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Caucasian Whortleberry

Scientific Name(s): Vaccinium arctostaphylos
Common Name(s): Caucasian blueberry, Cyah-gileh, Qaraqat

Medically reviewed by Drugs.com. Last updated on May 1, 2019.

Clinical Overview

Use

Fruit and leaves of Caucasian whortleberry have been used to treat diabetes and high blood pressure. Limited data from 3 small, short-duration, randomized, placebo-only, controlled trials showed some beneficial effects from the plant’s fruit extract in 2 trials on glycemic and lipid parameters in patients with type 2 diabetes mellitus or hyperlipidemia. However, only 1 of the 3 trials measured A1c levels. Two small, short-duration, placebo-only controlled trials in patients without diabetes demonstrated favorable effects on lipid profiles.

Dosing

Fruit extract (standardized to 21% anthocyanins) has been used at dosages of 350 mg 3 times daily for up to 2 months.

Contraindications

Contraindications have not been identified; data are limited.

Pregnancy/Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

No adverse events have been reported in clinical trials. Data are limited.

Toxicology

Due to the resemblance of Caucasian whortleberry (V. arctostaphylos) to Atropa belladonna, accidental poisonings have been reported after mistaken consumption.

Botany

Vaccinium species include cranberries, bilberries, blueberries, and whortleberries. V. arctostaphylos L. is 1 of approximately 200 species of the genus Vaccinium (Ericaceae). It is a compact deciduous shrub (1.5 to 2.5 m tall) with numerous ascending branches. It grows mainly along the Black Sea from southwestern Bulgaria, through European and Asiatic Turkey, to the Caucasus—a region between the Caspian and Black seas where Europe and Asia converge. The berries are purple-black to black. It is the only Vaccinium species endemic to Iran, where it grows in the northern forests between 1,600 to 1,800 m above sea level. In northeastern Anatolia, Turkey, it can be found at altitudes of 600 to 1,250 m near the cities of Artvin, Rize, Trabzon, Gumushane, and Ordu. In the Caucasian mountains in the northern region of the Republic of Georgia, it grows at elevations of approximately 900 to 1,500 m.Lätti 2009, Gvozdetsky 2015, Nickavar 2004, Abidov 2006

History

Traditionally, decoctions and infusions of Caucasian whortleberry leaves have been used as a hypoglycemic agent for treating diabetes and "prediabetes" (impaired glucose tolerance). Its dried berries have also been used to treat diabetes and high blood pressure at a dose of 5 g/day. The leaves and berries are harvested for both commercial sale as well as household consumption.Lätti 2009, Nickavar 2004, Abidov 2006, Kianbakht 2013, Zhu 2015

The polyphenols (ie, anthocyanins) in Vaccinium berries have been reported to have positive effects on degenerative diseases, diabetes, vision, obesity, cardiovascular disease, and neurological disorders.

Chemistry

The berries of Vaccinium species contain high levels of a variety of anthocyanins that contribute to their color. Anthocyanins are water-soluble pigments comprised of an aglycone (anthocyanidin) and a sugar moiety that have a wide range of biological activity, including antioxidant and anti-inflammatory properties. All of the most common anthocyanidins (ie, delphinidin, cyaniding, petunidin, peonidin, pelargonidin, malvidin) are found in Vaccinium berries; the most common sugars bonded to anthocyanidins are galactose, glucose, arabinose, xylose, and rhamnose in the mono-, di-, or trisaccharide form.Lätti 2009, Nickavar 2004

V. arctostaphylos berries are rich sources of anthocyanins, differentiated from the berries of other Vaccinium species by their high concentrations of delphinidin (41%) and glucoside conjugates (61%), plus the presence of diglycosides (sambubiosides). Analyses of 5 cultivars of V. arctostaphylos berries—harvested in August 2007 and 2008 from their native habitat in northeastern Anatolia, Turkey—revealed 19 anthocyanins, 15 of which are also found in bilberry. The 5 aglycones (delphinidin, cyanidin, petunidin, peonidin, malvidin) were glycosylated with 6 sugar moieties (galactose, glucose, arabinose, sambubiose, pentose, xylose). The total anthocyanin content calculated on a fresh weight basis was 261 +/− 21 mg/100 g; the 3 major anthocyanidins were delphinidin (41 +/− 41%), petunidin (19 +/− 1%), and malvidin (20 +/− 3%).Lätti 2009, Gvozdetsky 2015, Nickavar 2004

The average proportions of sugar moieties were glucosides (61 +/− 7%), arabinosides (22 +/− 4%), galactosides (11 +/− 2%), and xylosides (5 +/− 1%).Lätti 2009 The spring leaves of V. arctostaphylos contain the highest concentrations of chlorogenic acid (3,4-caffeoylquinic acid) compared with more mature leaves.Abidov 2006

Uses and Pharmacology

Diabetes

Animal data

V. arctostaphylos fruit extract (VFE) was administered at 200 and 400 mg/kg body weight to Wistar rats with alloxan-induced diabetes. Postprandial blood glucose levels were reduced (18%) within the first 24 hours following single-dose administration of VFE as well as longer term (35%) following 3 weeks of daily VFE administration (P < 0.0001 for each). The short-term effect of the 400 mg/kg dose was similar to the 52% glucose decrease observed with acarbose 20 mg/kg (positive control), P < 0.0001. Insulin and glucose transporter-4 mRNA gene expression were elevated by VFE (P < 0.005 and P < 0.0001, respectively) compared with diabetic controls. In vitro data also indicated that VFE inhibited sucrose and maltase activity by 55.6% and 46.4%, respectively. The higher dose of VFE, but not the lower dose, also increased the activity of antioxidant enzymes erythrocyte superoxide dismutase by 57%, glutathione peroxidase by 35%, and catalase by 19%.Feshani 2011

Clinical data

The effect of Blueberin supplement (containing chlorogenic acid 50 mg extracted from V. arctostaphylos leaves plus at least myricetin flavonoid 50 mg extracted from bayberry) on fasting plasma glucose, liver enzymes (ALT, AST, gamma-glutamyltransferase [GGT]), and C-reactive protein was evaluated in 42 women with type 2 diabetes mellitus in a 4-week, randomized, placebo-controlled trial.

Participants received dietary advice, and food and beverages were provided. Supplementation with Blueberin 300 mg 3 times daily improved fasting plasma glucose (mean change: 39 mg/L, P < 0.001) compared with placebo, which was correlated with the reduction in C-reactive protein (mean reduction from 5.18 to 2.14 mg/L; P < 0.05). Plasma levels of ALT, AST, and GGT were also significantly reduced (P < 0.05) with Blueberin, suggesting relevant antioxidant and anti-inflammatory effects.Abidov 2006

Fasting blood glucose, 2-hour postprandial glucose, HbA1c, and liver/kidney function were assessed after administrating a standardized fruit extract from Caucasian whortleberry in a randomized, double-blind, placebo-controlled trial in Iranian adults with type 2 diabetes (N = 74) who were resistant to conventional, oral antihyperglycemic medications and who refused necessary insulin therapy. The Caucasian whortleberry fruit extract capsules were standardized to 21% anthocyanin content; one 350 mg capsule was taken orally every 8 hours for 2 months with oral antihyperglycemic drugs. Dietary modifications were also encouraged for both groups, which included restricting the intake of processed carbohydrates. Patients receiving the extract experienced significantly improved fasting blood glucose (P = 0.007), 2-hour postprandial glucose (P < 0.001), and HbA1c (P = 0.005) levels compared with the placebo group; no significant effects were seen in ALT, AST, or creatinine. Percent changes compared with baseline for the extract were also significantly reduced (P < 0.001 for all) for fasting glucose, postprandial glucose, and HbA1c levels (16.3%, 13.5%, 7.3%, respectively), whereas percent changes compared with baseline in the placebo group increased nonsignificantly (4.7%, 6.5%, 3.3%, respectively).Kianbakht 2013 A 2015 multicenter, randomized, placebo-controlled trial reported significant improvements compared with baseline and controls but not compared with placebo for fasting blood glucose, 2-hour postprandial glucose, and insulin sensitivity in adults with type 2 diabetes resistant to oral hypoglycemic agents. However, study methodology was not clearly presented because some participants were reported as "double-participants" who received 2 study capsules twice daily, whortleberry preparation was not clearly defined, and placebo data were not reported.Mirfeizi 2016

Hyperlipidemia

Animal data

In contrast to a metformin (100 mg/kg)-treated group, VFE reduced triglycerides by 41% (P < 0.002) at the 200 mg/kg dose and by 75% (P < 0.0001) at the 400 mg/kg dose; total cholesterol and very low density lipoprotein were also reduced by both doses of VFE without any significant changes in high density lipoprotein (HDL) or low density lipoprotein (LDL).Feshani 2011

Clinical data

A randomized, double-blind, placebo-controlled trial assessed the effects of standardized Caucasian whortleberry fruit extract on biomarkers in Iranian adults (N = 80) with newly diagnosed primary hyperlipidemia. Patients were advised to restrict fatty foods. Whortleberry improved all biomarkers: total cholesterol (P < 0.001), LDL (P = 0.002), HDL (P < 0.001), and triglycerides (P = 0.002) compared with placebo; no significant effects were observed on liver enzymes (ALT, AST) or creatinine. Percent changes from baseline were also improved in the extract group compared with the placebo group; total cholesterol decreased 27.6% vs 2.2%, triglycerides were reduced 19.2% vs 9.3%, LDL decreased 26.3% vs 8.2%, and HDL increased 37.5% vs 3.3%, respectively. No adverse events were reported.Feshani 2011 In a 2015 meta-analysis of random clinical trials evaluating effects of Vaccinium berries on lipid parameters (N = 16 studies; N = 1,109 participants), 2 studies with a total of 65 subjects studied whortleberry. Both were conducted in Iran with data published in 2014. The anthocyanin dosage and duration of Caucasian whortleberry supplementation were 7.35 mg/day for 8 weeks and 90 mg/day for 4 weeks. In contrast to studies of other Vaccinium berries, whortleberry treatment resulted in significant improvements in total cholesterol and triglycerides compared with placebo, with a mean difference of −1.44 mmol/L (95% confidence interval [CI]: −2.32, −0.56; P = 0.001) and −0.36 (95% CI: −0.49, −0.24; P = 0.02), respectively. In addition to bilberry, whortleberry showed statistically significant benefits on LDL and HDL cholesterols with a mean difference of −0.71 mmol/L (95% CI: −1.0, −0.41; P < 0.001) and 0.32 mmol/L (95% CI: 0.26, 0.38; P < 0.001), respectively. No adverse effects were observed.Zhu 2015

Other uses

Animal data

In rats gavaged with indomethacin, those treated with a V. arctostaphylos extract demonstrated reduced gastric ulcer development compared with controls.Fallah 2013

Dosing

Diabetes

Trials report oral dosages of Caucasian whortleberry standardized fruit extract (21% anthocyanins) of 350 mg every 8 hours for up to 2 months.Kianbakht 2013

Hyperlipidemia

Trials report oral dosages of Caucasian whortleberry standardized fruit extract (21% anthocyanins) of 350 mg every 8 hours for up to 2 months. Based on results from a 2015 meta-analysis of RCTs, the anthocyanin doses in these 2 studies were 7.5 mg/day for 8 weeks and 9 mg/day for 4 weeks.Zhu 2015, 1Kianbakht 2014

Pregnancy / Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking. Pregnant and breast-feeding women were excluded from studies assessing the effects of Caucasian whortleberry on glycemic or lipid parameters.Kianbakht 2013, Mirfeizi 2016, Kianbakht 2014

Interactions

None well documented. Caucasian whortleberry was used in combination with conventional oral hypoglycemic agents in 2 RCTs with no interactions or adverse events reported; patients on medications for hyperlipidemia were excluded.Kianbakht 2013, Mirfeizi 2016, Kianbakht 2014

Adverse Reactions

No adverse events have been reported in clinical trials. Data are limited.

Toxicology

Due to the resemblance of Caucasian whortleberry (V. arctostaphylos) to A. belladonna, accidental poisonings have been reported after mistaken consumption.Cikla 2011

References

Abidov M, Ramazanov A, Jimenez Del Rio M, Chkhikvishvili I. Effect of Blueberin on fasting glucose, C-reactive protein and plasma aminotransferases, in female volunteers with diabetes type 2: double-blind, placebo controlled clinical study. Georgian Med News. 2006;(141):66-72.17261891
Cikla U, Turkmen S, Karaca Y, Ayaz FA, Turedi S, Gunduz A. An Atropa belladonna L. poisoning with acute subdural hematoma. Human Exp Toxicol. 2011;30(12):1998-2001.21540312
Fallah Huseini H, Kianbakht S, Hoormand M. Protective effects of Vaccinium arctotaphylos L., Berberis thunbergii var. atropurpurea chenault, Elaeagnus angustifolia L. and Launaea acanthodes (Boiss) O. Kuntze against indomethacin-induced gastric ulcers in rats. J Med Plants. 2013;12(47):62-69.
Feshani AM, Kouhsari SM, Mohammadi S. Vaccinium arctostaphyos, a common herbal medicine in Iran: molecular and biochemical study of its antidiabetic effects on alloxan-diabetic Wistar rats. J Ethnopharmacol. 2011;133(1):67-74.20850514
Gvozdetsky NA. Caucasus. Encyclopedia Britannica. http://www.britannica.com/place/Caucasus. Updated May 20, 2015. Accessed October 30, 2015.
Kianbakht S, Abasi B, Dabaghian FH. Anti-hyperglycemic effect of Vaccinium arctostaphylos in type 2 diabetic patients: a randomized controlled trial. Forsch Komplementmed. 2013;20(1):17-22.23727759
Kianbakht S, Abasi B, Hashem Dabaghian F. Improved lipid profile in hyperlipidemic patients taking Vaccinium arctostaphylos fruit hydroalcoholic extract: a randomized double-blind placebo-controlled clinical trial. Phytother Res. 2014;28(3):432-436.23686894
Lätti AK, Kainulainen PS, Hayirlioglu-Ayaz S, Ayaz FA, Riihinen KR. Characterization of anthocyanins in Caucasian blueberries (Vaccinium arctostaphylos L.) native to Turkey. J Agric Food Chem. 2009;57(12):5244-5249.19480388
Mirfeizi M, Mehdizadeh Tourzani Z, Mirfeizi SZ, Asghari Jafarabadi M, Rezvani HR, Afzali M, Gholami MJ. Controlling diabetes mellitus type 2 with herbal medicines: A triple blind, randomized clinical trial of efficacy and safety. J Diabetes. 2016;8(5):647-656.26362826
Nickavar B, Amin G. Anthocyanins from Vaccinium arctostaphylos berries. Pharm Biol. 2004;42(4-5):289-291.
Zhu Y, Miao Y, Meng Z, Zhong Y. Effects of Vaccinium berries on serum lipids: a meta-analysis of randomized controlled trials. Evid Based Complement Alternat Med. 2015;2015:79032926345230

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