Efficacy and safety of Amomum villosum extracts in obese adults: A randomized, double-blind, placebo-controlled trial

1 Introduction

Obesity is the most common contributor to the probability of numerous metabolic diseases and chronic illnesses like diabetes, heart disease, and some types of cancer (Guo et al., 2018). Frequency of overweight and obesity has reached crisis levels globally over the past 50 years (Yanovski, 2018; NCD Risk Factor Collaboration, 2017; NCD Risk Factor Collaboration, 2016). The most comprehensive data on changes in obesity prevalence around the world over the past 40 years has been supplied by researchers from the Noncommunicable diseases (NCDs) Risk Factor Collaboration (NCD Risk Factor Collaboration, 2017).

Obesity rates grew throughout each country between 1975 and 2016 according to the current study that provides patterns in BMI for all countries worldwide depending on the measurement of body mass and heights data from 128.9 million individuals including children, adolescents, and adults (NCD Risk Factor Collaboration, 2017). Obesity is defined by an increase in body mass and fat tissue as a result of chronically consuming more calories than one expends (Spiegelman and Flier, 2001). As a result of the energy deficit, adipose cells store too many calories followed by triglyceride buildup that causes fat cell enlargement, and abnormal fat cell differentiation causes hyperplasia of fat cells (Hara-Chikuma et al., 2005).

The production of adipocytokines, free fatty acids, and inflammatory mediators is sparked by the hypertrophy, hyperplasia, and associated intracellular malfunction of adipocytes, which results in overall ill health and the beginnings of obesity (De Ferranti and Mozaffarian, 2008). Medicinal plants based medication is a popular management method nowadays, although the majority of synthetic medications have negative outcomes (Schroll et al., 2016). As an example, orlistat works to treat adiposity through blocking activity of lipase and decreasing the long-chain triglycerides absorption. But there is a large list of adverse effects associated with orlistat, including fecal incontinence, oily spotting, diarrhea, and far more significant adverse effects such acute hepatotoxicity (Rucker et al., 2007).

A nutritional supplement is a material designed to complement one or more nutritional elements, such as protein, vitamins, and minerals (Ahmad et al., 2020). The use of natural supplements has become increasingly widespread worldwide. Weight-loss products are one of the key contributors and the estimated value of the 123 billion USD global market for dietary supplements in 2015 (Sun et al., 2016). In the prevention and treatment of various diseases, the bioactive elements of dietary and medicinal plants drawn increased awareness due to their lack of toxicity or low toxicity (Xu et al., 2020).

Additionally, various plants, including white bean, Yerba Mate, garcinia, and green tea have been produced as natural dietary supplements for weight loss (Jayawardena et al., 2020). Various researches have revealed that numerous medicinal plants, including lingonberries, ginger can combat obesity (Walid et al., 2018). Additionally, several plant-based bioactive substances with anti-obesity properties include capsaicin, dioscin, kaempferol, anthocyanin, and quercetin have been reported previously (Poudel et al., 2014). Furthermore, the major weight-loss strategies encompass suppressing appetite, lowering carbohydrate and lipid absorption, inhibiting adipogenesis and lipid synthesis, controlling lipid metabolic activity, increasing energy expenditure, controlling intestinal microbiota, and reducing inflammation caused by obesity (Walid et al., 2018; Poudel et al., 2014).

AVE is an herbal extract prepared from A. villosum Lour. (AV). According to a prior study, AV showed substantial pharmacological effects on ulcer, inflammation, and diarrhea (Huang et al., 2014). Previous studies have also demonstrated that AV extract (AVE) therapy had a substantial impact on postprandial glycemia and insulin secretion in healthy subjects (Kim et al., 2020) and high fat diet (HFD) and high cholesterol diet (HCD)-induced obesity in mice models (Kim et al., 2021, Kim et al., 2022). Additionally, AVE significantly reduced a-glucosidase activity (Kim et al., 2022).

In the current investigation, we conducted a 12-week, double-blind, randomized, placebo-controlled trial to look at the efficacy of AVE on reducing adiposity in obese people. In order to assess AVE efficiency, we have applied dual-energy X-ray absorptiometry (DEXA) to analyze total and regional body fats, anthropometric measurements, and metabolic markers.

2 Materials and methods

3 Results

3.1

3.1 Baseline characteristics

This clinical investigation was conducted from June 2020 to January 2021. Eighty (80) subjects were randomized into two different (active and placebo) groups. Due to withdrawal of consent (n = 1) and adverse event (n = 1), there were two individuals in the placebo group who were dropped from the study. Two individuals from each group (two from the active group and two from the placebo group) Four people, two from each group were excluded during the efficacy analysis as a result of protocol breaks. In terms of body height, gender distribution, age, weight, BMI, hip to waist ratio, body fat mass, diastolic blood pressure (DBP), systolic blood pressure (SBP), thyroid stimulating hormone (TSH), pulse, alcohol intake, and smoking, there was no statistically significant difference between the study groups. Fig. 1 shows a flowchart of the study population. Table 2 lists the baseline characteristics of the two different study groups. In each group, there were more female subjects (n = 34) than male (n = 6) ones, with a mean subject age of 37.20 ± 8.94 years.

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Fig. 1

Clinical trial flowchart.

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Table 2 Baseline characteristics of the subjects.

Parameters	AVE (n = 40)	Placebo (n = 40)	Total (n = 80)	p-value1)
Sex (M/F)	6/34	6/34	12/68	1.0002)
Age (years)	36.98 ± 9.08	37.43 ± 8.91	37.20 ± 8.94	0.824
Height (cm)	163.78 ± 6.58	162.85 ± 6.95	163.31 ± 6.74	0.824
Weight (kg)	69.90 ± 9.70	70.57 ± 13.04	70.23 ± 11.43	0.797
BMI (kg/m2)	26.03 ± 3.05	26.52 ± 3.92	26.27 ± 3.50	0.533
Waist circumference (cm)	89.70 ± 7.57	89.40 ± 10.05	89.55 ± 8.84	0.881
Hip circumference (cm)	100.39 ± 4.89	99.95 ± 7.69	100.17 ± 6.41	0.758
Waist to hip ratio	0.89 ± 0.05	0.89 ± 0.06	0.89 ± 0.06	0.923
Percent body fat (%)	35.37 ± 6.57	35.88 ± 5.72	35.63 ± 6.12	0.713
TSH (μIU/mL)	1.98 ± 1.06	2.17 ± 1.23	2.08 ± 1.15	0.468
SBP (mmHg)	125.73 ± 10.69	124.45 ± 13.82	125.09 ± 12.29	0.646
DBP (mmHg)	74.95 ± 9.16	76.88 ± 6.89	75.91 ± 8.11	0.291
Pulse (beats/min)	80.00 ± 10.80	83.53 ± 10.11	81.76 ± 10.54	0.136
Alcohol (n, %)	25 (62.50)	20 (50.00)	45 (56.25)	0.2602)
Alcohol (units/week)	5.50 ± 3.96	5.39 ± 4.38	5.45 ± 4.10	0.933
Smoking (n, %)	4 (10.00)	5 (12.50)	9 (11.25)	1.0003)

Values are presented as mean ± SD or number (%).

TSH, thyroid stimulating hormone; SBP, systolic blood pressure; DBP, diastolic blood pressure.

1) Analyzed by independent t-test.

2) Analyzed by chi-square test.

3) Analyzed by Fisher's exact test.

4 Discussion

In this research article, we examined the impact of AVE supplementation on obese adults. The risk of metabolic diseases rises with obesity. Numerous studies on medications and foods with special functions that can prevent obesity are being done as a result of the fast spreading worldwide obesity epidemic.

It is challenging methodologically to compare AVE to other fat-consuming weight-loss medications like orlistat, chitosan, or Litramine®. After receiving chitosan therapy for twelve weeks, Ho et al. noticed no significant alterations in body mass from base point (Ho et al., 2001). After twelve weeks of consumption, a medication with the patented fiber combination Litramine® resulted in a 3.8 kg weight reduction (Grube et al., 2013). According to a research by Anderson et al., orlistat (a gastric and pancreatic lipase inhibitor) influenced a 3.05 kg body weight reduction in obese participants after sixteen weeks treatment at 180 mg per each day (Anderson et al., 2006), whereas it contributed a body mass decline of 8.3 kg after twelve weeks in overweight subjects at a high dosage of 360 mg per each day. According to our research, AVE considerably reduced, percent body fat, body fat mass, BMI, VAT in addition to SAT. The probability of non - alcoholic fatty liver disease, diabetes, and coronary heart disease may all be reduced by treatment with AVE if body fat mass, percent body fat, VAT and SAT, an indicator of abdominal fat content, decreases (Flint et al., 2010; Clemente et al., 2016; Gautier et al., 2010). According to the current study, 31 of 38 individuals (81.6 %) lost weight before and after AVE treatment. The current clinical investigation also shows that 26 of 38 individuals (68.4 %) lost weight and body fat mass before and after AVE treatment.

Leptin and adiponectin are two adipokines that are produced by adipose tissue and are involved in the control of the energy balance and have an impact on cellular metabolic processes. Leptin regulates appetite and keeps the body's energy levels balanced. Its levels rise in cases of obesity (Klok et al., 2007). Unlike leptin, adiponectin levels drop in cases of obesity. Adiponectin mediates anti-inflammatory, anti-atherosclerotic, and anti-hyperglycemic activities (Matsubara et al., 2002). A widespread shift in the levels of many adipokines in the bloodstream is associated with the disproportional formation of white adipose tissue in overweight and obesity. The increased risk of a number of associated diseases in obese persons is assumed to be caused by adipokine dysregulation and adipokine dysfunction, or at the very least, it is one of the major contributors to this risk. For example, higher levels of proinflammatory adipokines, such as leptin, and decline of anti-inflammatory adipokines, for example adiponectin, in obese people generate a chronic condition of low-grade inflammatory response that endorses the insulin resistance development, coronary heart disease, high blood pressure, and type-2 diabetes (Hotamisligil, 2017). In addition, because adiponectin also functions as an insulin-sensitizing hormone in the liver and muscles, reduced adiponectin level in obese people substantially increase peripheral insulin resistance (Saltiel and Olefsky, 2017). On the contrary, elevated levels of leptin in the blood cause hypothalamic leptin resistance, which suppresses signals related to anorexia and energy expenditure and worsens obesity (Waterson and Horvath, 2015).

In the current study, AVE significantly decreased serum leptin level and considerably increased serum adiponectin level suggested that its potential effects on augmentation of insulin sensitivity and anti-obesity nature. Our findings stand in line with previous results (Ghanbari et al., 2022; Kim et al., 2018). AVE therapy decreased hepatic triglyceride level and dramatically raised adiponectin expression in adipocytes in the preliminary investigation in mice fed a high-fat diet (Kim et al., 2021). Additionally, SREBP1, FAS, CCAAT/enhancer binding protein (C/EBP)-α, PPAR-γ, and tumor necrosis factor (TNF)-α mRNA expression were all considerably downregulated by AVE therapy, which further significantly reduced adipogenesis (Kim et al., 2021). In a similar manner, rats fed a high-cholesterol diet and given AVE treatment for four weeks exhibited significantly lower levels of blood TG, TC, LDL-C, and hepatic TG as well as lower liver, epididymal fat, and body weights. The AVE therapy also significantly increased the levels of mRNA expression for the HMG-CoA reductase (HMGCR), the sterol regulatory element-binding protein 2 (SREBP2), and the LDL receptor (LDLR) (Kim et al., 2022).

In the previous human investigation, AVE supplementation showed a substantial decrease in postprandial blood glucose and postprandial blood insulin level compared to the placebo group (Kim et al., 2020). The VAT and SAT of obese persons in this study were considerably reduced with AVE supplementation. Fat is divided into visceral and subcutaneous compartments in humans. In the relationship between obesity, metabolism, and health, many studies have demonstrated that the regional distribution of body fat is a more significant factor than the degree of generalized obesity (Leizorovicz et al., 1994), demonstrating that VAT and SAT were more strongly associated with a poor metabolic risk profile. Decreases in VAT and SAT may therefore have a favorable impact on metabolic risk factors (Aronsson et al., 2010; Wernsdorfer et al., 2009).

In conclusion, the current investigation showed that AVE supplementation had an antiobese impact by lowering the VAT and SAT in obesity people. The results of this investigation are consistent with those of earlier animal experiments. The findings, along with those of earlier research, point to the possibility that AVE may reduce adiposity in obese people.