The etiopathogenesis of obesity relies on the ability of adipocytes to transform the excess of energy into triglycerides, operating as an energy store. However, the excess of fatty drops in the adipocytes leads to insulin resistance, due to inflammatory responses, which limits their capacity to store the excess of energy [1
]. The location and quantity of body fat determine the health risks, limiting people with obesity. That fact has a great impact on several metabolic and chronic diseases, including heart disease, cancer, arthritis, obstructive sleep apnea, hypertension, hyperlipidemia, and type 2 diabetes associated with insulin resistance [2
This chronic condition of inflammation has especially been related to the generation of insulin resistance. Likewise, the inflammatory response modifies the metabolism of the organism, favoring or suppressing some pathways, such as insulin signaling pathway. That fact, when uncontrolled, may develop into a general inflammatory response than can perpetuate the chronic disfunction of the metabolism observed in obesity [3
]. Due to the interest in natural extracts over the last 20 years [4
], industry is strongly committed to nutraceuticals, either as a treatment for the disease or as a preventive treatment [5
Polyphenols are natural extracts that have been extensively studied over the last few years due to their antioxidant and anti-inflammatory capacity, besides their possible role in the prevention and management of several diseases such as cardiovascular diseases, hypertension, diabetes, cancer, or neurodegenerative diseases [6
]. Recently, polyphenols have attracted the attention of the scientific community because of their potential use in the reduction of obesity [9
]. The proposed mechanisms include inhibition of the differentiation of adipocytes [10
], enhanced fatty acid oxidation [8
], diminished fatty acid extraction [12
], increased thermogenesis and energy expenditure [13
], or inhibition of digestive enzymes [14
]. However, despite the popularity of this topic, the scientific literature is mainly based on animal and in vitro studies.
The basis of the present work is due to the lack of scientific reports on humans besides the promising use of Lippia citriodora
and Hibiscus sabdariffa
, recognized for their high content of polyphenols, powerful antioxidant molecules that may prevent several disease factors such as hypertension, oxidative stress, dyslipidemia, lipid mobilization, or endothelial stiffness [6
]. The present Hibiscus sabdariffa
and Lippia citriodora
(HS-LC) formula has been previously studied in various clinical studies, in order to help induce weight loss during a controlled diet program [15
]. The aim of the present study is to determine if the supplementation with Lippia citriodora
and Hibiscus sabdariffa
is useful for the treatment of obesity and/or weight control in the absence of a controlled diet.
2. Material and Methods
The study consisted of a double-blind, randomized, placebo controlled clinical trial, with two parallel branches of study depending on the extract consumed (experimental or placebo) and single center (Figure 1
). A total of 84 sedentary and healthy subjects of both sexes was included in the study after matching all the including criteria (age between 18 and 65 years, both sexes, body mass index (BMI) between 25 and 35 kg/m2
) and none of the exclusion criteria (illness, pharmacological treatment, toxicological habits, or allergies). After a full disclosure of the implications and restrictions of the protocol, subjects were required to sign the informed consent from. Finally, subjects followed their regular diets during the whole study and were monitored by food consumption diaries.
The extract under study (MetabolAid®
) consisted of a capsule including a mixture of extracts from Lippia citriodora
(LC) (325 mg) and Hibiscus sabdariffa
(HS) (175 mg), both recognized for their abundance in sambubioside derivatives (HS) and verbascoside derivatives (LC) that may help to reduce problems associated with obesity [16
]. The placebo capsules contained 500 mg of crystalline microcellulose, maintaining the same aspect as the product under study. MetabolAid®
was provided by Monteloeder S.L. (Alicante, Spain) (Patent Application Number P201731147). The polyphenolic composition of the product was quantified and reported in previous studies [17
The present study had a length of 84 days, in which subjects consumed the LC-HS extract or the placebo daily depending on the previous randomization. Therefore, 42 subjects were distributed in the placebo group, and the other 42 subjects were allocated to the LC-HS extract group. Each subject was assigned a code (generated by a number software generator (Epidat v4.1. Epidat, Spain) allocating them to one of the two study groups. Both the researchers and the subjects themselves did not know the composition of the groups.
Subjects came to the research center at the beginning of the study and at the end. At baseline, blood samples were obtained from the cubital veins of subjects from both groups. After blood collection and explaining the operation of the study, subjects received the LC-HS extract or placebo. In order to determine physical activity, every subject was equipped with an accelerometer (ActiGraph wGT3X-BT. ActiGraph, Pensacola, FL, USA) prior to the beginning of the study. Finally, the body composition of the volunteers (total fat mass, fat mass of the trunk, and fat mass of the lower body) was determined by two different methods, bioimpedance (Tanita BC-420M. Tanita Corporation, Arlington Heights, IL, USA) and densitometry (Norland XR-4 using Dual Photonic Absorciometry. Swissray, Edison, NJ, USA).
Moreover, physical activity could partly be a determinant of the possible observed fat loss during the study, due to the importance of exercise with respect to weight control. Therefore, in order to prove if some strategies are effective for the treatment of obesity, physical exercise must be measured and regulated. For this purpose, physical exercise was measured by the metabolic equivalent of task (MET), which led to the determination of metabolic equivalents, relating the intensity of physical activity to the kilocalories consumed by subjects. MET values were determined in accordance with the “Compendium of Physical Activities” [19
Finally, blood analysis was performed for the monitoring of glycemic (glycemia and glycated hemoglobin) and lipidemic parameters (total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), and total triglycerides). The Reflotron Plus system (Roche Diagnostics S.L., Sant Cugat del Vallès, Barcelona, Spain) was used to obtain the glycemic and lipidemic values.
The study was conducted in accordance with the Declaration of Helsinki (randomized controlled trials registration number: NCT04105192), and the protocol was approved by the Ethics Committee of UCAM (CE011815).