Bilberry - Medicinal Uses, Interactions, Side Effects, Dosage

Bilberry:
Bilberry is related to the American blueberry. Bilberries and other closely related members of the Vaccinium genus are also referred to as European blueberries, bog blueberries, whortleberries, and huckleberries.
Uses and Benefits:
Bilberry fruit extracts are currently marketed in the U.S. as "vision" and "capillary" herbal supplements. In World War II, there were rumors that British Royal Air Force aviators experienced increased night vision after eating bilberry jam. This led to support for treating poor night vision and a variety of ophthalmic and microvascular disorders-including myopia, glaucoma, cataracts, diabetic retinopathy, and retinal degeneration, as well as capillary fragility, varicose veins, venous insufficiency, and hemorrhoids­with European bilberry extracts. Bilberry contains antioxidants that are also used as herbal supplements in anti-aging diets . Traditionally, bilberry leaves and fruit have been employed for their astringent and antiseptic properties to treat diarrhea, dyspepsia, infections, and burns, and also for diabetes, scurvy, and other disorders.
Pharmacology:
The berries are rich in flavonoids, the most well defined being the anthocyanins (also called anthocyanosides), which are the pigments that impart the intense indigo blue color to the ripe fruit . Anthocyanins and other polyphenolic flavonoids are effective antioxidants and free radical scavengers. They have significant biochemical and physiologic effects on cells and tissues; these effects are related to their antioxidant properties, activity on specific enzymes, and regulation of extracellular matrix protein synthesis and degradation. In experimental studies, anthocyan ins have been reported to increase the endothelium barrier effect and reduce capillary permeability, inhibit edema, and protect microvessels from cholesterol-induced atheroscierosis. Anthocyanins also inhibit the synthesis and secretion of elastase and collagenase (proteases important in extra cellular matrix remodeling and vascular permeability) and may stimulate rhodopsin regeneration in the retina.
Anti-platelet activity of anthocyan ins and bilberry extracts has been demonstrated in vitro and in rodents, in which extremely large oral doses prolong the bleeding time. In humans, a standardized oral dose of a bilberry extract (480 mg/day of Myrtocyan, containing 36% anthocyan ins) affected platelets such that ADP­and collagen-induced aggregation was inhibited ; increased bleeding times have not been reported, however. In animal studies, anthocyan ins also have been reported to reduce plasma glucose and triglyceride levels in rats with induced diabetes, increase lipoprotein catabolism, protect against carbon tetra­chloride induced-hepatotoxicity, and have anti-tumor cell activity in vitro.
Clinical Trials:
Benefits of bilberry extracts (sometimes com­hined with beta-carotene or vitamin E) on ophthalmic and other microvascular disorders have been reported in numerous stud­ies. 1 ,2 Almost 40 such trials have been published, primarily in the Italian and French literature; most used proprietary extracts con­taining 25-36% anthocyan ins, such as Tegens or Myrtocyan. Few well-designed randomized, controlled trials have been published in peer-reviewed English-language journals; only controlled trials are reviewed here.
. Ophthalmic Uses-Improvements in night vision and quicker adaptation to darkness were originally reported in several studies from the 1960s, which have been reviewed by others. 1 ,2 Two placebo-controlled trials found statistically significant benefits in subjects after a single dose of bilberry extract, but not after multi­ple doses. 2 A double-blind study in 40 healthy subjects reported an enhanced pupillary light reflex with a single dose of bilberry anthocyanins; however, a similar percentage of subjects had en­hanced reflexes in the placebo group.16 In addition, more recent crossover trials that were randomized, double-blind, and placebo­controlled have failed to find any effect on night vision tests in healthy volunteers. One trial used a single dose and another used multiple small doses of anthocyanins (24-48 mg/day; Strix, Sweden) combined with beta-carotene. 17 ,1s Negative results were
also verified with larger doses in a recent, well-designed, U.S. study; no significant differences were found on night vision testing in 15 healthy male subjects given an extract or placebo t.i.d. for 3 weeks. This double-blind crossover trial used 480 mg/day of a product containing 25% anthocyanins, a dose similar to that used in the European trials.
Other studies have reported ophthalmic benefits such as im­proved visual perception in myopia and glaucoma, and improved retinopathy in patients with diabetes, hypertension, and other dis­orders. 1 ,2 Only three trials were appropriately controlled. Two re­portedly double-blind, placebo-controlled trials evaluated the progression of diabetic retinopathy in 36 and 40 patients, over 1 and 12 months, respectively.2o,21 Patients taking Tegens 160 mg b.i.d. exhibited improvements or stabilization in ophthalmoscopic or fluorangiographic examinations compared to placebo. Although the first study was randomized, the second study was not, nor was the data analyzed statistically. Bilberry products were also re­ported to halt the progression of mild senile cataracts in a double­blind and placebo-controlled trial of 50 patients, but details are not available in English.
Peripheral Vascular and Other Disorders-Bilberry extracts have been evaluated in many studies for ulcerative dermatitis, chronic venous insufficiency, varicose veins, hemorrhoids, bleed­ing and other postoperative complications, and dysmenorrhea. Of these studies, only four are placebo-controlled; none are pub­lished in English-language journals; and all used the Myrtocyan product. These studies have been summarized by others,1 al­though study methods have not been adequately assessed.
In one double-blind trial of 47 patients with various peripheral vascular disorders, treatment with 480 mg/day for 30 days was associated with significant improvements in subjective symptoms, such as paraesthesia and pain. In a single-blind, 30-day trial of 60 patients with venous insufficiency, treatment with 480 mg/day was also associated with a significant reduction in the severity of edema and subjective symptoms (pressure, paraesthesia, and cramps). In a double-blind trial, 30 patients with chronic primary dysmenorrhea were treated with 320 mg/day for 3 days before and during menses, which resulted in a significant improvement of symptoms over the 2-month treatment period. Lastly, in a single-blind study of 181 operative patients, pre-treatment with 160-320 mg/day for 10 days was reported to decrease intra- and postoperative bleeding and prevent onset of subsequent hemor­rhagic complications.
Adverse Effects:
There are no significant adverse effects of bilberry extracts reported in the clinical trials. Myrtocyan was well tolerated in a European post-marketing surveillance study of 2295 patients, in which 94 subjects (4.1 %) reported side effects that included mainly gastrointestinal, skin, or nervous system complaints.
Side Effects and Interactions:
There are no documented drug interactions.
Cautions:
Bilberry anthocyanins have antiplatelet effects in animal and human studies, but effects do not appear to be clinically significant with usual doses; bleeding problems and relevant drug interactions have not been reported in clinical trials or case reports. One study reported less intraoperative bleeding and hemorrhagic complications with bilberry pretreatment. Bilberry's safety during pregnancy and lactation has not been established. Consumption of 160-480 mg/day of anthocyanins during the last 3 months of pregnancy had no adverse effects on standard serum laboratory values.
Preparations & Doses:
Specific standardized European extracts used in the clinical trials usually contained 25-36% antho­cyanins, and were given as 160-480 mg/day (40-120 mg/day anthocyan ins) in two to three divided doses. The concentrated extract in one of these products, Tegens (containing 25% anthocyanins), is also marketed in the U.S. as Bilberry Extract by Enzymatic Therapy/PhytoPharmaca, and Bilberry Extract by Solaray. Many other preparations containing concentrated anthocyanins are also available on the U.S. market in encapsulated and other forms. Bilberry leaves and dried fruits are employed in traditional herbal medicine, usually as a decoction or extract.
Summary Evaluation
Numerous European clinical trials, supported by pharmacologic studies, suggest that anthocyanin-rich bilberry extracts with antioxidant properties may provide benefits in a variety of ophthalmic and peripheral vascular disorders. Improvement of diabetic retinopathy, cataracts, chronic venous insufficiency, and dysmenorrhea are supported by placebo controlled studies in the European literature, although many of these studies have not been adequately evaluated. In view of bilberry's apparent safety, there is little harm in patients and consumers trying this herb in conjunction with standard medical therapies for these indications. However, controlled studies of good methodologic quality are limited, and none of these indications have been proven beyond a reasonable doubt. Although often promoted to improve night vision based on early European studies, recent well-designed clinical trials have failed to verify this effect, which also raises doubts about the validity of other claims for bilberry.

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