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An Evidence-Based Systematic Review of Bilberry ( Vaccinium myrtillus ) by the Natural Standard Research Collaboration

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An evidence-based systematic review including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.
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... However, older texts and the European Pharmacopoeia refer to bilberry as Myrtilli fructus [24]. The Danish word bollebar, which denotes a dark fruit, is the first appearance of the name bilberry [25]. Since ancient times, bilberries have been used to cure skin ulcers, hemorrhoids, nausea, vomiting, diarrhea, and inflammation of the mucosal tissues. ...
... Furthermore, shrub growth and berry yield is affected by numerous environmental elements, such as meteorological conditions, soil type, light, or cultivation conditions [29,30]. The berries contain numerous tiny, shiny, brownish-red seeds [25]. Bilberries reportedly contain sugars, vitamins, pectin, and phenolics. ...
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Inflammation is important in the pathogenesis of several chronic diseases. The anti-inflammatory properties of berries have been investigated but the anti-inflammatory activity of bilberry has received little attention and a detailed review is yet to be published. Therefore, we compiled information on the phytochemicals of bilberry and preclinical and clinical studies of its anti-inflammatory properties. The review was based on studies from 2007 to date. Phytoconstituents of bilberries were phenolic acids, organic acids, anthocyanins, coumarins, flavonols, flavanols, tannins, terpenoids, and volatile chemicals. Data from cell and animal model studies show that bilberry has an anti-inflammatory effect by lowering tumor necrosis factor-α, interleukin (IL)-6, and IL-1β expression, inducing nitric oxide synthases and cyclooxygenases, and altering the nuclear factor kappa B and Janus kinase-signal transducer and activator of transcription signaling pathways. Bilberry supplementation as fruits (frozen, processed, and whole), juices, and anthocyanins reduced levels of inflammatory markers in most clinical studies of metabolic disorders. Therefore, bilberry may be useful for the prevention and treatment of chronic inflammatory disorders.
... It has been eaten as fresh fruit or used to make jams, juices and bases for liqueurs. Furthermore, it is widely used as an ingredient for supplementation and nutraceuticals to improve oxidative stress, inflammation and night vision [21,22]. Antioxidant, anti-inflammatory and hypolipidemic properties of BE related to the prevention of CVD are reported in vitro and in animals [23][24][25][26][27]. ...
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Bilberry (Vaccinium myrtillus L.), rich in polyphenols, has been claimed to have lipid-lowering effects, but its underlying mechanisms remain unclear. The effects of bilberry extract (BE) with antioxidant properties on hepatic lipid metabolism were investigated by measuring the genes for cholesterol biosynthesis and flux in HepG2 cells. The mRNA and protein levels of genes involved in cholesterol biosynthesis such as sterol regulatory element-binding protein 2 and 3-hydroxy-3-methylglutaryl coenzyme A reductase were decreased in BE-treated cells. BE posttranscriptionally upregulated low-density lipoprotein receptor in HepG2 cells. There was a marked reduction in genes for very low-density lipoprotein assembly by BE treatment. Furthermore, the expression of canalicular transporter for cholesterol and bile acids, such as ABCG8 and ABCB11, was significantly elevated by BE treatment. Downregulation of lipogenic genes and upregulation of fatty acid oxidation-related genes were observed in BE-treated HepG2 cells. The expressions of sirtuins were altered by BE treatment. These results support that the effects of BE on hepatic cholesterol metabolism may be attributed to the regulation of genes for hepatic cholesterol biosynthesis, transport and efflux.
... Characteristic compositions of blueberry, bilberry and chokeberry and their health benefits are reviewed based on the literatures [93][94][95][96][97][98][99][100][101][102]. However, in fact, considerable variations in the characteristic compositions and contents of berry materials, whether within interspecies or among different families, have not been reviewed before. ...
Article
The fruit-based dietary supplement business is flourishing, and many plant bioactive compounds exhibit beneficial effects on health. Polyphenols, including anthocyanins, proanthocyanidins, flavanols, phenolic acids and flavanols in bilberry, blueberry and chokeberry, are the bio-factors that determine the biological activities of the three berries. Many reports on phenolic compounds and their biological activities in berries have been published. Therefore, it is urgent to make a systematic comparison among them. We reviewed these scientific researches about phenolic substances including their compositions, contents and bioavailability from the bilberry, blueberry and chokeberry. On this basis, the phenolic compounds regarding monomer components and their contents in the three berries were systematically summarized. Variations of anthocyanidins within interspecies and different families were explained. Biological properties including biostability and bioavailability of anthocyanin and prospects for further study on berries were contained.
... Natural Standard Research collaboration assessed the clinical evidence on bilberry and its extracts for several indications including diabetes mellitus, glaucoma, retinopathy, cataracts and night vision in 2009. All indications have been assessed with grade C-"Unclear or conflicting scientific evidence", except for night vision, which was assessed one grade lower, D-"Fair negative scientific evidence" (Ulbricht et al., 2009). ...
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Bilberry (Vaccinium myrtillus L.) fruits are an important part of local diets in many countries and are used as a medicinal herb to treat various disorders. Extracts from fruits are often a part of eye health-promoting supplements, whereas extracts from leaves are advertised for type 2 diabetes mellitus and glycemic control. This review provides an overview of the current knowledge of the phytochemical contents of bilberry fruits and leaves and their bioactivities, critically summarizes origins of the health claims and the outcome of clinical trials, with special attention towards those published in the past 10 years. Overall, the three most referenced indications, which are type 2 diabetes mellitus, vision disorders and circulatory diseases, all include contradictory results with no clear conclusion as to the benefits and recommended dosages. Moreover, the indications for vision disorders and diabetes originate from unproven or false claims that have been repeated in research since the 20th century without consistent fact-checking. Beneficial clinical results have been attested for the treatment of dyslipidemia and chronic inflammatory disorders when applied as dietary supplementation of fresh bilberries or as anthocyanin-rich bilberry fruit extracts. However, there is a general lack of double-blinded controlled research with larger sample sizes.
... Yes (both hypoglycemic and anticonvulsant effects) (Collins et al., 2006;Grace et al., 2009) -Gastrointestinal discomfort Mild modulation of CYP enzymes (Prokop et al., 2019) -Drop in blood pressure -Bleeding risk (Ulbricht et al., 2009) Nettle (Urtica dioica) ...
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Introduction: Millions all over the world live with epilepsy, and they may require long-term drug treatment. The use and interest in complementary and alternative medicine (CAM) have grown over the previous years. Coadministration of herbal products with medicines may result in adverse drug reactions (ADRs) and/or unfavorable interactions. The aims of this study were to determine the prevalence of CAM use among patients with epilepsy, to compare the results to those of the patients with diabetes mellitus (DM), to reveal factors that may drive the use of CAM, and to measure outcomes and adherence. It was also our intent to have state-of-the-art information on CAM use in our region among patients with the two diseases above. Materials and Methods: We conducted a non-interventional study using a self-developed questionnaire. It was distributed among adult patients with either epilepsy or DM who also suffered from cardiovascular consequences. A database was compiled from the anonymous questionnaires filled in voluntarily by the patients. Basic statistics were used to analyze this database. Results: A total of 227 questionnaires were filled in by 127 patients (55.9%) with epilepsy and 100 patients (44.1%) with DM. Mean age was 54.54 ± 17.33 years. Of the patients, 50.2% were male. Average body weight was 80.3 ± 17.3 kg. Of the patients, 22 (9.7%) used CAM because they believed in CAM. Two of them reported ADRs. Among the patients with epilepsy, the ratio was only 7.9% compared to 12% among those with DM. While the number of CAM users was higher among younger patients with epilepsy, it was the elderly patients with DM who tended to use CAM. Conclusion: Attention should be paid to reliance on CAM during the follow-up. Our finding that health-conscious patients tend to use CAM more often (than the general population) may indicate it is necessary to discuss CAM usage sincerely. CAMs modulating cytochrome P450 (CYP) enzymes were the most common, leading to interactions with medication used and resulting in ADRs. This shows the importance of educating patients and treating team including clinical pharmacists in this field.
... It has been widely used as folklore medicine for diarrhea, dysentery, scurvy, diabetes, stroke, and mouth and throat inflammation [23]. It has been commonly used as a dietary and supplement ingredient to alleviate oxidative stress, inflammation, and ocular health [24]. Bilberry has been reported to have protective effects against oxidative stress, inflammation, hyperglycemia, and lipid metabolism, which are associated with the initiation and progression of CVD [25][26][27][28][29][30][31][32][33]. ...
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Hypercholesterolemia is one of the modifiable and primary risk factors for cardiovascular diseases (CVD). Emerging evidence suggests the stimulation of transintestinal cholesterol excretion (TICE), the nonbiliary cholesterol excretion, using natural products can be an effective way to reduce CVD. Bilberry (Vaccinium myrtillus L.) has been reported to have cardioprotective effects by ameliorating oxidative stress, inflammation, and dyslipidemia. However, the role of bilberry in intestinal cholesterol metabolism is not well understood. To examine the effects of bilberry in intestinal cholesterol metabolism, we measured the genes for cholesterol flux and de novo synthesis in anthocyanin-rich bilberry extract (BE)-treated Caco-2 cells. BE significantly decreased the genes for cholesterol absorption, i.e., Niemann-Pick C1 Like 1 and ATP-binding cassette transporter A1 (ABCA1). In contrast, BE significantly upregulated ABCG8, the apical transporter for cholesterol. There was a significant induction of low-density lipoprotein receptors, with a concomitant increase in cellular uptake of cholesterol in BE-treated cells. The expression of genes for lipogenesis and sirtuins was altered by BE treatment. In the present study, BE altered the genes for cholesterol flux from basolateral to the apical membrane of enterocytes, potentially stimulating TICE. These results support the potential of BE in the prevention of hypercholesterolemia.
... In a review of 30 studies of the effect of bilberry on night vision, only five satisfied scientific requirements whereof four showed no correlation (Canter & Ernst, 2004). Another review of the effect of bilberry on cataract, retinopathy and night vision did not show any clear relationship (Ulbricht et al., 2009). The Danish Ophthalmologic Society recommends the AREDS-formula to patients with wet AMD in one eye, to patients with several large drusen and visual impairment, and even to patients with drusen and relatives with visual impairment caused by AMD (Dansk Oftalmologisk Selskab, 2015). ...
Article
Nutritional supplements for eye health are very popular, but the size of the market makes it difficult to grasp for the clinician. To guide patients and clinicians in the subject it would therefore be valuable to have a list of available products and their content. The purpose of this study was to investigate the ocular nutritional supplements available on the Scandinavian market and how their doses relate to current evidence. A list of nutritional supplements for ocular health available on the Scandinavian market was compiled by structured internet searches, and the products and their contents were compared with current evidence and legislated upper tolerable levels. Out of 104 products on the Scandinavian market, only two products reached the Age-Related Eye Disease Study 2 (AREDS2)-formula at the recommended dose. One additional product reached the same formula if the recommended dose was exceeded. As only two nutritional supplements for ocular health on the Scandinavian market reached the AREDS2-dose at recommended dose, clinicians offering such substances need to have knowledge not only about the substances but also of the doses. In the future it would be welcome if the health claims for nutritional supplements were based on placebo-controlled intervention studies, to avoid ineffective products.
... In a review of 30 studies of the effect of bilberry on night vision, only five satisfied scientific requirements whereof four showed no correlation (Canter & Ernst, 2004). Another review of the effect of bilberry on cataract, retinopathy and night vision did not show any clear relationship (Ulbricht et al., 2009). The Danish Ophthalmologic Society recommends the AREDS-formula to patients with wet AMD in one eye, to patients with several large drusen and visual impairment, and even to patients with drusen and relatives with visual impairment caused by AMD (Dansk Oftalmologisk Selskab, 2015). ...
Article
Full-text available
Nutritional supplements for eye health are very popular, but the size of the market makes it difficult to grasp for the clinician. To guide patients and clinicians in the subject it would therefore be valuable to have a list of available products and their content. The purpose of this study was to investigate the ocular nutritional supplements available on the Scandinavian market and how their doses relate to current evidence. A list of nutritional supplements for ocular health available on the Scandinavian market was compiled by structured inter-net searches, and the products and their contents were compared with current evidence and legislated upper tolerable levels. Out of 104 products on the Scandinavian market, only two products reached the Age-Related Eye Disease Study 2 (AREDS2)-formula at the recommended dose. One additional product reached the same formula if the recommended dose was exceeded. As only two nutritional supplements for ocular health on the Scandinavian market reached the AREDS2-dose at recommended dose, clinicians offering such substances need to have knowledge not only about the substances but also of the doses. In the future it would be welcome if the health claims for nutritional supplements were based on placebo-controlled intervention studies, to avoid ineffective products.
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Traumatic brain injury may trigger the secondary brain injury, whichhas the potential to be reversible and thus preventable. Anthocyanins are phylotherapeutic plants, which are reported to exhibit anti-inflammatory properties. This study aimedto evaluate the therapeutic efficiency of an anthocyanin, namely Vaccinium myrtillus, to alleviate secondary brain injury and identify possible mechanism of actions. It is hypothesized that lipid peroxidation and Na+-K+-ATPase activity may be involved in neuronal ischemia. Thus, brain tissue Malondialdehyde content, Na+-K+-ATPase content, and cleaved caspase-3 content was investigated following moderate head trauma in a rat model. Twenty-four Sprague-Dawley male rats were allocated into four groups: Control, Trauma, Solvent-Control, and Treatment. Trauma and Solvent-Control groups showed more prominent brain edema, neuronal ischemia, vascular congestion, increase in brain tissue Malondialdehyde and cleaved caspase-3 levels, and decreased Na+-K+-ATPase activity compared to the Control group. Although the Treatment group had comparable histological signs to the Trauma and Solvent-Control groups, Malondialdehyde level and Na+-K+-ATPase activity was similar to Control group, and cleaved caspase-3 levels were lower compared to Trauma and Solvent-Control groups. We conclude that anthocyanin extracts may alleviate secondary brain injury via anti-oxidative and anti-apoptotic mechanisms.
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Introduction: Diabetes mellitus is one of WHO’s priority issues. It requires immediate resolution as the epidemiological situation is gaining alarming proportions – the number of diabetic patients is increasing every year along with the number of deaths and disabilities due to the development of angiopathies [1]. Therefore, the optimization of pharmacotherapy, search and study of new drugs with antidiabetic activity for the prevention and treatment of this disease and its complications is a top issue of pharmacy. Particular attention deserve the combinations of different medicinal plants, because such herbal mixtures will have more biologically active substances that will influence on the all links of the pathogenetic mechanism of development of diabetes mellitus and its complications [2, 3]. Thus, the aim of our research was to study the influence of herbal mixture on the protein metabolism in dexamethasone-induced insulin resistant rats. Materials and methods: It was selected the aqueous extract (1:10) of the herbal mixture (Urtica dioica leaf, Taraxacum officinale roots, Vaccinium myrtillus leaf, Rosa majalis fruits, Mentha piperita herb), which is used in folk medicine for the treatment and prevention of diabetes mellitus type 2 [4]. The study was performed on male albino rats of the Wistar strain with induction of insulin resistance by dexamethasone (1 mg/kg/day) during 15 days [5]. Results: The administration of dexamethasone to linear rats caused the disorders of protein metabolism due to decrease in total serum protein by 17% relative to the intact group. The introduction of aqueous extract of the herbal mixture increased the total protein content by 20% in insulin resistant rats. Conclusions: The results from the present study showed that aqueous extract of the herbal mixture exhibits the ability to regulate protein metabolism on the background of insulin resistance in rats. References: 1. American Diabetes Association. Standards of Medical Care in Diabetes. Diabetes care. 2020;43:1–1212. 2. Bindu J, Narendhirakannan RT. Role of medicinal plants in the management of diabetes mellitus: a review. 3 Biotech. 2019;9(1):4. 3. Savych AO, Marchyshyn SM, Kozyr HR, Skrinchuk OY. Basic principles for the using of medicinal plants and their collections for the treatment and prevention of diabetes type 2. Phypotherapy chasopys. 2019;4:43–46. 4. Tovstuha YS.Golden Recipes of Ukrainian Folk Medicine. Kraina Mriy Publishers. Kyiv. 2010:550. 5. Savych A, Marchyshyn M, Basaraba R, Lukanyuk M. Antihyperglycemic, hypolipidemic and antioxidant properties of the herbal mixtures in dexamethasone-induced insulin resistant rats. Pharmacologyonline. 2020;2:73-82.
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Purpose; Amhocynosides in a multiple oral dose reportedly improve night vision tests in normal individuals. We evaluated in this study the effect of multiple oral anlhocyanosidcs administration on 1 night vision tests, wholefield scolopic retinal threshold (SRT), mesopic contrast sensitivity (MCS) and dark adaptation rate (DAR) These 3 night vision tests have a significant predicthc value of the ability to detect real targets at night. Materials and Methods: In this double blin1, placebo controlled. cross-over study 18 young volunteers were randomh assignee to a multiple oral administration of anthocyanosides or placebo Amhocyanosides (bluebcrn extract tablets iStnxi which contain 12mg anthocyanoside per labiet) and placebo (ground food starch) were given as a gift (CTS. Israel) Anthocyanosides were given in doses of 12mg or 24mg twice daiK for 4 days DAR, SRT and MCS were studied immediately before and ai day 1, 2, 3 and 4 during the treatment period. Results: No significant effect was found on my of the above mentioned night vision tests during 4 days oral administration of 12mg or 24mg anthoaanosidcs twice daily. Conclusion: Multiple oral anthocvanosides .idmmistiation of 12mg and 24mg twice a day appears to lack significant effect on night vision tests.
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V. myrtillus is a deciduous small shrublet belonging to the Ericaceae family and growing on hilly and mountainous regions of Europe, Asia and Northern America. Fruits and leaves have been traditionally used in folk medicine of several European countries. In the last decades, some components of the fruits received particular interest due to their pharmacological properties. In particular, anthocyanosides have been investigated for their effect on blood vessels and in ophthalmology. At present, pharmaceutical proprietary products containing standardized extracts from V. myrtillus fruits are available for the therapy of alterated conditions of capillary fragility and permeability and for the normalization of some ophthalmological disorders.