Flavonoids

promote venous strength and integrity. Most trials of flavonoids in patients with CVI have used a type of flavonoid called hydroxyethylrutosides (HR), which is derived from rutin. These double-blind and other controlled trials have consistently shown a beneficial effect of HR in clearing leg swelling and other signs of CVI. Positive results from a double-blind trial have been obtained using 500 mg of HR taken twice per day for 12 weeks. In this trial, the preparation was found to add further benefit to that provided by compression stockings commonly used to treat CVI. Similar results were obtained in another controlled trial. It is unclear whether other flavonoids are as effective as HR for CVI. HR has also been used successfully as a topical preparation for the treatment of CVI.

Catechin, a , has helped people with acute viral hepatitis, as well as individuals with chronic hepatitis, though not all trials have found a benefit. A typical amount used in successful trials is 500–750 mg three times per day. Although catechin is found in several plants, none contain sufficient amounts to reach the level used in the trials; thus, catechin supplements are needed. However, because of its potential to cause side effects on rare occasions, catechin should be used only under medical supervision.

Doctors often suggest that people who experience easy bruising supplement with 100 mg to 3 grams of vitamin C per day for several months. Controlled research is limited, but vitamin C supplements have been shown to reduce bruising in people with low vitamin C intake. are often recommended along with vitamin C. Flavonoids are vitamin-like substances that can help strengthen capillaries and therefore may also help with bruising. Flavonoids may also increase the effectiveness of vitamin C; citrus flavonoids, in particular, improve the absorption of vitamin C. Older preliminary research suggested that vitamin C, 400–800 mg per day, in combination with 400–800 mg per day of the flavonoid, hesperidin, reduced bruising in menopausal women. A small, preliminary trial in Germany gave three people with progressive pigmented purpura (a chronic bruising disorder) 1,000 mg per day of vitamin C and 100 mg per day of the flavonoid rutoside. After four weeks, noticeable bruising was no longer apparent and did not recur in the three month period after treatment was stopped. Controlled research is needed to better establish whether vitamin C and flavonoids are effective for easy bruising.

Vitamin C has been shown to inactivate herpes viruses in the test tube. In one study, people with herpes infections received either a placebo or 200 mg of vitamin C plus 200 mg of , each taken three to five times per day. Compared with the placebo, vitamin C and flavonoids reduced the duration of symptoms by 57%.

The niacin form of vitamin B3 has been reported to be effective in relieving menstrual cramps in 87% of a group of women taking 200 mg of niacin per day throughout the menstrual cycle. They then took 100 mg every two or three hours while experiencing menstrual cramps. In a follow-up study, this protocol was combined with 300 mg of vitamin C and 60 mg of the flavonoid rutin per day, which resulted in a 90% effectiveness for relieving menstrual cramps. Since these two preliminary studies were published many years ago, no further research has explored the relationship between niacin and dysmenorrhea. Niacin may not be effective unless taken for seven to ten days before the onset of menstrual flow.

People who are deficient in vitamin C may be at increased risk for periodontal disease. When a group of people with periodontitis who normally consumed only 20–35 mg of vitamin C per day were given an additional 70 mg per day, objective improvement of periodontal tissue occurred in only six weeks. It makes sense for people who have a low vitamin C intake (e.g., people who eat few fruits and vegetables) to supplement with vitamin C in order to improve gingival health.

For people who consume adequate amounts of vitamin C in their diet, several studies have found that supplemental vitamin C has no additional therapeutic effect. Research, including double-blind evidence, shows that vitamin C fails to significantly reduce gingival inflammation in people who are not vitamin C deficient. In one study, administration of vitamin C plus (300 mg per day of each) did improve gingival health in a group of people with gingivitis; there was less improvement, however, when vitamin C was given without flavonoids. Preliminary evidence has suggested that flavonoids by themselves may reduce inflammation of the gums.

In a double-blind study, supplementation with 50 mg per day of anthocyanins (a type of flavonoid) from black currants for 2 years significantly decreased the amount of visual field loss, compared with a placebo, in patients with open-angle glaucoma. The treatment had no effect on intraocular pressure.

A number of have been shown to have anti-inflammatory effects and/or to strengthen blood vessels. These effects could, in theory, be beneficial for people with hemorrhoids. Most, but not all, double-blind trials using a group of semisynthetic flavonoids (hydroxyethylrutosides derived from rutin) have demonstrated significant improvements in itching, bleeding, and other symptoms associated with hemorrhoids when people used supplements of 600–4,000 mg per day.

Other trials have evaluated Daflon, a product containing the food-derived flavonoids diosmin (90%) and hesperidin (10%). An uncontrolled trial reported that Daflon produced symptom relief in two-thirds of pregnant women with hemorrhoids. Double-blind trials have produced conflicting results about the effects of Daflon in people with hemorrhoids. Amounts of flavonoids used in Daflon trials ranged from 1,000 to 3,000 mg per day. Diosmin and hesperidin are available separately as dietary supplements.

Some doctors recommend flavonoid supplements for people with hemorrhoids. However, many different flavonoids occur in food and supplements, and additional research is needed to determine which flavonoids are most effective against hemorrhoids.

Hesperidin is a flavonoid found primarily in oranges and other citrus fruits. Orange juice is a rich source of hesperidin and several controlled trials have found regular consumption of orange juice reduces blood pressure in healthy volunteers. In a placebo-controlled trial that included 159 participants with borderline or high blood pressure, drinking a hesperidin-enriched orange juice providing 600 mg of hesperidin daily for 12 weeks reduced systolic blood pressure more than unenriched orange juice providing 345 mg of hesperidin per day, and both orange juice drinks reduced blood pressure more than a placebo drink. In addition, pulse pressure decreased in both groups given orange juice, indicating improvement in blood vessel stiffness. A similar placebo-controlled trial in overweight men found drinking orange juice and hesperidin-enriched orange juice for 4 weeks significantly decreased diastolic, but not systolic, blood pressure. Another placebo-controlled trial in 64 participants with type 2 diabetes found 500 mg of hesperidin lowered systolic blood pressure and levels of C-reactive protein, a marker of systemic inflammation. Not all trials have found benefits from orange juice or hesperidin supplements: two meta-analyses that each included ten randomized controlled trials concluded that neither orange juice nor hesperidin supplements significantly lowered blood pressure. Because hesperidin is not biologically active until it has been processed by intestinal microbes, it is thought differences in gut microbial presence may explain some of the variability in its effects on blood pressure.

Certain , known as hydroxyethylrutosides (HR), have been reported to improve symptoms of MD in one double-blind study. In this study, 2 grams per day of HR for three months resulted in either stabilization of or improvement in hearing. Other types of flavonoids have not been studied as treatments for MD.

Some cases of MD are associated with otosclerosis, a disease affecting the small bones of the inner ear. Otosclerosis often goes undiagnosed in people with MD, although the coexistence is well documented. While preliminary reports suggest otosclerosis may be a cause of MD, the relationship between these two conditions remains unclear. Sodium fluoride, a mineral compound available only by prescription, is reported to improve otosclerosis. In a preliminary study, people with MD and otosclerosis were given supplements of 50 mg of sodium fluoride, 200 mg calcium carbonate, and a multiple vitamin supplying 400–800 IU of vitamin D per day, for periods ranging from six months to over five years. Many participants also had blood sugar abnormalities, and were asked to follow a modified hypoglycemia diet as described above. Significant improvement in vertigo was reported within six months, but improvements in hearing required one to two years. Because most participants used both diet and supplements, the importance of fluoride, calcium, and/or vitamin D to the overall results of this trial is unclear.

A double-blind trial found that a combination of 900 mg per day of diosmin and 100 mg per day of hesperidin, two members of the family, resulted in significantly greater healing of venous leg ulcers after two months. Related flavonoids known as hydroxyethylrutosides have also been investigated for venous ulcer healing. While one controlled study reported significant additional benefit when 2,000 mg per day of hydroxyethylrutosides were added to compression stocking therapy, another double-blind trial using 1,000 mg per day found no effect on ulcer healing; a second double-blind trial found no effect of 1,000 mg per day hydroxyethylrutosides on the prevention of venous ulcer recurrences.

Many of the effects of allergic reactions are caused by the release of histamine, which is the reason antihistamine medication is often used by allergy sufferers. Some natural substances, such as vitamin C and , including quercetin, have demonstrated antihistamine effects in test tube, animal, and other preliminary studies. However, no research has investigated whether these substances can specifically reduce allergic reactions in humans.

Compounds called may help strengthen weakened capillaries. In test tube and animal studies, they have been shown to protect collagen, one of the most important components of capillary walls. A preliminary study found that proanthocyanidins (flavonoids extracted from grape seeds), 150 mg per day, increased capillary strength in people with hypertension and/or diabetes. A double-blind trial found a combination of two flavonoids (900 mg per day of diosmin and 100 mg per day hesperidin) for six weeks reduced symptoms of capillary fragility. Use of vitamin C with flavonoids, particularly quercetin, rutin, and hesperidin, is sometimes recommended for capillary fragility. Doctors often recommend 400 mg of rutin or quercetin three times per day or 1 gram of citrus flavonoids three times per day.

People who are deficient in vitamin C may be at increased risk for periodontal disease. When a group of people with periodontitis who normally consumed only 20–35 mg of vitamin C per day were given an additional 70 mg per day, objective improvement of periodontal tissue occurred in only six weeks. It makes sense for people who have a low vitamin C intake (e.g., people who eat few fruits and vegetables) to supplement with vitamin C in order to improve gingival health.

For people who consume adequate amounts of vitamin C in their diet, several studies have found that supplemental vitamin C has no additional therapeutic effect. Research, including double-blind evidence, shows that vitamin C fails to significantly reduce gingival inflammation in people who are not vitamin C deficient. In one study, administration of vitamin C plus (300 mg per day of each) did improve gingival health in a group of people with gingivitis; there was less improvement, however, when vitamin C was given without flavonoids. Preliminary evidence has suggested that flavonoids by themselves may reduce inflammation of the gums.

Many years ago, the rutin was reported to increase the effectiveness of conventional medication in people with glaucoma. The amount used—20 mg three times per day—was quite moderate. In that study, 17 of 26 eyes with glaucoma showed clear improvement. Modern research on the effects of rutin or other flavonoids in people with glaucoma is lacking.

are nutrients found in the white, pithy parts of fruits and vegetables. In preliminary laboratory research, certain flavonoids have been found to inhibit the infectivity of measles virus in the test tube. Whether flavonoid supplements could be effective in preventing or treating measles is unknown.

In 1964, a preliminary trial reported that 1,200 mg each of vitamin C and the hesperidin taken over the course of the day helped relieve hot flashes. Although placebo effects are strong in women with hot flashes, other treatments used in that trial failed to act as effectively as the flavonoid/vitamin C combination. Since then, researchers have not explored the effects of flavonoids or vitamin C in women with menopausal symptoms.

Both vitamin C and protect capillaries (small blood vessels) from damage. In so doing, they might protect against the blood loss of menorrhagia. In one small study, 88% of women with menorrhagia improved when given 200 mg vitamin C and 200 mg flavonoids three times per day. In another study, 70% of women with excessive menstrual bleeding experienced at least a 50% reduction in bleeding after taking a flavonoid product. The preparation used in this study contained 90% diosmin and 10% hesperidin and was given in the amount of 1,000 mg per day, beginning five days prior to the expected start of menstruation and continuing until the end of bleeding for three cycles.

Quercetin (a ) has been shown to inhibit the enzyme, aldose reductase. This enzyme appears to contribute to worsening of diabetic retinopathy. However, because the absorption of quercetin is limited, it is questionable whether supplementing with quercetin can produce the tissue levels that are needed to inhibit aldose reductase. Although human studies have not been done using quercetin to treat retinopathy, some doctors prescribe 400 mg of quercetin three times per day. Another flavonoid, rutin, has been used with success to treat retinopathy in preliminary research.

A controlled clinical trial found that oral supplementation with hydroxyethylrutosides (HR), a type of that is derived from rutin, improved varicose veins in a group of pregnant women. Further research is needed to confirm the benefits observed in this preliminary trial. A typical amount of HR is 1000 mg per day.