Although still defined in diverse terms, metabolic syndrome is a common disorder arising as a result of the increased prevalence of obesity throughout the world 1. Metabolic syndrome, also known as insulin resistance syndrome and Syndrome X, has 3 main potential etiologic categories: obesity and disorders of adipose tissue; insulin resistance; and a constellation of independent factors (e.g., molecules of hepatic, vascular, and immunologic origin) that mediate specific components of the metabolic syndrome 2.

In the United States, over 60% of the adult population is now overweight or obese 3 and 47 million people have metabolic syndrome, which will soon overtake cigarette smoking as the number one risk factor for heart disease 45. Globally, the disorder has become a major public health challenge. (In Cameroon, approximately 25% of the population is now considered obese.)

Obesity has been shown to contribute to high serum cholesterol, low HDL cholesterol and hyperglycemia, all of which increase the chances of cardiovascular disease (CVD) 678. Correlations between central obesity and high blood pressure, high blood cholesterol, low levels of high density lipoprotein-cholesterol, and high fasting blood glucose levels have been shown for both sexes in various racial and ethnic groups 678910.

Since it has been determined that abdominal fat poses a greater health risk than fat stored in the lower half of the body 11, waist circumference has become a major factor in body-fat assessment 1213. A large waist circumference (>88 cm in women and 102 cm in men) is associated with an increased risk for type 2 diabetes, dyslipidemia, hypertension and CVD in patients with a body mass index (BMI) 25–34 8. Moreover, for obese patients with metabolic complications, changes in waist circumference are useful predictors of CVD risk factors 1314. Thus, in addition to weight (kg), fat (%) and BMI, changes in waist measurement (cm) was one of the primary endpoints in this study.

Because of its links with obesity, it is difficult to identify a unique role for insulin resistance in patients with metabolic syndrome. Although insulin resistance generally rises with increasing body fat content, one finds a broad range of insulin sensitivities at all levels 6. Although most people with BMI ≥ 30 have postprandial hyperinsulinemia and relatively low insulin sensitivity, there is variation in insulin sensitivity even within the obese population 67. Overweight persons (BMI 25–29) also exhibit a spectrum of insulin sensitivities, which seems to suggest an inherited component to insulin resistance.

The increased chance of CVD and type 2 diabetes require therapeutic consideration for the vast numbers of overweight/obese persons now at high risk for these diseases 1. The current International Diabetes Foundation recommendations for preventing or delaying the development of diabetes include both primary and secondary interventions. The former emphasizes lifestyle changes such as calorie restriction and increased physical activity, and the latter (for people at high risk for CVD) uses pharmacological agents 15 that specifically target individual components of metabolic syndrome 151617181920. When used by obese patients in combination with dietary regimes, these agents can produce some weight loss and some reversal of accompanying complications. The role of pharmacotherapy, however, has been compromised by safety issues leading to the withdrawal of some medications from the market 2122. The combination of safety concerns and high costs have forced many populations to continue to rely on traditional healing methods using the indigenous pharmacopoeia.

Cissus quadrangularis, for example, is used by common folk in India to hasten the fracture healing process 232425262728. In Cameroon, the whole plant is used in oral re-hydration, while in Africa and Asia the leaf, stem, and root extracts are utilized in the management of various ailments 2930313233. Phytochemical analyses of Cissus quadrangularis reveal a high content of ascorbic acid, carotene, phytosterol substances and calcium 3435, and there have also been reports of the presence of β-sitosterol, δ-amyrin and δ-amyrone 36. All these components have potentially different metabolic and physiologic effects 3738. Although researchers have investigated several uses of Cissus quadrangularis, its potential application against metabolic syndrome has not yet been reported.

Several other dietary supplements (green tea, soy, chromium, selenium, B-vitamins) have only marginal effects in treating obesity but they address other metabolic syndrome symptoms and thus were included in the formulation. Green tea (Camellia sinensis) extracts contain high concentrations of epigallocatchin gallate and may work with other chemicals to increase levels of fat oxidation and thermogenesis 3940. Numerous studies on soy (Glycine max) protein show it is associated with a reduction in serum cholesterol and triglyceride levels and suggest it may protect against the development of coronary heart disease 41. Chromium helps insulin metabolize fat, turn protein into muscle, and convert sugar into energy 42; thus, chromium supplementation can favorably influence glucose/insulin metabolism, reduce levels of harmful LDL cholesterol, and increase HDL cholesterol 43. Both humans and animals require selenium for the optimal functioning of the selenoproteins, which reduce the risk of CVD by decreasing lipid peroxidation and influencing the metabolism of the cell-signaling prostaglandins 44. Lastly, B-vitamins (B-6, B-12 and folic acid) regulate energy metabolism 45, which plays a critical role in obesity management; they also maintain lower homocysteine levels 46, which are closely associated with cardiovascular health benefits.

The purpose of the present study was to examine the efficacy of a Cissus quadrangularis formulation (Cylaris™) containing the above agents in the management of obesity and metabolic syndrome.

The study was a prospective, randomized, double blind, placebo-controlled design conducted by the Laboratory for Nutrition and Nutritional Biochemistry at the University of Yaoundé I, Cameroon, Africa. The Cameroon National Ethics Committee approved the protocol. Applicants were advised of the study's purpose, nature, and potential risks, and all gave their written informed consent before participation. The study was conducted in accordance with the Helsinki Declaration (1983 version).

Our results support the hypothesis that the use of a Cissus quadrangularis formulation has efficacy in the management of weight loss and metabolic syndrome, particularly for central obesity. The use of the formulation (which also contains green tea, soy, chromium, selenium, and B-vitamins) over an 8-week period brought about a significant reduction in many of the anthropomorphic measures: weight, % body fat, BMI and, especially, waist circumference of obese and overweight patients, regardless of calorie-controlled diet (see Table 2).

Waist circumference is a particularly important factor in weight and body-fat assessment since fat distribution, rather than total body fat, is currently the key indicator of weight-related health problems. The dramatic reduction in waist circumference that accompanied the 8-week use of the Cissus quadrangularis formulation for both the diet and no diet groups is particularly important because waist circumference is a major criterion in the diagnosis of obesity and metabolic syndrome 2 and is generally considered a surrogate measure for abdominal visceral fat 1213. Moreover, not only does the risk of type 2 diabetes increase with the degree and duration of obesity it, too, is associated with central obesity 67.

The reduction in the primary anthropomorphic measurements can be attributed to the synergistic effects of Cylaris™, Glycine max extract, Camellia sinensis extract and ChromeMate™ ingredients in the formula, all of which have previously been shown to affect weight loss activity 3235394142.

Cissus quadrangularis phytosterols and fiber extracts have been shown to have anti-lipase, and anorexiant properties that reduce the absorption of dietary fats and enhance satiation by increasing serum serotonin levels 47. In 1999, Swiss researchers found that men who were given a combination of caffeine and green tea catechin extract burned more calories than those given only caffeine or a placebo. It was postulated that the catechins and caffeine combination sustained the effect of norepinephrine on thermogenesis longer than caffeine alone 39. Numerous studies on chromium supplementation have also demonstrated weight loss in overweight and obese people 4849. Grant et al. (1997) reported that chromium with a moderate diet and exercise regimen influences weight loss and body composition 50.

The modification of certain serological characteristics (blood parameters) (see Table 3) by Cissus formulation may or may not be dependent on weight loss. Only the reduction of LDL-cholesterol followed a similar pattern to weight loss over the 8-week trial period. The circulating concentration of total cholesterol and triglycerides, though reduced by the formulation, could be independent of weight loss since all treatment groups (diet/no diet) showed significant cholesterol reduction. The increase in the concentration of circulating HDL-cholesterol in the treatment groups shows a reduction in the ratio of total cholesterol to HDL-cholesterol as well as LDL-cholesterol to HDL-cholesterol. This reduced ratio also implies a reduction in the risk of atherosclerosis and coronary heart disease 51.

Although the exact mechanisms for the formulation's cholesterol-lowering ability needs further study, the various ingredients might interact in a manner similar to statins, fibrates, probucol, nicotinic acid or cholesterol absorption inhibitors. Green tea catechins have a number of antioxidant activities related to cholesterol regulation. For example, the inhibition of the oxidation of low-density lipoproteins and the antithrombotic activity both aid in lowering total cholesterol/LDL-cholesterol and increasing HDL-cholesterol levels 5253. Also, the phytochemical constituents (phytosterols, β-sitosterol, δ-amyrin and δ-amyrone), in Cissus quadrangularis may have activity similar to other plant sterols. The molecular structure of phytosterols, for example, is practically identical to that of cholesterol.

Recent studies show that metabolic syndrome causes an inflammatory process in the blood vessels that leads to arteriosclerosis. This inflammatory process can be gauged by blood levels of C-reactive protein 54 and, as our results showed, Cissus formulation significantly reduced the circulating concentrations of CRP thereby inhibiting the inflammatory process and possibly reducing individual components of metabolic syndrome 54. In metabolic syndrome, the body becomes resistant to insulin, and high levels of glucose remain trapped in the blood. In response, the pancreas produces more insulin. The extra insulin temporarily allows glucose to enter the cells and also increases cholesterol and triglyceride levels.

In sum, Cissus formulation administered twice daily to obese and overweight persons with symptoms of metabolic syndrome results in both weight reduction and an improvement in the symptoms associated with metabolic syndrome. It has also shown efficacy in the control and lowering of triglyceride concentrations, total cholesterol, LDL-cholesterol, and fasting blood glucose. The formulation may also have applications in other metabolic diseases, such as diabetes mellitus.

JO conceived, designed, coordinated and drafted the manuscript; DK carried out blood sampling and performed statistical analyses; GA participated in the design and carried out analytical work; CM participated in the design and carried out analytical work; XT participated in the formulation of the extract.

All the authors read and approved the final manuscript.