A combination of Citrus aurantifolia fruit rind and Theobroma cacao seed extracts supplementation enhances metabolic rates in overweight subjects: a randomized, placebo-controlled, cross-over study.

Background and objective: LN19183 is a proprietary, synergistic combination of Citrus aurantifolia fruit rind and Theobroma cacao seed extracts that increased resting energy expenditure (REE) in high-fat diet (HFD)-fed obese rats. The objective of this study was to validate the thermogenic potential of LN19183 in obese Sprague Dawley (SD) rats and to assess its clinical efficacy in a proof-of-concept, randomized, placebo-controlled, cross-over human trial. Methods: In the rat study, HFD-fed obese rats were supplemented with either HFD alone or with 45, 90, or 180 mg LN19183 per kg body weight (BW) for 28 days. In the human study, 60 overweight adults (male and female, aged 20-39 years) were randomized. Subjects took LN19183 (450 mg) or a matched placebo capsule on two consecutive days in phases one and two of the study, separated by a 10-day washout period. In each phase, on day 1, REE at pre-dose, 60-, 120-, and 180-min post-dose, and on day 2, metabolic rates at pre-dose and post-dose during and 20 min after exercise were measured using indirect calorimetry. Results: In rats, LN19183 significantly increased REE, reduced BW gain and fat masses, and increased fat and carbohydrate metabolism marker proteins including beta 3 adrenergic receptor (ß3-AR), phospho-AMP-activated protein kinase (AMPK), glucagon-like peptide-1 receptor (GLP-1R) in the liver, and serum adiponectin levels. Furthermore, LN19183-supplemented human volunteers increased (P < 0.05, vs. placebo) the metabolic rates at rest and with exercise; their fat oxidation was increased (P < 0.05, vs. placebo) at rest and 20 min post-exercise. The groups' systolic and diastolic blood pressure (BP), heart rates (HR), and safety parameters were comparable. Conclusion: These observations suggest that LN19183 is a thermogenic botanical composition with no stimulatory effects on BP and HR.

A Synergistic Botanical Composition Increases Resting Energy Expenditure and Reduces Adiposity in High-Fat Diet-Fed Rats.

OBJECTIVE: An imbalance between dietary energy intake and energy expenditure may result in body fat gain or obesity. Increasing resting energy expenditure (REE) is an attractive strategy for managing body fat gain. The objective of the current study was to generate proof-of-concept data on a synergistic composition (LN19183) of Citrus aurantifolia fruit rind (CA) and Theobroma cacao seed (TC) extracts to increase REE and reduce body fat gain in a high-fat diet (HFD)-fed rats. METHOD: In in vitro cell-based experiments, CA, TC, or LN19183 were tested for fibroblast growth factor 21 (FGF-21) production from 3T3-L1 mouse adipocytes. Uncoupling protein 1 (UCP-1) and beta3-adrenergic receptor (ß3-AR) protein expressions in LN19183-treated 3T3-L1 lysates were also tested. The 56-day in vivo study in male Sprague Dawley (SD) rats (age: 12-14 weeks; body weight [b.w.]: 115-197 g) contained 2 phases of 28 days each of induction and supplementation. Seven rats received a regular rodent diet (RD) over 56 days. In the induction phase, 21 rats received HFD; in the supplementation phase, the obese rats (n = 7) received either HFD alone or in concurrence with a daily oral dose of either 100 or 250 mg/kg b.w. of LN19183 for 28 days. RESULTS: In 3T3-L1 adipocytes, LN19183 synergistically increased FGF-21 production and dose-dependently increased ß3-AR and UCP-1 protein expression. In HFD-fed rats, both doses of LN19183 supplementation significantly (p < 0.05) decreased the body weight gain, total fat mass, and liver weight and increased (p < 0.05) REE. High-dose LN19183 also significantly (p < 0.05) increased fat oxidation and UCP-1 protein expression in white fat tissue and reduced liver triglyceride (TG) level. LN19183-supplemented groups substantially reduced serum TG and glucose levels compared to the HFD rats. CONCLUSIONS: LN19183 reduces body fat mass and weight gain via increased REE and fat oxidation in HFD-fed obese rats.

The Impact of Lab4 Probiotic Supplementation in a 90-Day Study in Wistar Rats.

The anti-inflammatory and cholesterol lowering capabilities of probiotic bacteria highlight them as potential prophylactics against chronic inflammatory diseases, particularly cardiovascular disease. Previous studies in silico, in vitro, and in vivo suggest that the Lab4 probiotic consortium may harbour such capabilities and in the current study, we assessed plasma levels of cytokines/chemokines, short chain fatty acids and lipids and faecal levels of bile acids in a subpopulation of healthy Wistar rats included in 90-day repeat dose oral toxicity study. In the rats receiving Lab4, circulating levels of pro-inflammatory interleukin-6, tumour necrosis factor-α and keratinocyte chemoattractant/growth regulated oncogene were significantly lower compared to the control group demonstrating a systemic anti-inflammatory effect. These changes occurred alongside significant reductions in plasma low density lipoprotein cholesterol and increases in faecal bile acid excretion implying the ability to lower circulating cholesterol via the deconjugation of intestinal bile acids. Correlative analysis identified significant associations between plasma tumour necrosis factor-α and the plasma total cholesterol:high density lipoprotein cholesterol ratio and faecal levels of bifidobacteria in the Lab4 rats. Together, these data highlight Lab4 supplementation as a holistic approach to CVD prevention and encourages further studies in humans.