Excess adipose tissue increases the workload of the cardiovascular system, adversely alters immune function, and dramatically increases the risk of heart disease, non-insulin-dependent diabetes mellitus, obstructive pulmonary disease, arthritis and a variety of cancers [1]. Although once considered a major health problem isolated to developed countries, obesity is now recognized as a global problem with potentially catastrophic consequences for health economics. In Cameroon, for example, the reported incidence of obesity in urban areas ranges from 17–21% [2]. This dramatic change reflects the social, nutritional, and lifestyle changes involved in rural-urban migration and the urbanization of rural areas. Worthy of note in this context are the changes from traditional high fibre diets and high-activity lifestyles to diets rich in saturated fat and low in fibre, further compounded by reduction in physical activity levels [3, 4]. Insulin resistance, caused by the concomitant, complex interaction of environment (e.g. diet, activity level, elevated body mass, excess visceral adiposity) and genetic factors, is a fundamental pathophysiologic cause of the metabolic syndrome, a recognized risk factor for cardiovascular disease [5, 6]. Like many other obesity-related conditions, the incidence of the metabolic syndrome is also on the rise in Cameroon [7].

Nutritional management, especially caloric restriction for the purpose of weight reduction, can improve insulin action on target tissues like skeletal muscle, hepatocytes, and peripheral and visceral adipocytes [8, 9].

The consumption of Irvingia gabonensis, a fleshy West African fruit, is common in traditional Nigerian and Cameroonian cuisine. Initial observations suggested beneficial changes in metabolic parameters were associated with the high fiber content of Irvingia gabonensis [10]. Results of subsequent analysis suggested that the earlier observations of the beneficial effects of Irvingia gabonensis could not be accounted for by fiber content alone [11]. A recent in vitro study using a validated experimental model (murine 3T3-L1 adipocytes) provides compelling data that Irvingia gabonensis seed extract may inhibit adipogenesis through modulation of PPAR gamma and glycerol-3 phosphate dehydrogenase in addition to beneficial impact upon leptin and adiponectin [12].

The current clinical study was designed to evaluate if the in vitro data could translate into in vivo clinical efficacy in overweight and/or obese human volunteers.

The 120 volunteers (mean age 34, range 19–50) were divided into 2 groups, with 60 randomly assigned to placebo and 60 to IGOB131 (active). Of these initial 120 volunteers, 102 completed the 10 week study; 50 from the placebo group, and 52 from the IGOB131 group. Eighteen volunteers [placebo (n = 12) and IGOB131 (n = 6)] dropped out of the study for the following reasons – not experiencing rapid weight loss (n = 10); influenza attack (n = 3); dryness of mouth (n = 3); no reason given (n = 2).

Food Intake

The mean daily energy intake in the IGOB131 group was 2767 ± 187 kcal of which 56% was from carbohydrate, 29% from protein, and 15% from fat. In the placebo group, the mean daily energy intake was 3156 ± 185 kcal of which 56% was from carbohydrate, 29% was from protein, and 15% was from fat. Seven-day dietary and activity assessment of the subjects at baseline showed similar food intake habits and energy levels.

Body weight, waist size and body fat

Baseline characteristics of the two groups were well-matched and without significant differences at baseline (Table 1). There were no significant differences in the baseline body weight, waist circumference and serum leptin measurements between the placebo and experimental group (Table 1). However, by the tenth week, significant differences were observed between the placebo and experimental intervention groups, respectively, for body weight (95.7 kg vs. 85.1 kg, respectively, p < 0.01), waist circumference (101.1 cm vs. 88.1 cm, respectively, p < 0.05). Body fat decreased over time in both groups but the experimental group lost significantly more body fat (6.3%, p < 0.05) compared to the placebo group (1.9%) (Table 1).

			Time (weeks)
Variables	Group	Base line	4	8	10	Over change
Weight (Kg)	Placebo	96.4 ± 12.3	95.8 ± 8.2	95.1 ± 10.6	95.7 ± 15.2	-0.7
	IGOB131	97.9 ± 9.1	94.3 ± 5.5 a	89.7 ± 4.7 a	85.1 ± 3.1b	-12.8
Waist (cm)	Placebo	106.4 ± 10.8	102.7 ± 10.6	101.1 ± 14.8	101.1 ± 15.8b	-5.3
	IGOB131	105.1 ± 6.3	98.0 ± 8.4a	90.1 ± 8.70a	88.1 ± 7.6	-16.19
Leptin (ng/ml)	Placebo	31.3 ± 1.8	29.4 ± 1.4	28.1 ± 1.8	28.4 ± 1.8	-2.9
	IGOB131	32.9 ± 1.6	18.1 ± 1.3a	16.8 ± 1.2a	16.9 ± 1.3b	-16.0
Fat (%)	Placebo	34.7 ± 8.6	33.31 ± 10.9	32.9 ± 11.9	32.7 ± 15.7	-1.99
	IGOB131	34.2 ± 7.9	31.6 ± 5.4a	28.2 ± 6.6a	27.9 ± 5.5a	-6.3
LDL cholesterol (mg/dL)	Placebo	77.4 ± 9.2	76.5 ± 8.9	74.1 ± 9.3	73.7 ± 8.3	-3.75
	IGOB131	82.2 ± 8.1	71.8 ± 5.9b	64.7 ± 8.9b	59.8 ± 5.0b	-22.44
Total cholesterol (mg/dL)	Placebo	145.2 ± 22.4	143.9 ± 12.2	142.1 ± 13.6	142.4 ± 12.1	-2.8
	IGOB131	151.7 ± 18.5	133.7 ± 16.6a	120.1 ± 11.9 a	111.9 ± 5.8a	-39.8
C-reactive protein (mg/L)	Placebo	1.46 ± 0.05	1.46 ± 0.04	1.445 ± 0.03	1.455 ± 0.05	-0.01
	IGOB131	1.49 ± 0.041	0.91 ± 0.05a	0.71 ± 0.04b	0.72 ± 0.05b	-0.78
Glucose (mg/dL)	Placebo	81.4 ± 9.6	79.5 ± 10.1	77.8 ± 9.4	77.1 ± 7.8	-4.3
	IGOB131	85.55 ± 5.59	76.6 ± 10.3a	68.7 ± 9.3a	66.3 ± 4.9a	-19.3
Adiponectin (mg/L)	Placebo	12.1 ± 3.2	15.2 ± 3.5	14.6 ± 3.5	14.94 ± 3.9	+ 2.8
	IGOB131	12.2 ± 3.0	24.8 ± 3.8a	31.0 ± 4.0b	31.6 ± 3.9a	+ 19.4

^a P < 0.05; ^b P < 0.01 compared with Placebo

When corrected for placebo response, the pattern of relative changes in weight and waist circumference was found to be different between the two groups, consistent with a difference in response to the intake of the extract (Figure 1).

Total and LDL cholesterol, C-reactive proteins, leptin

These variables decreased from baseline, though at different rates and magnitudes associated with duration of the study, with the experimental group showing statistically significant changes compared with the placebo group at week-10 (Table 1).

While baseline levels of serum lipids were similar in the two groups, significant differences were observed between the two as the study progressed with the experimental group showing progressively greater improvement. At week-10, significant differences were observed for total cholesterol (placebo: 142.5 mg/dl vs. IGOB131: 111.9 mg/dl, p < 0.05) and LDL cholesterol (placebo: 77.7 mg/dl vs IGO131: 59.77 mg/dl, p < 0.01). Compared to baseline values, total cholesterol decreased by 1.9% in the placebo group as opposed to 26.2% for the IGOB131 group while LDL cholesterol levels fell by 4.8% in the placebo compared to 27.3% in the IGOB131 group. Correcting for placebo values, the relative change in the total cholesterol and LDL cholesterol was observed to follow a similar pattern (Figure 2) in the experimental group, suggesting a similar response mechanism to IGOB131 intake.

Like in the case of the other parameters measured, C-reactive protein and leptin levels decreased over time in both groups. The rate of decrease was however accelerated in the IGOB131 relative to the placebo-group. Serum levels of CRP fell by 1.2% in the placebo group as opposed to 52.0% in the experimental group relative to baseline. On the other hand, leptin levels decreased by 9.3% in the placebo group compared to a 48.6% in the IGOB131 group over the 10-week experimental period.

Fasting blood glucose levels

Blood glucose levels in the experimental group (85.6 mg/dl ± 5.6 mg/dl) and in the placebo group (81.4 ± 9.6 mg/dl) were similar at baseline but decreased to significantly different levels (P < 0.05) at week-10 of the study (Table 1). In relative terms, decreases in placebo and treatment groups were 5.3% vs. 22.5%, respectively (Figure 3). Corrected for the placebo values, the changes in blood glucose levels were similar to that of lipids (Figure 2).

Adiponectin levels

Baseline serum adiponectin levels were comparable between the two groups (placebo: 12.1 mg/l ± 3.21 mg/l; IGOB131: 12.16 mg/l ± 3.04 mg/l), but increased with time (Table 1). By week-10 of the study adiponectin levels in the placebo group increased by 23.4% compared to 159.8% in the experimental group. Corrected for placebo values, the rate of increase in serum adiponectin levels in IGOB131 group followed an exponential curve (Figure 4).

The present study suggests that IGOB131, a seed extract of Irvingia gabonensis, safely and significantly reduces body weight in overweight and/or obese subjects, and has a favorable impact upon a variety of other metabolic parameters. The current clinical study shows IGOB131 administration is associated with increases in plasma adiponectin levels and decreases in leptin and CRP levels in comparison with the placebo group. These observations support the results of a recent in vitro study [12] which suggests a favorable impact upon adipogenesis associated with IGOB131.

Insulin resistance is the hallmark of the metabolic syndrome and is strongly associated with excess adiposity [16]. A variety of adipocyte-derived biologically active molecules have been identified, including leptin, resistin, TNF-α, and IL-6, that may contribute to obesity-linked metabolic abnormalities [17]. Since plasma leptin levels are closely correlated with the level of adipose tissue [18], the decreases in plasma leptin level associated with IGOB131 treatment may be attributable to the decrease of adipose tissue induced as a consequence of weight loss.

According to McTernan et al. [17], adipose tissue plays a prominent role in the clinical expression of metabolic syndrome, most likely mediated by the increased release and peripheral tissue action of non-esterified fatty acids and by the dysregulated production of adipocyte-secreted proteins, including leptin, adiponectin, resistin, TNF-α, and IL-6. Adiponectin, known to correlate with endothelial function and vascular health, is exclusively expressed in adipose tissue and abundant in human plasma, and appears to be decreased in individuals with obesity and type 2 diabetes, risk factors for atherosclerosis[19].

The observation of a significant weight loss, as well as an increase in adiponectin is consistent with earlier reports in the literature observing an association between weight loss and an increase in adiponectin levels [20].

IGOB131 is relatively rich in plant-derived protein and antioxidants. A study by Baum et al, [21] had earlier shown a reduction of both total cholesterol and triglycerides levels in a hypercholesterolemic man who was fed a plant protein diet. Other studies have shown metabolic syndrome-preventive activity of antioxidant components (e.g. vitamin C, polyphenols). A number of polyphenols such as epigallocatechin gallate have anti-obesity activity and may improve metabolic disorders via modulation of adipokines and growth factors, including metabolic improvement of leptin function [22–24]. Although the active principles of IGOB131 have not yet been fully identified, it is possible that it contains some of the above mentioned compounds.

In conclusion, Irvingia gabonensis extract administered twice a day to healthy, overweight and obese individuals resulted in both weight reduction (body weight, body fat, waist size) and an improvement in metabolic parameters associated with insulin resistance. The current results suggest that IGOB131 may be a helpful adjunct in the management of overweight and/or obesity, supporting previous suggestions from our laboratory [25].