Vol. 3, # 29
August 5, 2006
 
Q:  What are bioflavonoid? - Layperson
 
A:  Researchers have reported over eight hundred different bioflavonoids. Most of these are the yellow pigments found in citrus fruit as well as other fruits and vegetables, these are referred to as flavonoids.

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

Bioflavonoids are also referred to as vitamin P, a name that nutrition scientists object to because it has not been proved that they are essential to human nutrition and health. Many researchers are studying bioflavonoids and many reports have been given about their possible functions. Some researchers believe that bioflavonoids help maintain capillaries. Capillaries are microscopic blood vessels that allow the oxygen, hormones, nutrients, and antibodies to pass from the body’s bloodstream to individual cells. If a capillary’s walls are too fragile they will allow blood to drain out of the vessels and into the cells. The result of this is easy bruising, brain and retinal hemorrhages, bleeding gums and other abnormalities.

Bioflavonoids also in recent studies have been shown to help the blood clot, this alone can be helpful in treating phlebitis and other clotting disorders. Many bioflavonoids prevent the cellular damage caused by free radicals; these are unstable molecules that are formed when the body burns oxygen. Some bioflavonoids are used as food preservatives to prevent fats from oxidation. Some reports show bioflavonoids are useful in enhancing the antioxidant action of certain nutrients.

Bioflavonoids and vitamin C are found in many of the same foods and the body metabolizes both of these in the same manner. Researchers have discovered that some of the functions that vitamin C is credited with is actually from the bioflavonoids. Since they work so close together numerous reports have stated that vitamin C and many bioflavonoids need each other to produce the effects that they have on the immune system.

All these uses of bioflavonoids are the main reason that they are accredited with the use they have at preventing many heart diseases. Many laboratory studies show how bioflavonoids stop or slow the growth of malignant cells, they also help protect against cancer-causing substances invading the heart and blood cells. Bioflavonoids also act as natural antibiotics for the human body. Some bioflavonoids destroy certain bacteria that are found in foods, this prevents food spoilage and protects humans from food-borne infections.

Bioflavonoids are under study for many medical uses such as prevention of easy bruising and many other bleeding abnormalities. Rutin, which is a bioflavonoids that is found in wheat leaves and some other plants, are being studied for reducing tissue damage. All these and many others bioflavonoids are available as nutritional supplements

Are there any side effects or interactions?

No consistent side effects have been linked to the flavonoids except for catechin, which can occasionally cause fever, anemia from breakdown of red blood cells, and hives. These side effects subsided when treatment was discontinued.

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

In 1980, quercetin was reported to induce cancer in animals. Most further research did not find this to be true, however. While quercetin is mutagenic in test tube studies, it does not appear to be mutagenic in animal studies. In fact, quercetin has been found to inhibit both tumor promoters and human cancer cells. People who eat high levels of flavonoids have been found to have an overall lower risk of getting a wide variety of cancers, though preliminary human research studying only foods high in quercetin has found no relation to cancer risk one way or the other. Despite the confusion, in recent years experts have shifted their view of quercetin from concerns that it might cause cancer in test tube studies to guarded hope that quercetin has anticancer effects in humans.

The flavonoids work in conjunction with vitamin C. Citrus flavonoids, in particular, improve the absorption of vitamin C.

 

Bioflavonoids:  Rutin and Hesperidin share left / right-sided cell receptors and may be considered
essential to human health.  (Bio)flavonoids comprise the most abundant group of plant Polyphenols,
next to Phenolic acids (found in a variety of foods), Stilbenes (resveratrol, pinosylvin, isorhapontin),
and Lignans (nuts, seeds, whole grain cereals).  Several thousand flavonoids have been identified,
which provide much of the flavor and color in fruits and vegetables, and also berries and flowers.
As a group with other polyphenols, flavonoids have been linked to reduced cardiovascular disease,
cancer and osteoporosis, and many other health benefits as a result of their antioxidant, antibacterial,
antiviral, anti-inflammatory, anti-allergenic properties.
Following are some of about a dozen researched categories on flavonoids or bioflavonoids:
 FlavonolsFlavanonesFlavonesFlavanololsFlavanols
 vegetables,citrus fruit,celery, parsley,milk thistle,tea, cocoa,
 fruits, onions,licorice,red peppers,garcinia epuctata,chocolate,
 grape seed,chamomile, mint,propolis,azaleas,
 pine bark, ginkgo biloba,grape seed,
 RutinHesperidinFlavoneSilymarinFlavan
 FisetinHesperitinApigeninSilibininCatechin
 MorinNaringinApigetrinTaxifolinEpicatechin
 MyricetinNaringeninLuteolinPinobanksinGallocatechin
 MyricitrinEriodictyolBaicalein
 QuercetinPinocembrinChrysin
 QuercetrinLikvirtinTechtochrysin
 GalanginLiquiritinDiosmin
 SpirenosideLiquiritigeninDiosmetin
 RobininEriocitrinHispidulin
 RhamnetinNeohesperidinTangeretin
 KaempferolPoncirinEupafolin
 KaempferideIsosakuranetinEupatilin
Flavonoids / Bioflavonoids (bioflavinoids) are accessory nutrients to form an ascorbic acid or
Vitamin C complex.  Rutin and hesperidin are part of this Vitamin P group and function synergistically
with Vitamin C in regard to maintaining healthy capillaries, to help form collagen in connective tissue,
to help heal wounds, and to support a healthy immune system.
Rutin and/or hesperidin, when low, frequently result in predictable, and even side-specific medical
problems that include a greater risk for vascular degeneration, bruising / capillary fragility, nose bleeds,
periodontal bleeding, varicose veins, hemorrhoids and aneurysm, with few individuals exhibiting optimal
levels, even after mega-supplementation.  One reason is the chemical interaction of bioflavonoids with
other nutrients, which can have a synergistic or inhibiting effect on them.  Various drugs are also able to
interact with (bio)flavonoids and affect their efficacy.
Copper is the most common and potent inhibitor of hesperidin and Vitamin C, being the reason why
high levels of copper create a greater risk for vascular degeneration, which in turn requires greater
intake of Vitamin C, sulfur, chromium, or molybdenum to lower copper - to make it more bioavailable,
otherwise hesperidin levels will
not
go up, no matter how much is supplemented.
 
Abnormal liver functions, triggered by drugs, hormones - particularly
 
elevated estrogen - alcohol, etc., or the structural changes experienced during pregnancy, as well as
lack of exercise and excessive amounts of time spent in a sitting position can be equally responsible
to promote vascular degeneration.
Hesperidin has a right-sided cell receptor (as has copper), so medical problems associated with its
deficiency, and/or with copper excesses, are invariably right-sided as well.  It is not unusual to see
hemorrhoids or varicose veins being noticeably worse on one side only.  
Rutin
is inhibited mostly by
chromium, and since chromium levels are on average not as high as copper levels, rutin levels are
invariably higher than hesperidin levels as long as dietary intake of rutin and hesperidin are similar.

 
Graph1 - flavonoid / mineral interactions
Vanadium and selenium support rutin uptake, and molybdenum and sulfur support hesperidin uptake.
Rutin + hesperidin are associated the same way as calcium + magnesium, in that taking only the one
can over time deplete the other.  For instance, the need to supplement rutin alone (without hesperidin)
can only be justified when there is either a notable deficiency ratio-wise to hesperidin, or when there
is a significant vascular problem, which is confined to the left side only.

Measuring the actual levels of bioflavonoids will help establish whether they, or other aspects such as
impaired liver functions or drugs are causative factors with vascular degeneration.  Low to moderate
intake of alcohol or blood thinning medications favorably enhance the activity of flavonoids, however
excessive intake compromises not only Vitamin K, but causes a sharp drop with rutin and hesperidin
levels. (see also Acu-Cell "Osteoporosis" on details on Vitamin K and its DRI / RDA).

Citrus Bioflavonoids are the most commonly supplemented forms of flavonoids.  Unless there is an
allergy or intolerance to citrus (some individuals find that flavonoids, particularly from citrus worsen their
eczema), there are no other adverse or overdose reactions known, even when very high amounts are
supplemented every day.  Since citrus bioflavonoid tablets are usually quite large, brands should be
chosen that either supply oval-shaped tablets, caplets, or capsules for easier swallowing.

Anthocyanins and their precursors Proanthocyanins (also called condensed tannins) are chemically
related to quercetin, and they are another class of flavonoids that are excellent antioxidants with similar
benefits to other bioflavonoids.  Pycnogenol, which comes from the bark of the French Maritime Pine
(pinus maritima), is a particularly promoted and well-known source of proanthocyanidins.  While their
cost is several times that of citrus bioflavonoids, tablet sizes are only a fraction of those containing other
types of flavonoids, so they are easier to take for individuals with swallowing difficulties, or children.

 • Anthocyanidins are found in tea, beets, cherries, plums, red grapes, hawthorn, and some berries,
   (cyanidin, delphinidin, pelargonidin, peonidin, petunidin, malvidin).

 • Proanthocyanidins are found in tea, bilberry, apple, pear, grape seed, pine bark, beer, red wine,
  cranberry, red beans, (procyanidin, prodelphinidin, propelargonidin).

Isoflavones from soy products (genistein, daidzein, glycitein), are another class of flavonoids that
function as antioxidants and in addition possess phytoestrogenic properties that can be effective for
menopausal symptoms and to promote bone density in post-menopausal women.  They may also be
beneficial in the treatment and prevention of cardiovascular disease (inhibition of lipoprotein oxidation,
thrombin formation and platelet activation), and cancer (inhibition of angiogenesis, and tyrosine kinase
activity - an enzyme that promotes cancer growth), although there are conflicting opinions on the tumor-
protective benefits in light of new evidence of also a possible pro-tumor effect following high soy intake.
Isoflavones are mostly found in soybeans, garbanzo beans, chick peas, red clover and legumes.

Cocoa is an excellent source of catechins, which are polyphenols of the flavanol group, and which are
believed to protect against heart disease, cancer, and various other medical conditions.  While health
benefits apply to some isolated compounds in cocoa - as a whole - they do not apply to processed
cocoa products such as Chocolate any longer because of other less desirable ingredients offsetting
these health benefits (i.e. added sugar, corn syrup, milk fats / dairy cream, hydrogenated oils, etc...),
and also since the actual cocoa content may be less than 20% in most chocolate bars sold.  (see also
Acu-Cell "Chocolate" for more details on some of the positive / negative health effects of chocolate).

Theobromine, found in chocolate, can be toxic or even lethal to domestic animals such as dogs, cats,
horses and many other animals as a result of affecting their kidneys, heart, and central nervous system.
In addition, cocoa products contain a high level of copper, which - with few exceptions - is already too
high in many individuals, and so consuming a lot of chocolate aggravates many high copper-related
medical conditions, or creates additional ones (see also Acu-Cell Nutrition "Chromium & Copper").

Horse Chestnuts contain flavonoids, sterols, and tannins.  Studies have identified a saponin known
as Aescin as the active constituent in horse chestnut extracts, which has been found effective in the
treatment of chronic venous insufficiency, varicose veins and edema, and can be taken topically or
internally.  Extracts of the seeds, leaves and bark of the horse chestnut tree (aesculus hippocastanum)
have been traditionally used in Europe for vascular degeneration, hemorrhoids, water retention, cough,
rheumatism, phlebitis, skin problems and other ailments.
People with kidney or liver conditions should avoid horse chestnuts or any horse chestnut extracts, as
the aescin may worsen their functions. Reactions such as nausea, stomach upsets, and itching are
another possibility in people sensitive to horse chestnuts.

Quercetin (quercitin, quercetrin) is chemically related to a class of flavonoids called (pro)anthocyanins.
Early research on quercetin suggested that ingesting higher amounts may induce cancer, after it failed
a standard - but somewhat controversial laboratory test called the Ames Test.  This test supposedly
identifies chemicals that might be carcinogenic.  Subsequent studies however disputed those earlier
findings and attributed cancer-protective or cancer-fighting properties to quercetin instead.
In addition, quercetin has been found to be an effective hyperthermia sensitizer, making it a potential
adjunct therapeutic agent in the treatment of various cancers that are sensitive to heat stress (prostate,
ovarian, uterine, or cervical cancer, leukemia, melanoma, colon adenocarcinoma, and others).

However, I have seen a few patients who developed cancerous tumors after supplementing quercetin -
which proves that positive outcomes in experimental studies are not necessarily reflected in positive
outcomes when applied in a "real world" environment.  At the same time, patient feedback on the touted
anti-allergenic and anti-inflammatory aspects of quercetin has not been all that favorable either, so while
this is not intended to discourage anyone from using it for a specific condition (particularly when found
beneficial), quercetin nevertheless fits the "Caveat Emptor" category.

Quercetin isn't the first to be listed among naturally occurring carcinogens and mutagens found in foods
and beverages.  Many phytochemicals contained in common fruits, vegetables, spices, grains, seeds,
nuts, mushrooms, coffee, tea, and herbs are rodent carcinogens, while for instance Psoralens (found
in parsnips, parsley and celery), are considered to be human carcinogens, as is acrylamide, contained
in crisp breads and rolls, which is also a neurotoxin.  Ingesting large amounts of Grape Seed Extract
has shown liver toxicity in some animal studies as well.
Nevertheless, test tube and animal studies - where many times astronomical amounts of food fractions
are used - have generally little relevance to normal human consumption of these same types of foods,
but they make great headlines, or they may assure next year's research grant for an otherwise starving
research team. 
 


Dietary Reference Intake (DRI) is the latest term replacing daily dietary reference values such as
Adequate Intake (AI), Tolerable Upper Intake Level (UL), Estimated Average Requirements (EAR),
Nutrient Reference Value (NRV),  and Recommended Dietary Allowance / Intake (RDA / RDI).

Rutin:Hesperidin:

DRI (RDA, EAR):DRI (RDA, EAR):
0-6 months1mg0-6 months1mg
6-12 months3mg6-12 months3mg
1-18 years5-10mg1-18 years5-10mg
18 years +10-25mg+18 years +10-25mg+
pregnant / lactating+ 25mgpregnant / lactating+ 25mg

Therapeutic Range:50mg - 500mg+Therapeutic Range:50mg - 500mg+

Usually taken in the form of Citrus Bioflavonoids: Therapeutic Range: 500mg - 5,000mg+

Rutin and Hesperidin (and related flavonoid compounds):

Low Levels / Deficiency - Symptoms and/or Risk Factors:
Vascular degeneration, vascular bleeding (bruising / capillary fragility, nose bleeds, periodontal
bleeding, varicose veins, hemorrhoids and aneurism),

High levels / Overdose / Toxicity / Negative Side Effects - Symptoms and/or Risk Factors:
Allergic reactions, skin rash, stomach ache,

Sources of Rutin and Hesperidin:
Mainly found in the rind, pulp, skin of fruits such as lemons, grapefruits, oranges, lime, grapes, cherries,
plums, peaches, apricots, apples, berries..., vegetables such as green and yellow peppers, tomatoes,
onions, broccoli, parsley..., also bee propolis, green tea, black tea, whole grains such as buckwheat

The bioflavonoids are relatively safe to use, but, as usual, consult the appropriate healthcare professional familiar with the use of bioflavonoids.


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DISCLAIMER:  The information in this column, is NOT intended to diagnose and/or treat any health related issues and is provided solely for informational purposes only. Consult the appropriate healthcare professional before making any changes to your healthcare regime. Even what may seem like simple changes in the diet for example, can interact with, and alter, the efficiency of medications and/or the body's response to the medications. Many herbs and supplements exert powerful medicinal effects. Neither the author, nor the website designers, assume any responsibility for the reader's use or misuse of this information.

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