Chu W, Cheung SCM, Lau RAW, et al. Bilberry (Vaccinium myrtillus L.) In: Benzie IFF, Wachtel-Galor S, editors. Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. Boca Raton (FL): CRC Press/Taylor & Francis; 2011. Chapter 4.Available from: https://www.ncbi.nlm.nih.gov/books/NBK92770/

Publication Date: "2011"

Peer Reviewed: Yes

Study Design: "Experimental studies and controlled human supplementation trials"

Methodology: Animal studies, in vitro work, human supplementation trials with various biomarkers measured.

Sample Size: "31 subjects" (in one of the human trials)

Controls Used: "Control subjects"

Dose Used: "330 mL/day bilberry juice (diluted to 1 L with water) for 4 weeks"

Statistical Significance Declared: "No significant changes in biomarkers of antioxidant status or oxidative stress" (Karlsen et al. 2010)

Adverse Events due to Bilberry Supplementation: None directly linked to bilberry supplementation mentioned.

Conflict of Interest: None declared in the provided text.

Riva A, Togni S, Franceschi F, et al. The effect of a natural, standardized bilberry extract (Mirtoselect®) in dry eye: a randomized, double blinded, placebo-controlled trial. Eur Rev Med Pharmacol Sci. 2017;21(10):2518-2525.

Publication Date: "2017"

Peer Reviewed: Yes

Study Design: "randomized, double-blinded, placebo-controlled, parallel group comparison study."

Methodology: Rats given bilberry extract or anthocyanin-rich extract; blood samples analyzed by UV spectrophotometry; 22 humans with dry eye symptoms randomized to receive bilberry extract or placebo; Schirmer’s test, pupil constriction, d-ROMs test, and BAP test performed.

Sample Size: "22 otherwise healthy subjects" and "5 male rats."

Controls Used: "placebo group."

Dose Used: "80 mg of Mirtoselect®" in each tablet, "160 mg Mirtoselect® daily."

Statistical Significance Declared: "Schirmer’s test values...p=0.019", "BAP significantly increased (p=0.003)."

Adverse Events due to Bilberry Supplementation: None directly linked to bilberry supplementation mentioned.

Conflict of Interest: "AR, ST, FF are employees of Indena S.p.A. LG is a consultant of Indena S.p.A."

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

Publication Date: "Available online 17 December 2015"

Peer Reviewed: Yes.

Study Design: "A prospective, randomized, double-blind, placebo-controlled study."

Methodology: Randomized to BE (480 mg/day) or placebo, took capsules daily for 8 weeks, CFF, NPA, contrast visual acuity, functional visual acuity, keratoconjunctival epithelial damage, and fluorescein tear film break-up time were measured, and 18 subjective symptoms evaluated by questionnaire.

Sample Size: "Two hundred eighty-one office workers aged 20–40 years...88 having relatively lower levels of CFF and NPA were enrolled...37 control and 43 BE group subjects completed the study."

Controls Used: "Placebo capsules containing only vehicles (starch, crystalline cellulose, and calcium stearate)."

Dose Used: "480 mg/day."

Statistical Significance Declared: "The VDT load-induced reduction in CFF was alleviated after 8 weeks of BE supplementation (95% confidence interval, 0.10–1.60; p=0.023)."

Adverse Events due to Bilberry Supplementation: "Five of 43 subjects (11.6%) in the BE group, and 5 of 37 subjects (13.5%) in the placebo group reported a collective total of 15 minor adverse events...All these self-recorded adverse events were mild in intensity, were only temporary, and were deemed by the investigator to be unrelated to the intervention."

Conflict of Interest: "This work was conducted by Wakasa Seikatsu Co. Ltd., of which E.O., and S.K., are employees, and from which Y.O. and K.T. receive financial support for the other study. M.K., E.I., and A.S. have no conflict of interest."

Sharma A, Lee HJ. Anti-Inflammatory Activity of Bilberry (Vaccinium myrtillusL.). Curr Issues Mol Biol. 2022;44(10):4570-4583. Published 2022 Sep 30. doi:10.3390/cimb44100313

Publication Date: "30 September 2022"

Peer Reviewed: Yes

Study Design: "Review"

Methodology: Compilation of studies from 2007 to date, based on in vitro, in vivo, and clinical studies.

Sample Size: "13 preclinical and 11 clinical studies"

Controls Used: Water controls, dietary controls

Dose Used: "Bilberry juice (330 mL per day for 4 weeks), 100 g frozen whole bilberries for 33–35 days, fresh bilberry (400 g daily), 320 mg pure anthocyanins daily for 4 weeks, 320 mg/day bilberry and blackcurrant for 24 weeks."

Statistical Significance Declared: Various studies reported significant reductions in inflammatory markers and improvements in lipid profiles, e.g., "significantly reduced the serum levels of hsCRP and IL-12" in MetS patients.

Adverse Events due to Bilberry Supplementation: "Bilberry and bilberry extracts are not associated with adverse effects."

Conflict of Interest: "The authors declare no conflict of interest."

Yu WY, Chan LYL, Chung A, Lee PH, Woo GC. Bilberry-containing supplements on severe dry eye disease in young and middle-aged adults: A 3-month pilot analysis. Front Nutr. 2023;10:1061818. Published 2023 Jan 19. doi:10.3389/fnut.2023.1061818

Publication Date: "19 January 2023"

Peer Reviewed: Yes

Study Design: "prospective examiner-masked, parallel controlled pilot study"

Methodology: "Subjects were randomly assigned to bilberry treatment and control groups. Standardized tests and forms were used to evaluate both objective and subjective symptoms of DED. Mean changes in OSDI score, NITBUT, PRT, and percentage of meibomian gland openings were used as outcome measures."

Sample Size: "A total of 24 subjects were recruited in this study with 12 subjects randomly assigned to the intervention group and 12 subjects to the control group."

Controls Used: "The control group did not take any supplements."

Dose Used: "600 mg bilberry extract and 240 mg docosahexaenoic acid-refined fish oil once daily for 3 months."

Statistical Significance Declared: "Cohen’s d effect size (dOSDI = 1.72; dNITBUT = 1.60 and dPRT = 5.84)"

Adverse Events due to Bilberry Supplementation: "No major side effects have been reported on its use as a dietary supplement."

Conflict of Interest: "The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."

Tian L, Tan Y, Chen G, et al. Metabolism of anthocyanins and consequent effects on the gut microbiota. Crit Rev Food Sci Nutr. 2019;59(6):982-991. doi:10.1080/10408398.2018.1533517

Publication Date: "Published online: 30 Dec 2018"

Peer Reviewed: Yes

Study Design: "review article"

Methodology: Summarizes recent data on absorption and metabolism of anthocyanins in human/animal and their interaction with gut microbiota.

Sample Size: Not applicable (review article)

Controls Used: Not applicable (review article)

Dose Used: Not applicable (review article)

Statistical Significance Declared: Not applicable (review article)

Adverse Events due to Bilberry Supplementation: Not directly stated in the study.

Conflict of Interest: "This study was supported by the Natural Science Foundation of China (NSFC, No.31871816 and No.31771983), the Science and Technology Program of Guangzhou (201704020050), the Fundamental Research Funds for the Central Universities (21617324) and the Research Funds for Talented Scholars of Jinan University (88016675)."

Chan SW, Tomlinson B. Effects of Bilberry Supplementation on Metabolic and Cardiovascular Disease Risk. Molecules. 2020;25(7):1653. Published 2020 Apr 3. doi:10.3390/molecules25071653

Publication Date: "3 April 2020"

Peer Reviewed: Yes

Study Design: "Review"

Methodology: Electronic literature searches using PubMed, Web of Science, and Google Scholar; 1034 articles identified; bibliographies scanned; articles extracted independently based on relevance and quality.

Sample Size: Not applicable

Controls Used: Not applicable

Dose Used: Various doses used across different studies

Statistical Significance Declared: Not applicable

Adverse Events due to Bilberry Supplementation: "No serious clinical adverse events nor alterations in the safety laboratory parameters" and "No known adverse effect of bilberry and bilberry extract has been reported in other studies."

Conflict of Interest: "The authors declare no conflict of interest."

de Mello VD, Lankinen MA, Lindström J, et al. Fasting serum hippuric acid is elevated after bilberry (Vaccinium myrtillus) consumption and associates with improvement of fasting glucose levels and insulin secretion in persons at high risk of developing type 2 diabetes. Mol Nutr Food Res. 2017;61(9):10.1002/mnfr.201700019. doi:10.1002/mnfr.201700019

Publication Date: "3 April 2020"

Peer Reviewed: Yes

Study Design: "Review"

Methodology: Electronic literature searches using PubMed, Web of Science, and Google Scholar, selecting studies based on relevance and quality.

Sample Size: N/A (review study)

Controls Used: N/A (review study)

Dose Used: Various dosages reported across different studies.

Statistical Significance Declared: N/A (review study)

Adverse Events due to Bilberry Supplementation: "No serious clinical adverse events nor alternations in the safety laboratory parameters."

Conflict of Interest: "The authors declare no conflict of interest."

Vendrame S, Adekeye TE, Klimis-Zacas D. The Role of Berry Consumption on Blood Pressure Regulation and Hypertension: An Overview of the Clinical Evidence. Nutrients. 2022;14(13):2701. Published 2022 Jun 29. doi:10.3390/nu14132701

Publication Date: "Published: 29 June 2022"

Peer Reviewed: Yes

Study Design: "double-blind, placebo-controlled, crossover intervention"

Methodology: Daily administration of bilberry extract or puree, measured effects on SBP and DBP, used crossover and parallel arms designs.

Sample Size: "20 participants", "27 overweight or obese subjects", "36 healthy subjects"

Controls Used: "placebo"

Dose Used: "1.4 g dose of bilberry extract", "200 g bilberry puree plus 40 g dried bilberries (equivalent to a total of 400 g fresh berries)", "456 mg of ACN, given three times per week"

Statistical Significance Declared: "did not significantly affect SBP or DBP"

Adverse Events due to Bilberry Supplementation: Not related to Bilberry supplementation.

Conflict of Interest: "Previous research projects by D.K.Z. and S.V. received partial funding from the Wild Blueberry Association of North America (WBANA) and the National Processed Raspberry Council (NPRC)."

Hong J, Kim M, Kim B. The Effects of Anthocyanin-Rich Bilberry Extract on Transintestinal Cholesterol Excretion. Foods. 2021;10(11):2852. Published 2021 Nov 18. doi:10.3390/foods10112852

Publication Date: "18 November 2021"

Peer Reviewed: Yes

Study Design: "In vitro study using Caco-2 cells"

Methodology: BE was tested on Caco-2 cells at concentrations of 50 or 100 μg/mL for 24 h; gene and protein expressions were measured using qRT-PCR and Western blot; LDL uptake and cholesterol levels were assessed.

Sample Size: "n = 6"

Controls Used: "Cells incubated without BE served as a control for all experiments."

Dose Used: "50 or 100 μg/mL of BE for 24 h"

Statistical Significance Declared: "p < 0.05"

Adverse Events due to Bilberry Supplementation: None stated directly linked to Bilberry supplementation.

Conflict of Interest: "The authors declare no conflict of interest."

Zhang S, Wang Y, Ye J, et al. Dietary supplementation of bilberry anthocyanin on growth performance, intestinal mucosal barrier and cecal microbes of chickens challenged with Salmonella Typhimurium. J Anim Sci Biotechnol. 2023;14(1):15. Published 2023 Jan 20. doi:10.1186/s40104-022-00799-9

Publication Date: "2023"

Peer Reviewed: Yes.

Study Design: "randomly allocated to 4 treatments, each with 6 replicates."

Methodology: "240 hatchling chickens were randomly allocated to 4 treatments, each with 6 replicates. Birds were fed a basal diet supplemented with 0 (CON, and ST), 100 (ACL) and 400 (ACH) mg/kg of AC for 60 days, and orally challenged with PBS (CON) or 10^9 CFU/bird (ST, ACL, ACH) Salmonella Typhimurium at days 14 and 16."

Sample Size: "240 hatchling chickens."

Controls Used: "Birds in the control group (CON) and Salmonella infected group (ST) were fed the basal diets."

Dose Used: "100 or 400 mg/kg bilberry AC."

Statistical Significance Declared: "P < 0.05 for body weight, average daily gain, number of Salmonella cells, contents of NO, inflammatory cytokines, ileal villus height, crypt depth, V/C ratio, alpha-diversity, and relative abundance of bacteria."

Adverse Events due to Bilberry Supplementation: None directly linked to Bilberry supplementation.

Conflict of Interest: Not stated in the provided text.

Roth S, Spalinger MR, Gottier C, et al. Bilberry-Derived Anthocyanins Modulate Cytokine Expression in the Intestine of Patients with Ulcerative Colitis. PLoS One. 2016;11(5)
. Published 2016 May 6. doi:10.1371/journal.pone.0154817

Publication Date: "May 6, 2016"

Peer Reviewed: Yes

Study Design: "open label clinical trial"

Methodology: Colon specimens analyzed by immunohistochemistry, cytokine levels quantified by ELISA, cell culture experiments using THP-1 monocytic cells.

Sample Size: "13 patients with current mild to moderate UC underwent a first sigmoidoscopy with biopsy taking 7 days prior to and 11 patients underwent a second sigmoidoscopy at the last day of the six-week bilberry intake period"

Controls Used: None mentioned (open label study)

Dose Used: "anthocyanin-rich bilberry preparation"

Statistical Significance Declared: "Significant results are marked as follows: * = p<0.05; ** = p<0.01; *** = p<0.001; n.s. = not significant."

Adverse Events due to Bilberry Supplementation: No direct adverse events linked to bilberry supplementation stated.

Conflict of Interest: "The authors have declared that no competing interests exist."

Li N , Li J , Hao J , et al. Bilberry anthocyanin improves the serum cholesterol in aging perimenopausal rats via the estrogen receptor signaling pathway [published correction appears in Food Funct. 2021 Sep 7;12(17):8208]. Food Funct. 2019;10(6):3430-3438. doi:10.1039/c9fo00639g

Publication Date: "13 May 2019."

Peer Reviewed: Yes.

Study Design: "Experimental study."

Methodology: Female Sprague-Dawley rats (10 and 3 months old) were acclimated, divided into six groups, treated with bilberry anthocyanin or isoflavones, and gavaged for 8 weeks.

Sample Size: "Sixty female Sprague-Dawley (SD) rats approximately 10 months of age and 12 female SD rats approximately 3 months of age."

Controls Used: "Young control group," "middle-aged control group," "soybean isoflavone group (positive control)."

Dose Used: "35 mg per kg of bodyweight," "70 mg per kg of bodyweight," "140 mg per kg of bodyweight."

Statistical Significance Declared: "The serum TC content of the middle-aged control group increased and showed an extremely significant difference (P < 0.01)." "The TG of the positive control and the low, medium, and high-dose groups reduced by 14.09%, 12.12%, 20.70%, and 19.55%, respectively (P < 0.05)." "The HDL-C content in the positive control group and the low, medium, and high dose groups promoted by 12.35%, 24.76%, 3.24%, and 5.20%, respectively (P < 0.05)." "The LDL-C content of the positive control group and the low, medium, and high dose groups reduced by 47.41%, 44.83%, 27.25%, and 34.89%, respectively (P < 0.01)." "The MDA content in the positive control group and the low, medium, and high BA dose groups decreased by 28.21%, 32.06%, 13.45%, and 32.15%, respectively (P < 0.05)." "The T-SOD activity of the positive control group and the low, medium, and high dose group increased by 28.17%, 25.58%, 30.15%, and 26.65%, respectively (P < 0.05)." "The CAT activity in the serum of the positive control group and the low, medium, and high dose groups was increased by 12.30%, 9.21%, 17.09%, and 10.53%, respectively (P < 0.01)."

Adverse Events due to Bilberry Supplementation: The study does not state any adverse events directly linked to Bilberry supplementation.

Conflict of Interest: "The authors declare no conflict of interest.”

Boyle, Manuela. "An evidence-based critical review of the botanicals bilberry fruit, black cohosh, bladderwrack and St John's wort in clinical practice." Journal of the Australian Traditional-Medicine Society, vol. 24, no. 2, winter 2018, pp. 89+. Gale Academic OneFile, link.gale.com/apps/doc/A550547748/AONE?u=anon~530e463&sid=googleScholar&xid=42542e87.

Publication Date: "Winter 2018"

Peer Reviewed: Yes

Study Design: "Randomised controlled intervention"

Methodology: Participants consumed either a diet rich in bilberries or a control diet; measured biomarkers of inflammation and cardiometabolic risk.

Sample Size: "15"

Controls Used: "Control diet"

Dose Used: "400g fresh bilberries daily"

Statistical Significance Declared: "Significant (p= 0.024) decrease in serum high-sensitivity C-reactive protein, IL-6, IL-12, and in LPS concentrations."

Adverse Events due to Bilberry Supplementation: "Very minimal adverse effects were experienced (4% of the subjects overall), with only 1% complaining of gastrointestinal discomfort and less than 1% experiencing nausea or heartburn."

Conflict of Interest: No conflicts of interest declared.

Hubert PA, Lee SG, Lee S-K, Chun OK. Dietary Polyphenols, Berries, and Age-Related Bone Loss: A Review Based on Human, Animal, and Cell Studies. Publication Date: "11 March 2014"

Peer Reviewed: Yes

Study Design: "A review based on human, animal, and cell studies."

Methodology: Literature review using PubMed database with specific keywords.

Sample Size: Not applicable (review study).

Controls Used: Not applicable (review study).

Dose Used: Not applicable (review study).

Statistical Significance Declared: Not applicable (review study).

Adverse Events due to Bilberry Supplementation: None stated directly related to Bilberry supplementation.

Conflict of Interest: "The authors declare no conflict of interest."

Borowiec, K., et al. "The influence of bilberry fruit on memory and the expression of parvalbumin in the rat hippocampus." Polish Journal of Veterinary Sciences 3 (2019): 481-487.

Publication Date: "2014"

Peer Reviewed: Yes

Study Design: "Randomized controlled trial"

Methodology: Wistar rats divided into four groups; control received standard feed; experimental groups received feed with bilberry at 2 g, 5 g, 10 g/kg b.w./day; modified elevated plus-maze test performed after three months; brains collected and PV-ir neurons visualized immunohistochemically after 32 weeks.

Sample Size: "Forty Wistar rats"

Controls Used: "The control group received standard feed (210 g/week)."

Dose Used: "2 g (group I), 5 g (group II), and 10 g/kg b.w./day (group III)."

Statistical Significance Declared: "Transfer latency examined 2 h and 24 h after the acquisition session was significantly shorter (p<0.05) in the group II in comparison with the control group." "In CA1 and CA2/CA3 hippocampal fields as well as dentate gyrus of all experimental groups, a significant (p<0.05) decrease in number of PV-ir neurons were found." "Brain weight was significantly higher (p<0.05) in experimental groups fed bilberry in comparison with the control group." "Rats in the groups II and III had a significantly (p<0.05) increased body weight during the study." "The consumption of standard feed enriched with bilberry fruit was notably (p<0.05) increased over the period."

Adverse Events due to Bilberry Supplementation: "No significant adverse events related to Bilberry supplementation were reported in the study."

Conflict of Interest: "Financial support for this research was provided by the Scientific Project POIG 01.01.02-00-061/09."