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Bilberry

Plant Part Used

Berry/leaf.

Active Constituents

Anthocyanosides, flavonoid compounds. (1) , (2) [span class=alert]

This section is a list of chemical entities identified in this dietary supplement to possess pharmacological activity. This list does not imply that other, yet unidentified, constituents do not influence the pharmacological activity of this dietary supplement nor does it imply that any one constituent possesses greater influence on the overall pharmacological effect of this dietary supplement.[/span]

Introduction

Bilberry is one of the most popular herbs on the market today. During World War II when British air pilots ate bilberries, they reported an improved ability to adjust to glare and an increase in their visual acuity and nighttime vision. (3) Bilberry extracts show promise in the areas of diabetic retinopathy, macular degeneration, cataracts, glaucoma, and varicose veins. (4)

Interactions and Depletions

Interactions

Dosage Info

Dosage Range

80-240mg (standardized extract) daily, in divided doses.

Tea: 1 cup, 2 to 3 times daily with one gram of herb per cup. (5)

A 10% decoction is prepared for external use. (5)

Most Common Dosage

80mg (standardized extract), 2 times daily.

Tea: 1 cup, 2 times daily with one gram of herb per cup.

A 10% decoction is prepared for external use.

Standardization

[span class=doc]Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.[/span]

The most current available medical and scientific literature indicates that this dietary supplement should be standardized to 25% anthocyanosides, calculated as anthocyanidins, per dose.

Uses

Frequently Reported Uses

  • Antioxidant
  • Eye health
  • Cardiovascular health
Other Reported Uses
  • Blood sugar regulation
  • Hyperlipidemia
  • Cancer prevention
  • Chemotherapy adjunct

Toxicities & Precautions

General

No known toxicity. (5)

Health Conditions

Based on pharmacology, use in caution in individuals with bleeding disorders.

Pregnancy/ Breast Feeding

Use with caution in pregnancy. (6)

Age Limitations

Do not use in children under 2 years of age unless recommended by a physician.

Pharmacology

Bilberry is reported in laboratory and human studies to be a powerful antioxidant.(4) Anthocyanins extracted from Bilberry have demonstrated vasoprotective and antiinflammatory properties in laboratory animals.(7) Berry anthocyanins trigger genetic signaling in promoting human health and disease prevention.(26)

Antioxidant/Anti-inflammatory activity

Bilberry is claimed to exert a collagen stabilizing activity.(8) Collagen is responsible for the integrity of tendons, ligaments, and cartilage. In conditions such as arthritis, where the connective tissue is attacked and vascularized, anthocyanosides may be helpful. Bilberry reportedly strengthens the cross-linking of the collagen matrix and stimulates the production of collagen and mucopolysaccharides.(8) Bilberry compounds reportedly inhibit mediators of inflammation such as histamine, protease, leukotrienes, and prostaglandins.(4) Anthocyanosides may also decrease capillary permeability.(9) This is of particular importance because of the heightened integrity, which occurs at the blood/brain barrier. By strengthening collagen, brain capillary integrity can be improved, as well as a reduction in infiltration by potential toxins. Bilberry has the ability to stimulate gastric mucus production, which may be of value for those on nonsteroidal anti-inflammatory drugs.(11)

Bilberry extract was found in a laboratory animal study to decrease plasma ALT levels in stress-induced liver damage.(27) In addition, Bilberry extracts increased glutathione (GSH) and vitamin C levels and significantly decreased MDA and nitric oxide (NO) levels in the liver tissue, suggesting Bilberry extract plays an important role in antioxidant protection against restraint stress-induced liver damage by both scavenging free radical activity and inhibiting lipid peroxidation. Laboratory animal studies have also reported that Bilberry extracts may decrease oxidative stress markers in the brain, along with altering dopamine neurotransmitter levels, suggesting Bilberry’s potential  usefulness for the treatment of cerebral disorders related to oxidative stress.(28),(29) The antioxidant effects of Bilberry have also been reported in a laboratory study to have nephroprotective effects, normalizing serum BUN and creatinine to normal levels and decreased kidney malondialdehyde (MDA), nitric oxide (NO), and xanthine oxidase (XOD) levels.(30)

Eye health activity

With age, oxidative stress due to free radicals increases in some people more than in others. This damage to ocular tissues may lead to various eye pathologies. If it improves the oxygenation of tissue, Bilberry may show promise in the areas of prevention for diabetic retinopathy, minimizing the advance of macular degeneration, and arresting cataract progression.(13),(14) A human study of Bilberry’s activity on night visual acuity and contrast sensitivity reported that 160mg 3 times daily (containing 25% anthocyanosides per dose) did not improve this condition when compared to placebo.(15)

 

A laboratory study found that Bilberry extract may be beneficial for the physiological renewal and homeostasis of corneal epithelial cells.(31) An in vitro study found that Bilberry extract significantly reduced UVA-stimulated ROS formation in keratinocytes., along with preventing or reducing UVA-caused lipid peroxidation and depletion of intracellular glutathione.(32) Another laboratory study reported that Bilberry extract significantly inhibited SIN-1-induced neurotoxicity and free radical activation when given intravenously, supporting the antioxidative mechanism of Bilberry in retinal diseases.(33) In a laboratory study, Bilberry was found to be effective against retinal diseases involving angiogenesis.(34)

 

Cardiovascular activity

Flavonoids including anthocyanosides from Bilberry have been reported to be effective against cardiovascular disease, including vascular health and cholesterol balance.(22),(35) The anthocyanosides of Bilberry are also reported effective in promoting and enhancing arteriolar rhythmic diameter changes, which play a role in the redistribution of microvascular blood flow and interstitial fluid formation.(23) A laboratory study also found that Bilberry exerts ACE inhibiting effects.(25)

A small clinical study found that supplementation with Bilberry juice resulted in significant decreases in plasma concentrations of C-reactive protein (CRP), interleukin (IL)-6, IL-15, and monokine induced by INF-gamma (MIG).(36) However, the study also reported an increase in the plasma concentration of tumor nuclear factor-alpha (TNF-alpha).

Bilberry leaf extract may also be effective in helping control blood cholesterol levels. One in-vitro study reported the antioxidative potential of this extract on human LDL cholesterol.(16) The results demonstrated that Bilberry leaf may exert a protective action on LDL cholesterol particles during in vitro copper-mediated oxidation. An animal study in rats reported that a Bilberry leaf extract decreased plasma triglycerides by 39% following treatment, claiming that Bilberry leaf extract is comparable to ciprofibrate in lowering triglycerides.(17) Both agents reduced triglyceride levels of rats on hyperlipidemic diets in a dose-dependent fashion. Unlike ciprofibrate, Bilberry leaf failed to prevent a rise in plasma triglycerides elicited by fructose and did not affect free fatty acid levels.

Anthocyanosides reportedly inhibit platelet aggregation.(10) Platelet aggregation tendencies relate to atherosclerotic and blood clotting tendencies.

Other activity

Literature reviews have indicated that Bilberry may also have a potential beneficial role in treating chronic fatigue syndrome.(12)

Other uses of Bilberry include diabetes and cancer support.(18) Research has also reported that the proanthocyanidins isolated from Bilberry have exhibited anti-carcinogenic activity in- vitro.(19),(20) A small clinical study found that Bilberry anthocyanins decreased tumor growth in patients with colorectal cancer.(37) Bilberry extract was also found in a laboratory study to have protective potential against the antineoplastic drug 5-fluorouricil (5-FU)-induced myelotoxiciy and/or the ability to enhance the chemotherapeutic effectiveness of 5-FU.(24) Alterations in the capillary filtration of macromolecules are well documented in diabetic patients and experimental diabetes.(21) A laboratory study found that Bilberry extract activates AMP-activated protein kinase (AMPK) leading to a significant reduction in blood glucose concentration and enhancing insulin sensitivity.(38)

It should be noted that many of the reports of Bilberry’s activity against hypercholesterolemia and capillary fragility in diabetes was performed on the flavonoids in the leaf extract, but the berry also has a high quantity of these flavonoids.

References

  1. Salvayre R, et al. Comparison of the Scavenger Effect of Bilberry Anthocyanosides with Various Flavanoids. Proc Intern Bioflav Symp. 1981:437-42.
  2. View Abstract: Nyman NA, Kumpulainen JT. Determination of anthocyanidins in berries and red wine by high-performance liquid chromatography. J Agric Food Chem. Sep2001;49(9):4183-7.
  3. Jayle GE, et al. Study Concerning the Action of Anthocyanoside Extracts of Vaccinium myrtillus on Night Vision. Ann Ocul. Paris. 1965;198(6):556-62.
  4. Morazonni P, et al. Vaccinium myrtillus. Fitoterapia. 1996; vol. LXVII, no. 1:3-29.
  5. PDR for Herbal Medicines, 2nd edition. Montvale, NJ: Medical Economics Company; 2000:77.
  6. View Abstract: Morazzoni P, et al. Vaccinium myrtillus Anthocyanosides Pharmacokinetics in Rats. Arzneim-Forsch/Drug Res. 1991;41(2):128-31.
  7. View Abstract: Lietti A, Cristoni A, Picci M. Studies on Vaccinium myrtillus Anthocyanosides. I. Vasoprotective and Antiinflammatory Activity. Arzneimittelforschung. 1976;26(5):829-32.
  8. Jonadet M, et al. Anthocyanosides Extracted from Vitis vinifera, Vaccinium myrtillus and Pinus maritimus, I. Elastase-inhibiting Activities in Vitro, II. Compared Angioprotective Activities in Vivo. J Pharm Belg. 1983;38(1):41-46.
  9. View Abstract: Detre Z, et al. Studies on Vascular Permeability in Hypertension: Action of Anthocyanoside. Clin Physiol Biochem. 1986;4(2):143-49.
  10. Bottecchia D, et al. Vaccinium myrtillus. Fitoterapia. 1977;48:3-8.
  11. Wichtl M, in Bisset NA, ed. Herbal Drugs and Phytopharmaceuticals. Stuttgart: Scientific Press; 1994: 351-52.
  12. View Abstract: Logan AC, Wong C. Chronic fatigue syndrome: oxidative stress and dietary modifications. Altern Med Rev. Oct2001;6(5):450-9.
  13. Bonanni R, et al. Clinical Study of the Action of Myrtillis Alone or Associated with Betacarotene on Normal Subjects and on Patients with Degenerative Changes of the Fundus Oculi. Atti Accad Fisiocrit Siena. 1968; 17(2):1470-88.
  14. View Abstract: Varma SD, et al. Diabetic Cataracts and Flavonoids. Science. 1977;195:205-06.
  15. View Abstract: Muth ER, et al. The effect of bilberry nutritional supplementation on night visual acuity and contrast sensitivity. Altern Med Rev. Apr2000;5(2):164-73.
  16. View Abstract: Laplaud PM, Lelubre A, Chapman MJ. Antioxidant Action of Vaccinium myrtillus Extract on Human Low Density Lipoproteins In Vitro: Initial Observations. Fundam Clin Pharmacol. 1997;11(1):35-40.
  17. View Abstract: Cignarella A, Nastasi M, Cavalli E, et al. Novel Lipid-lowering Properties of Vaccinium myrtillus L. Leaves, A Traditional Antidiabetic Treatment, in Several Models of Rat Dyslipidaemia: a Comparison with Ciprofibrate. Thromb Res. Dec1996;84(5):311-22.
  18. View Abstract: Katsube N, Iwashita K, Tsushida T, Yamaki K, Kobori M. Induction of Apoptosis in Cancer Cells by Bilberry (Vaccinium myrtillus) and the Anthocyanins. J Agric Food Chem. Jan2003;51(1):68-75.
  19. View Abstract: Bomser J, Madhavi DL, Singletary K, et al. In Vitro Anticancer Activity of Fruit Extracts from Vaccinium Species. Planta Med. Jun1996;62(3):212-6.
  20. Seeger PG. The Anthocyans of Beta vulgaris var. rubra (red beets), Vaccinium myrtillis (whortleberries), Vinum rubrum (red wine) and Their Significance as Cell Respiratory Activators for Cancer Prophylaxis and Cancer Therapy. Arztl Forsch. Feb1967;21(2):68-78.
  21. View Abstract: Vervoort G, Lutterman JA, Smits P, et al. Transcapillary Escape Rate of Albumin is Increased and Related to Haemodynamic Changes in Normo-albuminuric Type 1 Diabetic Patients. J Hypertens. Dec1999;17(12 Pt 2):1911-6.
  22. View Abstract: Cohen-Boulakia F, Valensi PE, Boulahdour H, et al. In Vivo Sequential Study of Skeletal Muscle Capillary Permeability in Diabetic Rats: Effect of Anthocyanosides. Metabolism. Jul2000;49(7):880-5.
  23. View Abstract: Colantuoni A, Bertuglia S, Magistretti MJ, et al. Effects of Vaccinium myrtillus Anthocyanosides on Arterial Vasomotion. Arzneimittelforschung. Sep1991;41(9):905-9.
  24. Choi EH, Ok HE, Yoon Y, Magnuson BA, Kim MK, Chun HS. Protective effect of anthocyanin-rich extract from Bilberry (Vaccinium myrtillus L.) against myelotoxicity induced by 5-fluorouracil. Biofactors. 2007;29(1):55-65.
  25. Persson IA, Persson K, Andersson RG. Effect of Vaccinium myrtillus and its polyphenols on angiotensin-converting enzyme activity in human endothelial cells. J Agric Food Chem. 10 Jun 2009;57(11):4626-4629.
  26. Zafra-Stone S, Yasmin T, Bagchi M, Chatterjee A, Vinson JA, Bagchi D. Berry anthocyanins as novel antioxidants in human health and disease prevention. Mol Nutr Food Res. Jun 2007;51(6):675-683. Review.
  27. Bao L, Yao XS, Yau CC, Tsi D, Chia CS, Nagai H, Kurihara H. Protective effects of Bilberry (Vaccinium myrtillus L.) extract on restraint stress-induced liver damage in mice. J Agric Food Chem. 10 Sep 2008;56(17):7803-7807. Epub 2008 Aug 9.
  28. Yao Y, Vieira A. Protective activities of Vaccinium antioxidants with potential relevance to mitochondrial dysfunction and neurotoxicity. Neurotoxicology. Jan 2007;28(1):93-100. Epub 2006 Jul 31.
  29. Rahman MM, Ichiyanagi T, Komiyama T, Sato S, Konishi T. Effects of anthocyanins on psychological stress-induced oxidative stress and neurotransmitter status. J Agric Food Chem. 27 Aug 2008;56(16):7545-7550. Epub 2008 Jul 29.
  30. Bao L, Yao XS, Tsi D, Yau CC, Chia CS, Nagai H, Kurihara H. Protective effects of Bilberry (Vaccinium myrtillus L.) extract on KBrO3-induced kidney damage in mice. J Agric Food Chem. 23 Jan 2008;56(2):420-425. Epub 2007 Dec 20.
  31. Song J, Li Y, Ge J, et al. Protective effect of Bilberry (Vaccinium myrtillus L.) extracts on cultured human corneal limbal epithelial cells (HCLEC). Phytother Res. 2010; Epub ahead of print].
  32. Svobodová A, Rambousková J, Walterová D, Vostalová J. Bilberry extract reduces UVA-induced oxidative stress in HaCaT keratinocytes: a pilot study. Biofactors. 2008;33(4):249-266.
  33. Matsunaga N, Imai S, Inokuchi Y, Shimazawa M, Yokota S, Araki Y, Hara H. Bilberry and its main constituents have neuroprotective effects against retinal neuronal damage in vitro and in vivo. Mol Nutr Food Res. Jul 2009;53(7):869-877.
  34. Matsunaga N, Chikaraishi Y, Shimazawa M, Yokota S, Hara H. Vaccinium myrtillus (Bilberry) Extracts Reduce Angiogenesis In Vitro and In Vivo. Evid Based Complement Alternat Med. 27 Oct 2007. [Epub ahead of print].
  35. Mauray A, Milenkovic D, Besson C, Caccia N, Morand C, Michel F, Mazur A, Scalbert A, Felgines C. Atheroprotective effects of Bilberry extracts in apo E-deficient mice. J Agric Food Chem. 9 Dec 2009;57(23):11106-11111.
  36. Karlsen A, Paur I, Bøhn SK, Sakhi AK, Borge GI, Serafini M, Erlund I, Laake P, Tonstad S, Blomhoff R. Bilberry juice modulates plasma concentration of NF-kappaB related inflammatory markers in subjects at increased risk of CVD. Eur J Nutr. 2 Feb 2010. [Epub ahead of print]
  37. Thomasset S, Berry DP, Cai H, et al. Pilot study of oral anthocyanins for colorectal cancer chemoprevention. Cancer Prev Res. 2009;2(7):625-633.
  38. Takikawa M, Inoue S, Horio F, Tsuda T. Dietary Anthocyanin-Rich Bilberry Extract Ameliorates Hyperglycemia and Insulin Sensitivity via Activation of AMP-Activated Protein Kinase in Diabetic Mice. J Nutr. 20 Jan 2010. [Epub ahead of print]

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