy
• enhances insulin secretion
• protects pancreatic beta cells from free radical damage

• antiviral activity

• activity vs. herpes virus type 1, parainfluenzae3, polio virus type 1, and respiratory syncytial virus
• in vivo, inhibits viral infection
• may be of some benefit in the common cold

Citrus Bioflavonoids

• antioxidant effects
• increase intracellular Vitamin C, rutin, hesperidin, and HER
• beneficial effects on capillary permeability and blood flow like PCOs
• anti-allergy and anti-inflammatory effects like quercetin

Green Tea Polyphenols

• potent antioxidant effects
• increase activity of antioxidant enzymes in the small intestines, liver, lungs, and small bowel
• inhibit formation of cancer causing compounds like nitrosamines in vitro

• suppressing activation of carcinogens
• trapping cancer causing agents
• forms of cancer that green tea prevents best:

1. cancers of GI tract (stomach, small intestine, pancreas, colon)
2. cancer of the lungs
3. estrogen related cancers (inhibits estrogen interaction with its receptor)

• consumption of green tea with meals inhibits formation of nitrosamines (nitrites combined with amino acids)

Principle Uses

PCOs

• Treatment of venous and capillary disorders

• venous insufficiency
• varicose veins
• capillary fragility

• Diabetic retinopathy and macular degeneration
• Prevention of heart disease and strokes
• Lowers blood cholesterol levels
• Shrinks size of cholesterol deposits in the artery
• Inhibits platelet aggregation and vascular constriction

Quercetin

• In vitro, helps virtually all inflammatory and allergic conditions

1. asthma
2. hay fever
3. rheumatoid arthritis
4. lupus

• Beneficial in diabetes and cancer

Citrus Bioflavonoids

• Venous insufficiency
• Improve microvascular blood flow and clinical symptoms (pain, tired legs, night cramps, and restless legs)
• Improve venous function
• Relieve hemorrhoidal signs and symptoms in pregnant women

Green Tea Polyphenols

• Used principally to prevent cancer

Available Forms

PCOs

• Grape seed extract (92%-95%) and pine bark extract (80%-85%)
• Used interchangeably, but grape seed extract is preferred
• Grape seed extract is considered more potent and more effective than pine bark extract because only grape seed extract has gallic esters of proanthocyanidins which are the most active free radical scavenging PCOs

Quercetin

• Available in powder and capsule forms
• For anti-inflammatory effects, combination of Bromelain (pineapple enzyme) may provide additional benefit by enhancing absorption of quercetin
• Amount of Bromelain should equal quercetin

Citrus Bioflavonoids

• Mixed preparations are most widely used
• Least active and quantified source of flavonoids

Green Tea Polyphenols

• Commercial preparations that have been decaffeinated and concentrated for polyphenols (60%-80%)
• 1 cup = 300-400 mg of polyphenols
• Downside = this dose also contains 50-100 mg of caffeine

Dosage Ranges

PCOs

• Preventive and antioxidant=50 mg/day of grape seed extract or pine bark extract
• Therapeutic purposes dose=150-300 mg/day of either extract

Quercetin

• 200-400 mg taken 20 minutes before meals three times a day

Citrus Bioflavonoids

• 2000-6000 mg/day

Green Tea Polyphenols

• For green tea extract standardized for 80% polyphenols and 55 % epigallocatechin gallate, the dose=300-400 mg/day

*Look for level of epigallocatechin gallate and total content of polyphenol

Safety Issues

PCOs

• safe, no toxicities, no side effects

Quercetin

• Well-tolerated in humans
• no side effects when taken in large quantities for long periods of time
• safe for use in pregnancy
• allergic reaction may occur-uncommon, but should result in discontinuation of product

Citrus Bioflavonoids

• extremely safe
• no side effects
• safe in pregnancy

Green Tea Polyphenols

• no side effects or toxicities
• if product contains caffeine, overconsumption may result in a stimulant effect

Interactions

• Do not interact with any drugs
• citrus bioflavonoids containing naringin may interact with drugs

1. naringin is found in grapefruit juice
2. can increase oral bioavailability of drugs like nifedipine, felodipine, verapamil, and terfenadine
3. inhibits breakdown of various drugs including: caffeine, coumarins, and estrogens

• Vitamin C-Bioflavonoids may enhance the effects of vitamin C

References

• Evans CA and Miller NJ. "Antioxidant activities of flavonoids as bioactive components of food." Biochemical Society Transactions. 24(3):790-795, 1996.
• Hertog Michael, et al. "Flavonoid Intake and Long-term Risk of Coronary Heart Disease and Cancer in the Seven Countries Study." Archives of Internal Medicine. 155:381-386, 1995.
• Kandaswami Chithan, et al. "Ascorbic acid-enhanced antiproliferative effect of flavonoids on squamous cell carcinoma in vitro." Anti-Cancer Drugs. 4:91-95, 1993.
• Lale A, Herbert JM, et al. "Ability of Different Flavonoids to Inhibit the Procoagulant Activity of Adherent Human Monocytes." Journal of Natural Products. 59:273-276, 1996.
• Murray MT. "Flavonoids." Encyclopedia of Nutritional Supplements. p. 320-331.
• So Felicia, et al. "Inhibition of proliferation of estrogen receptor positive MCF-7 human breast cancer cells by flavonoids in the presence and absence of excess estrogen." Cancer Letters. 112:127-133, 1997.
• Wiseman H. "Role of dietary phyto-oestrogens in the protection against cancer and heart disease." Biochemical Society Transactions. 24(3):785-789, 1996.
• Xiao-duo Ji, et al. "Interactions of Flavonoids and Other Phytochemicals with Adenosine Receptors." Journal of Medicinal Chemistry. 39:781-787, 1996.