BILBERRY

BACKGROUND

Ingredient Type: Botanical, Extract

Also Known As: European blueberry, Vaccinium myrtillus L., Hurtleberry, Optiberry, Airelle, Whortleberry, Huckleberry, Wineberry, Heidelberry, Dyeberry (1,2)

The bilberry plant is a deciduous, perennial shrub that is native to northern Europe, the northern United States, and Canada.  It currently grows wild in heaths, moors, and woods in most of Europe, northern Asia, and in the mountain and subalpine areas of western North America (3).  Bilberry grows 35-60cm in height and produces a fruit similar to the American blueberry.  The dried, ripe fruit contains tannins and several interesting anthocyanidin (anthocyanoside) constituents including cyanidin, delphinidin, peonidin, petunidin, malvidin, and others (2).

The modern use of bilberry in the treatment of various visual disorders dates to World War II.  British Royal Air Force pilots reported that the ingestion of bilberry jam just prior to missions seemed to improve their vision.  Poor-quality studies during the 1960s and 1970s purportedly supported these claims.  Recently, there have been several open trials and some randomized trials in the European literature investigating the use of bilberry in treating and preventing various visual disorders (4). 

TRADITIONAL USES

Bilberry’s medicinal use was described by the 12th Century German herbalist Hildegard von Bingen (1098-1179), who purportedly recommended it for the induction of menses.  Herbalists in the 1700s reported its use as well.  Decoctions of the dried fruit have a long history of oral use to treat diarrhea and of topical use to treat mild inflammation of the mouth and mucous membranes.  Bilberry preparations have also been used to help stop the flow of breast milk and as a treatment for urinary complaints, including nephrolithiasis and urinary tract infections.  Tea made from bilberry leaves has also been used medicinally, mainly for the management of diabetes mellitus (5).   

Today, bilberry extracts are used in natural medicinal practices as prophylaxis against cataracts, diabetic retinopathy, glaucoma, macular degeneration, and impaired night vision.  Some European surgeons also use the extract from the plant to promote surgical wound healing (2). 

WHAT DOES SCIENCE TELL US?

  Bilberry Probably Does Not Improve Night Vision:

Two double-blind, placebo-controlled, crossover studies indicate that bilberry may have no effect on night vision. In one study, 15 young men with good vision consumed 160mg bilberry extract three times per day for 21 days and experienced no changes in night vision (6).

In the second study, 195 healthy participants with impaired night and twilight vision ingested 160mg/day standardized bilberry extract for 28 days. No significant differences were observed from baseline to the end of the trial between the treatment and placebo group. The few significant treatment results which occurred (p<0.05) such as improvements in visual acuity and initial pupil diameter proved to be contradictory, suggesting the effect of simple chance on the results. It is noteworthy that the contradictory and inconclusive results of this study may be due to a lack of methodological sensitivity, and the use of a low dosage of bilberry (7).

  Bilberry Might Support Eye Health:

There is mixed evidence on the benefits of bilberry to eyesight. Some studies suggest that the fruit may improve symptoms of myopia, eye fatigue, and the functional vision of patients with Normal Tension Glaucoma (NGT). 

400mg/day fermented bilberry extract was ingested by 30 healthy myopic middle-aged participants in a 4-week prospective, randomized, placebo-controlled study. A post-treatment decrease was observed in the mesopic area under the log (AUL) contrast sensitivity function from 1.04±0.16 to 1.13±0.17 (p=0.009). The mean amplitude of accommodation also increased, from 4.62±1.88 D before treatment, to 5.33±2.03 D (p=0.002) (8). This suggests that bilberry may be effective in improving the visual outcomes of myopic eyes.

A bilberry anthocyanin extract (60mg/capsule twice daily) was consumed by 332 subjects, either normal or with a diagnosis of normal tension glaucoma (NGT) in a retrospective study lasting 6 to 53 months with an average of 24.32±10.43 months. For the 132 subjects in the bilberry group, the post-treatment average of best-corrected visual acuity underwent a beneficial decline from 0.16 (±0.34) to 0.11 (±0.18) logMAR units (p=.008). The average deviation of the Humphrey Visual Field test also saw an improvement from -6.44 (±7.05) to -5.34 (±6.42) (p=.001). These results indicate that bilberry anthocyanin may improve functional vision in normal tension glaucoma (9).

In a prospective, randomized, double-blind, placebo-controlled study, 80 office workers who used acute video display terminals (VDTs) ingested three 160mg bilberry extract capsules daily for 8 weeks. Typically, office workers exposed to VDTs experience reductions in critical flicker fusion (CFF) and near point accommodation (NPA). With the use of the bilberry capsules, the decline in CFF was reduced (p=0.023). Reductions in ocular pain, foreign body sensation, eye heaviness, ocular fatigue sensation and uncomfortable sensation were significantly higher in the treatment group at week 8 (p<0.05) as compared to the placebo group (10).

  Bilberry Possibly Helps Support a Healthy Digestive Tract:

In an open, prospective, non-blinded and non-controlled pilot trial, 13 patients with mild to moderate ulcerative colitis consumed 160g Symrise bilberry preparation per day (equivalent to 600g fresh bilberry) for 6 weeks. 63.4% of subjects went into remission after 6 weeks of treatment, and a total of 90.9% responded to the treatment. A decrease in the Mayo score indicating the severity of ulcerative colitis was also observed at week 7 (p<0.001). At the end of treatment, 4 patients realized undetectable levels of faecal calprotectin while overall faecal calprotectin levels were significantly reduced in all participants (baseline: mean 778 μg/g, range 192-1790 μg/g; end of treatment: mean 305 μg/g, range <30-1586 μg/g; p=0.049). However, on the discontinuation of the treatment, increases were observed for both faecal calprotectin and the activity of ulcerative colitis (11).

  Bilberry Might Help Reduce Inflammation:

There is consistent evidence supporting the alleviating effect of bilberry consumption on inflammation. In ¾ studies, bilberry was used as a stand-alone treatment, while in the 4th, the bilberry treatment included the consumption of fish and whole-grain cereals.

In a randomized, controlled dietary intervention, 27 participants ate 400g/day fresh bilberries for 8 weeks. Inflammation scores decreased significantly in the treatment group as compared to the control group (p=0.024). Decreases were also observed in the expression of chemoreceptors associated with the function of macrophage- and monocyte-associated genes. Additional effects were observed for cytoplasmic ribosomal proteins, toll-like receptor signaling, and B-cell receptor pathways (12).

An undisclosed quantity of bilberry juice was consumed by 62 subjects in a 4-week randomized controlled trial investigating the effect of bilberry on inflammatory biomarkers. In the bilberry group, increases were observed for the plasma concentration of tumor nuclear factor-α, p-coumaric acid, and Plasma quercetin. Decreases were observed in the plasma concentrations of interleukin, C-reactive protein, and monokine induced by INF-γ (13).

In another randomized controlled trial, 24 gingivitis patients not receiving standard treatment ingested 250mg or 500mg bilberries for 7 days. Levels of the inflammation biomarkers cytokines were reduced by 41% in the group consuming 250mg bilberries, by 59% in the 500mg bilberries group, by 31% in the placebo group, and by 58% in the reference group using standard gingivitis treatment. A significant decline in the cytokines IL-6 (p=0.012), IL-1b (p=0.025), and VEGF (p=0.017) was observed in the gingival cervicular fluid of the treatment group ingesting 500mg/day bilberries. No other group achieved a significant decrease in cytokine levels (14).

As previously indicated, bilberry has also been studied in combination with other ingredients, yielding positive anti-inflammatory results. In a double-blind, randomized, parallel-group, and placebo-controlled trial, 44 overweight or obese subjects with impaired glucose metabolism consumed 300g/day fresh bilberries along with 100-150g fish thrice weekly, and cereals that were at least 50% whole-grain. After this 12-week trial a decline was observed in Plasma E-selectin (a biomarker of inflammatory response), associated with an increase in fiber intake and the plasma concentration of very-long-chain n-3 fatty acids (p<0.05) (15).

  Bilberry Possibly Support Balanced Cholesterol Levels:

The action of bilberry on cardiovascular (CVD) risk was evaluated in a pre-post dietary intervention. 150g frozen bilberries were consumed thrice weekly over 6 weeks by 36 healthy volunteers. The male treatment group experienced the enhancement of γ-glutamyltransferase (p=.013), total cholesterol (p=.004), HDL-C(p=.009), albumin (p=.028), aspartate aminotransferase (p=.012), and glucose (p=.015). The male treatment group also experienced an increase in LDL-C (p=.007). The overall treatment group declines were achieved for glucose (p=.005), γ-glutamyltransferase (p=.046), LDL-C (p=.0347), albumin (p=.001), total cholesterol (p=.017), and triglycerides (p=.001) along with an enhancement in HDL-C (p=.044) (16).

  Bilberry Might Help Control Blood Sugar:

There is mostly consistent (7/9 studies) evidence suggesting that bilberry increases glycaemic control. It is important to note (5/7) studies supporting the use of bilberry for glycaemic control did not provide treatments in which bilberry was consumed in isolation. Rather, the bilberry treatments included other foods such as fish and bread (1,12,17,18,19,20,21,22,23).

A significant increase in fasting plasma insulin was observed (p=0.048) after a 33-35 days bilberry treatment in which 100g/day fresh bilberry was consumed by 110 female subjects in a randomized cross-over study design (19).

In a double-blind, crossover matched-pair trial, 8 men consumed 0.47 g Mirtoselect capsule, equivalent to approximately 50g fresh bilberries/day in a single dosage with a 2-week washout period followed by a trial reversion. Post-treatment, a significant decline in the incremental Area Under Curve (AUC) was observed for insulin (p=0.03) and glucose (p=0.003) (17).

In a 12-week randomized parallel controlled dietary intervention, 37 participants with impaired glucose metabolism experiencing 2 or more other symptoms of metabolic syndrome ate 300g/day fresh bilberries along with 100-150g fish thrice weekly, and bread yielding a low postprandial glucose and insulin response. Decreases were observed in 2-hour postprandial glucose concentration and AUC for glucose (p<0.05). Increased insulin secretion and glucose disposal were also observed (18).

Within a randomized, controlled, single-blind cross-over study, 37.5g each of bilberry, strawberry, cranberry and black currants combined with 35g sucrose was consumed by 12 healthy participants in a 3-hour trial. There was a significant decline in post-treatment plasma glucose concentrations at 15 minutes (p<0.05) and 30 minutes (p<0.01) followed by a significant increase at 150 minutes (p<0.05) as compared to the placebo group. The maximum glucose concentration from baseline was smaller for the treatment group (1.0 mmol/l, p=0.002) and was achieved at 45 minutes, while the peak concentration for the control group was achieved at 30 minutes. At the 3-hour mark, there were no significant changes in the area under the curve for glucose concentration (21).

Contrary to these studies are 2 studies in which bilberry had no significant effect on glucose or insulin response. In one study, 400g/day fresh bilberry was consumed by 27 participants over 8 weeks in a randomized, controlled dietary intervention (12).  In the other study, 100g/day frozen bilberry was consumed by 80 overweight women for 33 to 35 days in a randomized crossover trial (1).

  Bilberry Possibly Has Antioxidant Properties:

The evidence supporting the effect of bilberry on antioxidant activities in inconclusive. Of the 3 studies on the topic, the 2 in support both provided bilberry mixed with other berries, while the opposing study is the only one to administer bilberry as a stand-alone treatment.

In a randomized parallel dietary intervention, 40 healthy 60-year-old men consumed 100g/day of alternating bilberries, blackcurrants, and lingonberries for 8 weeks. There was a significant increase in serum quercetin levels in the berry group as compared to the control group (p=0.039 with repeated measures ANCOVA). The average serum quercetin concentrations for the berry group was 32-51% higher than the control group over the trial period (24).

330ml of a 20% bilberry juice, 80% red grape juice drink; or 330 ml of a 20% bilberry puree, 80% red grape juice smoothie or a placebo juice was ingested by 30 healthy women for 14 days in a randomized cross-over study. The consumption of the berry juices lead to declines in the concentrations of urinary and plasma malondialdehyde (<0.001). Significant increases were observed for the Trolox equivalent antioxidant capacity for the smoothie (p<0.01) and the juice (p<0.001) trials, and both trials yielded increases in catalase activities and plasma levels of superoxide dismutase (p<0.001) as compared to the placebo group. No significant effect was observed for inflammatory biomarkers, plasma glutathione peroxidase, 8-OH-2-deoxyguanosine, and erythrocyte superoxide dismutase (25).

However, a single dose of 0.47g Mirtoselect capsule, (equivalent to approximately 50g fresh bilberries/day) yielded no significant effect between the treatment and control groups for the antioxidant responses of the ferric-reducing ability of plasma or the Trolox equivalent antioxidant capacity. The double-blind, crossover matched-pair trial was conducted on 8 male patients with type 2 diabetes or with impaired glucose tolerance (17).

  Bilberry Possibly Helps Reduce Blood Pressure:

There is contradictory evidence on the effect of bilberry on blood pressure. Two articles support the alleviating effect of bilberry, while a third suggests that bilberry increases blood pressure, while a fourth study indicates that bilberry has no significant effect on blood pressure. None of these four articles administered bilberry in isolation, but instead along with other foods such as gingko biloba or red grapes. Consequently, the results of the following studies should be evaluated with caution regarding the definite effect of bilberry consumption on blood pressure (26,27,28,29).

In a randomized, double-blinded, placebo-controlled trial, 134 healthy participants with high normal range blood pressure, or stage 1-2 hypertension ingested 500ml/day of MANA Blue, a polyphenol-enriched juice of bilberries (5.8%), chokeberries, cherries and red grapes over 12 weeks. A significant decline was experienced in systolic blood pressure as compared to the other treatment groups both for the entire study (6·9 and 3.4 mmHg; p= 0.01) and especially for the hypertensive patients (1.4 and 1.7 mmHg; p= 0·03). Since the effects of bilberry were not isolated in the analysis of this study, one should use caution in the evaluation of bilberry’s effect on blood pressure. No significant effects were observed for diastolic blood pressure (27).

A 60mg combination of bilberry, ginkgo biloba and quercetin, blended with 100mg green tea, 330mg grape extract, and 60mg resveratrol were administered daily to 18 hypertensive participants over 28 days in a double-blinded, placebo-controlled, crossover trial. The treatment yielded a trend towards a decline in average arterial pressure (p=0.052) as well as a 4.4mm Hg reduction in diastolic pressure (p=0.024). Post-treatment increases were observed in urinary nitrite and nitrate concentrations (p=0.022). No significant change was observed for systolic pressure (28).

In contrast to these results, no significant effect on blood pressure was observed in a double-blind, randomized, parallel-group, and placebo-controlled trial in which 20 participants with eye fatigue consumed 59mg/day anthocyanidin bilberry extract along with omega-3 fatty acid-rich fish oil (docosahexaenoic acid 783 mg/day, eicosapentaenoic acid 162 mg/day) and lutein (17.5 mg/day) collectively in the form of a soft gel capsule for 4 weeks (26).

Further contradiction may be found in a cohort study in which 9,732 participants used at least one of 37 supplements at least once per week over the prior year. The supplement list included bilberry, milk thistle, garlic and ginkgo biloba. Results indicate that a significantly higher average in both systolic and diastolic blood pressure was observed in users of bilberry (29).

SAFETY

Bilberry is generally considered safe for human consumption. The fruit of the plant is safe when ingested in typical quantities gained from food intake for short treatment trials. Amounts of fresh bilberry fruit administered daily in studies range from 100g (19) to 400g (12). The leaves of the plant, however, may be dangerous when orally consumed for long trials or in high doses (3).

Bilberry presented no adverse reactions in a randomized, controlled dietary intervention in which 400g/day fresh bilberries was ingested over 8 weeks (n=27) (12). Similar results were observed in a prospective, randomized, double-blind, placebo-controlled study in which 80 office workers who use acute video display terminals (VDTs) ingested 160mg/bilberry extract capsule, 3 times daily for 8 weeks (10).

Interactions:

Moderate

• Despite contrasting results, some studies indicate that bilberry is effective in increasing insulin response (18,19). Caution should, therefore, be exercised in diabetic patients being treated with insulin.
• Bilberry may reduce blood pressure (27,28), therefore patients at cardiovascular risk or with cardiovascular diagnoses taking treatment or blood thinners should inform their doctor of bilberry consumption due to possible mediation of drug effects.

Side-Effects:

• Dark blue to black discoloration of the tongue and faces
• Mild to moderate flatulence
• Mild heartburn (11)

REFERENCES

1. Larmo PS, Kangas AJ, Soininen P, et al. Effects of sea buckthorn and bilberry on serum metabolites differ according to baseline metabolic profiles in overweight women: a randomized crossover trial. Am J Clin Nutr. 2013;98(4):941-951. doi:10.3945/ajcn.113.060590
2. Ulbricht C, Basch E, Basch S, et al. An Evidence-Based Systematic Review of Bilberry ( Vaccinium myrtillus ) by the Natural Standard Research Collaboration. J Diet Suppl. 2009;6(2):162-200. doi:10.1080/19390210902861858
3. National Center for Complementary and Integrative Health. Bilberry | NCCIH. National Institutes of Health. https://nccih.nih.gov/health/bilberry. Published 2016. Accessed March 31, 2018.
4. Bilberry. https://www.webmd.com/vitamins/ai/ingredientmono-202/bilberry. Accessed June 26, 2018.
5. Hoffmann F, Manning M J. Herbal Medicine and Botanical Medical Fads. https://books.google.com/books?id=FovJAwAAQBAJ&pg=PA34&lpg=PA34&dq=bilberry+12th+Century+German+herbalist+Hildegard+von+Bingen&source=bl&ots=lM0EfpQAMT&sig=0pyaPCy6CRf2s82PPeyE3r5KHpM&hl=en&sa=X&ved=0ahUKEwjLgpPqhPTbAhWdGTQIHfliDO4Q6AEIOzAH#v=onepage&q&f=false. Accessed June 27, 2018.
6. Muth ER, Laurent JM, Jasper P. The effect of bilberry nutritional supplementation on night visual acuity and contrast sensitivity. Altern Med Rev. 2000;5(2):164-173.
7. Clinical Study Synopsis for Public Disclosure. https://trials.boehringer-ingelheim.com/public/trial_results_documents/1147/1147.2_U00-0049.pdf#page=1. Accessed March 31, 2018.
8. Kamiya K, Kobashi H, Fujiwara K, Ando W, Shimizu K. Effect of Fermented Bilberry Extracts on Visual Outcomes in Eyes with Myopia: A Prospective, Randomized, Placebo-Controlled Study. J Ocul Pharmacol Ther. 2013;29(3):356-359. doi:10.1089/jop.2012.0098
9. Shim SH, Kim JM, Choi CY, Kim CY, Park KH. Ginkgo biloba Extract and Bilberry Anthocyanins Improve Visual Function in Patients with Normal Tension Glaucoma. J Med Food. 2012;15(9):818-823. doi:10.1089/jmf.2012.2241
10. Ozawa Y, Kawashima M, Inoue S, et al. Bilberry extract supplementation for preventing eye fatigue in video display terminal workers. J Nutr Health Aging. 2015;19(5):548-554. doi:10.1007/s12603-014-0573-6
11. Biedermann L, Mwinyi J, Scharl M, et al. Bilberry ingestion improves disease activity in mild to moderate ulcerative colitis — An open pilot study. J Crohn’s Colitis. 2013;7(4):271-279. doi:10.1016/j.crohns.2012.07.010
12. Kolehmainen M, Mykkänen O, Kirjavainen P V., et al. Bilberries reduce low-grade inflammation in individuals with features of metabolic syndrome. Mol Nutr Food Res. 2012;56(10):1501-1510. doi:10.1002/mnfr.201200195
13. Karlsen A, Paur I, Bøhn SK, et al. Bilberry juice modulates plasma concentration of NF-κB related inflammatory markers in subjects at increased risk of CVD. Eur J Nutr. 2010;49(6):345-355. doi:10.1007/s00394-010-0092-0
14. Widén C, Coleman M, Critén S, Karlgren-Andersson P, Renvert S, Persson G. Consumption of Bilberries Controls Gingival Inflammation. Int J Mol Sci. 2015;16(12):10665-10673. doi:10.3390/ijms160510665
15. de Mello VDF, Schwab U, Kolehmainen M, et al. A diet high in fatty fish, bilberries and wholegrain products improves markers of endothelial function and inflammation in individuals with impaired glucose metabolism in a randomised controlled trial: The Sysdimet study. Diabetologia. 2011;54(11):2755-2767. doi:10.1007/s00125-011-2285-3
16. Habanova M, Saraiva JA, Haban M, et al. Intake of bilberries (Vaccinium myrtillus L.) reduced risk factors for cardiovascular disease by inducing favorable changes in lipoprotein profiles. Nutr Res. 2016;36(12):1415-1422. doi:10.1016/j.nutres.2016.11.010
17. Hoggard N, Cruickshank M, Moar K-M, et al. A single supplement of a standardised bilberry (Vaccinium myrtillus L.) extract (36 % wet weight anthocyanins) modifies glycaemic response in individuals with type 2 diabetes controlled by diet and lifestyle. J Nutr Sci. 2013;2:e22. doi:10.1017/jns.2013.16
18. Lankinen M, Schwab U, Kolehmainen M, et al. Whole grain products, fish and bilberries alter glucose and lipid metabolism in a randomized, controlled trial: the Sysdimet study. PLoS One. 2011;6(8):e22646. doi:10.1371/journal.pone.0022646
19. Lehtonen H-M, Suomela J-P, Tahvonen R, et al. Different berries and berry fractions have various but slightly positive effects on the associated variables of metabolic diseases on overweight and obese women. Eur J Clin Nutr. 2011;65(3):394-401. doi:10.1038/ejcn.2010.268
20. Granfeldt YE, Björck IM. A bilberry drink with fermented oatmeal decreases postprandial insulin demand in young healthy adults. Nutr J. 2011;10(1):57. doi:10.1186/1475-2891-10-57
21. Törrönen R, Sarkkinen E, Tapola N, Hautaniemi E, Kilpi K, Niskanen L. Berries modify the postprandial plasma glucose response to sucrose in healthy subjects. Br J Nutr. 2009;103(8):1. doi:10.1017/S0007114509992868
22. Törrönen R, Sarkkinen E, Niskanen T, Tapola N, Kilpi K, Niskanen L. Postprandial glucose, insulin and glucagon-like peptide 1 responses to sucrose ingested with berries in healthy subjects. Br J Nutr. 2012;107(10):1445-1451. doi:10.1017/S0007114511004557
23. Törrönen R, Kolehmainen M, Sarkkinen E, Poutanen K, Mykkänen H, Niskanen L. Berries Reduce Postprandial Insulin Responses to Wheat and Rye Breads in Healthy Women. J Nutr. 2013;143(4):430-436. doi:10.3945/jn.112.169771
24. Erlund I, Marniemi J, Hakala P, Alfthan G, Meririnne E, Aro A. Consumption of black currants, lingonberries and bilberries increases serum quercetin concentrations. Eur J Clin Nutr. 2003;57(1):37-42. doi:10.1038/sj.ejcn.1601513
25. Kuntz S, Kunz C, Herrmann J, et al. Anthocyanins from fruit juices improve the antioxidant status of healthy young female volunteers without affecting anti-inflammatory parameters: results from the randomised, double-blind, placebo-controlled, cross-over ANTHONIA (ANTHOcyanins in Nutrition Investigation Alliance) study. Br J Nutr. 2014;112(6):925-936. doi:10.1017/S0007114514001482
26. Kawabata F, Tsuji T. Effects of dietary supplementation with a combination of fish oil, bilberry extract, and lutein on subjective symptoms of asthenopia in humans. Biomed Res. 2011;32(6):387-393.
27. Tjelle TE, Holtung L, Bøhn SK, et al. Polyphenol-rich juices reduce blood pressure measures in a randomised controlled trial in high normal and hypertensive volunteers. Br J Nutr. 2015;114(7):1054-1063. doi:10.1017/S0007114515000562
28. Biesinger S, Michaels HA, Quadros AS, et al. A combination of isolated phytochemicals and botanical extracts lowers diastolic blood pressure in a randomized controlled trial of hypertensive subjects. Eur J Clin Nutr. 2016;70(1):10-16. doi:10.1038/ejcn.2015.88.
29. McCarty CA, Berg RL, Rottscheit CM, Dart RA. The use of dietary supplements and their association with blood pressure in a large Midwestern cohort. BMC Complement Altern Med. 2013;13(1):339. doi:10.1186/1472-6882-13-339.

See the National Center for Complementary and Integrative Health entry for bilberry, the European Medicines Agency public summary for Myrtilli fructus recens, or the Penn State Hershey Health Information Library entry for bilberry for more information.