Bilberry

Bilberry/Drug Interactions:

  • AntiangiogenicsAntiangiogenics: In human research, bilberry demonstrated improvements in levels of "pathologic proteins" (collagen and structural lipoprotein levels) in diabetic microangiopathy (65). Other studies have reported effects on parameters of retinopathy and microangiopathy in humans (60).
  • AntibioticsAntibiotics: According to in vitro research, bilberry leaves may have antibacterial properties (2).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: There is a theoretical bleeding risk, based on the antiplatelet and potential anticoagulant actions of bilberry extract in cellular and human research, although there has been a lack of human reports of bleeding in the available literature (35; 37; 38; 34; 36; 39).
  • Antidiabetic agentsAntidiabetic agents: In animal research, bilberry leaf extract lowered glycemic levels in diabetic rats, normal dogs, and depancreatized dogs (13; 40; 41). However, another study using healthy rats found that an alcoholic extract of Vaccinium myrtillus leaves increased serum glucose levels compared to controls (42). In human research, dietary interventions incorporating bilberry, either alone or coadministered with whole grains and fatty fish, demonstrated glucose-lowering effects (43; 44).
  • AntidiarrhealsAntidiarrheals: According to secondary sources, bilberry contains tannins that have been used medicinally as astringents and to treat diarrhea.
  • AntihypertensivesAntihypertensives: Bilberry has been theorized to potentially drop blood pressure, based on preclinical evidence of vascular smooth muscle-relaxing properties (25; 61; 62). Anthocyanoside extracts have been shown to have smooth muscle-relaxing activity, which may account for its purported effects in one series of women with dysmenorrhea (57). Bioflavonoids and extracts of anthocyanosides (such as those present in bilberry) have been shown to relax vascular smooth muscles in experimental models, possibly via stimulation of prostaglandins (25; 61; 62). In human research, a diet rich in various types of berries reduced systolic blood pressure, particularly in individuals with an elevated baseline blood pressure (39).
  • Anti-inflammatory agentsAnti-inflammatory agents: In human research, bilberry supplementation with mixed berry-derived anthocyanin isolates (Medox?) (66), single-component dietary interventions (44; 51; 52), and multicomponent dietary interventions (67) have demonstrated anti-inflammatory effects.
  • AntilipemicsAntilipemics: In human research, mixed berry-derived anthocyanins and mixed berry-rich diets have been shown to increase plasma concentration of high-density lipoprotein (HDL) cholesterol and decrease low-density lipoprotein (LDL) cholesterol (68; 39), although other human studies have reported a lack of effect on lipid metabolism (51).
  • Antineoplastic agentsAntineoplastic agents:In vitro, bilberry (Vaccinium myrtillus L.) inhibited cancer cell growth (12).
  • Antiulcer agentsAntiulcer agents: In animal research, large doses of cyanidin chloride from bilberry and IdB1027, a natural flavonoid from bilberry VMA extract, demonstrated antiulcer activity (22; 21; 20; 23; 24).
  • Cardiovascular agentsCardiovascular agents: In human research, mixed-berry derived anthocyanins and a healthy diet comprising, in part, regular bilberry consumption improved various biomarkers of endothelial function, including flow-mediated dilation (FMD), cGMP, soluble vascular adhesion molecule-1 (sVCAM-1), and E-selectin (68; 67).
  • Gastrointestinal agentsGastrointestinal agents: In human research, a combination formulation containing aerial agrimony parts, cinnamon quills, powdered bilberry fruit, and slippery elm bark was shown to mitigate various symptoms of irritable bowel syndrome (e.g., abdominal pain, bloating, flatulence, straining) in spite of a lack of efficacy in improving bowel habit; the frequency of bowel movements increased following combination bilberry treatment (45).
  • EstrogensEstrogens: In a comparative study, bilberry extract inhibited absorption of estrogens in the intestine by 75.5% (p<0.01) (63).
  • HepatotoxinsHepatotoxins: In animal research, anthocyans exerted a protective effect on liver cells (69).
  • ImmunosuppressantsImmunosuppressants: In human research, dietary consumption of fresh bilberries decreased expression of CCR2 and MMD transcripts in genes associated with monocyte and macrophage function (51).
  • Insulin preparationsInsulin preparations: In healthy humans, a fermented oatmeal drink with 10% added bilberry fruit reduced postprandial insulin demand in spite of an elevated glucose response (70).
  • Ophthalmic agentsOphthalmic agents: In human research, the multi-ingredient product MirtogenolT lowered intraocular pressure and improved ocular blood flow (71).

    • Bilberry/Herb/Supplement Interactions:

  • AntiangiogenicsAntiangiogenics: In human research, bilberry demonstrated improvements in levels of "pathologic proteins" (collagen and structural lipoprotein levels) in diabetic microangiopathy (65). Other studies have reported effects on parameters of retinopathy and microangiopathy in humans (60).
  • AntibacterialsAntibacterials: According to an in vitro study, bilberry leaves may have antibacterial properties (2).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: There is a theoretical bleeding risk, based on the antiplatelet and potential anticoagulant actions of bilberry extract in cellular and human research, although there has been a lack of human reports of bleeding in the available literature (35; 37; 38; 34; 36; 39).
  • AntidiarrhealsAntidiarrheals: According to secondary sources, bilberry contains tannins that have been used medicinally as astringents and to treat diarrhea.
  • Anti-inflammatory agentsAnti-inflammatory agents: In human research, bilberry supplementation with mixed berry-derived anthocyanin isolates (Medox?) (66), single-component dietary interventions (44; 51; 52), and multicomponent dietary interventions (67) demonstrated anti-inflammatory effects.
  • AntilipemicsAntilipemics: In human research, mixed berry-derived anthocyanins and mixed berry-rich diets have been shown to increase plasma concentration of HDL cholesterol and decrease LDL cholesterol (68; 39), although other human studies have reported a lack of effect on lipid metabolism (51).
  • AntineoplasticsAntineoplastics: In vitro, bilberry (Vaccinium myrtillus L.) inhibited cancer cell growth (12).
  • AntioxidantsAntioxidants: Bilberry contains anthocyanosides that are flavonoid derivatives of anthocyanins (the blue, red, or violet pigments found in many berry varieties), which are closely related in structure and activity to flavonoids (46) and possess free radical-scavenging and antioxidant properties. Antioxidant properties have been attributed to bilberry in in vitro studies (4; 5; 6; 7; 8; 9), although studies in humans are lacking. In human research, dietary consumption of 160g of mixed berries (bilberries, black currants, chokeberries, lingonberries) daily for eight weeks increased the plasma level of various polyphenols compared to placebo, including quercetin, caffeic acid, p-coumaric acid, protocatechuic acid, homovanillic acid, vanillic acid, 3-hydroxyphenylacetic acid, and 3-(3-hydroxyphenyl)propionic acid (72).
  • Antiulcer agentsAntiulcer agents: In animal research, large doses of cyanidin chloride from bilberry and IdB1027, a natural flavonoid from bilberry VMA extract, demonstrated antiulcer activity (22; 21; 20; 23; 24).
  • Cardiovascular agentsCardiovascular agents: In human research, mixed-berry derived anthocyanins and a healthy diet comprising, in part, regular bilberry consumption improved various biomarkers of endothelial functions, including FMD, cGMP, sVCAM-1, and E-selectin (68; 67).
  • Gastrointestinal agentsGastrointestinal agents: In human research, a combination formulation containing aerial agrimony parts, cinnamon quills, powdered bilberry fruit, and slippery elm bark was shown to mitigate various symptoms of irritable syndrome (e.g., abdominal pain, bloating, flatulence, straining) in spite of a lack of efficacy in improving bowel habit; the frequency of bowel movements increased following combination bilberry treatment (45).
  • Hepatotoxic herbsHepatotoxic herbs: In animal research, anthocyans exerted a protective effect on liver cells (69).
  • Hormonal agentsHormonal agents: In a comparative study, bilberry extract inhibited absorption of estrogens in the intestine by 75.5% (p<0.01) (63).
  • HypoglycemicsHypoglycemics: In animal research, bilberry leaf extract lowered glycemic levels in diabetic rats, normal dogs, and depancreatized dogs (13; 40; 41). However, another study using healthy rats found that an alcoholic extract of Vaccinium myrtillus leaves increased serum glucose levels compared to controls (42). In human research, dietary interventions incorporating bilberry, either alone or coadministered with whole grains and fatty fish, demonstrated glucose-lowering effects (43; 44).
  • HypotensivesHypotensives: Bilberry has been theorized to potentially drop blood pressure, based on preclinical evidence of vascular smooth muscle-relaxing properties (25; 61; 62). Anthocyanoside extracts have been shown to have smooth muscle-relaxing activity, which may account for its purported effects in one series of women with dysmenorrhea (57). Bioflavonoids and extracts of anthocyanosides (such as those present in bilberry) have been shown to relax vascular smooth muscles in experimental models, possibly via stimulation of prostaglandins (25; 61; 62). In human research, a diet rich in various types of berries reduced systolic blood pressure, particularly in individuals with an elevated baseline blood pressure (39).
  • ImmunosuppressantsImmunosuppressants: In human research, dietary consumption of fresh bilberries decreased expression of CCR2 and MMD transcripts in genes associated with monocyte and macrophage function (51).
  • PhytoestrogensPhytoestrogens: In a comparative study, bilberry extract inhibited absorption of estrogens in the intestine by 75.5% (p<0.01) (63).
  • QuercetinQuercetin: Bilberry may be a source of bioavailable quercetin; therefore, additive effects may be seen with concomitant administration (73).
  • ResveratrolResveratrol: In laboratory research, bilberry contained resveratrol (74; 75); therefore, additive effects may be seen with concomitant administration.
  • Vitamin CVitamin C: In a clinical study of subjects with normal platelet aggregation, ingestion of Vaccinium myrtillus anthocyanins and ascorbic acid additively reduced platelet aggregation (35).
  • Vitamin EVitamin E: In an uncontrolled case series, coadministration of bilberry-derived anthocyanosides slowed the progression of lens opacities in elderly adults with early stage cataracts (76).

    • Bilberry/Food Interactions:

  • BerriesBerries: In human research, a diet rich in various types of berries, including whole bilberries, crushed lingonberry nectar, black currant or strawberry puree, and chokeberry and raspberry juice, reduced systolic blood pressure, particularly in individuals with an elevated baseline blood pressure (39). Mixed berry interventions have also been shown to improve plasma concentration of HDL and LDL cholesterol (68; 39), as well as various biomarkers of endothelial function, including FMD, cGMP, sVCAM-1, and E-selectin (68).
  • Fatty fishFatty fish: In human research, a healthy diet of bilberries, whole grains, and fatty fish demonstrated glucose-lowering effects (43; 44), anti-inflammatory effects (67), and improved various biomarkers of endothelial function, including FMD, cGMP, sVCAM-1, and E-selectin (67).
  • OatmealOatmeal: In healthy humans, a fermented oatmeal drink with 10% added bilberry fruit reduced postprandial insulin demand in spite of an elevated glucose response (70).
  • Whole grainsWhole grains: In human research, a healthy diet of bilberries, whole grains, and fatty fish demonstrated glucose-lowering effects (43; 44), anti-inflammatory effects (67), and improved various biomarkers of endothelial function, including FMD, cGMP, sVCAM-1, and E-selectin (67).

    • Bilberry/Lab Interactions:

  • Blood pressureBlood pressure: Bilberry has been theorized to potentially drop blood pressure, based on preclinical evidence of vascular smooth muscle-relaxing properties (25; 61; 62). Anthocyanoside extracts have been shown to have smooth muscle-relaxing activity, which may account for its purported effects in one series of women with dysmenorrhea (57). Bioflavonoids and extracts of anthocyanosides (such as those present in bilberry) have been shown to relax vascular smooth muscles in experimental models, possibly via stimulation of prostaglandins (25; 61; 62). In human research, a diet rich in various types of berries reduced systolic blood pressure, particularly in individuals with an elevated baseline blood pressure (39).
  • Coagulation panelCoagulation panel: In cellular and human research, bilberry extract has been shown to have potential anticoagulant and antiplatelet actions, although there has been a lack of human reports of bleeding in the available literature (34; 35; 36; 37; 38; 39).
  • Inflammatory markersInflammatory markers: In human research, bilberry supplementation with mixed berry-derived anthocyanin isolates (Medox?), single-component dietary interventions, and multicomponent dietary interventions has decreased levels of E-selectin, high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-4, IL-6, IL-8, IL-12, IL-13, IL-15, interferon-alpha (IFN-alpha), lipopolysaccharide (LPS), monokine induced by IFN-gamma (MIG), and regulated upon activation, normal T cell expressed and secreted (RANTES) (66; 51; 67; 52). Mixed findings have been found with regard to tumor necrosis factor-alpha (TNF-alpha), with some research demonstrating decreased levels following dietary bilberry consumption (frozen whole berries) (44) and others demonstrating increases (bilberry juice) (52).
  • LipidsLipids: In human research, mixed berry-derived anthocyanins and mixed berry-rich diets have been shown to increase plasma concentration of HDL cholesterol and decrease LDL cholesterol (68; 39), although other human studies have reported a lack of effect on lipid metabolism (51).
  • Serum glucoseSerum glucose: In animal research, bilberry leaf extract lowered glycemic levels in diabetic rats, normal dogs, and depancreatized dogs (13; 40; 41), although in healthy rats, an alcoholic extract of Vaccinium myrtillus leaves increased serum glucose levels compared to controls (42). In human research, dietary interventions incorporating bilberry, either alone or coadministered with other food components, demonstrated glucose-lowering effects (43; 44).