Cardiovascular Effects

EGb 761 at a dose of 200 mg administered to 60 patients intravenously for 4 days improved skin perfusion and decreased blood viscosity without affecting plasma viscosity (19). Another GB extract, LI 1730, increased blood flow in nailfold capillaries and decreased erythrocyte aggregation compared to placebo in 10 volunteers at a dose of 112.5 mg (26). Blood pressure, heart rate, packed cell volume, and plasma viscosity were unchanged. A study in subjects with type 2 diabetes mellitus complicated with retinopathy evaluated the effects of administration of GB (EGb 761) for 3 months on erythrocyte hemorrheology (27). At the end of the treatment period, it was observed that blood viscosity was significantly reduced, fibrinogen levels were decreased, and erythrocytes were more deformable. Finally, retinal capillary blood flow was improved. However, in a double-blind, placebo-controlled trial of GB in the treatment of Raynaud's disease, after 10 weeks of treatment there was no improvement in hemorrheology between the two groups (28). There was a significant decrease in the number of attacks per day.

Studies have been conducted to examine the effects on GB administration on blood pressure and blood flow. In one study, either GB or placebo was administered in a double-blind, placebo-controlled crossover design to healthy volunteers and forearm blood flow was measured (29). Forearm blood flow was significantly higher during GB therapy than with placebo and mean arterial pressure remained unchanged, thus rendering the forearm vascular resistance significantly lower during active treatment. In a related study, Jezova and colleagues studied the effect of GB (EGb 761) treatment on changes in blood pressure and cortisol release following exposure to stress stimuli (30). The rise in systolic blood pressure following stress stimuli was significantly lower (~20 mmHg rise in subjects receiving EGb 761 vs an ~30 mmHg rise in subjects receiving placebo) in the GB group. Differences in diastolic pressure rise were similar (~10 mmHg difference between GB and placebo) between the two groups. GB did inhibit the stress-induced increase in cortisol release in the male subjects but had no effect in the female subjects.

Because of effects noted with in vitro studies demonstrating that ginkgolides are capable of inhibiting platelet-activating factor (PAF), which is involved in platelet aggregation and inflammatory processes such as those seen in asthma, ulcerative colitis, and allergies (reviewed in 5,19,31), it has been suggested that bleeding parameters might be affected also. Several case reports of bleeding disorders among people receiving GB have been described (see Subheading 7.1.). However, at least in healthy volunteers, changes in platelet function or coagulation have not been substantiated. In a double-blind, placebo-controlled study of 32 healthy male volunteers receiving EGb 761 at three doses (120, 240, and 480 mg/day) for 14 days, no changes in platelet function or coagulation were noted (32). Similarly, Kohler and colleagues studied the influence of the same GBE (EGb 761) on bleeding time and coagulation in healthy volunteers (33). This double-blind, placebo-controlled study was carried out for 7 days in 50 healthy volunteers. No differences in bleeding time, coagulation parameters, or platelet activity were noted between the placebo and GB treatment groups. In a study of patients on chronic peritoneal dialysis, Kim and colleagues randomized the 66 patients into two groups; those receiving GB (160 mg/day) and those receiving no treatment (34). There was no placebo control. Except for a small but statistically significant change in the plasma D-dimer concentration, the administration of GB had no effect on any bleeding parameters. Finally, Kudolo and colleagues studied the effect of GBE on platelet aggregation and urinary prostanoid excretion in healthy subjects and patients with type 2 diabetes (35). Administration of GB had no effect on any parameter of coagulation or prostanoid excretion in the patients with type 2 diabetes. In the healthy volunteers, a modest but statistically significant decrease in thromboxane B2, PGI2, and prostanoid metabolite ratio was noted following GB treatment. It is of note that a placebo control was not included for either group.

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