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A lot of posts recently on Daflon 500, or the flavonoid compound of 90% diosmin/10% hesperidin on affects on the endothelial wall, or the lining of our veins. I thought it might be good for folks to understand how flavonoids affect the endothelium and how they might be helpful in our diets. Daflon is not the only flavonoid.....

Flavonoids are the naturally occuring compounds found in fruits, vegetables and beverages. Flavonoids are what give fruits and veggies their bright colors. Diosmin, which is most of Daflon 500, comes from oranges, and hesperiden comes from oranges and lemons. These flavonoids are selected to treat hemorrhoids and varicose veins, because citrus flavonoids are vasoconstrictors, or tighten veins. Over 4,000 flavonoids have been identified, many of which occur in fruits, vegetables and beverages (tea, coffee, beer, wine and fruit drinks). The flavonoids have aroused considerable interest recently because of their potential beneficial effects on human health-they have been reported to have antiviral, anti-allergic, antiplatelet, anti-inflammatory, antitumor and antioxidant activities. The flavonoid in red wine, resveratrol, has gotten a lot of press.

One aspect that flavonoids address, which can be helpful for people w/MS, is blocking the adhesion, or immobilization, of leukocytes to the endothelial wall. Flavonoids keep the leukocytes moving....

The immobilization and firm adhesion of leukocytes to the endothelial wall is another major mechanism responsible for the formation of oxygen-derived free radicals, but also for the release of cytotoxic oxidants and inflammatory mediators and further activation of the complement system. Under normal conditions, leukocytes move freely along the endothelial wall. However, during ischemia and inflammation, various mainly endothelium-derived mediators and complement factors may cause adhesion of the leukocytes to the endothelial wall, thereby immobilizing them and stimulating degranulation of the neutrophil. As a result, oxidants and inflammatory mediators are released, resulting in injury to tissues. Oral administration of a purified micronized flavonoid fraction was reported to decrease the number of immobilized leukocytes during reperfusion (23). The decrease in the number of immobilized leukocytes by flavonoids may be related to the decrease in total serum complement and is a protective mechanism against inflammation-like conditions associated with, for example, reperfusion injury

Another aspect is antithrombogenic, or the ability to break up clots or hypercoagulation of blood.

Platelet aggregation contributes to both the development of atherosclerosis and acute platelet thrombus formation, followed by embolization of stenosed arteries. Activated platelets adhering to vascular endothelium generate lipid peroxides and oxygen free radicals, which inhibit the endothelial formation of prostacyclin and nitrous oxide. It was shown in the 1960s that tea pigment can reduce blood coagulability, increase fibrinolysis, and prevent platelet adhesion and aggregation (72). Selected flavonoids, such as quercetin, kaempferol, and myricetin were shown to be effective inhibitors of platelet aggregation in dogs and monkeys (73). Flavonols are particularly antithrombotic because they directly scavenge free radicals, thereby maintaining proper concentrations of endothelial prostacyclin and nitric oxide (74). One study showed that flavonoids are powerful antithrombotic agents in vitro and in vivo because of their inhibition of the activity of cyclooxygenase and lipoxygenase pathways (75).

another aspect is vasodilation and the antioxidant properties that balance nitric oxide.

Several flavonoids, including quercetin, result in a reduction in ischemia-reperfusion injury by interfering with inducible nitric-oxide synthase activity (14). Nitric oxide is produced by several different types of cells, including endothelial cells and macrophages. Although the early release of nitric oxide through the activity of constitutive nitric-oxide synthase is important in maintaining the dilation of blood vessels (15), the much higher concentrations of nitric oxide produced by inducible nitric-oxide synthase in macrophages can result in oxidative damage. In these circumstances, activated macrophages greatly increase their simultaneous production of both nitric oxide and superoxide anions. Nitric oxide reacts with free radicals, thereby producing the highly damaging peroxynitrite. Nitric oxide injury takes place for the most part through the peroxynitrite route because peroxynitrite can directly oxidize LDLs, resulting in irreversible damage to the cell membrane. When flavonoids are used as antioxidants, free radicals are scavenged and therefore can no longer react with nitric oxide, resulting in less damage .

another aspect is the anti-viral component

The antiviral activity of flavonoids was shown in a study by Wang et al (80). Some of the viruses reported to be affected by flavonoids are herpes simplex virus, respiratory syncytial virus, parainfluenza virus, and adenovirus. Quercetin was reported to exhibit both antiinfective and antireplicative abilities. The interaction of flavonoids with the different stages in the replication cycle of viruses was previously described (81). For example, some flavonoids work on the intracellular replication of viruses, whereas others inhibit the infectious properties of the viruses.

http://www.ajcn.org/content/74/4/418.full

The flavonoids I researched and recommended in the Endothelial Heath program are bromelain (pineapple), quercetin (the red in apples and red onions) and EGCG (green tea)...because these specific flavonoids have anti-inflammatory, anti-thrombic, anti-oxidant, anti-viral and vasodilating properties. And they have the potential to help mitigate damage from CCSVI. All of these supplements can be purchased through natural health food stores...but please, always discuss supplements with your doctor.

You don't have to take Daflon 500 to get the benefits of flavonoids. You can eat more fruits and veggies...the more colorful, the better. The reason citrus fruits were used as the chosen flavonoids for venous disease of the legs was because of their vasoconstrictive abilities, because citrus fruits tighten blood vessels and help varicose veins.... but the more helpful aspects of flavonoids can be found in other compounds which do not close vessels.

There is not one pill that will stop venous disease. There is only a holistic lifestyle which includes colorful fresh fruits and vegetables.
"Let food be thy medicine and medicine be thy food." Hippocrates.

hope that helps!
cheer

I wonder how many fruits, vegetables, etc one would have to consume in order to obtain the same amount that is in Daflon 500?

dania wrote:I wonder how many fruits, vegetables, etc one would have to consume in order to obtain the same amount that is in Daflon 500?

500 mg. of flavonoids are in each Daflon 500 pill.
Jeff takes 1000mg. of quercetin, 500 mg. of bromelain, and 1000mg of EGCG daily as supplements--all flavonoids- plus all of the leafy greens, bright fruits and veggies. No prescription flavonoids...and his GP approved it all. Here's a list of all the flavonoid content in foods--
http://ejeafche.uvigo.es/component/opti ... w/gid,720/
Here's Jeff this week...out in 90 deg. heat, in the Italian sun, in a black wool suit. He's lost 20 lbs, is in great shape, still doing well, thanks to Dr. Zamboni and Dr. Dake, and all of the lifestyle changes he's made.


cheer

Thanks Cheer.

Highest flavonoids in case of fresh vegetables fruits and were present in tomato (183.08 mg\kg) and
strawberries (80.0 mg\kg) respectively. While in case of preserved products in strawberry
jam (85.0 mg\kg) and garlic paste (177.0 mg\kg) respectively.

The only problem I see is one would have to eat about 6.5 pounds of tomatoes or about 14 pounds of strawberries to equal 1 tablet of Daflon. They recommend 2 tablets twice a day.

which is why they're called "supplements", dania. I'm sorry if I wasn't clear. Jeff takes 2000mg of flavonoids daily as supplement pills, in addition to his mostly veggie diet....the point I was making is that they are non-prescription, and available in Canada.
best,
cheer

I've just purchased a Bioflavonoid Complex tablet, with Hesperiden 280mg and Rutin 50mg
from a local health shop. Diosmin is apparently a derivative of hesperiden anyway.
I'll give it a go, two a day, and up my coloured fruit & veg also.
Seems a pretty natural thing, worth a try.
My Dr doesn't have a clue on these types of supplements!

Again thank you Cheer.
I worked for 13 years in the quality control labs of 2 pharmaceutical companies. I do not trust supplements for the following reason, they do not have to do any quality control testing of their products. It has been shown when tested, some supplements have 100% of what is on the label, while the same product from another company when tested had zero and the other companies were in the middle.
Look at what I found, it is quite disturbing.
http://www.medscape.com/viewarticle/406715_11
"Who is the manufacturer? Choosing a reputable manufacturer is another important step for ensuring that customers receive the optimal benefit from dietary supplements. Even with trusted brands, however, inconsistencies may occur. For example, an independent lab hired by the Boston Globe conducted a potency study of various brands of St. John's wort.[29] Of the seven national brands tested, only one contained 0.3% hypericin as claimed on all of the product labels. Another study found that nearly one-third of 25 major brands of supplements containing glucosamine and/or chondroitin (used for treating osteoarthritis) did not contain all of the ingredients listed on the label.
Yet another disturbing problem is contamination of herbal products with pesticides and other adulterants. For example, 8 of 22 brands of ginseng were found to contain high levels of specific pesticides, and some products contained significant levels of lead.[3"

Bethr wrote:I've just purchased a Bioflavonoid Complex tablet, with Hesperiden 280mg and Rutin 50mg
from a local health shop. Diosmin is apparently a derivative of hesperiden anyway.
I'll give it a go, two a day, and up my coloured fruit & veg also.
Seems a pretty natural thing, worth a try.
My Dr doesn't have a clue on these types of supplements!

sounds good, Bethr...(hope I explained that hesperiden and citrus flavonoids are vasoconstrictive. That's why they're recommended for hermorrhoids and varicose veins.)
Sorry your doc isn't up on supps! In southern CA, we're extremely blessed to have sunshine, organic food and supps and naturopathic docs.
Dr. Wahls is a great resource on food as medicine.
http://www.terrywahls.com/
cheer

Thanks Cheer, I've done quite a bit of reading on it over the past few days.
I get haemorroids and spider veins, and then reynauds syndrome last year and have the varicose veins just starting to kick in (family trait I'm afraid ).
So I feel hesperidin may do some good, especially with it's iron chelating properties as a bonus.
I've had three litres of blood taken so far (plus menstruation), and still have not been able to get
my iron down to the levels recommended! But feeling better every time

I had leukocytosis last year and have permanent lymphosytosis due to a trauma splenectomy as a child. So good idea to keep those little blighters flowing through the veins!

cheerleader wrote:Here's Jeff this week...out in 90 deg. heat, in the Italian sun, in a black wool suit. He's lost 20 lbs, is in great shape, still doing well, thanks to Dr. Zamboni and Dr. Dake, and all of the lifestyle changes he's made.


cheer

He looks great! Such a good outcome.

Citrus polyphenol hesperidin stimulates production of nitric oxide in endothelial cells while improving endothelial function and reducing inflammatory markers in patients with metabolic syndrome.
Rizza S, Muniyappa R, Iantorno M, Kim JA, Chen H, Pullikotil P, Senese N, Tesauro M, Lauro D, Cardillo C, Quon MJ.
SourceDepartment of Internal Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.

Abstract
CONTEXT: Hesperidin, a citrus flavonoid, and its metabolite hesperetin may have vascular actions relevant to their health benefits. Molecular and physiological mechanisms of hesperetin actions are unknown.

OBJECTIVE: We tested whether hesperetin stimulates production of nitric oxide (NO) from vascular endothelium and evaluated endothelial function in subjects with metabolic syndrome on oral hesperidin therapy. DESIGN, SETTING, AND INTERVENTIONS: Cellular mechanisms of action of hesperetin were evaluated in bovine aortic endothelial cells (BAEC) in primary culture. A randomized, placebo-controlled, double-blind, crossover trial examined whether oral hesperidin administration (500 mg once daily for 3 wk) improves endothelial function in individuals with metabolic syndrome (n = 24).

MAIN OUTCOME MEASURE: We measured the difference in brachial artery flow-mediated dilation between placebo and hesperidin treatment periods.

RESULTS: Treatment of BAEC with hesperetin acutely stimulated phosphorylation of Src, Akt, AMP kinase, and endothelial NO synthase to produce NO; this required generation of H(2)O(2). Increased adhesion of monocytes to BAEC and expression of vascular cell adhesion molecule-1 in response to TNF-α treatment was reduced by pretreatment with hesperetin. In the clinical study, when compared with placebo, hesperidin treatment increased flow-mediated dilation (10.26 ± 1.19 vs. 7.78 ± 0.76%; P = 0.02) and reduced concentrations of circulating inflammatory biomarkers (high-sensitivity C-reactive protein, serum amyloid A protein, soluble E-selectin).

CONCLUSIONS: Novel mechanisms for hesperetin action in endothelial cells inform effects of oral hesperidin treatment to improve endothelial dysfunction and reduce circulating markers of inflammation in our exploratory clinical trial. Hesperetin has vasculoprotective actions that may explain beneficial cardiovascular effects of citrus consumption.

http://www.ncbi.nlm.nih.gov/pubmed/21346065

An interesting study of hesperidin. The reason I was looking at it's effect on
metabolic syndrome is because my sister with MS has just had a check-up with our neurologist.
As usual, nothing gained from the visit, bar a prescrption for Vit.D and a sense of frustration.
She hasn't seen him in over a decade, and has never taken any drugs.
He was amazed that she still worked full time, and still runs her own business.
But had nothing to say about her highish iron levels, or why her transferrin levels were also high (this usually points to anemia).

After much research I found that highish iron levels coupled with high transferrin is
associated with metabolic syndrome (diabetes, overweight etc).
She also has quite bad circulation, like me.
Anyway I'm on the same dose of hesperidin as the study above, so I'll be the guinea pig
for a while and if all seems OK, she may try it too.

DiosVein Diosmin/Hesperidin

http://www.swansonvitamins.com/SWU310/ItemDetail

Hey Bethr--
Exactly--it's all about the affect on nitric oxide....my favo, quercetin, has also shown great success in metabolic syndrome because of how it works on NO.

In conclusion, the present results show for the first time that the chronic daily administration of both 2 and 10 mg/kg of body weight of quercetin reduces insulin resistance, dyslipidemia, and hypertension in the experimental model of metabolic syndrome of obese Zucker rats. The higher dose of quercetin also reduces weight gain, while at the same time there is an important improvement in the inflammatory status present in this model, as shown by the increase in plasma adiponectin and the reduction in plasma NOx concentration and VAT TNF- production, together with a downregulation of fat iNOS expression and an improvement of eNOS expression in VAT. Although further studies are required to explain the mechanisms involved, our findings reinforce dietary recommendations for diabetes treatment, encouraging a high intake of plant foods, rich in bioactive agents such as quercetin, and also the use of supplements of this flavonoid, as it reduces cardiovascular risk factors such as hypertension or dyslipidemia, as well as insulin resistance in this experimental model of metabolic syndrome.

http://www.nature.com/oby/journal/v16/n ... 8315a.html

Flavonoids are just plain great for our blood vessels. Fresh fruits and veg and less meat and more plant proteins are the best. Healing the endothelium is a multi-faceted process. There isn't one pill that can do it. Exercise heals the endothelium, quitting smoking, not eating processed foods or sugar, taking a vitamin D supplement, laughing, reducing stress, increasing B12 and reducing homocysteine...it's a lifestyle.
http://www.ccsvi.org/index.php/helping- ... ial-health

I suppose why I keep coming back here is because I fear sometimes people learn about a new supplement and say "THIS IS IT!" (capital letters intentional I know you understand there's more to it.
There isn't just one pill. I've watched my husband totally change his life, diet and exercise...and it's been awe-inspiring. He's never looked and felt so good, but it wasn't easy. But it is possible,
cheer

For sure Cheer and thanks for keeping on coming back .
My sister eats a very good diet, and also grows her own veges.
Maybe that is why she has never really got much worse, but in saying that
MS does affect her life, stopping her doing many things she loved to do once
upon a time.
We both have to be very careful on what we take in the way of drugs and supplements
as we can react. My whole family is like that. My father went into a coma whilst in
hospital after being put on an antibiotic, it nearly killed him! But that's another problem, maybe associated, maybe not. We tend to take one thing at a time or the waters get muddy and you can't tell what you are reacting to.

I like the part of the "6-week cocoa intervention trial" in the paragraph Vascular Endothelial Function. Big chocolate lover.
http://lpi.oregonstate.edu/infocenter/p ... lavonoids/