Caucasian Whortleberry
Scientific Name(s): Vaccinium arctostaphylos
Common Name(s): Caucasian blueberry, Cyah-gileh, Qaraqat
Medically reviewed by Drugs.com. Last updated on Feb 20, 2024.
Clinical Overview
Use
The fruit and leaves of Caucasian whortleberry have been used historically to treat type 2 diabetes, hyperlipidemia, and high blood pressure. Limited data from a few small randomized, placebo-controlled trials of short duration in patients with type 2 diabetes mellitus or hyperlipidemia demonstrated beneficial effects with use of Caucasian whortleberry fruit extract. However, there is limited quality clinical evidence to recommend Caucasian whortleberry for any indication.
Dosing
Clinical trials report standardized Caucasian whortleberry fruit extract dosages of 350 mg orally every 8 hours for up to 2 months in patients with type 2 diabetes or hyperlipidemia.
Contraindications
Contraindications have not been identified.
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
No data.
Scientific Family
- Ericaceae (heath)
Botany
Vaccinium species include cranberries, bilberries, blueberries, and whortleberries. V. arctostaphylos L. is one of approximately 200 species of the genus Vaccinium (Ericaceae). It is a compact deciduous shrub (1.5 to 2.5 m in height) 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. V. arctostaphylos 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.(Abidov 2006, Gvozdetsky 2019, Lätti 2009, Nickavar 2004)
Related/similar drugs
turmeric, Ginkgo Biloba
History
Traditionally, decoctions and infusions of Caucasian whortleberry leaves have been used as a hypoglycemic agent for treating type 2 diabetes and prediabetes (impaired glucose tolerance). The dried berries have also been used to treat type 2 diabetes and high blood pressure at a dosage of 5 g/day. The leaves and berries are harvested for both commercial sale and household consumption.(Abidov 2006, Kianbakht 2013, Lätti 2009, Nickavar 2004, 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, which contribute to their color. Anthocyanins are water-soluble pigments composed 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). In analyses of 5 cultivars of V. arctostaphylos berries harvested in August 2007 and 2008 from their native habitat in northeastern Anatolia, Turkey, 19 anthocyanins were identified, 15 of which are also found in bilberry. The 5 aglycones (delphinidin, cyanidin, petunidin, peonidin, and malvidin) were glycosylated with 6 sugar moieties (galactose, glucose, arabinose, sambubiose, pentose, and xylose). The total anthocyanin content calculated on a fresh weight basis was 261±21 mg per 100 g; the 3 major anthocyanidins were delphinidin (41%±41%), petunidin (19%±1%), and malvidin (20%±3%).(Gvozdetsky 2019, Lätti 2009, Nickavar 2004)
The average proportions of sugar moieties were 61%±7% glucosides, 22%±4% arabinosides, 11%±2% galactosides, and 5%±1% xylosides.(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 and in vitro data
V. arctostaphylos fruit extract (VFE) was administered at 200 and 400 mg/kg of 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 (decrease of 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 activity of the antioxidant enzymes erythrocyte superoxide dismutase (by 57%), glutathione peroxidase (by 35%), and catalase (by 19%).(Feshani 2011)
Clinical data
In a randomized, double-blind, placebo-controlled trial of Iranian adults with type 2 diabetes (N=74) who were resistant to conventional oral antihyperglycemic medications and who refused insulin therapy, fasting blood glucose, 2-hour postprandial glucose, HbA1c, and liver/kidney function were assessed after administration of a standardized fruit extract from Caucasian whortleberry. 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, including restricting 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. Percentage reductions in fasting glucose, postprandial glucose, and HbA1c levels were significant in the whortleberry group compared with baseline (16.3%, 13.5%, and 7.3%, respectively; P<0.001 for all); levels increased nonsignificantly in the placebo group (4.7%, 6.5%, and 3.3%, respectively).(Kianbakht 2013) In a 2015 multicenter, randomized, triple-blind, placebo-controlled trial in adults with type 2 diabetes resistant to oral hypoglycemic agents (N=105), supplementation with whortleberry 1 g/day for 90 days resulted in improvements compared with baseline and controls, but not compared with placebo, for fasting blood glucose, 2-hour postprandial glucose, and insulin sensitivity. However, study methodology was not clearly presented: Some participants were reported as "double-participants" who received 2 study capsules twice daily, the whortleberry preparation was not clearly defined, and placebo data were not reported.(Mirfeizi 2016)
Gastric ulcers
Animal data
In rats gavaged with indomethacin, those treated with a V. arctostaphylos extract demonstrated reduced gastric ulcer development compared with controls.(Fallah Huseini 2013)
Hyperlipidemia
Animal data
In a study in alloxan-diabetic Wistar rats, VFE reduced triglycerides by 41% (P<0.002) at a 200 mg/kg dose and by 75% (P<0.0001) at a 400 mg/kg dose compared to a metformin (100 mg/kg)–treated group. Total cholesterol and VLDL were also reduced by both doses of VFE, without any significant changes in HDL or LDL.(Feshani 2011)
Clinical data
A randomized, double-blind, placebo-controlled trial assessed the effects of standardized Caucasian whortleberry fruit extract (dosed at 350 mg every 8 hours for 2 months [total anthocyanins per each 350 mg capsule: 2.45 mg]) on biomarkers in Iranian adults with newly diagnosed primary hyperlipidemia (N=80). Patients were advised to restrict their intake of fatty foods. Whortleberry improved all biomarkers compared with placebo: total cholesterol (P<0.001), LDL (P=0.002), HDL (P<0.001), and triglycerides (P=0.002); no significant effects were observed on liver enzymes (ALT, AST) or creatinine. Improvements from baseline were also observed in the extract group compared with the placebo group: Total cholesterol decreased by 27.6% versus 2.2%, triglycerides were reduced by 19.2% versus 9.3%, LDL decreased by 26.3% versus 8.2%, and HDL increased by 37.5% versus 3.3%, respectively. No adverse events were reported.(Kianbakht 2014) In a 2015 meta-analysis of randomized clinical trials evaluating the effects of Vaccinium berries on lipid parameters (16 studies; N=1,109), 2 studies evaluated whortleberry (n=65). Both were conducted in Iran, with data published in 2014. The anthocyanin dosages and durations 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 mean differences of −1.44 mmol/L (95% CI, −2.32 to −0.56; P=0.001) and −0.36 (95% CI, −0.49 to −0.24; P=0.02), respectively. Compared to bilberry, whortleberry showed statistically significant benefits on LDL and HDL cholesterol levels, with mean differences of −0.71 mmol/L (95% CI, −1 to −0.41; P<0.001) and 0.32 mmol/L (95% CI, 0.26 to 0.38; P<0.001), respectively. No adverse effects were observed.(Zhu 2015)
Hypertension
Clinical data
A 3-month, double-blind, randomized, placebo-controlled trial investigated the safety and efficacy of V. arctostaphylos berry extract as an adjunct to antihypertensive therapy in 100 overweight and obese Iranian patients. At the end of the study, a statistically significant improvement was seen in both systolic (−10.3 mm Hg, P<0.001) and diastolic (−5.5 mm Hg, P=0.001) blood pressure outcomes with the intervention compared with placebo. No adverse events or adverse drug interactions were observed.(Kianbakht 2019)
Dosing
Diabetes
Clinical trials report standardized Caucasian whortleberry fruit extract (21% anthocyanins) dosages of 350 mg orally every 8 hours for up to 2 months.(Kianbakht 2013)
Hyperlipidemia
Clinical trials report standardized Caucasian whortleberry fruit extract dosages of 350 mg every 8 hours for 2 months (total anthocyanins per each 350 mg capsule: 2.45 mg). Based on results from a 2015 meta-analysis of randomized controlled trials, the 2 studies evaluating whortleberry for hyperlipidemia reported anthocyanin dosages of 7.35 mg/day for 8 weeks and 90 mg/day for 4 weeks.(Kianbakht 2014, Zhu 2015)
Pregnancy / Lactation
Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking. Pregnant and breastfeeding women were excluded from studies assessing the effects of Caucasian whortleberry on glycemic or lipid parameters.(Kianbakht 2013, Kianbakht 2014, Mirfeizi 2016)
Interactions
None well documented. Caucasian whortleberry was used in combination with conventional oral hypoglycemic agents in 2 randomized controlled trials, with no interactions or adverse events reported; however, patients taking medications for hyperlipidemia were excluded.(Kianbakht 2013, Kianbakht 2014, Mirfeizi 2016)
Adverse Reactions
No adverse events have been reported in clinical trials. Data are limited.
Toxicology
Accidental poisonings have been reported after mistaken consumption of A. belladonna, which resembles Caucasian whortleberry.(Cikla 2011)
References
Disclaimer
This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.
This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.
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