Bilberry

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Vaccinium myrtillus L.

[Fam. Ericaceae]

Overview

Bilberry is the name of a small European blueberry. Dietary supplements made from the standardized extract of bilberry have become popular in the United States over the past decade. Sales in the mainstream retail markets ranked 13th of all herbs in 2000 (Blumenthal, 2001). The standardized, concentrated extract of bilberry is used by consumers to help treat or prevent ocular, microcirculatory, and vascular-related disorders. Bilberry leaf extract (not the fruit that is covered in this monograph) was used as a treatment for diabetes before the availability of insulin. It was found effective in adult onset diabetes as a method of reducing glycosuria and postprandial hyperglycemia (Allen, 1927). For that reason, the leaf extract is contraindicated for diabetes patients taking insulin (Bailey and Day, 1989).

Description

Bilberry preparations consist of the whole, dried, ripe, black or bluish-black fruit of Vaccinium myrtillus L. [Fam. Ericaceae]. Some concentrated extracts are standardized to anthocyanosides, calculated as 25% anthocyanidins, but may actually contain about 37% by weight (Pizzorno and Murray, 1999).

Primary Uses

Gastrointestinal

Diarrhea: The German Commission E approved crude (i.e. non-concentrated) fruit preparations for acute diarrhea (Blumenthal et al., 1998), particularly in children (Blumenthal et al., 1998; Ofek et al., 1996)

Ophthalmic

Retinopathy, hypertensive (Repossi et al., 1987), and diabetic (Ghiringhelli et al., 1978; Treviso et al., 1979; Scharrer et al., 1981; Grismondi et al., 1981; Orsucci et al., 1983; Perossini et al., 1987; Repossi et al., 1987)

Vascular

Peripheral vascular disorders and blood purpuras (Allegra et al., 1982)

Venous insufficiencies (Gatta et al., 1988; Teglio et al., 1987), varicose veins (Ghiringhelli et al., 1978), capillary fragility (Coget and Merlen, 1980; Grismondi et al., 1980; Mian et al., 1977; Neumann, 1973; Treviso et al., 1979), and kidney capillary fragility (Pennarola et al., 1980)

Other Potential Uses

Blindness, night and day (Jayle et al., 1965; Gloria and Peria, 1966; Sala et al., 1979; Caselli, 1985; Vannini et al., 1986; Zavarise et al., 1987)

Cataracts (Bravetti et al., 1989)

Gargle for inflamed oral and pharyngeal mucous membranes (Blumenthal et al., 1998)

Macular degeneration, retinitis pigmentosa, hemorrhagic retinopathy (Scharrer and Ober, 1981)

Dysmenorrhea (Colombo and Vescovini, 1985)

Reduction of intra- and post-operative bleeding (Gentile et al., 1987; Cerutti et al., 1984)

Dosage

Crude Preparations

Dried, ripe fruit: 20–60 g daily (4–8 g with water, several times daily) (Braun et al., 1993; Meyer-Buchtela, 1999; Wichtl and Bisset, 1994).

Infusion/decoction: 20–60 g daily. The berries are prepared by placing 5–10 g crushed, dried fruit in 150 ml cold water. This mixture is boiled for approximately 10 minutes; then strained while hot. The preparation is drunk cold several times daily until the diarrhea subsides (Braun et al., 1993; Meyer-Buchtela, 1999; Wichtl and Bisset, 1994).

Cold macerate: 20–60 g daily. The berries are prepared by soaking 5–10 g crushed dried fruit in 150 ml cold water for 2 hours, allowing the fruit to swell. The preparation is drunk cold several times daily (Braun et al., 1993; Meyer-Buchtela, 1999; Wichtl and Bisset, 1994).

Gargle: Mouthwash containing 10% decoction (prepared as described above) for local application in the treatment of mild inflammation of oral and pharyngeal mucous membranes (Blumenthal et al., 2000).

Fluid extract: 1:1 (g/ml), 2–4 ml, 3 times daily (Anderhuber, 1991; Cunio, 1993).

Standardized Preparations

Dry standardized extract: (25% anthocyanidins) 80–160 mg, 3 times daily (Pizzorno and Murray, 1999).

Note: Doses may range from 160–480 mg daily depending on the conditions being treated (see the following table, “Clinical Studies on Bilberry”). Therapeutic benefits appear to take effect in 4–8 weeks.

Duration of Administration

Crude Preparations

Diarrhea: Not more than 3–4 days.

Standardized Preparations

Vascular and ocular-related disorders: 2–6 months depending on the condition.

Chemistry

Dried bilberries contain 5–10% catechins (tannins), ca. 30% invertose (invert sugar) (Schulz et al., 2001), and flavonoids. Bilberry contains a small amount of anthocyanosides (0.1–0.25% in fresh fruit) consisting of 3-O-glycosides of cyanidin, delphinidin, malvidin, peonidin, and petunidin (Baj et al., 1983), and proanthocyanidins B1-B4 (Bruneton, 1999).

Pharmacological Actions

Crude Preparations

Astringent (Blumenthal et. al., 2000).

Standardized Preparations

Human

Anti-platelet aggregation (Pulliero et al., 1989) (ex vivo); collagen-stabilizing activity (Mian et al., 1977); decreased vascular permeability associated with injury (Mian et al., 1977).

Animal

Antiplatelet aggregation (Morazzoni and Magistretti, 1990; Zaragoza et al., 1985; Bottecchia et al., 1987); anti-ulcer (Cristoni and Magistretti, 1987); decreased capillary fragility (anti-inflammatory activity) (Detre et al., 1986; Lietti et al., 1976); collagen-stabilizing (Detre et al., 1986); vascular smooth muscle relaxant (Bettini et al., 1984a; Bettini et al., 1984b); vascular permeability regulator (Detre et al., 1986; Lietti and Forni, 1976); increased regeneration of rhodopsin (a light-sensitive pigment found in rods and retina) (Alfieri et al., 1966; Cluzel et al., 1969).

In vitro

Antioxidant (Meunier et al., 1989); free radical scavenger (Pietta et al., 1998; Martin-Aragon et al., 1998); inhibits cAMP phosphodiesterases (Ferretti et al., 1988); chemopreventative (Bomser et al., 1996); inhibits lipid peroxidation (Meunier et al., 1989).

Note: The pharmacological actions — antioxidant, anti-inflammatory, decreases in capillary permeability, and stabilization of collagen — are further supported by research conducted on flavonoids in general (Gabor, 1972; Kuhnau, 1976; Havsteen, 1983; Monboisse et al., 1983).

Mechanism of Action

Inhibits enzymatic cleavage of collagen by enzymes secreted by leukocytes during inflammation (Mian et al., 1977)

Increases the endothelium barrier effect through stabilizing the membrane phospholipids and increasing the biosynthesis of the acid mucopolysaccharides of the connective ground substance, thus restoring the altered mucopolysaccharide pericapillary sheath (Mian et al., 1977)

Decreases basement membrane collagen hydrolysis by significantly reducing permeability of the blood-brain barrier (BBB), and increases recovery rate of the BBB caused by permeability-increasing agents (Robert et al., 1977)

Prevents the liberation of lactate dehydrogenase in heart, plasma, and cardiac isoenzymes (Marcollet et al., 1970)

May result in retinal protection due to the inhibition of retinal phosphoglucomutase and glucose-6-phosphatase (Cluzel et al., 1969)

Reduces microvascular impairments due to ischemia reperfusion injury, with preservation of endothelium, attenuation of leukocyte adhesion, and improvement of capillary perfusion (Bertuglia et al., 1995)

Produces dose-dependent inhibition of platelet aggregation and clot retraction (Bottecchia, 1987)

Contraindications

None known.

Pregnancy and Lactation: No known restrictions.

Adverse Effects

None known (at therapeutic doses).

Drug Interactions

None known. It has been inferred, based on pharmacological studies, that very high doses (>170 mg anthocyanins per day for 30–60 days) may interact with warfarin or other antiplatelet drugs (Bone and Morgan, 1997). Leaf only: There have also been claims that bilberry leaf, as mentioned in the overview, may reduce insulin requirements. Therefore, conventional antidiabetic therapy would require close monitoring or adjustment (De Smet et al., 1993; Bailey and Day, 1989).

American Herbal Products Association (AHPA) Safety Rating

Class 1: Can be safely consumed when used appropriately (McGuffin et al., 1997).

Regulatory Status

Austria: Dried fruit official in the 1990 Austrian Pharmacopoeia, 1991 Addendum II (Meyer-Buchtela, 1999; ÖAB, 1991; Wichtl and Bisset, 1994).

Canada: Multiple-ingredient Traditional Herbal Medicines (THMs) containing bilberry, in tea infusion form, and homeopathic mono-preparations of bilberry are scheduled OTC drugs requiring premarket registration and assignment of a drug identification number (DIN) (Health Canada, 2001).

France: Fresh or dried fruits are permitted for oral or topical use (Bruneton, 1999).

Germany: Dried fruit, for tea infusions and other equivalent galenical dosage forms, is an approved nonprescription drug of the German Commission E monographs (Blumenthal et al., 1998). Dried fruit is official in the German Drug Codex supplement to the German Pharmacopoeia (DAC, 1998). Bilberry dried-fruit tea is an approved nonprescription drug listed in the German Standard License (St. Zul.) monographs (Braun et al., 1993). The fresh, ripe fruit for preparation of hydro-alcoholic mother tincture and liquid dilutions is an official drug of the German Homeopathic Pharmacopoeia (GHP, 1993).

Italy: Dried hydro-alcoholic extract is listed in the Italian Pharmacopoeia (Morazzoni and Bombardelli, 1996).

Sweden: Classified as foodstuff (De Smet et al., 1993). As of January 2001, no bilberry products are listed in the Medical Products Agency (MPA) “Authorised Natural Remedies” (MPA, 2001).

Switzerland: Dried fruit is official in the Swiss Pharmacopoeia (Meyer-Buchtela, 1999; Ph.Helv.VII, 1987–1997; Wichtl and Bisset, 1994). A semipurified extract (Myrtaven^®), standardized to 58 mg anthocyanosides per capsule, is a Category C nonprescription drug with sale limited to pharmacies (Morant and Ruppanner, 2001).

U.K.: Not listed in General Sale List (GSL). No monograph in the British Pharmacopoeia.

U.S.: Dietary Supplement (USC, 1994). Tincture of the ripe berries is a Class D over-the-counter drug of the Homeopathic Pharmacopoeia of the United States (HPUS, 1993).

Clinical Review

Fifteen studies are outlined in the following table, “Clinical Studies on Bilberry,” including a total of 694 participants. All but one of the studies (Muth et al., 2000) demonstrate positive effects for indications, including various ocular conditions (night/day vision and retinopathy), and vascular conditions, including venous insufficiencies and micro- and macroperipheral circulation. Two double-blind, placebo-controlled (DB, PC) studies (Perossini et al., 1987; Repossi et al., 1987) focused on retinopathy and confirmed results of two earlier open studies (Orsucci et al., 1983; Scharrer and Ober, 1981). One DB, PC study (Vannini et al., 1986) on nighttime vision confirmed preliminary findings of five previous open studies (Jayle and Auber, 1964; Jayle et al., 1965; Gloria and Peria, 1966; Sala et al., 1979; Terrasse et al., 1966). A recent DB, PC, crossover study (Muth et al., 2000) failed to find an effect of a bilberry extract (25% anthocyanosides) on night vision or night contrast sensitivity. One DB, PC study conducted on peripheral vascular disorder (Allegra et al., 1982) concluded positive results for Raynaud’s sufferers. Another DB, PC study (Colombo and Vescovini, 1985) on chronic dysmenorrhea was positive and further supports pharmacological findings (Bettini et al., 1984a, Bettini et al., 1984b). One single-blind, PC study on venous insufficiencies in 60 participants (Gatta et al., 1988) further supported the findings of four similar studies, including two open studies (Ghiringhelli et al., 1977; Mian et al., 1977), and two using pregnant subjects (Teglio et al., 1987; Grismondi et al., 1980). Bleeding was investigated in a SB, PC study (Gentile et al., 1987), finding bilberry reduced intra- and postoperative bleeding and prevented subsequent hemorrhaging. Another study (Cerutti et al., 1984) focused on bleeding associated with intrauterine devices. The most comprehensive review of research and clinical information on bilberry was compiled by Morazzoni and Bombardelli (1996).

Branded Products*

Difrarel 100^TM: Laboratoires Chibret / c/o Societe Anonyme Corporation / 200 Boulevard Etienne-Clementel Clermont-Ferrand / Puy-de-Dome / France. No product information available; no longer manufactured.

Myrtocyan^®: Indena S.p.A. / Viale Ortles 12 / 20139 Milano / Italy / Tel: +39-02-57-4961 / Fax: +39-02-57-4046-20 / Email: indenami@tin.it. Extract standardized to 25% anthocyanidins containing 36% anthocyanosides.

Tegens^TM: Synthelabo-Pharma SA of France / 11 Rue de Veyrot, 1217 Meyrin / France / Tel: +33-02-29-89-0147 / Fax: +33-02-29-89-0188. The product is standardized to 25% anthocyanidins containing 36% anthocyanosides by the extract Myrtocyan^®.

American equivalents, if any, are found in the Product Table beginning on page 398.

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