Family

Ericaceae.

Related Species

There is considerable bioregional diversity of wild blue-fruited Vaccinium spp., whose berries are very similar nutritionally and medicinally to the official species, V. myrtillus L. (e.g., in the U.S. Pacific Northwest alone, V. ovatum Pursh., V uliginosum L., V. occidentale Gray., V ovalifolium Smith., V deliciosum Smith., V . membranaceum, Dougl.). Horticultural cultivars are also common.

Parts Used

Fruit (berries); the leaf, a separate remedy, has been used in traditional herbal medicine but currently is not widely used.

Common Forms

• Leaf:   Dried leaf (infusion), dried-leaf hydroethanolic extract.

• Berry (Fruit):   Dried whole fruit; hydroethanolic tincture and liquid extracts; standardized extract (Myrtocyan, Tegens, MirtoSelect) in capsule form containing 25% anthocyanidins, with 36% anthocyanosides.

Strategic Considerations

Bilberry is currently best known for the properties of the anthocyanidin (Greek antos, “flower,” and kyanos, “blue”) and proanthocyanidin content of the fruit (berries). Anthocyanidins and proanthocyanidins are naturally occurring polyphenolic flavonoids widely present in berries and other fruit, also responsible for the blue-red pigmentation in many flowers and fruits. The chemistry and biological activities of the anthocyanidins and anthocyanins (aglycones and glycosides, respectively) have been extensively studied; the representative compound is cyanidin and its glycosides. ^1,2

Although the phytomedical literature on bilberry is dominated by the pharmacology of the anthocyanins and proanthocyanins and their glycosides, these are present at a level of only 0.1% to 0.25% in the fresh fruit. The catechin (tannin) content of the fruit, however, is actually an order of magnitude higher, 5% to 10%. This implies that standardized extracts that are widely used in commerce represent a highly concentrated product, and the safe therapeutic dose range is wide, from 120 to 480 mg standardized extract per day (equivalent to upper dose of ∼500.0 g fresh, or ∼100.00 g dry, berry/day). At these dose levels, bilberry concentrated extracts can be considered as a “phytonutriceutical” product, better classified with other concentrated flavonoid supplements, such as quercitin, rutin, and the oligomeric proanthocyanidins (OPCs). Resveratrol and the related compound pterostilbene may also be present in significant quantities in the concentrated extracts. Pterostilbene appears to have hypocholesterolemic properties mediated by its binding affinity to the peroxisome proliferator activated receptor (PPAR) and shares some of the chemopreventive and antioxidant characteristics of resveratrol. ^3,4

The German literature describes use of 10% dried bilberry fruit decoction as a safe supportive treatment of nonspecific diarrhea, including pediatric cases, and for topical inflammations of the mouth and throat, including oral candidiasis. ^5-8These uses are not widespread in North American clinical practice and are unlikely to invoke interactions with pharmaceutical agents.

The concentrated extracts, enriched in anthocyanins, have a range of pharmacological actions, including antioxidant, chemoprotective, vasoprotective, antiulcer, anti-inflammatory and antiatherogenic, antiaggregatory, and ophthalmic effects. Clinical evidence supports their use in peripheral vascular disorders (e.g., venous insufficiency, capillary fragility) and in ophthalmic disorders. Recent reviews of these data include the therapeutic monograph from the European Scientific Cooperative on Phytotherapy (ESCOP) ⁹ and a survey by McKenna et al. ¹⁰ Data relating to berry and fruit polyphenols and cancer chemoprevention has been reviewed by Prior and Joseph. ¹¹ Experimental data demonstrating direct anticancer effects of anthocyanins is emerging. ¹² In clinical practice, concentrated bilberry extracts are most likely to be used for disorders of microcirculation, and the specific advantage of the anthocyanins is their affinity for ophthalmic neurovasculature; conditions such as optic neuritis of multiple sclerosis, macular degeneration, glaucoma, and diabetic retinopathy are often the key prescribing indications.

Interactions between standardized bilberry extracts and pharmaceutical drugs have received minimal study. A single study reported a reduction in platinum compound toxicity without compromise to antitumor efficacy in an Ehrlich tumor rodent model using oral anthocyanins at 300 mg/kg coadministered with cisplatin. ¹³ No English translation of this report has been published, and the platinum interaction has not been confirmed by other studies or clinical reports and is not reviewed further here.

Pharmacokinetic data suggest that human intestinal flora are essential for hydrolysis of the glycoside form to the anthocyanin and proanthocyanin aglycones. ^14-16This suggests that iatrogenic reduction in microflora populations induced by antibiotics may reduce the bioavailability of the bilberry polyphenols, although evidence for this is not available.

Effects on Drug Metabolism and Bioavailability

Effects of bilberry extracts, or anthocyanins and proanthocyanins, on drug metabolism have not been well studied. Chemopreventive effects of fruits and berries have been examined in a few studies examining the mechanism of these effects, including possible inhibition of cytochrome P450 (CYP) 1A1 and 2E1 xenobiotic (aryl hydrocarbon carcinogen)–metabolizing enzymes. ^17-20The data are inconclusive but suggest low or minimal effects on these enzymes. Resveratrol, present in small amounts in bilberries, may inhibit CYP1B1, but this is not a significant drug-metabolizing cytochrome in humans although it is overexpressed in hormone-dependent tumor tissue. ²¹ Recent experimental evidence suggests that bilberry extracts potently inhibit organic anion-transporting polypeptide B (OATP-B), which is an intestinal transporter responsible for mediating absorption of several drugs. ²² The flavonoid fraction of bilberry seems likely to be the active inhibitory component, but the in vivo significance of this inhibition remains to be established. Pharmacokinetic interactions between bilberry extracts or ingredients have not been reported.

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