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Life Extension Magazine February 2010


The use of a Cissus quadrangularis/Irvingia gabonensis combination in the management of weight loss: a double-blind placebo-controlled study.

AIM: To evaluate the effects of two formulations, Cissus quadrangularis-only and a Cissus quadrangularis/Irvingia gabonensis combination, on weight loss in overweight and obese human subjects. METHODS: The study was a 10 week randomized, double-blind, placebo-controlled design involving 72 obese or overweight participants (45.8% male; 54.2% female; ages 21-44; mean age = 29.3). The participants were randomly divided into three equal (n = 24) groups: placebo, Cissus quadrangularis-only, and Cissus quadrangularis/Irvingia gabonensis combination. Capsules containing the placebo or active formulations were administered twice daily before meals; no major dietary changes nor exercises were suggested during the study. A total of six anthropomorphic and serological measurements (body weight, body fat, waist size; total plasma cholesterol, LDL cholesterol, fasting blood glucose level) were taken at baseline and at 4, 8 and 10 weeks. RESULTS: Compared to the placebo group, the two active groups showed a statistically significant difference on all six variables by week 10. The magnitude of the differences was noticeable by week 4 and continued to increase over the trial period. CONCLUSION: Although the Cissus quadrangularis-only group showed significant reductions on all variables compared to the placebo group, the Cissus quadrangularis/Irvingia gabonensis combination resulted in even larger reductions. This apparently synergistic formulation should prove helpful in the management of obesity and its related complications.

Lipids Health Dis. 2008 Mar 31;7:12

IGOB131, a novel seed extract of the West African plant Irvingia gabonensis, significantly reduces body weight and improves metabolic parameters in overweight humans in a randomized double-blind placebo controlled investigation.

BACKGROUND: A recent in vitro study indicates that IGOB131, a novel seed extract of the traditional West African food plant Irvingia gabonensis, favorably impacts adipogenesis through a variety of critical metabolic pathways including PPAR gamma, leptin, adiponectin, and glycerol-3 phosphate dehydrogenase. This study was therefore aimed at evaluating the effects of IGOB131, an extract of Irvingia gabonensis, on body weight and associated metabolic parameters in overweight human volunteers. METHODS: The study participants comprised of 102 healthy, overweight and/or obese volunteers (defined as BMI > 25 kg/m2) randomly divided into two groups. The groups received on a daily basis, either 150 mg of IGOB131 or matching placebo in a double blinded fashion, 30-60 minutes before lunch and dinner. At baseline, 4, 8 and 10 weeks of the study, subjects were evaluated for changes in anthropometrics and metabolic parameters to include fasting lipids, blood glucose, C-reactive protein, adiponectin, and leptin. RESULTS: Significant improvements in body weight, body fat, and waist circumference as well as plasma total cholesterol, LDL cholesterol, blood glucose, C-reactive protein, adiponectin and leptin levels were observed in the IGOB131 group compared with the placebo group. CONCLUSION: Irvingia gabonensis administered 150 mg twice daily before meals to overweight and/or obese human volunteers favorably impacts body weight and a variety of parameters characteristic of the metabolic syndrome. This is the first double blind randomized placebo controlled clinical trial regarding the anti-obesity and lipid profile modulating effects of an Irvingia gabonensis extract. The positive clinical results, together with our previously published mechanisms of gene expression modulation related to key metabolic pathways in lipid metabolism, provide impetus for much larger clinical studies. Irvingia gabonensis extract may prove to be a useful tool in dealing with the emerging global epidemics of obesity, hyperlipidemia, insulin resistance, and their co-morbid conditions.

Lipids Health Dis. 2009 Mar 2;8:7

Inhibition of Irvingia gabonensis seed extract (OB131) on adipogenesis as mediated via down regulation of the PPARgamma and leptin genes and up-regulation of the adiponectin gene.

BACKGROUND: Endeavors to manage obesity have been heavily reliant on controlling energy intake and expenditure equilibrium, but have failed to curtail the overweight and obesity epidemic. This dynamic equilibrium is more complex than originally postulated and is influenced by lifestyle, calorie and nutrient intake, reward cravings and satiation, energy metabolism, stress response capabilities, immune metabolism and genetics. Fat metabolism is an important indicator of how efficiently and to what extent these factors are competently integrating. We investigated whether an Irvingia gabonensis seed extract (IGOB131) would provide a more beneficial comprehensive approach influencing multiple mechanisms and specifically PPAR gamma, leptin and adiponectin gene expressions, important in anti-obesity strategies. METHODS: Using murine 3T3-L1 adipocytes as a model for adipose cell biology research, the effects of IGOB131 were investigated on PPAR gamma, adiponectin, and leptin. These adipocytes were harvested 8 days after the initiation of differentiation and treated with 0 to 250 microM of IGOB131 for 12 and 24 h at 37 degree C in a humidified 5 percent CO2 incubator. The relative expression of PPAR gamma, adiponectin, and leptin in 3T3-L1 adipocytes was quantified densitometrically using the software LabWorks 4.5, and calculated according to the reference bands of beta-actin. RESULTS: The IGOB131 significantly inhibited adipogenesis in adipocytes. The effect appears to be mediated through the down-regulated expression of adipogenic transcription factors (PPAR gamma) [P less than 0.05] and adipocyte-specific proteins (leptin) [P less than 0.05], and by up-regulated expression of adiponectin [P less than 0.05]. CONCLUSION: IGOB131 may play an important multifaceted role in the control of adipogenesis and have further implications in in-vivo anti obesity effects by targeting the PPAR gamma gene, a known contributory factor to obesity in humans.

Lipids Health Dis. 2008 Nov 13;7:44

Adiponectin is a link among inflammation, insulin resistance, and high-density lipoprotein cholesterol but is not associated with paraoxonase activity in premenopausal women.

The aim of this study was to evaluate whether insulin sensitivity, inflammatory response, and plasma lipid profile are associated with circulating adiponectin levels in nondiabetic healthy women. The authors also assessed whether adiponectin has any effect on high-density lipoprotein cholesterol-linked paraoxonase 1 (PON-1) activity and on the susceptibility of low-density lipoproteins to oxidation. Plasma adiponectin was measured in 91 nondiabetic premenopausal women, and the patients were then divided into quartiles. Circulating adiponectin was found to be associated with body mass index (r=.55, P<.001). After adjustment for body mass index, adiponectin showed an inverse correlation with the homeostasis model assessment of insulin resistance (HOMA-IR) (r=-.41, P<.001) and a positive correlation with high-density lipoprotein cholesterol (r=.43, P<.001). In linear regression analysis, HOMA-IR, tumor necrosis factor alpha, and high-density lipoprotein cholesterol levels were found to be independently associated with adiponectin. However, high-density lipoprotein cholesterol-linked PON-1 activity and the susceptibility of low-density lipoproteins to in vitro oxidation did not seem to be related to plasma adiponectin concentrations.

J Clin Hypertens (Greenwich). 2009 Nov;11(11):672-7

Effects of long-term calorie restriction and endurance exercise on glucose tolerance, insulin action, and adipokine production.

Calorie restriction (CR) slows aging and is thought to improve insulin sensitivity in laboratory animals. In contrast, decreased insulin signaling and/or mild insulin resistance paradoxically extends maximal lifespan in various genetic animal models of longevity. Nothing is known regarding the long-term effects of CR on glucose tolerance and insulin action in lean healthy humans. In this study we evaluated body composition, glucose, and insulin responses to an oral glucose tolerance test and serum adipokines levels in 28 volunteers, who had been eating a CR diet for an average of 6.9 +/- 5.5 years, (mean age 53.0 +/- 11 years), in 28 age-, sex-, and body fat-matched endurance runners (EX), and 28 age- and sex-matched sedentary controls eating Western diets (WD). We found that the CR and EX volunteers were significantly leaner than the WD volunteers. Insulin sensitivity, determined according to the HOMA-IR and the Matsuda and DeFronzo insulin sensitivity indexes, was significantly higher in the CR and EX groups than in the WD group (P = 0.001). Nonetheless, despite high serum adiponectin and low inflammation, approximately 40% of CR individuals exhibited an exaggerated hyperglycemic response to a glucose load. This impaired glucose tolerance is associated with lower circulating levels of IGF-1, total testosterone, and triiodothyronine, which are typical adaptations to life-extending CR in rodents.

Age (Dordr). 2009 Nov 11

Adipocytokines and the metabolic syndrome among older persons with and without obesity - the InCHIANTI Study.

SUMMARY Objective: Adipose tissue-derived inflammation may contribute to metabolic alterations and eventually to the metabolic syndrome (MetS). The purpose of this study was to: 1) examine the role of adipocytokines in the association between obesity and the MetS; and 2) to determine whether the association is different in obese and non-obese persons. Design: Cross-sectional population-based InCHIANTI study. Subjects: 944 community-dwelling adults aged 65 years and older living in Tuscany, Italy. Measurements: Obesity was defined as body mass index >/= 30 kg/m(2) and MetS as >/= 3 of the ATP-III criteria. Circulating levels of CRP, IL-6, IL-1ra, IL-18, TNF-alpha R1, adiponectin, resistin, and leptin were measured. Additionally, insulin resistance was determined using the homeostasis model assessment (HOMA-IR). Results: The prevalence of the MetS was 32%. Both overall and abdominal obesity were significantly associated with the MetS after adjusting for inflammatory cytokines, adipokines and lifestyle factors. After adjusting for multiple confounders and HOMA-IR, IL-1ra, TNF-alpha R1 and adiponectin (p < 0.05) remained significantly associated with the MetS. Having multiple cytokines in the highest tertile increased the likelihood of having the MetS in both obese (p for trend 0.002) and non-obese persons (p for trend 0.001) independent of insulin resistance. Conclusions: Non-obese and obese individuals who develop an intense pro-inflammatory state may be more prone to develop the MetS than those with lower levels of inflammation.

Clin Endocrinol (Oxf). 2009 Oct 31

Antidiabetic and antioxidant effects of polyphenols in brown alga Ecklonia stolonifera in genetically diabetic KK-A(y) mice.

The dietary intake and control of blood glucose levels are very important in hyperglycemic patients and alpha-glucosidase inhibitors are a cost-effective means to preventing the progression of diabetes. In search of a natural inhibitor from food materials, alpha-glucosidase inhibitory activity and the anti-hyperglycemic effects of a brown alga, Ecklonia stolonifera, were investigated using non-insulin dependent diabetic mice. Methanolic extract of E. stolonifera (MEE), which contains a high content of polyphenols, showed strong inhibition of alpha-glucosidase in vitro. Male KK-A(y) mice, a genetically non-insulin dependent diabetic model, showed hyperglycemia with aging, but the ingestion of MEE suppressed the increase in plasma glucose and lipid peroxidation levels in unfasted KK-A(y) mice dose dependently. In KK-A(y) mice, which were fed the MEE diet for 4 weeks, MEE moderated the elevation of plasma glucose levels after the oral administration of maltose. The polyphenols in MEE were estimated to be phlorotannins by HPLC-PDA and LC/MS analyses. These results demonstrate that E. stolonifera, seaweed typically used as a health food, has strong antidiabetic and antioxidant effects in vivo, thus, it may have beneficial properties in the prevention of diabetes and could be useful in the development of an antidiabetic pharmaceutical and functional food.

Plant Foods Hum Nutr. 2008 Dec;63(4):163-9

Hypoglycemic activity of several seaweed extracts.

The hypoglycemic activity of several seaweed extracts on rabbits was studied. Ethanol extracts of Laminaria ochroleuca, Saccorhiza polyschides and Fucus vesiculosus were administered orally to normal animals and their effects on glycemia and triglyceridemia evaluated. Crude polysaccharides and protein solutions from Himanthalia elongata and Codium tomentosum were also assayed. Polysaccharides and proteins from H. elongata caused a significant reduction in blood glucose 8 h after intravenous administration. A case of 5 mg/kg of crude polysaccharide lowered glycemia about 18% in normal rabbits and by about 50% in alloxan-diabetic animals, while the protein solution lowered glycemia in diabetic rabbits by about 30%.

J Ethnopharmacol. 1989 Nov;27(1-2):35-43

Antidiabetic properties of polysaccharide- and polyphenolic-enriched fractions from the brown seaweed Ascophyllum nodosum.

We screened seaweed species from Atlantic Canada for antidiabetic activity by testing extracts for alpha-glucosidase inhibitory effect and glucose uptake stimulatory activity. An aqueous ethanolic extract of Ascophyllum nodosum was found to be active in both assays, inhibiting rat intestinal alpha-glucosidase (IC50 = 77 microg/mL) and stimulating basal glucose uptake into 3T3-L1 adipocytes during a 20-minute incubation by about 3-fold (at 400 microg/mL extract). Bioassay-guided fractionation of the A. nodosum extract showed that alpha-glucosidase inhibition was associated with polyphenolic components in the extract. These polyphenolics, along with other constituents appeared to be responsible for the stimulatory activity on glucose uptake. However, attempts to further concentrate this activity through fractionation techniques were unsuccessful. A crude polyphenol extract (PPE), an enriched polyphenolic fraction (PPE-F1) and a polysaccharide extract (PSE) were prepared from commercial A. nodosum powder and administered to streptozotocin-diabetic mice for up to 4-weeks by daily gavage at 200 mg/kg body mass. PPE and PPE-F1 improved fasting serum glucose level in diabetic mice; however, the effect was only statistically significant at day 14. In addition, PPE-F1 was shown to blunt the rise in blood glucose after an oral sucrose tolerance test in diabetic mice. Mice treated with PPE and PPE-F1 had decreased blood total cholesterol and glycated serum protein levels compared with untreated diabetic mice, whereas PPE also normalized the reduction in liver glycogen level that occurred in diabetic animals. All 3 A. nodosum preparations improved blood antioxidant capacity.

Can J Physiol Pharmacol. 2007 Nov;85(11):1116-23

Lipid-lowering treatment in metabolic syndrome.

During the last decades, metabolic syndrome has become an important healthcare problem worldwide. Main components of metabolic syndrome are insulin resistance (resulting often in impaired glucose tolerance and diabetes mellitus), dyslipidemia, hypertension and abdominal obesity. Incidence of metabolic syndrome is high and it substantially increases the risk of cardiovascular diseases. Dyslipidemia is a prominent factor contributing to the increased cardiovascular risk in metabolic syndrome, and lipid-lowerign therapy plays an important role in treating patients with this disorder. Most patients with dyslipidemia are treated with statins and/or fibrates. Statins are used for treatment of hypercholesterolemia; fibrates are indicated for treatment of hypertriglyceridemia and/or low HDL-cholesterol. In high risk patients with severe mixed hyperlipidemia, combination ofstatins with fibrates may be necessary to achieve the lipid goals.

Vnitr Lek. 2009 Jul-Aug;55(7-8):626-30

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