Diabetes and Herbal (Botanical) Medicine

William T. Cefalu; Jaqueline M. Stephens; David M. Ribnicky

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Benzie IFF, Wachtel-Galor S, editors. Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. Boca Raton (FL): CRC Press/Taylor & Francis; 2011.

Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition.

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Chapter 19Diabetes and Herbal (Botanical) Medicine

William T. Cefalu, Jaqueline M. Stephens, and David M. Ribnicky.

19.1. INTRODUCTION

The epidemic rise in the number of new cases of diabetes is one of the most alarming statistics regarding health issues on a worldwide basis. The major concern regarding this observation relates to the development of the chronic complications associated with the condition. Specifically, the complications of diabetes have been classified as either microvascular—retinopathy, nephropathy, and neuropathy—or macrovascular—cardiovascular disease (CVD), cerebrovascular accidents (CVA), and peripheral vascular disease (PVD). It is well recognized that the complications cause considerable morbidity and mortality worldwide and, as such, negatively affect the quality of life in individuals with diabetes, with an increase in disability and death. The costs of caring for diabetes and its related complications are staggering. For example, in the United States alone, the total estimated financial burden of diabetes was US$174 billion in 2007, and it is expected to be US$330 billion by 2020 due to the expected increase in new cases.

In an individual with diabetes, on a clinical level the major objective is to design a regimen that will improve the metabolic factors associated with the development and progression of complications. As such, it is well recognized that a primary strategy is to achieve the target levels recommended for blood pressure, lipids, and glycemia. This strategy may consist of lifestyle modification alone, but more commonly it consists of lifestyle management, that is, dietary modification and enhanced physical activity, combined with pharmacological intervention from agents in multiple classes (Riddle 2005). However, as providers caring for patients with diabetes, we recognize that the patients are very interested in alternative (complementary) strategies that consist of dietary supplementation with over-the-counter agents. Supplementing conventional approaches to medical care with alternative means is extensively practiced by a large number of patients. Interestingly, more times than not, these practices appear to be undertaken without consultation with a medical provider. It is also recognized that this is not a trivial practice and not without substantial financial cost. Specifically, data from the Food and Drug Administration (FDA) of the United States suggest that more than 29,000 different nutritional supplements are available to consumers. It also appears that more than US$12 billion per year may be spent on supplements (Neuhouser 2003; Gibson and Taylor 2005).

Patients may choose to supplement their pharmacological regimen with dietary supplementation in many forms, for example, vitamin and/or mineral mixtures, but the most popular supplements taken by the patients are those considered to be from natural products, that is, herbal or botanical sources. Unfortunately, considerable controversy exists regarding the efficacy of dietary supplements in general and of botanical supplements, particularly regarding pathophysiological factors related to the treatment of patients with type 2 diabetes. The controversy exists because reported efficacy data for many of the natural products are only in the form of uncontrolled studies and anecdotal reports. Poor quality control measures may also cause inconsistent effects for certain natural products. Currently, there is a paucity of consistent and reproducible efficacy data in humans to suggest any recommendations for most botanical or bioactive supplements as adjunct treatments for risk factors related to metabolic syndrome or type 2 diabetes. Firm recommendations for general use would also require an understanding of the mechanism of action, which is not known for most botanicals.

19.2. HISTORICAL USE OF BOTANICALS

From the patient perspective, it is considered very acceptable to include herbal or botanical extracts as part of the medical intervention based on the recognition that the herbal intervention is considered to be natural and that the practice may have been part of the culture for many generations. In this regard, the use of plants and plant extracts to treat a specific disease and/or disease symptoms appears to have been part of medical care as observed for thousands of years. Although the use of plant extracts is no longer a major aspect of medical care as practiced in Western populations, it is still extremely popular in large numbers of the world’s population, particularly in Asia and Europe (Griggs 1981). However, for medicine as practiced in Western countries, one observation that appears to be forgotten is that many of the pharmaceutical agents currently prescribed appear to have been derived from natural compounds found in traditional medicinal plants (Evans 2003). As a specific example, biguanide metformin is considered one of the first-line agents used for the treatment of type 2 diabetes, and its use can be traced to the traditional use of Galega officinalis to treat diabetes and the subsequent search to identify active compounds with reduced toxicity (Cusi and Defronzo 1998). However, it has been reported that more than 1200 traditional plants may have been used for real or perceived benefit of medicinal purposes for the treatment of diabetes (Marles and Farnsworth 1995; Jung et al. 2006). In this regard, the reader is referred to a number of published reviews on the topic that contain information related to the following: (1) the botanical source of the extract; (2) the history of use by the population; (3) the specific geographic region in the world for which its use has been documented; (4) the proposed benefit of the extract; (5) known side effects; and (6) proposed mechanisms of action (Griggs 1981; Marles and Farnsworth 1995; Roman-Ramos, Flores-Saenz, and Alarcon-Aguilar 1995; Oubre et al. 1997; Dey, Attele, and Yuan 2002; Grover, Yadov and Yats 2002; Shapiro and Gong 2002; Evans 2003; Jung et al. 2006).

19.3. PROPOSED MECHANISMS OF BOTANICAL ACTIONS

Despite the historical use of botanicals to treat diabetes and its related symptoms, one of the major concerns for this area of study is the paucity of definitive and consistent data on efficacy, and more importantly, a lack of knowledge about precise mechanism(s) of action. These are significant limitations, and in large part these limitations explain why there is considerable skepticism regarding the effectiveness of herbal remedies in Western medicine. However, there is growing evidence in this area, and if a botanical is demonstrated to have a favorable effect on a given mechanism, that will provide the rationale for further and more definitive studies on a particular botanical.

The physiological parameters that regulate glucose metabolism and the pathophysiological changes that occur and that give rise to diabetes have been studied for years. These involve the interplay and function of multiple peripheral tissues, such as liver, muscle, and adipose tissue. In order to exert an effect, botanicals may theoretically modulate glucose at several different levels in multiple tissues (Table 19.1; Cefalu and Ribnicky 2009). Thus, based on reported abnormalities for type 2 diabetes, botanicals could be proposed to affect the whole-body metabolism by modulating adipocyte function and thus, regulating endocrine secretions that play a role to enhance the skeletal muscle insulin action. In addition, based on the known abnormalities, botanicals may regulate hepatic processes, that is, hepatic gluconeogenesis, and may affect the whole-body glucose levels. In this regard, a specific agent termed a “biguanide” (metformin) and derived from botanical sources appears to improve hyperglycemia by regulating hepatic processes. Type 2 diabetes is clearly a disorder that involves insulin secretory defects, and enhancing pancreatic β-cell function is another proposed pathway by which botanicals may theoretically work. Enhancing insulin secretory function may not be solely an acute effect. But as intensively pursued in preclinical and clinical trials, if a particular agent is shown to enhance proliferation and/or modulate apoptosis of islet tissue, this may markedly impact the natural progression of diabetes. There is no evidence to date that any of these postulated effects are consistently noted with any botanical supplement presently available. Finally, another postulated pathway by which botanicals may work is by direct regulation of insulin action in peripheral tissues such as skeletal muscle and adipose tissue. In this regard, there is evidence to support the botanical modulation of these processes.

TABLE 19.1

Postulated Mechanisms by Which Botanicals May Alter Whole-Body Carbohydrate Metabolism.

19.4. INSULIN RESISTANCE IN TYPE 2 DIABETES

One of the major abnormalities in obesity and type 2 diabetes is insulin resistance. Insulin resistance has been shown to be present in prediabetes, and at this stage of the natural history of diabetes, insulin secretion is observed to be increased, that is, hyperinsulinemia, in order to compensate for the insulin resistance. Given the compensation, glucose levels remain at or near the normal level. However, when insulin secretory function begins to decline, full compensation of insulin resistance is not observed, and hyperglycemia is noted at that time. Clearly, insulin resistance is a key pathophysiological feature of type 2 diabetes and is strongly associated with cardiovascular risk factors and accelerated atherosclerosis. Given the central role of insulin resistance to diabetes, one of the most desirable goals of treatment for subjects with type 2 diabetes is directed at increasing the insulin sensitivity in vivo. Caloric restriction and enhanced physical activity are well known to enhance insulin sensitivity. Unfortunately, maintenance of lifestyle intervention for patients is difficult in the long term. Therefore, a very attractive approach to improve the insulin sensitivity has been proposed with the use of botanical supplementation.

Insulin action in peripheral tissues, such as adipose tissue and muscle, involves receptor binding and enhanced intracellular signaling. The initial step is the binding of insulin to the α-subunit of its receptor. This binding leads to autophosphorylation of specific tyrosine residues of the β-subunit and enhanced tyrosine kinase activity of the receptor toward other protein substrates (Cefalu 2001; Figure 19.1). Enhanced insulin receptor tyrosine kinase activation results in tyrosine phosphorylation of insulin receptor substrates, activation of PI-3 kinase, and the resulting cellular processes associated with insulin action (glucose transport, GLUT-4 translocation, glycogen synthesis, protein synthesis, antilipolysis, and gene expression; Cefalu 2001). On theoretical grounds, a botanical may be capable of altering insulin action by modulating any of the steps in the insulin receptor signaling cascade.

FIGURE 19.1

The insulin signaling cascade. (From Cefalu, W. T. 2001. Exp Biol Med (Maywood) 226:13–26. With permission.)

19.5. BOTANICALS AND MECHANISMS RELEVANT TO TYPE 2 DIABETES

A limited list of selected botanicals that are reported to alter carbohydrate metabolism is given in Table 19.2. However, it is important to note that consistent documentation of a glucose- or insulin-lowering effects has not yet been shown for any specific botanical. Each botanical having historical use, current use in herbal supplements, or potential for clinical efficacy based on proposed mechanisms is briefly described in Sections 19.5.1 through 19.5.12.

TABLE 19.2

Selected Botanical Therapeutics and Proposed Action on Carbohydrate Metabolism.

19.5.1. Bitter Melon (Momordica charantia)

Bitter melon is a traditional plant of Asian origin that has been a popular botanical proposed for treatment of diabetes and diabetes-related complications (Leung et al. 2009). The mechanism of action is believed to be secondary to multiple bioactives, one of which, polypeptide-p, is reported to have a structure similar to insulin as found in animals, and as such, is proposed to have glucose-lowering effects (Basch, Gabardi, and Ulbricht 2003; Evans 2003; Grover and Yadav 2004; Krawinkel and Keding 2006). Specifically, bitter melon fruit contains cucurbitane-type triterpenoids, steroidal saponins called “charantins,” insulinlike peptides, and alkaloids, which are postulated to have effects on carbohydrate metabolism (Leung et al. 2009). As reported, clinical results with the use of bitter melon are inconsistent, as only about half the studies demonstrate efficacy. Clearly, there is controversy regarding the reported observations, and there are concerns with study design and the adequacy of statistical analyses.

Another variable that may contribute to inconsistent results is the preparation of the test material. Test material is comprised of fresh juice, dried whole fruit, fresh fruit, dried seedless fruit, seeds, aqueous extract, methanolic extract, or tablets (Ahmad et al. 1999; Rathi, Grover, and Vats 2002; Grover and Yadav 2004; Leung et al. 2009). Such variation would greatly affect the bioactive content of the preparation and the bioavailability of the active compounds. Ahmad et al. (1999) reported on a relatively large (n = 100) intervention study with freshly prepared bitter melon fruit given to type 2 diabetic patients after a 3-day washout period of oral medications. The investigators reported an overall decrease in fasting glucose and postprandial glucose (Ahmad et al. 1999). Other data have suggested the beneficial effects of bitter melon for related complications of diabetes, such as renal disease, neuropathy, gastrointestinal disturbances, and ophthalmologic complications, that is, cataracts, in addition to a possible beneficial effect on dyslipidemia (Ahmed et al. 2001; Grover et al. 2001; Grover, Yadav, and Vats 2002; Grover, Rathi, and Vats 2002; Rathi et al. 2002; Chaturvedi 2005; Fernandes et al. 2007).

19.5.2. Fenugreek (Trigonella foenum-graecum)

Fenugreek has a long and storied history of medicinal use and has been used worldwide for the treatment of diabetes (Basch et al. 2003; Evans 2003). Specifically, fenugreek is described as a leguminous herb that is cultivated in India and North Africa. The seeds are used as a food ingredient and spice, and they are reported to contain high amounts of protein and fiber. Fenugreek is reported to have hypoglycemic and hypocholesterolemic actions in both animal and human studies (Srinivasan 2006). The clinical effects of fenugreek, and particularly, the hypoglycemic effects, may be secondary to the fiber content, which potentially may affect gastric emptying and may result in a decrease in postprandial blood glucose levels. Many other bioactive compounds, such as the alkaloid trigonel-line and steroidal saponins, have been reported. 4-hydroxyisoleucine is considered to be an active compound in fenugreek and reportedly has an insulinlike effect (Broca et al. 1999, 2000).

As noted with several herbal preparations, inconsistent clinical results also have been observed with fenugreek that may have resulted from inadequate study design, lack of precise end points, underpowered studies, or variability in the test substance. However, fenugreek seed powder has been reported to favorably affect the glycemic index of food and glucose tolerance in both control and diabetic subjects (Gopalpura, Jayanthi, and Dubey 2009). Additional studies have suggested that treatment of diabetic subjects for 8 weeks resulted in improvements in fasting glucose and dyslipidemia (triglycerides; Kassaian et al. 2009). Interestingly, more consistent results are obtained when fenugreek is provided at larger doses of 10–20 g/day, and this may be related to an effect on digestive processes (Srinivasan 2006).

19.5.3. Gymnema (Gymnema sylvestre)

Gymnema sylvestre, known as gurmar, is native to Africa, Middle East, and India, and it has historical use in the treatment of diabetes and is commonly used (Grover, Yadov, and Vats 2002). The gymnema leaf or its extract is reported to be the most commonly used preparation of the plant. Potential antidiabetic compounds include oleanane triterpenoid saponins (i.e., gymnemic acids), dammarane saponins called gymnemosides, and a polypeptide called gurmarin (Porchezhian and Dobriyal 2003). There are extensive studies in animal models. Particularly, the effect of Gymnema sylvestre extract on carbohydrate metabolism has been suggested to be secondary to improving glucose uptake in peripheral tissues and increasing insulin secretion and β cell number in the pancreas (Dey, Attele, and Yuan 2002). However, there has been a paucity of definitive clinical studies that would allow one to provide clear guidelines on efficacy and safety (Leach 2007). In addition to the proposed systemic hypoglycemic activity in vivo, gymnema preparations are postulated to suppress the taste sensation of sweet, decrease the uptake of glucose from the small intestine, improve glucose metabolism, decrease HbA1c, and improve insulin secretion and dyslipidemia (Baskaran et al. 1990; Porchezhian and Dobriyal 2003; Ramkumar et al. 2008; Daisy, Eliza, and Mohamed Farook 2009). Clearly, completion of well-designed clinical studies is needed before definitive recommendations can be made for Gymnema.

19.5.4. Hoodia (Hoodia gordonii)

The prevalence and incidence of obesity worldwide have reached epidemic proportions. Specifically, obesity is a key pathophysiological feature that contributes to the development of the metabolic syndrome and type 2 diabetes. In general, lifestyle modifications such as dietary restriction and enhanced physical activity are very effective in promoting weight loss and decreasing rates of progression of metabolic syndrome to type 2 diabetes (Knowler et al. 2002). However, lifestyle modifications alone are rarely sustained over a long-term period. Thus, a botanical that effectively alters energy balance, that is, increasing energy expenditure or lowering energy intake, would be of great interest to public health. In this regard, hoodia is currently marketed as an appetite suppressant component of many diet products. Data suggest that the botanical appears to have an anorexic effect in preclinical studies, and a steroidal pregnane glycoside (P57AS3) has been purified from the plant and is suggested to be the responsible anorexic compound (MacLean and Luo 2004). However, there are more than 30 pregnane glycosides identified from hoodia, all of which potentially could contribute to the overall clinical effect (Shukla et al. 2009). Nonetheless, it is important to note that there is no published or definitive clinical evidence demonstrating that hoodia does effectively reduce appetite. There is another concern that relates to the adulteration of hoodia products currently available on the market (Avula et al. 2008).

19.5.5. Prickly Pear Cactus (Opuntia spp.)

Prickly pear is a common cactus, and its fleshy stems and pearlike fruits are consumed as both medicine and food. It is a widely known and a commonly used herbal treatment for glucose control in Central and South America (Roman-Ramos, Flores-Saenz, and Alarcon-Aguilar 1995; Evans 2003). Prickly pear cactus is reported to have a very high-soluble fiber and pectin content that may prevent the absorption of sugars (Marles and Farnsworth 1995). This may be the most likely reason for regulatory effects on blood glucose on a whole-body level, but other mechanisms also have been suggested (Marles and Farnsworth 1995; Roman-Ramos, Flores-Saenz, and Alarcon-Aguilar 1995; Evans 2003). Isorhamnetic-3-glucoside is reported to be one of the many active flavonoids isolated from Opuntia (Ginestra et al. 2009). In preclinical studies, Opuntia spp., pectin, seed oil, and powder significantly lowered total cholesterol, low-density lipoprotein (LDL)-cholesterol, and triglyceride levels (Fernandez et al. 1992; Li et al. 2005; Ennouri et al. 2006; Oh and Lim 2006). Favorable effects on dyslipidemia were confirmed in a pilot study of 24 nondiabetic male subjects. Specifically, Opuntia robusta pectin lowered total cholesterol by 12%, LDL cholesterol by 15%, triglycerides by 12%, blood glucose by 11%, and insulin levels by 11% (Wolfram et al. 2002). Two controlled short-term studies of 14 and 22 human subjects, respectively, reported decreased fasting glucose and insulin levels in patients with type 2 diabetes (Frati et al. 1990; El Kossori et al. 1998).

19.5.6. Ginseng (Panax spp.)

Ginseng has been a very popular botanical that has been suggested to control diabetes (Griggs 1981; Marles and Farnsworth 1995; Vogler, Pittler, and Ernst 1999; Evans 2003). A review of controlled trials (Vogler, Pittler, and Ernst 1999) using ginseng extracts (mostly Panax ginseng [Asian ginseng] and Panax quinquefolius [American ginseng]) concluded that there was insufficient evidence to support the efficacy for lipid or glycemic indications. Buettner et al. (2006) summarized a comprehensive database analysis of the reported studies of ginseng (Panax spp.) for efficacy related to cardiovascular risk factors, including blood pressure, lipid profiles, and blood glucose. The overall analysis suggested that ginseng was noted to slightly decrease blood pressure compared with placebo (range: 0–4%), but they observed mixed results for an effect on lipids. Furthermore, they found several studies showing that ginseng lowers blood glucose, but overall they concluded that the results were inconsistent (Buettner et al. 2006).

19.5.7. Cinnamon (Cinnamomum cassia, Verum, and Others)

Cinnamon has not only been used historically for the treatment of diabetes but is a supplement that is gaining in popularity, and many cinnamon products are currently available as dietary supplements. The bioactives considered to be responsible for antidiabetic effects are not precisely known, but polyphenol type-A polymers are believed to represent some of the active components of cinnamon that may have insulin-mimetic effects (Jarvill-Taylor, Anderson, and Graves 2001; Anderson et al. 2004). As such, there are data suggesting an effect in preclinical studies that have evaluated cinnamon in murine models of diabetes. There is a growing database of clinical studies on cinnamon, but similar to clinical results as observed with other herbal products, the results are not entirely consistent. Again, selection criteria of the cohort, clinical end points selected, appropriate dose, and source of cinnamon bioactives are all factors that potentially contribute to the variable clinical results (Dugoua et al. 2007). However, studies have suggested a positive effect in some settings. Specifically, Crawford (2009) evaluated 109 diabetic patients who were previously treated with diet and exercise. The intervention consisted of 1 g/day dose of cinnamon for 90 days and seemed to be effective to significantly lower antecedent glycemia, as assessed with HbA1c, in the treatment group relative to the control group. Other studies also suggested beneficial effects on glucose and lipids (Khan et al. 2003; Anderson 2008; Mang et al. 2006), whereas other investigations failed to reveal an effect on glycemia or lipids (Altschuler et al. 2007; Blevins et al. 2007). Other effects of cinnamon on cardiovascular risk factors such as antihypertensive effects have been suggested in preclinical and small clinical trials evaluating subjects with metabolic syndrome (Preuss et al. 2006; Ziegenfuss et al. 2006).

19.5.8. Russian Tarragon (Artemisia dracunculus L.)

Over the recent past, an ethanolic extract of Artemisia dracunculus L. (commonly known as Russian tarragon) has been demonstrated to have antidiabetic properties. Its antidiabetic effects were shown in several preclinical studies evaluating both chemically induced (i.e., streptozotocin-induced) and genetically diabetic (i.e., KK-A(y) mice) murine models (Ribnicky et al. 2006). Bioactives that have been identified as part of the extract include 4,5-di-O-caffeolquinic acid, davidigenin, 6-demethoxycapillarison, and 2′, 4′-dihydroxy-4-methoxydihydrochalcone as aldose reductase inhibitors (Logendra et al. 2006) and 2′, 4′-dihydroxy-4-methoxydihydrochalcone, 2′ 4-dihydroxy-4′-methoxydihydrochalcone, and sakuranetin as protein tyrosine phosphatase-1B inhibitors (Wang et al. 2008), whereas 6-demethoxycapillarisin and 2′, 4′-dihydroxy-4-methoxydihydrochalcone inhibited PEPCK gene expression in cultured liver cells (Govorko et al. 2007). Both in vitro and preclinical studies strongly suggest that the primary effect of the extract is to favorably affect insulin signaling in the muscle (Wang et al. 2008, 2010). The improved cellular signaling has been related to enhanced whole-body insulin sensitivity. A pilot human trial in a small number of insulinresistant subjects suggested that the alcoholic extract of Artemisia dracunculus L. enhanced insulin sensitivity in subjects randomized to the Artemisia extract compared to the baseline value, but it was not significantly changed compared to the placebo group. No changes in insulin sensitivity at the end of the study were noted compared to baseline in the placebo group. In addition, no changes in body weight or body fat composition between the treatment groups were observed. Of note, this pilot study was the first to show that specific bioactive compounds from the botanical extract of Artemisia dracunculus L. (i.e., davidigenin, chalcone, and sakuranetin) that had been noted to have significant effects in vitro from preclinical studies could be identified in the plasma of subjects after extract ingestion (Ribnicky et al. in press).

19.5.9. Garlic (Allium sativum)

Garlic is one of the more intriguing herbal remedies used historically. The range of beneficial effects of garlic is very broad and has been traditionally used as an antithrombotic, antihypertensive, cholesterol-lowering, antioxidant, antimutagenic, and antimicrobial agent. As would be expected for an herbal remedy proposed to have such broad effects, there has been a tremendous amount of research interest into its actions. In particular, a number of preclinical and clinical studies report the hypotensive effect of garlic, which appears to be more consistent in animal studies, as opposed to clinical studies (Ali et al. 2000; Sharifi, Darabi, and Akbarloo 2003; Cruz et al. 2007). The precise mechanism of action by which garlic lowers blood pressure is not known. However, it is proposed that garlic modulates endothelial production of nitric oxide (NO), inhibits angiotensin-converting enzyme (ACE) activity, decreases the production of vasoconstrictive agents thromboxane-B2 and prostaglandin-E2 and has potent free-radical scavenging activity (Al-Qattan et al. 2001; Ku et al. 2002; Sharifi, Darabi, and Akbarloo 2003; Medina-Campos et al. 2007). As with other herbal preparations, the variability in the clinical results may stem from differences in garlic preparations used for study or the specific content of bioactives represented in the preparation. Some bioactives have been reported to include unstable sulfur-containing compounds, polyphenols, flavonoids, anthocyanins, tannins, and others (Rahman and Lowe 2006; Chen et al. 2009).

A recent meta-analysis was conducted on clinical studies over the past half-century. The meta-analysis was based on 11 clinical studies between 1955 and 2007, and it included true placebo groups, used garlic-only preparations, and reported mean systolic and/or diastolic blood pressure (SBP/DBP) and standard deviations in their statistical analyses. This analysis concluded that individuals treated with garlic had better outcomes, and superior effects in lowering blood pressure in hypertensive individuals were observed compared with the placebo-treated group. The mean (SD) decrease in blood pressure reported in the hypertensive subgroup was 8.4 (2.8) mm Hg (n = 4; p < .001) for systolic and 7.3 (1.5) mm Hg for diastolic (n = 3; p < .001) blood pressure (Ried et al. 2008).

19.5.10. Ginkgo (Ginkgo biloba)

Ginkgo, a popular herbal remedy for centuries in China, has also become popular in Europe and America. One of the proposed indications has been to improve circulation. The focus of several studies has been to evaluate ginkgo leaf extract and measure the modulation of calcium levels in the endothelium and vasodilation (Chen et al. 2009). Ginkgo was reported to have a hypotensive effect in preclinical studies (Kubota et al. 2006a, 2006b; Koltermann et al. 2007). However, other studies have demonstrated that long term intake may not be useful (Tada et al. 2008). Clinical data have also suggested that ginkgo may lower blood pressure in healthy subjects over a treatment course of 3 months and within a single treatment for temporary stress-induced hypertension (Kudolo 2000; Jezova et al. 2002). However, controversy exists as other clinical studies have failed to confirm an effect (Chen et al. 2009).

19.5.11. Ivy Gourd

Historically, ivy gourd was used in Ayurvedic medicine, a traditional East Indian healing system, to treat glycosuria. Reports suggest that active compounds in the plant may mimic the action of insulin and suppress the activity of certain enzymes involved in glucose production. Clinical research studies with ivy gourd extract have suggested its effect on fasting and postprandial blood glucose levels of the treated patient groups (Kuriyan et al. 2007).

19.5.12. Aloe (Aloe vera)

Aloe vera has also been used in the medicinal treatment of diabetes in India and the Arabian peninsula (Vogler and Ernst 1999; Evans 2003). The gel, which is obtained from the inner portion of the leaves, may contain glucomannan, a water-soluble fiber that reportedly has hypoglycemic and insulin-sensitizing actions (Vuksan et al. 1999, 2000). Preclinical studies have reported inconsistent results (Yeh et al. 2003). However, small-scale clinical research trials suggested an improvement in fasting glucose levels with the extract (Bunyapraphatsara et al. 1996; Yongchaiyudha et al. 1996; Yeh et al. 2003). In a comprehensive review of the effects of herbals on glycemia, Yeh et al. (2003) concluded that the preliminary data suggest a potential effect of Aloe vera in glycemic control; however, further validation is needed.

19.6. CONCLUSIONS

Botanical extracts have been widely used as medicinal agents throughout human history. Many are now available in commercial supplements and are promoted for general health benefits or for prevention and treatment of specific diseases. As such, the public’s interest in the potential benefit of botanical supplements on carbohydrate metabolism is quite high. The advantage of a botanical extract is that if botanicals are shown to be effective to improve metabolism and/or risk factors on a clinical level, these remedies, in general, are commonly available and therefore could potentially aid the general public with regard to obesity and diabetes. Unfortunately, although most of the popular botanicals have a long history in folk medicine, there is a paucity of definitive clinical data, particularly as it relates to consistently improving carbohydrate metabolism. There is insufficient evidence, based on currently available data, to actively recommend the use of any particular botanical product to treat either high blood glucose or other related risk factors. However, there are active investigations in many areas for which botanical preparations are consistent, and defined clinical studies are still ongoing. We need to await the results of these carefully conducted studies.

ACKNOWLEDGMENTS

This study is supported by P50AT002776-01 from the National Center for Complementary and Alternative Medicine and the Office of Dietary Supplements, which fund the botanical research center at Pennington Biomedical Research Center (LSU System) and Rutgers University.

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