We examined the antihypertensive effects of ginkgo biloba in elderly men and women from the GEM study. The major finding of this analysis was that ginkgo biloba had no effect on BP or PP in this population. We found similar reductions in systolic and diastolic BP and PP in the ginkgo biloba and placebo groups. Baseline hypertension status did not modify the antihypertensive effects of ginkgo biloba; however, it did influence the changes in BP observed during follow-up. Hypertensives had significant reductions in all three BP variables, while normotensives had significant increases in systolic BP and PP. On the other hand, BP and PP remained fairly stable in pre-hypertensives. These findings are consistent with regression to the mean and were unchanged even after excluding participants on antihypertensive medications at baseline or adjusting for changes in medication use over time. We also found no evidence that ginkgo biloba reduces the incidence of hypertension.
Surprisingly, there are only a few studies that have investigated the potential antihypertensive properties of ginkgo biloba
in humans. Kalus et al. reported no significant differences in systolic or diastolic BP in young (mean age: 23 yrs), normotensive subjects randomized to 240 mg/day of gingko biloba
for 7 days compared to the placebo group.9
Similarly, Mehlsen et al. reported no differences in BP in a slightly older (median age: 32 yrs), normotensive population after 6 weeks of gingko biloba
(28.8 mg ginkgoflavonglucoside and 7.2 mg terpenlactones/day).8
These data are consistent with findings in rat studies, which show that ginkgo biloba
has no effect on BP in normotensive controls.3–7
In contrast, ginkgo biloba
has significant BP-lowering effects in hypertensive rats, and this effect occurs early in the development of hypertension. In this regard, one study found that in pre-hypertensive adults aged 21 to 57 yrs, the intake of ginkgo biloba
(120 mg/day) for 3 months led to a 6% and 21% reduction in systolic and diastolic BP, respectively.10
In our study, ginkgo biloba
had no effect on BP in elderly pre-hypertensives. However, the lack of a significant change in BP among those with pre-hypertension precludes observing any differences due to treatment. To our knowledge, no other studies have reported the effects of long-term ginkgo biloba
supplementation on BP in hypertensive individuals or in an older population. Nevertheless, other beneficial effects on the vasculature have been reported after acute and chronic gingko biloba
intake in humans, including increases in coronary, ocular, and forearm blood flow, improvements in endothelium-dependent vasodilation, and reductions in peripheral vascular resistance.8, 14, 15
This suggests that, despite the absence of an antihypertensive effect of ginkgo biloba
in the present study, it is possible that other unmeasured markers of vascular health may have actually improved.
It should be noted that the age of the GEM study population could be a factor contributing to the lack of significant findings. Most of the rat studies showing a significant BP-lowering effect of ginkgo biloba
were conducted in young hypertensive rats (i.e. 5–10 weeks old). However, one study found that 4 weeks of gingko biloba
was unable to attenuate the rise in BP or PP in 50 week-old hypertensive rats.16
The authors suggested that in elderly hypertensives, long-term ginkgo biloba
supplementation may not be useful in improving cardiovascular function. Indeed, it is possible that the antihypertensive effects of ginkgo biloba
may not be evident in elderly persons, particularly those with prolonged exposure to high BP. Moreover, a recent analysis in the REASON study demonstrated that among individuals with uncomplicated hypertension, those with the highest aortic stiffness had the smallest BP reduction in response to treatmenet.15
The authors concluded that aortic stiffness is a major determinant of the effectiveness of antihypertensive therapy. It is possible that increased aortic stiffness may also reduce the antihypertensive effects of ginkgo biloba
. In the REASON study, PP increased significantly across tertiles of aortic stiffness from 59 mmHg to 68 mmHg. In our study population, the mean PP was 64 mmHg, suggesting that our participants potentially had increased aortic stiffness as well. Taken together, it seems plausible that age-related changes in the vasculature may affect the ability of ginkgo biloba
to lower BP in elderly individuals.
There were a few limitations in this study. The study population included a select cohort of elderly adults at increased risk for dementia; thus, our results may have limited generalizability. Also, we could not fully control for the effect of antihypertensive medications. Although we did a secondary analysis excluding participants who were on these medications at baseline, over 96% of baseline non-users eventually started taking antihypertensive medications at some point during follow-up. Thus, it is possible that the effects of these medications washed out any potential effect of ginkgo biloba
. Moreover, there is some indication that ginkgo biloba
may interact with specific classes of antihypertensive medications to alter their pharmacological effects.17–19
For this reason, we are currently examining the interaction between type of antihypertensive medication and treatment group on BP in the GEM study. There was also no data collected on self-reported hypertension during follow-up. Thus, in our definition of incident hypertension, we could not account for confounding by indication. As such, we may have included participants who were not hypertensive, thereby diluting our ability to find an association with treatment. Nevertheless, these medications affect BP whether prescribed for that purpose or not, and our results were unchanged even after adjusting for medication use over time. These limitations notwithstanding, this is the first and largest controlled, randomized clinical trial to examine the effects of ginkgo biloba
on BP. In addition, a commonly-prescribed dose and a standardized formulation of ginkgo biloba
extract were used in this study. Other strengths include the duration of exposure (median, 6.1 yrs; maximum, 7.3 yrs) and the low drop-out rate (<10%).11
In summary, ginkgo biloba was not effective in reducing BP or the incidence of hypertension in elderly men and women in the GEM study. Despite the negative results, this study begins to address an important question regarding the effectiveness of ginkgo biloba in improving hemodynamics and vascular function in elderly persons, which is an area of research that has been largely unexplored. Future studies should determine whether these findings are applicable to a slightly younger population (e.g. 60–75 yrs) that is pre-hypertensive or hypertensive and not on BP-lowering medications. Additionally, it would be useful to assess other measures of vascular health, such as endothelial function or arterial stiffness, which could provide cardioprotective benefits even in the absence of reductions in BP.