Wednesday, June 5, 2024

Review: Bilberry Health Benefits

INTRODUCTION

genus Vaccinium; family Ericaceae; species Vaccinium myrtillus L

Bilberry or European blueberry is a low-growing shrub. Bilberry grows abundantly in the mountainous areas of Europe. Bilberry has sharp edged, green branches and black wrinkled berries. Bilberry is closely related to American Blueberry. Bilberry grows in very acidic, nutrient-poor soils throughout the temperate and subarctic regions of the world. Bilberry has a creamy white meat.  Bilberry fruit is smaller and darker than that of blueberry.

Bilberry may has a wide range of health benefits. It is suggested to improve night vision; there is a story that bilberry was used by pilots in World War II to use improve night vision. [10, 3, 19] However, a recent study suggests that consumption of bilberry may not have such effects. On the other hand, probably because it is rich in antioxidants, it may have many other health benefits, related to its high antioxidant contents. First, bilberry fruits contain tannins. Thus, it may help treat diarrhea, sore throat, and mouth inflammations. [18] Further, Bilberry contains various anthocyanosides, which may fortify blood vessel walls, improve blood flow and maintain good circulation. They may also strengthen collagen to maintain healthy connective tissue. [19] It is known that potassium bromate an oxidizing agent used as a food additive, may cause kidney damage by the generation of oxygen free radicals. In a study, researchers found five-day oral administration of bilberry extract at dosages of 50, 100, and 200 mg/kg resulted in a reversal in serum BUN and creatinine to normal levels and decreased kidney malondialdehyde, nitric oxide, and xanthine oxidase levels. Further, bilberry extract/supplement improved oxygen radical absorbance capacity levels in kidney tissue. [29]

Bilberry has been used in many food products, such as jams, pies, cobblers, and cakes. Bilberry tea is also available. To prepare bilberry jam, combine 3 lb. of bilberry fruit with 1.5 lb of sugar and 1 cup of water. Boil for 40 minutes. [18]

Bilberry extracts are made from bilberries; the fruit of the bilberry plant. The bilberries are extracted and concentrated to fortify the anthocyanins levels. Anthocyanins are the coloring agents in the skin and juice of the bilberry. These bilberry anthocyanins are flavonoids.

POTENTIAL BILBERRY HEALTH BENEFITS - RESEARCH FINDINGS

Bilberry is one of the most frequently suggested herbal remedies in Italy.[10] Bilberry may possess of various potential health benefits. Moderate consumption of bilberry extract may have the benefits of lowering the risk of cardiovascular disease or improving  visual functions and improving night vision. Bilberry fruits have been traditionally used as an astringent, and a remedy for diarrhoea, discharges, dysentery, scurvy and urinary issues. A decoction of bilberry leaves or bark of its root is traditionally used for ulcers in the mouth and throat.  [18] Bilberry extracts have been thought to have benefits of capillaries strengthening. Some people even call bilberry - a circulatory micro-plumber. Anyway, their primary use is for eye health and vision, microcirculation, spider veins and varicose veins. In this section, we are going to review the research findings regarding to bilberry health benefits.

Anti-oxidative Activities

Bilberry anthocyanins are antioxidants, these antioxidants contribute the health benefits of bilberry. Bilberry anthocyanins protect cells from damage caused by free radicals. Bilberry anthocyanins are believed to have specific effects on both the blood vessels and on the blood cells. Through bilberry action, the capillaries become better for stretching. Blood flow increases and red blood cells can deform easily into a shape to pass through very narrow capillaries.

The antioxidant protection toward lipid oxidation was best provided by lingonberry and bilberry phenolics followed by black currant and raspberry phenolics. Bilberry phenolics exhibited very good overall antioxidant activity toward protein oxidation. In bilberries, anthocyanins contributed the most to the antioxidant effect by inhibiting the formation of both hexanal and protein carbonyls. [11] Twelve major bilberry anthocyanins have been identified that could react with nitric oxide (N)) and peroxynitrite (ONOO-) using capillary zone electrophoresis. [12]

Reducing Risks of Atherosclerosis

Anthocyanosides may strengthen blood vessels, improve circulation, and prevent the oxidation of LDL ("bad") cholesterol, cholesterol is a major risk factor for atherosclerosis. Atherosclerosis may lead to heart attack and stroke.

A study of 55 healthy subjects suggests that anthocyanin supplementation exerts anti-atherogenicity effects by improving cardiometabolic risk factors and reducing thrombogenicity in a metabolic syndrome population. [B1]

Reducing Risks of Cancers

Bilberry extract contains anthocyanins and these chemicals allows bilberry possess of anticancer activity. Three mechanisms for bilberry's anti-tumor activities: (1) antioxidation (2) anticarcinogensis and (3) apoptosis induction of tumor cells may be involved. [3] In vitro study, bilberry extract was effective to inhibit the growth of HL60 human leukemia cells and HCT116 colon carcinoma cells. Bilberry extract contains a large amount of anthocyanins. Pure delphinidin and malvidin (isolated from the bilberry) induced apoptosis in HL60 cells while delphinidon and the glycoside (isolated from the bilberry extract) inhibited the growth of HCT116 cells [4]. Some other studies also demonstrated the anti-cancer activities of bilberry. [5]. Bilberry extracts were shown to inhibit the growth of colon-cancer-derived HT-29 cells. [6] Bilberry was shown to sinhibit both H2O2 as well as TNF alpha induced VEGF expression by the human keratinocytes. [13]

Reducing Risks of Chronic Venous Insufficiency

This condition occurs when valves in veins in the legs that carry blood to the heart are damaged. Researchers have studied the potential benefits of bilberry extracts on circulatory insufficiency. Clinical trials have shown bilberry's effectiveness on venous insufficiency of the lower limbs. Bilberry induced increase both in flexibility of the capillaries, bilberry restored normal blood flow. [23, 24] Another study demonstrated bilberry extract was
able to treat varicose veins in the legs. [25] Subjects treated with bilberry test demonstrated improvement in varicose syndrome such as cramps, heaviness, swelling of the calf and ankle etc.

Reducing Risks of Chronic Allergic Contact Dermatitis

In a study, BALB/c mice with chronic allergic contact dermatitis induced by 3 weeks of repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB) were administered Bilberon-25 (a bilberry extract) orally for 3 weeks after sensitization with TNCB. TNCB is a chemical causing pruritus and inflammation. Treatment with the bilberry extract significantly attenuated the TNCB-induced increase in scratching behaviour, but dexamethasone did not. In contrast, ear swelling was ameliorated by dexamethasone treatment, and significantly decreased by the bilberry extract. Thus, anthocyanins from bilberry may have health benefits of treating chronic pruritus which can occur in patients suffered from inflammatory skin
diseases such as atopic dermatitis. [A3] It is nice to see the bilberry extract worked better than dexamethasone in the study, but more studies are needed to support the health claim.

Reducing Risks of Diabetes Mellitus

Blberry may benefit diabetic patients, by preventing the complications of diabetes mellitus. [17] Animal studies suggest bilberry may have benefits for managing blood sugar levels. However, more research is needed.

Reducing Risks of Infections

Bilberry fruits contain antimicrobial compounds, eg phenolics and organic acids, intake of bilberry may benefit people at risk of certain infections. Bilberry possesses activities against Salmonella and Staphylococcus. [9] Bilberry extract may have inhibitory effect on Helicobacter pylori growth in in vitro studies. [8]

Reducing Risks of Macular degeneration and Cataracts

Cataracts and macular degeneration remain the major cause of blindness and acuity of vision deterioration in the elderly. Both pathology have been attributed to damage by free radicals, there has been a great deal of interest in antioxidants. Bilberry's flavonoids are known as potent antioxidants, scavenging free radicals and used for multiple age-related ocular disorders. Thus, bilberry may have health benefits on these conditions. In a study of OXYS rats, rats were given control diets or those supplemented with 25% bilberry extract (dosage- 20 mg on kg of body weight including 4.5 mg of antocianidin) or vitamin E (dosage- 40 mg/kg). The testing at 3 month have showed that more then 70% of control OXYS rats had cataract and macular degeneration while the supplementation of bilberry extract completely prevented impairments in the lenses and retina. [A2] This study does suggests the potential health benefits of bilberry on certain eye conditions, but more studies are needed to confirm the results.

Memory

Epidemiological studies suggest that diets with a high intake of vegetables and fruits may reduce the incidence of degenerative disorders including Alzheimer's disease. In a study of rats, prolonged administration of blueberry / bilberry at dosage of 3.2 mg kg(-1)day (oral), of the anthocyanins significantly enhanced short-term memory, but not long-term memory in cognitive performance using step-down inhibitory avoidance, open field, elevated plus-maze, and radial maze tasks. Another interesting finding was that lyophilised bilberry/blueberry improved working memory in the radial maze, with significant differences observed during earlier sessions.  These results suggest that lyophilised bilberry / blueberry may have health benefit of preventing memory deficits, one of the symptoms related to Alzheimer's disease. However, more studies are needed to verify this health benefit claim. [A1]

NIGHT VISION (EYE)

People always say, "Bilberry is good for eye." How does bilberry benefit our eye? Cells taken up bilberry anthocyanins could modulate adverse effects of pyridinium bisretinoid A2E. Pyridinium bisretinoid A2E is an autofluorescent pigment; it accumulates in retinal pigment epithelial cells with age and in some retinal disorders. It can mediate a detergent-like perturbation of cell membranes and light-induced damage to the cell. [7] Bilberry may also benefit cataract and glaucoma patients. [14]. While, some researchers couldn't find any effect of bilberry on eye nor draw a conclusion about bilberry's effect on eye [1,2]

Retina Inflammation

In a study, researchers generated a mouse model of endotoxin-induced uveitis (EIU) that shows retinal inflammation, as well as uveitis, by injecting lipopolysaccharide. We pretreated the mice with anthocyanin-rich bilberry extract and analyzed the effect on the retina. Anthocyanin-rich bilberry extract prevented the impairment of photoreceptor cell function, as measured by electroretinogram. [A4]


ABSORPTION OF BILBERRY ANTHOCYANINS

The maximum plasma concentration of total bilberry anthocyanins happens within 1.5 hr after ingestion of bilberry anthocyanins in 4 healthy elderly women. [22] Bilberry anthocyanins are efficiently absorbed from the small in rats. [16] Bilberry anthocyanins are also efficiently absorbed in anesthetized rats. [21]

BILBERRY DEGRADATION IN PROCESSING

Processing can degrade the quercetin in bilberry seriously. Quercetin content decreased markedly (40%) in bilberries during 9 months of storage at 20 C. [15]

DOSAGE OF BILBERRY EXTRACTS

Based on most commercial bilberry products, the standardized bilberry extract contains 36% bilberry anthocyanosides. The dosage is usually from 160 to 320 mg of bilberry extract. However, the website of University of Maryland suggests dosage of 80-120 mg daily of bilberry extract (25% anthocyanidin) for general purpose.

BILBERRY SIDE EFFECTS....

Bilberry side effects can be serious. Bilberry possesses anti-platelet activity, it may interact with NSAIDs, particularly aspirin. [26] Excessive drinking bilberry juice may cause diarrhea. [27] One study of 2295 people given bilberry extract found a 4% incidence of side effects or adverse events. Further, bilberry side effects may include mild digestive distress, skin rashes and drowsiness. [20] Chronic uses of the bilberry leaf may lead to serious side effects. High doses of bilberry leaf can be poisonous.

Statement

The information is for reference only, more studies are needed to support the health claims. It is not a medical advice. Please consult with your medical doctor before starting any supplements. 

REFERENCES

1. Muth et al, The effect of bilberry nutritional supplementation on night visual acuity and contrast sensitivity, Altern Med Rev. 2000 Apr;5(2):164-73. 
2. Canter et al. Anthocyanosides of Vaccinium mrtillus (bilberry) for night vision-a systematic review of placebo-controlled trials. 2004Jan-Feb;49(1):38-50.
3. Hou DX, Potential Mechanisms of Cancer Chemoprevention by Anthocyanins, Curr Mol Med. 2003 Mar,3(2):149-59.
4. Katsube et al Induction of apoptosis in cancer cells by Bilberry (Vaccinium myrtillus) and the anthocyanins., J Agric Food Chem. 2003 Jan 1;51(1):68-75. 
5. Bomser et al, In vitro anticancer activity of fruit extracts from Vaccinium species, Planta Med. 1996 Jun;62(3):212-6. 
6. Zhao C et al, Effects of commercial anthocyanin-rich extracts on colonic cancer and nontumorigenic colonic cell growth, J Agric Food Chem. 2004 Oct 6;52(20):6122-8. 
7. Jang YP et al, Anthocyanins Protect Against A2E Photooxidation and Membrane Permeabilization in Retinal Pigment Epithelial Cells, Photochem Photobiol. 2005 Dec 1. 
8. Chatterjee A et al, Inhibition of Helicobacter pylori in vitro by various berry extracts, with enhanced susceptibility to clarithromycin, Mol Cell Biochem. 2004 Oct;265(1-2):19-26. 
9. Puupponen-Pimia R et al, Bioactive berry compounds-novel tools against human pathogens, Appl Microbiol Biotechnol. 2005 Apr;67(1):8-18. Epub 2004 Dec 2. 
10. Cicero AF et al, What do herbalists suggest to diabetic patients in order to improve glycemic control? Evaluation of scientific evidence and potential risks. Acta Diabetol. 2004
Sep;41(3):91-8. 
11. Viljanen K et al, Inhibition of protein and lipid oxidation in liposomes by bilberry phenolics, J Agric Food Chem. 2004 Dec 1;52(24):7419-24.
12. Ichiyanagi T et al, Simultaneous comparison of relative reactivities of twelve major anthocyanins in bilberry towards reactive nitrogen species, Chem Pharm Bull (Tokyo). 2004 Nov;52(11):1312-5. 
13 Roy S, Anti-angiogenic property of edible bilberries, Free Radic Res. 2002 Sep;36(9):1023-31.
14. Head KA, Natural therapies for ocular disorders, part two: cataracts and glaucoma, Altern Med Rev. 2001 Apr;6(2):141-66. 
15. Influence of domestic processing and storage on flavonol contents in bilberries  J Agric Food Chem. 2000 Jul;48(7):2960-5. 
16. Talavera S et al, Anthocyanins are efficiently absorbed from the small intestine in rats, J Nutr. 2004 Sep;134(9):2275-9. 
17. Savickiene N et al, Importance of biologically active components and plants in
the prevention of complications of diabetes mellitus, Medicina (Kaunas). 2002;38(10):970-5. 
18. Bilberry, Botanical.com, A Modern Herbal by Mrs. M. Grieve, April 21, 2005. 
19. Wholehealthmd.com, April 21, 2005. 
20. Eandi M. Post Marketing Investigation on TegensW preparatin with respect to side effects. Unpublished resuts. Cited by Morazoni P et al, Vaccinium myrtillus Bilberry, Fitoterapia 1996;67:3-19. 
21. Talavera S. found that bilberry anthocyanins are efficiently absorbed in anesthetized rats. J Nutr. 2003 Dec;133(12):4178-82. 
22. Cao G et al, Anthocyanins are absorbed in glycated forms in elderly women: a pharmacokinetic study. Am J Clin Nutr. 2001 May; 73(5):920-6. 
23. guerrini M. Report on clinical trial of bilberry anthocyanosides in the treatment of venous insufficiency of the lower limbs. Instituto di Patalogia Speciale Medica e Methodologia Clinica, Universita di Siena. 1987 
24. Corsi S. Report on trial of bilberry anthocyanosides (Tegens - Inverni delta Beffa) in the medical treatment of venous insufficiency of the lower limbs. Casa di Cura S. Chiara, Florence, Italy.
1987. 
25. Gatta L. Controlled clinical trial among patients designed to assess the therapeutic efficacy and safety of Tegens 160. Ospedale Filippo del Ponte, Varese, Italy 1982. 26. Herbal medication: potential for adverse interactions with analgesic drugs. Abebe W.  J Clin Pharm Ther. 2002 Dec;27(6):391-401. 
27. Hoekstra JH et al Fruit juice malabsorption: not only fructose. Acta Paediatr. 1995 Nov;84(11):1241-4. 
28. www.richters.com online publication Bilberry Poisonous? Conrad Richter, December 20, 1999. 
29. Bao L et al, Protective effects of bilberry (Vaccinium myrtillus L.) extract on KBrO3-induced kidney
damage in mice. J Agric Food Chem. 2008 Jan 23;56(2):420-5. Epub 2007 Dec 20 
A1 Ramirez MR, et al, Effect of lyophilised Vaccinium berries on memory, anxiety and locomotion in adult rats. Pharmacol Res. 2005 Dec;52(6):457-62. 
A2 Fursova AZh et al, Dietary supplementation with bilberry extract prevents
macular degeneration and cataracts in senesce-accelerated OXYS rats Adv Gerontol. 2005;16:76-9. 
A3 Yamaura K et al,, Anthocyanins from bilberry (Vaccinium myrtillus L.) alleviate pruritus in a mouse model of chronic allergic contact dermatitis. Pharmacognosy Res. 2011 Jul;3(3):173-7. 
A4  Miyake S et al, Vision preservation during retinal inflammation by anthocyanin-rich bilberry extract: cellular and molecular mechanism. Lab Invest. 2011 Sep 5.
B1. Anahita Aboonabi et al, Anthocyanins in berries exhibited anti-atherogenicity and antiplatelet activities in a metabolic syndrome population. Nutr Res. 2020 Apr:76:82-93.

Review: Melatonin Health Benefits and Side Effects

INTRODUCTION Melatonin (N-acetyl-5-methoxytryptamine [7]) is a lipophilic hormone, mainly produced and secreted at night by the  pineal glan...