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Acu-Cell Nutrition: Flavonoids, bioflavonoids, rutin, hesperidin, quercetin & polyphenols.
Bioflavonoids
Rutin - Hesperidin
When assessing Cellular Nutrition with Acu-Cell Analysis, only essential, biological elements that have
their own cell receptors are measured.  They are neurologically arranged into left-sided and right-sided
groups and are discussed in associated pairs, as they function as an inseparable, interdependent unit:
       _______________________________________________________________________

        CalciumMagnesium  PhosphorusSodium
        IronManganese  ZincPotassium
        SeleniumSulfur  TinIodine
        GermaniumSilicon  BismuthLithium
        NickelCobalt  ChromiumCopper
        FluorideChloride  VanadiumMolybdenum
       _______________________________________________________________________

        |  Boron  |  Bromine  |  Strontium  |  Bioflavonoids  |  Vit A D K  |  B12 B15 C E  |  B-Complex  |
       _______________________________________________________________________

Trace mineral symptoms of excess or deficiency are generally one-sided, depending on their ratios to
other chemical members, and depending which group they are neurologically assigned to.  In the event
of calcification, it is not a high calcium level that results in the formation of a stone or spur, but calcium
being high in ratio to associated or interactive elements.
For instance, phosphorus and zinc have both left-sided cell receptors, so if either level is low in ratio
to calcium, calcification would only take place on the left side of the body, whereas the cell receptors of
manganese or magnesium are right-sided, as a result, any calcification would develop on the right side
of the body only.
The same rules apply to most nutrition-related inflammatory or degenerative conditions, so successful,
non-symptomatic treatments require the application of those same principles.  Since intracellular and
serum levels of nutrients represent different physiological and pathological processes, abnormal levels
seen in one medium are not necessarily reflected in the other, so they need to be interpreted differently.

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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 aneurism, 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. (see also Acu-Cell
"Vitamin C Supplementation").  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.
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, blood thinning medications, or blood-thinning supplements and spices (Vitamin E,
ginkgo biloba, fish oils, garlic...) favorably enhance the activity of flavonoids, however excessive intake
not only compromises Vitamin K, but causes a sharp drop with rutin and hesperidin levels.

Although spinach and other green, leafy vegetables contain significant amounts of Vitamin K, the high
oxalic acid content in spinach or other sources such as rhubarb, Swiss chard, beets / beet greens, and
parsley, etc., promotes vascular degeneration and increases the risk for bleeding in prone individuals.

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 applied 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.
A number of research studies have come to the final conclusion that low concentrations of flavonoids
are protective in rat H4IIE cells, whereas
high concentrations cause DNA damage and cell apoptosis.

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.  ¤

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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. ¤

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Vitamin K:

Vitamin K1  (phylloquinone, phytonadione)  =  from plants sources
Vitamin K2  (menaquinone, menatetrenone)  =  made by intestinal bacteria
Vitamin K3  (menadione, menadiol, menaquinone, menaphthone)  =  synthetic

DRI (RDA):
0-12 months10-20mcg
1-10 years15-60mcg
11-18 years50-100mcg
18 years +100mcg+

Therapeutic Range:100mcg - 10mg+
______________________________________________________________________________

Cellular / Intracellular Attributes and Interactions:

Vitamin K Synergists:Vitamin K Antagonists:
Calcium, copper, Vitamin B5, Vitamin D,Vitamin A, Vit E, mineral oil, oxalates, alcohol,
[(Bio)flavonoids],blood thinners / anticoagulants (coumadin),
 Antibiotics - by killing intestinal bacteria,

Low Levels / Deficiency - Symptoms and/or Risk Factors:
Bleeding, abnormal / prolonged blood clotting time, bruising, osteoporosis, cardiovascular disease,
stroke, calcification, behavioral problems, failure to grow and develop normally in infants

Vitamin K3 only:

High levels / Overdose / Toxicity / Negative Side Effects - Symptoms and/or Risk Factors:
Liver impairment / damage, hemolytic anemia, stomach upset, skin rash, brain damage in infants.
______________________________________________________________________________

Vitamin K Sources:
Green tea, kale, collards, spinach, cauliflower, cabbage, alfalfa, soybeans, tomatoes, oats, liver, egg
yolk, meat, fish liver oils, blackstrap molasses.  Vitamin K is also made by bacteria in the intestines. ¤

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General recommendations for nutritional supplementation:  To avoid stomach problems and promote
better tolerance, supplements should always be taken earlier, or in the middle of a larger meal.  When
taken on an empty stomach or after a meal, there is a greater risk of some tablets causing irritation, or
eventually erosion of the esophageal sphincter, resulting in Gastroesophageal Reflux Disease (GERD).
It is also advisable not to lie down immediately after taking any pills.
When taking a very large daily amount of a single nutrient, it is better to split it up into smaller doses to
not interfere with the absorption of other nutrients in food, or nutrients supplemented at lower amounts.

______________________________________________________________________________
Copyright © 2000-2008  Ronald Roth    Acu-Cell Nutrition: Flavonoids / Bioflavonoids, Rutin & Hesperidin
  
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