A review of the hypoglycemic effects of five commonly used herbal food supplements.

Hyperglycemia is a pathological condition associated with prediabetes and diabetes. The incidence of prediabetes and diabetes is increasing and imposes great burden on healthcare worldwide. Patients with prediabetes and diabetes have significantly increased risk for cardiovascular diseases and other complications. Currently, management of hyperglycemia includes pharmacological interventions, physical exercise, and change of life style and diet. Food supplements have increasingly become attractive alternatives to prevent or treat hyperglycemia, especially for subjects with mild hyperglycemia. This review summarized current patents and patent applications with relevant literature on five commonly used food supplements with claims of hypoglycemic effects, including emblica officinalis (gooseberry), fenugreek, green tea, momordica charantia (bitter melon) and cinnamon. The data from human clinical studies did not support a recommendation for all five supplements to manage hyperglycemia. Fenugreek and composite supplements containing emblica officinalis showed the most consistency in lowering fasting blood sugar (FBS) or glycated hemoglobin (HbA1c) levels in diabetic patients. The hypoglycemic effects of cinnamon and momordica charantia were demonstrated in most of the trials with some exceptions. However, green tea exhibited limited benefits in reducing FBS or HbA1c levels and should not be recommended for managing hyperglycemia. Certain limitations are noticed in a considerable number of clinical studies including small sample size, poor experimental design and considerable variations in participant population, preparation format, daily dose, and treatment duration. Future studies with more defined participants, standardized preparation and dose, and improved trial design and size are warranted.

Hypolipidemic, antioxidant, and antiinflammatory activities of microalgae Spirulina.

Spirulina is free-floating filamentous microalgae growing in alkaline water bodies. With its high nutritional value, Spirulina has been consumed as food for centuries in Central Africa. It is now widely used as nutraceutical food supplement worldwide. Recently, great attention and extensive studies have been devoted to evaluate its therapeutic benefits on an array of diseased conditions including hypercholesterolemia, hyperglycerolemia, cardiovascular diseases, inflammatory diseases, cancer, and viral infections. The cardiovascular benefits of Spirulina are primarily resulted from its hypolipidemic, antioxidant, and antiinflammatory activities. Data from preclinical studies with various animal models consistently demonstrate the hypolipidemic activity of Spirulina. Although differences in study design, sample size, and patient conditions resulting in minor inconsistency in response to Spirulina supplementation, the findings from human clinical trials are largely consistent with the hypolipidemic effects of Spirulina observed in the preclinical studies. However, most of the human clinical trials are suffered with limited sample size and some with poor experimental design. The antioxidant and/or antiinflammatory activities of Spirulina were demonstrated in a large number of preclinical studies. However, a limited number of clinical trials have been carried out so far to confirm such activities in human. Currently, our understanding on the underlying mechanisms for Spirulina's activities, especially the hypolipidemic effect, is limited. Spirulina is generally considered safe for human consumption supported by its long history of use as food source and its favorable safety profile in animal studies. However, rare cases of side-effects in human have been reported. Quality control in the growth and process of Spirulina to avoid contamination is mandatory to guarantee the safety of Spirulina products.

Food and food supplements with hypocholesterolemic effects.

Hypercholesterolemia is a predominant risk factor for atherosclerosis and associated coronary and cerebrovascular diseases. Control of cholesterol levels through therapeutic drugs, notably statins, have significantly reduced the risk for developing atherosclerosis and associated cardiovascular diseases. However, adverse effects associated with therapeutic drugs warrant to find other alternative approaches for managing hypercholesterolemia, especially for those with borderline cholesterol levels. Food supplements have increasingly become attractive alternatives to prevent or treat hypercholesterolemia and reduce the risk for cardiovascular diseases. This review summarized current patents on food supplements with claims of hypocholesterolemic effects. They can be mainly divided into four categories based on the active ingredients in the supplements: 1) plant sterols or stanols; 2) fiber or polysaccharides; 3) microorganism-derived; and 4) soy protein and phytoestrogens. The efficacy, mechanisms of action and potential side effects are reviewed for each of the four categories. The hypocholesterolemic effects of plant sterols, fiber, Monascus products and soy protein preparations have been consistently demonstrated in clinical trails whereas the efficacy of some probiotic bacteria and phytoestrogens-containing supplements remains to be established. Accumulative clinical data show that plant sterols, fiber, soy protein and phytoestrogen are generally considered safe and cause no obvious side effects. However, additional clinical studies are required to establish the safety profiles of certain probiotic bacteria as food supplements.

Effect of guggulsterone and cembranoids of Commiphora mukul on pancreatic phospholipase A(2): role in hypocholesterolemia.

Guggulsterone (7) and cembranoids (8-12) from Commiphora mukul stem bark resin guggul were shown to be specific modulators of two independent sites that are also modulated by bile salts (1-6) to control cholesterol absorption and catabolism. Guggulsterone (7) antagonized the chenodeoxycholic acid (3)-activated nuclear farnesoid X receptor (FXR), which regulates cholesterol metabolism in the liver. The cembranoids did not show a noticeable effect on FXR, but lowered the cholate (1)-activated rate of human pancreatic IB phospholipase A2 (hPLA2), which controls gastrointestinal absorption of fat and cholesterol. Analysis of the data using a kinetic model has suggested an allosteric mechanism for the rate increase of hPLA2 by cholate and also for the rate-lowering effect by certain bile salts or cembranoids on the cholate-activated hPLA2 hydrolysis of phosphatidylcholine vesicles. The allosteric inhibition of PLA2 by certain bile salts and cembranoids showed some structural specificity. Biophysical studies also showed specific interaction of the bile salts with the interface-bound cholate-activated PLA2. Since cholesterol homeostasis in mammals is regulated by FXR in the liver for metabolism and by PLA2 in the intestine for absorption, modulation of PLA2 and FXR by bile acids and selected guggul components suggests novel possibilities for hypolipidemic and hypocholesterolemic therapies.

Therapeutic effects of guggul and its constituent guggulsterone: cardiovascular benefits.

Oleogum resin (known as guggul) from the guggul tree, Commiphora mukul, found in India, Bangladesh, and Pakistan, has been used to treat various diseases including hyper-cholesterolemia, atherosclerosis, rheumatism, and obesity over several thousands of years. Guggulsterone isolated from guggul has been identified as the bioactive constituent responsible for guggul's therapeutic effects. Since the first study demonstrating the therapeutic effects of guggul in an animal model in 1966, numerous preclinical and clinical trails have been carried out. Although differences in study design, methodological quality, statistical analysis, sample size, and subject population result in certain inconsistencies in the response to therapy, the cumulative data from in vitro, preclinical, and clinical studies largely support the therapeutic claims for guggul described in the ancient Ayurvedic text. However, future clinical studies with much larger size and longer term are required to confirm these claims. The cardiovascular benefits of the therapy are derived from the multiple pharmacological activities associated with guggul or guggulsterone, notably its hypolipidemic, antioxidant, and antiinflammatory activities. It has been established that guggulsterone is an antagonist at farnesoid x receptor (FXR), a key transcriptional regulator for the maintenance of cholesterol and bile acid homeostasis. The FXR antagonism by guggulsterone has been proposed as a mechanism for its hypolipidemic effect. A recent study demonstrates that guggulsterone upregulates the bile salt export pump (BSEP), an efflux transporter responsible for removal of cholesterol metabolites, bile acids from the liver. Such upregulation of BSEP expression by guggulsterone favors cholesterol metabolism into bile acids, and thus represents another possible mechanism for its hypolipidemic activity. Guggulsterone has been found to potently inhibit the activation of nuclear factor-kappaB (NF-kappaB), a critical regulator of inflammatory responses. Such repression of NF-kappaB activation by guggulsterone has been proposed as a mechanism of the antiinflammatory effect of guggulsterone.