Hypertension is a major health risk that significantly contributes to cardiovascular disease and stroke. Further, the incidence of hypertension increases with age, affecting approximately 30% of all adults and more than 60% of adults over 65 years of age (1
). Persistent hypertension triples the incidence of heart disease and stroke and magnifies the adverse effects of other cardiovascular risk factors, e.g., smoking, type 2 diabetes, etc. (2
). While most studies examining the mechanisms of hypertension have focused on men, it is clear that women also experience significant morbidity and mortality from effects related to hypertension, but there is a significant gender disparity in the incidence of hypertension and cardiovascular disease. Prior to menopause, blood pressure and cardiovascular disease is significantly lower in women than age-matched men. However, following menopause, the incidence of hypertension and cardiovascular disease increases dramatically in women, eventually approximating the incidence in men (4
). While the mechanism underlying this increase is unknown, the loss of estrogen traditionally has been considered the primary factor.
The close correlation between estrogen loss and hypertension, cardiovascular disease, bone density loss and hot flashes made the use of hormone replacement therapy (HRT) commonplace throughout the last half of the 20th Century. The cardioprotective effects of HRT were supported by numerous basic research reports and clinical observations demonstrating a reduction of hypertension, atherosclerosis and cardiovascular disease in postmenopausal women on HRT. However, an increase in breast cancer rates in woman receiving HRT led some researchers to question the safety of the treatment. The Women’s Health Initiative and other contemporary studies further questioned the safety of HRT by demonstrating increased risk in thrombolytic events and heart attacks in HRT recipients. As a result, HRT has been strongly discouraged by most physicians and medical societies. The reported adverse effects of HRT have led many clinicians and users to seek alternative methods including the use of dietary supplements to provide the health benefits of HRT without the unfavorable effects.
While reports vary, most surveys suggest that over 50% of adults in the United States regularly take a dietary supplement (most frequently multivitamins), and about 33% of women of perimenopausal/postmenopausal age (45–60 years of age) regularly take some form of botanical supplement (6
). The widespread use of supplements extends worldwide, where the majority of people rely on traditional medication (predominantly the use of plant extracts) for primary prevention/treatment of disease (10
). The significant increase in US consumption of these supplements reflects increased desire for effective, safe, non-pharmaceutical therapies. Further, compliance with these treatments is better than that for most common pharmaceutical treatments, increasing their potential effectiveness when compared to drug therapies. While many of these supplements are taken for their presumed estrogenic actions, most of them appear to be only weakly or non-estrogenic.
Some of the most common botanicals used are soy, Ginko biloba, Kava kava, grape derivatives, Echinacea and black cohosh (7
). However, the efficacy of botanicals as primary treatments for most diseases lacks basic and clinical research documentation. Botanical supplements appear to be useful as adjutants to pharmaceutical therapy and as preventative treatments, but the increasingly widespread usage of botanicals presents significant safety concerns. Botanical supplements are not as closely regulated as pharmaceutical products, and therefore, many may be adulterated with unexpected metabolites that could cause adverse reactions. Also, the concentration of active ingredients in botanical extracts can be very high compared to their concentration in whole plants, and therefore, toxicity may result from their ingestion. Further, the lack of basic and clinical research translates into an absence of reliable dosage guidelines. This problem is exacerbated by the belief that “if a little helps, a little more helps more” (11
). Dietary intake of soy isoflavones chronically taken in excess (150mg versus 50 mg in Western diet or 100 mg in Japanese diet) can stimulate endometrial hyperplasia (12
). A second more publicized example of adverse effects of botanicals relates to ephedra, which is a very effective weight loss dietary supplement for middle age and older adults. But it can have catastrophic results when younger adults take in it in large excess (13
). St. John’s wort decreases depression in many users, but it also stimulates the pregnane X receptor and, thereby, alters hepatic metabolism of other pharmacological therapies (15
). Similarly, Kava kava appeared to be an effective anxiolytic and to possibly exert a wide range of other heath benefits. However, hepatotoxicity linked to kava ingestion led to a ban on the botanical and careful consideration of its mechanisms of adverse action (17
). Clearly, Kava kava is not hepatotoxic on its own, but increasing evidence suggests that its ability to alter drug metabolism in the body can lead to the serious side effects. Thus, supplements cannot be assumed to be safe just because they are “natural.” Even for the “safe” botanicals, one must be vigilant to both the beneficial and the adverse interactions between the botanical and diet.
Many of the botanicals display estrogenic-like binding and appeared to be promising for the alleviation of affective postmenopausal symptoms. Thus, studies have explored the potential of botanicals as alternatives to HRT for ameliorating hot flushes/flashes and night sweats. However, none of the tested botanicals has proven as effective as HRT. Black cohosh is the best candidate for alleviating these primary symptoms (18
), but it remains very controversial since several large scale trials have not demonstrated any beneficial, postmenopausal effects, e.g., (19
This review summarizes recent findings in relation to the utility of botanicals in other menopausal and aging symptoms, i.e., rise in arterial pressure, cognitive decline, insulin resistance and hyperlipidemia. While considerable caution should be exercised in the translation of animal findings to humans, several studies suggest that some commonly used botanical supplements may be useful adjuvants in reducing these symptoms.