The bilberry plant is reputed to possess antidiabetic properties, and its berries and leaves (as well as those of other Vaccinium species) have been used for centuries to ameliorate the symptoms of diabetes. In a survey of 685 Italian herbalists, bilberry ranked fourth in a list of herbal remedies recommended for improvement of glycemic control.
The reported hypoglycemic effect of bilberry is a desirable effect for helping to prevent or control type 2 diabetes, which is a highly prevalent condition caused by insulin resistance and B cell failure (ADA 2010). Type 2 diabetes is associated with increased oxidative stress, inflammation, and dyslipidemia, and is accompanied by an increased risk of CVD, cancer, and vision loss through cataract and retinopathy. The hypoglycemic effect of bilberry may be mediated in part by interference with enzyme action, especially α-glucosidase activity, and also by effects on insulin secretion and glucose transport. Anthocyanins were found to stimulate insulin secretion from cultured rodent pancreatic B cells, with cyanidins and delphinidins showing the greatest effect among different anthocyanins tested. In addition, low-bush blueberry, which belongs to the same family as bilberry, at 12.5 μg/mL was demonstrated to enhance glucose transport into muscle cells and adipocytes in the absence of insulin. In an animal study with a water–alcohol extract of bilberry leaves given to streptozotocin-induced diabetic mice (3 g/kg/day for 4 days), a significant decrease (26%) was seen in plasma glucose. Blood glucose was significantly decreased (by 33% and 51%, respectively) after administration of a phenolic-rich extract (containing approximately 287 mg/g anthocyanin) and an anthocyanin-enriched fraction (containing approximately 595 mg/g) from a Vaccinium blueberry extract at a dose 500 mg/kg to diabetic (C57b1/6J) mice (Grace et al. 2009). In gavage treatment with pure anthocyanins (300 mg/kg), malividin-3-O-glucoside was found to have a significant hypoglycemic effect in these animals, but delphinidin-3-O-glucoside did not (Grace et al. 2009). As shown in Table 4.1, the malvidin-3-O-glucoside concentration of bilberry is 3.35% (Upton 2001). Significant decreases in serum glucose and fructosamine were shown in alloxan-induced diabetic mice at, respectively, 120 minutes and 7 days after being given a 20 mg/kg dose of “antidiabetis,” an herbal preparation that included bilberry.
Obesity is a strong predisposing factor for type 2 diabetes. Berry polyphenols may help prevent obesity by inhibiting digestive enzymes, such as lipase, thereby lowering fat absorption. Cyanidin-3-glucoside has been shown to suppress the development of obesity in mice fed a high-fat diet and to regulate human adipocyte function. Human preadipocytes were collected from subcutaneous adipose tissue, cultured, and differentiated into adipocytes before being treated with anthocyanins for 24 hours. Adiponectin, an anti-inflammatory cytokine, was upregulated, and there was downregulation of the proinflammatory cytokine IL-6 and also of the plasminogen activator inhibitor-1 (PAI-1); the anthocyanin treatment also activated adenosine monophosphate (AMP)-activated protein kinase (AMPK) in adipocytes without increasing the AMP/adenosine triphosphate (ATP) ratio. Together, these changes indicate a role for anthocyanins in preventing metabolic syndrome, an increasingly common condition associated with insulin resistance, hypertension, and dyslipidemia that often progresses to type 2 diabetes. In a follow-up study, Tsuda and coworkers reported that a bilberry extract added to the diet of diabetic mice (27 g/kg diet, which gave an anthocyanin content of 10 g/kg diet) lowered serum glucose and improved insulin sensitivity. There were no differences in body weight or serum adiponectin levels between the bilberryfed and the control animals, but the antidiabetic effects of the bilberry extract were associated with AMPK activation in white adipose tissue and skeletal muscle and liver, and were accompanied by increased glucose transporter 4 (GLUT 4) in white adipose and skeletal tissue and lower hepatic gluconeogenesis.
Although there are some published human studies of the hypoglycemic effects of berries (e.g., cranberry, chokeberry), strong evidence from human trials is lacking. To our knowledge, there are no published controlled human studies with bilberry on diabetes patients. The two published human supplementation studies with bilberry studied subjects at elevated risk of CVD, but they were not diabetic. It is unlikely that significant effects of bilberry would be seen in subjects with normal glucose tolerance No differences were seen in plasma glucose levels in 60 nondiabetic dyslipidemic subjects who took a mixed bilberry and blackcurrant anthocyanins supplement (120 mg/day anthocyanins) for 12 weeks. In the study by Karlsen et al. (2010), which investigated the effect of 4 weeks of supplementation with 330 mL/day of bilberry juice in subjects with at least one risk factor for CVD, no glucose data were shown.
Although we lack human data on the antidiabetic effects of bilberry, numerous in vitro and animal studies provide good evidence of a role for bilberry in treating or preventing type 2 diabetes. This could be a very rewarding area of future research given the huge socioeconomic problem posed by this highly prevalent disease. In addition to the clear benefits that would come from increasing insulin secretion and glucose transport, other effects of bilberry, such as its antioxidant, anti-inflammatory, and lipid-lowering effects, would help delay the serious vascular complications of diabetes. Controlling obesity would help prevent many cases of type 2 diabetes. Also, there is increasing evidence of increased risk of cancer with hyperglycemia to hyperglycemia. The Metabolic Syndrome and Cancer (Me-Can) Project is a large prospective study of six European cohorts, with a total of over 500,000 subjects, and after an average follow-up of 10.4 years, results strongly support high blood glucose as a risk factor for incident cancer at many specific sites and for cancer deat. Oxidative stress, inflammation, and increased amounts of growth factors, including IGF-1, also increase cancer risk and are high in those with type 2 diabetes. The combination of antioxidant, anti-inflammatory, and hypoglycemic effects of an herb or a functional food would bring significant long-term benefits, particularly to those with type 2 diabetes, and studies of bilberry focusing on these effects in this group are warranted.